Relative muscle indices and healthy reference values for sarcopenia assessment using T10 through L5 computed tomography skeletal muscle area.

Sarcopenia is the age-related loss of skeletal muscle mass and function. Computed tomography (CT) assessments of sarcopenia utilize measurements of skeletal muscle cross-sectional area (SMA), radiation attenuation (SMRA), and intramuscular adipose tissue (IMAT). Unadjusted SMA is strongly correlated with both height and body mass index (BMI); therefore, SMA must be adjusted for body size to assess sarcopenic low muscle mass fairly in individuals of different heights and BMI. SMA/height (rather than S M A / h e i g h t 2 ) provides optimal height adjustment, and vertebra-specific relative muscle index (RMI) equations optimally adjust for both height and BMI. Since L3 measurement is not available in all CT scans, sarcopenic low muscle mass may be assessed using other levels. Both a mid-vertebral slice and an inferior slice have been used to define 'L3 SMA', but the effect of vertebral slice location on SMA measurements is unexplored. Healthy reference values for skeletal muscle measures at mid- and inferior vertebra slices between T10 and L5, have not yet been reported. We extracted T10 through L5 SMA, SMRA, and IMAT at a mid-vertebral and inferior slice using non-contrast-enhanced CT scans from healthy, adult kidney donor candidates between age 18 and 73. We compared paired differences in SMA between the mid-vertebral slice versus the inferior slice. We calculated the skeletal muscle gauge as S M G HT = S M R A ∗ S M I HT . We used allometric analysis to find the optimal height scaling power for SMA. To enable comparisons with other published reference cohorts, we computed two height-adjusted measures; S M I HT = S M A / h e i g h t (optimal) and S M I H T 2 = S M A / h e i g h t 2 (traditional). Using the young, healthy reference cohort, we utilized multiple linear regression to calculate relative muscle index z-scores ( R M I HT , R M I H T 2 ), which adjust for both height and BMI, at each vertebra level. We assessed Pearson correlations of each muscle area measure versus age, height, weight, and BMI separately by sex and vertebra number. We assessed the differences in means between age 18-40 versus 20-40 as the healthy, young adult reference group. We reported means, standard deviations, and sarcopenia cutpoints (mean-2SD and 5th percentile) by sex and age group for all measures. Sex-specific allometric analysis showed that height to the power of one was the optimal adjustment for SMA in both men and women at all vertebra levels. Differences between mid-vertebra and inferior slice SMA were statistically significant at each vertebra level, except for T10 in men. S M I HT was uncorrelated with height, whereas S M I H T 2 was negatively correlated with height at all vertebra levels. Both S M I HT and S M I H T 2 were positively correlated with BMI at all vertebra levels. R M I HT was uncorrelated with BMI, weight, and height (minimal positive correlation in women at L3 inf , L4 mid , and L5 inf ) whereas R M I H T 2 was uncorrelated with BMI, but negatively correlated with height and weight at all levels. There were no significant differences in SMA between 18-40 versus 20-40 age groups. Healthy reference values and sarcopenic cutpoints are reported stratified by sex, vertebra level, and age group for each measure. Height to the power of one (SMA/height) is the optimal height adjustment factor for SMA at all levels between T10 mid through L5 inf . The use of S M A / h e i g h t 2 should be discontinued as it retains a significant negative correlation with height and is therefore biased towards identifying sarcopenia in taller individuals. Measurement of SMA at a mid-vertebral slice is significantly different from measurement of SMA at an inferior aspect slice. Reference values should be used for the appropriate slice. We report sarcopenic healthy reference values for skeletal muscle measures at the mid-vertebral and inferior aspect slice for T10 through L5 vertebra levels. Relative muscle index (RMI) equations developed here minimize correlation with both height and BMI, producing unbiased assessments of relative muscle mass across the full range of body sizes. We recommend the use of these RMI equations in other cohorts.

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.

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.

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.

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.

Morphomic calcification score from clinical CT scans: A proxy for coronary artery calcium.

BACKGROUND: 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.

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.

Computed tomography correlation of skeletal landmarks and vascular anatomy in civilian adult trauma patients: Implications for resuscitative endovascular balloon occlusion of the aorta.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (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 computed tomography (CT) correlations of skeletal landmarks with vascular lengths. METHODS: Between 2000 and 2015 at a single civilian tertiary care center, 2,247 trauma patients with CT imaging were identified, yielding 1,789 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 (interquartile range, 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 that 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%). CONCLUSION: Computed tomography morphometry suggests that 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 TE. 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. LEVEL OF EVIDENCE: Prognostic/epidemiological, level III.

Skeletal muscle cutoff values for sarcopenia diagnosis using T10 to L5 measurements in a healthy US population.

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.

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.

Relationships of Vancomycin Pharmacokinetics to Body Size and Composition Using a Novel Pharmacomorphomic Approach Based on Medical Imaging.

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.