Determining Biomarkers of Myosteatosis for Sarcopenia and Cachexia Using MRI and Ultrasound

Abstract

BackgroundLung cancer patients have low survival rates resulting in over 131,000 deaths in the US in 2021. Muscle health decline from sarcopenia and cachexia increases the risk of death among patients with lung cancer. Though muscle mass is often used for sarcopenia diagnosis and non‐tissue specific weight loss is typically used for cachexia diagnosis, both conditions have no consensus definitions. Therefore, the need for quantitative biomarkers that reflect muscle health changes due to aging and weight loss is critical to mitigate sarcopenia and cachexia. We propose using highly accurate MRI‐based proton density fat fraction (PDFF) as a reference measure of muscle health to develop bedside ultrasound measures as biomarkers of muscle health. We hypothesized that PDFF is associated with ultrasound‐based echointensity (EI) and shear wave elastography (SWE), and that all three modalities are sensitive to muscle health differences between healthy young, healthy older, and older adults undergoing treatment for lung cancer.MethodsWe compared muscle health operationalized as myosteatosis in the mid‐thigh of the rectus femoris using ultrasound‐based brightness‐mode for EI, ultrasound‐based SWE for tissue elasticity, and MRI‐based PDFF for percent fat, which was the reference measure. We compared the 3 measures among young healthy (n=10), older healthy (n=10), and older adults with non‐small cell lung cancer (n=10) in a cross‐sectional pilot study. We also compared non‐myosteatosis measures including subcutaneous adipose tissue thickness and rectus femoris thickness via ultrasound, whole‐leg cross‐sectional area via MRI, and BMI between groups and between myosteatosis measures. We used ANOVAs with Tukey post‐hoc comparisons to assess muscle health between groups and Pearson correlations to determine muscle health measure associations between imaging modalities.ResultsWe found young healthy adults had significantly lower PDFF than older healthy adults and older adults with lung cancer (0.33% vs 2.83% vs 2.93%, respectively; p=0.001). Young adults also had significantly lower EI than older healthy adults, but not older adults with cancer (48.58 vs 81.81 vs 75.35; p=0.008). When comparing between measures, PDFF was highly associated with EI (r=0.62, p<0.001) and moderately inversely associated with SWE (r=‐0.41, p=0.025) but not BMI, rectus femoris thickness, or rectus femoris cross‐sectional area.ConclusionPDFF was sensitive to myosteatosis differences between young and both older adult groups. EI was less sensitive to myosteatosis differences between groups, yet EI was highly associated with PDFF unlike BMI. Our results suggest that the ultrasound measures could serve to determine muscle health at the bedside and are more sensitive to muscle health differences than BMI, which could improve interventions for cachexia and patient outcomes.