164 Chapter 8 The WHIMAS study proposed in Chapter 7 will hopefully help to answer several different questions raised in the field. Preclinical studies suggest that glymphatic system dysfunction is not only an important factor in neurodegenerative diseases, but also in SVD.7,8 Several novel non-invasive techniques are used in the MRI protocol as measures of glymphatic activity.9,10 Both a clinical MRI scanner as well as a ultra-high field system (7T MRI) will be used not only for imaging the brain clearance system, but also to improve WMH shape assessment. Ultra-high field MRI allows imaging at a higher spatial resolution, which will allow a better identification of WMH-shape and its structural correlates. Higher spatial resolution and increased sensitivity to e.g. iron deposition will also help improve the quality of other markers of cerebrovascular diseases. In this way, we can explore the added value of 7T MRI in dementia. Novel and advanced MRI techniques can be combined with other techniques or already established SVD markers (such as e.g. WMHs, microbleeds) in order to highlight different features of SVD. Combined, these data can provide important insights into the structural correlates of SVD. Longitudinal data is valuable to track both brain changes and clinical outcomes over time. It would therefore be important to extend the WHIMAS study into a longitudinal study. In our informed consent form we did prepare participants for such an extension. Smaller studies focused on a specific patient population can gather important insights into SVD markers, such as WMH shape. Specific MRI markers can be identified in such smaller, cross-sectional studies, such as the WHIMAS. Thereafter, larger studies in the general population are needed to validate the findings and to gain more generalizability for the newly developed MRI markers. This will in later research stages aid in translation of results to radiological clinical practice and thus to individual patients. The field is struggling with a lack of understanding of what WMH consist of and an accurate description of their heterogeneity. Pathology studies are rare, especially those directly linking histopathology to individual lesions visible on MRI. Pathological changes detected in such studies were ischemic damage, demyelination, axonal loss, as well as arteriosclerosis.11–13 WMH are not only developing in various neurological diseases, such as SVD and multiple sclerosis (neuroinflammatory pathology), but they also appear with ageing. Therefore, their heterogeneity needs to be both accurately captured and understood. MRI is a versatile and elegant method to noninvasively investigate the human brain in health and disease and MRI is sensitive to microstructural changes, resulting in a highly diverse imaging modality. In pure imaging studies, however, one can only speculate about the pathological processes causing or co-existing with abnormalities seen on MRI. Image-guided histology
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