Quantifying tissue water compartmentation for assessing specific histopathological changes in dystrophic skeletal muscle

Motivation: Developing an objective measure of specific histopathological changes in the skeletal muscle in Duchene Muscular Dystrophy. Goal(s): To investigate distinct histopathological changes in dystrophic muscle by assessing histological tissue water compartmentation in vivo. Approach: A cohort of Golden Retriever Muscular Dystrophy (GRMD), carrier, and wild type dogs underwent quantitative MRI. Tissue water compartmentation, microvascular fraction (f) and extracellular volume (ECV) were assessed using multi-component water-T2 relaxometry, Intravoxel Incoherent Motion (IVIM) and T1 maps acquired before and after gadolinium (Gd) injection. Results: In GRMD, ECV, f, long-T2 fraction and main-T2 value were increased. Carrier dogs displayed mild non-significant abnormalities. Impact: Evaluating tissue water compartmentation in GRMD provided histopathologic specificity, distinguishing vascular from parenchymal changes in dystrophic muscle. The ability to assess histopathologic changes non-invasively will drastically improve our understanding of the disease evolution, treatment strategies and, ultimately, therapeutic development.