Long-Term Blood–Brain Barrier Permeability Changes in Binswanger Disease

Abstract

Background and Purpose The blood brain-barrier (BBB) is disrupted in small vessel disease (SVD) patients with lacunes and white matter hyperintensities (WMHs). The relationship of WMHs and regional BBB permeability changes has not been studied. We hypothesized that BBB disruption occurs in normal appearing WM (NAWM) and regions near the WMHs. To test the hypothesis, we repeated BBB permeability measurements in patients with extensive WMHs related to Binswanger’s disease (BD). Methods We selected a subset of 22 BD subjects from a well-characterized larger prospective vascular cognitive impairment cohort. We used 16 age-matched controls for comparison. The abnormal WM permeability (WMP) was measured twice over several years using dynamic contrast-enhanced MRI (DCEMRI). WMP maps were constructed from voxels above a predetermined threshold. Scans from first and second visits were co-registered. WM was divided into 3 regions: NAWM, WMH ring and WMH core. The ring was defined as 2mm on each side of the WMH border. WMP was calculated in each of the three specific regions. We used paired t-test, ANOVA and Fisher’s exact test to compare individual changes. Results WMP was significantly higher in subjects than controls (p<0.001). There was no correlation between WMH load and WMP. High permeability regions had minimal overlap between first and second scans. Nine percent of WMP was within the WMHs, 49% within the NAWM, and 52% within the WMH ring (p<0.001; ANOVA). Conclusions Increased BBB permeability in NAWM and close to the WMH borders supports a relationship between BBB disruption and development of WMHs.

Multimodal imaging findings in normal-appearing white matter of leucoaraiosis: a review

“…25 26 Recently, a study among patients with Binswanger disease demonstrated that abnormal WM permeability (WMP) was more frequently detected in NAWM than in WMHs, with the highest frequency in a 4 mm width ring surrounding the WMHs, which coincided with the aforementioned finding that the surrounding NAWM was vulnerable, leading to progression of WMHs. 27 Histopathological and postmortem imaging findings in NAWM Autopsy studies confirmed that the underlying pathological changes of LA extended into the NAWM. Among six AD patients with LA, neuropathological examination revealed much more extensive changes in WM than did parallel postmortem MRI, with a mean of 54% larger abnormal areas.…”

Neuroimaging in vascular cognitive impairment: a state-of-the-art review

“…Diffusion tensor imaging provides another indicator of structural damage to white matter [58]. Finally, DCEMRI is a functional measure of the leakiness of blood vessels, which indicates the presence of neuroinflammation [59, 60]. The combination of multiple modalities provides a clear picture of the extent of damage and the possible etiology of the injury in white matter.…”

Blood-brain barrier permeability of normal-appearing white matter in patients with vestibular schwannoma: A new hybrid approach for analysis of T 1 -W DCE-MRI

“…4,[17][18][19][20][21][22][23][24] Recent work has also identified changes in permeability in NAWM following whole brain radiotherapy in patients with cerebral tumors. 25 The increase in BBB permeability induced by whole-brain radiotherapy has been used to improve penetration of therapeutic agents for the treatment of primary central nervous system (CNS) lymphoma and metastatic disease typically depending on simultaneous measurement of cerebrospinal fluid (CSF) and plasma concentrations of the therapeutic agent.…”