Population trends in human rib cross-sectional shapes.

Rib fractures remain the most frequent thoracic injury in motor vehicle crashes. Computational human body models (HBMs) can be used to simulate these injuries and design mitigation strategies, but they require adequately detailed geometry to replicate such fractures. Due to a lack of rib cross-sectional shape data availability, most commercial HBMs use highly simplified rib sections extracted from a single individual during original HBM development. This study provides human rib shape data collected from chest CT scans of 240 females and males across the full adult age range. A cortical bone mapping algorithm extracted cross-sectional geometry from scans in terms of local periosteal position with respect to the central rib axis and local cortex thickness. Principal component analysis was used to reduce the dimensionality of these cross-sectional shape data. Linear regression found significant associations between principal component scores and subject demographics (sex, age, height, and weight) at all rib levels, and predicted scores were used to explore the expected rib cross-sectional shapes across a wide range of subject demographics. The resulting detailed rib cross-sectional shapes were quantified in terms of their total cross-sectional area and their cortical bone cross-sectional area. Average-sized female ribs were smaller in total cross-sectional area than average-sized male ribs by between 20% and 36% across the rib cage, with the greatest differences seen in the central portions of rib 6. This trend persisted although to smaller differences of 14%-29% when comparing females and males of equal intermediate weight and stature. Cortical bone cross-sectional areas were up to 18% smaller in females than males of equivalent height and weight but also reached parity in certain regions of the rib cage. Increased age from 25 to 80 years was associated with reductions in cortical bone cross-sectional area (up to 37% in females and 26% in males at mid-rib levels). Total cross-sectional area was also seen to reduce with age in females but to a lesser degree (of up to 17% in mid-rib regions). Similar regions saw marginal increases in total cross-sectional area for male ribs, indicating age affects rib cortex thickness moreso than overall rib cross-sectional size. Increased subject height was associated with increased rib total and cortical bone cross-sectional areas by approximately 25% and 15% increases, respectively, in mid-rib sections for a given 30 cm increase in height, although the magnitudes of these associations varied by sex and rib location. Increased weight was associated with approximately equal changes in both cortical bone and total cross-sectional areas in males. These effects were most prominent (around 25% increases for an addition of 50 kg) toward lower ribs in the rib cage and had only modest effects (less than 12% change) in ribs 2-4. Females saw greater increases with weight in total rib area compared to cortical bone area, of up to 21% at the eighth rib level. Results from this study show the expected shapes of rib cross-sections across the adult rib cage and across a broad range of demographics. This detailed geometry can be used to produce accurate rib models representing widely varying populations.

Morphomics-informed population pharmacokinetic and physiologically-based pharmacokinetic modeling to optimize cefazolin surgical prophylaxis.

INTRODUCTION: Cefazolin is the leading antibiotic used to prevent surgical site infections worldwide. Consensus guidelines recommend adjustment of the cefazolin dose above and below 120 kg without regard to body composition. Algorithms exist to repurpose radiologic data into body composition (morphomics) and inform dosing decisions in obesity. OBJECTIVES: To compare the current standard of body weight to morphomic measurements as covariates of cefazolin pharmacokinetics and aid dose stratification of cefazolin in patients with obesity undergoing colorectal surgery. METHODS: This prospective study measured cefazolin plasma, fat, and colon tissue concentrations in colorectal surgery patients in order to develop a morphomics-informed population pharmacokinetic (PopPK) model to guide dose adjustments. A physiologically-based pharmacokinetic (PBPK) model was also constructed to inform tissue partitioning in morbidly obese patients (n = 21, body mass index ≥35 kg/m2 with one or more co-morbid conditions). RESULTS: Morphomics and pharmacokinetic data were available in 58 patients with a median [min, max] weight and age of 95.9 [68.5, 148.8] kg and 55 [25, 79] years, respectively. The plasma-to-subcutaneous fat partition coefficient was predicted to be 0.072 and 0.060 by the PopPK and PBPK models, respectively. The estimated creatinine clearance (eCLcr ) and body depth at the third lumbar vertebra (body depth_L3) were identified as covariates of cefazolin exposure. The probability of maintaining subcutaneous fat concentrations above 2 µg/mL for 100% of a 4-h surgical period was below 90% when eCLcr ≥105 mL/min and body depth_L3 ≥ 300 mm and less sensitive to the rate of infusion between 5 and 60 min. CONCLUSIONS: Kidney function and morphomics were more informative than body weight as covariates of cefazolin target site exposure. Data from more diverse populations, consensus on target cefazolin exposure, and comparative studies are needed before a change in practice can be implemented.

Reference distributions of aortic calcification and association with Framingham risk score.

Evidence supporting aortic calcification as a leverageable cardiovascular risk factor is rapidly growing. Given aortic calcification's potential as a clinical correlate, we assessed granular vertebral-indexed calcification measurements of the abdominal aorta in a well curated reference population. We evaluated the relationship of aortic calcification measurements with Framingham risk scores. After exclusion, 4073 participants from the Reference Analytic Morphomic Population with varying vertebral levels were included. The percent of the aortic wall calcified was used to assess calcification burden at the L1-L4 levels. Descriptive statistics of participants, sex-specific vertebral indexed calcification measurements, relational plots, and relevant associations are reported. Mean aortic attenuation was higher in female than male participants. Overall, mean aortic calcium was higher with reference to inferior abdominal aortic measurements and demonstrated significant differences across all abdominal levels [L3 Area (mm[Formula: see text]): Females 6.34 (sd 16.60), Males 6.23 (sd 17.21); L3 Volume (mm[Formula: see text]): Females 178.90 (sd 474.19), Males 195.80 (sd 547.36); Wall Calcification (%): Females (L4) 6.97 (sd 16.03), Males (L3) 5.46 (13.80)]. Participants with elevated calcification had significantly higher Framingham risk scores compared to participants with normal calcification scores. Opportunistically measuring aortic calcification may inform further cardiovascular risk assessment and enhance cardiovascular event surveillance efforts.

Variation in aorta attenuation in contrast-enhanced CT and its implications for calcification thresholds.

BACKGROUND: CT contrast media improves vessel visualization but can also confound calcification measurements. We evaluated variance in aorta attenuation from varied contrast-enhancement scans, and quantified expected plaque detection errors when thresholding for calcification. METHODS: We measured aorta attenuation (AoHU) in central vessel regions from 10K abdominal CT scans and report AoHU relationships to contrast phase (non-contrast, arterial, venous, delayed), demographic variables (age, sex, weight), body location, and scan slice thickness. We also report expected plaque segmentation false-negative errors (plaque pixels misidentified as non-plaque pixels) and false-positive errors (vessel pixels falsely identified as plaque), comparing a uniform thresholding approach and a dynamic approach based on local mean/SD aorta attenuation. RESULTS: Females had higher AoHU than males in contrast-enhanced scans by 65/22/20 HU for arterial/venous/delayed phases (p < 0.001) but not in non-contrast scans (p > 0.05). Weight was negatively correlated with AoHU by 2.3HU/10kg but other predictors explained only small portions of intra-cohort variance (R2 < 0.1 in contrast-enhanced scans). Average AoHU differed by contrast phase, but considerable overlap was seen between distributions. Increasing uniform plaque thresholds from 130HU to 200HU/300HU/400HU produces respective false-negative plaque content losses of 35%/60%/75% from all scans with corresponding false-positive errors in arterial-phase scans of 95%/60%/15%. Dynamic segmentation at 3SD above mean AoHU reduces false-positive errors to 0.13% and false-negative errors to 8%, 25%, and 70% in delayed, venous, and arterial scans, respectively. CONCLUSION: CT contrast produces heterogeneous aortic enhancements not readily determined by demographic or scan protocol factors. Uniform CT thresholds for calcified plaques incur high rates of pixel classification errors in contrast-enhanced scans which can be minimized using dynamic thresholds based on local aorta attenuation. Care should be taken to address these errors and sex-based biases in baseline attenuation when designing automatic calcification detection algorithms intended for broad use in contrast-enhanced CTs.

Rib cortical bone thickness variation in adults by age and sex.

Rib fractures are a common and serious outcome of blunt thoracic trauma and their likelihood is greater in older individuals. Osteoporotic bone loss is a well-documented aging phenomenon with sex-specific characteristics, but within rib bones, neither baseline maps of regional thickness nor the rates of bone thinning with age have been quantified across whole ribs. This study presents such data from 4014 ribs of 240 adult subjects aged 20-90. A validated cortical bone mapping technique was applied to clinical computed tomography scans to obtain local rib cortical bone thickness measurements over the surfaces of ribs 2 through 11. Regression models to age and sex gave rates of cortex thinning in local zones and aggregated across whole ribs. The statistical parametric mapping provided these relationships regionally as a function of rib surface location. All models showed significant reductions in bone thickness with age (p < 0.01). Average whole-rib thinning occurred at between 0.011 to 0.032 mm/decade (males) and 0.035 to 0.043 mm/decade (females), with sex and age accounting for up to 37% of population variability (R2 ). Rates of thinning differed regionally and by rib, with the highest bone loss of up to 0.074 mm/decade occurring in mid-rib cutaneous and superior regions of ribs 2-6. Rates were consistently higher in females than males (significantly so across whole ribs but not all local regions) and were more pronounced in cutaneous, superior, and inferior rib aspects (average 0.025 mm/decade difference in ribs 4-8) compared to pleural aspects which had the thickest cortices but saw only minor differences in thinning rates by sex (0.045 mm/decade for females and 0.040 mm/decade for males). Regional analysis showed male and female bone thickness differences that were not statistically significant at 20 years of age (p > 0.05 across practically all regions) but subsequent cortex thinning meant that substantial pleural and cutaneous regions were thinner (p < 0.05) in females than males by 55 years of age. The techniques and results from this study can be applied to assess rib bone content loss in clinical settings across wide populations. Additionally, average cortex thickness results can be mapped directly to finite element models of the thorax, and regression results are used to modify such models to represent the ribs of men and women across their full adult lifespan.

Healthy US population reference values for CT visceral fat measurements and the impact of IV contrast, HU range, and spinal levels.

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.

Muscle mass affects paclitaxel systemic exposure and may inform personalized paclitaxel dosing.

AIMS: 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.

Analytic Morphomics Are Related to Outcomes After Lung Volume Reduction Surgery.

: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.

A correction score to compare aortic calcification in contrast enhanced and non-contrast measurements from computed tomography scans.

BACKGROUND: 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 ß 0.74 (95% CI 0.72, 0.76) and ACA ß 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 (ß 0.69-0.82) in ACP and (ß 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.

Psoas Muscle Mass can Predict Postsurgical Outcomes in Patients Who Undergo Radical Cystectomy and Urinary Diversion Reconstruction.

OBJECTIVE: To morphometrically measure to muscle mass which may reflect physical components of frailty. Hence, we evaluated the association between L4 total psoas area (TPA) and operative outcome after radical cystectomy (RC) for bladder cancer. METHODS: In a retrospective single-center study, bladder cancer patients who underwent RC and urinary diversion between 2007 and 2012 were enrolled. TPA was evaluated in the cross-sectional imaging. The psoas muscles were normalized with the height. Male patients with a psoas mass index ≤7.4 cm2/m2 and female patients with a psoas mass index ≤5.2 cm2/m2 were classified as sarcopenic. Outcome measures were 30- and 90-day readmission and complications, and survival. Multivariable logistic and Cox proportional-hazards regression models were used to determine relevant predictors. RESULTS: The median age of the 441 participants and follow up time was 68 years (IQR 59-75) and 1.2 years (IQR 0.5-1.9), respectively. One hundred forty-three patients (32.4%) were sarcopenic. The 30-day readmission and the complication rates were 13.8% and 44.7%, respectively. The 90-day readmission and complication rates were 23.9% and 53.1%, respectively. The 1-year mortality rate was 11.6% (95%CI 8.7-15.4). Multivariable logistic regression analysis revealed an association between increased TPA and lower odds of 30-day complications after RC (OR 0.95, 95%CI 0.92-0.99, P = .02); similarly, an increase in TPA was of prognostic value, although not statistically significant in the multivariable model (P = .05) once adjusting for other patient factors. CONCLUSION: Sarcopenia predicted early complications and showed an informative trend for overall survival after RC, and thus may inform models predicting postsurgical outcomes.

Does a "Cushion Effect" Really Exist? A Morphomic Analysis of Vulnerable Road Users with Serious Blunt Abdominal Injury.

Introduction: 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.

Predicting outcomes of abdominal surgical emergencies in the elderly population using a CT muscle gauge.

BACKGROUND: 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.

Optimal body size adjustment of L3 CT skeletal muscle area for sarcopenia assessment.

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 [Formula: see text] 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 [Formula: see text] and [Formula: see text], 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 ([Formula: see text], [Formula: see text]) adjusted for BMI. [Formula: see text] was less correlated with height in both males and females ([Formula: see text], [Formula: see text] and [Formula: see text], [Formula: see text]) than [Formula: see text] ([Formula: see text] and [Formula: see text], [Formula: see text]). [Formula: see text] was uncorrelated with BMI and weight, and minimally correlated with height in males and females ([Formula: see text], [Formula: see text] and [Formula: see text], [Formula: see text]). The final [Formula: see text] equation was: [Formula: see text], where [Formula: see text], [Formula: see text], [Formula: see text], and sex = 1 if male, 0 if female. We propose [Formula: see text] for optimal height adjustment and the [Formula: see text] score for optimal height and BMI adjustment. By minimizing correlations with height and BMI, the [Formula: see text] score produces unbiased assessments of relative L3 skeletal muscle area across the full range of body sizes.

The psoas muscle index distribution and influence of outcomes in an Asian adult trauma population: an alternative indicator for sarcopenia of acute diseases.

BACKGROUND: 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 (ß 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.

CT validation of SVC-RA junction location for pediatric central line placement: is vertebral bodies below the carina accurate?

PURPOSE: 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. CONCLUSION: 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.

Comparing FE human body model rib geometry to population data.

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.

Comparison of Body Size, Morphomics, and Kidney Function as Covariates of High-Dose Methotrexate Clearance in Obese Adults with Primary Central Nervous System Lymphoma.

BACKGROUND: 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.

BACKGROUND: 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.

A Morphomic Index Is an Independent Predictor of Survival After Lung Cancer Resection.

BACKGROUND: 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.

Bedside Measures of Frailty and Cognitive Function Correlate with Sarcopenia in Patients with Cirrhosis.

BACKGROUND: Frailty and sarcopenia are associated with mortality and poor outcomes among patients with cirrhosis. Frailty is multifactorial but due in part to sarcopenia and cognitive dysfunction. Data are limited regarding the correlation of bedside frailty and cognitive function measures with sarcopenia. AIMS: To evaluate the correlations between frailty measures and muscle indices from computed tomography (CT). METHODS: We prospectively enrolled 106 patients with clinically compensated cirrhosis (and no prior hepatic encephalopathy). All patients underwent CT scan and cognitive testing (via inhibitory control test, ICT), and were subject to hand grip, 30-s chair stands, mid-arm muscle area (MAMA), and a four-question algorithm based on the Sickness Impact Profile (SIP) predictive of minimal HE. We evaluated Spearman correlations between all measures as well as the sensitivity and specificity of each measure for falls. RESULTS: In total, 106 (35.3%) patients (55 men) had CT scans to measure skeletal muscle area and quality. Hand grip correlated strongly with skeletal muscle area (correlation coefficient 0.64, p < 0.001) and mildly with ICT performance (0.34, p = 0.002). However, for women, the strongest correlation with hand grip was ICT performance (0.60, p < 0.001). Chair stand performance correlated best with SIP (correlation coefficient - 0.35, p < 0.001). MAMA was not correlated with CT-based muscle indices among women but was for men. Poor chair stand performance (< 10/30-s) had a sensitivity/specificity for falls of 73%/54%; low muscle radiation attenuation (density) was 40%/80% sensitive/specific. CONCLUSION: Bedside measures of physical function, muscle bulk, and cognitive performance are correlated with CT-based muscle measures. Bedside measures of frailty may provide an advantage over sarcopenia for outcome assessment that should be confirmed prospectively.