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 using novel imaging biomarkers. Blood-brain barrier (BBB) imaging 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. Microstructural white matter injury is also being studied using diffusion tensor imaging (DTI). DTI is a noninvasive technique that measures the direction and magnitude of water movement in the extracellular space. DTI can reflect transient response to injury such as vasogenic edema in addition to more permanent changes such as white matter microstructural degradation. DTI changes precede WMH, and global meausures are more closely linked to cognitive processing speed. DTI is sensitive to both the acute microstructural tissue changes in stroke and the chronic changes that contribute to WMH and vascular cognitive impairment. 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 and/or changes in microstructure 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.