Neuromuscular Diseases (NMDs) affect > 7 million people worldwide. NMDs are often difficult to accurately diagnose, with over 200 different genetic causes with overlapping clinical presentations. Muscle Magnetic Resonance Imaging (Muscle MRI) allows for non-invasive, comprehensive, and reproducible evaluation of disease-affected and spared muscles. The selective replacement of muscle tissue by fat is the main contributor to pathological patterns determined by T1-weighted Muscle MRI. Although the diagnostic utility of Muscle MRI has been emphasized in the last years, the very low incidence of NMDs (rate .01 to 15 per 100,000 population), and the challenge to attain sufficient sample sizes to study the imaging characteristics of these patients have limited their acceptance as first-line, non-invasive diagnostic procedures. The purpose of this study is to examine the selective pattern of muscle pathology as detected by MRI of different sub-types of NMDs and validate this technique as an important and helpful non-invasive diagnostic screening tool.

This study will prospectively assemble a well-defined cohort of 1000 patients with NMDs undergoing whole body Muscle MRI from 7 Canadian and 7 international centers. It will develop a high-standard methodological approach for MRI diagnosis in this cohort, based on T1 weighted imaging characteristics, and will validate this method by testing the developed algorithm in a different cohort of patients. Muscle MRI scans will be collected by a well-established network of neuromuscular disease (NMD) centers to ensure comparability between the different centers.

The primary objectives of this study are:

1. Establish a large, well-defined international cohort of patients with NMDs with Muscle MRI
2. Identify diagnostic patterns of muscle involvement for patients with rare NMDs using Muscle MRI
3. Validate diagnostic patterns of muscle pathology detected by MRI for patients with rare NMDs

Additional objective of this study:

1. Provide practice-changing information regarding the optimal use of Muscle MRI in patients suspected of having an NMD

Whole Body Muscle MRI is emerging as a tool to identify diseased muscles that are not readily evaluated by clinical examination, where patterns of involvement may be associated with specific Neuromuscular Diseases (NMDs) and may provide additional evidence to rule in/out a particular genetic variant. Previous studies have outlined more common NMDs, and the majority of rare NMDs do not have large cohorts of patients to clearly establish "specific" muscle patterns. Progress has also been limited by a lack of international standards to acquire MRIs and identifying MRI patterns of affected muscles.

By collectively pooling MRI scans for patients with different NMDs, this study will help improve the characterization of selective patterns of muscle atrophy, fatty degeneration, and muscle edema in specific diseases and avoid misdiagnosis of genetic or acquired NMDs. Recognizing patterns of pathology by muscle or nerve imaging can help to guide or confirm genetic testing and to avoid the more invasive procedure of a muscle biopsy. Finally, this project will inform quantitative MRI approaches by identifying the most appropriate regions of interest to be scanned in clinical trials for specific NMDs.

Inclusion Criteria:

1.Clinical diagnosis of neuromuscular disease: Potential participants will have a diagnosis of NMD, based on clinical testing, electrodiagnostic studies and antibody testing or genetic testing of a pathogenic variant based on the American College of Medical Genetics criteria [63]. Standard-of-care assessments include a detailed NMD examination by neurogenetics or neuromuscular physician, a three-generation family history, genetic testing, electrophysiological studies, and standard myopathy serology (e.g., creatine kinase level), muscle biopsy, muscle ultrasound, etc. will be considered for this study.

Exclusion Criteria:

1. Patients with contraindications to MRI 1.1 Including non-MR compatible cardiac pacemaker or electronic devices 1.2 Severe claustrophobia
2. Patients with clinical presentation not consistent with confirmed NMD
3. Patients with advanced disease with severe quadriparesis (Medical Research Council Muscle Rating score of <3 in >10 muscle groups) or asymptomatic patients, as severe fatty replacement of muscle tissue in the late disease of most muscles or normal scans, will limit the value of diagnosis by imaging.

Neuromuscular Diseases