Collaborative MS Research Center Award
||Anne H. Cross, MD
Department of Neurology
Washington University School of Medicine, St. Louis
Joseph J.H. Ackerman, PhD
Departments of Radiology, Chemistry and Internal Medicine
John H. Russell, PhD
Department of Molecular Biology and Pharmacology
Sheng-Kwei "Victor" Song, PhD
Departments of Radiology and Chemistry
A major effort to apply new magnetic resonance technology to tracking brain tissue damage and recovery in MS.
Multiple sclerosis is a disease that can be very different between individuals in terms of its clinical course, the type of tissue damage involved, and response to available therapies. It is currently not possible to differentiate or predict the type of MS an individual will experience.
Since MRI emerged in the early 1980s, great advances have taken place in developing and applying magnetic resonance imaging technologies—MRI and its cousins—to the study of disease activity in individuals with MS. While they've provided a remarkable window to the activity of brain and spinal cord lesions (areas of disease activity or damage), unfortunately these technologies still cannot reliably distinguish between areas of damage to the myelin insulation that encases nerve fibers and damage to the nerve fibers themselves.
Now seasoned MS investigator Dr. Anne Cross has assembled an interdisciplinary team to apply a novel MR technology to tackle this problem. Armed with a new National MS Society Collaborative MS Research Center Award, the team of neurologists, radiologists, biophysicists, biomedical engineers and pharmacologists at Washington University in St. Louis will use "diffusion tensor MR imaging," or DTI, to differentiate types of tissue damage and repair in MS lesions—first in mice and eventually in people with MS.
DTI reveals how many protons in water molecules are moving in tissue, and in what direction. If fatty myelin is intact, then water should be repelled, but if it is damaged, water will infiltrate the tissue. Recent reports indicate that damage to axons (nerve fibers) underneath the myelin also can affect the flow of water, and thus be detected by DTI.
In an earlier, National MS Society-funded pilot research project, team member Sheng-Kwei Song, PhD, had used DTI in a mouse model similar to MS that involves damage to myelin but no damage to the axon beneath. By comparing these mice to others with damage to both myelin and axons, he found that water flowed in different directions, depending on whether just myelin was damaged, or both myelin and axons. Thus DTI may be useful in determining the extent of MS damage with greater tissue specificity than MRI.
In the course of the five-year Center award, Drs. Cross and Song are enlisting the expertise of Joseph J. H. Ackerman, PhD, a leader in the application of MR technology to living systems—from isolated cells to humans—and John H. Russell, PhD, a prolific investigator who has published pathbreaking results on the mechanisms of immune damage and regulation in disease. These investigators will create DTI profiles of tissue damage using animal models of myelin damage, axonal damage, and combinations of inflammation, myelin loss and re-growth, and axonal damage.
Once they know what each of these types of damage and repair look like using DTI, they will use the same techniques to examine people with and without MS, and people with optic neuritis (inflammation of the nerve sending signals from the eye to the brain, which is often damaged early in MS and which is fairly easy to study) which has shown either full recovery or little recovery.
Ultimately, these experiments will open a new window to view the types and amount of tissue damage and tissue recovery in persons with MS. Having such a tool would help doctors make treatment decisions to help their patients, and would greatly improve the ability to evaluate the effectiveness of new therapies.