Using MRI to Understand Disease States that Occur at the Interface of the Brain and the Cerebral Circulation

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The Neuro Vascular Brain Imaging (NVBI) unit studies pathologic states that occur at the interface between blood vessels and the brain. This encompasses acute cerebral ischemia caused by an occluded blood vessel as well as chronic cerebral ischemia that can be associated with dementia. Specifically, the NVBI unit is investigating why some patients who have had a stroke subsequently develop cognitive decline and dementia in association with changes on their MRI. This phenomenon is being studied in protocol 18-N-0020, The Natural History of Blood-Brain Barrier Disruption in Stroke Patients with White Matter Hyperintensities (A Cohort Study). This study is currently enrolling and is listed on https://clinicaltrials.gov/ct2/show/NCT03366129. It has long been known that changes seen on MRI, often referred to as white matter hyperintensities (WMH), are a hallmark for vascular cognitive impairment and dementia (VCID). However, it is not fully understood why these lesions develop, and thus we do not currently have a way to stop their progression. It is clear that progression (expansion) of WMH is associated with worsening cognition. The NVBI is studying what causes WMH to progress. Specifically, a novel biomarker for imaging the bloods-brain barrier (BBB) is being employed to determine if disruption of the BBB precedes the progression of WMH. The BBB results from a complex interaction of cells and cell structures and serves as the gateway between the blood vessels and the brain. When it becomes dysfunctional, cells and molecules can enter the brain that otherwise would not cross the BBB; additionally, a dysfunctional BBB may prevent facilitated transport out of the brain. The primary objective of our research is to determine if patients with a history of previous stroke and WMH on MRI will experience progression of their WMH in a manner that can be predicted by disruption of their BBB detected using MRI prior to the progression. This would allow us to identify patients at risk for cognitive decline and may shed light on its mechanisms which could help identify targets for treatment. By elucidating the genesis of WMH, we aim to reduce the morbidity and mortality associated with cerebrovascular disease.