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Imaging Technology Advances Multiple Sclerosis Research

In This Article

  • Researchers focused on studying multiple sclerosis (MS) at Massachusetts General Hospital are conducting novel research to understand the pathology of MS
  • The work is made possible by advanced imaging capabilities, including diffusion imaging and the Connectome 2.0 scanner
  • Studies are also beginning to elucidate the mechanisms of progression, as well as biomarkers that may predict progression and symptoms such as cognitive impairment
  • The research is expanding the understanding of MS pathophysiology

Massachusetts General Hospital researchers are developing and testing new imaging technologies to understand multiple sclerosis (MS) better. Their results are shedding light on the pathology that leads to physical symptoms and cognitive impairment associated with MS and on biomarkers that may help clinicians diagnose and monitor MS.

"Imaging has already demonstrated utility to help with the diagnosis and treatment of MS. Imaging biomarkers have been very helpful in developing therapeutics, specifically related to the inflammatory component of relapsing-remitting MS," says Eric Klawiter, MD, MSc, director of the Multiple Sclerosis and Neuromyelitis Optica Unit in the Department of Neurology at Mass General. "Our goals are to improve on those biomarkers so they can be used for therapies for progressive MS and potentially for remyelinating therapies, which are two large unmet needs."

Using Mass General's Imaging Technology to Improve Multiple Sclerosis Research

Discoveries in MS have been possible due to significant advancements in imaging hardware at Mass General.

The Athinoula A. Martinos Center for Biomedical Imaging in the Department of Radiology offers diffusion imaging, a MRI technique that visualizes the motion of water molecules in the brain to provide information about tissues. The center also has a one-of-a-kind scanner, the Connectome 2.0, which can image the human brain in vivo with unprecedented accuracy. The scanner's very high gradient strength optimizes researchers' ability to examine and measure brain structures and connections.

"There has been a really productive collaboration between neurology and radiology in applying these imaging modalities to neurologic disease. Multiple sclerosis was an ideal disease to apply these techniques to," he explains.

"The Connectome 2.0 scanner and other cutting-edge MRI scanners being developed at the Martinos Center enable us to map tissue-level changes in MS in real-time, as patients experience changes in their disease status, without the risk of radiation or invasive tissue biopsy," says Susie Huang, MD, PhD, a neuroradiologist at Mass General and Martinos faculty member leading the Connectome 2.0 effort.

Dr. Klawiter and colleagues are using these technologies to examine the underlying tissue microstructure of white matter in human brains. They are working to improve the measurement of myelin, the damaged coating on nerve fibers in multiple sclerosis.

Additionally, novel imaging technologies are used to map axonal integrity in the brains of those with multiple sclerosis, as highlighted in a recent publication in eLife by colleague Caterina Mainero, MD, PhD, director of Multiple Sclerosis Research at the Martinos Center. In this study, her Lab demonstrated that axonal damage could be detected in the early stages of multiple sclerosis.

Previous research in pre-clinical models and post-mortem human tissue suggests that increased axon size could indicate axonal damage, but measuring axons in vivo in humans is not possible with traditional imaging techniques. Using advanced diffusion imaging protocols from Connectome 2.0, the axon diameter is estimated through an experimental framework called Axcaliber. The Connectome 2.0 with AxCaliber demonstrates a unique ability to detect, non-invasively, in vivo increase in axonal size associated with white matter degeneration in humans.

Studying Changes in Gray Matter as an MS Biomarker

Research in MS has focused mostly on white matter, which is traditionally considered the main area of MS pathology. However, Dr. Klawiter says pathological changes also occur in gray matter. These changes can begin early and lead to diffuse atrophy.

To better understand this process, he and his colleagues explored the microstructures in gray matter, specifically the cortex and thalamus, using the Connectome 2.0 scanner and a type of diffusion imaging technology called the Soma and Neurite Density MRI (SANDI) methodology.

"We looked at reduced cortical cell body density, which we think is a good surrogate for gray matter disease. Essentially, we found that there was a decrease in this measure in the multiple sclerosis group compared to healthy controls in both the cortex and in the thalamus, a deep gray matter structure," he says. The results were published in Brain Communications.

"We are ultimately striving to develop biomarkers that can help us monitor MS progression and give us information on the preservation of neurons," Dr. Klawiter says. "We're hopeful that some of these measures may indicate early changes that occur even before we see tissue volume loss or clinical signs and symptoms."

Testing Therapeutic Options for MS

Another recent study by Dr. Klawiter and colleagues involved Ibudilast, a potential therapeutic option for progressive MS, a subtype with a large unmet need. A previous study of the drug published in the NEJM failed to demonstrate a strong anti-inflammatory effect in MS. But that research did find that this treatment may preserve brain volume and prevent atrophy.

Dr. Klawiter and colleagues conducted a post-hoc analysis looking at the volume of the thalamus, which often progressively decreases starting early in MS. The study, published in Multiple Sclerosis Journal, found Ibudilast appears to have a protective effect on thalamus volume in people with primary progressive MS. Notably, the researchers documented longitudinal changes in thalamic volume that were related to worsening physical and cognitive disability.

Although it's unclear whether Ibudilast will move into Phase 3 clinical trials, Dr. Klawiter points out that the study helps "move toward improving our ability to look at specific structures like the thalamus and incorporate them to a greater extent in clinical trials and ultimately into being able to measure changes in clinical practice."

Interdisciplinary Advances in Brain Imaging

He and collaborators will continue to use the advanced imaging to better understand temporal changes in the brain. Dr. Klawiter says he'd like to use different imaging technologies together to enhance understanding.

"The Martinos Center has been at the forefront of developing next-generation imaging technologies that are now allowing us to see into the human brain with unprecedented spatial and temporal resolution," explains Dr. Huang. "We are now in the midst of a large-scale modernization and expansion effort to install the latest scanners that we developed at the MGH research campus. These instruments, like the Connectome 2.0, will provide new insights into disease processes like MS, ultimately allowing us to intervene at an earlier stage."

Mass General continues to push the envelope and develop imaging technologies and capabilities, allowing for productive collaboration between neurology and radiology. Applying these unprecedented imaging modalities allows researchers and clinicians to identify the brain's microstructures underlying neurologic disease.

Learn more about the Martinos Center for Biomedical Imaging

Learn more about the Department of Neurology

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