Quantitative MRI as a Biomarker of Disease Severity in Neuromuscular Disease

Abstract

Introduction: Oculopharyngeal muscular dystrophy (OPMD) is a slowly progressive disorder marked by ptosis, dysphagia, and proximal muscle weakness. Reliable biomarkers for monitoring are limited, making progression difficult to track in clinics and future trials. Quantitative MRI (qMRI), particularly fat-fraction (FF) and water measures offer a non-invasive way to assess muscle involvement and follow change over time. Aim: To evaluate 97 muscles in OPMD using qMRI and determine if diffusion-related MRI markers [apparent diffusion coefficient (ADC) intravoxel incoherent motion (IVIM)], and T2 relaxation time identify earlier signs of disease activity compared to muscle FF. Methods: The study included 52 participants, 40 patients with OPMD and 12 controls with whole body 3T qMRI. For FF and ADC, 97 muscles were segmented and 24 thigh muscles were segmented for IVIM and T2 map using ITK SNAP version 3.8.0. Statistical analyses used GraphPad Prism and R-studio using, Wilcoxon unpaired tests and Spearman correlation p <0.05. Results: Muscles such as adductor magnus (41.2±28.9 %), soleus (39.2±25.9 %), and biceps femoris long head (BL) (33.8±25.2 %), showed higher FF. Higher FF was linked to a stronger negative correlation between FF-ADC, adductor magnus (spearman’s ρ = -0.90), soleus (spearman’s ρ =-0.83), biceps femoris long head (spearman’s ρ = -0.87)), and FF-IVIM true diffusion (spearman’s ρ =-0.89 CI, -0.94, -0.80 respectively). IVIM perfusion-fraction correlated positively with FF in adductor magnus and biceps femoris long head (spearman’s ρ = 0.80) in the early disease duration period (0-5 years). Exploratory disease-duration stratification showed ADC did not rise prior to fat replacement, as might occur with inflammation and edema; instead, ADC decreased as fat replacement increased. Discussion: FF is a sensitive marker of disease severity and shows a strong negative correlation with diffusivity markers. In this cross-sectional analysis, diffusion values do not rise before fat replacement onset. Identifying sensitive biomarkers of OPMD severity and disease progression is important to identify treatment windows for future trials.