WHIte MAtter hyperintensity Shape (WHIMAS) Study

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. The
most common mixed pathology is Alzheimer*s dementia and the neurovascular
disease of cerebral small vessel disease (SVD). SVD even contributes to the
clinical dementia phenotype in around 45% of 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 7
T MR imaging techniques WMH lesions can be detected with a higher sensitivity
and resolution than on 3 T MRI. Our hypothesis is that different pathological
mechanisms of cerebral SVD lead to variations in the complexity of 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.

Our overall aim is to study how different pathological mechanisms in cerebral
SVD influence WMH shape.

Primary objective

To study the association of a more complex WMH shape with abnormalities in
small vessel morphology.

Secondary objective

To study the association between WMH shape and cognition/other cerebral SVD
markers. To study the association of novel MRI markers of glymphatics with
cerebral small vessel disease markers and cognition.

WMH shape is assessed as follows: Convexity, solidity, concavity index, and
fractal dimension are calculated for periventricular/confluent WMHs. A lower
convexity and solidity, and higher concavity index and fractal dimension
indicate a more irregular shape of periventricular/confluent WMH. For deep
WMHs, fractal dimension and eccentricity are determined. A higher eccentricity
and fractal dimension indicate a more complex shape of deep WMH.

Cross-sectional study that will be conducted at the Leiden University Medical
Center (LUMC).

The study group will not directly benefit from the results of the study.
However, their contribution to the study will add important information about
the pathophysiology of the cerebrovascular pathology that contributes to
dementia. Therefore, it is not possible to study the research question in a
different population group. The ultra-high field 7 T MRI system is widely used
in a research setting and since its first introduction in the 1990s no serious
adverse events have been reported. Important temporary side-effects are
vertigo, nausea and involuntary eye motion due to forces on ion currents in the
semicircular loops. As all MRI scans are performed within a maximum of 60
minutes and without any contrast agents, the participant burden is seen as a
non-substantial burden.