MRI-based in vivo histology of Multiple Sclerosis

Multiple sclerosis (MS) is the most common cause of acquired, non-traumatic disability in young people. Previously viewed primarily as an inflammatory disease of the brain`s white matter, it is now considered a complex disorder involving focal and diffuse pathological processes throughout the brain, including the cerebral cortex, which contains the nerve cells. Infiltration of inflammatory cells, activation of phagocytic cells in the brain, and subsequent demyelination (loss of myelin sheaths that ensure nerve conduction velocity in the brain) occur throughout the central nervous system, including the gray matter, and shape the symptoms of affected individuals over time. These processes can vary considerably in space and time between different people with MS, contributing to significant differences in treatment response. The progressive and continuous increase in limitations in daily life is associated with widespread diffuse chronic inflammation and loss of nerve cells. Remyelination, or the restoration of myelin sheaths, represents a means of repairing demyelination, protecting nerve cell processes and nerve cells themselves. Failure of remyelination leads to an unfavorable clinical course. Mitigating the long-term disability of people with MS is a central clinical concern and requires early diagnosis, prediction of disease activity, and timely, individualized treatment. Currently, MS experts base their diagnostic and therapeutic decisions on information obtained from patients` symptoms, neurological examinations, and conventional magnetic resonance imaging (MRI) scans. Unfortunately, conventional MRI is not specific to the pathological mechanisms in people with MS and has low sensitivity and specificity for changes in the cerebral cortex. Treating chronic inflammation and promoting remyelination are essential to protect against nerve cell loss. However, this requires the development of sensitive and specific, non-invasive imaging markers for assessing and prognosticating neuroinflammation, demyelination, and remyelination. This is a crucial step in evaluating new treatment strategies. With this project, we aim to utilize additional tissue contrasts, such as those derived from brain iron, by examining tissue samples from the brains of deceased individuals with MS in modern, high-resolution 7-Tesla MRI scanners and employing the latest sequence combinations. This will improve the visualization of myelin in the cerebral cortex. We believe this will also enhance the visualization of protective remyelination in the cerebral cortex in living subjects, enabling the testing of new therapies.