154 Chapter 7 field (7T) brain MRI. Furthermore, we aim to study the relation between WMH shape and glymphatics markers and cognitive functioning. The WHIMAS study will generate data that can be used to postulate underlying mechanisms related to WMH shape variations as we will study the association between a more complex WMH shape and advanced structural and functional markers of cerebral SVD. We expect to gain a better understanding of the structural correlates of WMH shape variation using and combining the advanced measurements at 7T MRI. WMH shape has previously been related to an increased long-term dementia risk18 and increased long-term stroke- and mortality risk.19 In our study we expect that a more irregular shape of WMH will be related to disease severity (captured by other SVD markers) and cognition (memory, executive function, visuoconstruction, and processing speed). Moreover, we expect to capture WMH shape and other structures that may influence shape (such as veins) better at 7T MRI due to an increased spatial resolution. This will allow a more precise investigation of WMH shape in relation to other SVD markers and structural changes. Animal studies suggest that dysfunction of the glymphatic system plays a major role in the initiation and progression of not only neurodegenerative pathologies, but also SVD.45 Novel non-invasive markers of brain clearance that we will use in our study will allow us to study brain clearance in vivo in a non-invasive way. In our study we expect to find an association between CSF mobility and disease severity. Moreover, the BOLD-CSF coupling has been found to be reduced in patients with Alzheimer’s disease46 and cerebral amyloid angiopathy.47 Therefore, in our study we expect that the CSF-BOLD coupling will be reduced in our patient population, and will show an association with disease severity. Biomarkers early in the disease process of cerebral SVD are extremely important as they may represent a basis for future patient selection for lifestyle interventions and as outcome markers of treatment trials aimed at prevention or treatment of dementia. The results of our study will contribute as a body of evidence for novel brain MRI markers that could hopefully serve as early biomarkers for SVD. Strengths of our study include the specific patient population and the use of advanced ultra-high field 7T MRI state of the art imaging techniques in combination with advanced image processing techniques largely developed within our research group. The current study serves to steer future investigations and could be extended into a longitudinal study.
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