Specialized PET scan shows chronic inflammation tied to MS progression

Some inflammatory signs aren't captured in standard MRI scans

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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A specialized imaging approach was able to detect signs of persistent inflammation in the brains of people with multiple sclerosis (MS) that aren’t readily captured by standard MRI scans.

This so-called smoldering inflammation was also observed among those patients taking high-efficacy disease-modifying therapies (DMTs), where a higher degree of it was associated with greater disability and fatigue.

“One of the perplexing challenges for clinicians treating patients with MS is after a certain amount of time, patients continue to get worse while their MRIs don’t change,” Tarun Singhal, MD, a professor of neurology at Brigham and Women’s Hospital (BWH) in Boston and study lead author, said in a press release.

“This study tells us something new about the disease and may be giving us an important clue as to what is driving disease progression in patients,” said Rohit Bakshi, MD, a study author who’s also at BWH.

The study, “Glial Activity Load on PET Reveals Persistent “Smoldering” Inflammation in MS Despite Disease-Modifying Treatment,” was published in Clinical Nuclear Medicine.

In MS, active lesions on MRI scans reflect areas of ongoing inflammation where the immune system is attacking otherwise healthy tissue. This is an indicator of disease activity often linked to relapses.

But even when MRI scans don’t show new signs of inflammatory activity, patients may still have disease progression and see their symptoms worsen in the absence of relapses, even those on highly effective DMTs.

Recent research has pointed to a unique type of damage called smoldering inflammation to explain this progression. This refers to areas of persistent and chronic inflammation that remain even when active inflammatory attacks aren’t occurring.

Microglia, the brain’s resident immune cells, are thought to be key players in this process. When chronically active, as they are in several neurological diseases, the cells can do more harm than good.

Still, it isn’t easy to monitor smoldering inflammation because its not readily captured by MRI. This means it’s generally in the background, driving disease progression without doctors even knowing it’s there, said the researchers, who’ve been working on an imaging approach that visualizes activated microglia to detect it. Called F18 PBR 06 PET imaging, it involves injecting a tracer dye that binds to microglia and can be visualized with a positron emission tomography (PET) scan.

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Astrocytes, much like immune cells, can drive inflammation in MS

A new imaging approach to see inflammation

In a small clinical study (NCT02649985), they sought to validate this approach by performing specialized PET scans on 22 MS patients and eight healthy people, who served as controls. MS patients had an increased microglial load compared with controls, as well as lower brain volume.

Patients using highly effective DMTs, including rituximab, Tysabri (natalizumab), or Gilenya (fingolimod), had a lower microglia burden than those not taking DMTs or who were on low-efficacy DMTs, including glatiramer acetate or interferon medications. But high-efficacy DMTs didn’t completely eliminate smoldering inflammation. Patients who used them still had higher microglial activation than healthy people.

The finding indicates inflammation can persist, even with the best treatments.

“Our therapies are excellent in that we’ve definitely improved MS patients’ lives,” Bakshi said. “There’s no doubt about that, but we’re still not at the finish line.”

Many high-efficacy treatments target inflammation in the body, but don’t reach the brain and spinal cord, which may explain why immune activation in brain tissue remains, the researchers said.

The extent of smoldering inflammation was also linked to the severity of certain symptoms. Among those on highly effective DMTs, a greater microglia load was associated with more disability, fatigue, and higher blood biomarkers of inflammation, along with lower brain tissue volume.

“It’s very exciting that our novel approach worked and correlated so strongly with clinical measures we assessed,” Singhal said. “It means our approach is relevant clinically.”

Because the findings come from a small patient group, they’ll still need to be validated in larger studies. Also, the tracer dye must be approved by regulators to be used in the clinic, but can be used as a research tool until then.

“This is a new approach that is potentially going to be very helpful for the field, for research, and hopefully for clinical use,” Singhal said.