Summary: Researchers have identified a promising new biomarker for multiple sclerosis (MS): the thickness of the inflammatory rim that surrounds chronic brain lesions. This rim thickness, observable with molecular imaging and confirmed in tissue studies, predicts how rapidly and severely a patient’s disease will progress.
By integrating in vivo PET imaging with detailed post-mortem tissue analysis, the international research team demonstrated that broader inflammatory rims are associated with more aggressive tissue damage and faster clinical decline. This finding may help clinicians identify patients who need earlier, more intensive treatment and provide a measurable imaging endpoint for testing new therapies, especially for progressive MS.
Key Facts:
- Predictive biomarker: A broader myeloid/inflammatory rim around MS lesions correlates with faster and more severe disease progression.
- Early intervention potential: Detecting broad rim lesions may allow clinicians to stratify patients for earlier, targeted therapies.
- Drug development utility: Rim measurements using PET imaging offer a quantifiable outcome to evaluate candidate therapies aimed at central nervous system inflammation.
Source: University of Turku
Researchers at the University of Turku, Finland, together with colleagues in Germany and the Netherlands, have described a new imaging and pathological biomarker that links lesion-associated inflammation to rapid multiple sclerosis progression.
The study found a clear relationship between the width of an inflammatory cell rim encircling demyelinated brain lesions and the subsequent pace and severity of MS. In other words, lesions with a pronounced rim of activated myeloid cells—microglia and macrophages—are more likely to drive irreversible tissue injury and faster clinical decline.
Led by Professor Laura Airas at the University of Turku, the study is published in Nature Medicine. The investigators combined two complementary data sources: molecular PET imaging of 114 living MS patients and extensive histopathological and spatial transcriptomic analysis of an autopsy cohort derived from the Netherlands Brain Bank (186 donors). Together these approaches allowed the team to identify and validate a distinct lesion subtype they call “broad rim lesions.”
How the biomarker was identified
In the post-mortem cohort, researchers performed unbiased histology and spatial transcriptomics. They discovered lesions characterized by an extensive rim of myeloid cells showing transcriptional signatures of innate immune activation, cytokine production, unfolded protein response, and apoptosis. The presence of these broad rim lesions was associated with donors who experienced rapid clinical progression during life.
An independent imaging study using translocator protein 18-kDa (TSPO) PET in 114 individuals validated that lesions with a broad myeloid cell rim detected in vivo correspond to faster disease progression. TSPO PET served as a practical, noninvasive way to visualize lesion-associated microglial activation and rim width in living patients.
Clinical and research implications
These findings have several important implications. Clinically, identifying patients with broad rim lesions could help neurologists prioritize more aggressive or targeted therapeutic approaches for those at higher risk of rapid progression. For drug development, rim width measured by TSPO PET or similar imaging biomarkers provides a biologically grounded outcome for trials aiming to reduce central nervous system–intrinsic inflammation and slow progression.
Professor Airas notes, “When microglial cells form a thick rim around MS lesions, their harmful activity extends into adjacent healthy tissue, leading to irreversible damage. Detecting these lesion types in patients allows us to identify who may need more intensive treatment earlier and gives us a way to measure whether candidate therapies can reduce this damaging rim activity.”
About this multiple sclerosis research news
Author: Tuomas Koivula
Source: University of Turku
Contact: Tuomas Koivula – University of Turku
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Broad rim lesions are a new pathological and imaging biomarker for rapid disease progression in multiple sclerosis” by Laura Airas et al. Nature Medicine
Abstract
Broad rim lesions are a new pathological and imaging biomarker for rapid disease progression in multiple sclerosis
Current MS therapies effectively reduce relapse activity but have limited impact on the gradual progression that leads to long-term disability. Clinical trials aimed at slowing progression frequently struggle because the mechanisms driving progression are incompletely understood and because reliable biomarkers are lacking.
To address this gap, the investigators analyzed a clinically well-characterized MS autopsy cohort from the Netherlands Brain Bank (186 individuals) and selected donors with contrasting clinical courses—those with slow progression versus those with rapid decline. Through comprehensive histology and spatial transcriptomics, the team identified a previously underrecognized lesion phenotype marked by an expansive rim of activated myeloid cells and molecular signs of innate immune activation and cellular stress.
The presence of these broad rim lesions correlated with rapid disease progression. Complementary TSPO PET imaging in an independent cohort of 114 individuals validated that broad myeloid rims visible in vivo associate with a faster clinical course. Together, these results illuminate a pathophysiological mechanism behind MS progression and propose broad rim lesions as a candidate biomarker for identifying high-risk patients and for selecting participants or endpoints in future trials targeting central nervous system–intrinsic inflammation.