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Updated: Jul 14, 2025
Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases
Published on: July 28, 2013
Diffusion tensor free water MRI predicts progression of FLAIR white matter hyperintensities after ischemic stroke
Kyle C Kern1, Marwah S Zagzoug1, Rebecca F Gottesman1
1Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States.
Background:
The progression of FLAIR white matter hyperintensities (WMHs) on MRI heralds vascular-mediated cognitive decline. Even before FLAIR WMH progression, adjacent normal appearing white matter (NAWM) already demonstrates microstructural deterioration on diffusion tensor imaging (DTI). We hypothesized that elevated DTI free water (FW) would precede FLAIR WMH progression, implicating interstitial fluid accumulation as a key pathological step in the progression of cerebral small vessel disease.
Methods:
Participants at least 3 months after an ischemic stroke or TIA with WMH on MRI underwent serial brain MRIs every 3 months over the subsequent year. For each participant, the WMHs were automatically segmented, serial MRIs were aligned, and a region of WMH penumbra tissue at risk was defined by dilating lesions at any time point and subtracting baseline lesions. Penumbra voxels were classified as either stable or progressing to WMH if they were segmented as new lesions and demonstrated increasing FLAIR intensity over time. Aligned DTI images included FW and FW-corrected fractional anisotropy (FATissue) and mean diffusivity (MDTissue). Logistic regression and area under the receiver-operator characteristic curve (AUC) were used to test whether baseline DTI predicted voxel-wise classification of stable penumbra or progression to WMH while covarying for clinical risk factors.
Results:
In the included participants (n = 26, mean age 71 ± 9 years, 31% female), we detected a median annual voxel-wise WMH growth of 2.9 ± 2.6 ml. Each baseline DTI metric was associated with lesion progression in the penumbra, but FW had the greatest AUC of 0.732 (0.730 - 0.733) for predicting voxel-wise WMH progression pooled across participants.
Discussion:
Baseline increased interstitial fluid, estimated as FW on DTI, predicted the progression of NAWM to WMH over the following year. These results implicate the presence of FW in the pathogenesis of cerebral small vessel disease progression.
Insights
Elevated interstitial fluid, measured as free water (FW) on diffusion tensor imaging (DTI), predicts white matter hyperintensity (WMH) progression in patients with cerebral small vessel disease.
Area of Science:
- Neuroimaging
- Cerebrovascular Diseases
- White Matter Hyperintensities
Background:
- White matter hyperintensities (WMHs) on MRI are linked to cognitive decline.
- Microstructural changes in normal-appearing white matter (NAWM) precede WMH progression.
- Interstitial fluid accumulation may be a key factor in cerebral small vessel disease (CSVD).
Purpose of the Study:
- To investigate if elevated free water (FW) on diffusion tensor imaging (DTI) precedes WMH progression.
- To determine if interstitial fluid accumulation is an early pathological step in CSVD progression.
Main Methods:
- Serial brain MRIs were acquired over one year in patients post-stroke or TIA.
- WMH progression was assessed using automated segmentation and lesion expansion.
- DTI metrics, including FW, were analyzed to predict WMH progression in the WMH penumbra.
Main Results:
- A median annual WMH growth of 2.9 ± 2.6 ml was observed.
- Baseline FW on DTI showed the highest predictive value (AUC = 0.732) for WMH progression.
- All DTI metrics were associated with lesion progression in the penumbra.
Conclusions:
- Increased interstitial fluid (FW) on DTI predicts the progression of NAWM to WMH.
- These findings implicate FW in the pathogenesis of CSVD progression.
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