Baseline Blood-Brain Barrier Leakage and Longitudinal Microstructural Tissue Damage in the Periphery of White Matter Hyperintensities

Neurology. 2021 Apr 27;96(17):e2192-e2200. doi: 10.1212/WNL.0000000000011783. Epub 2021 Mar 24.


Objective: To investigate the 2-year change in parenchymal diffusivity, a quantitative marker of microstructural tissue condition, and the relationship with baseline blood-brain barrier (BBB) permeability, in tissue at risk, i.e., the perilesional zone surrounding white matter hyperintensities (WMH) in patients with cerebral small vessel disease (cSVD).

Methods: Patients with sporadic cSVD (lacunar stroke or mild vascular cognitive impairment) underwent 3T MRI at baseline, including dynamic contrast-enhanced MRI to quantify BBB permeability (i.e., leakage volume and rate) and intravoxel incoherent motion imaging (IVIM), a diffusion technique that provides parenchymal diffusivity D. After 2 years, IVIM was repeated. We assessed the relation between BBB leakage measures at baseline and change in parenchymal diffusivity (∆D) over 2 years in the perilesional zones (divided in 2-mm contours) surrounding WMH.

Results: We analyzed 43 patients (age 68 ± 12 years, 58% male). In the perilesional zones, ∆D increased 0.10% (confidence interval [CI] 0.07-0.013%) (p < 0.01) per 2 mm closer to the WMH. Furthermore, ∆D over 2 years showed a positive correlation with both baseline BBB leakage volume (r = 0.29 [CI 0.06-0.52], p = 0.013) and leakage rate (r = 0.24 [CI 0.02-0.47], p = 0.034).

Conclusion: BBB leakage at baseline is related to the 2-year change in parenchymal diffusivity in the perilesional zone of WMH. These results support the hypothesis that BBB impairment might play an early role in subsequent microstructural white matter degeneration as part of the pathophysiology of cSVD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Blood-Brain Barrier / pathology*
  • Blood-Brain Barrier / physiopathology*
  • Cerebral Small Vessel Diseases / physiopathology*
  • Cognitive Dysfunction / physiopathology
  • Diffusion Magnetic Resonance Imaging / methods
  • Female
  • Gray Matter / physiopathology
  • Humans
  • Leukoaraiosis / physiopathology
  • Male
  • Middle Aged
  • White Matter / physiopathology*