With nearly 70 published papers on Analytic Morphomics®, and subject matter ranging from how different body types endure motor vehicle crashes, to how to predict surgical outcomes based on the measurement of core muscles there is an ever growing body of research. These publications highlight the wide range of uses for Analytic Morphomics®.
2022
Analytic Morphomics Are Related to Outcomes After Lung Volume Reduction Surgery.
Lin J, Weir WB, Grenda T, Zhang P, Derstine BA, Enchakalody B, Underhill J, Reddy RM, Chang AC, Wang SC
Lung volume reduction surgery continues to have a high morbidity despite National Emphysema Treatment Trial selection criteria. This study evaluated the association between analytic morphomics on chest computed tomography scans and outcomes after lung volume reduction surgery. In a retrospective review of 85 lung volume reduction surgery patients from 1998-2013, dorsal muscle group area, subcutaneous and visceral fat area, and bone mineral density were assessed using analytic morphomics. Lung density was divided into five levels of increasing density (Lung density 1, emphysema; 2, normal lung; 4-5, scarring). Outcomes including survival, hospital length of stay, readmission at 30 days, and pulmonary complications were analyzed using univariate and multivariable techniques. Pulmonary complications developed in 27.1% (23/85). Mortality at 90 days was 9.4% (8/85). On multivariable analysis, lower bone mineral density (Odds ratio 0.61; 95% confidence interval 0.39-0.95) was associated with decreased survival, longer length of stay (0.83; 0.77-0.89), and readmissions (0.39; 0.15-1.00). Higher lung density 5:lung density 2 volume (1.84; 1.05-3.23), possibly due to scarring, was associated with pulmonary complications and longer length of stay (1.32; 1.23-1.41) while lower subcutaneous fat area:height was associated with readmissions which may reflect decreased metabolic reserve (0.35; 0.13-0.93). Patients with signs of frailty including lower bone mineral density may be at increased risk of adverse outcomes including decreased survival after lung volume reduction surgery. The results of this hypothesis-generating study will need to be confirmed in larger, multicenter trials to determine whether analytic morphomics can improve risk stratification and patient selection.
Muscle mass affects paclitaxel systemic exposure and may inform personalized paclitaxel dosing.
Hertz DL, Chen L, Henry NL, Griggs JJ, Hayes DF, Derstine BA, Su GL, Wang SC, Pai MP
Patients with low muscle mass have increased risk of paclitaxel-induced peripheral neuropathy, which is dependent on systemic paclitaxel exposure. Dose optimization may be feasible through the secondary use of radiologic data for body composition. The objective of this study was to interrogate morphomic parameters as predictors of paclitaxel pharmacokinetics to identify alternative dosing strategies that may improve treatment outcomes.
METHODS:
This was a secondary analysis of female patients with breast cancer scheduled to receive 80 mg/m2 weekly paclitaxel infusions. Paclitaxel was measured at the end of initial infusion to estimate maximum concentration (Cmax). Computed tomography (CT) scans were used to measure 29 body composition features for inclusion in pharmacokinetic modelling. Monte Carlo simulations were performed to identify infusion durations that limit the probability of exceeding Cmax > 2885 ng/mL, which was selected based on prior work linking this to an unacceptable risk of peripheral neuropathy.
RESULTS:
Thirty-nine patients were included in the analysis. The optimal model was a two-compartment pharmacokinetic model with T11 skeletal muscle area as a covariate of paclitaxel volume of distribution (Vd). Simulations suggest that extending infusion of the standard paclitaxel dose from 1 hour to 2 and 3 hours in patients who have skeletal muscle area 4907-7080 mm2 and <4907 mm2, respectively, would limit risk of Cmax > 2885 ng/mL to <50%, consequently reducing neuropathy, while marginally increasing overall systemic paclitaxel exposure.
CONCLUSION:
Extending paclitaxel infusion duration in ~25% of patients who have low skeletal muscle area is predicted to reduce peripheral neuropathy while maintaining systemic exposure, suggesting that personalizing paclitaxel dosing based on body composition may improve treatment outcomes.
A correction score to compare aortic calcification in contrast enhanced and non-contrast measurements from computed tomography scans.
Horbal SR, Brown E, Derstine BA, Zhang P, Bidulescu A, Sullivan JA, Ross BE, Su GL, Holcombe SA, Wang SC
Aortic wall calcification shows strong promise as a cardiovascular risk factor. While useful for visual enhancement of vascular tissue, enhancement creates heterogeneity between scans with and without contrast. We evaluated the relationship between aortic calcification in routine abdominal computed tomography scans (CT) with and without contrast.
METHODS:
Inclusion was limited to those with abdominal CT-scans with and without contrast enhancement within 120 days. Analytic Morphomics, a semi-automated computational image processing system, was used to provide standardized, granular, anatomically indexed measurements of aortic wall calcification from abdominal CT-scans. Aortic calcification area (ACA) and aortic wall calcification percent (ACP) and were the outcomes of interest. Multiple linear regression was used to evaluate the relationship of aortic measurements. Models were further controlled for age and sex. Stratification of measurements by vertebral level was also performed.
RESULTS:
A positive association was observed for non-contrast calcification in ACP β 0.74 (95% CI 0.72, 0.76) and ACA β 0.44 (95% 0.43, 0.45). Stratified results demonstrated the highest coefficient of determination at L2 for percent and L3 for area models [R2> 0.91 (ACP) 0.74 (ACA)]. Adjusted lumber-level associations between non-contrast and contrast measurements ranged from (β 0.69-0.82) in ACP and (β 0.37-0.54) in ACA.
CONCLUSION:
A straightforward correction score for comparison of abdominal aortic calcification measurements in contrast-enhanced and non-contrast scans is discussed. Correction of aortic calcification from CT scans can reduce scan heterogeneity and will be instrumental in creating larger cardiovascular cohorts as well as cardiovascular risk surveillance programs.
Healthy US population reference values for CT visceral fat measurements and the impact of IV contrast, HU range, and spinal levels.
Derstine BA, Holcombe SA, Ross BE, Wang NC, Wang SC, Su GL
Measurements of visceral adipose tissue cross-sectional area and radiation attenuation from computed tomography (CT) scans provide useful information about risk and mortality. However, scan protocols vary, encompassing differing vertebra levels and utilizing differing phases of contrast enhancement. Furthermore, fat measurements have been extracted from CT using different Hounsfield Unit (HU) ranges. To our knowledge, there have been no large studies of healthy cohorts that reported reference values for visceral fat area and radiation attenuation at multiple vertebra levels, for different contrast phases, and using different fat HU ranges. Two-phase CT scans from 1,677 healthy, adult kidney donors (age 18-65) between 1999 and 2017, previously studied to determine healthy reference values for skeletal muscle measures, were utilized. Visceral adipose tissue cross-sectional area (VFA) and radiation attenuation (VFRA) measures were quantified using axial slices at T10 through L4 vertebra levels. T-tests were used to compare males and females, while paired t-tests were conducted to determine the effect (magnitude and direction) of (a) contrast enhancement and (b) different fat HU ranges on each fat measure at each vertebra level. We report the means, standard deviations, and effect sizes of contrast enhancement and fat HU range. Male and female VFA and VFRA were significantly different at all vertebra levels in both contrast and non-contrast scans. Peak VFA was observed at L4 in females and L2 in males, while peak VFRA was observed at L1 in both females and males. In general, non-contrast scans showed significantly greater VFA and VFRA compared to contrast scans. The average paired difference due to contrast ranged from 1.6 to - 8% (VFA) and 3.2 to - 3.0% (VFRA) of the non-contrast value. HU range showed much greater differences in VFA and VFRA than contrast. The average paired differences due to HU range ranged from - 5.3 to 22.2% (VFA) and - 5.9 to 13.6% (VFRA) in non-contrast scans, and - 4.4 to 20.2% (VFA) and - 4.1 to 12.6% (VFRA) in contrast scans. The - 190 to - 30 HU range showed the largest differences in both VFA (10.8% to 22.2%) and VFRA (7.6% to 13.6%) compared to the reference range (- 205 to - 51 HU). Incidentally, we found that differences in lung inflation result in very large differences in visceral fat measures, particularly in the thoracic region. We assessed the independent effects of contrast presence and fat HU ranges on visceral fat cross-sectional area and mean radiation attenuation, finding significant differences particularly between different fat HU ranges. These results demonstrate that CT measurements of visceral fat area and radiation attenuation are strongly dependent upon contrast presence, fat HU range, sex, breath cycle, and vertebra level of measurement. We quantified contrast and non-contrast reference values separately for males and females, using different fat HU ranges, for lumbar and thoracic CT visceral fat measures at multiple vertebra levels in a healthy adult US population.
2021
The psoas muscle index distribution and influence of outcomes in an Asian adult trauma population: an alternative indicator for sarcopenia of acute diseases.
Tee YS, Cheng CT, Wu YT, Kang SC, Derstine BA, Fu CY, Liao CH, Su GL, Wang SC, Hsieh CH
Sarcopenia has been shown to be an independent negative predictor in various diseases. The measurement of pre-defined criteria of skeletal muscle in patients with acute disease is usually unavailable. Therefore, we evaluate the psoas muscle area based on computed tomography (CT) imaging as an alternative for sarcopenia in an Asian trauma population.
METHODS:
939 trauma patients were enrolled and had CT imaging performed primarily for trauma indications. The cross-sectional area of psoas muscle at the base of the fourth lumbar vertebral was measured on these CTs. Psoas muscle index (PMI) was calculated and analyzed to determine sex-specific cut-off values to define the "extremely low psoas muscle index" (ELPMI) group.
RESULTS:
Psoas muscle index was significantly higher in males (1065.09 ± 230.51 mm2/m2 in males vs 719.57 ± 147.39 mm2/m2 in females, p < 0.001) and decreased gradually with aging (p < 0.001). PMI of the subset of patients aged 18-40 (n = 462) weas analyzed to determine sex-specific cut-off values for ELPMI. PMI cut-off values for ELPMI (2 SD below mean) were 675 mm2/m2 for males and 490 mm2/m2 for females. The entire trauma cohort was further analyzed, and ELPMI was identified as an independent risk factor for a longer length of intensive unit stay (β coefficient = 3.881, p = 0.011).
CONCLUSION:
Data from young trauma adults were used to establish cut-off values for ELPMI, which is a longer ICU stay predictor. These cut-off values for ELPMI may apply to other acute disease entities.
Automated Measurements of Body Composition in Abdominal CT Scans Using Artificial Intelligence Can Predict Mortality in Patients With Cirrhosis.
Zou WY, Enchakalody BE, Zhang P, Shah N, Saini SD, Wang NC, Wang SC, Su GL
Body composition measures derived from already available electronic medical records (computed tomography [CT] scans) can have significant value, but automation of measurements is needed for clinical implementation. We sought to use artificial intelligence to develop an automated method to measure body composition and test the algorithm on a clinical cohort to predict mortality. We constructed a deep learning algorithm using Google's DeepLabv3+ on a cohort of de-identified CT scans (n = 12,067). To test for the accuracy and clinical usefulness of the algorithm, we used a unique cohort of prospectively followed patients with cirrhosis (n = 238) who had CT scans performed. To assess model performance, we used the confusion matrix and calculated the mean accuracy of 0.977 ± 0.02 (0.975 ± 0.018 for the training and test sets, respectively). To assess for spatial overlap, we measured the mean intersection over union and mean boundary contour scores and found excellent overlap between the manual and automated methods with mean scores of 0.954 ± 0.030, 0.987 ± 0.009, and 0.948 ± 0.039 (0.983 ± 0.013 for the training and test set, respectively). Using these automated measurements, we found that body composition features were predictive of mortality in patients with cirrhosis. On multivariate analysis, the addition of body composition measures significantly improved prediction of mortality for patients with cirrhosis over Model for End-Stage Liver Disease alone (P < 0.001). Conclusion: The measurement of body composition can be automated using artificial intelligence and add significant value for incidental CTs performed for other clinical indications. This is proof of concept that this methodology could allow for wider implementation into the clinical arena.
Predicting outcomes of abdominal surgical emergencies in the elderly population using a CT muscle gauge.
Tee YS, Cheng CT, Wu YT, Hsu CP, Kang SC, Hsieh CH, Derstine BA, Su GL, Wang SC, Fu CY, Liao CH
Frailty has been shown to be an independent negative predictor of surgical outcomes in geriatric patients. Traditional measurements of muscle strength and mass are impractical in emergency settings, and computed tomography (CT)-measured skeletal muscle mass has been proposed as an alternative. However, the cutoff values for low muscle mass are still unknown, and their impact on abdominal emergencies in the elderly population is unclear.
METHODS:
A total of 462 young trauma patients aged 18-40 years were analyzed to establish sex-specific reference cutoff values for the CT-measured muscle index (MI) and muscle gauge (MG) values. The impacts of low MI and MG values were investigated in 1192 elderly patients (aged ≥ 65 years) undergoing abdominal surgery.
RESULTS:
The sex-specific cutoff values for MI and MG were determined by adopting European Working Group on Sarcopenia in Older People 2 guidelines. The correlation between MG and aging was significantly stronger than that between MI and ageing. With regard to the MG, the L4 psoas muscle gauge (L4 PMG) was further investigated in an elderly cohort owing to its high predictive value and ease of use in the clinical setting. A low L4 PMG value was an independent risk factor for overall complications and mortality in elderly patients with abdominal emergencies.
CONCLUSION:
The current study was the largest study investigating the correlations between MG values and aging in the Asian population. A low L4 PMG value may help surgeons during preoperative decision making regarding geriatric patients with abdominal emergencies.
Does a "Cushion Effect" Really Exist? A Morphomic Analysis of Vulnerable Road Users with Serious Blunt Abdominal Injury.
Tee YS, Cheng CT, Hsieh CH, Kang SC, Fu CY, Derstine BA, Su GL, Wang SC
The severity of injury from motor vehicle crashes (MVCs) depends on complex biomechanical factors, and the bodily features of the injured person account for some of these factors. By assuming that vulnerable road users (VRUs) have limited protection resulting from vehicles and safety equipment, the current study analyzed the characteristics of fat distribution measured by computed tomography (CT) imaging and investigated the existence of a "cushion effect" in VRUs. Materials and Methods: This retrospective study enrolled 592 VRUs involved in MVCs who underwent CT scans. Visceral fat area and subcutaneous fat cross-sectional area were measured and adjusted according to total body area (TBA) and are presented as the visceral fat ratio and the subQ fat ratio (subcutaneous fat ratio). Risk factors for serious abdominal injury (maximum abbreviated injury scale (MAISabd ≥ 3)) resulting from MVCs were determined by univariate and multivariate analysis. Results: MAISabd ≥ 3 was observed in 104 (17.6%) of the patients. The subQ fat ratio at the L4 vertebral level was significantly lower in the MAISabd ≥ 3 group than in the MAISabd < 3 group (24.9 ± 12.0 vs. 28.1 ± 11.9%; p = 0.015). A decreased L4 subQ fat ratio was associated with a higher risk for MAISabd ≥ 3 in multivariate analysis (odds ratio 0.063; 95% CI 0.008-0.509; p = 0.009). Conclusion: The current study supported the "cushion effect" theory, and protection was apparently provided by subcutaneous fat tissue. This concept may further improve vehicle and safety designation in the future.
Field Data Study of the Effect of Knee Airbags on Lower Extremity Injury in Frontal Crashes.
Schafman MA, Meitzner M, Baker D, Beebe MA, Bentz J, Sadrnia H, Kleinert J, Wang SC
Knee airbags (KABs) are one countermeasure in newer vehicles that could influence lower extremity (LEX) injury, the most frequently injured body region in frontal crashes. To determine the effect of KABs on LEX injury for drivers in frontal crashes, the analysis examined moderate or greater LEX injury (AIS 2+) in two datasets. Logistic regression considered six main effect factors (KAB deployment, BMI, age, sex, belt status, driver compartment intrusion). Eighty-five cases with KAB deployment from the Crash Injury Research and Engineering Network (CIREN) database were supplemented with 8 cases from the International Center for Automotive Medicine (ICAM) database and compared to 289 CIREN non-KAB cases. All cases evaluated drivers in frontal impacts (11 to 1 o’clock Principal Direction of Force) with known belt use in 2004 and newer model year vehicles. Results of the CIREN/ICAM dataset were compared to analysis of a similar dataset from NASS-CDS (5441 total cases, 418 KAB-deployed). KABs were associated with a reduced rate of LEX injury in the CIREN/ICAM dataset (OR = 0.612, p=0.065), but were inconclusive in the NASS-CDS dataset (OR=0.946, p=0.761). KABs were associated with a reduced rate of knee/thigh/hip injury in CIREN/ICAM (OR = 0.555, p = 0.035) but had no measurable effect on below knee injury in CIREN/ICAM (OR = 0.928, p = 0.765) or NASS-CDS (OR=1.102, p=0.641). In conclusion, KABs were associated with reduced rates of LEX and knee/thigh/hip injury in the CIREN/ICAM dataset and had no measurable effect on below knee injury for drivers in frontal crashes in either dataset.
Optimal body size adjustment of L3 CT skeletal muscle area for sarcopenia assessment.
Derstine BA, Holcombe SA, Ross BE, Wang NC, Su GL, Wang SC
Measurements of skeletal muscle cross-sectional area (SMA) at the level of the third lumbar (L3) vertebra derived from clinical computed tomography (CT) scans are commonly used in assessments of sarcopenia, the loss of skeletal muscle mass and function associated with aging. As SMA is correlated with height and Body Mass Index (BMI), body size adjustment is necessary to fairly assess sarcopenic low muscle mass in individuals of different height and BMI. The skeletal muscle index, a widely used measure, adjusts for height as but uses no BMI adjustment. There is no agreed upon standard for body size adjustment. We extracted L3 SMA using non-contrast-enhanced CT scans from healthy adults, split into ‘Under-40’ and ‘Over-40’ cohorts. Sex-specific allometric analysis showed that height to the power of one was the optimal integer coefficient for height adjusted SMA in both males and females. We computed two height-adjusted measures and , comparing their Pearson correlations versus age, height, weight, and BMI separately by sex and cohort. Finally, in the ‘Under-40’ cohort, we used linear regression to convert each height-adjusted measure into a z-score (, ) adjusted for BMI. was less correlated with height in both males and females (, and , ) than ( and , ). was uncorrelated with BMI and weight, and minimally correlated with height in males and females (, and , ). The final equation was: , where , , , and sex = 1 if male, 0 if female. We propose for optimal height adjustment and the score for optimal height and BMI adjustment. By minimizing correlations with height and BMI, the score produces unbiased assessments of relative L3 skeletal muscle area across the full range of body sizes.
2020
Gastroesophageal resuscitative occlusion of the aorta: Physiologic tolerance in a swine model of hemorrhagic shock.
Resuscitative endovascular balloon occlusion of the aorta (REBOA) has been shown to be effective for management of noncompressible torso hemorrhage. However, this technique requires arterial cannulation, which can be time-consuming and not amendable to placement in austere environments. We present a novel, less invasive aortic occlusion device and technique designated gastroesophageal resuscitative occlusion of the aorta (GROA). In this study, we aimed to characterize the physiological tolerance and hemodynamic effects of a prototype GROA device in a model of severe hemorrhagic shock and resuscitation and compare with REBOA.
METHODS:
RSwine (N = 47) were surgically instrumented for data collection. A 35% controlled arterial hemorrhage was followed by randomizing animals to 30-minute, 60-minute, or 90-minute interventions of GROA, REBOA, or control. Following intervention, devices were deactivated, and animals received whole blood and crystalloid resuscitation. Animals were monitored for an additional 4 hours.
RESULTS:
All animals except one GROA 90-minute application survived the duration of their intervention periods. Survival through resuscitation phase in GROA, REBOA, and control groups was similar in the 30-minute and 60-minute groups. The 90-minute occlusion groups exhibited deleterious effects upon device deactivation and reperfusion with two GROA animals surviving and no REBOA animals surviving. Mean (SD) arterial pressure in GROA and REBOA animals increased across all groups to 98 (31.50) mm Hg and 122 (24.79) mm Hg, respectively, following intervention. Lactate was elevated across all GROA and REBOA groups relative to controls during intervention but cleared by 4 hours in the 30-minute and 60-minute groups. Postmortem histological examination of the gastric mucosa revealed mild to moderate inflammation across all GROA groups.
CONCLUSION:
In this study, the hemodynamic effects and physiological tolerance of GROA was similar to REBOA. The GROA device was capable of achieving high zone II full aortic occlusion and may be able to serve as an effective method of aortic impingement.
Comparing FE human body model rib geometry to population data.
Holcombe SA, Agnew AM, Derstine B, Wang SC
Biomech Model Mechanobiol. 2020 Dec; 19(6):2227-2239
Finite element human body models (HBMs) are used to assess injury risk in a variety of impact scenarios. The ribs are a key structural component within the chest, so their accuracy within HBMs is vitally important for modeling human biomechanics. We assessed the geometric correspondence between the ribs defined within five widely used HBMs and measures drawn from population-wide studies of rib geometry, focusing on (1) rib global shape, (2) rib cross-sectional size and shape, and (3) rib cortical bone thickness. A parametric global shape model fitted to all HBM ribs was compared to expected rib parameters calculated for each HBM's subject demographic using population reference data. The GHBMC M50 and THUMS M50 male HBMs showed 24% and 50% of their fitted rib shape parameters (6 parameters per each 12 ribs) falling outside 1SD from population expected values, respectively. For female models the GHBMC F05, THUMS F05, and VIVA F50 models had 21%, 26%, and 19% of their rib shape parameters falling outside 1SD, respectively. Cross-sectional areas and inertial moments obtained along the HBM ribs were compared to average ± 1SD corridors for male and female ribs drawn from reference population data. The GHBMC M50, THUMS M50, and VIVA F50 model ribs were all larger in overall cross-sectional area than their targeted average population values by 0.9SDs (average across the rib's full length), 1.7SDs, and 1.3SDs, respectfully. When considering cortical bone cross-sectional area, the THUMS and VIVA models-which each define a constant bone thickness value across the entire rib-overestimated bone content on average by 1.1SDs and 1.2SDs, respectively. HBMs have traditionally performed poorly when predicting rib fracture onset or fracture site, and in all HBMs in this study the rib regions with the most extreme cortical bone thickness and cross-sectional area discrepancies (compared to average reference data) corresponded to regions toward the sternal end of the ribs where rib fractures most frequently occur. Results from this study highlight geometrical components of current HBM ribs that differ from the rib geometry that would be expected from within those models' target demographics, and help researchers prioritize improvements to their biofidelity.
Morphomic calcification score from clinical CT scans: A proxy for coronary artery calcium.
Horbal SR, Rossman AH, Brown E, Shah NV, Ross BE, Bidulescu A, Sullivan JA, Su GL, Wang SC
Screening of cardiovascular risk is essential in preventing cardiac events and quantifying asymptomatic risk. Coronary artery calcium (CAC) scores are a well-established in predicting cardiovascular risk, but require specialized computed tomography (CT) scans. Given the relationship of aortic calcification with cardiovascular risk, we sought to determine whether aortic calcification measures from incidental CT scans may approximate CAC.
STUDY DESIGN:
Retrospective CT scans and corresponding volumetric CAC scores were obtained from patients at the University of Michigan. Aortic calcifications were measured in 166 scans. Correlations between a novel morphomic calcium (MC) percent score and CAC score were evaluated using Kendall's correlation coefficients. Comparison of receiver operating characteristic (ROC) curves based on MC at different vertebral levels showed the highest predictive values for measures taken at L4.
RESULTS:
MC at L4 shows promise in predicting CAC (AUC 0.90 in non-contrast scans, 0.70 in post-contrast scans). Proposed MC threshold are (4.21% for best sensitivity, B 12.93% for balance, C = 19.26% for specificity) in scans without contrast enhancement and (D = 7.31 for sensitivity, E 8.06 for specificity) in scans with contrast enhancement.
CONCLUSION:
The MC score demonstrates promising potential in approximating CAC, particularly at the L4 level. The utilization of MC from incidental CT scans may be useful for assessment of cardiovascular risk. The ability to extract MC from contrast scans makes it especially valuable to patients receiving additional medical or surgical care. Recognition of high-risk patients would allow the use of indicated preventative strategies to avoid hard cardiovascular events in at risk patients.
CT validation of SVC-RA junction location for pediatric central line placement: is vertebral bodies below the carina accurate?
Hirschl JR, Gadepalli SK, Derstine BA, Holcombe SA, Smith EA, Wang SC, Ehrlich PF, Jarboe MD
The key landmark for tip position of a central venous catheter (CVC) is the SVC-RA junction. In adults, localization of the SVC-RA junction may be assessed as a function of vertebral body units (VBU) below the carina during CVC placement. We investigated the relationship between the SVC-RA junction and the carina in children.
MATERIALS AND METHODS:
584 CT scans of 0-18 years were analyzed. The carina was marked automatically by software while the SVC-RA junction and vertebrae were marked manually. The SVC-RA junction to carina (JC) distance was the primary study measurement reported in both VBU and mm.
RESULTS:
The data show an average JC distance of 1.25 VBU for 0-1 year, 1.27 VBU for 1-4 years, 1.34 VBU for 4-9 years, 1.53 VBU for 9-15 years, and 1.64 VBU for 15-18 years. A positive relationship between weight and JC distance was also demonstrated.
DISCUSSION:
JC distance is a useful predictor of SVC-RA junction location in children. Significant relationships were shown between JC distance and both age and weight. Due to small differences between age groups, however, average JC distance for all comers (1.48 VBU, 95% CI 0.7 - 2.3) can be used for SVC-RA junction identification in CVC placement.
Automated measurement of muscle mass using deep learning can predict clinical outcomes in patients with liver disease.
Wang NC, Zhang PC, Tapper EB, Saini S, Wang SC, Su GL.
There is increasing recognition of the central role of muscle mass in predicting clinical outcomes in patients with liver disease. Muscle size can be extracted from computed tomography (CT) scans, but clinical implementation will require increased automation. We hypothesize that we can achieve this by using artificial intelligence.
METHODS:
Using deep convolutional neural networks, we trained an algorithm on the Reference Analytic Morphomics Population (n = 5,268) and validated the automated methodology in an external cohort of adult kidney donors with a noncontrast CT scan (n = 1,655). To test the clinical usefulness, we examined its ability to predict clinical outcomes in a prospectively followed cohort of patients with clinically diagnosed cirrhosis (n = 254).
RESULTS:
Between the manual and automated methodologies, we found excellent inter-rater agreement with an intraclass correlation coefficient of 0.957 (confidence interval 0.953-0.961, P < 0.0001) in the adult kidney donor cohort. The calculated dice similarity coefficient was 0.932 ± 0.042, suggesting excellent spatial overlap between manual and automated methodologies. To assess the clinical usefulness, we examined its ability to predict clinical outcomes in a cirrhosis cohort and found that automated psoas muscle index was independently associated with mortality after adjusting for age, gender, and child's classification (P < 0.001).
DISCUSSION:
We demonstrated that deep learning techniques can allow for automation of muscle measurements on clinical CT scans in a diseased cohort. These automated psoas size measurements were predictive of mortality in patients with cirrhosis showing proof of principal that this methodology may allow for wider implementation in the clinical arena.
The psoas muscle index distribution and influence of outcomes in an Asian adult trauma population: an alternative indicator for sarcopenia of acute diseases.
Tee Y-S, Cheng C-T, Wu Y-T, Kang S-C, Derstine BA, Fu C-Y, Liao C-H, Su GL, Wang SC, Hsieh C-H.
Sarcopenia has been shown to be an independent negative predictor in various diseases. The measurement of pre-defined criteria of skeletal muscle in patients with acute disease is usually unavailable. Therefore, we evaluate the psoas muscle area based on computed tomography (CT) imaging as an alternative for sarcopenia in an Asian trauma population.
METHODS:
939 trauma patients were enrolled and had CT imaging performed primarily for trauma indications. The cross-sectional area of psoas muscle at the base of the fourth lumbar vertebral was measured on these CTs. Psoas muscle index (PMI) was calculated and analyzed to determine sex-specific cut-off values to define the "extremely low psoas muscle index" (ELPMI) group.
RESULTS:
Psoas muscle index was significantly higher in males (1065.09 ± 230.51 mm2/m2 in males vs 719.57 ± 147.39 mm2/m2 in females, p < 0.001) and decreased gradually with aging (p < 0.001). PMI of the subset of patients aged 18-40 (n = 462) weas analyzed to determine sex-specific cut-off values for ELPMI. PMI cut-off values for ELPMI (2 SD below mean) were 675 mm2/m2 for males and 490 mm2/m2 for females. The entire trauma cohort was further analyzed, and ELPMI was identified as an independent risk factor for a longer length of intensive unit stay (β coefficient = 3.881, p = 0.011).
CONCLUSIONS:
Data from young trauma adults were used to establish cut-off values for ELPMI, which is a longer ICU stay predictor. These cut-off values for ELPMI may apply to other acute disease entities.
2019
Morphomic Index Is an Independent Predictor of Survival After Lung Cancer Resection.
Ferguson MK, Mitzman B, Derstine B, Lee SM, Pienta MJ, Wang SC, Lin J.
Ann Thorac Surg. 2019 Dec 17;. doi: 10.1016/j.athoracsur.2019.10.064. [Epub ahead of print] PubMed PMID: 31862495.
Sarcopenia, visceral fat volume, and bone density have been associated with lung cancer survival. We developed a morphomic index based on computed tomographic measurements of these components, and assessed its relationship to survival after lung cancer resection.
METHODS:
Patients who underwent lung cancer resection from 1995 to 2014 were evaluated. A morphomic index (range of 0 to 3) was developed as the sum of the scores for three body components-dorsal muscle area, vertebral trabecular bone density, and visceral fat area-measured at vertebral levels T10 to T12, with a point assigned to each component when in the lowest tercile. The relationship of the morphomic index to overall survival was assessed by the log rank test. Overall survival was assessed using Cox proportional hazards models adjusted for relevant covariates.
RESULTS:
We included 944 patients (451 women; 48%). The mean age was 66.4 ± 10.3 years. Median follow-up was 4.5 years. Median survival was associated with the morphomic index scores on univariate analysis (P < .001). Morphomic index scores of 2 (P = .026) and 3 (P = .004) referenced to score 0 or 1 were independent predictors of survival on Cox regression analysis.
CONCLUSIONS:
A morphomic index is an independent predictor of survival after lung cancer resection. The index may help in calibrating patient expectations and in shared decision making regarding lung cancer surgery.
Comparison of Body Size, Morphomics, and Kidney Function as Covariates of High-Dose Methotrexate Clearance in Obese Adults with Primary Central Nervous System Lymphoma.
Pai MP, Debacker KC, Derstine B, Sullivan J, Su GL, Wang SC.
Pharmacotherapy. 2020 Feb 23;. doi: 10.1002/phar.2379. [Epub ahead of print] PubMed PMID: 32090349.
High-dose methotrexate (HD-MTX) is used to treat primary central nervous system lymphoma (PCNSL), but potential differences in MTX clearance (CL) due to obesity have not been studied. We characterized the relationship between HD-MTX CL and computed tomography (CT)-generated body composition (morphomic), body size descriptors, and laboratory measurements in a cohort of obese and non-obese patients with PCNSL.
METHODS:
Medical records from adult patients with PCNSL treated with HD-MTX over a 10-year period were queried. Individuals with CT data within 30 days of the first cycle of treatment were included. Population pharmacokinetic analysis was performed using a 2-compartment base structural model. We specifically compared body surface area (BSA) to standard body size, morphomic, and renal function estimation methods as covariates of HD-MTX CL.
RESULTS:
The final data set consisted of non-obese (n=45) and obese (n=28) patients with 291 observations (3-7 samples per patient) with a mean (standard deviation) weight of 69.8 (11.6) kg and 104 (14.9) kg, respectively (p=0.0001). Vertebral body height was more informative than BSA of MTX CL. Similarly, a CL model incorporating age, albumin, and serum creatinine was more informative than kidney function equations and body size. The final model of MTX CL was based on age, albumin, serum creatinine, and vertebral body height.
CONCLUSIONS:
Common clinical variables coupled with vertebral body height are more predictive of first cycle MTX CL than BSA, alternate body size descriptors, and commonly used kidney function equations.
Morphomic Factors Associated With Complete Response to Neoadjuvant Therapy in Esophageal Carcinoma.
Chiu CH, Zhang P, Chang AC, Derstine BA, Ross BE, Enchakalody B, Shah NV, Wang SC, Chao YK, Lin J.
In patients undergoing neoadjuvant chemoradiotherapy (nCRT) followed by surgery for locally advanced esophageal squamous cell carcinoma (ESCC), patients with a pathologic complete response (pCR) have the greatest benefit. The purpose of this study was to identify morphomic factors obtained from pretreatment computed tomography scans associated with a pCR in ESCC.
METHODS:
We retrospectively analyzed patients with ESCC treated with nCRT who underwent esophagectomy between 2006 and 2016. Clinical and morphomic characteristics pre-nCRT were analyzed to identify factors associated with pCR using univariate and multivariable analyses.
RESULTS:
There were 183 patients with ESCC included in this study, and 45 (24.6%) patients achieved pCR. The overall survival in patients with pCR was better than that in patients without pCR (5.8 years vs 1.2 years; P < .001). On univariate analysis, increased age, radiation dose greater than or equal to 4000 cGy, and larger subcutaneous adipose tissue area were correlated with pCR. On multivariable logistic regression, increased age (odds ratio, 1.53; P = .03), radiation dose greater than or equal to 4000 cGy (odds ratio, 2.19; P = .04), and larger dorsal muscle group normal-density area (odds ratio, 1.59; P = .03) were independently associated with pCR.
CONCLUSIONS:
Increased age, radiation dose greater than or equal to 4000 cGy, and larger dorsal muscle group normal-density area were significantly associated with pCR. These factors may be useful in determining which patients are most likely to benefit from nCRT followed by esophagectomy.
Morphomic Signatures Derived from Computed Tomography Predict Hepatocellular Carcinoma Occurrence in Cirrhotic Patients.
Liang KH, Zhang P, Lin CL, Wang SC, Hu TH, Yeh CT, Su GL.
Dig Dis Sci. 2019 Nov 2; doi: 10.1007/s10620-019-05915-w. [Epub ahead of print] PubMed PMID: 31677071.
Computed tomography (CT) provides scans of the human body from which digitized features can be extracted. The aim of this study was to examine the role of these digital biomarkers for predicting subsequent occurrence of hepatocellular carcinoma (HCC) in cirrhotic patients.
METHODS:
A cohort of 269 patients with cirrhosis were recruited and prospectively followed for the occurrence of HCC in Taiwan. CT scans were retrospectively retrieved and computationally processed using analytic morphomics. A predictive score was constructed using Cox regression and the generalized iterative modeling method, maximizing the log likelihood of the time to HCC development. An independent cohort of 274 patients from University of Michigan was utilized to examine the predictive validity of this score in a Western population.
RESULTS:
Of the 27 digitized features at the 12th thoracic vertebral level, six features were significantly associated with HCC occurrence. Two digitized features (fascia eccentricity and the bone mineral density) were able to stratify patients into high- and low-risk groups with distinct cumulative incidence of HCC in both the training and validation cohorts (P = 0.015 and 0.044, respectively). When the two digitized features were tested in the Michigan cohort, only bone mineral density remained an effective predictor.
CONCLUSIONS:
Digitized features derived from the CT were effective in predicting subsequent occurrence of HCC in cirrhosis patients. The bone mineral density measured on CT was an effective predictor for patients in both Taiwan and USA.
Assessing Small Bowel Stricturing and Morphology in Crohn's Disease Using Semi-automated Image Analysis.
Stidham RW, Enchakalody B, Waljee AK, Higgins PDR, Wang SC, Su GL, Wasnik AP, Al-Hawary M.
Inflamm Bowel Dis. 2019 Aug 29;. doi: 10.1093/ibd/izz196. [Epub ahead of print] PubMed PMID: 31504540.
Evaluating structural damage using imaging is essential for the evaluation of small intestinal Crohn's disease (CD), but it is limited by potential interobserver variation. We compared the agreement of enterography-based bowel damage measurements collected by experienced radiologists and a semi-automated image analysis system.
METHODS:
Patients with small bowel CD undergoing a CT-enterography (CTE) between 2011 and 2017 in a tertiary care setting were retrospectively reviewed. CT-enterography studies were reviewed by 2 experienced radiologists and separately underwent automated computer image analysis using bowel measurement software. Measurements included maximum bowel wall thickness (BWT-max), maximum bowel dilation (DIL-max), minimum lumen diameter (LUM-min), and the presence of a stricture. Measurement correlation coefficients and paired t tests were used to compare individual operator measurements. Multivariate regression was used to model identification of strictures using semi-automated measures.
RESULTS:
In 138 studies, the correlation between radiologists and semi-automated measures were similar for BWT-max (r = 0.724, 0.702), DIL-max (r = 0.812, 0.748), and LUM-min (r = 0.428, 0.381), respectively. Mean absolute measurement difference between semi-automated and radiologist measures were no different from the mean difference between paired radiologists for BWT-max (1.26 mm vs 1.12 mm, P = 0.857), DIL-max (2.78 mm vs 2.67 mm, P = 0.557), and LUM-min (0.54 mm vs 0.41 mm, P = 0.596). Finally, models of radiologist-defined intestinal strictures using automatically acquired measurements had an accuracy of 87.6%.
CONCLUSIONS:
Structural bowel damage measurements collected by semi-automated approaches are comparable to those of experienced radiologists. Radiomic measures of CD will become an important new data source powering clinical decision-making, patient-phenotyping, and assisting radiologists in reporting objective measures of disease status.
Crash Telemetry-Based Injury Severity Prediction is Equivalent to or Out-Performs Field Protocols in Triage of Planar Vehicle Collisions.
With the increasing availability of vehicle telemetry technology, there is great potential for Advanced Automatic Collision Notification (AACN) systems to improve trauma outcomes by detecting patients at-risk for severe injury and facilitating early transport to trauma centers.
METHODS:
National Automotive Sampling System Crashworthiness Data System (NASS-CDS) data from 1999-2013 were used to construct a logistic regression model (injury severity prediction [ISP] model) predicting the probability that one or more occupants in planar, non-rollover motor vehicle collisions (MVCs) would have Injury Severity Score (ISS) 15+ injuries. Variables included principal direction of force (PDOF), change in velocity (Delta-V), multiple impacts, presence of any older occupant (≥55 years old), presence of any female occupant, presence of right-sided passenger, belt use, and vehicle type. The model was validated using medical records and 2008-2011 crash data from AACN-enabled Michigan (USA) vehicles identified from OnStar (OnStar Corporation; General Motors; Detroit, Michigan USA) records. To compare the ISP to previously established protocols, a literature search was performed to determine the sensitivity and specificity of first responder identification of ISS 15+ for MVC occupants.
RESULTS:
The study population included 924 occupants in 836 crash events. The ISP model had a sensitivity of 72.7% (95% Confidence Interval [CI] 41%-91%) and specificity of 93% (95% CI 92%-95%) for identifying ISS 15+ occupants injured in planar MVCs. The current standard 2006 Field Triage Decision Scheme (FTDS) was 56%-66% sensitive and 75%-88% specific in identifying ISS 15+ patients.
CONCLUSIONS:
The ISP algorithm comparably is more sensitive and more specific than current field triage in identifying MVC patients at-risk for ISS 15+ injuries. This real-world field study shows telemetry data transmitted before dispatch of emergency medical systems can be helpful to quickly identify patients who require urgent transfer to trauma centers.
CT Correlation of Skeletal Landmarks and Vascular Anatomy in Civilian Adult Trauma Patients Implications for Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA).
Eliason J L, Derstine BA, Horbal SR, Wang NC, Holcombe SA, Chiu C-H, Ross BE, Bromwell B, Morrison J, Wang SC.
J Trauma Acute Care Surg: Mar 1, 2019. Vol Pub Ahead of Print Issue doi: 10.1097/TA.0000000000002247.
REBOA is a valuable resuscitative adjunct in a variety of clinical settings. In resource-limited or emergency environments, REBOA may be required with delayed or absent image-guidance or verification. Catheter insertion lengths may be informed by making CT correlations of skeletal landmarks with vascular lengths.
METHODS:
2247 trauma patients with CT imaging between 2000-2015 at a single civilian tertiary care center were identified, yielding 1789 patients with adequate contrast opacification of the arterial system in the chest, abdomen, and pelvis. Individual scans were analyzed using MATLAB software, with custom high-throughput image processing algorithms applied to correlate centerline vascular anatomy with musculoskeletal landmarks. Data were analyzed using R version 3.3.
RESULTS:
The median centerline distance from the skin access to the aortic bifurcation was longer by 0.3 cm on the right than on the left side. Median Aortic Zone I length was 21.6 (IQR, 20.3-22.9) cm, while Zone III was 8.7 (7.8-9.5) cm. Torso extent (TE) correlation to Zone I was much higher than for Zone III (R2 0.58 vs 0.26 (right) and 0.58 vs. 0.27 (left), p<0.001). Assuming a 4 cm balloon length, optimal fixed insertion length would be 48 cm and 28 cm for Zones I and III (Error 0.4% vs 33.3%), respectively, although out of zone placements can be reduced if adjusted for TE (Error 0% vs 26.4%).
CONCLUSIONS:
CT morphometry suggests a fixed REBOA catheter insertion length of 48 cm for Zone I and 28 cm for Zone III is optimal (on average, for average-height individuals), with improved accuracy by formulaic adjustments for torso extent. High residual error for Zone III placement may require redesign of existing catheter balloon lengths or consideration of the relative risk associated with placing the balloon catheter too low or too high.
An Anatomic Indexing System for Costal Cartilage and Its Application in Calcification Representation in Finite-Element Human Body Models.
Huang Y, Zhou Q, Wang SC, Nie BB, Holcombe SA.
International Research Council on Biomechanics of Injury, IRC-19-32.
Costal cartilage plays an important role in the structural stiffness of the ribcage as segments that flexibly connect the bony ribs to the sternum. Calcification of costal cartilage occurring throughout adult life can substantially change local material properties and stiffen the structural mechanical response. Current finite element (FE) human body models (HBMs) have a simplified representation of costal cartilage with homogeneous material properties, yet the FE meshes allow for discrete regions within a given mesh to be modeled using separate materials. To represent costal cartilage and its calcification across the population, this study proposed a consistent indexing system shared between HBMs as well as the real humans they represent. In this system, spatial positions in the costal cartilage are identified using a continuous coordinate space. This study also proposed a modeling framework to represent costal cartilage calcification in multiple models in a consistent fashion with real human data. This study successfully applied the indexing system to several current commercial FE HBMs and tested the ability of the framework with a limited set of real human data. The indexing system and modeling framework are expected to be a precursor to future study on the influence of calcification on mechanical responses of the ribcage.
Computed Tomography Evidence of Psoas Muscle Atrophy Without Concomitant Tendon Wasting in Early Sepsis.
Kubiak CA, Ranganathan K, Matusko N, Jacobson JA, Wang SC, Park PK, Levi BL.
Morphomic studies have demonstrated a correlation between sarcopenia and clinical outcomes in septic patients. However, tendon morphomics has not yet been studied in this context. The purpose of the present study was to evaluate tendon morphology in septic patients through analytic morphomics. We hypothesized that morphomic analyses would reveal concomitant muscle and tendon wasting in sepsis patients. The results of this study may help to implement different rehabilitation modalities for critically ill patients.
MATERIALS AND METHODS:
The volume and fat content of bilateral psoas muscles and tendons were measured on abdominal computed tomography scans of 25 ICU septic and 25 control trauma patients admitted to the University of Michigan between 2011 and 2012. Univariate and multivariate analyses were performed to determine the relationship between psoas muscle and tendon morphometric data, and the association with clinical variables such as smoking and comorbidities.
RESULTS:
Average psoas muscle volume was 12.21 ± 5.6 cm3 for control patients and 9.318 ± 3.3 cm3 in septic patients (P = 0.0023). The average psoas muscle/fat ratio for septic patients was 0.0288 ± 0.071 cm3, compared with 0.0107 ± 0.008 cm3 in the control group (P = 0.075). Average tendon volume in the septic population (0.508 ± 0.191 cm3) was not different than the control cohort (0.493 ± 0.182 cm3) (P = 0.692).
CONCLUSIONS:
Our results demonstrate significantly smaller psoas muscle volume in septic patients than in age-, gender-, and BMI-matched trauma patients but no demonstrable change in tendon morphology between patient groups. These findings begin to define the boundaries of clinical application within the field of morphomics.
The accuracy of local rib bone geometry measurement using full body CT images.
Holcombe SA, Wang SC.
International Research Council on Biomechanics of Injury, 2019, Paper ID 1767.
The ribs play a key structural role in the chest during dynamic loading, and future safety advancements will increasingly rely on the biofidelity of Human Body Models (HBMs). Rib geometry in HBMs is typically obtained via global imaging from CT, however for thin cortices such as those in ribs, traditional histogram-based segmentation is known to produce unacceptably high error. Here we test the accuracy of a new cortical bone mapping (CBM) algorithm in resolving these local geometries from globally obtained full-body CT scans, as well as from higher resolution scans of isolated ribs. Results from 11 cadaveric subjects' scanned ribs are compared to ground truth histology obtained from specific rib sections. The CBM methodology resolved the local thickness of cortical bone from isolated rib scans to within 0.01&0.14mm (mean±SD) error, and from full body scans to -0.04±0.20mm error. Average positional error in the placement of the rib's periosteal border was -0.01±0.13mm from full body scans using CBM, compared to
0.81±0.42mm for histogram-based thresholding of those same scans. Consequently, important mechanical properties are resolved to much higher accuracy using CBM, with total rib cross sectional area error reduced from 39±12% under traditional thresholding to under 5±2% when obtained using CBM. This study has shown that - given appropriate extraction methodologies - local geometric properties of rib
bones can be obtained from full-body CT imaging of human subjects. Results from this study open the door for subject-specific rib cortical bone thickness maps to be obtained for HBM validation and improvement
Validation of a DIXON-based fat quantification technique for the measurement of visceral fat using a CT-based reference standard.
Heckman KM, Otemuyiwa B, Chenevert TL, Malyarenko D, Derstine BA, Wang SC, MS.
The purpose of the study is to determine whether a novel semi-automated DIXON-based fat quantification algorithm can reliably quantify visceral fat using a CT-based reference standard.
METHODS:
This was an IRB-approved retrospective cohort study of 27 subjects who underwent abdominopelvic CT within 7 days of proton density fat fraction (PDFF) mapping on a 1.5T MRI. Cross-sectional visceral fat area per slice (cm2) was measured in blinded fashion in each modality at intervertebral disc levels from T12 to L4. CT estimates were obtained using a previously published semi-automated computational image processing system that sums pixels with attenuation - 205 to - 51 HU. MR estimates were obtained using two novel semi-automated DIXON-based fat quantification algorithms that measure visceral fat area by spatially regularizing non-uniform fat-only signal intensity or de-speckling PDFF 2D images and summing pixels with PDFF ≥ 50%. Pearson's correlations and Bland-Altman analyses were performed.
RESULTS:
Visceral fat area per slice ranged from 9.2 to 429.8 cm2 for MR and from 1.6 to 405.5 cm2 for CT. There was a strong correlation between CT and MR methods in measured visceral fat area across all studied vertebral body levels (r = 0.97; n = 101 observations); the least (r = 0.93) correlation was at T12. Bland-Altman analysis revealed a bias of 31.7 cm2 (95% CI [- 27.1]-90.4 cm2), indicating modestly higher visceral fat assessed by MR.
MR- and CT-based visceral fat quantification are highly correlated and have good cross-modality reliability, indicating that visceral fat quantification by either method can yield a stable and reliable biomarker.
Quantification of Sternum Morphomics and Injury Data.
Bunn B, Johannson S, Kohoyda-Inglis CJ, Parenteau C, Holcombe SA, Wang SC.
SAE international journal of transportation safety. 2019 January. doi:10.4271/2019-01-1217.
Crash safety researchers have an increased concern regarding the decreased thoracic deflection and the contributing injury causation factors among the elderly population. Sternum fractures are categorized as moderate severity injuries, but can have long term effects depending on the fragility and frailty of the occupant. Current research has provided detail on rib morphology, but very little information on sternum morphology, sternum fracture locations, and mechanisms of injury. The objective of this study is two-fold (1) quantify sternum morphology and (2) document sternum fracture locations using computed tomography (CT) scans and crash data. Thoracic CT scans from the University of Michigan Hospital database were used to measure thoracic depth, manubriosternal joint, sternum thickness and bone density.
The sternum fracture locations and descriptions were extracted from 63 International Center for Automotive Medicine (ICAM) crash cases, of which 22 cases had corresponding CT scans. The University of Michigan Internal Review Board (HUM00043599 and HUM00041441) approved the use of crash cases and CT scan data.The sternum morphomics data showed the thoracic depth increased, except for the 60-74-year-old age group. The average sternum thickness was greater in the older age groups. The sternum bone density decreased from youngest to oldest age groups. The angle between the manubrium and the sternum body decreased by 5.6° between the youngest and oldest age groups. The frequency of sternum fractures increased after age 45. Fractures were most frequent in the sternum body. The seat belt webbing was coded as the source of 54% of the sternum fractures.
Taking Control of Your Surgery: Impact of a Prehabilitation Program on Major Abdominal Surgery.
Howard R, Yin YS, McCandless L, Wang S, Englesbe M, Machado-Aranda D.
J Am Coll Surg. 2019 Jan;228(1):72-80. doi: 10.1016/j.jamcollsurg.2018.09.018. Epub 2018 Oct 22. PubMed PMID: 30359831; PubMed Central PMCID: PMC6309718.
Surgery is a major physiologic stress comparable to intense exercise. Diminished cardiopulmonary reserve is a major predictor of poor outcomes. Current preoperative workup focuses mainly on identifying risk factors; however, little attention is devoted to improving cardiopulmonary reserve beyond counseling. We propose that patients could be optimized for a "surgical marathon" similar to the preparation of an athlete.
STUDY DESIGN:
The Michigan Surgical and Health Optimization Program (MSHOP) is a formal prehabilitation program that engages patients in 4 activities before surgery: physical activity, pulmonary rehabilitation, nutritional optimization, and stress reduction. We prospectively collected demographic, intraoperative (first hour), and postoperative data for patients enrolled in MSHOP undergoing major abdominal surgery. Statistical analysis was performed using 2:1 propensity score matching to compare the MSHOP group (n = 40) to emergency (n = 40) and elective, non-MSHOP (n = 76) patients.
RESULTS:
Overall, 70% of MSHOP patients complied with the program. Age, sex, American Society of Anesthesiologists (ASA) classification, and BMI did not differ significantly between groups. One hour intraoperatively, MSHOP patients showed improved systolic and diastolic blood pressures and lower heart rate (Figure). There was a significant reduction in Clavien-Dindo class 3 to 4 complications in the MSHOP group (30%) compared with the nonprehabilitation (38%) and emergency (48%) groups (p = 0.05). This translated to total hospital charges averaging $75,494 for the MSHOP group, $97,440 for the nonprehabilitation group, and $166,085 for the emergency group (p < 0.001).
CONCLUSIONS:
Patients undergoing prehabilitation before colectomy showed positive physiologic effects and experienced fewer complications. The average savings of $21,946 per patient represents a significant cost offset for a prehabilitation program, and should be considered for all patients undergoing surgery.
2018
Morphomic Malnutrition Score: A Standardized Screening Tool for Severe Malnutrition in Adults.
Lee C, Raymond E, Derstine BA, Glazer JM, Goulson R, Rajasekaran A, Cherry‐Bukowiec J, Su GL, Wang SC.
JPEN J Parenter Enteral Nutr. 2018 May 22. doi: 10.1002/jpen.1175. [Epub ahead of print] PubMed PMID: 29786877.
Granular diagnostic criteria for adult malnutrition are lacking.
OBJECTIVE:
This study uses analytic morphomics to define the Morphomic Malnutrition Score (MMS), a robust screening tool for severe malnutrition.
METHODS:
The study population (n = 643) consisted of 2 cohorts: 1) 124 emergency department patients diagnosed with severe malnutrition by a registered dietitian (RD) and an available computed tomography (CT) scan within 2 days of RD evaluation, and 2) 519 adult kidney donor candidates to represent a healthy cohort. Body composition markers of muscle area and abdominal adiposity were measured from patient CT scans using analytic morphomic assessment, and then converted to sex- and age-adjusted percentiles using the Reference Analytic Morphomics Population (RAMP). RAMP consists of 6000 patients chosen to be representative of the general population. The combined cohort was then randomly divided into training (n = 453) and validation (n = 190) sets. MMS was derived using logistic regression. The model coefficients were transformed into a score, normalized from 0 to 10 (10 = most severe).
RESULTS:
Severely malnourished patients had lower amounts of muscle and fat than kidney donors, specifically for dorsal muscle group area at the twelfth thoracic vertebral level (P < 0.001), psoas muscle area at the fourth lumbar vertebral level (P < 0.001), and subcutaneous fat area at the third lumbar vertebral level (P < 0.001)-all parameters in MMS. MMS for severely malnourished patients was higher than kidney donors (7.7 ± 2.2 vs 3.8 ± 2.0, respectively; P-value < 0.001). An MMS > 6.1 was accurate in determining nutrition diagnosis (82.1% sensitivity; 88.3% specificity; 85.2% balanced accuracy).
CONCLUSIONS:
MMS provides an evidence-based, granular assessment to distinguish severely malnourished adults from a healthy population.
Measuring rib cortical bone thickness and cross section from CT.
This study assesses the ability to measure local cortical bone thickness, and to obtain mechanically relevant properties of rib cross-sections from clinical-resolution computed tomography (CT) scans of human ribs. The study utilized thirty-four sections of ribs published by Perz et al. (2015) in three modalities: standard clinical CT (clinCT), high-resolution clinical CT (HRclinCT), and microCT (µCT). Clinical-resolution images were processed using a Cortical Bone Mapping (CBM) algorithm applied to cross-cortex signals resampled perpendicularly to an initial smooth periosteal border. Geometric constraints were applied to remove outlier signals from consideration, and final predicted periosteal and endosteal borders from HRclinCT and clinCT were developed. Target values for local cortical thickness and for overall cross-sectional area and inertial properties were obtained from segmentation of the periosteal and endosteal borders on each corresponding µCT image. Errors in prediction (mean ± SD) of local cortical bone thickness for HRclinCT and clinCT resolutions were -0.03±0.17 mm and -0.05±0.22 mm, respectively, with R2 coefficients of determination from linear regression of 0.82 and 0.71 (p < 0.0001 for both). Predicted cortical shell measures derived from the periosteal and endosteal borders included total cross-sectional area (prediction errors of 6 ± 3% and -1±5% respectively for HRclinCT and clinCT with R2 correlations of 0.99 and 0.96), cortical shell area (errors of -3±8% and -8±11% with R2 correlations of 0.91 and 0.87), and principal area moment of inertia (errors of 2 ± 8% and -3±11% with R2 correlations of 0.98 and 0.95). Results here show substantial reductions in rib cross-sectional measurement error compared to past histogram-based thresholding methods and provide first validation of the CBM method when applied to rib bones. With the ubiquity of clinical CT scans covering the thorax and ribs, this study opens the door for individualized and population-wide quantification of rib structural properties and their corresponding effects on rib injury.
Thoracolumbar Spine Fracture occurring in Obese People involved in Motor Vehicle Crashes.
Ejima S, Holcombe SA, Zhang PC, Derstine BA, Goulson RL, MacWilliams J, Kohoyda-Inglis CJ, Wang SC.
International Research Council on the Biomechanics of Impact. 2018 September; :157-166.
Crash data from the International Center of Automotive Medicine (ICAM) database, with analytic morphomics, were used to evaluate thoracolumbar spine fractures for obese occupants in frontal crashes. Two BMI (Body Mass Index) groups (non‐obese and obese) with a maximum abbreviated injury scale (MAIS) in the spine region of >2 (MAIS-6S 2+) were categorised and compared. The fracture types were assessed based on
AIS for each occupant. Univariate analyses were conducted to investigate the association between analytic morphomics measures and thoracolumbar spine fracture.
The results indicate that MAIS 2+ injury occurred mainly in severe crashes with high delta‐V and large intrusion. Transverse process fractures were the most common AIS 2+ fractures, followed by minor compression type fractures (≤ 20% anterior height). Compared to the non‐obese occupants, the majority of obese occupants sustained transverse process fractures at lumbar vertebra with a higher incidence ratio. A statistical analysis was conducted, using vehicle, demographic, and morphomic variables, to explain the difference between transverse process fractures and vertebra body compression fractures. Transverse process fractures were related to BMI and vehicle factors (intrusion) in the obese group. In addition, morphomics related to fat distribution, muscle area, and cortical bone density are the major difference between non‐obese and obese occupants.
Skeletal muscle cutoff values for sarcopenia diagnosis using T10 to L5 measurements in a healthy US population.
Derstine BA, Holcombe SA, Ross BE, Wang NC, Su GL, Wang SC
Measurements of skeletal muscle cross-sectional area, index, and radiation attenuation utilizing clinical computed tomography (CT) scans are used in assessments of sarcopenia, the loss of skeletal muscle mass and function associated with aging. To classify individuals as sarcopenic, sex-specific cutoffs for 'low' values are used. Conventionally, cutoffs for skeletal muscle measurements at the level of the third lumbar (L3) vertebra are used, however L3 is not included in several clinical CT protocols. Non-contrast-enhanced CT scans from healthy kidney donor candidates (age 18-40) at Michigan Medicine were utilized. Skeletal muscle area (SMA), index (SMI), and mean attenuation (SMRA) were measured at each vertebral level between the tenth thoracic (T10) and the fifth lumbar (L5) vertebra. Sex-specific means, standard deviations (s.d.), and sarcopenia cutoffs (mean-2 s.d.) at each vertebral level were computed. Associations between vertebral levels were assessed using Pearson correlations and Tukey's difference test. Classification agreement between different vertebral level cutoffs was assessed using overall accuracy, specificity, and sensitivity. SMA, SMI, and SMRA L3 cutoffs for sarcopenia were 92.2 cm2, 34.4 cm2/m2, and 34.3 HU in females, and 144.3 cm2, 45.4 cm2/m2, and 38.5 HU in males, consistent with previously reported cutoffs. Correlations between all level pairs were statistically significant and high, ranging from 0.65 to 0.95 (SMA), 0.64 to 0.95 (SMI), and 0.63 to 0.95 (SMRA). SMA peaks at L3, supporting its use as the primary site for CT sarcopenia measurements. However, when L3 is not available alternative levels (in order of preference) are L2, L4, L5, L1, T12, T11, and T10. Healthy reference values reported here enable sarcopenia assessment and sex-specific standardization of SMA, SMI, and SMRA in clinical populations, including those whose CT protocols do not include L3.
Measurement of Skeletal Muscle Area Improves Estimation of Aminoglycoside Clearance across Body Size
Crass RL, Ross BE, Derstine BA, Lichty M, Sullivan JA, Su GL, Wang SC, Pai MP.
ABSTRACT: A consistent approach to the dosing of aminoglycosides across the modern body size distribution has been elusive. We evaluated whether radiologically derived measures of body composition could explain more of the interpatient variability in aminoglycoside pharmacokinetics (PK) than standard body size metrics. This retrospective study included adult patients treated with gentamicin or tobramycin with at least three drug concentrations and computed tomography (CT) imaging available. Aminoglycoside volume and clearance (CL) estimates were computed using a two-compartment model by Bayesian analysis. Morphomic data were extracted from CT images using a custom algorithm. Bivariable and multivariable linear regression were used to assess relationships between PK parameters and covariates. A total of 335 patients were included with a median (minimum, maximum) of 4 (3, 16) aminoglycoside concentrations per patient. The median (minimum, maximum) age, height, and weight of included patients were 57 (21, 93) years, 170 (145, 203) centimeters, and 81 (42, 187) kilograms. Both standard and morphomic measures poorly explained variability in volume (R2 < 0.06). Skeletal muscle area and volume explained more of the interpatient variability in CL than weight or sex. Higher precision was observed using a modified Cockcroft-Gault equation with skeletal muscle area at L3 (R2= 0.38) or L4 (R2= 0.37) than the standard Cockcroft-Gault equation using lean (R2= 0.23), adjusted (R2= 0.23), or total (R2= 0.22) body weights. These results highlight that skeletal muscle measurements from CT images obtained in the course of care can improve the precision of aminoglycoside CL estimation over current body size scalars.
Patient Engagement Drives the Positive Impact of Prehabilitation.
Owen H. Brown, BS; Brooke C. Kenney, MPH; Brian A. Derstine, MS; Dane R. Grenda, DO; June A. Sullivan, MBA; William C. Palazzolo, PA-C; Stewart C. Wang, MD, PhD; Michael J. Englesbe, MD
MJM Michigan Journal of Medicine 2018 April. DOI: 10.3998/mjm.13761231.0003.106.
BACKGROUND: The Michigan Surgical & Health Optimization Program (MSHOP) is a multimodal surgical prehabilitation program. Enrollment in MSHOP has been associated with significant reductions in length of stay (LOS) and cost of care. It remains unclear whether a relationship exists between patient participation level in program interventions and the cost-saving impact.
METHODS: We completed a retrospective analysis of patients enrolled in MSHOP between September 1, 2014, and December 31, 2015. Patients were categorized into two groups according to their degree of participation in the program: engaged or not engaged. We defined engaged patients as those who recorded steps in our system a minimum of three times per week for the majority (≥ 50%) of weeks they were enrolled in the program. Univariate analysis was used to compare hospital costs and expected payer payment for surgical admissions within each participation group. Five program intervention variables were regressed against actual cost using a linear mixed model to determine the intervention-specific effect on engaged patients.
RESULTS: A total of 82.7% of patients (N=370) were engaged in MSHOP. For engaged patients, the median actual cost (IQR) was $18,448 (range, $12,128-$26,955), and the median expected payment (IQR) was $22,397 (range, $14,736-$31,104), P<0.0001. No significant differences were observed in patients who were not engaged in the program. In multivariate analysis, total days enrolled and average weekly step count were associated with significant reductions in total cost among engaged patients (P=0.0029 and P=0.0296, respectively).
CONCLUSION: Patients who take an active role in surgical prehabilitation amplify the cost-savings impact compared to patients who merely enroll and participate.
Evaluating the "cushion effect" among children in frontal motor vehicle crashes
Harbaugh CM, Zhang P, Henderson B, Derstine BA, Holcombe SA, Wang SC, Kohoyda-Inglis C, Ehrlich PF.
. J Pediatr Surg. 2018 Feb 10. pii: S0022-3468(18)30096-4. doi: 10.1016/j.jpedsurg.2018.02.042. [Epub ahead of print] PubMed PMID: 29519566.
BACKGROUND: The "Cushion Effect," the phenomenon in which obesity protects against abdominal injury in adults in motor vehicle accidents, has not been evaluated among pediatric patients. This work evaluates the association between subcutaneous fat cross-sectional area, quantified using analytic morphomic techniques and abdominal injury.
METHODS: This retrospective study includes 119 patients aged 1 to 18years involved in frontal impact motor vehicle accidents (2003-2015) with computed tomography scans. Subcutaneous fat cross-sectional area was measured and converted to age- and gender-adjusted percentiles from population-based normative data. Multivariable analysis determined the risk of the primary outcome, Maximum Abbreviated Injury Scale (MAIS) 2+ abdominal injury, after adjusting for age, weight, seatbelt status, and impact rating.
RESULTS: MAIS 2+ abdominal injuries occurred in 20 (16.8%) of the patients. Subcutaneous fat area percentile was not significantly associated with MAIS 2+ abdominal injury on multivariable logistic regression (adjusted Odds Ratio, 0.86; 95% CI, 0.72-1.03; p=0.10).
DISCUSSION: The "cushion effect" was not apparent among pediatric frontal motor vehicle crash victims in this study. Future work is needed to investigate other analytic morphomic measures. By understanding how body composition relates to injury patterns, there is a unique opportunity to improve vehicle safety design.
Analytic Morphomics Predict Outcomes After Lung Transplantation.
Pienta MJ, Zhang P, Derstine BA, Enchakalody B, Weir WB, Grenda T, Goulson R, Reddy RM, Chang AC, Wang SC, Lin J.
Ann Thorac Surg. 2018 Feb;105(2):399-405. doi: 10.1016/j.athoracsur.2017.08.049. Epub 2017 Dec 2. PubMed PMID: 29198627; PubMed Central PMCID: PMC5783736.
BACKGROUND: The purpose of this study was to identify morphomic factors on standard, pretransplantation computed tomography (CT) scans associated with outcomes after lung transplantation.
METHODS: A retrospective review of 200 patients undergoing lung transplantation at a single institution from 2003 to 2014 was performed. CT scans obtained within 1 year before transplantation underwent morphomic analysis. Morphomic characteristics included lung, dorsal muscle group, bone, and subcutaneous and visceral fat area and density. Patient data were gathered from institutional and United Network for Organ Sharing databases. Outcomes, including initial ventilator support greater than 48 hours, length of stay, and survival, were evaluated using univariate and multivariable analyses.
RESULTS: On multivariable Cox regression, subcutaneous fat/total body area (hazard ratio [HR] 0.60, p = 0.001), lung density 3 volume (HR 0.67, p = 0.013), and creatinine (HR 4.37, p = 0.010) were independent predictors of survival. Initial ventilator support more than 48 hours was associated with decreased vertebral body to linea alba distance (odds ratio [OR] 0.49, p = 0.002) and Zubrod score 4 (OR 14.0, p < 0.001). Increased bone mineral density (p < 0.001) and increased cross-sectional body area (p < 0.001) were associated with decreased length of stay, whereas supplemental oxygen (p < 0.001), bilateral transplantation (p = 0.002), cardiopulmonary bypass (p < 0.001), and Zubrod score 3 (p < 0.001) or 4 (p = 0.040) were associated with increased length of stay.
CONCLUSIONS: Morphomic factors associated with lower metabolic reserve and frailty, including decreased subcutaneous fat, bone density, and body dimensions were independent predictors of survival, prolonged ventilation, and increased length of stay. Analytic Morphomics® using pretransplantation CT scans may improve recipient selection and risk stratification.
2017
Quantifying Sarcopenia Reference Values Using Lumbar and Thoracic Muscle Areas in a Healthy Population.
Derstine BA, Holcombe SA, Goulson RL, Ross BE, Wang NC, Sullivan JA, Su GL, Wang SC.
J Nutr Health Aging. 2017;21(10):180-185. doi: 10.1007/s12603-017-0983-3.
BACKGROUND: Sarcopenia is defined as the loss of skeletal muscle mass and function associated with aging. Muscle mass can be reliably and accurately quantified using clinical CT scans but reference measurements are lacking, particularly in healthy US populations.
METHODS: Two-phase CT scans from healthy kidney donors (age 18-40) at the University of Michigan between 1999-2010 were utilized. Muscle mass was quantified using two thoracic and two lumbar muscle cross-sectional area (CSA) measures. Indexed measurements were computed as area divided by height-squared. Paired analyses of non-contrast and contrast phases and different Hounsfield Unit (HU) ranges for muscle were conducted to determine their effect on CSA muscle measures. We report the means, standard deviations, and 2SD sarcopenia cutoffs from this population.
RESULTS: Healthy population CSA (cm2) cutoffs for N=604 males/females respectively were: 34.7/20.9 (T12 Dorsal Muscle), 91.5/55.9 (T12 Skeletal Muscle), 141.7/91.2 (L3 Skeletal Muscle), 23.5/14.3 (L4 Total Psoas Area), and 23.4/14.3 (L4 Psoas Muscle Area). Height-indexed CSA (cm2/m2) cutoffs for males/females respectively were: 10.9/7.8 (T12 Dorsal Muscle), 28.7/20.6 (T12 Skeletal Muscle), 44.6/34.0 (L3 Skeletal Muscle), 7.5/5.2 (L4 Total Psoas Area), and 7.4/5.2 (L4 Psoas Muscle Area). We confirmed that a mask of -29 to 150 HU is optimal and shows no significant difference between contrast-enhanced and non-contrast CT scan CSA measurements.
CONCLUSIONS: We quantified reference values for lumbar and thoracic muscle CSA measures in a healthy US population. We defined the effect of IV contrast and different HU ranges for muscle. Combined, these results facilitate the extraction of clinically valuable data from the large numbers of existing scans performed for medical indications.
Calcification of costal cartilage in the adult rib cage
248. Holcombe SA, Wang SC.
The 2017 IRCOBI Conference, Proceedings of the 2017 International Research Council on the Biomechanics of Impact.
ABSTRACT: Costal cartilage bridges the sternum and the ribs and plays a key role in the biomechanics of the chest. Costal cartilage is known to calcify in local regions with age, which can substantially stiffen its overall response to loading. However, the rate of accumulation of the calcified volume is not well quantified. Current computational models of the thorax assign a homogeneous soft material to cartilage segments, yet their finite element meshes are well suited to the specification of interstitial calcification zones, should applicable data become available.
This study measures volumes and extents of costal cartilage calcification from 205 live subject CT scans. Significant increases in volume calcification – both in a given cartilage segment and in the lengthwise extent of those segments that experience calcification – are seen with age (p<0.0001). Age and sex accounted for 35% of all inter‐individual population variability. Specific recommendations for introducing person‐age via regional calcification to models of the costal cartilage are that (1) calcification volume within a segment should increase at the rate of 0.9 mm (for an equivalent cube edge length) per decade, and (2) should involve an increasing lengthwise extent of the cartilage segment at a rate of at least 7% per decade.
The Effect of Rib Fracture Pattern in the Obese
Ejima S, Holcombe SA, Zhang P, Derstine BA, Goulson RL, MacWilliams J, Kohoyda-Inglis C, Wang SC.
The 2017 IRCOBI Conference, Proceedings of the 2017 International Research Council on the Biomechanics of Impact.
ABSTRACT: In this study, Analytic Morphomics® is applied to understand rib fractures in obese occupants in frontal and nearside crashes. Rib fracture patterns were examined in occupants involved in crashes from the International Center for Automotive Medicine database. Among these occupants, two BMI groups (nonobese and obese) with a maximum abbreviated injury scale in the chest region of > 3 (MAISthx3+) were categorized and compared. Univariate analyses were conducted for the BMI groups to compare the rib fracture incidence ratio in each rib and occupant factors based on morphomics variables. In frontal crashes, rib fractures were mainly located under the path of shoulder belt. For the obese group, fracture patterns tended to be located on the lower ribs (#6-8). In the nearside crashes, rib fractures were located in the lateral and posterior regions. For the obese group, fracture patterns tended to be located more laterally rather than posteriorly. Morphomics related to rib angle, fat in the back, and subcutaneous fat are the major differences between the groups. The current results for rib orientation and fat distribution can highlight the importance of considering these morphomics characteristics when assessing chest injury and creating obese computer models.
Second generation AACN injury severity prediction algorithm: development and real-world validation
Wang SC, Kohoyda-Inglis C, Ejima S, MacWilliams JB, Zhang P, Stacey L, Melocchi A, Gorman D, Kral J., Joyner, J.
Proceedings of 25th International Technical Conference on Enhanced Safety of Vehicles (ESV), Detroit, Michigan. June 2017. Paper No. 17-0133.
ABSTRACT: Advanced automatic collision notification(AACN)based injury severity prediction (ISP) has great potential to improve post-crash care.The national Expert Panel for Field Triage set 20% risk of Injury Severity Score (ISS) 15+ injury as the threshold for urgent transport to a trauma center.Earlier, we published an Injury Severity Prediction algorithm (ISP v1) that was developed using data from the National Automotive Sampling System Crashworthiness Data System (NASS_CDS) for the calendar years 1999-2008.In a field trialpublished at ESV 2015,this ISP algorithm version 1 demonstratedbetter than predicted sensitivity to detect seriously injured (ISS15+) crash occupants.In the current study, wesought to a) update the ISP algorithm using more current NASS-CDS data, b) improve predictive accuracy by refining the granularity of the input data, and c)validate the ability of this updated algorithm (ISP v2) using real-world crash cases involving GM vehicles equipped with OnStar.
NASS-CDS data (1999-2013) was used to develop a functional logistic regression model to predict the probability that a crash-involved vehicle would contain one or more occupants with ISS15+ injuries in planar, non-rollover crash events involving Model Year 2000 and newercars, light trucks, and vans. Two of the parameters used in the original ISP algorithm were modified (principal direction of force [PDOF], older occupant age) and a new parameter was created and involved the presence of a right-sided passenger.This study was approved by the IRB of the Michigan Department of Health and Human Services (formerly the Michigan Department of Community Health). The initial 924 occupants in 836 crashes published in the 2015 study were again opened for review and injury severity predictions from the updated algorithm werecompared to the observed injury outcomes.
The updated ISP v2, which employs the functional data analysis technique to model the effect of PDOF to ISS 15+ injury as a continuous cyclic function, showed an improved predictive performance (AUC 0.872, AIC 2370) over the original ISP v1 (AUC 0.865, AIC 2377) that used only 4 crash directions. The original elderly age cutoff of 55 performed better than an age cutoff of 60, so age ≥55 was retained as a parameter in ISP v2.Using field data for validation, the updated ISP algorithm had significantly improved sensitivity for detecting seriously injured (ISS15+) occupants (72.7% vs. 63.4%) with minimal changes in specificity (93% vs 94%). The AUROC for ISP v2 was 0.946, an improvement over the AUROC for ISP v1 (AUROC 0.932).
This study confirms under real world field conditions that occupant injury severity can be predicted using vehicle telemetry data. The updated ISPv2algorithm’s ability to predict a 20% or greater risk of severe (ISS15+) injury confirms ISP’s utility for the field triage of crash subjects.
Relationships of Vancomycin Pharmacokinetics to Body Size and Composition Using a Novel Pharmacomorphomic Approach Based on Medical Imaging.
Pai MP, Derstine BA, Lichty M, Ross BE, Sullivan JA, Su GL, Wang SC.
Antimicrob Agents Chemother. 2017 Oct 24;61(11). pii: e01402-17. doi: 10.1128/AAC.01402-17. Print 2017 Nov. PubMed PMID: 28807918; PubMed Central PMCID: PMC5655058.
Antibiotics such as vancomycin are empirically dosed on the basis of body weight, which may not be optimal across the expanding adult body size distribution. Our aim was to compare the relationships between morphomic parameters generated from computed tomography images to conventional body size metrics as predictors of vancomycin pharmacokinetics (PK). This single-center retrospective study included 300 patients with 1,622 vancomycin concentration (52% trough) measurements. Bayesian estimation was used to compute individual vancomycin volume of distribution of the central compartment (Vc) and clearance (CL). Approximately 45% of patients were obese with an overall median (5th, 95th percentile) weight and body mass index of 87.2 (54.7, 123) kg and 28.8 (18.9, 43.7) kg/m2, respectively. Morphomic parameters of body size such as body depth, total body area, and torso volume of the twelfth thoracic through fourth lumbar vertebrae (T12 to L4) correlated with Vc. The relationship of vancomycin Vc was poorly predicted by body size but was stronger with T12-to-L4 torso volume (coefficient of determination [R2] = 0.11) than weight (R2 = 0.04). No relationships between vancomycin CL and traditional body size metrics could be discerned; however, relationships with skeletal muscle volume and total psoas area were found. Vancomycin CL independently correlated with total psoas area and inversely correlated with age. Thus, vancomycin CL was significantly related to total psoas area over age (R2 = 0.23, P < 0.0001). This proof-of-concept study suggests a potential role for translation of radiographic information into parameters predictive of drug pharmacokinetics. Prediction of individual antimicrobial pharmacokinetic parameters using Analytic Morphomics® has the potential to improve antimicrobial dose selection and outcomes of obese patients.
The 'Cushion Effect' Is Not Protective for Children Involved in Motor Vehicle Crashes.
Calista Harbaugh, MD, Brianna Henderson, Peng Zhang, PhD, Brian Derstine, Sven A. Holcombe, PhD, Stewart Wang, MD, PhD, Peter F. Ehrlich, MD, FACS
Journal of the American College of Surgeons, October 2017. Volume 225, Issue 4, e187 - e188
INTRODUCTION: Analytic Morphomics® (AM) applies computa- tional image processing algorithms to cross-sectional images to perform detailed measurements on morphological features in 3D space. In adults, data suggests that body composition can impact the risk and pattern of injury in motor vehicle crashes (MVC) with increased BMI protecting against abdominal injuries and pelvic fractures. This is known as the "cushion effect." The purpose of this study is to examine the impact of the "cushion effect" on thoracic, abdominal and spine injuries in children involved in fron- tal MVC.
METHODS: Retrospective chart review and AM were performed on 617 patients admitted to the University of Michigan after MVC. Injury severity was assessed using maximum abbreviated injury score (MAIS) and crash impact rating was derived from crash reporting forms (UD-10). AM measures included visceral fat cross-sectional area, subcutaneous fat cross-sectional area, trabecular bone density and psaos muscle area at L4 vertebral level.
RESULTS: Of the 617 MVC, 212 were frontal crashes and included in the study. The population was 45% male with average age 12.4 ± 5.0 years. Sex, age and impact rating did not correlate with MAIS. Subcutaneous fat cross-sectional area, visceral fat cross-sectional area, bone density and psoas muscle area did not correlate with injury severity for MAIS 2+ abdominal, thoracic or spinal injuries.
CONCLUSIONS: Though subcutaneous fat has previously correlated with decreased abdominal and pelvic injury in adults, this study shows that subcutaneous fat does not impact the risk of thoracic, abdominal or spine injuries in children involved in frontal crashes.
Morphometric age and survival following kidney transplantation.
Terjimanian MN, Underwood PW, Cron DC, Augustine JJ, Noon KA, Cote DR, Wang SC, Englesbe MJ, Woodside KJ.
Clin Transplant. 2017 Oct;31(10). doi: 10.1111/ctr.13066. Epub 2017 Aug 28. Erratum in: Clin Transplant. 2017 Dec 16;:. PubMed PMID: 28758236.
BACKGROUND: As patients with chronic kidney disease become older, there is greater need to identify who will most benefit from kidney transplantation. Analytic Morphomics® has emerged as an objective risk assessment tool distinct from chronologic age. We hypothesize that morphometric age is a significant predictor of survival following transplantation.
METHODS: A retrospective cohort of 158 kidney transplant patients from 2005 to 2014 with 1-year preoperative imaging was identified. Based on a control population comprising of trauma patients and kidney donors, morphometric age was calculated using the validated characteristics of psoas area, psoas density, and abdominal aortic calcification. The primary outcome was post-transplant survival.
RESULTS: Cox regression showed morphometric age was a significant predictor of survival (hazard ratio, 1.06 per morphometric year [95% confidence interval, 1.03-1.08]; P < .001). Chronological age was not significant (hazard ratio, 1.03 per year [0.98-1.07]; P = .22). Among the chronologically oldest patients, those with younger morphometric age had greater survival rates compared to those with older morphometric age.
CONCLUSIONS: Morphometric age predicts survival following kidney transplantation. Particularly for older patients, it offers improved risk stratification compared to chronologic age. Morphomics may improve the transplant selection process and provide a greater assessment of prospective survival benefits.
Using Analytic Morphomics® to describe body composition associated with post-kidney transplantation diabetes mellitus.
Cron DC, Noon KA, Cote DR, Terjimanian MN, Augustine JJ, Wang SC, Englesbe MJ, Woodside KJ.
BACKGROUND: Better risk assessment tools are needed to predict post-transplantation diabetes mellitus (PTDM). Using analytic morphomic measurements from computed tomography (CT) scans, we aimed to identify specific measures of body composition associated with PTDM.
METHODS: We retrospectively reviewed 99 non-diabetic kidney transplant recipients who received pre-transplant CT scans at a single institution between 1/2005 and 5/2014. Analytic morphomic techniques were used to measure abdominal adiposity, abdominal size, and psoas muscle area and density, standardized by gender. We measured the associations of these morphomic factors with PTDM.
RESULTS: One-year incidence of PTDM was 18%. The morphomic factors significantly associated with PTDM included visceral fat area (OR=1.84 per standard deviation increase, P=.020), body depth (OR=1.79, P=.035), and total body area (OR=1.67, P=.049). Clinical factors significantly associated with PTDM included African American race (OR=3.01, P=.044), hypertension (OR=2.97, P=.041), and dialysis vintage (OR=1.24 per year on dialysis, P=.048). Body mass index was not associated with PTDM (OR=1.05, P=.188). On multivariate modeling, visceral fat area was an independent predictor of PTDM (OR=1.91, P=.035).
CONCLUSIONS: Analytic Morphomics® can identify pre-transplant measurements of body composition that are predictive of PTDM in kidney transplant recipients. Pre-transplant imaging contains a wealth of underutilized data that may inform PTDM prevention strategies.
Dorsal Muscle Attenuation May Predict Failure to Respond to Interleukin-2 Therapy in Metastatic Renal Cell Carcinoma.
Otemuyiwa B, Derstine BA, Zhang P, Wong SL, Sabel MS, Redman BG, Wang SC, Alva AS, MS.
RATIONALE AND OBJECTIVES: To explore whether the sarcopenia body type can help predict response to interleukin-2 (IL-2) therapy in metastatic renal cell carcinoma (RCC).
MATERIALS AND METHODS: Institutional review board approval was obtained for this Health Insurance Portability and Accountability Act-compliant retrospective cohort study of 75 subjects with metastatic RCC who underwent pretreatment contrast-enhanced computed tomography within 1 year of initiating IL-2 therapy. Cross-sectional area and attenuation of normal-density (31-100 Hounsfield units [HU]) and low-density (0-30 HU) dorsal muscles were obtained at the T11 vertebral level. The primary outcome was partial or complete response to IL-2 using RECIST 1.1 criteria at 6 weeks. A conditional inference tree was used to determine an optimal HU cutoff for predicting outcome. Bonferroni-adjusted multivariate logistic regression was conducted to investigate the independent associations between imaging features and response after controlling for demographics, doses of IL-2, and RCC prognostic scales (eg, Heng and the Memorial Sloan Kettering Cancer Center [MSKCC]).
RESULTS: Most subjects had intermediate prognosis by Heng (65% [49 of 75]) and the MSKCC (63% [47 of 75]) criteria; 7% had complete response and 12% had partial response. Mean attenuation of low-density dorsal muscles was a significant univariate predictor of IL-2 response after Bonferroni correction (P = 0.03). The odds of responding to treatment were 5.8 times higher for subjects with higher-attenuation low-density dorsal muscles (optimal cutoff: 18.1 HU). This persisted in multivariate analysis (P = 0.02). Body mass index (P = 0.67) and the Heng (P = 0.22) and MSKCC (P = 0.08) clinical prognostic scales were not significant predictors of response.
CONCLUSIONS: Lean cross-sectional attenuation of low-density dorsal muscles (ie, sarcopenia) may predict IL-2 response in metastatic RCC. Clinical variables are poor predictors of response.
Elderly populations have a higher risk of rib fractures and other associated thoracic injuries than younger adults, and the changes in body morphology that occur with age are a potential cause of this increased risk. Rib centroidal path geometry for 20,627 ribs was extracted from computed tomography (CT) scans of 1042 live adult subjects, then fitted to a six-parameter mathematical model that accurately characterizes rib size and shape, and a three-parameter model of rib orientation within the body. Multivariable regression characterized the independent effect of age, height, weight, and sex on the rib shape and orientation across the adult population, and statistically significant effects were seen from all demographic factors (P < 0.0001). This study reports a novel aging effect whereby both the rib end-to-end separation and rib aspect ratio are seen to increase with age, producing elongated and flatter overall rib shapes in elderly populations, with age alone explaining up to 20 percent of population variability in the aspect ratio of mid-level ribs. Age was not strongly associated with overall rib arc length, indicating that age effects were related to shape change rather than overall bone length. The rib shape effect was found to be more strongly and directly associated with age than previously documented age-related changes in rib angulation. Other demographic results showed height and sex being most strongly associated with rib size, and weight most strongly associated with rib pump-handle angle. Results from the study provide a statistical model for building rib shapes typical of any given demographic by age, height, weight, and sex, and can be used to help build population-specific computational models of the thoracic rib cage. Furthermore, results also quantify normal population ranges for rib shape parameters which can be used to improve the assessment and treatment of rib skeletal deformity and disease.
Body Composition Predicts Survival in Patients with Hepatocellular Carcinoma Treated with Transarterial Chemoembolization.
PURPOSE: The prognosis of patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) is often uncertain. We aimed to utilize Analytic Morphomics®, a high-throughput imaging analysis, to assess if body composition is predictive of post-TACE survival.
MATERIALS AND METHODS: MATERIALS AND METHODS: We included patients from a single center (Ann Arbor VA)who had TACE as the primary treatment forHCC and had a pre-treatment computed tomography scans. Univariate analysis and multivariate conditional inference tree analysis were utilized to identify the morphomic characteristics predictive of 1-year survival. Results were validated in an external cohort(University of MichiganHealth System) ofHCC patientswho underwent TACE as their primary treatment.
RESULTS: In the 75 patients in the derivation cohort, median survival was 439 (interquartile range, 377 to 685) days from receipt of TACE, with 1-year survival of 61%. Visceral fat density (VFD) was the only morphomic factor predictive of overall and 1-year survival (p < 0.001). Patients with VFD above the 56th percentile had a 1-year survival of 39% versus 78% for those below the 56th percentile. VFD also correlated with 1-year survival in the external validation cohort (44% vs. 72%, p < 0.001). In a secondary analysis, patients with higher VFD were significantly more likely to experience hepatic decompensation after TACE (p < 0.001).
CONCLUSIONS: VFD served as an objective predictor of mortality in patients undergoing TACE, possibly through its ability to predict hepatic decompensation. VFD may serve as a radiographic biomarker in predicting TACE outcomes.
Can Comprehensive Imaging Analysis with Analytic Morphomics® and Geriatric Assessment Predict Serious Complications in Patients Undergoing Pancreatic Surgery?
Benjamin AJ, Buschmann MM, Schneider A, Derstine BA, Friedman JF, Wang SC, Dale W, Roggin KK
We aimed to determine whether comprehensive imaging analysis with Analytic Morphomics® (AM) enhances or replaces geriatric assessment (GA) in risk-stratifying pancreatic surgery patients. One hundred thirty-four pancreatic surgery patients were identified from a prospective cohort. Sixty-three patients in the cohort had preoperative CT scans in addition to comprehensive geriatric assessments. CT scans were processed using AM. Associations with National Surgical Quality Improvement Program (NSQIP) serious complications were evaluated using univariate analysis and robust elastic net modeling to obtain AUROC curves by adding AM and GA measures to our previously defined clinical base risk model (age, body mass index, American Society of Anesthesiologists classification, and Charlson comorbidity index). NSQIP serious complications were associated with low psoas Hounsfield units (HUs) (p = 0.002), low-density (0 to 30 HU) psoas area (p = 0.01), visceral fat HU (p ≤ 0.001), visceral fat area (p = 0.009), subcutaneous fat HU (p = 0.023), and total body area (p = 0.012) on univariate analysis. Elastic net models incorporating the base model with geriatric assessment and psoas HU (AUC = 0.751), and AM alone (AUC = 0.739) have greater predictive value than the base model alone (AUC = 0.601). The model utilizing AM and GA in combination had the highest predictive value (AUC = 0.841). When combined, AM and GA improve prediction of NSQIP serious complications compared to either technique alone. The additive nature of these two modalities suggests they likely capture unique aspects of a patient's fitness for surgery.
The Michigan Surgical Home and Optimization Program is a scalable model to improve care and reduce costs.
Englesbe MJ, Grenda DR, Sullivan JA, Derstine BA, Kenney BN, Sheetz KH, Palazzolo WC, Wang NC, Goulson RL, Lee JS, Wang SC.
Surgery. 2017 Feb 4. pii: S0039-6060(16)30880-7. doi: 10.1016/j.surg.2016.12.021. [Epub ahead of print]
The Michigan Surgical Home and Optimization Program is a structured, home-based, preoperative training program targeting physical, nutritional, and psychological guidance. The purpose of this study was to determine if participation in this program was associated with reduced hospital duration of stay and health care costs.
METHODS
We conducted a retrospective, single center, cohort study evaluating patients who participated in the Michigan Surgical Home and Optimization Program and subsequently underwent major elective general and thoracic operative care between June 2014 and December 2015. Propensity score matching was used to match program participants to a control group who underwent operative care prior to program implementation. Primary outcome measures were hospital duration of stay and payer costs. Multivariate regression was used to determine the covariate-adjusted effect of program participation.
RESULTS
A total of 641 patients participated in the program; 82% were actively engaged in the program, recording physical activity at least 3 times per week for the majority of the program; 182 patients were propensity matched to patients who underwent operative care prior to program implementation. Multivariate analysis demonstrated that participation in the Michigan Surgical Home and Optimization Program was associated with a 31% reduction in hospital duration of stay (P < .001) and 28% lower total costs (P < .001) after adjusting for covariates.
CONCLUSION
A home-based, preoperative training program decreased hospital duration of stay, lowered costs of care, and was well accepted by patients. Further efforts will focus on broader implementation and linking participation to postoperative complications and rigorous patient-reported outcomes.
SPECT/CT in the Evaluation of Frostbite
Kraft C1, Millet JD, Agarwal S, Wang SC, Chung KC, Brown RK, Levi B.
J Burn Care Res. 2017 Jan/Feb;38(1):e227-e234. doi: 10.1097/BCR.0000000000000359.
Frostbite remains a challenging clinical scenario with multiple treatment algorithms and variable results. Currently, frostbite management often follows a conservative approach with rewarming followed by wound care and delayed amputation. We review seven patients where single-photon emission computed tomography (SPECT) fused with conventional computed tomography was used to evaluate tissue viability for earlier directed debridement and limb salvage. The goal of this report is to evaluate SPECT/CT as an appropriate modality for the screening of necrotic bone for earlier amputation in patients with frostbite. We retrospectively analyzed the records of seven patients (19 extremities) with frostbite who received SPECT/CT scans to evaluate deep tissue necrosis before digit amputation. All patients who presented within the first 24 hr following their injury without contraindications were initially treated with tissue plasminogen activator. Three patients met criteria and were treated with tissue plasminogen activator. Of the seven patients analyzed, none required revision amputation beyond the level predicted on SPECT/CT scan. No patients had viable tissue distal to the most distal extent of bone perfusion. In six of the patients, the SPECT/CT scan led to more distal amputation with proximal debridement of soft tissues thus maintaining extremity length. Frostbite remains a challenging clinical scenario for which there are a wide number of clinical algorithms. SPECT/CT appears to be valuable in the evaluation of frostbite to determine the need for amputation. Fusion of the nuclear images with the CT allows for more exact delineation of the level of amputation than a bone scan alone.
Personalized medicine: Enhancing our understanding of pediatric growth with Analytic Morphomics®.
Harbaugh CM, Zhang P, Henderson B, Derstine BA, Holcombe SA, Wang SC, Kohoyda-Inglis C, Ehrlich PF.
J Pediatr Surg. 2017 Jan 29. pii: S0022-3468(17)30063-5. doi: 10.1016/j.jpedsurg.2017.01.030. [Epub ahead of print]
Analytic Morphomics® is being used to identify 3-D biologic measures with superior clinical utility and risk stratification over traditional factors such as age, height, and weight. The purpose of this study is to define age and gender specific Pediatric Reference Analytic Morphomics® Population (PRAMP™) growth charts.
METHODS
This retrospective study population contains 2591 individual CT scans of a normative reference population of males and females (1-20years old). Growth curves were constructed at the 5th, 25th, 50th, 75th, and 95th quantiles for morphomic variables, including psoas muscle area, trabecular bone density, and visceral fat area by age and gender.
RESULTS
Total psoas muscle area increases over time until late adolescence. Trabecular bone density remains stable until adolescence, decreases during adolescence, and increases in young adulthood. Visceral fat area increases over time with greater variation between the 5th and 95th percentile with increasing age.
CONCLUSIONS
The PRAMP™ data have been used to construct age- and sex-specific reference growth curves. This may be used to better define "abnormal" in efforts to create unique risk-categorization algorithms specific to particular clinical and global health investigations.
LEVEL OF EVIDENCE
Level II
Preoperative Psoas Muscle Size Predicts Postoperative Delirium in Older Adults Undergoing Surgery: A Pilot Cohort Study.
Miller AL, Englesbe MJ, Diehl KM, Chan CL, Cron DC, Derstine BA, Palazzolo WC, Hall KE, Wang SC3, Min LC.
J Am Geriatr Soc. 2017 Jan;65(1):e23-e24. doi: 10.1111/jgs.14571. Epub 2016 Dec 19.
The authors previously reported that adenosine triphosphate (ATP) stimulates biofilm formation and removal of the ATP could reduce biofilm formation. The main objective of this study was to evaluate the effects of the ATP-hydrolyzing enzyme, apyrase, on control of Acinetabacter baumannii infection in the burn wound as well as to assess host skin antimicrobial responses. The authors found that apyrase stimulated nitric oxide formation at the wound site and reduced CD55 expression, thereby inducing the assembly of membrane attack complexes. Apyrase treatment nearly eradicated multidrug-resistant A. baumannii from burn wounds in the absence of antibiotics. Apyrase may be an effective therapy against antibiotic-resistant bacterial infections in burns.
Variation in Optimal Sagittal Alignment of the Femoral Component in Total Knee Arthroplasty
Hood B, Blum L, Holcombe SA, Wang SC, Urquhart AG, Goulet JA, Maratt JD.
Orthopedics. 2016 Nov 11:1-5. doi: 10.3928/01477447-20161108-04. [Epub ahead of print]
Accurate sagittal alignment of the femoral component in total knee arthroplasty is crucial for prosthesis longevity, improved function, and patient satisfaction. However, there is variation in the techniques used to attain optimal sagittal femoral component placement in total knee arthroplasty. Femoral component flexion in imageless navigation is based on the mechanical axis rather than the distal femoral anatomy, and there is significant variability in the anatomy of the distal femur. The purpose of this study was to accurately determine the mean distal femoral flexion angle of a representative population and whether variability of the distal femoral flexion angle correlates with race, femur length, or radius of curvature. The mean degree of distal femoral flexion was determined by assessing distal femoral anatomy on computed tomography scans of paired femurs of 1235 patients without evidence of previous fracture, deformity, or surgical implants. The mean±SD distal femoral flexion angle was 2.90º±1.52º, with 80.2% of knees within 3º±2º. Therefore, placing the component in 3º of flexion from the mechanical axis would attain a satisfactory position in most cases. However, further analysis of the patient data revealed 11.4% of Asians, 7.3% of African Americans, and 8.3% of whites had a distal femoral flexion angle greater than 5º. Additionally, the data revealed a moderately strong negative correlation between the distal femoral flexion and the overall radius of curvature of the femur. This preliminary study highlights the need for improved methods for selecting femoral component position in the sagittal plane when using navigation for total knee arthroplasty. [Orthopedics. 201x; xx(x):xxx-xxx.].
Previous studies of frontal crash databases reported that ankle fractures are among the most common lower extremity fractures. While not generally life threatening, these injuries can be debilitating. Laboratory research into the mechanisms of ankle fractures has linked dorsiflexion with an increased risk of tibia and fibula malleolus fractures. However, talus fractures were not produced in the laboratory tests and appear to be caused by more complex loading of the joint. In this study, an analysis of the National Automotive Sampling System - Crashworthiness Data System (NASS-CDS) for the years 2004-2013 was conducted to investigate foot-ankle injury rates in front seat occupants involved in frontal impact crashes. A logistic regression model was developed indicating occupant weight, impact delta velocity and gender to be significant predictors of talus fracture (p<0.05). Separately, a specific set of Computed Tomography (CT) scans from the International Center for Automotive Medicine (ICAM) scan database was used to characterize the talar dome. This control population consisted of 207 adults aged 18 to 84, with no foot or ankle trauma, and scans that had suitable coverage of the talus. Size of the talus was determined using medial-to-lateral width and anterior-to-posterior depth measurements. Geometry was assessed by evaluating the radius of the articulating talus and strength was assessed using a combination of cross sectional area and density. Demographics were studied to investigate correlation with talus measurements from the CT scan database. A multi-variable linear regression model of the morphomics showed gender to be statistically significant (p<0.05) for talus depth, width, cross-sectional area, radius and strength. Body Mass Index (BMI) was significant for depth and radius. Weight was significant for depth, width, density and strength. Stature was significant for depth, cross-sectional area, radius and strength. Age was significant for radius and density.
This study investigates the isolated effect of rib shape on the mechanical characteristics of ribs subjected to multiple forms of loading. It aims to measure the variation in stiffness due to shape that is seen throughout the population and, in particular, provide a tool for researchers to better understand the influence of shape on resulting stiffness. A previously published six-parameter shape model of the central axis of human ribs was used. It has been shown to accurately model the overall rib path using intrinsic geometric properties such as size, aspect ratio, and skewness, through shapes based on logarithmic spirals with high curvature continuity. In this study the model was fitted to 19,500 ribs from 989 adult female and male CT scans having demographic distributions matching the US adult population. Mechanical loading was simulated through a simplified finite element model aimed at isolating rib shape from other factors influencing mechanical response. Four loading scenarios were used representing idealized free and constrained loading conditions in axial (body-anterior) and lateral directions. Characteristic rib stiffness and maximum stress location were tracked as simulation output measures. Regression models of rib stiffness found that all shape model parameters added information when predicting stiffness under each loading condition, with their linear combination able to account for 95% of the population stiffness variation due to shape in midlevel ribs for free axial loading, and 92%-98% in other conditions. Full regression models including interactive terms explained up to 99% of population variability. Results allow researchers to better evaluate the differences in stiffness results that are obtained from physical testing by providing a framework with which to explain variation due to rib shape.
The role of the adaptive immune system in burn-induced heterotopic ossification and mesenchymal cell osteogenic differentiation
Ranganathan K, Agarwal S, Cholok D, Loder S, Li J, Sung Hsieh HH, Wang SC, Buchman SR, Levi B.
Heterotopic ossification (HO) is the pathologic process of extraskeletal bone formation. Although the exact etiology remains unknown, inflammation appears to catalyze disease progression. The goal of this study is to determine the impact of the adaptive immune system on HO.
METHODS
HO was induced in 8-wk-old control C57BL/6 and immunocompromised Rag1tm1Mom (Rag1 KO) male mice deficient in B- and T-lymphocytes via combined Achilles tenotomy and burn injury. Microcomputed tomography quantified the extent of HO formation at the tenotomy site. Adipose-derived mesenchymal stem cells were harvested to evaluate osteogenic differentiation potential.
RESULTS
Areas of developing HO demonstrated substantial enrichment of CD45 + leukocytes at 3 wk after injury. HO from Rag1 KO mice was substantially less mature with foci of cartilage and disorganized trabecular bone present 12 wk after injury. Rag1 KO mice formed 60% less bone compared to immunocompetent controls (4.67 ± 1.5 mm versus 7.76 ± 0.65 mm; P = 0.001). Tartrate-resistant acid phosphatase staining and immunofluorescent analysis of osteoprotegerin and nuclear factor kappa-light-chain-enhancer of activated B cells demonstrated no appreciable difference in osteoclast number or activation. Alizarin red staining in vitro demonstrated a significant decrease in osteogenic potential in immunocompromised mice compared to controls (29.1 ± 0.54 mm versus 12.1 ± 0.14 mm; P < 0.001).
Application of Analytic Morphomics® for belted elderly occupants in frontal crashes
Ejima S, Holcombe SA, Zhang P, Derstine BA, Goulson RL, Williams JM, Kohoyda-Inglis C, Wang SC.
International Research Council on Biomechanics of Injury. 2016 Sep. Session S2-9 - Thorax Injury/Injury to the Upper Extremities: IRC-16-105.
In this study, we used Analytic Morphomics® to understand the mechanisms of rib fracture for older occupants in frontal crashes. Analytic Morphomics® extracts body features from computered tomography scans of people involved in vehicle crashes who have been treated at the University of Michigan, a Level-1 trauma center. Chest injury and rib fracture patterns were examined in belted, front row occupants involved in frontal crashes from the International Center for Automotive Medicine database. Among these occupants, two age groups (younger and older) with the maximum abbreviated injury scale of chest region ≥ 3(MAISthx3+) were categorized. The location of each rib fracture was compared between the groups. Regression analyses were conducted to investigate fracture outcomes considering risk factors including vehicle, demographics, and morphomics. The rib fractures of belted occupants were mainly located under the path of the shoulder belt. For the older group, fracture patterns tended to be located in the anterior region but also bilaterally. Moreover, morphomic factors related to rib shape are the major driver of rib fracture for the older group. The current results for rib shape can highlight the importance of considering these morphomics characteristics when assessing chest injury and creating elderly computer models.
Reference Analytic Morphomics® population (RAMP): A reference to measure occupant variability for crash injury analysis
Wang SC, Holcombe SA, Derstine BA, Goulson RL, Grenda DR, Ruan J, Rabban P, Wang NC, Friedman JF, Cron DC, Henderson BC, Sullivan JA, Kohoyda-Inglis C, Su GL, Ejima S, Zhang P.
International Research Council on Biomechanics of Injury. 2016 Sep. Session S2-4 - Accident Analysis/Vehicle Technology: IRC-16-80.
Real world crash injuries occur to a large and highly variable population. Analytic Morphomics® measures very detailed geometry and material characteristics for tissues, organs, and bones throughout the body using automated processing of medical imaging scans. We analyzed 416 occupants involved in motor vehicle crashes with full crash investigation as well as medical imaging scans and found that morphomic data improved risk stratification for thoracic 3+ injury in both frontal and side impact crashes. We then sought to define the population distribution of the morphomic factors identified to be significantly predictive of crash injury risk to the thorax. Chest, abdomen, and pelvis CT scans were collected from 5,268 patients, aged 16 to 91 years, at the University of Michigan, who were scanned primarily for trauma indications. This curated population, named the Adult Reference Analytic Morphomics® Population (RAMP), is representative of typical vehicle occupants in the United States. Customized software was used to perform automated processing of these CT scans and to store detailed body geometry and composition data in an anatomically-indexed format. Quantile regression was performed to generate curves of morphomic factors corresponding to the 5th, 25th, 50th, 75th, and 95th percentiles from ages 16-91 for both men and women respectively. This is a very detailed body composition study based on a large cohort of people.
Fat Thickness as a Risk Factor for Infection in Lumbar Spine Surgery
Lee JJ, Odeh KI, Holcombe SA, Patel RD, Wang SC, Goulet JA, Graziano GP.
Orthopedics. 2016 Aug 30:1-5. doi: 10.3928/01477447-20160819-05. [Epub ahead of print]
Body mass index does not account for body mass distribution. This study tested the hypothesis that subcutaneous fat thickness is a better indicator than body mass index of the risk of surgical site infection in lumbar spine procedures performed through a midline posterior approach. Charts were reviewed for previously identified risk factors for surgical site infection (age, diabetes, smoking, obesity, albumin level, multilevel procedures, previous surgery, and operative time) in 149 adult patients who underwent lumbar spine procedures through a midline posterior approach. Subcutaneous fat thickness was measured with a novel automated technique. Regression analysis was used to determine associations between risk factors and fat thickness with surgical site infection. In the study group, 15 surgical site infections occurred (10.1%). Bivariate analysis showed a significant association between surgical site infection and body mass index (P=.01), obesity (P=.02), and fat thickness (P=.002). With multivariate analysis, body mass index and obesity did not show significance, but fat thickness remained significant (P=.026). For every 1-mm thickness of subcutaneous fat there was a 6% (odds ratio, 1.06; 95% confidence interval, 1.02-1.10) increase in the odds of surgical site infection, and patients with fat thickness of greater than 50 mm had a 4-fold increase in the odds of surgical site infection compared with those with fat thickness of less than 50 mm. Body mass index and fat thickness were moderately correlated (r2=0.44). These results confirm the hypothesis that local subcutaneous fat thickness is a better indicator than body mass index of the risk of surgical site infection in lumbar spine procedures. [Orthopedics. 201x; xx(x):exxx-exxx.].
Bone mineral density predicts posttransplant survival among hepatocellular carcinoma liver transplant recipients
Sharma P, Parikh ND, Yu J, Barman P, Derstine BA, Sonnenday CJ, Wang SC, Su GL
Liver Transpl. 2016 Aug;22(8):1092-8. doi: 10.1002/lt.24458. Epub 2016 Jun 29.
Hepatocellular carcinoma (HCC) is a common indication for liver transplantation (LT). Recent data suggest that body composition features strongly affect post-LT mortality. We examined the impact of body composition on post-LT mortality in patients with HCC. Data on adult LT recipients who received Model for End-Stage Liver Disease exception for HCC between February 29, 2002, and December 31, 2013, and who had a computed tomography (CT) scan any time 6 months prior to LT were reviewed (n = 118). All available CT scan Digital Imaging and Communication in Medicine files were analyzed using a semiautomated high throughput methodology with algorithms programmed in MATLAB. Analytic Morphomics® measurements including dorsal muscle group (DMG) area, visceral and subcutaneous fat, and bone mineral density (BMD) were taken at the bottom of the eleventh thoracic vertebral level. Thirty-two (27%) patients died during the median follow-up of 4.4 years. The number of HCC lesions (hazard ratio [HR], 2.81; P < 0.001), BMD (HR = 0.90/Hounsfield units [HU]; P = 0.03), pre-LT locoregional therapy (HR = 0.14; P < 0.001), and donor age (HR = 1.05; P < 0.001) were the independent predictors of post-LT mortality. DMG area did not affect post-LT survival. In conclusion, in addition to number of HCC lesions and pre-LT locoregional therapy, low BMD, a surrogate for bone loss rather than DMG area, was independently associated with post-LT mortality in HCC patients. Bone loss may be an early marker of deconditioning that precedes sarcopenia and may affect transplant outcomes. Liver Transplantation 22 1092-1098 2016 AASLD.
Modeling female and male rib geometry with logarithmic spirals
In this study we present a novel six-parameter shape model of the human rib centroidal path using logarithmic spirals. It provides a reduction in parameter space from previous models of overall rib shape, while simultaneously reducing fitting error by 34% and increasing curvature continuity. Furthermore, the model directly utilizes geometric properties such as rib end-to-end span, aspect ratio, rib "skewness", and inner angle with the spine in its parameterization, making the effects of each parameter on overall shape intuitive and easy to visualize. The model was tested against 2197 rib geometries extracted from CT scans from a population of 100 adult females and males of uniformly distributed ages between 20 and 70. Significant size and shape differences between genders were identified, and shape model utility is demonstrated by the production of statistically average male and female rib shapes for all rib levels. Simulated mechanical loading of the resulting model rib shapes showed that the stiffness of statistically average male and female ribs matched well with the average rib stiffness from each separate population. This in-plane rib shape model can be used to characterize variation in human rib geometry seen throughout the population, including investigation of the overall changes in shape and resultant mechanical properties that ribs undergo during aging or disease progression.
Core muscle size and mortality following non-operative management of pelvic fractures
Patel PP, Scheidler WD, Holcombe SA, Wang SC, Goulet JA.
The Orthopaedic Journal at Harvard Medical School. 2016 June;17.
The incidence of pelvic fractures in the United States is 13 cases per 10,000 person-years, of which 94% are low-energy fractures in the geriatric population. This cohort has a 20% one-year mortality rate, yet there are limited data predicting post-fracture survival. Core muscle size, a proxy measure of patient frailty, may be one such variable to help risk stratify patients.
METHODS
We identified 405 patients undergoing non-operative management of a pelvic fracture who had a CT scan of their abdomen/pelvis within 90 days of fracture. We selected for fragility fractures by including females over 50 and males over 65, with an Injury Severity Score (ISS) less than 18. Core muscle size (cross-sectional area of the psoas muscles at L4, normalized to height) was correlated to post-fracture mortality.
RESULTS
One-hundred and three patients met our selection criteria (82.5% female). Twenty-four patients died within one year of their diagnosis (23.3%). Patients in the lower third of normalized psoas sizes had significantly higher one-year mortality rates compared to patients in the upper third (females: 39.3% vs. 6.9%, p = 0.005' males: 100.0%, p = 0.002).
CONCLUSION
In non-operatively managed pelvic fractures, our data indicate that decreased core muscle size leads to significantly higher mortality rates. Such objective measures of patient frailty may inform clinical decision-making and improve orthopaedic patient risk stratification.
Body Composition Features Predict Overall Survival in Patients With Hepatocellular Carcinoma
Singal AG, Zhang P, Waljee AK, Ananthakrishnan L, Parikh ND, Sharma P, Barman P, Krishnamurthy V, Wang L, Wang SC, Su GL
Clin Transl Gastroenterol. 2016 May 26;7:e172. doi: 10.1038/ctg.2016.31.
Existing prognostic models for patients with hepatocellular carcinoma (HCC) have limitations. Analytic Morphomics®, a novel process to measure body composition using computational image-processing algorithms, may offer further prognostic information. The aim of this study was to develop and validate a prognostic model for HCC patients using body composition features and objective clinical information.
METHODS
Using computed tomography scans from a cohort of HCC patients at the VA Ann Arbor Healthcare System between January 2006 and December 2013, we developed a prognostic model using Analytic Morphomics® and routine clinical data based on multivariate Cox regression and regularization methods. We assessed model performance using C-statistics and validated predicted survival probabilities. We validated model performance in an external cohort of HCC patients from Parkland Hospital, a safety-net health system in Dallas County.
RESULTS
The derivation cohort consisted of 204 HCC patients (20.1% Barcelona Clinic Liver Cancer classification (BCLC) 0/A), and the validation cohort had 225 patients (22.2% BCLC 0/A). The Analytic Morphomics® model had good prognostic accuracy in the derivation cohort (C-statistic 0.80, 95% confidence interval (CI) 0.71-0.89) and external validation cohort (C-statistic 0.75, 95% CI 0.68-0.82). The accuracy of the Analytic Morphomics® model was significantly higher than that of TNM and BCLC staging systems in derivation (P=0.001 for both) and validation (P=0.001 for both) cohorts. For calibration, mean absolute errors in predicted 1-year survival probabilities were 5.3% (90% quantile of 7.5%) and 7.6% (90% quantile of 12.5%) in the derivation and validation cohorts, respectively.
CONCLUSION
Body composition features, combined with readily available clinical data, can provide valuable prognostic information for patients with newly diagnosed HCC.
Using Analytic Morphomics® to Understand Short-Term Convalescence after Radical Cystectomy
Luckenbaugh AN, Hollenbeck BK, Montgomery JS, Lee CT, Gilbert SM, Dunn RL, Friedman JF, Englesbe MJ, Wang SC, Hollingsworth JM
Data from the general surgery literature suggests that patient morphometric data obtained from preoperative imaging may help predict a patient's risk around surgery.
OBJECTIVES
In this context, we evaluated for associations between psoas muscle area and short-term convalescence following radical cystectomy.
METHODS
After identifying patients who underwent radical cystectomy at our institution (2008 to 2013), we calculated their psoas muscle area from staging computed tomography scans using established analytic morphomic techniques. We then determined early recovery among patients with high and low psoas muscle area using the validated Convalescence and Recovery Evaluation (CARE) questionnaire-a 27-item survey, divided into four domains (activity, cognitive, gastrointestinal, and pain recovery). Finally, we assessed the relationship between psoas muscle area and changes in CARE scores with nested linear regression models.
RESULTS
Among the 86 men and among 31 women in our cohort, the median total psoas muscle area was 2,544 mm2 and 1,511 mm2, respectively (P < 0.001 for the comparison). While there was no association between psoas muscle area and recovery in men, women with higher (versus lower) total psoas muscle area had smaller decreases in their pain scores postoperatively and a quicker return to their baseline level (P = 0.05). Activity scores also approached baseline levels faster among women with higher psoas muscle area, although this finding did not reach statistical significance.
CONCLUSIONS
Psoas muscle area is potentially an important preoperative predictor of recovery for women undergoingradical cystectomy. More broadly speaking, Analytic Morphomics® may represent a novel approach to better understand perioperative risk.
Analytical morphomics focuses on extracting objective and quantifiable data from clinical computered tomography (CT) scans to measure patients' frailty. Studies are currently retrospective in nature; therefore, it would be beneficial to develop animal models for well-controlled, prospective studies. The aim of this study is to develop an in vivo microCT protocaol for the longitudinal acquisition of whole-body images suitable for morphomic analyses of bone.
METHODS
The authors performed phantom studies on 2 microCT systems (Inveon and CT120) to study tissue radiodensity and further characterize system performance for collecting animal data. The authors also describe their design of a phantom-immobilization device using phantoms and an ovariectomized (OVX) mouse.
RESULTS
The authors discovered increased consistency along the z-axis for scans acquired on the Inveon compared with CT120, and calibration by individual slice reduces variability. Objects in the field of view had more impact on measurement acquired using the CT120 compared with the Inveon. The authors also found that using the middle 80% of slices for data analysis further decreased variability, on both systems. Moreover, bone-mineral-density calibration using the QCT Pro Mini phantom improved bone-mineral-density estimates across energy spectra, which helped confirm our technique. Comparison of weekly body weights and terminal uterine mass between sham and OVX groups validated our model.
DISCUSSION
The authors present a refined microCT protocol to collect reliable and objective data. This data will be used to establish a platform for research animal morphomics that can be used to test hypotheses developed from clinical human morphomics.
Investigating the clinical significance of body composition changes in patients undergoing chemoradiation for oropharyngeal cancer using Analytic Morphomics®
Wang C, Vainshtein JM, Veksler M, Rabban PE, Sullivan JA, Wang SC, Eisbruch A, Jolly S.
The purpose is to investigate the clinical significance of body morphomics changes in stage III-IV oropharyngeal cancer patients during concurrent chemoradiotherapy (CRT).
METHODS
Fifty patients who underwent CRT were selected for body composition analyses by either availability of pre/post treatment DEXA scans or a novel CT-based approach of body morphomics analysis (BMA). BMA changes (lean psoas and total psoas area) were compared to total lean body mass changes by DEXA scans using two-sample t tests. Pearson correlation was used to compare the BMA measures to head and neck specific quality of life outcomes. Cox hazards model was used to predict mortality and tumor recurrence.
RESULTS
Clinically significant declines in total psoas area and lean body mass of similar magnitude were observed in both BMA and DEXA cohorts after CRT. Loss of psoas area (P < 0.05) was associated with greater frailty and mobility issues (3 out of 15 UWQ)L domains). Total psoas area is more sensitive for local recurrence than weight changes and T-stage on multivariate analyses.
CONCLUSIONS
BMA specifically evaluating psoas area appears to correlate with head and neck cancer quality of life physical domains. Pre- and post-treatment total psoas area at L4 appears prognostic for tumor recurrence.
Factors Influencing Specificity and Sensitivity of Injury Severity Prediction (ISP) Algorithm for AACN
Pal C, Okabe T, Kulothungan V, Sangolla N, Manoharan J, Wang SC, Combest J.
International Journal of Automotive Engineering. Vol. 7 (2016 Mar 25) No. 1 p. 15-22
To improve the accuracy of Injury Severity Prediction in the event of vehicle crash, a new methodology is proposed using the US vehicle accident database (NASS-CDS). This proposed method is an extension of the base algorithm introduced by Kononen et al. in which, some of the additional variables were introduced and branched logistic regression methodology was used. Results suggest that the proposed branching method has some advantage over the base algorithm due to better linearization of the complex multidimensional non-linear relationship of the input and output variables.
Psoas muscle size as a frailty measure for open and transcatheter aortic valve replacement
Paknikar R, Friedman J, Cron D, Deeb GM, Chetcuti S, Grossman PM, Wang S, Englesbe M, Patel HJ
To evaluate the use of sarcopenia as a frailty assessment tool for patients with aortic stenosis undergoing surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR).
METHODS
The study cohort comprised 295 patients who underwent either SAVR (n = 156) or TAVR (n = 139). The mean preoperative Society of Thoracic Surgeons mortality risk score was 4.7%. Preoperative computed tomography (CT) scans were used to calculate gender-standardized total psoas area (TPA), as a validated measure of sarcopenia.
RESULTS
For the entire cohort, independent predictors of a composite measure of 30-day death, stroke, renal failure, prolonged ventilation, and deep wound infection included preoperative STS major morbidity and mortality risk score (odds ratio [OR], 91.1; P = .02) and TPA (OR, 0.5; P = .024). Two-year survival was 85.7% in patients with sarcopenia, compared with 93.8% in patients without sarcopenia (P = .02). Independent predictors of late survival included TPA (hazard ratio, 0.47; P = .02). Male sex (OR, 0.52; P = .04) and TPA (OR, 0.6; P = .001) were predictive of high resource utilization. A separate analysis by treatment group found that TPA predicted high resource utilization after SAVR (OR, 0.4; P < .001), but not after TAVR (P = .66).
CONCLUSIONS
CT scan-derived measurement of TPA as an objective frailty assessment tool predicts early morbidity and mortality, high resource utilization, and late survival after treatment for aortic stenosis. The correlation observed between sarcopenia and resource utilization after SAVR versus TAVR suggests that this simple and reproducible risk assessment tool also may help identify those patients who will derive optimal benefit from catheter-based therapy.
Analytic Morphomics®: a novel CT imaging approach to quantify adipose tissue and muscle composition in allogeneic hematopoietic cell translation
Chughtai K, Song Y, Zhang P, Derstine B, Gatza E, Friedman J, Hully L, Inglis C, Goldstein S, Magenau J, Pawarode A, Reddy P, Riwes M, Yank G, Wang SC, Choi SW
Bone Marrow Transplant. 2016 Mar;51(3):446-50. doi: 10.1038/bmt.2015.267. Epub 2015 Nov 9.
Current measures of obesity do not accurately describe body composition. Using cross-sectional imaging, objective measures of musculature and adiposity are possible and may inform efforts to optimize liver transplantation outcomes.
METHODS
Abdominal visceral fat area and psoas muscle cross-sectional area were measured on CT scans for 348 liver transplant recipients. After controlling for donor and recipient characteristics, survival analysis was performed using Cox regression.
RESULTS
Visceral fat area was significantly associated with post-transplant mortality (p < 0.001; HR = 0.91 per cm(2), 95% CI: 0.88-0.94). Among patients with smaller TPA, the patients with high visceral fat area had 71.8% one-yr survival compared to 81.8% for those with low visceral fat area (p = 0.15). At five yr, the smaller muscle patients with high visceral fat area had 36.9% survival compared to 58.2% for those with low visceral fat area (p = 0.023).
CONCLUSIONS
Abdominal adiposity is associated with surival after liver transplantation, especially in patients with small trunk muscle size. When coupled with trunk musculature, abdominal adiposity offers direct characterization of body composition that can aid preoperative risk evaluation and inform transplant decision-making.
Limitations of the barcelona clinic liver cancer staging system with a focus on transarterial chemoembolization as a key modality of treatment of hepatocellular carcinoma
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is one of the leading causes of cancer-related death in the United States. Prognosis of HCC remains poor, driven by advanced tumor burden at diagnosis in two-thirds of cases.
Cancer staging systems are important for prognostication and determination of therapy. HCC has unique characteristics for which it is more difficult to use standard cancer staging strategies. First, there is enormous heterogeneity with regard to patient characteristics and HCC biology. Second, in the Western world, the majority of HCC occurs in patients with significant underlying liver disease, making liver function and functional status important in determining outcome. Lastly, tissue diagnosis is not often required, and radiological diagnosis is often the standard. Various staging systems (Table 1) have been proposed to incorporate these variables, but there is no universal worldwide consensus. Two of these staging systems [Barcelona Clinic Liver Cancer (BCLC) and Groupe d'ETUDE et de Traitement du Carcinome Hepatocellulaire (GRETCH)] include performance status, with the BCLC being validated in various geographical settings and with very large data sets. As a result, the BCLC staging system is the most accepted system in the United States, having received the endorsement of both the American Association for the Study of Liver Diseases and the European Association for the Study of Liver Diseases and the European Association for the Study of Liver diseases (Figure 1). Its main advantage is the unique way in which it provides therapy guidelines based on staging, making it a very useful clinical tool.
5th International ACC Symposium: Surgical Considerations in the Treatment of Adrenocortical Carcinoma: 5th International ACC Symposium Session: Who, When and What Combination?
Miller, BS.
Horm Cancer. 2016 Feb;7(1):24-8. doi: 10.1007/s12672-0150243-0. Epub 2016 Jan 4.
Significant progress has been made in the understanding of how surgical technique impacts outcome in patients with adrenal cancer. Current and future areas of investigation center on expanding the role of surgery in patients with locally recurrent or metastatic disease, use of neoadjuvant therapy as a bridge to surgery, the impact of formal lymphadenectomy on survival, and improved diagnosis, prognosis, and selection of patients for surgery and other treatments using morphomic analysis.
2015
Sarcopenia and failure to rescue following liver transplantation
Underwood PW, Cron DC, Terjimanian MN, Wang SC, Englesbe MJ, Waits SA
Clin Transplant. 2015 Dec;29(12):1076-80. doi: 10.1111/ctr.12629. Epub 2015 Oct 15.
Sarcopenic liver transplant recipients have higher rates of mortality, but mechanisms underlying these rates remain unclear. Failure to rescue (FTR) has been shown to be a primary driver of mortality following major general and vascular surgery. We hypothesized that FTR is common in sarcopenic liver transplant recipients.
METHODS
We retrospectively reviewed 348 liver transplant recipients with perioperative CT scans. Analytic morphomic techniques were used to assess trunk muscle size via total psoas area (TPA). One-yr major complication and FTR rates were calculated across TPA tertiles.
RESULTS
The one-yr complication rate was 77% and the FTR rate was 19%. Multivariate regression showed TPA as a significant predictor of FTR (OR = 0.27 per 1000 mm(2) increase in TPA, p < 0.001). Compared to patients in the largest muscle tertile, patients in the smallest tertile had 1.4-fold higher adjusted complication rates (91% vs. 66%) and 2.8-fold higher adjusted FTR rates (22% vs. 8%).
DISCUSSION
These results suggest that mortality in sarcopenic liver transplant recipients may be strongly related to FTR. Efforts aimed at early recognition and management of complications may decrease postoperative mortality. Additionally, this work highlights the need for expanded multicenter collaborations aimed at collection and analysis of postoperative complications in liver transplant recipients.
Starting a Surgical Home
Englesbe MJ, Lussiez AD, Friedman JF, Sullivan JA, Wang SC
Ann Surg. 2015 Dec;262(6):901-3. doi: 10.1097/SLA.0000000000001250.
It is well established that sarcopenic patients are at higher risk of postoperative complications and short-term health care utilization. Less well understood is how these patients fare over the long term after surviving the immediate postoperative period. We explored costs over the first postoperative year among sarcopenic patients.
METHODS
We identified 1279 patients in the Michigan Surgical Quality Collaborative database who underwent inpatient elective surgery at a single institution from 2006-2011. Sarcopenia, defined by gender-stratified tertiles of lean psoas area, was determined from preoperative computed tomography scans using validated Analytic Morphomics®. Data were analyzed to assess sarcopenia's relationship to costs, readmissions, discharge location, intensive care unit admissions, hospital length of stay, and mortality. Multivariate models were adjusted for patient demographics and surgical risk factors.
RESULTS
Sarcopenia was independently associated with increased adjusted costs at 30, 90, and 180 but not 365 d. The difference in adjusted postsurgical costs between sarcopenic and nonsarcopenic patients was $16,455 at 30 d and $14,093 at 1 y. Sarcopenic patients were more likely to be discharged somewhere other than home (P < 0.001). Sarcopenia was not an independent predictor of increased readmission rates in the postsurgical year.
CONCLUSIONS
The effects of sarcopenia on health care costs are concentrated in the immediate postoperative period. It may be appropriate to allocate additional resources to sarcopenic patients in the perioperative setting to reduce the incidence of negative postoperative outcomes.
Morphomics predicts response to ipilimumab in patients with stage IV melanoma
Sabel MS, Lee J, Wang A, Lao C, Holcombe S; and Wang SC
Factors predictive of response to immunotherapy are needed to select appropriate patients. As morphometric analysis can be an objective surrogate for underlying physiology, we explored the possibility that morphomics may predict response among stage IV melanoma patients treated with ipilimumab.
METHODS
We identified stage IV melanoma patients treated with ipilimumab who had an appropriate CT scan within a 6 month window. Using semi-automated algorithms, we acquired several morphomic measurements. Toxicity and response rate compared by quartile using Fisher's exact test or chi-square, while survival after initiation of ipilimumab was compared by quartile using the log-rank test.
RESULTS
While there was a significant correlation between toxicity and response (P < .003), morphomics failed to predict either severity of toxicity or specific side effects. Psoas density was significantly associated with response rate, both excluding stable disease (36.4% vs 9.1%, P = .054), and including stable disease (54.5% versus 18.2%, P = 0.045). Survival after initiation of ipilimumab was significantly associated with psoas density (P = 0.04) and visceral fat distance (P = 0.022).
DISCUSSION
In an exploratory study of patients with metastatic melanoma being treated with ipilimumab, psoas density and spine-fascia distance correlated with response and survival. Pre-treatment morphomic analysis, as a correlate of underlying physiology, may help predict response to immunotherapy.
A Computed tomography study of gender differences in acetabular version and morphology: implications for femoroacetabular impingement
Tannenbaum EP, Zhang P, Maratt JD, Gombera MM, Holcombe SA, Wang SC, Bedi A, Goulet JA.
Arthroscopy. 2015 Jul;31(7):1247-54. doi: 10.1016/j.arthro.2015.02.007. Epub 2015 May 13.
To assess the prevalence of acetabular retroversion in a large population of patients with asymptomatic hips. Furthermore, we sought to identify gender differences in acetabular morphology to address the current thinking that retroversion and pincer-type femoroacetabular impingement (FAI) are more common in women.
METHODS
We retrospectively reviewed morphologic features of acetabula from a consecutive series of trauma-protocol computed tomography scans of patients without pelvis injury. An automated algorithm determined the acetabular rim profile and center of the femoral head, normalized the frontal plane of the pelvis, and calculated version and coverage. We then compared male and female rim profiles, specifically focusing on version and acetabular wall coverage in the 1-o'clock (anterosuperior), 2-o'clock (central), and 3-o'clock (inferior) positions.
RESULTS
Of 1,088 patients in the database, 878 had complete data (i.e., age, ethnicity, and body mass index) and were therefore included in the final analysis. Of these, 34.3% were women and 65.7% were men. Mean global acetabular version was 19.1° for men and 22.2° for women (P < .001). Mean acetabular version for men and women was 15.5° and 18.3°, respectively, in the 1-o'clock position; 21.5° and 24.0°, respectively, in the 2-o'clock position; and 20.2° and 24.3°, respectively, in the 3-o'clock position (P < .001 for all 3). True retroversion (<0°) was observed only in the 1-o'clock position. The prevalence of true acetabular retroversion in the 1-o'clock position for men and women was 4.3% and 3%, respectively (P = .36).
CONCLUSIONS
Mean global and focal acetabular anteversion was greater in women, and the prevalence of focal cephalad retroversion in the 1-o'clock position was not significantly different compared with men. Acetabular retroversion and anterior overcoverage are not more prevalent in women in the anterosuperior acetabulum, where femoroacetabular impingement most commonly occurs.
LEVEL OF EVIDENCE
Level III, diagnostic study.
Sarcopenia is associated with autologous transplant-related outcomes in patients with lymphoma
Caram MV, Bellile EL, Englesbe M, Terjimanian M, Wang SC, Griggs JJ, Couriel D.
Leuk Lymphoma. 2015;56(10):2855-62. doi: 10.3109/10428194.2015.1014359. Epub 2015 Jun 18.
Sarcopenia is associated with treatment-related complications and shorter overall survival in patients with cancer. Psoas area indices were calculated for 121 patients with lymphoma who underwent autologous transplant. Controlling for age, body mass index, comorbidities and performance status for the 73 men included, the hazard ratio (95% confidence interval, CI) for non-relapse mortality was 2.37 (1.01, 5.58), p = 0.048 for every 100 unit decrease in total psoas index and 2.67 (1.04, 6.86), p = 0.041 for every 100 unit decrease in lean psoas index. Men with a lower total psoas index experienced more complications (p = 0.001) and spent more days in hospital (p = 0.03) during the transplant admission. A strong association existed between sarcopenia and number of hospital days in the 100 days following transplant among both men (p < 0.0001) and women (p < 0.0001). Sarcopenia may impact negative outcomes after autologous transplant thereby serving as a potentially modifiable predictor of outcomes and aiding in treatment selection.
Morphometric analysis of abdominal organs and rib cage: Implication for risk of solid organ injuries in children.
Harbaugh CM, Shlykov MA, Tsuchida RE, Holcombe SA, Hirschl J, Wang SC, Ehrlich PF.
J Trauma Acute Care Surg. 2015 Jun;78(6):1129-33. doi: 10.1097/TA.0000000000000644.
Motor vehicle crashes are the leading cause of injury-related mortality in children, with a higher rate of multiorgan injuries than in adults. This may be related to increased solid organ volume relative to abdominal cavity and decreased protection of an underdeveloped cartilaginous rib cage in young children. To date, these anatomic relationships have not been fully described. Our study used Analytic Morphomics® to obtain precise measures of the pediatric liver, spleen, kidneys, and ribs.
METHODS
This pilot study included 215 trauma patients (aged 0-18 years) with anonymized computed tomography (CT) scans. Liver, spleen, and kidney volumes were modeled using semiautomatic algorithms (MATLAB 2013a, MathWorks Inc., Natick, MA). Thirty-one scans were adequate to model the rib cage. Pearson's r was used to correlate absolute organ volume, fractional organ volume, and organ exposure with age and weight.
RESULTS
Spleen, right and left kidney, and liver volumes increased with age and weight (p < 0.01). Right/left kidney and liver fractional volumes decreased with age (p < 0.01), whereas spleen fractional volume remained relatively constant. Exposed surface area of the liver only significantly decreased with age in the anterior (p < 0.01), right (p < 0.01), and posterior views (p = 0.02).
DISCUSSION
With this study, we have demonstrated the ability to model solid organ and rib cage anatomy of children using cross-sectional imaging. In younger children, there may be a decrease in fractional organ volume and increase in liver surface exposure, although analysis of a larger sample size is warranted. In the future, this information may be used to improve the design of safety restraints in motor vehicles.
Body fat composition assessment using Analytic Morphomics® predicts infectious complications after bowel resection in Crohn's disease
Stidham RW, Waljee AK, Day NM, Bergmans CL, Zahn KM, Higgins PD, Wang SC, Su GL
Decisions between medical and surgical management of Crohn's disease (CD) incorporate risk assessments for potential complications of each therapy. Analytic Morphomics® is a novel method of image analysis providing quantifiable measurements of body tissue composition, characterizing body fat more comprehensively than body mass index alone. The aim of this study was to determine the risk factors associated with postoperative complications in CD, incorporating fat composition analysis using Analytic Morphomics®.
METHODS
We performed a retrospective review of adults undergoing bowel resection for CD between 2004 and 2011 at a single center. Computed tomography obtained within 30 days prior to surgery underwent morphomic analysis for fat characterization. Postoperative infectious complications were defined as the need for a postoperative abdominal drain, intravenous antibiotics, or reoperation within 30 days. Bivariate and multivariate analyses using logistic regression were used to generate a prediction model of infectious complications.
RESULTS
A total of 269 subjects met selection criteria; 27% incurred postoperative infectious complications. Bivariate analysis showed hemoglobin, albumin, surgical urgency, high-dose prednisone use, and subcutaneous-to-visceral fat volume distribution as predictors of complications. Body mass index, anti-tumor necrosis factor alpha therapies, and immunomodulator use were not predictors of complication. Multivariate modeling demonstrated a c-statistic of 0.77 and a negative predictive value of 81.1% with surgical urgency (odds ratio = 2.78: 95% confidence interval, 1.46-6.02; P = 0.004), subcutaneous-to-visceral fat distribution (odds ratio = 2.01; 95% confidence interval, 1.20-3.19; P = 0.006), and hemoglobin (odds ratio = 0.69; 95% confidence interval, 0.55-0.85; P = 0.001) as predictors of infectious complication.
CONCLUSIONS
Fat subtype and distribution are predictive of postoperative infectious complications after bowel resection for CD. Analytic Morphomics® provides additional body composition detail not captured by body mass index.
Predicting Wound Complications with Preoperative CT Scans
Strobel RJ, Lee CS, Friedman JF, Grenda DR, Inglis CW, Derstine BA, Bahroloomi SM, Hammoud AM, Leary KC, Peltier AR, Wang SC, Englesbe MJ.
Wound complications – such as incisional hernia, ventral hernia, and wound dehiscence– are common following major abdominal surgery. Despite advances in surgical care, these complications remain prevalent. We hypothesized that Analytic Morphomics®, a novel objective risk assessment tool, would explain the relationship between preoperative tissue composition and postoperative wound complications.
METHODS
This is an observational study of 1,409 patients undergoing major abdominal surgery and who had a preoperative CT scan, all selected from the Michigan Surgical Quality Collaborative Database. The primary outcome is a composite of local wound complications, including incisional hernia, ventral hernia, wound dehiscence and major wound complications. Analytic morphomic measures of a single slice at the L4 vertebral level were investigated, along with variables related to patient demographics, medical history, admissions status, and comorbid disease. A p < 0.05 threshold in univariate analysis was employed for considering variables to be included in multivariable analysis.
RESULTS
Wound complications occurred in 11.9% of patients. Analytic morphomic variables associated with wound complications are detailed in the figure. The final, single-slice model was assembled via backwards stepwise selection, and included 4 preoperative variables: subcutaneous fat area @ L4 (odds ratio [OR] = 1.67, 95% confidence interval [Cl] 1.03-2.78, P = 0.040), pack-years (OR = 1.18, 95% CI 0.99-1.38, P = 0.046), albumin (OR = 0.84, 95% CI 0.72-1.00, P = 0.044), and immunosuppressive therapy (OR = 1.97, 95% CI 1.15-3.26, P = 0.010).
CONCLUSION
Patients with a large subcutaneous fat area have a higher risk of wound complication. This may inform surgeon decision-making in the operating room.
Analytic Morphomics® identifies predictors of new-onset diabetes after liver transplantation
Vaughn V, Cron DC, Terjimanian MN, Gala ZS, Wang SC, Su GL, Volk ML
Among liver transplant recipients, development of post-transplant complications such as new-onset diabetes after transplantation (NODAT) is common and highly morbid. Current methods of predicting patient risk are inaccurate in the pre-transplant period, making implementation of targeted therapies difficult. We sought to determine whether Analytic Morphomics® (using computed tomography scans) could be used to predict the incidence of NODAT. We analyzed peri-transplant scans from 216 patients with varying indications for liver transplantation, among whom 61 (28%) developed NODAT. Combinations of visceral fat, subcutaneous fat, and psoas area were considered in addition to traditional risk factors. On multivariate analysis adjusting for usual risk factors such as type of immunosuppression, subcutaneous fat thickness remained significantly associated with NODAT (OR = 1.43, 95% CI 1.00-1.88, p = 0.047). Subgroup analysis showed that patients with later-onset of NODAT had higher visceral fat, whereas subcutaneous fat thickness was more correlated with earlier-onset of NODAT (using 10 months post-transplant as the cut-off).
CONCLUSION
Analytic Morphomics® may be used to help assess NODAT risk in patients undergoing liver transplantation.
Implications of sarcopenia in major surgery
Friedman J, Lussiez A, Sullivan J, Wang S, Englesbe M.
Sarcopenia, defined as a decrease in skeletal muscle mass and strength, is an important risk factor in clinical medicine associated with frailty, mortality, and worse surgical and nonsurgical outcomes. Conventional measures of sarcopenia rely on the subjective "eyeball test" and do not adequately describe risk. Computed tomography (CT) imaging studies may be used to objectively measure sarcopenia and may be used for surgical risk stratification and identification of patients for inclusion in a novel clinical remediation program.
METHODS
We describe results observed in the general, vascular, and liver transplant surgery populations determined by Analytic Morphomics®--an analysis of CT scans in a semiautomated process using MATLAB v13.0. A perioperative optimization program has been implemented with the objective of remediating sarcopenia through improvement of patient mental and physical status prior to surgery.
RESULTS
Using Analytic Morphomics®, we have noted significantly higher cost and increased rates of mortality and surgical complications among sarcopenic patients. The training program shows initial success, and among participating patients, we have observed reductions in payer and hospital costs and a decrease in length of hospital stay for patients following surgery.
CONCLUSIONS
Through Analytic Morphomics®, we are able to quantify markers of sarcopenia and identify patients at risk for increased mortality and poor surgical outcomes. Early identification of patients offers us the opportunity to remediate sarcopenia through perioperative training and support. Participating patients spend less time in the hospital and have lower healthcare costs. This program has the potential to improve the perioperative patient experience and ease financial burdens.
Morphomic analysis as an aid for preoperative risk stratification in patients undergoing major head and neck cancer surgery
Rinkinen J, Agarwal S, Beauregard J, Aliu O, Benedict M, Buchman SR, Wang SC, Levi B
Patients undergoing major head and neck cancer surgery (MHNCS) may develop significant postoperative complications. To minimize the risk of complications, clinicians often assess multiple measures of preoperative health in terms of medical comorbidities. One emerging method to decrease surgical complications is preoperative assessment of patient frailty measured by specific tissue characteristics. We hypothesize that morphomic characteristics of the temporalis region serve as predictive markers for the development of complications after MHNCS.
METHODS
We performed a retrospective review of 69 patients with available computed tomography (CT) imaging who underwent MHNCS from 2006-2012. To measure temporalis region characteristics, we used morphomic analysis of available preoperative CT scans to map out the region. All available CT scans had been performed as part of the patient's routine work-up and were not ordered for morphomic analysis. We describe the correlation among temporalis fat pad volume (TFPV), mean zygomatic arch thickness, and incidence of postoperative complications.
RESULTS
We noted significant difference in the zygomatic bone thickness and TFPV between patients who had medical complications, surgical complications, or total major complications and those who did not. Furthermore, by use of binary logistic regression, our data suggest decreased TFPV and zygomatic arch thickness are stronger predictors of developing postoperative complications than previously studies preoperative characteristics.
CONCLUSIONS
We describe morphomic analysis of the temporalis region in patients undergoing MHNCS to identify patients at risk for complications. Regional anatomic morphology may serve as a marker to objectively determine a patient's overall health. Use of the temporalis region is appropriate in patients undergoing MHNCS because of the availability of preoperative scans as part of routine work up for head and/or neck cancer.
Visceral adiposity is negatively associated with bone density and muscle attenuation
Zhang P, Peterson M, Su GL, Wang SC
Am J Clin Nutr. 2015 Feb;101(2):337-43. doi: 10.3945/ajcn.113.081778. Epub 2014 Nov 26.
The storage of adipose tissue in ectopic compartments is a hallmark attribute linking greater body mass index (BMI) with cardiometabolic diseases. Despite ample evidence to confirm that increased visceral adipose tissue (VAT) deposition occurs with obesity, the interrelations between altered fat partitioning and regional muscle and bone quality are less well understood.
OBJECTIVE
We examined the association between adiposity and spinal muscle and bone quality across a large, heterogeneous cohort of adults.
DESIGN
We identified 8833 thoracic or abdominal computed tomography scans from patients in the University of Michigan Health System who were aged 18-64.9 y. We measured trabecular bone densities, cortical bone densities, VAT areas, and subcutaneous adipose tissue (SAT) areas at vertebral levels T7 to L5. Psoas muscle attenuation (an indicator of fat infiltration in muscle) was measured at the L4 level.
RESULTS
Muscle attenuation as well as trabecular and cortical bone densities revealed negative correlations with BMI, SAT, and VAT. The correlation between BMI and psoas attenuation was -0.321, between BMI and the density of cortical bone was -0.250, and between BMI and trabecular bone was -0.143 (all P < 0.001). However, correlations between VAT and lower muscle attenuation were stronger as were those between VAT and lower bone densities. Inverse correlations between VAT and densities of psoas muscle and cortical and trabecular bone were -0.460, -0.407, and -0.434, respectively (P < 0.001). Even after adjustment for age, sex, and BMI, partial correlations between VAT, muscle attenuation, and bone densities remained significant at -0.250, -0.119, and -0.216, respectively (P < 0.001).
CONCLUSIONS
Contrary to previous reports that high body mass is associated with increased bone quality, our data show a significant negative association between BMI and muscle and bone densities, suggesting fat infiltration into these tissues. More importantly, correlations between VAT and decreased bone and muscle densities remained statistically significant even after adjustment for age, sex, and BMI.
Use of Analytic Morphomics® of liver, spleen, and body composition to identify patients at risk for cirrhosis
Krishnamurty V, Zhang P, Ethiraj S, Enchakalody B, Waljee AK, Wang L, Wang SC, Su GL
A diagnosis of cirrhosis can be made on the basis of findings from imaging studies, but these are subjective. Analytic Morphomics® uses computational image processing algorithms to provide precise and detailed measurements of organs and body tissues. We investigated whether morphomic parameters can be used to identify patients with cirrhosis.
METHODS
In a retrospective study, we performed Analytic Morphomics® on data collected from 357 patients evaluated at the University of Michigan from 2004 to 2012 who had a liver biopsy within 6 months of a computed tomography scan for any reason. We used logistic regression with elastic net regularization and cross-validation to develop predictive models for cirrhosis, within 80% randomly selected internal training set. The other 20% data were used as internal test set to ensure that model overfitting did not occur. In validation studies, we tested the performance of our models on an external cohort of patients from a different health system.
RESULTS
Our predictive models, which were based on Analytic Morphomics® and demographics (morphomics model) or Analytic Morphomics®, demographics, and laboratory studies (full model), identified patients with cirrhosis with area under the receiver operating characteristic curve (AUROC) values of 0.91 and 0.90, respectively, compared with 0.69, 0.77, and 0.76 for aspartate aminotransferase-to-platelet ratio, Lok Score, and FIB-4, respectively, by using the same data set. In the validation set, our morphomics model identified patients who developed cirrhosis with AUROC value of 0.97, and the full model identified them with AUROC value of 0.90.
CONCLUSIONS
We used Analytic Morphomics® to demonstrate that cirrhosis can be objectively quantified by using medical imaging. In a retrospective analysis of multi-protocol scans, we found that it is possible to identify patients who have cirrhosis on the basis of analyses of preexisting scans, without significant additional risk or cost.
Effects of aging on osteogenic response and heterotopic ossification following burn injury in mice
Peterson JR, Ebody ON, Brownley RC, Cilwa KE, Pratt LE, De La Rosa S, Agarwal S, Buchman SR, Cederna PS, Morris MD, Wang SC, Levi B.
Stem Cells Dev. 2015 Jan 15;24(2):205-13. doi: 10.1089/scd.2014.0291.
Heterotopic ossification (HO) is a common and debilitating complication of burns, traumatic brain injuries, and musculoskeletal trauma and surgery. Although the exact mechanism of ectopic bone formation is unknown, mesenchymal stem cells (MSCs) capable of osteogenic differentiation are known to play an essential role. Interestingly, the prevalence of HO in the elderly population is low despite the high overall occurrence of musculoskeletal injury and orthopedic procedures. We hypothesized that a lower osteogenicity of MSCs would be associated with blunted HO formation in old compared with young mice. In vitro osteogenic differentiation of adipose-derived MSCs from old (18-20 months) and young (6-8 weeks) C57/BL6 mice was assessed, with or without preceding burn injury. In vivo studies were then performed using an Achilles tenotomy with concurrent burn injury HO model. HO formation was quantified using µCT scans, Raman spectroscopy, and histology. MSCs from young mice had more in vitro bone formation, upregulation of bone formation pathways, and higher activation of Smad and nuclear factor kappa B (NF-κB) signaling following burn injury. This effect was absent or blunted in cells from old mice. In young mice, burn injury significantly increased HO formation, NF-κB activation, and osteoclast activity at the tenotomy site. This blunted, reactive osteogenic response in old mice follows trends seen clinically and may be related to differences in the ability to mount acute inflammatory responses. This unique characterization of HO and MSC osteogenic differentiation following inflammatory insult establishes differences between age populations and suggests potential pathways that could be targeted in the future with therapeutics.
Morphomic Factors are Important for Assessing Risk of Cardiovascular Complications in Trauma Patients
J. Li, N. Wang, J. Friedman, D. Cron, O. Juntila, M. Terjimanian, E. Chang, S. C. Wang.
Motor vehicle crashes (MVCs) are a major cause of traumatic injury in the US, and in- hospital cardiac complications are associated with increased morbidity and mortality in this population. Risk of cardiovascular complications is often difficult to predict using only injury severity and vital signs upon presentation to the trauma center. The utility of Analytic Morphomics® have previously been established in perioperative risk assessment and may provide improved clinical insight in the trauma setting. We hypothesized that morphomic factors may serve as significant predictors of in-hospital cardiac complications for patients involved in MVCs.
Methods
Our study included 3,187 MVC adult patients admitted to the University of Michigan Health System who underwent an abdominal CT scan near the time of injury. Exclusion criteria include ISS less than 5 or head-and-neck AIS of 5 or greater. Morphomic factors were measured at the L4 vertebral level using established algorithms. We utilized univariate analysis to determine the relationship of patient demographics, comorbidities, morphomics, and vital signs upon hospital admission with the development of cardiac complications, defined as myocardial infarction (MI), cerebrovascular accident (CVA), and other cardiac events. Injury severity was stratified by mild (5<ISS<16), moderate (16<ISS<25), and severe (ISS>25) trauma.
Results
Of the 3,187 eligible patients in our study, 121 (3.8%) developed cardiovascular complications. CVA and MI history, bone mineral density, and BMI were significant predictors of cardiovascular events (p<0.05) in mild trauma. Decreased average psoas radiodensity and increased age were found to be significant predictors for cardiovascular events (p<0.01) in moderate trauma. Glasgow Coma Scale and increased anterior body depth were the two most significant predictors of cardiovascular events in severe trauma (p<0.05). Table 1 shows the results of the univariate analysis between the complications and non- complications group for all three levels of trauma. Non-significant predictors of cardiovascular complications across all trauma levels include gender (p=0.17, 1.0, 0.11) and history of diabetes (p=0.37, 0.65, 0.19) or hypertension (p=0.50, 0.07, 0.35).
Discussion/Conclusion
Following a MVC, in-hospital cardiovascular events are serious, life-threatening complications. Psoas radiodensity, bone mineral density, and anterior body depth are significant factors associated with cardiovascular complications. Thus, morphomic factors obtained from cross-sectional imaging are significant predictors of cardiovascular events and may aid clinical decision making for higher risk patients.
Kidney-specific Morphomic Factors are Associated with AKI after Major General Surgery Operations
J. Li, E. Chang, N. C. Wang, D. Cron, P. Zhang, S. C. Wang
Acute kidney injury (AKI) occurs in approximately 20% of hospitalized adults in the US and is associated with increased morbidity, mortality, and cost for patients of general surgery procedures. Numerous studies have suggested the utility of using patient CT imaging data to predict risk of AKI. Analytic Morphomics®, which is a quantitative approach to processing cross-sectional imaging data, has shown utility in evaluating perioperative risk and postoperative outcome. Thus, we hypothesized that individualized morphomic factors would be significantly associated with AKI after major general surgery procedures.
Methods
326 adult patients undergoing major, elective, intra-abdominal general surgery operations from January 2008 to September 2011 were selected. Exclusion criteria include patients undergoing isolated appendectomy or cholecystectomy procedures, patients with a preoperative creatinine value of 1.6 or greater, a history of ESRD, or a prior nephrectomy. Preoperative CT scans within 365 days prior to the operation were analyzed for kidney, vertebral, and fascia-associated parameters such as length, area, volume, and radiodensity. Demographic factors include patient age, gender, and BMI. Univariate analysis was utilized to determine the strength of the association between patient morphomic and demographic factors and development of postoperative AKI as defined by the KDIGO criteria within 30 days of the surgery.
Results
Of the 238 eligible patients, 31 (13%) developed AKI. Average pixel radiodensity of the total kidney (p<0.001) and kidney parenchyma (p<0.001) were found to be significantly lower for the group that developed postoperative AKI than for those that did not. No significant differences between AKI and non-AKI patients were found for total kidney volume (p=0.19), parenchymal volume (p=0.16), anterior body depth (p=0.32), and patient demographic factors (p>0.15). Table 1 contains the results of the univariate analysis including the means between the AKI and non-AKI group of several factors.
Conclusion
For patients undergoing noncardiac, nonvascular surgical procedures, our analysis showed that kidney pixel radiodensity factors are the most significant in predicting postoperative AKI risk.
Image Related Factors Important for AKI Risk Assessment After Colectomies
E. T. Chang, A. Lussiez, J. Li, N. Wang, S. C. Wang
Acute kidney injury (AKI) occurs in approximately 20% of hospitalized adults and costs the US $10 billion annually. Prolonged hospital stay, cost, and mortality have been shown to be increased in these patients and those requiring renal replacement therapy have an even higher mortality rate. In the setting of colon surgery, a recent large scale study found several associated factors with postoperative AKI including advanced age, chronic renal failure, and total colectomy. However, a surgical decision informed by standard clinical data alone may not be sufficient. We set out to study the relationship between AKI and quantitative kidney morphomic factors from cross-sectional preoperative imaging for patients undergoing colectomies and comparing the results with demographic and intra-operative data. We hypothesized that individualized kidney characteristics would correlate with the risk of postoperative AKI development.
Methods
A retrospective review of prospectively gathered data from adult patients undergoing colectomies from 2006-2012 at the University of Michigan was conducted. 390 initial subjects without elevated baseline creatinine values, ESRD, a prior nephrectomy, or renal injury were included. Polycystic kidneys or other kidney abnormalities identified on imaging were excluded resulting in 326 subjects. AKI was defined by the KDIGO criteria within 30 days of injury. Demographic and intraoperative factors were evaluated along with measurements of pertinent kidney morphomic data including volume, surface area, and average Hounsfield Units (HU) which were subjected to univariate analyses.
Results
Of the 326 patients, 60 developed AKI (18.4%). Of demographic factors, advanced age (p=0.0002) and a higher BMI (p=0.02) were associated with AKI. Comorbidities associated with AKI included hypertension (p=0.008) and diabetes (p=0.013). Interestingly, intraoperative factors including surgical time (p=0.13), blood transfusions (p=0.14), blood loss (p=0.42), and hypotensive episodes (p=0.17) were not significantly associated with AKI. Table 1 shows the results of the univariate analysis of the morphomic factors.
Conclusion
AKI is a serious complication and the prevalence after colorectal surgery at our institution was 18.4%. Our analysis shows that a lower average parenchymal HU was the most significant morphomic factor associated with postoperative AKI. This study is the first to provide information that morphomic analysis can be useful in clinical practice to determine which patients are at risk for developing AKI after a colectomy.
2014
Cross-sectional area of the abdomen predicts complication incidence in patients undergoing sternal reconstruction
Kozlow JH, Lisiecki J, Terjimanian MN, Rinkinen J, Brownley RC, Agarwal S, Wang SC, Levi B
Sternal reconstruction with vascularized flaps is central to the management of sternal wound infections and mediastinitis but carries a high risk of complications. There is a need to identify reliable predictors of complication risk to help inform patients and clinicians in preparation for surgery. Unfortunately, body mass index and serum albumin may not be reliable predictors of complication rates. Analytic Morphomics® provides a robust quantitative method to measure patients' obesity as it pertains to their risk of complications in undergoing sternal reconstruction.
METHODS
We identified 34 patients with preoperative computed tomography scans of the abdomen from a cohort of sternal reconstructions performed between 1997 and 2010. Using semiautomated Analytic Morphomics®, we identified the patients' skin and fascia layers between the ninth and 12th thoracic spine levels; from these landmarks, we calculated morphomic measurements of the patients' abdomens, including their total body cross sectional area and the cross sectional area of their subcutaneous fat. We obtained the incidence of complications from chart review and correlated the incidence of complications (including seroma, hematoma, recurrent wounds, mediastinitis, tracheostomy, and death) with patients' morphomic measurements.
RESULTS
Sixty-two percent of patients (n = 21) suffered complications after their operation. Those who suffered from complications, relative to those who did not have complications, had increased visceral fat area (12,547.2 mm(2)versus 6569.9 mm(2), P = 0.0080), subcutaneous fat area (16,520.2 mm(2)versus 8020.1 mm(2), P = 0.0036), total body area (91,028.6 mm(2)versus 67,506.5 mm(2), P = 0.0022), fascia area (69,238.4 mm(2)versus 56,730.9 mm(2), P = 0.0118), total body circumference (1101.8 mm versus 950.2 mm, P = 0.0017), and fascia circumference (967.5 mm versus 868.1 mm, P = 0.0077). We also demonstrated a significant positive correlation between the previously mentioned morphomic measurements and the incidence of complications in multivariate logistic regression models, with odds ratios ranging from 1.19-3.10 (P values ranging from 0.010-0.022).
CONCLUSIONS
Increases in abdominal morphomic measurements correlate strongly with the incidence of complications in patients undergoing sternal reconstruction. This finding may influence preoperative risk stratification and surgical decision making in this patient population.
Morphomic analysis for preoperative donor site risk assessment in patients undergoing abdominal perforator flap breast reconstruction: a proof of concept study
Levi B, Rinkinen J, Kidwell KM, Benedict M, Stein IC, Lisiecki J, Enchakalody B, Wang SC, Kozlow JH, Momoh AO
Morphomics are three-dimensional measurements of aspects of the human anatomy generated by computed tomographic (CT) imaging. The purpose of this study was to generate preliminary data on the efficacy of morphomics, as a potential risk stratification tool, in predicting abdominal donor site wound-healing complications in patients undergoing abdominal perforator flap breast reconstruction.
PATIENTS & METHODS
In total, 58 consecutive patients undergoing deep inferior epigastric perforator (DIEP) flap breast reconstruction were evaluated. Using preoperative CT scan data, we quantified patients' body area, visceral and subcutaneous fat, fascia area, and body depth between T12 and L4. Associations between morphomic measures and complication rates were examined using t-tests and logistic regression.
RESULTS
Of the 58 patients, 11 (19%) patients developed a wound dehiscence and 47 (81%) patients healed their abdominal incision without complications. Patients with a dehiscence had a significantly higher body mass index (BMI) (34.32 vs. 29.26 kg/m2, p = 0.014) than patients without a dehiscence. Multiple morphometric measures including higher visceral fat area (p = 0.003) were significant predictors of abdominal donor site wound dehiscence. BMI (odds ratio [OR], 1.16; 95% confidence interval [CI], 1.03–1.32; p = 0.017) and visceral fat area (OR, 1.24; 95% CI, 1.08–1.42; p = 0.002) were independently significant predictors for wound dehiscence in the entire sample. Only visceral fat area retained its predictive ability in patients with a BMI > 30 kg/m2.
CONCLUSIONS
Morphomic measurements correlate with the likelihood of developing postoperative donor site dehiscence after DIEP flap breast reconstruction. As a proof of concept study, this demonstrates that objective data obtained from CT scans may help in preoperatively assessing the risk for donor site wound healing complications in patients undergoing DIEP flap breast reconstruction.
Analytic Morphomics® corresponds to functional status in older patients
Miller AL, Min LC, Diehl KM, Cron DC, Chan CL, Sheetz KH, Terjimanian MN, Sullivan JA, Palazzolo WC, Wang SC, Hall KE, Englesbe MJ
Older patients account for nearly half of the United States surgical volume, and age alone is insufficient to predict surgical fitness. Various metrics exist for risk stratification, but little work has been done to describe the association between measures. We aimed to determine whether Analytic Morphomics®, a novel objective risk assessment tool, correlates with functional measures currently recommended in the preoperative evaluation of older patients.
MATERIALS & METHODS
We retrospectively identified 184 elective general surgery patients aged >70 y with both a preoperative computed tomography scan and Vulnerable Elderly Surgical Pathways and outcomes Assessment within 90 d of surgery. We used Analytic Morphomics® to calculate trunk muscle size (or total psoas area [TPA]) and univariate logistic regression to assess the relationship between TPA and domains of geriatric function mobility, basic and instrumental activities of daily living (ADLs), and cognitive ability.
RESULTS
Greater TPA was inversely correlated with impaired mobility (odds ratio [OR] = 0.46, 95% confidence interval [CI] 0.25-0.85, P = 0.013). Greater TPA was associated with decreased odds of deficit in any basic ADLs (OR = 0.36 per standard deviation unit increase in TPA, 95% CI 0.15-0.87, P < 0.03) and any instrumental ADLs (OR = 0.53, 95% CI 0.34-0.81; P < 0.005). Finally, patients with larger TPA were less likely to have cognitive difficulty assessed by Mini-Cog scale (OR = 0.55, 95% CI 0.35-0.86, P <0.01). Controlling for age did not change results.
CONCLUSIONS
Older surgical candidates with greater trunk muscle size, or greater TPA, are less likely to have physical impairment, cognitive difficulty, or decreased ability to perform daily self-care. Further research linking these assessments to clinical outcomes is needed.
Paraspinous muscle as a predictor of surgical outcome
Canvasser LD, Mazurek AA, Cron DC, Terjimanian MN, Chang ET, Lee CS, Alameddine MB, Claflin J, Davis ED, Schumacher TM, Wang SC, Englesbe MJ
Objective measures for preoperative risk assessment are needed to inform surgical risk stratification. Previous studies using preoperative imaging have shown that the psoas muscle is a significant predictor of postoperative outcomes. Because psoas measurements are not always available, additional trunk muscles should be identified as alternative measures of risk assessment. Our research assessed the relationship between paraspinous muscle area, psoas muscle area, and surgical outcomes.
METHODS
Using the Michigan Surgical Quality Collaborative database, we retrospectively identified 1309 surgical patients who had preoperative abdominal computerized tomography scans within 90 d of operation. Analytic morphomic techniques were used to measure the cross-sectional area of the paraspinous muscle at the T12 vertebral level. The primary outcome was 1-y mortality. Analyses were stratified by sex, and logistic regression was used to assess the relationship between muscle area and postoperative outcome.
RESULTS
The measurements of paraspinous muscle area at T12 were normally distributed. There was a strong correlation between paraspinous muscle area at T12 and total psoas area at L4 (r = 0.72, P <0.001). Paraspinous area was significantly associated with 1-y mortality in both females (odds ratio = 0.70 per standard deviation increase in paraspinous area, 95% confidence interval 0.50-0.99, P = 0.046) and males (odds ratio = 0.64, 95% confidence interval 0.47-0.88, P = 0.006).
CONCLUSIONS
Paraspinous muscle area correlates with psoas muscle area, and larger paraspinous muscle area is associated with lower mortality rates after surgery. This suggests that the paraspinous muscle may be an alternative to the psoas muscle in the context of objective measures of risk stratification.
Dorsal muscle group area and surgical outcomes in liver transplantation
Lee CS, Cron DC, Terjimanian MN, Canvasser LD, Mazurek AA, Vonfoerster E, Tishberg LM, Underwood PW, Chang ET, Wang SC, Sonnenday CJ, Englesbe MJ
Clin Transplant. 2014 Oct;28(10):1092-8. doi: 10.1111/ctr.12422. Epub 2014 Aug 11.
Better measures of liver transplant risk stratification are needed. Our previous work noted a strong relationship between psoas muscle area and survival following liver transplantation. The dorsal muscle group is easier to measure, but it is unclear if they are also correlated with surgical outcomes.
METHODS
Our study population included liver transplant recipients with a preoperative CT scan. Cross-sectional areas of the dorsal muscle group at the T12 vertebral level were measured. The primary outcomes for this study were one- and five-yr mortality and one-yr complications. The relationship between dorsal muscle group area and post-transplantation outcome was assessed using univariate and multivariate techniques.
RESULTS
Dorsal muscle group area measurements were strongly associated with psoas area (r = 0.72; p < 0.001). Postoperative outcome was observed from 325 patients. Multivariate logistic regression revealed dorsal muscle group area to be a significant predictor of one-yr mortality (odds ratio [OR] = 0.53, p = 0.001), five-yr mortality (OR = 0.53, p < 0.001), and one-yr complications (OR = 0.67, p = 0.007).
CONCLUSION
Larger dorsal muscle group muscle size is associated with improved post-transplantation outcomes. The muscle is easier to measure and may represent a clinically relevant postoperative risk factor.
Development of a 10-year-old full body geometric dataset for computational modeling
Mao HM, Holcombe SA, Shen M, Jin X, Wagner CD, Wang SC, Yang KH, King AI
Ann Biomed Eng. 2014 Oct;42(10):2143-55. doi: 10.1007/s10439-014-1078-5. Epub 2014 Aug 13.
The objective of this study was to create a computer-aided design (CAD) geometric dataset of a 10-year-old (10 YO) child. The study includes two phases of efforts. At Phase One, the 10 YO whole body CAD was developed from component computed tomography and magnetic resonance imaging scans of 12 pediatric subjects. Geometrical scaling methods were used to convert all component parts to the average size for a 10 YO child, based on available anthropometric data. Then the component surfaces were compiled and integrated into a complete body. The bony structures and flesh were adjusted as symmetrical to minimize the bias from a single subject while maintaining anthropometrical measurements. Internal organs including the liver, spleen, and kidney were further verified by literature data. At Phase Two, internal characteristics for the cervical spine disc, wrist, hand, pelvis, femur, and tibia were verified with data measured from additional 94 10 YO children. The CAD dataset developed through these processes was mostly within the corridor of one standard deviation (SD) of the mean. In conclusion, a geometric dataset for an average size 10 YO child was created. The dataset serves as a foundation to develop computational 10 YO whole body models for enhanced pediatric injury prevention.
Quantitative detection of cirrhosis: towards the development of computer-assisted detection method
Huhdanpaa HT, Zhang P, Krishnamurthy VN, Douville C, Enchakalody B, Ethiraj S, Wang SC, Su GL
There are distinct morphologic features of cirrhosis on CT examinations; however, such impressions may be subtle or subjective. The purpose of this study is to build a computer-aided diagnosis (CAD) method to help radiologists with this diagnosis. One hundred sixty-seven abdominal CT examinations were randomly divided into training (n = 88) and validation (n = 79) sets. Livers were analyzed for morphological markers of cirrhosis and logistic regression models were created. Using the area under curve (AUC) for model performance, the best model had 0.89 for the training set and 0.85 for the validation set. For radiology reports, sensitivity of reporting cirrhosis was 0.45 and specificity 0.99. Using the predictive model adjunctively, radiologists' sensitivity increased to 0.63 and specificity slightly decreased to 0.97. This study demonstrates that quantifying morphological features in livers may be utilized for diagnosing cirrhosis and for developing a CAD method for it.
Subcutaneous fat distribution in the human torso
Holcombe SA, Wang SC
International Research Council on Biomechanics of Injury. 2014 Sep. Session S1-5 - Tissue Biomechanics/Tissue Characterization 2: IRC-14-43.
With obesity becoming a major health issue in recent years and a topic of interest in vehicle occupant safety, there is a need for detailed descriptions of body fat distribution in order to develop accurate models of the human body. In this study subcutaneous fat measurements were obtained from over 17,000 CT scans using planar distance maps from skin surface locations to the fascial envelope. Measures were taken as a map registered by vertebral level (from T6 down to L5, extended to the sacrum) and body location around the body perimeter. Multivariate regression maps were calculated showing the individual effect of demographics on the subcutaneous layer thickness. Regression coefficients were statistically significant, with results showing the progression of 20 years of age producing a migration of 3mm of fat from mid‐abdominal to lower‐ abdominal regions and female occupants having thicker subcutaneous regions compared to males by between 6 and 24mm with accumulation peaks near the buttocks and breasts. Each 20kg of added body weight produce regional fat increases between 2 and 14mm across the torso, with a primary peak near the hips and secondary peak near the lower abdomen.
Perioperative changes in trunk musculature on postoperative outcomes
Zarinsefat A, Terjimanian MN, Sheetz KH, Stein IC, Mazurek AA, Waits SA, Sullivan JA, Wang SC, Englesbe MJ
Surgeons often face difficult decisions in selecting which patients can tolerate major surgical procedures. Although recent studies suggest the potential for trunk muscle size, as measured on preoperative imaging, to inform surgical risk, these measures are static and do not account for the effect of the surgery itself. We hypothesize that trunk muscle size will show dynamic changes over the perioperative period, and this change correlates with postoperative mortality risk.
METHODS
A total of 425 patients who underwent inpatient general surgery were identified to have both a 90-d preoperative and a 90-d postoperative abdominal computed tomography scan. The change in trunk muscle size was calculated using analytic morphomic techniques. The primary outcome was 1-y survival. Covariate-adjusted outcomes were assessed using multivariable logistic regression.
RESULTS
A total of 82.6% patients (n = 351) experienced a decrease in trunk muscle size in the time between their scans (average 62.1 d). When stratifying patients into tertiles of rate of change in trunk muscle size and adjusting for other covariates, patients in the tertile of the greatest rate loss had significantly increased risk of 1-y mortality than those in the tertile of the least rate loss (P = 0.002; odds ratio = 3.40 95% confidence interval, 1.55-7.47). The adjusted mortality rate for the tertile of the greatest rate loss was 24.0% compared with 13.3% for the tertile of the least decrease.
CONCLUSIONS
Trunk muscle size changes rapidly in the perioperative period and correlates with mortality. Trunk muscle size may be a critical target for interventional programs focusing on perioperative optimization of the surgical patient.
Abdominal wall dynamics after component separation hernia repair
Lisiecki J, Kozlow JH, Agarwal S, Ranganathan K, Terjimanian MN, Rinkinen J, Brownley RC, Enchakalody B, Wang SC, Levi B
The component separation technique (CST) is an important technique now used frequently in complex ventral hernia repair (VHR). Although this technique has demonstrated superior success rates, there is a paucity of research describing how release of the external obliques coupled with rectus myofascial advancement alters the morphology of the abdominal architecture. In this study, we apply the new concept of Analytic Morphomics® to describe the immediate changes in morphology of the abdomen that take place after VHR by CST.
METHODS
We identified 21 patients who underwent VHR by CST and received both preoperative and postoperative computed tomography scans between 2004 and 2009 in our clinical database. The surgical technique involved incisional release of the external oblique muscle lateral to the linea semilunaris with rectus abdominis myofascial advancement in all patients. Using semiautomated morphomic analysis, we measured the pre- and post-operative dimensions of the abdominal wall including the anterior-posterior distance from the anterior vertebra-to-skin and fascia along with the circumferential area of the skin and fascial compartments. Paired Student t-tests were used to compare pre- and post-operative values.
RESULTS
After hernia repair, there was a decrease in the anterior vertebra-to-skin distance (16.6 cm-15.8 cm, P = 0.007). There were also decreases in total body area (968.0 cm(2)-928.6 cm(2), P = 0.017) and total body circumference (113.6 cm-111.4 cm, P = 0.016). The distance from fascia to skin decreased as well, almost to the point of statistical significance (3.3 cm-2.9 cm, P = 0.0505). Interestingly, fascia area and circumference did not decrease significantly after the operation (578.2 cm(2)-572.5 cm(2), P = 0.519, and 89.1 cm-88.6 cm, P = 0.394, respectively).
CONCLUSIONS
Morphomic analysis can be used to compare and pre- and post-operative changes in patients undergoing abdominal surgery. Our study demonstrates that component separation affects the dimensions of the entire abdomen, but leaves the fascia area and circumference relatively unchanged. These changes in the abdominal wall may help explain the muscular changes observed as a result of this operation and demonstrate that this is a functional operation that restores fascial area. By better defining the effects of this procedure, we can better understand the reason for its clinical success.
Transsacral screw safe zone size by sacral segmentation variations
Lee JJ, Rosenbaum SL, Martusiewicz A, Holcombe SA, Wang SC, Goulet JA
Abstract
Variations in sacral segmentation may preclude safe placement of transsacral screws for posterior pelvis fixation. We developed a novel automated 3D technique to determine the safe zone size for transsacral screws in the upper two sacral segments in 526 adult pelvis computed tomography scans. Safe zone sizes were then compared by gender and sacral segmentation variations (number of neuroforamen and the presence/absence of lumbosacral transitional vertebrae, ± LSTV). Ten millimeters was used as the safety threshold for a large screw. 3 (0.6%), 366 (70%), and 157 (30%) sacra had 3, 4, or 5 neuroforamen, respectively. Eighty-eight (17%) were +LSTV. Safe zone size depended on gender, number of neuroforamen in -LSTV sacra and presence of LSTV (p < 0.001) but not on the uni- or bilateral nature of the LSTV. 17% of -LSTV sacra were below the safety threshold in S1, 27% in S2, whereas 3% of +LSTV sacra were below in S1, 74% in S2. Of -LSTV sacra that cannot take an S1 screw safely, 77% can do so in S2, leaving only 4% of sacra that cannot accommodate a screw safely in either upper segment. The results demonstrate a predictable pattern of safe zone size based on gender and sacral segmentation variations.
Quantification of pediatric and adult cervical vertebra-anatomical characteristics by age and gender for automotive application
Parenteau CS, Wang NC, Zhang P, Caird MS, Wang SC
Traffic Inj Prev. 2014 May 27;15(6):572-82. doi: 10.1080/15389588.2013.843774.
The cervical anatomy has been shown to affect injury patterns in vehicle crashes. Characterizing the spine anatomy and changes associated with growth and gender is important when assessing occupant protection. In this study, selected cervical characteristics were quantified.
METHODS
Computed tomography (CT) scans of 750 patients were selected from the University of Michigan trauma database&59; 314 were children and 436 were adults. Four variables were obtained: the maximum spinal canal radius, vertebral body depth, facet angles, and retroversion angles.
RESULTS
The cervical spine measurements varied with age and gender. The body depth increased nonlinearly with age. The average vertebral body depth at C4 was 9.2 ± 0.38 mm in the 0-3 age group, 15.7 ± 0.29 mm in the 18-29 age group, and 17.2 ± 0.46 mm in the 60+ age group. Pediatric and adult males had larger vertebral body depth than females overall, irrespective of vertebral level (P <.001). Compared to females, the vertebral body depth was 8-9 percent greater in male children and 13-16 percent greater in adult males. The average radius varied with gender, with male children generally having a larger radius than females irrespective of vertebral level (P <.001). Overall, spinal canal radius was smallest in the 0-3 and 60+ age groups and largest in the 18-29 age group. The C4 radius was 5.91 ± 0.17, 6.28 ± 0.14, and 6.73 ± 0.17 mm respectively. The radius was larger in the 4-7 age group than in the 0-3 age group, irrespective of vertebral level (P <.0001). There were nonsignificant radius changes between the 4-7 and 8-11 age groups and the 8-11 and age 12-17 groups, suggesting that the size of the spinal cord reaches near maturation by the age of 7. Facet angles decreased with age in children and increased with age in adults. The average facet angles were largest in the 0-3 age group (P <.1, C2-C6). Adult facet angles were greater in the 60+ age group than in the 18-29 age group (P <.0001, C2-C6). Males had larger facet angles than females overall (P <.01 at C2, C5-C7). The retroversion angles were largest at C6 and C7. They increased with age in children and decreased in the adult population; they were larger (5-22%) in the 18-29 age group than in the 60+ age group (P <.0001, C2-C6).
CONCLUSIONS
The results obtained in this study help explain variations in cervical anatomical changes associated with age and gender. The information is useful when assessing differences in injury patterns between different segments of the population. Anatomical measurements of the cervical spine should be considered for the development of models used to assess injury mechanisms for various occupant age groups.
Use of morphomic assessment of body composition to quantify risk of surgical-site infection in patients undergoing component separation ventral hernia repair
Levi B, Zhang P, Lisiecki J, Terjimanian MN, Rinkinen J, Agarwal S, Holcombe SA, Kozlow JH, Wang SC, Kuzon WM
Body mass index does not allow accurate risk stratification for individuals undergoing component separation repair of ventral hernias. The authors hypothesized that tissue morphology measurements (morphomics) of preoperative computed tomography scans stratify the risk of surgical site infection in patients undergoing ventral hernia repair with a component separation technique.
METHODS
The authors identified 93 patients who underwent component release ventral hernia repair (2004 to 2012). The surgical technique involved release of the external oblique muscle lateral to the linea semilunaris. Using analytic morphomic techniques, the authors measured patients' morphology using routine preoperative computed tomography scans. Two-sample t test was used to evaluate the effect of morphomic and demographic factors on surgical-site infection. Separate logistic regression analyses were performed on these morphomic factors to evaluate their predictive value in assessing the risk of surgical site infection, controlling for demographic covariates.
RESULTS
Surgical site infections were observed in 31 percent (n = 29) of the population. Subcutaneous fat area, total body area, and total body circumference had increased odds ratios for surgical site infection (p = 0.004, 0.014, and 0.012, respectively), indicating that these measures are better associated with surgical site infection than body mass index. These calculations control for demographic covariates, confirming that these morphomic parameters are predictive of surgical site infection.
CONCLUSION
Specific morphomic values serve as superior predictors of surgical site infection in patients undergoing component separation technique hernia repair than currently used values such as body mass index.
CLINICAL QUESTION/LEVEL OF EVIDENCE
Risk, III.
Morphometric age and mortality after liver transplant
Waits SA, Kim EK, Terjimanian MN, Tishberg LM, Harbaugh CM, Sheetz KH, Sonnenday CJ, Sullivan JA, Wang SC, Englesbe MJ
Morphometric assessment has emerged as a strong predictor of postoperative morbidity and mortality. However, a gap exists in translating this knowledge to bedside decision making. We introduced a novel measure of patient-centered surgical risk assessment: morphometric age.
OBJECTIVE
To investigate the relationship between morphometric age and posttransplant survival.
DATA SOURCES
Medical records of recipients of deceased-donor liver transplants (study population) and kidney donors/trauma patients (morphometric age control population).
STUDY SELECTION
A retrospective cohort study of 348 liver transplant patients and 3313 control patients. We assessed medical records for validated morphometric characteristics of aging (psoas area, psoas density, and abdominal aortic calcification). We created a model (stratified by sex) for a morphometric age equation, which we then calculated for the control population using multivariate linear regression modeling (covariates). These models were then applied to the study population to determine each patient's morphometric age.
DATA EXTRACTION AND SYNTHESIS
All analytic steps related to measuring morphometric characteristics were obtained via custom algorithms programmed into commercially available software. An independent observer confirmed all algorithm outputs. Trained assistants performed medical record review to obtain patient characteristics.
RESULTS
Cox proportional hazards regression model showed that morphometric age was a significant independent predictor of overall mortality (hazard ratio, 1.03 per morphometric year [95% CI, 1.02-1.04; P < .001]) after liver transplant. Chronologic age was not a significant covariate for survival (hazard ratio, 1.02 per year [95% CI, 0.99-1.04; P = .21]). Morphometric age stratified patients at high and low risk for mortality. For example, patients in the middle chronologic age tertile who jumped to the oldest morphometric tertile have worse outcomes than those who jumped to the youngest morphometric tertile (74.4% vs 93.2% survival at 1 year [P = .03]; 45.2% vs 75.0% at 5 years [P = .03]).
CONCLUSIONS & RELEVANCE
Morphometric age correlated with mortality after liver transplant with better discrimination than chronologic age. Assigning a morphometric age to potential liver transplant recipients could improve prediction of postoperative mortality risk.
Use of morphomic analysis for preoperative risk stratification in patients undergoing major head and neck cancer surgery
Rinkinen J, Agarwal S, Terjimanian M, Beauregard J, Ranganathan K, Benedict M, Hiltzik D, Stein I, Lisiecki J, Wang SC, Buchman SR, Levi B.
The psoas muscle has been shown to predict patient outcomes based on the quantification of muscle area using computed tomography (CT) scans. The accuracy of morphomic analysis on other muscles has not been clearly delineated. In this study, we determine the correlation between temporalis muscle mass, psoas muscle area, age, body mass index (BMI), and gender.
METHODS
Temporalis and psoas muscle dimensions were determined on all trauma patients who had both abdominal and maxillofacial CT scans at the University of Michigan between 2004 and 2011. Age, BMI, and gender were obtained through chart review. Univariate and multivariate analyses were performed to determine the relative relationship between morphomic data of the temporalis and psoas muscles and the ability of such information to correspond with clinical variables, such as BMI, age, and gender.
RESULTS
A total of 646 patients were included in the present study. Among the 249 (38.5%) women and 397 (61.5%) men, the average age was 49.2 y. Average BMI was 27.9 kg/m2. Total psoas muscle area directly correlated with mean temporalis muscle thickness (r = 0.57, P < 0.001). There was an indirect correlation between age and psoas muscle area (r = -0.52, P < 0.001) and temporalis muscle thickness (r = -0.36, P < 0.001). Neither psoas nor temporalis measurements correlated strongly with BMI (r = 0.18, P < 0.001; r = 0.14, P = 0.002), although stronger correlations were found in a more "frail," subgroup as defined by a BMI of <20 (r = 0.59, P = 0.002).
CONCLUSIONS
We demonstrate that dimensions of the temporalis muscle can be quantified and may serve as a proxy for age. Going forward, we aim to assess the utility of temporalis and psoas morphomics in predicting complication rates among trauma patients admitted to the hospital to predict outcomes in the future.
Characterization of vertebral angle and torso depth by gender and age groups with a focus on occupant safety
The human body changes as it becomes older. The automotive safety community has been interested in understanding the effect of age on restraint performance. Focus has been placed on characterizing the body's structural changes associated with age and gender. In this study, spine alignment and torso depth were assessed, because both variables have been shown to affect injury risk.
METHODS
The data was obtained from computed tomography (CT) scans of more than 24,000 patients aged 16 and older. The data consisted of thoracic and lumbar vertebral angles relative to a fixed plane, as well as vertebra-to-front skin and spine-to-back skin distances. Angle measurements were taken in the sagittal plane at each vertebra level from T1 to L5; distance measurements were taken from T6 to L5. The data were analyzed as a function of gender and age with the young group defined as 16 to 29 years old and the older group as 75 and up.
RESULTS
Vertebral angles were different depending on location. They varied from -24.5 ± 8.9° at T2 to 12.2 ± 5.6° at L1. The vertebral angles also varied with age. Angles in the older male group were 1.74 times larger at T1 and 2.03 times larger at T7 than in the young male group. Similar findings were observed for females. The effect of age and gender was modeled with forward/backward selection using a regression model. The vertebra-to-front skin distance also differed depending on vertebral level. It was highest at T10 at 162.5 ± 30.9 mm and lowest at L4 at 125.3 ± 37.3 mm for the entire study population. On average, males had larger distances than females. The spine-to-back distances were greatest in the lumbar area. The spine-to-back distance increased with lower vertebral level, regardless of age. The vertebral angle and distance data were analyzed for a male subgroup approximating the height and weight of a 50th percentile male dummy. The results showed that the vertebra-to-front skin distance increased with age. There was not a clear trend for the spine-to-back skin distance and L1 vertebral angle.
CONCLUSIONS
The changes in the vertebral angles, as well as the anterior and posterior spine-to-skin distances along the sagittal plane, were determined as a function of age and gender. The effect was greatest in the mid-thoracic area. Spine alignment and body shape differences need to be considered in human mathematical models used to develop safety countermeasures for the older population, because they may affect the loading path and lead to different seating postures or belt positioning. Supplemental materials are available for this article. Go to the publisher's online edition of Traffic Injury Prevention to view the supplemental file.
2013
The quantification of liver anatomical changes and assessment of occupant liver injury patterns
Parenteau CS, Ehrlich P, Ma L, Su GL, Holcombe S, Wang SC
Liver injuries can be significant in vehicle crashes. In this study, the liver anatomy was quantified in both adult and pediatric populations as a function of gender and age. Five anatomical liver measurements were determined using CT scans of 260 normal livers. These measurements include the area and volume, and the length, width, and girth of the liver (IRB HUM00041441). To characterize geometrical shape, an inscribed sphere and circumscribed ellipsoid were fitted on the measurements. In the pediatric population the liver area and volume continuously increased with age. When normalized by patient weight, volume measurements show a decrease in volume with age, suggesting that the liver occupies a smaller proportion of the body with age. In the adult population, liver measurements varied with gender. The superior and inferior locations of the liver were also recorded with respect to the spine. The lower portion was at the L3 in small children and at L2 as children approached puberty. It stayed in that area through the 60+ group, offering more ribcage protection. Liver injury patterns were also assessed in crash occupants. Seventy-two occupants with moderate to severe (AIS 2+) liver injuries were investigated. A new methodology was presented and consisted of quantifying blood volumes. The results were compared to overall liver volume and injury scales. No clear distinction on the injury pattern was observed by age group. Liver injuries were more commonly associated with AIS 2+ thoracic injuries in adults than in children. Most injuries occurred in the right lobe.
Prediction of thoracic injury severity in frontal impacts by selected anatomical morphomic variables through model-averaged logistic regression approach
Zhang PC, Parenteau CS, Wang L, Holcombe S, Kohoyda-Inglis C, Sullivan J, Wang SC
This study resulted in a model-averaging methodology that predicts crash injury risk using vehicle, demographic, and morphomic variables and assesses the importance of individual predictors. The effectiveness of this methodology was illustrated through analysis of occupant chest injuries in frontal vehicle crashes. The crash data were obtained from the International Center for Automotive Medicine (ICAM) database for calendar year 1996 to 2012. The morphomic data are quantitative measurements of variations in human body 3-dimensional anatomy. Morphomics are obtained from imaging records. In this study, morphomics were obtained from chest, abdomen, and spine CT using novel patented algorithms. A NASS-trained crash investigator with over thirty years of experience collected the in-depth crash data. There were 226 cases available with occupants involved in frontal crashes and morphomic measurements. Only cases with complete recorded data were retained for statistical analysis. Logistic regression models were fitted using all possible configurations of vehicle, demographic, and morphomic variables. Different models were ranked by the Akaike Information Criteria (AIC). An averaged logistic regression model approach was used due to the limited sample size relative to the number of variables. This approach is helpful when addressing variable selection, building prediction models, and assessing the importance of individual variables. The final predictive results were developed using this approach, based on the top 100 models in the AIC ranking. Model-averaging minimized model uncertainty, decreased the overall prediction variance, and provided an approach to evaluating the importance of individual variables. There were 17 variables investigated: four vehicle, four demographic, and nine morphomic. More than 130,000 logistic models were investigated in total. The models were characterized into four scenarios to assess individual variable contribution to injury risk. Scenario 1 used vehicle variables;
Scenario 2, vehicle and demographic variables; Scenario 3, vehicle and morphomic variables; and Scenario 4 used all variables. AIC was used to rank the models and to address over-fitting. In each scenario, the results based on the top three models and the averages of the top 100 models were presented. The AIC and the area under the receiver operating characteristic curve (AUC) were reported in each model. The models were re-fitted after removing each variable one at a time. The increases of AIC and the decreases of AUC were then assessed to measure the contribution and importance of the individual variables in each model. The importance of the individual variables was also determined by their weighted frequencies of appearance in the top 100 selected models. Overall, the AUC was 0.58 in Scenario 1, 0.78 in Scenario 2, 0.76 in Scenario 3 and 0.82 in Scenario 4. The results showed that morphomic variables are as accurate at predicting injury risk as demographic variables. The results of this study emphasize the importance of including morphomic variables when assessing injury risk. The results also highlight the need for morphomic data in the development of human mathematical models when assessing restraint performance in frontal crashes, since morphomic variables are more "tangible" measurements compared to demographic variables such as age and gender.
Cost of major surgery in the sarcopenic patient
Sheetz KH, Waits SA, Terjimanian MN, Sullivan J, Campbell DA, Wang SC, Englesbe MJ
J Am Coll Surg. 2013 Nov;217(5):813-8. doi: 10.1016/j.jamcollsurg.2013.04.042. Epub 2013 Oct 9.
Sarcopenia is associated with poor outcomes after major surgery. There are currently no data regarding the financial implications of providing care for these high-risk patients.
STUDY DESIGN
We identified 1,593 patients within the Michigan Surgical Quality Collaborative (MSQC) who underwent elective major general or vascular surgery at a single institution between 2006 and 2011. Patient sarcopenia, determined by lean psoas area (LPA), was derived from preoperative CT scans using validated analytic morphomic methods. Financial data including hospital revenue and direct costs were acquired for each patient through the hospital's finance department. Financial data were adjusted for patient and procedural factors using multiple linear regression methods, and Mann-Whitney U test was used for significance testing.
RESULTS
After controlling for patient and procedural factors, decreasing LPA was independently associated with increasing payer costs ($6,989.17 per 1,000 mm(2) LPA, p < 0.001). The influence of LPA on payer costs increased to $26,988.41 per 1,000 mm(2) decrease in LPA (p < 0.001) in patients who experienced a postoperative complication. Further, the covariate-adjusted hospital margin decreased by $2,620 per 1,000 mm(2) decrease in LPA (p < 0.001) such that average negative margins were observed in the third of patients with the smallest LPA.
CONCLUSIONS
Sarcopenia is associated with high payer costs and negative margins after major surgery. Although postoperative complications are universally expensive to payers and providers, sarcopenic patients represent a uniquely costly patient demographic. Given that sarcopenia may be remediable, efforts to attenuate costs associated with major surgery should focus on targeted preoperative interventions to optimize these high risk patients for surgery.
Can anatomical morphomic variables help predict abdominal injury rates in frontal vehicle crashes?
Parenteau CS, Zhang P, Holcombe S, Kohoyda-Inglis C, Wang SC
Traffic Inj Prev. 2013 Oct 11;15(6):619-26. doi: 10.1080/15389588.2013.852665.
Abdominal injuries resulting from vehicle crashes can be significant, in particular when undetected. In this study, abdominal injuries for occupants involved in frontal impacts were assessed using crash and medical data.
METHODS
Injury rates and patterns were first assessed with respect to thoracic injuries. A statistical analysis was then conducted to predict abdominal injury outcome using 18 covariate variables, including 4 vehicle, 4 demographic, and 10 morphomic, derived from computed tomography (CT) scans. More than 260,000 logistic regression models were fitted using all possible variable combinations. The models were ranked using the Akaike information criterion (AIC) and combined through the model-averaging approach to produce the optimal predictive model. The performance of the models was then assessed using the area under the curve (AUC).
RESULTS
The rate of serious thoracic injury was 2.49 times higher than the rate of abdominal injury. The associated odds ratio was 2.31 (P <.01). These results suggest a strong association between serious abdominal and thoracic injuries. The optimal model AUC was 0.646 when using solely vehicle data, 0.696 when combining vehicle and demographic data, 0.866 when combining vehicle and morphomic data, and 0.879 when combining vehicle, demographic, and morphomic data. These results suggest that morphomic variables better predict abdominal injury outcomes than demographic variables. The most important morphomics variables included visceral fat area, trabecular bone density, and spine angulation.
CONCLUSION
This study is the first to combine vehicle, demographic, and anatomical data to predict abdominal injury rates in frontal crashes.
Decreased core muscle size is associated with worse patient survival following esophagectomy for cancer
Sheetz KH, Zhao L, Holcombe SA, Wang SC, Reddy RM, Lin J, Orringer MB, Chang AC
Dis Esophagus. 2013 Sep-Oct;26(7):716-22. doi: 10.1111/dote.12020. Epub 2013 Jan 25.
Preoperative risk assessment, particularly for patient frailty, remains largely subjective. This study evaluated the relationship between core muscle size and patient outcomes following esophagectomy for malignancy. Using preoperative computed tomography scans in 230 subjects who had undergone transhiatal esophagectomy for cancer between 2001 and 2010, lean psoas area (LPA), measured at the fourth lumbar vertebra, was determined. Cox proportional hazards regression was employed to analyze overall survival (OS) and disease-free survival (DFS) adjusted for age, gender, and stage, and the Akaike information criterion was used to determine each covariate contribution to OS and DFS. Univariate analysis demonstrated that increasing LPA correlated with both OS (P = 0.017) and DFS (P = 0.038). In multivariate analysis controlling for patient and tumor characteristics, LPA correlated with OS and DFS in patients who had not received neoadjuvant treatment (n = 64), with higher LPA associated with improved OS and DFS. Moreover, LPA was of equivalent, or slightly higher importance than pathologic stage. These measures were not predictive among patients (n = 166) receiving neoadjuvant chemoradiation. Core muscle size appears to be an independent predictor of both OS and DFS, as significant as tumor stage, in patients following transhiatal esophagectomy. Changes in muscle mass related to preoperative treatment may confound this effect. Assessment of core muscle size may provide an additional objective measure for risk stratification prior to undergoing esophagectomy.
Temporal morphomics as a model for determining preoperative risk of blood transfusion in non-syndromic craniosynostasis patients
Rinkinen J, Terjimanian M, Benedict M, Hiltzik D, Seyi A, Lisiecki J, Wang SC, Buchman SR, Levi B.
Estimates of blood loss during craniosynostosis surgeries have ranged from 42 to 126 percent of infant's total blood volume. Currently, no risk model has been developed to determine the likelihood of needing a blood transfusion. The authors propose an objective model, based on patients' three-dimensional anatomical characteristics, to stratify the likelihood of needing perioperative packed red blood cells.
METHODS
High-throughput image analysis from already ordered preoperative computed tomographic scans was used to reconstruct the three-dimensional anatomy of the temporalis muscle and overlying temporal fat pad. Using these morphomic measurements, the authors created a risk assessment model of the amount of packed red blood cells infused based on morphomic variations in temporal soft tissue.
RESULTS
The authors evaluated 139 infants with nonsyndromic craniosynostosis from the University of Michigan Health System. Results show the need for blood transfusion ranged from 94.1 percent among patients in the smallest quartile for temporal fat pad volume compared with 65.7 percent among the group with the largest quartile for temporal fat pad volume (p = 0.0057). Using multivariable linear regression, temporal fat pad volume (p = 0.012) and fat pad thickness (p = 0.036) were independent predictors for amount of packed red blood cells required.
CONCLUSIONS
The authors demonstrate that patients with diminished temporal fat pad volume are significantly more likely to need increased packed red blood cell transfusions. In addition, by use of multivariable linear regression, their data suggest that temporal fat pad volume and thickness were independent predictors for the amount of required transfusion of packed red blood cells.
Analytic morphometric assessment of patients undergoing colectomy for colon cancer
Sabel MS, Terjimanian M, Conlon AS, Griffith KA, Morris AM, Mulholland MW, Englesbe MJ, Holcombe S, Wang SC
Analytic morphometrics provides objective data that may better stratify risk. We investigated morphometrics and outcome among colon cancer patients.
METHODS
An IRB-approved review identified 302 patients undergoing colectomy who had CT scans. These were processed to measure psoas area (PA), density (PD), subcutaneous fat (SFD), visceral fat (VF), and total body fat (TBF). Correlation with complications, recurrence, and survival were obtained by t-tests and linear regression models after adjusting for age and Charlson index.
RESULTS
The best predictor of surgical complications was PD. PMH, Charlson, BMI, and age were not significant when PD was considered. SF area was the single best predictor of a wound infection. While all measures of obesity correlated with outcome, TBF was most predictive. Final multivariate Cox models for survival included age, Charlson score, nodal positivity, and TBF.
CONCLUSIONS
Analytic morphometric analysis provided objective data that stratified complications and outcome better than age, BMI, or co-morbidities.
Analysis of Morphomics Parameters by Gender and BMI Groups: thorax shape and H-point location.
Parenteau CS, Zhang P, Holcombe S, Kohoyda-Inglis C, Wang SC
International Research Council on Biomechanics of Injury. 2013 Sep. Session S4-4 - Accident Analysis 2: IRC-13-81.
The automotive safety community is questioning the effect of obesity on the performance and assessment of occupant protection systems. This study analyzed CT scan measurements of 10,952 individuals older than 15 years by Body Mass Index (BMI) and gender, including the H‐point location defined relative longitudinal distance between the centroid of the femoral head and the most posterior skin measurement, vertebra‐to‐front‐skin distance, and spine‐to‐back‐skin distance along the sagittal plane. The distance data was obtained at each vertebra level.The average H‐point location increased with BMI and varied with gender. A regression analysis was fitted on the data. For females, it was equal to 55.90 +2.47*BMI in the normal size group, 86.25+1.30*BMI in the obese group, and 116.25+0.55*BMI mm in the morbidly obese group (p<0.01). For males the corresponding H‐point was 64.12+2.11*BMI, 77.28+1.62*BMI, and 95.13+1.17*BMI mm (p<0.01). The vertebra‐to‐front skin and spine‐ to‐back skin distances also increased with BMI and differed with gender. With the increasing worldwide concern for obese occupant protection, test devices representative of this segment of the population are necessary. Human math models provide the best option for a parametric analysis of protection systems designed and optimized for various BMI and gender groups. The morphomic data was analyzed to represent a 5th percentile female and 50th percentile male dummy. These results will be useful in the modifications of the current human mathematical models to represent obese occupants.
Restrained Male and Female Occupants in Frontal Crashes: Are We Different?
Parenteau CS, Zhang P, Holcombe S, Kohoyda-Inglis C, Wang SC
International Research Council on Biomechanics of Injury. 2013 Sep. Session S6-1 - Frontal Impacts: IRC-13-98.
The safety community is questioning the effect of gender on the performance and assessment of occupant protection systems. This study consists of: 1) an investigation of NASS‐CDS data with belted occupants involved in frontal vehicle crashes and 2) a comparison of dummy responses in two matched frontal tests. Because of recent work on a 50th female dummy neck, focus was placed on neck responses. An assessment of cervical facet angles was also carried out from computed tomography (CT) scans of 423 adult patients.The NASS‐CDS data showed that the relative risk of being seriously injured was higher in females than in males for crash severities up to 65 km/h. Females had higher overall risks of serious injury in all body regions except for the head and the abdomen. In 25 to 65 km/h crashes, females were more at risk of spine injuries than males. In the matched tests, the normalized results showed overall higher biomechanical responses in the female than in the male dummy, in particular in the neck region. Airbag interaction with the head/neck complex was noted with the female dummy. The CT scan data indicated that the cervical facet angles increased with age, becoming more horizontal. The increase was greater in females than in males. The quantification of anatomical changes associated with gender is needed to improve physical and/or numerical tools used to assess occupant responses and to understand differences in injury patterns.
Morphomic Measurement of the Temporalis Muscle and Zygomatic Bone as Novel Predictors of Hospital-Based Clinical Outcomes in Patients with Mandible Fracture
Lisiecki J, Zhang P, Wang L, Rinkinen J, De La Rosa S, Enchakalody B, Brownley RC, Wang SC, Buchman SR, Levi B
Patients with mandibular fracture often have comorbidities and concomitant injuries making the decision for when and how to operate a challenge. Physicians describe "temporalis wasting" as a finding that indicates frailty; however, this is a subjective finding without quantitative values. In this study, we demonstrate that decreased morphomic values of the temporalis muscle and zygomatic bone are an objective measure of frailty associated with increased injury-induced morbidity as well as negative impact on overall hospital-based clinical outcomes in patients with mandible fracture.
METHODS
Computed tomographic (CT) scans from all patients with a diagnosis of a mandible fracture in the University of Michigan trauma registry and with a hospital admission were collected from the years 2004 to 2011. Automated, high-throughput CT analysis was used to reconstruct the anatomy and quantify morphomic values (temporalis volume, area and thickness, and zygomatic thickness) in these patients using MATLAB v13.0 (MathWorks Inc, Natick, MA, USA). Subsequently, a subset of 16 individuals with a Glasgow Coma Scale of 14 or 15 was analyzed to control for brain injury. Clinical data were obtained, and the association between morphomic measurements and clinical outcomes was evaluated using Pearson correlation for unadjusted analysis and multiple regression for adjusted analysis.
RESULTS
The mean age of patients in the study was 47.1 years. Unadjusted analysis using Pearson correlation revealed that decreases in zygomatic bone thickness correlated strongly with increases in hospital, intensive care unit, and ventilator days (P < 0.0001, P = 0.0003, and P < 0.0017, respectively). Furthermore, we found that decreases in temporalis mean thickness correlated with increases in hospital and ventilator days (P = 0.0264 and P = 0.0306, respectively). Similarly, decreases in temporalis local mean thickness are significantly correlated with increases in hospital and ventilator days (P = 0.0232 and P = 0.0472, respectively).
CONCLUSIONS
Decreased thicknesses of the zygomatic bone and temporalis muscle are significantly correlated with higher hospital, ventilator, and intensive care unit days in patients with mandibular fracture receiving reconstructive operations. This morphomic methodology provides an accurate, quantitative means to evaluate craniofacial trauma patient frailty, injury, and outcomes using routinely obtained CT scans. In the future, we plan to apply this approach to determine preoperative risk stratification and assist in surgical planning.
Variation in the femoral bow: a novel high-throughput analysis of 3,922 femurs on cross-sectional imaging
Maratt J, Schilling PL, Holcombe S, Dougherty R, Murphy R, Wang SC, Goulet JA
J Orthop Trauma. 2013 June 11;28(1):6-9. doi: 10.1097/BOT.0b013e31829ff3c9.
To evaluate femoral radius of curvature in a large sample of computed tomography scans to definitively determine the relationship between radius of curvature and femoral length, age, gender, ethnicity, body mass index and cortical thickness.
METHODS
A retrospective review was conducted of the electronic medical records and advanced imaging of 1961 patients who underwent pulmonary embolism protocol computed tomography scans between December 1999 and March 2010. The computed tomography scans were imported from the clinical picture archiving and communication system archive into a research image archive and analysis system. Each scan was processed by an automated system that algorithmically determined bony landmarks, adjusted for body position within the scanner and measured the radius of curvature.
RESULTS
The mean medullary radius of curvature of 3922 femurs was 112 cm (SD = 26 cm). The mean anterior radius of curvature of the femurs was 145 cm (SD = 55 cm). There was a moderately strong positive correlation (0.36-0.39) between femoral length and radius of curvature (P < 0.0001) that was not affected by age, body mass index, cortical thickness, gender, or ethnicity. No significant relationship was found between either gender or ethnicity and radius of curvature independent of femoral length.
CONCLUSIONS
Differences in radius of curvature based on ethnicity and gender exist primarily because of the variation in average height, and therefore femur length, that exists between ethnic groups and genders. These data may prove useful in the design of safer intramedullary implants that accommodate a greater spectrum of anatomic variation.
Age-Based Predictive Model of the Pediatric Ribcage
Holcombe S, Kindig M, Zhang P, Parenteau C, Rabban P, Hully L, Wang SC
International Journal of Automotive Engineering. 2013 May 23. Vol. 5 (2014) No. 1 p. 15-22
Ribcage geometry of 327 boys and girls (aged 1-18) was extracted from CT scans, consisting of three dimensional curves fit through the centroidal path of 6306 individual ribs. Each rib was characterized by 7 parameters describing a rib's in-plane geometry, 2 describing its out-of-plane deviation, and 3 describing the rib orientation relative to anatomical planes. Parameters were predicted by age and gender to fully describe variation in size and shape of rib centroidal geometry as a continuous function following growth throughout childhood. A demographics-based model was also presented describing average ribcage geometry for children of any given age, weight, and height.
Novel application of human morphomics to quantify temporal soft tisues in Pierre Robin and Treacher Collins
Lisiecki J, Wan DC, Wang L, Zhang P, Enchakalody B, Zhang X, Kasten SJ, Wang SC, Buchman SR, Levi B.
J Craniofac Surg. 2012 June 7;24(1):158-62. doi: 10.1097/SCS.0b013e3182646411.
Pierre Robin sequence (PR) and Treacher Collins syndrome (TC) are congenital disorders associated with multiple craniofacial abnormalities. The mandibular malformations linked with these maladies are closely associated with the form and function of the temporalis muscle. Despite these associations, a paucity of research has been directed at quantifying how these malformations affect the tissues of the temporal region. In this paper, we seek to quantify differences in the temporalis muscle and the temporal fat pad using a novel CT-derived analytic program to examine craniofacial morphomic indices within these patient groups in comparison to normal age-matched controls. We posit that the temporalis muscle and temporal fat pad, like other derivatives of the first branchial arch, are hypoplastic in patients with TC and PR compared to age-matched controls.
METHODS
High-throughput image analysis was used to reconstruct the 3-dimensional (3D) anatomy and quantify morphomic measures of the temporalis muscle and temporal fat pad in children with PR, TC, and age-matched controls. These steps were completed in a semi-automated method using algorithms programmed in MATLAB v13.0. The 3D reconstructions were analyzed in 3 children with PR (6 temporal regions), 3 children with TC (6 temporal regions), and a control group of 19 children (38 temporal regions). We also quantified the same measurements in a localized "core" sample in the area of greatest thickness, providing a more consistent sample of the tissue position. Relationships between the temporal muscle and fat pad values and craniofacial abnormality type were assessed using Wilcoxon nonparametric test using exact distribution, with a P value of less than 0.05 being deemed significant.
RESULTS
The mean age of our patients was 6.0 years in PR and 4.5 years in TC cohorts. We were able to establish an automated methodology to quantify the temporalis muscle and temporal fat pad based on CT characteristics. Localized temporalis volume and localized temporalis area were significantly smaller in children with PR than in the control group. Total temporalis fat volume and localized temporalis area were significantly less in children with TC than in the control group. When compared to each other, the PR group had small morphomic values compared to TC group.
CONCLUSIONS
There are significant morphomic differences in the temporalis muscle and the temporal fat pad in children with either PR or TC when compared to age-matched control group which can be measured from pre-existing CT scans. Specifically, both of these test groups show decreases in the morphomic measures of the temporalis region. The quantification of these changes corroborates and objectifies the clinical findings associated with these congenital deformities while simultaneously allowing for preoperative planning. Furthermore, this finding confirms that the hypoplasia seen in these patient populations is not only hypoplasia of the mandible but also of the surrounding functional matrix, which includes the temporalis muscle and temporal fat pad.
The effect of age on fat and bone properties along the vertebral spine
Parenteau CS, Holcombe S, Zhang P, Kohoyda-Inglis C, Wang SC
SAE Int. J. Trans. Safety 1(2):226-240, 2013, doi:10.4271/2013-01-1244.
The human body changes as it becomes older. The automotive safety community has been interested in understanding the effect of aging on restraint performance. Recent research has been focused on assessing the structural and material changes associated with age. In this study, structural tissue distribution was determined using the computed tomography (CT) scan data of more than 19,000 patients, aged 16 and up. The data consisted of subcutaneous fat cross-sectional area, visceral fat cross-sectional area, and trabecular bone density taken at each vertebral level. The data was quantified as a function of five age groups with the youngest group defined as 16-29 years old and the oldest group as 75 and up. An additional analysis stratified on gender was carried out. Overall, visceral fat increased with age. Compared to the 16-29 group, the visceral fat measured at the L1 level was 1.97 in the 30-44 group, 2.55 in the 45-59 group, 3.33 in the 60-74 group and 3.21 times greater in the 75+ group. Subcutaneous fat also increased with age up to the 60-74-year-old group. The subcutaneous fat measured at L1 level was 1.34 in the 30-44 group, 1.39 in the 45-59 group, 1.38 in the 60-74 group and 1.09 times greater in the 75+ group than in the 16-29 group. A significant association between trabecular bone density and age was found. Trabecular bone density in Hounsfield units (HU) decreased as a function of age, by 2.57*age +0.0056*age2 for females and 2.57*age +0.0082*age2 for males. Gender differences were also observed. Females had 1.43 times more subcutaneous fat and 1.10 times higher trabecular bone density than males at L1, while males had 1.88 times more visceral fat than females. Females gained more subcutaneous fat at L1 as they increased in age up to the 45-59 group and then progressively lost subcutaneous fat. Males and females gained more visceral fat at L1 as they aged up to the 60-74 group. Both consistently lost bone density at L1 as they grew older. The data was also analyzed for a male subgroup approximating the height and weight of a 50th percentile male dummy. Visceral fat increased with age while trabecular bone density decreased. There was an overall-trend for an increase in subcutaneous fat with age. The results obtained in this study provide insight on the quantified effect of bone and fat distribution as a function of age, gender, and vertebral level. Fat and bone distribution needs to be considered in human mathematical models used to develop safety countermeasures for the older population.
Morphometric age and surgical risk
Englesbe MJ, Terjimanian MN, Lee JS, Sheetz KH, Harbaugh CM, Hussain A, Holcombe SA, Sullivan J, Campbell DA Jr, Wang SC, Sonnenday CJ
J Am Coll Surg. 2013 May;216(5):976-85. doi: 10.1016/j.jamcollsurg.2013.01.052. Epub 2013 Mar 21.
A cornerstone of a surgeon's clinical assessment of suitability for major surgery is best described as the "eyeball test." Preoperative imaging may provide objective measures of this subjective assessment by calculating a patient's morphometric age. Our hypothesis is that morphometric age is a surgical risk factor distinct from chronologic age and comorbidity and correlates with surgical mortality and length of stay.
STUDY DESIGN
This is a retrospective cohort study within a large academic medical center. Using novel analytic morphomic techniques on preoperative CT scans, a morphometric age was assigned to a random sample of patients having inpatient general and vascular abdominal surgery from 2006 to 2011. The primary outcomes for this study were postoperative mortality (1-year) and length of stay (LOS).
RESULTS
The study cohort (n = 1,370) was stratified into tertiles based on morphometric age. The postoperative risk of mortality was significantly higher in the morphometric old age group when compared with the morphometric middle age group (odds ratio 2.42, 95% CI 1.52 to 3.84, p < 0.001). Morphometric old age patients were predicted to have a LOS 4.6 days longer than the morphometric middle age tertile. Similar trends were appreciated when comparing morphometric middle and young age tertiles. Chronologic age correlated poorly with these outcomes. Furthermore, patients in the chronologic middle age tertile found to be of morphometric old age had significantly inferior outcomes (mortality 21.4% and mean LOS 13.8 days) compared with patients in the chronologic middle age tertile found to be of morphometric young age (mortality 4.5% and mean LOS 6.3 days, p < 0.001 for both).
CONCLUSIONS
Preoperative imaging can be used to assign a morphometric age to patients, which accurately predicts mortality and length of stay.
Abdominal aortic calcification and surgical outcomes in patients with no known cardiovascular risk factors
Harbaugh CM, Terjimanian MN, Lee JS, Alawieh AZ, Kowalsky DB, Tishberg LM, Krell RW, Holcombe SA, Wang SC, Campbell DA Jr., Englesbe MJ
Ann Surg. 2013 Apr;257(4):774-81. doi: 10.1097/SLA.0b013e31826ddd5f.
In the setting of cardiovascular (CV) risk evaluation before major elective surgery, current risk assessment tools are relatively poor for discriminating among patients. For example, patients with clinical CV risk factors can be clearly identified; but among those without appreciated clinical CV risk, there may be a subset with stigmata of CV disease noted during the preoperative radiographic evaluation. Our study evaluated the relationship between abdominal aortic (AA) calcification measured on preoperative computed tomography (CT) imaging and surgical complications in patients undergoing general elective and vascular surgery. We hypothesized that patients with no known CV risk factors but significant aortic calcification on preoperative imaging will have inferior surgical outcomes.
METHODS
The study group included 1180 patients from the Michigan Surgical Quality Collaborative (MSQC) database who underwent major general or vascular elective surgery between 2006 and 2009 and who had a CT scan of the abdomen specifically for preoperative planning. AA calcification was measured using novel analytic morphomic techniques and reported as a percentage of the total wall area containing calcification. Patients were divided into cohorts by clinical CV risk and extent of AA calcification. Univariate analysis was used to compare postoperative morbidity between patient cohorts. Multivariate logistic regression analysis was used to compare continuous AA calcification with overall morbidity in patients with no clinical CV risk factors.
RESULTS
AA calcification was strongly skewed to the right (53.5% had no AA calcification) and was significantly correlated with age (ρ = 0.43, P < 0.001). Unadjusted univariate analysis of morbidity showed no significant differences in complication rates between patients in the clinical CV risk and significant AA calcification (no known CV risk factor) categories. The clinical CV risk (P < 0.001) and significant AA calcification without CV risk factors (P = 0.009) populations both had significantly more infectious and overall complications than patients with no AA calcification and no clinical CV risk. Multivariate logistic regression confirmed that AA calcification was a significant predictor of morbidity in patients with no clinical CV risk factors (odds ratio = 1.35, P = 0.017).
DISCUSSION
This study suggests that AA calcification may be related to progression of CV disease and surgical outcomes. A better understanding of the complex interaction of patient physiology with overall ability to recover from major surgery, using novel approaches such as Analytic Morphomics®, has great potential to improve risk stratification and patient selection.
Novel temporalis muscle and fat pad morphomic analyses aids preoperative risk evaluation and outcome assessment in nonsyndromic craniosynostosis
Rinkinen J, Zhang P, Wang L, Enchakalody B, Terjimanian M, Holcombe S, Wang SC, Buchman SR, Levi B.
Analytical morphomics is the term we created to describe an innovative, highly automated, anatomically indexed processing of 3D medical imaging data captured during the course of a patients' preoperative CT scan. Our specific aim is to determine the efficacy of craniofacial morphomic indices (CMI) such as temporalis muscle and temporal fat pad morphometric values to predict blood transfusion requirement and hospital stay in a cohort of children with nonsyndromic craniosynostosis (NSC).
METHODS
High-throughput, semi-automated image analysis was used to reconstruct the 3-dimensional anatomy of the temporalis muscle and temporal fat pad and to quantify CMIs. The prognostic effect of CMI on clinical outcomes were evaluated among all NSC patients and compared across various craniosynostosis subtypes using Wilcoxon nonparametric tests and Kendall's τ to determine significance.
RESULTS
Using preoperative CT images, we evaluated 117 children with NSC from the University of Michigan Health System. Results demonstrate that increased temporal fat pad volume and local temporalis muscle volume are associated with better clinical outcomes in craniosynostosis patients. More specifically, temporal fat pad volume was shown to be a significant predictor of perioperative blood transfusion requirements (P = 0.0033) and increased temporal muscle volume correlated with decreased hospital stay (P = 0.016) when controlling for other covariates including age, sex, weight, and preoperative hematocrit. In addition, the same significant predictors were found when examining individual subtypes of craniosynostosis.
CONCLUSION
Our findings demonstrate that maxillofacial CT scans provide a useful quantitative index reflecting general patient health, risk stratification, and probabilities of intervention in addition to their previously established ability to determine the specific pathology of the patient. We demonstrate that temporal morphomics predict the incidence of blood transfusion, hospital stay, and serve as a proxy for fitness in patients undergoing craniosynostosis surgery.
2012
Quantifying the eyeball test: sarcopenia, Analytic Morphomics®, and liver transplantation
Assess the relationship between lean core muscle size, measured on preoperative cross-sectional images, and surgical outcomes.
BACKGROUND
Novel measures of preoperative risk are needed. Analytic morphomic analysis of cross-sectional diagnostic images may elucidate vast amounts of patient-specific data, which are never assessed by clinicians.
METHODS
The study population included all patients within the Michigan Surgical Quality Collaborative database with a computerized tomography(CT) scan before major, elective general or vascular surgery (N = 1453). The lean core muscle size was calculated using analytic morphomic techniques. The primary outcome measure was survival, whereas secondary outcomes included surgical complications and costs. Covariate adjusted outcomes were assessed using Kaplan-Meier analysis, multivariate cox regression, multivariate logistic regression, and generalized estimating equation methods.
RESULTS
The mean follow-up was 2.3 years and 214 patients died during the observation period. The covariate-adjusted hazard ratio for lean core muscle area was 1.45 (P = 0.028), indicating that mortality increased by 45% per 1000 mm(2) decrease in lean core muscle area. When stratified into tertiles of core muscle size, the 1-year survival was 87% versus 95% for the smallest versus largest tertile, whereas the 3-year survival was 75% versus 91%, respectively (P < 0.003 for both comparisons). The estimated average risk of complications significantly differed and was 20.9%, 15.0%, and 12.3% in the lower, middle, and upper tertiles of lean core muscle area, respectively. Covariate-adjusted cost increased significantly by an estimated $10,110 per 1000 mm(2) decrease in core muscle size (P = 0.003).
CONCLUSIONS
Core muscle size is an independent and potentially important preoperative risk factor. The techniques used to assess preoperative CT scans, namely Analytic Morphomics®, may represent a novel approach to better understanding patient risk.
Use of Temporal Morphomic Indices as a Clinically Important Variable in the Diagnosis of Nonsyndromic Craniosynostosis
Rinkinen J, Wang L, Zhang P, Lisiecki J, Enchakalody B, Holcombe S, Dombrowski A, Wang SC, Buchman SR, Levi B
Ann Plast Surg. 2012 Jul 31;73(1):86-91. doi: 10.1097/SAP.0b013e31826caf8d.
Preoperative computed tomography (CT) evaluation of patients with nonsyndromic craniosynostosis (NSC) has focused on the bony cranial vault while ignoring the surrounding soft tissues. In this study, we posit that novel CT-derived temporal muscle and temporal fat pad morphomics (tissue thickness, area, and volume) can be used to calculate temporal morphomic indices (TMIs), which are unique to each NSC subtype (metopic, coronal, and sagittal) and divergent from normal individuals.
METHODS
High-throughput image analysis was used to reconstruct the 3-dimensional anatomy and quantify a TMI. These steps were completed in a semiautomated method using algorithms programmed in MATLAB v13.0. Differences in TMI across various craniosynostosis subtypes were assessed using Wilcoxon nonparametric tests for both patients with NSC and a control cohort of patients with trauma.
RESULTS
Using preoperative CT images, we evaluated 117 children with NSC from the University of Michigan Health System and 50 age-matched control patients between 1999 and 2011. Results indicate significant differences in TMI among the normal and NSC groups, with normal patients having significantly higher TMI values than patients with metopic, sagittal, and coronal synostosis. In addition, significant differences were found to exist between each craniosynostosis category.
CONCLUSIONS
Patients with craniosynostosis demonstrate diminished temporalis muscle and overlying fat pad volume and thickness compared with control patients. The unique changes in temporal morphomics presented in this article demonstrate not only that the bony calvaria is affected by craniosynostosis but also that there exist quantifiable aberrations in the temporalis muscle and temporal fat pad. The methodologies described offer a novel methodology to use pre-existing CT scans to glean additional preoperative information on the soft tissue characteristics of patients with craniosynostosis.
Worsening central sarcopenia and increasing intra-abdominal fat correlate with decreased survival in patients with adrenocortical carcinoma
Miller BS, Ignatoski KM, Daignault S, Lindland C, Doherty M, Gauger PG, Hammer GD, Wang SC, Doherty GM
World J Surg. 2012 Jul;36(7):1509-16. doi: 10.1007/s00268-012-1581-5.
Accurate prediction of survival from adrenocortical carcinoma (ACC) is difficult and current staging models are unreliable. Central sarcopenia as part of the cachexia syndrome is a marker of frailty and predicts mortality. This study seeks to confirm that psoas muscle density (PMD), lean psoas muscle area (LPMA), lumbar skeletal muscle index (LSMI), and intra-abdominal (IA) or subcutaneous fat (SC) can be used in combination to more accurately predict survival in ACC patients.
METHODS
PMD, LPMA, IA, and SC fat were measured on serial CT scans of patients with ACC. Clinical outcome was correlated with quantitative data from patients with ACC and analyzed. A linear regression model was used to describe the relationship between PMD, LPMA, LSMI, IA, and SC fat, time to recurrence, and length of survival according to tumor stage.
RESULTS
One hundred twenty-five ACC patients (94 females) were treated from 2005 to 2011. Significant morphometric predictors of survival include PMD, LPMA, and IA fat (p ≤ 0.0001, ≤ 0.0024, <0.0001, respectively) and improve prediction of survival compared to using stage alone. A 100-mm(2) increase in LPMA confers an 8% lower hazard of death. LSMI does not change significantly between stages (p = 0.3196).
CONCLUSION
Decreased PMD, LPMA, and increased IA fat suggest decreased survival in ACC patients and correlate with traditional staging systems. A more precise prediction of survival may be achieved when staging systems and morphometric measures are used in combination. Serial measurements of morphometric data are possible. The rate of change of these variables over time may be more important than the absolute value.
Morphomic Analysis of Cervical Facet Angles
Wang NC, Holcombe SA, Cohan RD, Kohoyda-Inglis C, Wang, SC
Different vertebral facet angles in pediatric versus adult necks may explain their disparate biomechanical tolerance and motion under physical loading. We analyzed CT scans of the neck using novel semi-automated image processing software algorithms to characterize the morphology of each cervical vertebra, including precise measurement of facet angle relative to other vertebral landmarks. We observe clear and very significant changes in facet angle with aging for C2 through C7. These findings are useful, when analyzed in conjunction with vehicle crash and injury data, to identify occupant specific factors that may contribute to motor vehicle crash injury tolerance in live subjects.
Detailed measurement of Vehicle Occupants
Wang SC, Holcombe SA, Cohan RD, Wang NC, Kohoyda-Inglis C.
Occupants of vehicles involved in motor vehicle collisions vary substantially in body stature and condition. This variability contributes substantially to differences in injury severity and patterns in the real world. Demographic factors such as age, gender, height and weight are insufficient to describe human variability. We analyzed CT scans of trauma and control populations to measure the anthropometry and tissue quality of different body regions. We observe very significant variability which we have referenced to a large population of 50%ile males. These findings are useful to identify occupant specific factors that contribute to motor vehicle crash injury.
2011
Sarcopenia as a Prognostic Factor among Patients with Stage III Melanoma
Sabel MS, Lee J, Cai S, Englesbe MJ, Holcombe S, Wang SC
Ann Surg Oncol. 2011 Dec;18(13):3579-85. doi: 10.1245/s10434-011-1976-9. Epub 2011 Aug 6.
Several hypotheses proposed to explain the worse prognosis for older melanoma patients include different tumor biology and diminished host response. If the latter were true, then biologic frailty, and not age, should be an independent prognostic factor in melanoma.
METHODS
Our prospective institutional review board (IRB)-approved database was queried for stage III patients with computed tomography (CT) scans at time of lymph node dissection (LND). Psoas area (PA) and density (PD) were determined in semi-automated fashion. Kaplan-Meier (K-M) survival estimates and Cox proportional-hazard models were used to determine PA and PD impact on survival and surgical complications.
RESULTS
Among 101 stage III patients, PD was significantly associated with both disease-free survival (DFS) (P = 0.04) and distant disease-free survival (DDFS) (P = 0.0002). Cox multivariate modeling incorporating thickness, age, ulceration, and N stage showed highly significant association with PD and both DFS and DDFS. DDFS was significantly associated with Breslow thickness (P = 0.04), number of positive nodes (P = 0.001), ulceration (P = 0.04), and decreasing muscle density (P = 0.01), with hazard ratio of 0.55 [95% confidence interval (CI) 0.35-0.87]. PD also correlated with surgical complications, with odds ratio (OR) of 1.081 [95% CI 1.016-1.150, P = 0.01].
CONCLUSIONS
Decreased psoas muscle density on CT, an objective measure of frailty, was as important a predictor of outcome as tumor factors in a cohort of stage III melanoma patients. On multivariate analysis, frailty, not age, was associated with decreased disease-free survival and distant disease-free survival, and higher rate of surgical complications.
Development of a quantitative method for the diagnosis of cirrhosis
Huhdanpaa H, Douville C, Baum K, Krishnamurthy VN, Holcombe S, Enchakalody B, Wang L, Wang SC, Su GL
To develop a novel non-invasive, quantitative approach utilizing computed tomography scans to predict cirrhosis.
MATERIALS AND METHODS
A total of 105 patients (54 cirrhosis and 51 normal) who had CT scans within 6 months of a liver biopsy or were identified through a Trauma registry were included in this study. Patients were randomly divided into the training set (n = 81) and the validation set (n = 24). Each liver was segmented in a semi-automated fashion from a computed tomography scan using Mimics software. The resulting liver surfaces were saved as a stereo lithography mesh into an Oracle database, and analyzed in MATLAB(®) for morphological markers of cirrhosis.
RESULTS
The best predictive model for diagnosing cirrhosis consisted of liver slice-bounding box slice ratio, the dimensions of the liver bounding box, liver slice area, slice perimeter, surface volume and adjusted surface area. With this model, we calculated an area under the receiver operating characteristic curve of 0.90 for the training set, and 0.91 for the validation set. For comparison, we calculated an area under the receiver operating characteristic curve of 0.70 for our dataset when we used the lab value based aspartate aminotransferase-platelet ratio index, another reported model for predicting cirrhosis. Last, by combining the aspartate aminotransferase-platelet ratio index and our model, we obtained an area under the receiving operating characteristic of 0.95.
CONCLUSION
This study shows "proof of concept" that quantitative image analysis of livers on computed tomography scans may be utilized to predict cirrhosis in the absence of a liver biopsy.
A quantitative tool to assess degree of sarcopenia objectively in patients with hypercortisolism
Miller BS, Ignatoski KM, Daignault S, Lindland C, Gauger PG, Doherty GM, Wang SC
Muscle weakness and wasting are known manifestations of hypercortisolism (HC). Central sarcopenia is a marker of frailty and predicts mortality. The hypothesis of this study is that central sarcopenia can be used as a marker of disease severity and frailty in patients with HC.
METHODS
Psoas muscle area and psoas muscle density (PMD) were measured at specific points on CT scans of patients with HC using a defined protocol. We compared 24-hour urine cortisol (24HUC) levels by time point to each CT scan. A linear regression model was used to describe the relationship between 24HUC and morphometric variables. A comparison with matched non-HC patients was performed.
RESULTS
We identified 45 patients (34 female). The median age was 46 years (range, 14-80); the median 24HUC was 211 mg/dL (range, 9.5-39,500); the median PMD was 50.1 24HUC (range, 20-72). An inverse correlation (-0.29) between 24HUC levels and PMD was noted (P = .045). Intra-abdominal fat was also significantly and positively correlated with 24HUC: 27 non-HC patients matched for age, sex, and body-mass index showed higher (58 vs 51) PMD (P = .0127) compared to those with HC.
CONCLUSION
PMD and intra-abdominal fat are significantly related to 24HUC levels. Morphometric measures of the overall burden of HC may allow more precise assessment of disease severity.
Patterns of acetabular femoral head coverage
Holcombe S, Kohoyda-Inglis C, Wang L, Goulet JA, Wang SC, Kent RW
The size and shape of the acetabulum and of the femoral head influence the injury tolerance of the hip joint. The aim of this study is to quantify changes in acetabular cup geometry that occur with age, gender, height, and weight. Anonymized computed tomography (CT) scans of 1,150 individuals 16+ years of age, both with and without hip trauma, were used to describe the acetabular rim with 100 equally spaced points. Bilateral measurements were taken on uninjured patients, while only the uninjured side was valuated in those with hip trauma. Multinomial logistic regression found that after controlling for age, height, weight, and gender, each 1 degree decrease in acetabular anteversion angle (AAA) corresponded to an 8 percent increase in fracture likelihood (p<0.001). Age, weight, and gender were found to influence anteversion angle significantly, with each 10 years in age increasing AAA by 1.07 degrees, each 10 kg of weight decreasing AAA by 0.45 degrees, and being female resulting in 1.42 degrees greater AAA than males. Height was not found to relate significantly to AAA after other anthropometric factors were controlled for. Height, age, and weight, however, correlated with femoral head radius, thus establishing a relationship with acetabular rim size independent of rim shape. A parametric model of the 3D acetabular rim landmark points is reported, allowing for the creation of individualized acetabular geometry for any given age, gender, height, and weight. A custom-built tool to produce such geometry programmatically is also provided.
Surgical site infection and analytic morphometric assessment of body composition in patients undergoing midline laparotomy
Lee JS, Terjimanian MN, Tishberg LM, Alawieh AZ, Harbaugh CM, Sheetz KH, Holcombe SA, Wang SC, Sonnenday CJ, Englesbe MJ
Obesity is a known risk factor for surgical site infection (SSI). Our hypothesis is that morphometric measures of midline subcutaneous fat will be associated with increased risk of SSI and will predict SSI better than conventional measures of obesity.
STUDY DESIGN
We identified 655 patients who underwent midline laparotomy (2006 to 2009) using the Michigan Surgical Quality Collaborative database. Using novel, semiautomated analytic morphometric techniques, the thickness of subcutaneous fat along the linea alba was measured between T12 and L4. To adjust for variations in patient size, subcutaneous fat was normalized to the distance between the vertebrae and anterior skin. Logistic regression analyses were used to identify factors independently associated with the incidence of SSI.
RESULTS
Overall, SSIs were observed in 12.5% (n = 82) of the population. Logistic regression revealed that patients with increased subcutaneous fat had significantly greater odds of developing a superficial incisional SSI (odds ratio [OR] = 1.76 per 10% increase, 95% CI 1.10 to 2.83, p = 0.019). Smoking, steroid use, American Society of Anesthesiologists (ASA) classification, and incision-to-close operative time were also significant independent risk factors for superficial incisional SSI. When comparing subcutaneous fat and body mass index (BMI) as the only model variables, subcutaneous fat significantly improved model predictions of superficial incisional SSI (area under the receiver operating characteristic curve [AUC] 0.60, p = 0.023); BMI did not (AUC 0.52, p = 0.73).
CONCLUSIONS
Abdominal subcutaneous fat is an independent predictor of superficial incisional SSI after midline laparotomy. Novel morphometric measures may improve risk stratification and help elucidate the pathophysiology of surgical complications.
Central Adiposity and Surgical Site Infection in Patients Undergoing Midline Laparotomy
Lee JS, Terjimanian MN, Alawieh AZ, Tishberg LM, Harbaugh CM, Kowalsky DB, Sheetz KH, Holcombe Sa, Wang SC, Englesbe MJ
Obesity is a known risk factor for surgical site infection (SSI). Although body mass index (BMI) and body fat percentage are typically used to define obesity, these metrics do not directly assess body composition at the site of the wound. Within this context, measures of adiposity targeted at the surgical site may improve predictions of SSI risk. Such measures can be readily obtained from preoperative cross-sectional imaging. The objective of this study is to determine whether the amount of abdominal fat along the midline is correlated with SSI in patients undergoing procedures requiring midline laparotomy.
Safety Belt & Occupant Factors Influencing Thoracic and Upper Abdominal Injuries in Frontal Crashes
Lu H, Andreen M, Faust D, Furton L, Holcombe S, Kohoyda-Inglis C, Putala B, Yee J, Wang S.
This paper reports on a study that examines the effect of shoulder belt load limiters and pretensioners as well as crash and occupant factors that influence upper torso harm in real world frontal crashes. Cases from the University of Michigan International Center for Automotive Medicine (ICAM) database were analyzed. Additional information was used from other databases including the National Highway Traffic Safety Administration (NHTSA) New Car Assessment Program (NCAP), the Insurance Institute for Highway Safety (IIHS), the National Automotive Sampling System - Crashworthiness Data System (NASS-CDS), and patient data available from the University of Michigan Trauma Center. The ICAM database is comprised of information from real world crashes in which occupants were seriously injured and required treatment at a Level 1 Trauma Center. Cases from the database were included in this study if they met the following criteria: (a) the primary collision involved a frontal type crash and; (b) case occupants were seated in front outboard positions, restrained by 3-point safety belts and deployed frontal airbags. One hundred thirty three (133) case occupants who sustained nearly 1,800 injuries were selected for study from the ICAM database. The study included evaluations of skeletal, organ, and vessel injuries to the upper torso. Potential influencing factors were divided into three general categories: vehicle factors (i.e. seatbelt design); occupant factors; and crash related factors. Considering the challenges and limitations for analysis of field accident data and within the scope of this study, data indicated that: case occupants without shoulder belt load limiters experienced a higher level of upper torso harm in lower severity frontal crashes. The average Delta V for case occupants with shoulder belt load limiters was significantly higher (7.1 km/h, 34% greater crash energy) than that for the case occupants without load limiters. Case occupants with shoulder belt load limiters had significantly fewer clavicle fractures in frontal crashes. For the 62 case occupants with load limiters, the presence or absence of pretensioners did not appear to substantially change the crash severity associated with AIS ≥2 upper torso harm. Lower bone mineral density of the L4 vertebra was indicative of susceptibility to upper torso skeletal injuries. Smaller psoas muscle cross section area was indicative of susceptibility to upper torso internal and skeletal injuries.
2010
Sarcopenia and mortality after liver transplantation
Englesbe MJ, Patel SP, He K, Lynch RJ, Schaubel DE, Harbaugh C, Holcombe SA, Wang SC, Segev, DL, Sonnenday CJ
J Am Coll Surg. 2010 Jan;211(2):271-278. doi: 10.1016/j.jamcollsurg.2010.03.039
Surgeons frequently struggle to determine patient suitability for liver transplantation. Objective and comprehensive measures of overall burden of disease, such as sarcopenia, could inform clinicians and help avoid futile transplantations.
STUDY DESIGN
The cross-sectional area of the psoas muscle was measured on CT scans of 163 liver transplant recipients. After controlling for donor and recipient characteristics using Cox regression models, we described the relationship between psoas area and post-transplantation mortality.
RESULTS
Psoas area correlated poorly with Model for End-Stage Liver Disease score and serum albumin. Cox regression revealed a strong association between psoas area and post-transplantation mortality (hazard ratio = 3.7/1,000 mm2 decrease in psoas area; p < 0.0001). When stratified into quartiles based on psoas area (holding donor and recipient characteristics constant), 1-year survival ranged from 49.7% for the quartile with the smallest psoas area to 87.0% for the quartile with the largest. Survival at 3 years among these groups was 26.4% and 77.2%, respectively. The impact of psoas area on survival exceeded that of all other covariates in these models.
CONCLUSIONS
Central sarcopenia strongly correlates with mortality after liver transplantation. Such objective measures of patient frailty, such as sarcopenia, can inform clinical decision making and, potentially, allocation policy. Additional work is needed develop valid and clinically relevant measures of sarcopenia and frailty in liver transplantation.
Frailty, core muscle size, and mortality in patients undergoing open abdominal aortic aneurysm repair
Lee JS, He K, Harbaugh CM, Schaubel DE, Sonnenday CJ, Wang SC, Englesbe MJ, Eliason JL
J Vasc Surg. 2010 June 10-13;53(4):912-7. doi: 10.1016/j.jvs.2010.10.111. Epub 2011 Jan 7.
Determining operative risk in patients undergoing aortic surgery is a difficult process, as multiple variables converge to affect overall mortality. Patient frailty is certainly a contributing factor, but is difficult to measure, with surgeons often relying on subjective or intuitive influences. We sought to use core muscle size as an objective measure of frailty, and determine its utility as a predictor of survival after abdominal aortic aneurysm (AAA) repair.
METHODS
Four hundred seventy-nine patients underwent elective open AAA repair between 2000 and 2008. Two hundred sixty-two patients (54.7%) had preoperative computed tomography (CT) scans available for analysis. Cross-sectional areas of the psoas muscles at the level of the L4 vertebra were measured. The covariate-adjusted effect of psoas area on postoperative mortality was assessed using Cox regression.
RESULTS
Of the 262 patients, there were 55 deaths and the mean length of follow-up was 2.3 years. Cox regression revealed a significant association between psoas area and postoperative mortality (P = .003). The effect of psoas area was found to decrease significantly as follow-up time increased (P = .008). Among all covariates included in the Cox models (including predictors of mortality such as American Society of Anesthesiologists [ASA] score), the psoas area was the most significant.
CONCLUSION
Core muscle size, an objective measure of frailty, correlates strongly with mortality after elective AAA repair. A better understanding of the role of frailty and core muscle size may aid in risk stratification and impact timing of surgical repair, especially in more complex aortic operations.
2009
Analysis of injury trends in frontal University of Michigan CIREN cases in the context of crash tests
Four-hundred forty two U-M CIREN (University of Michigan Crash Injury Research and Engineering Network) cases have previously been compared to crash tests used in the automotive industry. The comparison demonstrated that the majority of cases were similar in crash configuration and extent to industry crash tests, while smaller proportions either had a greater extent of crash deformation or had different crash configurations than those commonly produced in crash tests. Of the 442 cases, 290 frontal cases were analyzed in greater detail to understand trends in injury causation while considering physical characteristics of occupants (gender, age, body mass index.) Those trends were then evaluated in the context of biomechanics of crash test tools such as Anthropomorphic Test Devices [ATDs] and injury risk curves. Several trends were identified and presented.
Comparison of University of Michigan CIREN cases to existing types of crash tests
A comparison of U-M CIREN (University of Michigan Crash Injury Research and Engineering Network) cases to crash tests used in the automotive industry is presented in this paper. 442 U-M CIREN crashes were compared to crash test configurations used throughout the industry. Of those 442 cases, 49% were similar in crash configuration and crash extent to industry crash tests. 32% of the cases were similar to one of the industry crash tests in configuration but had greater extent. 20% of the cases did not match any of the current industry crash tests. This analysis concluded that the majority of injuries in this study occurred in crash configurations similar to existing crash tests while only 20% of cases had crash configurations that were not represented by current crash tests. Any consideration of increasing test severity to address those crashes that produce a greater extent of crash deformation than that produced in crash tests must consider a broader spectrum of collisions including non-injury producing crashes. This analysis must be done in a way that does not increase the risk to the current uninjured population that is not included in the CIREN database.
Patterns of local and regional variation in ribcage anatomy
Holcombe S, Ejima S, Ono K, Huhdanpaa H, Baum K, Lange DC, Brede CM, Inglis C, Wang NC, Kohoyda-Inglis C, Garton H, Patel S, Wang SC
Japan Society of Automotive Engineers. 2009. JSAE Technical Paper #145-20095232
Standard medical chest and abdomen computed tomography (CT) scans were used to take detailed measurements of human rib geometry and material properties from a wide range of patients. Geometric quantities included rib cross-sectional area, aspect ratio and camber angle. Material-based quantities included rib cross-sectional average density, and inner and outer measurements of cortical bone thickness and cortical bone density. We found very significant local and regional variation both within and between individuals. Proposals are made for the use of these measurements to inform and improve human finite element chest models, allowing them to more accurately represent the human ribcage.
2008
Ribcage characterization for FE using automatic CT processing
Holcombe S, Ejima S, Huhdanpaa H, Jones A, Wang SC
Biomedical Imaging: From Nano to Macro, 2008. ISBI 2008. 5th IEEE International Symposium on 14-17 May 2008. doi: 10.1109/ISBI.2008.4541079.
Standard medical chest and abdominal computed tomography (CT) scans of 46 subjects were analyzed to characterize aspects of human ribcage geometry and bone density. A semi-automatic algorithm was developed to define framework curves for individual ribs. Measurements of this framework were taken to record anthropometric properties of the ribcage such as overall ribcage dimensions and individual rib lengths and angles. Furthermore, the ribcage framework was used to explore the voxel space of the CT images, recording local rib bone cross-sectional density properties. Proposals are made for the use of these measurement techniques to inform and improve human finite element (FE) chest models in terms of global geometry, material properties, and individuality.
2006
Factors influencing pediatric Injury Severity Score and Glasgow Coma Scale in pediatric automobile crashes: results from the Crash Injury Research Engineering Network
Ehrlich PF, Brown JK, Sochor MR, Wang SC, Eichelberger ME.
Motor vehicle crashes account for more than 50% of pediatric injuries. Triage of pediatric patients to appropriate centers can be based on the crash/injury characteristics. Pediatric motor vehicle crash/injury characteristics can be determined from an in vitro laboratory using child crash dummies. However, to date, no detailed data with respect to outcomes and crash mechanism have been presented with a pediatric in vivo model.
METHODS
The Crash Injury Research Engineering Network is comprised of 10 level 1 trauma centers. Crashes were examined with regard to age, crash severity (DeltaV), crash direction, restraint use, and airbag deployment. Multiple logistic regression analysis was performed with Injury Severity Score (ISS) and Glasgow Coma Scale (GCS) as outcomes. Standard age groupings (0-4, 5-9, 10-14, and 15-18) were used. The database is biases toward a survivor population with few fatalities.
RESULTS
Four hundred sixty-one motor vehicle crashes with 2500 injuries were analyzed (242 boys, 219 girls). Irrespective of age, DeltaV > 30 mph resulted in increased ISS and decreased GCS (eg, for 0-4 years, DeltaV < 30: ISS = 10, GCS = 13.5 vs DeltaV > 30: ISS = 19.5, GCS = 10.6; P < .007, < .002, respectively). Controlling for DeltaV, children in lateral crashes had increased ISS and decreased GCS versus those in frontal crashes. Airbag deployment was protective for children 15 to 18 years old and resulted in a lower ISS and higher GCS (odds ratio, 2.1; 95% confidence interval, 0.9-4.6). Front-seat passengers suffered more severe (ISS > 15) injuries than did backseat passengers (odds ratio, 1.7; 95% confidence interval, 0.7-3.4). A trend was noted for children younger than 12 years sitting in the front seat to have increased ISS and decreased GCS with airbag deployment but was limited by case number.
CONCLUSION
A reproducible pattern of increased ISS and lower GCS characterized by high severity, lateral crashes in children was noted. Further analysis of the specific injuries as a function and the crash characteristic can help guide management and prevention strategies.
Patterns of severe injury in pediatric car crash victims: Crash Injury Research Engineering Network database
Motor vehicle crashes (MVCs) account for 50% of pediatric trauma. Safety improvements are typically tested with child crash dummies using an in vitro model. The Crash Injury Research Engineering Network (CIREN) provides an in vivo validation process. Previous research suggest that children in lateral crashes or front-seat locations have higher Injury Severity Scale scores and lower Glasgow Coma Scale scores than those in frontal-impact crashes. However, specific injury patterns and crash characteristics have not been characterized.
METHODS
Data were collected from the CIREN multidisciplinary crash reconstruction network (10 pediatric trauma centers). Injuries were examined with regard to crash direction (frontal/lateral), restraint use, seat location, and change in velocity at impact (DeltaV). Injuries were limited to Abbreviated Injury Scale (AIS) scores of 3 or higher and included head, thoracic, abdominal, pelvic, spine, and long bone (orthopedic) injuries. Standard age groupings (0-4, 5-9, 10-14, and 15-18 years) were used. Statistical analyses used Fisher's Exact test and multiple logistic regressions.
RESULTS
Four hundred seventeen MVCs with 2500 injuries were analyzed (males = 219, females = 198). Controlling for DeltaV and age, children in lateral-impact crashes (n = 232) were significantly more likely to suffer severe injuries to the head and thorax as compared with children in frontal crashes (n = 185), who were more likely to suffer severe spine and orthopedic injuries. Children in a front-seat (n = 236) vs those in a back-seat (n = 169) position had more injuries to the thoracic (27% vs 17%), abdominal (21% vs 13%), pelvic (11% vs 1%), and orthopedic (28% vs 10%) regions (P < .05 for all). Seat belts were protective for pelvic (5% vs 12% unbelted) and orthopedic (15% vs 40%) injuries (odds ratio = 3, P < .01 for both).
CONCLUSION
A reproducible pattern of injury is noted for children involved in lateral-impact crashes characterized by head and chest injuries. The Injury Severity Scale scores were higher for children in front-seat positions. Increased lateral-impact safety measures such as mandatory side curtain airbags may decrease morbidity. Furthermore, continued public education for positioning children in the back seat of cars is warranted.
2005
Structural and material changes in the aging thorax and their role in crash protection for older occupants
Kent R, Lee S-H, Darvish K, Poster CD, Lange AW, Brede C, Lange D, Wang SC, Matsuoka F.
The human body undergoes a variety of changes as it ages through adulthood. These include both morphological (structural) changes (e.g., increased thoracic kyphosis) and material changes (e.g., osteoporosis). The purpose of this study is to evaluate structural changes that occur in the aging bony thorax and to assess the importance of these changes relative to the well-established material changes. The study involved two primary components. First, full-thorax computed tomography (CT) scans of 161 patients, age 18 to 89 years, were analyzed to quantify the angle of the ribs in the sagittal plane. A significant association between the angle of the ribs and age was identified, with the ribs becoming more perpendicular to the spine as age increased (0.08 degrees/year, p=0.012). Next, a finite element model of the thorax was used to evaluate the importance of this rib angle change relative to other factors associated with aging. A three-factor, two-level factorial design was used to assess the relative importance of rib cage morphology ("young" and "old" rib angle), thickness of the cortical shell (thick = "young" and thin = "old"), and the bone material properties ("young" and "old") on the force-deflection response and injury tolerance of the thorax. The simulations showed that the structural and material changes played approximately equal roles in modulating the force-deflection response of the thorax. Changing the rib angle to be more perpendicular to the spine increased the effective thoracic stiffness, while the "old" material properties and the thin cortical shell decreased the effective stiffness. The offsetting effects of these traits resulted in similar effective thoracic stiffness for the "elderly" and baseline thoracic models, which is consistent with cadaver data available in the literature. All three effects tended to decrease chest deflection tolerance for rib fractures, though the material changes dominated (a four- to six-fold increase in elements eliminated using a maximum strain criterion). The primary conclusion, therefore, is that an older person's thorax, relative to a younger, does not necessarily deform more in response to an applied force. The tolerable sternal deflection level is, however, much less.
2004
Potential applications (and limitations) of 3D imaging data from human crash subjects for biomechanical research
Wang SC, Lange AW, Poster CS, Brede C, Lange D.
Society of Automotive Engineers. 2004. Paper #2004-01-0331.
Most studies investigating the biomechanics of injury are limited by a paucity of data about the physical characteristics of the subject before the injury occurred. This is particularly the case with live human subjects from real-life cases, where little data except age, gender, height and weight have been available to date. With regard to the injuries themselves, previously available data has generally been descriptive and of insufficient granularity and anatomic specificity to provide insight into the path of force loading through the surrounding tissues or the mechanism of injury. Three-dimensional medical imaging has recently become part of the standard evaluation of injured subjects and a growing pool of this data is becoming available to the biomechanical research community. When reviewed in conjunction with detailed crash and vehicle information, this data can provide invaluable information regarding the baseline physical characteristics that may have affected the subject's injury tolerance as well as insight into injury mechanism. Taken out of the proper context or with improper image processing, portions of this imaging data can be misleading. The objective of this study is to review changes in medical imaging technology over the past two decades as well as changes in its utilization for the standard evaluation of injured patients. Analysis of 3D medical imaging data for biomechanical studies requires image data processing beyond that used during interpretation for clinical purposes; these processes will be reviewed so that members of the biomechanical research community can better understand the potential uses and limitations of this data. The argument will be made for the research community to adopt common standards and procedures. Individual case studies will demonstrate the conditions under which pre-injury body composition data can be extracted from post- injury 3D medical imaging data. Pooled data will demonstrate the association that exists between these body composition data and observed injury tolerance. The implications of this data for the design and validation of finite element models capable of accurately predicting body tolerances to injury will be discussed.
Gender Differences in Hip Anatomy: Possible Implications for Injury Tolerance in Frontal Collisions
Wang SC, Brede C, Lange D, Poster CS, Lange AW, Kohoyda-Inglis C, Sochor MR, Ipaktchi K, Rowe SA, Patel S, Garton H.
Annual Proceedings of the Association for the Advancement of Automotive Medicine. 2004; 48:287-301.
Male occupants in frontal motor vehicle collisions have reduced tolerance for hip fractures than females in similar crashes. We studied 92 adult pelvic CT scans and found significant gender differences in bony pelvic geometry, including acetabular socket depth and femoral head width. Significant differences were also noted in the presentation angle of the acetabular socket to frontal loading. The observed differences provide biomechanical insight into why hip injury tolerance may differ with gender. These findings have implications for the future design of vehicle countermeasures as well as finite element models capable of more accurately predicting body tolerances to injury.
The pattern and severity of crash injury depends on a complex interaction of biomechanical factors such as deceleration velocity at impact (delta-V), seat-belt and airbag use, and type of impact. Human body characteristics such as height and weight may play an important role. We hypothesized that body mass index (BMI) will influence crash injury patterns.
METHODS
The University of Michigan Program for Injury Research and Education database was queried. Three cohorts were analyzed, lean (BMI </= 25 kg/m2), overweight (BMI 25-30 kg/m2), and obese (BMI > 30 kg/m2)
RESULTS
There were 189 detailed crash cases, with 22 fatalities. There was an increased risk of fatal outcome associated with the obese cohort (adjusted odds ratio, 4.2 compared with lean; p = 0.04). Age, delta-V, seat-belt use, and type of impact were independent predictors of Injury Severity Score (ISS). After adjusting for other modifiers, being overweight was associated with decreased ISS (p = 0.03) and abdominal maximal Abbreviated Injury Scale (mAIS) score (p = 0.008) when compared with the lean cohort. However, the lower extremity mAIS score increased when overweight (p = 0.03) and obese cohorts (p = 0.001) were compared with the lean cohort.
CONCLUSION
Although no difference in ISS was identified between the lean and obese cohorts, there was an increase in mortality with the obese cohort. The severity of lower extremity injuries increased with increasing BMI. The overweight cohort was associated with lower ISS and abdominal mAIS score compared with the lean cohort. This protection may be attributable to an increase in insulating tissue, or a "cushion effect," without a significant increase in mass and momentum.
Increased Depth of Subcutaneous Fat is Protective Against Abdominal Injuries in Motor Vehicle Collisions
Wang SC, Bednarski B, Patel S, Yan A, Kennedy T, Link E, Rowe S, Sochor M, Arbabi S.
The objective of this study was to determine the effect of differences in subcutaneous fat depth on adult injury patterns in motor vehicle collisions. Sixty-seven consecutive adult crash subjects aged 19-65 who received computed tomography of their chest, abdomen and pelvis as part of their medical evaluation and who consented to inclusion in the Crash Injury Research Engineering Network (CIREN) study were included. Subcutaneous fat was measured just lateral to the rectus abdominus muscle in a transverse section taken through the subject at the level of L4. Women had significantly greater subcutaneous fat depth than men. Increased subcutaneous fat depth was associated with significantly decreased injury severity to the abdominal region of females. A similar trend was noted in males although it did not reach statistical significance. Our findings suggest that increased subcutaneous fat may be protective against injuries by cushioning the abdominal region against injurious forces in motor vehicle collisions.
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