Assessment of microvascular rarefaction in human brain disorders using physiological magnetic resonance imaging

Abstract

Cerebral microvascular rarefaction, the reduction in number of functional or structural small blood vessels in the brain, is thought to play an important role in the early stages of microvascular related brain disorders. A better understanding of its underlying pathophysiological mechanisms, and methods to measure microvascular density in the human brain are needed to develop biomarkers for early diagnosis and to identify targets for disease modifying treatments. Therefore, we provide an overview of the assumed main pathophysiological processes underlying cerebral microvascular rarefaction and the evidence for rarefaction in several microvascular related brain disorders. A number of advanced physiological MRI techniques can be used to measure the pathological alterations associated with microvascular rarefaction. Although more research is needed to explore and validate these MRI techniques in microvascular rarefaction in brain disorders, they provide a set of promising future tools to assess various features relevant for rarefaction, such as cerebral blood flow and volume, vessel density and radius and blood-brain barrier leakage.

Behavioral and Neural Activity-Dependent Recanalization of Plugged Capillaries in the Brain of Adult and Aged Mice

“…Given the fact that persistently obstructed capillaries are eventually pruned (Reeson et al, 2018), any intervention that promotes capillary recanalization could conceivably preserve blood supply and buttress the vasculature's ability to support cognitive functions. It has been demonstrated in a variety of species, including humans, that as we age the density of capillaries in the brain decreases (Buchweitz-Milton and Weiss, 1987;Riddle et al, 2003;Brown and Thore, 2011;Harb et al, 2013;van Dinther et al, 2022). This age-related loss of vessel density correlates with impaired cognitive function, and can be partially predicted by brain region specific vulnerability to capillary plugging (Mann et al, 1986;Iadecola, 2013;Langdon et al, 2018;Schager and Brown, 2020;Yoon et al, 2022).…”

Proteomic mapping reveals dysregulated angiogenesis in the cerebral arteries of rats with early-onset hypertension

“…Rarefaction can be due to fewer vessels connected in parallel, or due to a total closure of some of the vessels 29 . Vascular rarefaction is associated with the development of several clinical complications, such as cerebral microhaemorrhages and lacunar infarcts 30 . Reduced vascular density and angiogenesis has been demonstrated in the SHR 31 .…”

“…Hypertension is a major risk factor for vascular dementia and Alzheimer’s disease (AD). Accumulating evidence suggests that reduced cerebrovascular microcirculation plays a key role in the progression of (AD) 30,41 , a feature that is observed in hypertensive patients 42 . Furthermore, hypertension can cause vascular damage, neurovascular uncoupling, infarcts, and micro/macro bleeds, all favoring the pathogenesis of AD and therefore the risk of development 43 .…”

Basic Mechanisms of Brain Injury and Cognitive Decline in Hypertension

“…Functional rarefaction refers to reversible constriction and reduction of capillaries, while structural rarefaction is an irreversible loss of arterioles and capillaries. 30 It is hypothesized that long-term, functional rarefaction precedes the permanent structural changes. 30 Indeed, arteriolar and capillary rarefaction is observed in many animal models of hypertension 31 and in hypertensive patients, specifically at the earlier stages.…”

“…30 It is hypothesized that long-term, functional rarefaction precedes the permanent structural changes. 30 Indeed, arteriolar and capillary rarefaction is observed in many animal models of hypertension 31 and in hypertensive patients, specifically at the earlier stages. 32 The mechanisms underlying cerebral microvascular rarefaction in hypertension are complex and remain under investigation but have been suggested to be a consequence of the transmission of increased pressure to the brain microvessels, 6 and particularly precapillary arterioles and postcapillary venules are sensitive to the increased resistance in hypertension.…”