PET brain scans could reveal hidden inflammation in patients with multiple sclerosis

PET brain scans could reveal hidden inflammation in patients with multiple sclerosis

A new study from Brigham and Women's Hospital, a founding member of the Mass General Brigham Health System, suggests that brain scans using positron emission tomography (PET) could reveal hidden inflammation in patients with multiple sclerosis (MS) being treated with highly effective treatments. The results were published inClinical nuclear medicine.

"One of the perplexing challenges for physicians treating patients with MS is that patients continue to get worse over time while their MRI findings do not change," said lead author Tarun Singhal, MD, MBBS, associate professor of neurology in the Brigham Department of Neurology and director of the PET imaging program in the Ann Romney Center for Neurologic Diseases. “This is a new approach that will potentially be very helpful to the field, research and hopefully clinical use.”

Singhal worked with others at the Brigham Multiple Sclerosis Center and the Ann Romney Center. The study began when Singhal noticed that patients treated with the most effective MS treatments available were experiencing worsening symptoms. The team has been working for the past eight years to develop an approach to imaging cells called microglia. Microglia are immune cells in the brain that are thought to be involved in MS disease progression but are not visible with a routine MRI. The team developed a technique called F18 PBR 06 PET imaging. A tracer or dye is injected that binds to the microglial cells.

Rohit Bakshi, MD of the Department of Neurology and co-author of the paper, said increased microglial activity means more gray matter atrophy in the brain.

“This can impact cognition, movement, fine motor skills and other aspects of their life,” Bakshi said.

In their work, the authors describe the term “smoldering” inflammation. Just as a smoldering fire can burn slowly without producing smoke or flames, in patients with MS, smoldering inflammation can persist and lead to disease progression and symptoms even if it cannot be assessed with MRI.

The newly published study involved performing PET scans on 22 people with MS and eight healthy controls. The researchers measured glial activity load on the PET scans, a new measurement developed in Singhal's lab, where lab workers examined the extent of simmering inflammation caused by microglia in MS patients. They compared these scans to the patients' level of disability and fatigue and found not only that PET scans could show hidden inflammation caused by microglia, but that the damage to the patients' brains also correlated with the level of disability and fatigue they suffered. The researchers were also able to better classify patients with MS between high- and low-effective treatments. Those treated with low-efficacy treatments had more abnormalities in their PET scans, suggesting greater activation of microglial cells. Those who used highly effective treatments had lower levels of PET abnormalities than those who received no or low effectiveness, but still had abnormal increases in microglial activation compared to healthy people, suggesting that while highly effective treatments helped reduce neuroinflammation, there was residual inflammation despite treatment, which may be responsible for future deterioration and progression independent of relapse activity (PIRA) in these MS patients could.

“Our therapies are outstanding in that they have definitely improved the lives of MS patients,” said Bakshi. “There is no doubt about that, but we are not there yet.”

A limitation of the study is that the initial group was small. The authors point out that PET scans can also be expensive and can expose patients to some radiation, whereas MRIs do not. Singhal said that radiation could potentially be reduced due to the long half-life and the need for a lower administered dose of the F18 PBR06 tracer used. The tracer also offers better imaging properties compared to previously used tracers with shorter half-lives.

Bakshi said despite the limitations, the study sheds important light on the power of PET scanning, particularly for detecting microglial activation.

This study tells us something new about the disease and could give us an important clue about what drives disease progression in patients.”

Rohit Bakshi, MD, Department of Neurology

Singhal said before the technique can be used routinely in a clinical setting, it needs to be validated on a larger sample. Other PET tracers with longer half-lives have been approved by the FDA for clinical use, such as amyloid PET tracers for studying Alzheimer's disease. If approved, [F-18]PBR06 could also be used as a tool to personalize and predict a patient's treatment course for MS and other brain diseases. However, the authors point out that even before approval, [F-18]PBR06 can be used to advance drug development and conduct multicenter clinical trials.

“It is very exciting that our novel approach worked and correlated so strongly with the clinical measures we evaluated,” he said. “This means our approach is clinically relevant.”

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