Targeting Cerebral Small Vessel Disease With MRI

Abstract

Cerebral small vessel disease (SVD) is a severely debilitating disease affecting the smallest vessels in the brain. It is a major cause of cognitive decline, dementia, and functional disability in the elderly, and it is also responsible for ≈25% of all cerebral strokes.1,2 Still, treatment options are restricted to preventive risk management because there is currently no curative treatment available. Better understanding of both the pathogenesis of SVD and the subsequent pathophysiological mechanism by which SVD leads to macroscopic brain tissue damage (size ranging from mm to cm) could stimulate the development of more effective treatments. However, the nature of SVD hampers unraveling both its pathogenesis and the subsequent pathophysiological mechanisms that lead to macroscopic brain tissue damage. In the first place, SVD is a common term, grouping various pathology of the small arteries, arterioles, capillaries, and venules in the brain, regardless of the underlying pathogenesis.1 As a result, there are multiple potential cascades linking pathophysiological processes to SVD and to subsequent brain tissue damage and cognition loss. Most of these pathophysiological processes can coexist with mutual interaction, which makes it highly complex to unravel. Second, because SVD affects the smallest vessels in the brain, these vessels and their pathology are an order of magnitude below the imaging resolution of in vivo medical imaging equipment. Accordingly, current clinical markers of SVD do not reflect SVD itself but the consequences of SVD, such as loss of cognition. Similarly, image-based markers reflect macroscopic brain tissue damage secondary to SVD, such as (small) infarcts, white matter hyperintensities, perivascular spaces, microbleeds, and brain atrophy.3 These markers are marketed as indicators of SVD, even to such an extent that SVD has become synonymous with having macroscopic brain lesions on MRI.1 Trials testing the efficacy of new therapeutic treatments that …