Blood-Brain Barrier Permeability clinical trials

Blood-brain Barrier Quantification in Cerebral Small Vessel Disease

Cerebral small vessel disease (cSVD) encompasses all pathological processes that affect the small vessels of the brain. On brain-MRI cSVD is characterized by structural brain abnormalities such as white matter lesions (WMLs). Clinically, cSVD is related to acute syndromes as lacunar stroke but also to more chronic health problems such as cognitive decline. Recent literature suggests that a disrupted blood brain barrier (BBB), leading to elevated BBB permeability, may play a pivotal role in the aetiology of cSVD and lacunar stroke. The BBB is a complex system of neuronal, glial and vascular cells which main function is to shield the brain from toxic components and regulate the homeostasis. Elucidating the role of the BBB may have far reaching consequences for the treatment of cSVD patients and the reduction of recurrence rate of the disease. This could lead to a better quality of life among cSVD patients and reduce the economic burden on society. Currently the exact contribution and extent of a possibly defective BBB in cSVD remains largely unclear, due to the lack of a reliable method to accurately quantify the BBB permeability in cSVD patients. As a result, the current treatment consists of treating the cardiovascular risk factors, often with poor results. Quantification of the BBB permeability provides an objective measure of the integrity of the BBB and as such aids the study of the role of the BBB. The aim of this study is to realize a clinically applicable MRI-method to quantify the BBB permeability. Moreover, the method can be used to study the involvement of BBB disruption in other neuropathologies including Alzheimer's disease, vascular dementia, hypertension and diabetes. Primary Study Objective: To realize a clinically applicable quantification of BBB permeability using DCE-MRI by determining the reproducibility of the DCE-MRI method Secondary Study Objective: To achieve the shortest scan duration without compromising the reliability of the BBB permeability quantification. Hypotheses: 1. Using an optimized DCE-MRI method to quantify the BBB permeability, the BBB permeability can be reliably determined in cSVD patients. 2. The scan duration can be shortened without compromising the reliability of the BBB permeability quantification.