In neurodegenerative diseases (ND), such as Alzheimer disease or Amyotrophic Lateral Sclerosis (ALS), early diagnosis is critical for the most effective—or disease-modifying—treatments. Neuroinflammation, which is defined by increased levels of inflammation-causing proteins in the brain, is a key feature of these conditions.
Previous studies suggest neuroinflammation can be detected before other brain changes that are typically used to diagnose NDs appear. This means it could be a marker for earlier diagnosis. Unfortunately, many current diagnostic tools cannot detect signs of neuroinflammation—or they require invasive procedures.
A recent study from UHN’s Krembil Brain Institute (KBI) suggests free-water diffusion (FWD) MRI could fill this diagnostic gap. Free water is water in the brain that is not contained inside brain cells. FWD MRI measures how much of this water is present and how it moves. Changes in its amount, location, or movement can signal processes like neuroinflammation and cell death.
The KBI team analyzed MRI data and blood samples from 367 patients with various NDs collected through the Ontario Neurodegenerative Research Initiative (ONDRI) database. They assessed FWD patterns in brain scans and measured blood levels of two protein markers—GFAP (linked to neuroinflammation) and NfL (linked to cell damage).
Using machine learning, the researchers found that specific FWD patterns could predict GFAP levels, suggesting the technique may detect neuroinflammation. They also identified differences in FWD patterns between different NDs—hinting that FWD MRI could be used to help identify not only the presence of neuroinflammation but also the type of ND in its early stages.
“Further studies in larger and more diverse groups are needed to confirm reliability and effectiveness,” says the study’s senior author and a Krembil Clinician Investigator, Dr. Carmela Tartaglia. “But we believe FWD MRI has great potential as a diagnostic tool.”
As a non-invasive technique that uses existing technologies, FWD MRI offers a way to make ND diagnosis at an earlier stage easier and more widely available. For more patients, this could mean a better chance at effective management of and a life less impacted by neurodegeneration.
The first author of this study is Vishaal Sumra, a PhD candidate at the University of Toronto’s Institute of Medical Science.
The senior author is Dr. Carmela Tartaglia, a Clinician Investigator at UHN’s Krembil Brain Institute and a professor at the University of Toronto’s Tanz Centre for Neurodegenerative Diseases.
This work was supported by UHN Foundation. The ONDRI study was supported by the Ontario Brain Institute (OBI).
The authors report no competing interests for this work. For a full list of financial and personal interests, see the publication.
Sumra V, Hadian M, Dilliott AA, Farhan SMK, Frank AR, Lang AE, Roberts AC, Troyer A, Arnott SR, Marras C, Tang-Wai DF, Finger E, Rogaeva E, Orange JB, Ramirez J, Zinman L, Binns M, Borrie M, Freedman M, Ozzoude M, Bartha R, Swartz RH, Munoz D, Masellis M, Black SE, Dixon RA, Dowlatshahi D, Grimes D, Hassan A, Hegele RA, Kumar S, Pasternak S, Pollock B, Rajji T, Sahlas D, Saposnik G, Tartaglia MC; ONDRI Investigators. Regional free-water diffusion is more strongly related to neuroinflammation than neurodegeneration. J Neurol. 2025 Jun 25;272(7):478. doi: 10.1007/s00415-025-13201-1.