Non-Invasive Diagnosis of Canine Degenerative Myelopathy Using Diffusion Tensor Imaging; Opening Doors For Future Treatment Trials
Principal Investigator: Philippa Johnson
DESCRIPTION (provided by applicant):
Canine degenerative myelopathy (CDM) is a neurodegenerative condition of the spinal cord white matter that produces progressive neurological deterioration and often results in euthanasia within six to nine months of clinical onset. Currently there is no cure. The development of white matter lesions has been linked to a genetic mutation in Superoxide Dismutase 1 (SOD1) however not all SOD1 positive dogs develop clinical neurological deterioration. Currently, diagnosis of CDM is presumptive and relies on a characteristic neurological presentation and a positive SOD1 genetic test. The diagnosis is presumptive because standard structural magnetic resonance (MR) imaging does not detect CDM lesions and so the presence, extent and site of lesions cannot be confirmed. Identifying a way to visualize CDM lesions with non-invasive imaging would improve diagnosis and help with clinical decision making. Additionally, promising treatments that terminate neurological deterioration have emerged from recent pre-clinical studies in SOD1 mutant mice. This provides an opportunity for treatment trials in CDM. Being able to track lesion load and location over time would be a very valuable tool to assess response to treatment during these trials. Diffusion tensor imaging (DTI) is an advanced MRI technique that is highly sensitive for detecting alterations in water diffusion secondary to white matter lesions within the spinal cord. This approach has been used to successfully detect white matter lesion load in human patients with neurodegenerative disease and has been correlated to neurological status. We hypothesize that DTI is able to detect white matter lesions due to CDM in a cohort of clinically affected dogs when compared to an unaffected, neurologically normal control group. Additionally, we hypothesize that the extent of lesions identified using DTI correlates to neurological status in CDM dogs at the time of imaging