Q&A With Dr. Caterina Mainero, Director of the Multiple Sclerosis Imaging Laboratory

Multiple sclerosis (MS) is a chronic and potentially debilitating disease of the central nervous system in which damage to myelin sheaths surrounding and protecting nerve cells impacts the transmission of signals in parts of the nervous system. Symptoms of MS can include fatigue, muscle weakness, and sensory deficit.

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The Multiple Sclerosis Imaging Laboratory in the Martinos Center for Biomedical Imaging at Massachusetts General Hospital employs cutting-edge imaging technologies to understand better the mechanisms of MS, while also seeking new means of diagnosing and monitoring the disease. In the Q&A below, Lab Director Caterina Mainero, MD, PhD, discusses her group's research and the role of the advanced imaging methods available at Mass General in their many significant findings.

Q. Tell us about the work you do in the Multiple Sclerosis Imaging Laboratory.

Mainero: Our lab specializes in translating novel multimodal imaging techniques for investigating the structure, function, and pathology within the brain and spinal cord of people with multiple sclerosis. Our overall mission is to integrate novel and advanced imaging methods, many of which have been developed at the Martinos Center, with clinical and biological markers of the disease to investigate the brain mechanisms underlying disease activity and progression, and to define the most sensitive neuroimaging tools for improving disease diagnosis and monitoring.

Q. What imaging tools do you use in your work?

Mainero: For our work we often combine advanced imaging modalities to investigate the heterogenous aspects of multiple sclerosis pathology that include neuroinflammation, demyelination, neurodegeneration, and tissue repair.

For example, we use ultrahigh-field MRI at 7 Tesla (7T) for investigating the presence of very small demyelinating lesions, like those in the cortex, which are usually not easily detectable on routine MRI scans in the clinic but have been reported to be extremely common and diffuse in post-mortem examinations of multiple sclerosis brain specimens. Our group was the first to image and characterize in vivo, using ultrahigh-field 7T MRI, the different types of cortical multiple sclerosis lesions described by neuropathology, and to show that the cortical lesion load assessed at 7T is an independent and main predictor of disease progression.

We also use, in many of our studies, positron emission tomography (PET) to assess specific molecular aspects of multiple sclerosis lesions that are related to neuroinflammation, a main driver of multiple sclerosis pathology. The aim is to understand how neuroinflammation contributes to developing cortical demyelinating lesions and their progression.

In some cases, we combine these techniques with advanced diffusion MRI methods to probe tissue microstructure and, specifically the integrity of axons that often degenerate in multiple sclerosis leading to the development of irreversible disability.

Q. Can you describe recent findings using these tools?

Mainero: A main area of focus of the Lab is the study of the cortex and cortical lesions in people with multiple sclerosis. We have gathered extensive data at 7T and recently, using a machine learning approach, evaluated the role of cortical lesions in predicting disability progression along with other radiological markers of the disease. We found that cortical lesions are among the top three radiological predictors of the progression of neurological disability in patients.

Interestingly, we have also found that lesion accumulation occurs more rapidly for cortical as compared to other types of lesions. As the accumulation of the new lesions in the cortex has been consistently shown to contribute to their volume increase, tracking their development and evolution could be particularly important for clinical trials with reduced observation times.

Q. What's next in your research?

Mainero: We are very excited about a new project on PET molecular imaging of fibrin deposition in the brains of people with multiple sclerosis. Several experimental studies provide strong evidence that fibrin(ogen) and its degradation products, which are the main components of the coagulation cascade, represent the main triggers of the initiation and maintenance of the pathological processes responsible for damage to regions of the brain in multiple sclerosis. Despite this compelling evidence, the role of these coagulation proteins in determining brain inflammation, demyelination, and neurodegeneration in the disease is understudied because routine clinical imaging techniques cannot visualize and quantify them. The role of fibrin(ogen) brain deposition in vivo, therefore, is yet unknown.

We are using ⁶⁴Cu-FBP8, an MR-PET probe developed by investigators at Massachusetts General Hospital, which has demonstrated excellent safety and stability in animal and human studies, to image and quantify fibrin deposition in different regions of the brain in people with multiple sclerosis. We have obtained funding from the NIH and the Department of Defense to study this in patients at different stages of the disease.

Learn more about the Multiple Sclerosis Imaging Laboratory

Learn more about the Mass General Martinos Center for Biomedical Imaging