White Matter Hyperintensity Shape and Glymphatics

In a society with increased life expectancy, the economic, social and personal burden of dementia increases. Dementia is often caused by a combination of neurovascular and neurodegenerative diseases. Impaired brain clearance is suggested to be closely related to dementia development, as waste products (e.g. amyloid beta) accumulate in the brain, leading to neurodegeneration. Cerebral small vessel disease (SVD) is the most common neurovascular disease that even contributes to about 45% of dementia pathophysiology in patients with a diagnosis of Alzheimer's dementia. White matter hyperintensities of presumed vascular origin (WMH) are the key brain MRI manifestation of cerebral SVD. There is evidence that the currently known and MRI-visible WMH are landmarks of an already progressed stage of the underlying pathology. The pathophysiology of WMH has been attributed to multiple underlying mechanisms, such as hypoperfusion, defective cerebrovascular reactivity and blood-brain barrier dysfunction. Furthermore, different anatomical locations and different types of WMH are related to different underlying pathological changes. Using ultra-high field 7T MR imaging techniques WMH lesions can be detected with a higher sensitivity and resolution than on 3T MRI. The hypothesis is that different pathological mechanisms of cerebral SVD lead to variations in WMH shape. Moreover, the brain clearance ('glymphatic') system of the brain appears to be tightly connected to dementia pathology. Thus, novel markers of glymphatic activity could aid to describe and understand the pathology.