Donders Institute for Brain, Cognition and Behaviour
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Thesis defense Annemieke ter Telgte (Donders series 439)

9 June 2020

Promotors: prof. dr. H. de Leeuw,  dr. M. Duering
Co-promotor: dr. A. Tuladhar

On the origin of cerebral small vessel disease - from in vivo to ex vivo to histopathology

Cerebral small vessel disease (SVD) is the leading cause of vascular cognitive impairment and dementia, and contributes to up to a fifth of all strokes globally. Although at present the smallest cerebral blood vessels cannot be visualized on conventional MRI, MRI detects brain parenchymal changes attributed to SVD. These include changes of the cerebral white matter, termed white matter hyperintensities (WMH), lacunes or fluid-filled cavities, and microbleeds. Despite their clinical significance and high prevalence among the elderly, the pathophysiology of SVD is poorly understood. We investigated whether small, hyperintense lesions on diffusion-weighted imaging (DWI lesions), suggestive of acute infarcts, underlie MRI markers of SVD.

Therefore, we initiated the RUN DMC – InTENse study. 54 participants with SVD were invited to undergo 3T MRI monthly, for 10 consecutive months. To investigate whether DWI lesions are acute infarcts, we performed histopathological analysis of DWI lesions in a different study, using brains of patients who consented to donate their brain after death.

We demonstrated that small, asymptomatic DWI lesions develop into MRI markers of SVD. However, their contribution to the various markers of SVD varies; while their contribution to WMH is limited, they explain 80% of new lacunes. Furthermore, with our histopathology study we provided for the first time evidence that small hyperintense lesions on DWI reflect acute infarcts. Collectively, our data may be a stepping stone for future studies to investigate whether prevention of acute infarcts could contribute to halting part of the progression of SVD.