Magnetic resonance imaging for assessment of cerebrovascular reactivity in cerebral small vessel disease: A systematic review

Abstract

Cerebral small vessel disease (SVD) pathophysiology is poorly understood. Cerebrovascular reactivity (CVR) impairment may play a role, but evidence to date is mainly indirect. Magnetic resonance imaging (MRI) allows investigation of CVR directly in the tissues affected by SVD. We systematically reviewed the use of MRI to measure CVR in subjects with SVD. Five studies (total n ¼ 155 SVD subjects, 84 controls) provided relevant data. The studies included different types of patients. Each study used blood oxygen level dependent (BOLD) MRI to assess CVR but a different vasoactive stimulus and method of calculating CVR. CVR decreased with increasing white matter hyperintensities in two studies (n ¼ 17, 11%) and in the presence of microbleeds in another. Three studies (n ¼ 138, 89%) found no association of CVR with white matter hyperintensities. No studies provided tissue-specific CVR values. CVR decreased with age in three studies, and with female gender and increasing diastolic blood pressure in one study. Safety and tolerability data were limited. Larger studies using CVR appear to be feasible and are needed, preferably with more standardized methods, to determine if specific clinical or radiological features of SVD are more or less associated with impaired CVR.

BOLD‐based cerebrovascular reactivity vascular transfer function isolates amplitude and timing responses to better characterize cerebral small vessel disease

“…This study focused primarily on normal‐appearing WM CVR to further understand WMH, which is historically excluded from CSVD‐CVR analysis . The current study demonstrates that WM CVR information is informative and robust: namely, conventional CVR and VTF‐AUC in WM were lower in WMH groups compared with healthy participants, and VTF‐TTP was lower in healthy participants, compared with the moderate WMH group in WM.…”

“…CVR assessments via transcranial Doppler ultrasound support the notion that sporadic CSVD is associated with reduced global CVR . Findings from BOLD‐based CVR studies of sporadic CSVD are more mixed . Some report no association of whole brain CVR with white matter hyperintensities (WMHs), while others show reduced CVR in grey and white matter (GM and WM), whereas in CADASIL, a severe autosomal dominant phenotype, reduced CVR at initial assessment predicts larger increases in WMH lesions at follow‐up .…”

“…It is therefore necessary and instructive to study CSVD in terms of vasoactive properties of vessels in the human brain. Cerebrovascular reactivity (CVR) impairment has been implicated in numerous cerebrovascular diseases: CSVD, Binswanger disease, vascular dementia, and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and has been associated with vascular risk factors …”

Individual differences in regional cortical volumes across the life span are associated with regional optical measures of arterial elasticity

“…However, there is now considerable evidence that the cerebrovascular system may present specific alterations and pathologies with aging, which are somewhat independent of those observed in the rest of the body. Examples of such pathologies are small vessel brain disease (Blair et al, 2016, Van Norden et al, 2011) and cerebral amyloid angiopathy (Biffi & Greenberg, 2011). This suggests that the direct measurements of arterial pulse parameters in the cortex provided by the pulse-DOT measures used in the current study could potentially be useful for clinical purposes.…”

“…First, most studies have only used peripheral measures of arterial stiffness as an indirect index of cerebral arterial status. Although it is possible that an association between peripheral and cerebral measures exists, there is also evidence (based largely on MR studies) for the existence of a specific pathology of the cerebral vasculature that is to some extent independent from a generalized peripheral vasculature pathology (see for example Blair et al 2016; Peres et al, 2016; Shy et al, 2016; Van Norden et al, 2011). This underscores the importance of obtaining direct measurements of cerebrovascular status in the brain, which may better correlate with changes to brain anatomy and cognition.…”