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

Objective To investigate the two-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 two-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 2mm contours) surrounding WMH.

Results We analysed 43 patients (age 68±12 years, 58% male). In the perilesional zones, ∆D increased with 0.10 [CI = 0.78, 0.13]% (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.