My research focuses on animal models of clinically relevant MRI findings in multiple sclerosis (MS) and MS-related diseases. MRI findings are important components in the diagnostic criteria of demyelinating diseases. In addition, they serve as important biomarkers in monitoring disease activity and response to therapy.
MRI descriptors of demyelinating diseases can be categorized as lesional and non-lesional. In general, lesional findings are often the most obvious and easily detectable abnormalities and as such tend to be included in the diagnostic criteria and monitoring of demyelinating diseases. However, the correlation between lesional findings, especially the most commonly seen T2 hyperintense lesions and disability or future disability risk in multiple sclerosis tends to be moderate at best.
In contrast, non-lesional findings, including compartmentalized or global atrophy, changes in normal appearing gray and white matter, cortical and deep gray matter abnormalities often demonstrate much stronger correlation with functional outcome.
In general, these findings require more sophisticated MR acquisition and/or image processing tools; therefore their clinical utility remains limited. A common denominator of many of the above findings, lesional or non-lesional, is their relatively poorly understood pathogenesis.
Our laboratory has developed models for several key MS-related findings. We successfully demonstrated a number of lesional features, including:
T2 hyperintense and T1 hypointense lesion development
Chronic T1 hypointense brain lesions or T1 black holes
Fulminant/hemorrhagic demyelinating lesions
Spinal cord lesions
We also have relevant models of non-lesional findings, including, brain atrophy; spinal cord atrophy; deep gray matter T2 hypointensity; and abnormalities in normal appearing gray and white matter on advanced MRI methods.
All the above models are unique to our laboratory and our collaborators. These models allow for investigations focusing on the immunopathogenesis of these findings, with special attention to the relationship between clinically relevant MRI features and disability in murine demyelinating disease models.
Through our collaboration with the Nuclear Magnetic Resonance Core Facility at Mayo Clinic, we have access to a 7 Tesla and a 16.4 Tesla small-animal MRI system. In addition, we actively collaborate with a number of Mayo investigators, with whom we are studying the MRI characteristics of remyelination and tissue repair.