Understanding Muscle Before it's Gone: Multi-Parametric Characterization of Skeletal Muscle Biomarkers Derived From DXA and MRI in a Frail Population

Abstract

Approximately 23% of Canadians over the age of 65 are considered frail, with that number predicted to increase up to 40% for the population over the age of 85. Frailty is a geriatric syndrome defined by the natural decline in muscle mass and function caused by the natural aging process. When developing to an excessive degree, frailty may present as a disease state, which is recognized as sarcopenia. The exact definition of sarcopenia relies on the presence of low muscle mass, strength, and/or function, but quantitative cut-off values are still a topic of debate. Understanding how biomarkers measured via diagnostic imaging such as magnetic resonance imaging (MRI) and dual-energy x-ray absorptiometry (DXA) describe skeletal muscle can allow doctors to develop a profile of sarcopenia and define predictors to aide in preventative therapy. 4 male and 9 female (mean age = 78 ± 6.5 years) participants from a frailty study underwent full-body DXA and had their dominant thigh scanned using a 3.0T MRI. DXA-derived appendicular lean mass (ALM) and MRI-derived cross-sectional area (CSA), fat fraction (FF), T2 relaxation (T2), magnetization transfer ratio (MTR), fractional anisotropy (FA) and mean diffusivity (MD) from 4 muscle groups at the mid-thigh were defined as muscle biomarkers. Pearson's correlation was calculated to identify relationships between biomarkers and a Wilcoxon rank-sum test was performed to assess the agreement of low-muscle mass characterization between ALM normalized by height (ALMI), ALM normalized by BMI (ALM/BMI), and the gold standard MRI cross-sectional area. Strong positive correlations between muscle quantity biomarkers such as ALMI and CSA were recognized within the quadriceps (p=0.0095), adductors (p=0.035), and sartorius (p=0.00065) muscles while muscle quality biomarkers such as FF and T2 showed significant positive correlation within the quadriceps (p=3.58*10^-5) and the hamstring (p=0.0042) muscles. Finally, ALM/BMI displayed a much stronger agreement in muscle mass quantification with the gold-standard of MRI-CSA over the more commonly researched ALMI from DXA. The main purpose of this study was to collate a vast array of skeletal muscle biomarkers obtained using DXA and MRI on a frail population, and show that significant correlations can be recognized from a single MRI-slice located at the mid-thigh. Additionally, this study recognized the potential of ALM/BMI as the DXA-derived biomarker of choice in muscle mass assessment of frailty.