INTRODUCTION:
Leukoaraiosis, the presence of “incidental” white matter lesions in the aging brain, is increasingly recognized as a predictor for dementia, ischemic stroke, intracerebral hemorrhage and vascular death. The pathogenesis of leukoaraiosis remains controversial, with abnormalities of small arterioles hypothesized to play an important role. To investigate this hypothesis, we sought to characterize the temporal evolution of the individual lesions making up leukoaraiosis.
HYPOTHESIS:
Discrete occlusive events at the level of small arterioles play a key role in the pathogenesis of leukoaraiosis.
METHODS:
Participants were prospectively recruited through an outpatient neurology clinic (inclusion criteria: age > 60 years, Fazekas grade 3 leukoaraiosis burden; exclusion criteria: cortical infarct, cardioembolic disease, dissection, carotid stenosis > 50%). Subjects underwent an identical MRI protocol in each of 16 consecutive weeks, including diffusion tensor imaging (DTI) and multi-echo T2-weighted imaging. Parametric maps of the apparent diffusion coefficient (ADC), fractional anisotropy (FA) and T2 relaxation time were constructed and coregistered (Analysis of Functional NeuroImages, NIH; 3D Slicer, www.slicer.org; Matlab, The MathWorks). Images were reviewed for new diffusion restricting lesions, and such lesions were manually segmented. Plots of lesion ADC, FA and T2 were generated and temporally aligned to the onset of acute diffusion restriction.
RESULTS:
Five subjects (mean age 69 ± 8 years) met criteria and completed all 16 MRI scans. There were no lacunar or large artery infarcts during the study period. A total of 9 new diffusion restricting white matter lesions were identified (mean volume 0.06 ± 0.03 cc). Evolution of these lesions showed striking similarity to that of cerebral infarction, with acute reduction in ADC, followed by gradual rise in ADC and T2, and corresponding decline in FA. At 8 weeks, new lesions were indistinguishable from pre-existing white matter disease.
CONCLUSION:
Leukoaraiosis evolves through temporally and spatially discrete acute ischemic injuries. This supports the hypothesized role of small vessel arteriolar pathology as a key pathogenetic mechanism.
What does the water inside the brain tell us? Diffusion tensor imaging
