Muscle imaging of patients with RYR1-related myopathies and its significance to clinical features

RYR1-related myopathies (RYR1-RMs) have been reported to exhibit distinct clinical manifestations and muscle pathology. Muscle imaging has gained increasing importance in the diagnosis and the imaging data have also been used in clinical trials for some diseases. This study aims to identify fat replacement patterns among RYR1-RMs and to investigate their relationship with clinical manifestations. A total of 36 patients with RYR1-RMs were examined by quantifying fat replacement in 47 skeletal muscles using the modified Mercuri score (mMS). Patients were classified into 6 diseases: central core disease (CCD), congenital neuromuscular disease with uniform type 1 fiber, central core disease with atypical core, multiminicore disease (MmD), dusty core disease, and myopathy with central nuclei. For data analyses, we employed dimensionality reduction using uniform manifold approximation and projection (UMAP), and hierarchical clustering. The patients with RYR1-RMs were positioned close together on UMAP. Violin plot analysis identified chronological patterns of fat replacement in whole body. Significant correlations were observed between imaging data and clinical symptoms, including respiratory failure, ambulation impairment and scoliosis, and muscle pathology. The patients with RYR1-RMs share a common pattern of fat replacement. Progressive fat replacement was identified, providing a foundation for establishing muscle imaging as a marker for disease progression and treatment efficacy.