English

Abstract

Introduction Duchenne muscular dystrophy (DMD) is a severe neuromuscular disorder caused by mutation(s) in the gene encoding dystrophin. While recent advances in palliative care have increased life expectancy to 20–30 years of age, this disease remains invariably fatal. Muscle pathology and therapeutic efficacy is primarily assessed using invasive muscle biopsies or muscle strength measurements, both of which have considerable disadvantages. The use of non-invasive imaging to monitor DMD progression and efficacy of therapeutic intervention strategies may further be used for the development of treatments for this devastating childhood disorder. This review will highlight the use of three medical imaging technologies routinely used in clinics today that may be valuable in monitoring disease muscle pathology and therapeutic efficacy in animal models of muscular dystrophy and in DMD patients. Specifically, this review will focus on the use of various imaging modalities to assess disease progression in skeletal muscle tissue where myofiber degeneration is the hallmark pathology of DMD. Research Non-invasive assessment of skeletal muscle pathology and treatment for Duchenne muscular dystrophy K Gutpell1,3,4, L Hoffman1,2,3,4* involving magnetic resonance imaging (MRI), positron emission tomography (PET) and computed tomography (CT) will be reviewed and their potential use in future studies will be discussed. Conclusion While the research discussed in this review highlights the promise for the use of non-invasive imaging to monitor muscle degeneration/regeneration in DMD patients, a few key limitations must first be addressed before these techniques are implemented as a mainstay in DMD patient care. These limitations include long scan and study times that are not ideal for paediatric patients, potential health and safety concerns due to current radiation doses, inconsistent imaging protocols between imaging centres and limited access to imaging centres for some patients. Introduction Duchenne muscular dystrophy (DMD) is the most commonly diagnosed fatal childhood disorder, affecting approximately one in 3500 live male births. Although recent advances in palliative care have resulted in prolonged life span, this devastating disease remains invariably fatal by approximately 30 years of age. Considerable promising research is currently being conducted to treat DMD. These areas of research include viral (and other) delivery of mini or microdystrophin variants1,2, stem/ progenitor cell transplantation3, exon skipping4 and analog (eg. utrophin) upregulation5. While each of these approaches offer their own potential benefits, they are all hindered by one common limitation. Currently, the typical way to assess the impact of these approaches on muscle health is by invasive and painful muscle biopsies that may themselves contribute to further disease progression. In addition to the invasive nature of muscle biopsies, information gleaned from this tissue is limited to histological (H&E, Masson’s trichrome stains), biochemical and molecular (western blotting, gene expression) analyses, that preclude any sort of longitudinal, functional assessment6. Thus, there is a critical need for ways to non-invasively assess disease progression and subsequent efficacy of therapeutic interventions7. The purpose of this review is to examine the potential use of various non-invasive imaging modalities for their use in monitoring disease progression and/or therapeutic outcome in DMD patients. Specifically, this review will highlight the benefits and limitations of magnetic resonance imaging (MRI), positron emission tomography (PET) and computed tomography (CT) as they may pertain to DMD research. While this review focuses on the use of these imaging modalities as they pertain to skeletal muscle specifically, their use for monitoring disease progression and therapeutic approaches in DMD-related cardiomyopathy is also promising and relevant to this discussion. Magnetic resonance imaging Magnetic resonance imaging (MRI) is an ideal imaging modality for visualising the anatomy of soft tissue within the body, thus offering many potential benefits for use in assessing muscle pathogenesis in both animal models of DMD, DMD patients and other patients suffering from a broad spectrum of myopathies8–10. To this end, *Corresponding author Email: lhoffman@lawsonimaging.ca 1 Department of Anatomy and Cell Biology, Western University, London ON, CA , N6A 3K7 2 Department of Medical Biophysics, Western University, London ON, CA , N6A 3K7 3 Imaging Program, Lawson Health Research Institute, London ON, CA , N6A 4V2 4 Collaborative Molecular Imaging Program, Western University, London ON, CA , N6A 3K7