Grant: Project Grant

The central nervous system (CNS) contains a network of nerve cells that makes up the brain and spinal cord. Multiple sclerosis (MS) is a disease that affects the CNS and, in turn, affects a person's moving, thinking, learning, feeling and seeing. During MS, the body's own defense system attacks its myelin, a substance that covers and protects nerve fibers in the CNS. This causes holes (lesions) to develop in the myelin coating. Although standard MRI is good at detecting lesions in MS, it can only show a fraction of the disease burden that affects the whole brain. Our recent MRI studies have shown preliminary evidence of two under-appreciated features of brain structure that are altered during MS progression. First, cortical layer-specific lesions are present in certain highly myelinated areas of the brain. Second, certain brain structural connections linking to the cortical surface are impacted during progression of disease in MS. We need to be able to quantify these changes in living patients to know when they form, how they affect clinical disability and whether they respond to MS drugs. The research outlined in this grant will help address the following questions about brain structure and microglial activation in MS patients: (1) Is cortical and white matter tract damage linked to silent progression i.e. disability progression independent of MS relapses? (2) Where in the brain does cortical damage preferentially begin? (3) Is there a specific cortical immune cell component linked to silent progression? We will use an ultra-high field, 7T MRI scanner, similar to a very powerful microscope, to link measures of tissue damage on the surface of the brain to MS disability progression. We will then use Positron Emission Tomography (PET) imaging to study immune cell components which contribute to silent progression. Answers to the above questions may guide the development of new treatment strategies, as well as enhance our understanding of how MS affects the brain.