New Imaging Techniques May Aid MS Diagnosis, Management

Physician-researchers at Cedars-Sinai Medical Center, in California, are developing brain and eye imaging techniques to improve the diagnosis and management of multiple sclerosis (MS).

MS is characterized by the progressive loss of myelin, the fatty protective sheath around nerve fibers, in the brain and spinal cord due to abnormal immune responses and excessive inflammation.

The disease “can look very different in different people, and the path to diagnosis is equally varied,” Marwa Kaisey, MD, an MS specialist and an assistant professor of neurology at Cedars-Sinai Medical Center, said in a  press release.

“Diagnosis is complex because many other diseases mimic MS, and while we have a set of diagnostic criteria, there’s no single test that is definitive,” Kaisey added.

MRI is the main diagnostic tool in MS, with damage or loss of myelin showing up as white spots on brain and spinal cord scans. However, many other conditions — most commonly migraines — can cause white spots in MRIs.

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Notably, a previous study conducted by Kaisey and colleagues showed that “almost 1 in 5 new patients coming into our clinic with an existing diagnosis of MS turned out not to actually have MS” the neurologist said.

“When we talk to other MS specialists about this, they’re not surprised. They also see this trend of misdiagnosis,” Kaisey added.

Most of these misdiagnosed patients also had been taking costly MS medications unnecessarily for years, many of which have an associated risk of infection and may cause organ damage and reduce vaccine effectiveness.

As such, there is an urgent need for better diagnostic tools and biomarkers in MS.

“I didn’t really intend to go into this line of research, but being in clinic every day and seeing these problems firsthand, I just had to do something about them,” Kaisey said.

“Fortunately, these [new] imaging techniques could offer an invaluable solution.”

Central vein sign in MRI

Since MS lesions tend to form around tiny veins, through which immune cells enter and mount abnormal immune attacks, most of these lesions have a vein in the middle — called a central vein sign.

“We’ve known this for more than 100 years, but until recently we didn’t have a way to see it on an MRI,” Kaisey said.

Now, Pascal Sati, PhD, an associate professor of neurology and the director of the neuroimaging program at Cedars-Sinai, is leading the development of new MRI sequences to make central vein sign visible. An MRI sequence refers to a specific setting of radiofrequency pulses and gradients that result in a particular image appearance.

“Current MRI images don’t give us the whole picture, which is why we developed MRI sequences that improve image quality so that we can see very small veins … in the brain,” Sati said.

When overlapping such images with those from conventional MRI scans, researchers can determine “which brain lesions have a central vein and are likely caused by MS,” Sati added.

Notably, the innovative MRI technique can be performed with widely available MRI and can fit easily into the workflow of the typical radiology center.

The technique is being tested in 400 people at risk of developing MS who are being followed at Cedars-Sinai and 10 other MS centers in North America — the final step to scientifically validate central vein sign as a way to diagnose MS.

Sati also is developing a machine learning tool to make evaluation of the imaging results easier for physicians. Machine learning is a form of artificial intelligence that uses algorithms to analyze data, learn from its analyses, and then make a prediction about something.

“Once the image is taken, our deep learning algorithm can analyze it very quickly and tell the clinician how many lesions show the central vein sign,” Sati said, adding that “the number of lesions with the central vein sign can indicate whether or not the patient has MS.”

The central vein sign also might help monitor MS patients’ treatment responses by confirming that any new lesions are caused by MS and not something else.

“This information is empowering doctors to make decisions about whether to continue a patient’s current therapy, switch to a different MS therapy, or treat them for a completely new, or different, condition,” Sati said.

The eye as a window into MS

“Around 25% of MS patients experience vision loss or blurring as their first symptom, and as many as 80% experience vision problems at some point in the course of their disease,” said Nancy Sicotte, MD, chair of the department of neurology and the director of the Multiple Sclerosis and Neuroimmunology Program at Cedars-Sinai.

Omar Al-Louzi, MD, a neurologist and the director of the visual outcomes laboratory at Cedars-Sinai, is assessing whether a rapid, non-invasive, eye imaging technique called optical coherence tomography (OCT) can be used to detect MS.

OCT produces detailed pictures of the layers of the retina — the back part of the eye that contains the cells that sense light (photoreceptor cells) and the nerve cells that transmit signals from the eyes to the brain (ganglion cells).

OCT can be used to detect neurodegeneration (the progressive death of nerve cells) in the retina, and increasing efforts are focusing on its utility as a diagnostic and monitoring tool for MS.

“Shrinking of the ganglion cell layer often mirrors overall brain degeneration, and occurs in 70% to 80% of MS patients,” Al-Louzi said.

As such, ganglion cell imaging may help improve the diagnosis and monitoring of MS, the neurologist added.

In collaboration with Kaisey, Al-Louzi also is evaluating the diagnostic value of a related technique called optical coherence tomography angiography (OCTA) that allows the visualization of the tiny blood vessels in the retina.

The retinal blood vessel signature of MS is being compared “to that of other brain conditions involving blood vessels, such as migraine or small vessel disease, to see whether retinal vessels can help us distinguish between these different conditions,” Al-Louzi said.

“I think failing to use these imaging techniques is a missed opportunity,” and “our hope is that these tests will become widespread and shorten the time between symptom onset and getting the right diagnosis,”Al-Louzi said.