Work Description

Date: 1 May, 2024

Dataset Title: Relative muscle indices and healthy reference values for sarcopenia assessment using T10.5 through L5 computed tomography skeletal muscle area [Dataset]

Dataset Creators: Brian A Derstine, Sven A Holcombe, Nicholas C Wang, Brian E Ross, June A Sullivan, Stewart C Wang, Grace L Su

Dataset Contact: Brian Derstine, bderstin@med.umich.edu

Funding: None

Key Points:
- We extracted T10.5 through L5 skeletal muscle axial cross-sectional area, mean radiation attenuation (Hounsfield Units), and intramuscular adipose tissue area using non-contrast-enhanced CT scans from healthy, adult kidney donor candidates between age 18 and 73.

Research Overview:
According to the European Working Group on Sarcopenia in Older People (EWGSOP), sarcopenia is defined as the loss of both muscle mass and function. Assessments of muscle mass can be performed using computed tomography (CT) measurements of skeletal muscle cross-sectional area (SMA) at the third lumbar vertebra (L3), with cutpoints for low muscle mass consistent with sarcopenia set at two standard deviations below the mean (-2SD) of a healthy, young adult population. Muscle quality is assessed using skeletal muscle radiation attenuation (SMRA), intramuscular adipose tissue area (IMAT), and the skeletal muscle gauge (SMG) - the product of SMRA and skeletal muscle index (SMI).

Reference `young, adult' populations generally use an 18-40 or 20-40 age range. The upper bound of 40 is supported by the observation that muscle mass loss accelerates after age 40, while differences in the lower bound (18 vs. 20) have not been explored.

Other vertebrae besides L3 have also been used in certain situations. Furthermore, the particular slice used as `the L3 slice' has varied between groups. While we (and others) have used an inferior slice (e.g., `at the level of the inferior endplate') when extracting SMA measurements, others have used a mid-vertebral slice (e.g., `where both transverse processes were visible'). While multiple slices have been previously examined, it remains unclear how much difference (of one-half a vertebral body) the location of measurement affects the resulting skeletal muscle measures, or whether single-slice sarcopenic cutpoints developed at an inferior aspect slice would apply to mid-vertebral slice measures.

Revised EWGSOP guidelines note that `fundamentally, muscle mass is correlated with body size; i.e., individuals with a larger body size normally have larger muscle mass'. In prior work we confirmed this relationship between body size and muscle mass, and derived the optimal L3 SMA adjustment for height (SMA/height) using allometric analysis, a finding which has since been confirmed elsewhere. We also found that direct adjustment for weight (SMA/weight) or BMI (SMA/BMI) resulted in sub-optimal, highly biased indices which should be avoided, and that the traditional skeletal muscle index using height-squared (SMA/height^2) retained a significant negative correlation with height and positive correlation with BMI.

We proposed that the optimal body size adjusted skeletal muscle index meet two simple criteria: it should be uncorrelated with (1) height and (2) BMI in a young, healthy reference population. In doing so, it would exclude the variation in muscle quantity explained by height and BMI, resulting in a metric that distinguishes between `more muscular' and `less muscular' body compositions at any height or BMI. Therefore, we developed a relative muscle index (RMI) equation which converted L3 SMA into an index that is uncorrelated with height and BMI. L3 RMI_{HT} quantified sarcopenic low L3 muscle mass across the full range of human body sizes and was unbiased in tall, short, thin, or obese individuals. However, it was limited to measurements of SMA at the inferior L3 level.

In this manuscript and dataset, we expand our analysis of young, healthy adult skeletal muscle measurements to include both a mid-vertebral and inferior aspect slice for each vertebra from T10 to L5, enabling sarcopenia assessment in CT scan protocols that do not include L3. We assess the difference between SMA measured at a mid-vertebral versus inferior aspect slice, and the effect of age group 18-40 versus 20-40 on reference values. We perform allometric analysis of proper height adjustment and report RMI equations for SMA at each slice location. Finally, we report reference means, standard deviations, and cutpoints [mean-2SD (-2SD) and 5th percentile (P5)] for younger and older age groups (18-40, Over 40) to enable comparison with other published healthy adult reference values.

Methodology:
We retrospectively studied persons who underwent CT scans at the University of Michigan as part of evaluation for kidney donation between 1998 and 2017. Patient age, sex, height (m), and weight (kg) were obtained from their medical record proximal to the date of evaluation for kidney donation (using EMERSE). Candidates were included if they had a non-contrast-enhanced series CT scan performed as part of evaluation for kidney donation, with a complete fascia boundary visible in the display field of view for at least one vertebra between T10.5 and L5, had age, sex, height, and weight recorded in their electronic medical record, and were medically, surgically, and psycho-socially approved for donation. CT imaging was extracted for ****2,364**** total donor candidates between the ages of 18 and 73 scanned using the GE `Standard' reconstruction algorithm at 120 kVp and 5 mm slice thickness in a Discovery or LightSpeed scanner. Tube current was automatically modulated in proportion to body mass.

After being transferred into a spatial database, CT images were segmented using an updated version of Analytic Morphomics that uses fully-automated machine learning (ML) models. ML models written in Matlab (The Mathworks Inc, Natick, MA) identified and labelled vertebral bodies, then identified the outer abdominal fascia and inner ventral cavity to create enclosed regions of interest, which were then manually reviewed and edited as needed. SMA was measured as the area of pixels between -29 to +150 Hounsfield Units (HU) in the region of interest on two axial slices per vertebra, one slice nearest the inferior aspect of the vertebral body (e.g., L3) and one slice nearest the midpoint (e.g., L3.5). Skeletal muscle radiation attenuation (SMRA), a measure of tissue density, was measured as the mean attenuation (HU) of all SMA pixels. The skeletal muscle gauge (SMG) was calculated as SMG_{HT} = SMI_{HT} * SMRA. Intramuscular adipose tissue (IMAT) area was calculated as the area of pixels between -205 to -51 HU within the SMA region.

To describe the relationship between BMI and height-adjusted SMA in a young, healthy adult cohort, two multiple linear regression models were constructed for each vertebra level using the `Under-40' cohort; one for SMI_{HT} and one for SMI_{HT2}. In each model, the height-adjusted index (I = SMI_{HT} or SMI_{HT2}) was the response, while BMI, male sex, and their interaction were predictors, allowing for different intercept and slope by sex, e.g., I = b0 + b1*BMI + b2*sex + b3*sex*BMI.

Each height-adjusted index was converted into a relative muscle index (z-score with mean zero and standard deviation one) by subtracting the model's predicted value (I) and dividing by the sex-specific residual standard error (RSE), e.g., RMI_{HT} = (SMI_{HT} - I) / RSE(I).

Date Coverage: 1998-2017 (date range of candidate CT exams).

Instrument and/or Software specifications: MATLAB algorithms written at the Morphomic Analysis Group lab at University of Michigan were used to extract morphomic measurements from CTs. R was used for data post-processing and statistical analysis.

Files contained here:
derstine_sma_reference_2024.csv

Definition of Terms and Variables:
- record_id : an anonymized individual record identifier
- sex : M = male, F = female
- age : age in years
- cohort : 'Under-40' or 'Over-40' classification for analysis
- height_m : person height in meters (m)
- weight_kg : person weight in kilograms (kg)
- bmi : body mass index = weight_kg/(height_m^2) (kg/m^2)
- bmi_group : World Health Organization BMI classification
- race : self-reported race
- ethnicity : self-reported ethnicity
- manufacturer : Computed Tomography (CT) machine manufacturer name
- manufacturermodelname : CT machine model name
- convolutionkernel : CT exam convolution kernel name
- kvp : CT exam kilovoltage peak (kVp)
- xraytubecurrent : CT exam X-ray tube current (mA)
- slicethickness : CT exam slice thickness (mm)
- vlcround : Vertebra level coordinate (VLC) rounded to the nearest 0.5 ("L5" = 0, "L5.5" = 0.5, ..., "T10.5" = 7.5)
- vertebranumber : Vertebra label (e.g., "T10", "T10.5", ..., "L5.5", "L5")
- sma : Skeletal Muscle cross-sectional Area (cm^2)
- smra : Skeletal Muscle mean Radiation Attenuation (HU)
- imat : Intra-muscular adipose tissue cross-sectional area (cm^2)
- smi_ht : Skeletal muscle index = sma/height_m
- smi_ht2 : Skeletal muscle index2 = sma/(height_m^2)
- smg_ht : Skeletal muscle gauge = smi_ht * smra
- predicted_smi_ht : Predicted value of smi_ht from RMI regression equation given in manuscript (by vertebra number)
- sd_norm_smi_ht : Residual Standard Error (RSE) of smi_ht (by vertebranumber and sex)
- rmi_ht : Relative muscle index value for smi_ht; rmi_ht = (smi_ht - predicted_smi_ht)/sd_norm_smi_ht
- predicted_smi_ht2 : Predicted value of smi_ht2 from RMI regression equation given in manuscript (by vertebra number)
- sd_norm_smi_ht2 : Residual Standard Error (RSE) of smi_ht2 (by vertebranumber and sex)
- rmi_ht2 : Relative muscle index value for smi_ht2; rmi_ht2 = (smi_ht2 - predicted_smi_ht2)/sd_norm_smi_ht2

Related publication(s):
Derstine, B.A. et al. (2024). Relative muscle indices and healthy reference values for sarcopenia assessment using T10.5 through L5 computed tomography skeletal muscle area. ****Forthcoming.****

Use and Access:
This data set is made available under an Attribution-NonCommercial 4.0 International (CC BY-NC 4.0).

To Cite Data:
Derstine, B.A., Holcombe, S.A., Wang, N.C., Ross, B.E., Sullivan, J.A., Wang, S.C., & Su, G.L. (2024). Relative muscle indices and healthy reference values for sarcopenia assessment using T10.5 through L5 computed tomography skeletal muscle area [Dataset]. University of Michigan - Deep Blue. https://doi.org/10.7302/ccds-9q38