MICROIMAGING & SPECTROSCOPY OF MUSCLE DAMAGE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Throughout the progression of dystrophic myopathies, the affected muscle tissues undergo numerous cycles of degeneration and regeneration due to their high susceptibility to injury. Upon exhaustion of the regenerative capacity of these muscles, damaged fibers are progressively replaced by fat and connective tissue. Underlying this elevated vulnerability to damage is a deficiency in dystrophin or dystrophin associated glycoproteins (DAGs). Since the pathological effects are often due to the lack of a single protein, the muscular dystrophies are well suited for gene therapy, stem cell therapy, as well as pharmaceutical treatment. Current methods of monitoring efficacy of therapeutic intervention and diagnosis rely heavily on tissue biopsy and histology. The development of non-invasive imaging modalities is greatly needed to evaluate novel therapeutic approaches in their ability to restore the dystrophin/DAG complex. We have found significant differences in magnetization transfer characteristics of healthy and fibrotic dystrophic muscles which can be reversed following gene transfer. These results indicate that magnetization transfer contrast may provide a noninvasive measure of disease progression and therapeutic intervention for the dystrophies.