Two brain models against the blurry background of Prof. Inglese and two of her colleagues looking at a computer screen together.

Neurology

Pushing the boundaries in multiple sclerosis research

Clinicians and researchers are pioneers whose insights help us better understand and diagnose challenging diseases like cancer, neurodegenerative diseases, and complex musculoskeletal conditions.

4min

Doris Pischitz

Published on September 18, 2023

Professor Matilde Inglese, MD, PhD, is one such pioneer.

Matilde Inglese is professor of neurology at the University of Genoa, Italy, and head of the Multiple Sclerosis (MS) Center at IRCCS Policlinico San Martino Hospital. She coordinates the hospital’s disease management team on MS. During her time as a resident, Inglese was impressed by the way young patients were coping with the chronic, debilitating disease and how they had learned to live with it. This remains a strong motivating factor for her today.

“Every day, we witness very poignant stories. We see these young women and men that come to us because they have lost some ability or functionality in their body,” says Inglese.

A lifelong disease

MS leads to inflammation, demyelination, and neurodegeneration of the central nervous system. “We don't know the etiology of the disease, but we do know the pathophysiology is that of an autoimmune disease, where autoreactive peripheral lymphocytes react to an as yet unknown antigen,” says Inglese, summarizing current knowledge of MS. These lymphocytes can cross the blood-brain barrier, enter the central nervous systems, and trigger an inflammatory demyelinating reaction that leads to neurodegeneration and neuroaxonal loss.

What is myelin?

Myelin is a fatty substance that coats, protects, and insulates nerve fibers—called axons—in the brain and spinal cord.

MS is a multifactorial condition where both genetic and environmental factors could increase the risk of developing the disease.
Professor Matilde Inglese, MD, PhD, Professor of Neurology, University of Genoa, Italy, head of the Multiple Sclerosis (MS) Center, IRCCS Ospedale Policlinico San Martino

MS affects women two or three times more frequently than men, with symptoms appearing between 20 and 40 years of age [1]. “People are in the most productive period of their lives, both personally and professionally. It is a chronic disease: Patients have to live with it for the rest of their lives. And it is a debilitating disease: Patients progressively lose motor autonomy and other neurological functions,” Inglese explains.

The role of magnetic resonance imaging

“Today, MRI helps us find a correct diagnosis and select the right treatments, which can improve symptoms,” says Inglese.

Monitoring progression and treatment response

According to Inglese, new, disease-modifying treatments are very effective in reducing the inflammation. However, there are still limitations in the ability of these treatments to mitigate the progression of the disease.

MRI image of MS lesions in the brain

MS lesions manifest as hyperintense (i.e. bright) spots in the white matter if imaged using FLAIR (Fluid Attenuated Inversion Recovery). The lesions here are on the right side.

To better understand what is going on in the patients’ brains, Inglese once more turns to MRI: “While on conventional MRI, all lesions look alike when actually they are in different stages of their evolution, advanced MRI techniques such as diffusion MRI or myelin water fraction, magnetization transfer imaging, and so on, could provide pathological specificity.” These techniques help physicians and researchers like Inglese and her team distinguish between lesions that are inflamed, demyelinating, or remyelinating or evaluate the degree of new axonal damage.

What is diffusion MRI?

Diffusion-weighted MRI uses specific sequences that measure the diffusion of water molecules to generate contrast in MR images.

Overcoming current limitations

However, Inglese still sees room for improvement in MRI imaging and technology:

“The research that we are currently conducting in collaboration with our physicists and mathematicians has shown that we need a gradient amplitude of at least 150 millitesla per meter [mT/m] to accurately measure microscopic damage with diffusion MRI,” she says.

A high gradient slew rate would also improve other advanced MRI techniques that Inglese uses in her research. In addition, she expects that a stronger gradient will make the acquisition of these sequences more patient-friendly. “With MRI becoming more powerful, and consequently also more accurate, we will have advantages for both the diagnosis and prognosis of neurological diseases. And in addition, we will have more accurate instruments to monitor response to current and future treatments.” MS could become a model for studying inflammation and degeneration in many other neurological diseases, especially the most common conditions and neurodegenerative diseases such as Alzheimer, Parkinson, or amyotrophic lateral sclerosis (ALS).

MRI image of MS lesions in the brain

In contrast to FLAIR, this MPRAGE (Magnetization Prepared Rapid Acquisition with Gradient Echoes) image displays MS lesions as dark spots in the white matter. Again, the spots are on the right side.

Hope on the horizon

With over a dozen disease-modifying therapies for MS available today [2], and 33 that are currently in various states of clinical trials [3], prospects for patients continue to improve. MRI is helping researchers and physicians achieve correct diagnoses and select treatments that may stop the development of new lesions and lead to improved symptoms and quality of life.

“Seeing the possibility to offer treatment to change the progression of the disease is, of course, very rewarding and encouraging. And it also gives meaning to what we do every day,” says Inglese.

Prof. Inglese walking down the corridor of the research building, looking at her mobile phone.

Shaping healthcare in 2023 and beyond

Key visual for Siemens Healthineers Shape 23 Keynote

November 14, 2022

Siemens Healthineers Shape 23 Keynote

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Join us and hear some of the world’s most respected healthcare leaders share insights into how to address the challenges posed by cancer, how high-quality care can be brought to more patients, and how to address the workforce crisis.

By Doris Pischitz

Doris Pischitz is an editor in corporate communications at Siemens Healthineers. The team specializes in topics related to healthcare, medical technology, disease areas, and digitalization.

[1] Rising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS, third edition - PMC (nih.gov)

[2] Disease-modifying Therapies for Multiple Sclerosis (multiplesclerosisnewstoday.com)

[3] Medicines in development. 2021 report: neurodegenerative diseases. Pharmaceutical Research and Manufacturers of America. 12 October 2021

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