Identification of Muscle Wasting in Lung Cancer using MRI Proton Density Fat Fraction and Ultrasound

Abstract

BackgroundMuscle wasting, indicative of poor muscle health, is a hallmark of sarcopenia and cachexia and is one of the most consequential changes associated with aging and disease. Its presence is a strong predictor of frailty, impaired quality of life, and mortality. However, muscle wasting is inaccurately simplified to mean the quantitative loss of mass and reduced clinically to crude visual inspection. This disregards adipose tissue infiltration signifying declining ‘muscle quality’. Chemical‐shift encoded MRI to quantify proton density fat fraction (PDFF) is an established biomarker for quantifying tissue fat content, and provides an opportunity to objectively evaluate muscle quality. We aimed to determine how muscle quality changes with aging and disease using PDFF, in order to develop clinically implementable bedside ultrasound methods.MethodsA single‐center, cross‐sectional, observational pilot study enrolled 21 participants – 10 healthy, young adults; 5 adults with lung cancer undergoing outpatient systemic therapy; and 6 healthy, aged‐matched adults. Participants were scanned on a 3T MRI system (Signa Premier, GE Healthcare, Waukesha, WI) using a 30‐channel flexible coil (GE Healthcare, Waukesha, WI). The protocol included a commercial 3D multi‐echo spoiled gradient echo acquisition (IDEAL IQ, GE Healthcare, Waukesha, WI). Quantitative PDFF maps were reconstructed using a confounder‐corrected magnitude‐fitting least squares algorithm and a 2 cm2 region of interest was measured in the rectus femoris. Similarly, quantitative ultrasound (Acuson, Seimens, Malvern, PA) was used to measure sheer wave elastography (SWE) and echointensity (EI) in a similar area of the rectus femoris. All measurements of the rectus femoris were taken at the midpoint of the thigh between the patella and anterior superior iliac spine.ResultsThere was a strong association between ultrasound EI and PDFF (r=0.74, p<0.001). No associations were found with SWE. Mean PDFF and EI increased between young, older, and age‐matched lung cancer (0.63±0.44, 1.44±1.29, 3.36±2.52 and 53.36±19.84, 71.90±29.6, 92.38±30.5, respectively). The mean differences between the young and lung cancer group reached significance for both PDFF and EI (p<0.05), however not between the lung cancer group and age‐matched adults. Conversely, SWE decreased between young, older, and age‐matched lung cancer (10.34±1.68, 8.90 ±1.17, 8.49±0.85, respectively), but did not reach significance for between group differences.ConclusionMuscle quality decreases in aging and disease as evidenced by PDFF and EI. EI was highly correlated with PDFF as a measure of muscle fat content in the setting of muscle wasting. These results indicate a need for a larger, longitudinal study to examine ultrasound EI as a suitable bedside technique to evaluate muscle wasting in sarcopenia and cachexia.Support or Funding InformationNIH supported University of Wisconsin‐Madison ICTR Pilot Grant