Blood–Brain Barrier Permeability and Long-Term Clinical and Imaging Outcomes in Cerebral Small Vessel Disease

Abstract Background This is an exploratory study using a novel imaging modality, quantitative ultrashort time-to-echo, contrast enhanced (QUTE-CE) magnetic resonance imaging to evaluate the permeability of the blood brain barrier in a rat model of type 2 diabetes with the presumption that small vessel disease is a contributing factor to neuropathology in diabetes. Methods The BBZDR/Wor rat, a model of type 2 diabetes, and age-matched controls were studied for changes in blood brain barrier permeability. QUTE-CE, a quantitative vascular biomarker, generated angiographic images with over 500,000 voxels that were registered to a 3D MRI rat brain atlas providing site-specific information on blood-brain barrier permeability in 173 different brain areas. Results In this model of diabetes, without the support of insulin treatment, there was global capillary pathology with over 84% of the brain showing a significant increase in blood brain barrier permeability over wild-type controls. Areas of the cerebellum and midbrain dopaminergic system were not significantly affected.Conclusion Small vessel disease as assessed by permeability in the blood brain barrier in type 2 diabetes is pervasive and includes much of the brain. The increase in blood-brain barrier permeability is a likely contributing factor to diabetic encephalopathy and dementia.

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Blood-brain barrier impairment and hypoperfusion are linked in cerebral small vessel disease

Neurology ◽

10.1212/wnl.0000000000007263 ◽

2019 ◽

Vol 92 (15) ◽

pp. e1669-e1677 ◽

Cited By ~ 19

Author(s):

Sau May Wong ◽

Jacobus F.A. Jansen ◽

C. Eleana Zhang ◽

Erik I. Hoff ◽

Julie Staals ◽

...

Keyword(s):

White Matter ◽

Blood Brain Barrier ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Brain Barrier ◽

Small Vessel ◽

Dynamic Susceptibility ◽

Vessel Disease ◽

Blood Brain ◽

Bbb Permeability

ObjectiveTo investigate the link between blood-brain-barrier (BBB) permeability and cerebral blood flow (CBF) and the relation with white matter hyperintensities (WMH) in cerebral small vessel disease (cSVD).MethodsTwenty-seven patients with cSVD received dynamic susceptibility contrast and dynamic contrast-enhanced MRI to determine CBF and BBB permeability (expressed as leakage rate and volume), respectively. Structural MRI were segmented into normal-appearing white matter (NAWM) and WMH, for which a perilesional zone was defined. In these regions, we investigated the BBB permeability, CBF, and their relation using Pearson correlation r.ResultsWe found a decrease in CBF of 2.2 mL/min/100 g (p < 0.01) and an increase in leakage volume of 0.7% (p < 0.01) per mm closer to the WMH in the perilesional zones. Lower CBF values correlated with higher leakage measures in the NAWM and WMH (−0.53 < r < −0.40, p < 0.05). This relation was also observed in the perilesional zones, which became stronger in the proximity of WMH (p = 0.03).ConclusionBBB impairment and hypoperfusion appear in the WMH and NAWM, which increase in the proximity of the WMH, and are linked. Both BBB and CBF are regulated in the neurovascular unit (NVU) and the observed link might be due to the physiologic regulation mechanism of the NVU. This link may suggest an early overall deterioration of this unit.

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