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Diffusion MRI Identifies a Prolonged Pre-WMH Phase in Cerebral Small Vessel Disease
Prashanthi Vemuri1, Mingzhao Hu2, Emily S Lundt2
1Department of Radiology, Mayo Clinic-Rochester, Rochester, MN. (P.V., S.R., P.M.C., C.R.J.).
Stroke
|July 22, 2026
Summary
Diffusion MRI biomarkers show abnormalities up to a decade before white matter hyperintensities (WMH), indicating early cerebral small vessel disease. These findings highlight the potential of diffusion MRI for early detection and prevention strategies.
Area of Science:
- Neurology
- Radiology
- Biomarkers
Background:
- White matter hyperintensities (WMH) are late-stage indicators of cerebral small vessel disease.
- Diffusion MRI biomarkers may detect earlier microstructural damage, but their progression and risk factors are unknown.
Purpose of the Study:
- To investigate the temporal progression of WMH and diffusion MRI biomarkers.
- To explore risk factors associated with the progression of these markers.
Main Methods:
- Utilized longitudinal neuroimaging data from 2077 participants in the Mayo Clinic Study of Aging.
- Employed nonlinear mixed-effects models to analyze WMH and four diffusion MRI biomarkers (fractional anisotropy, peak width of skeletonized mean diffusivity, free water, Arteriolosclerosis-score).
- Incorporated risk factors like sex, education, APOE ε4 status, and cardiometabolic conditions.
Main Results:
- Diffusion MRI biomarkers became abnormal 7-16 years before WMH.
- Global markers showed correlations, suggesting shared injury mechanisms.
- Cardiometabolic conditions accelerated biomarker worsening; sex influenced the timing of specific abnormalities.
Conclusions:
- Diffusion MRI biomarkers precede WMH by up to a decade, revealing an extended early phase of small vessel disease.
- These findings underscore the potential of diffusion MRI for early detection and prevention of small vessel disease.
