Comprehensive quantitative magnetic resonance imaging assessment of skeletal muscle pathophysiology in golden retriever muscular dystrophy: Insights from multicomponent water T2 and extracellular volume fraction.

Abstract

Quantitative MRI and MRS have become important tools for the assessment and management of patients with neuromuscular disorders (NMDs). Despite significant progress, there is a need for new objective measures with improved specificity to the underlying pathophysiological alteration. This would enhance our ability to characterize disease evolution and improve therapeutic development. In this study, qMRI methods that are commonly used in clinical studies involving NMDs, like water T2 (T2) and T1 and fat-fraction (FF) mapping, were employed to evaluate disease activity and progression in the skeletal muscle of golden retriever muscular dystrophy (GRMD) dogs. Additionally, extracellular volume (ECV) fraction and single-voxel bicomponent water T2 relaxometry were included as potential markers of specific histopathological changes within the tissue. Apart from FF, which was not significantly different between GRMD and control dogs and showed no trend with age, T2, T1, ECV, and the relative fraction of the long-T2 component, A, were significantly elevated in GRMD dogs across all age ranges. Moreover, longitudinal assessment starting at 2 months of age revealed significant decreases in T2, T1, ECV, A, and the T2 of the shorter-T2 component, T2, in both control and GRMD dogs during their first year of life. Notably, insights from ECV and bicomponent water T2 indicate that (I) the elevated T2and T1 values observed in dystrophic muscle are primarily driven by an expansion of the extracellular space, likely driven by the edematous component of inflammatory responses to tissue injury and (II) the significant decrease of T2and T1 with age in control and GRMD dogs reflects primarily the progressive increase in fiber diameter and protein content during tissue development. Our study underscores the potential of multicomponent water T2 relaxometry and ECV to provide valuable insights into muscle pathology in NMDs.