Cerebrovascular reactivity and white matter integrity

Abstract

Objective: To compare the diffusion and perfusion MRI metrics of normal-appearing white matter (NAWM) with and without impaired cerebrovascular reactivity (CVR).Methods: Seventy-five participants with moderate to severe leukoaraiosis underwent blood oxygen level-dependent CVR mapping using a 3T MRI system with precise carbon dioxide stimulus manipulation. Several MRI metrics were statistically compared between areas of NAWM with positive and negative CVR using one-way analysis of variance with Bonferroni correction for multiple comparisons.Results: Areas of NAWM with negative CVR showed a significant reduction in fractional anisotropy by a mean (SD) of 3.7% (2.4), cerebral blood flow by 22.1% (8.2), regional cerebral blood volume by 22.2% (7.0), and a significant increase in mean diffusivity by 3.9% (3.1) and time to maximum by 10.9% (13.2) (p , 0.01), compared to areas with positive CVR.Conclusions: Impaired CVR is associated with subtle changes in the tissue integrity of NAWM, as evaluated using several quantitative diffusion and perfusion MRI metrics. These findings suggest that impaired CVR may contribute to the progression of white matter disease. Changes in the periventricular and subcortical white matter are observed on both CT and MRI scans of elderly individuals.1 The affected areas appear hyperintense on T2-weighted MRI, and are labeled as white matter hyperintensities (WMHs) if they are of presumed vascular origin. 2They are associated with an increased risk of dementia, 3 stroke, 4 and cognitive disability, 5 and correlated with age; as many as 95% of individuals over age 50 have WMHs.6,7 Therefore, preventing or slowing the progression of WMHs has the potential to lower the disease burden. Although several modifiable risk factors have been associated with WMH progression, such as smoking and high blood pressure, 8 the detailed pathogenesis of WMHs remains controversial. Nevertheless, the prevailing view is that a chronic low-grade ischemic injury is the final common pathway for these lesions, 9,10 and this view was the motivation for our study. Accordingly, this study characterized vascular pathophysiology in normal-appearing white matter (NAWM) before progression to overt leukoaraiosis by measuring cerebrovascular reactivity (CVR); the change in cerebral blood flow in response to a vasodilatory stimulus. Negative CVR values represent steal physiology, in which blood flow is redistributed from regions of exhausted cerebral vasodilatory reserve to areas with preserved vasodilatory capacity. 11 WeFrom the Department of Physiology

Cerebral blood flow in normal aging adults: cardiovascular determinants, clinical implications, and aerobic fitness

“…), microstructural damage of the cerebral white matter (Sam et al . ), and increased mortality (Portegies et al . ).…”

“…Mechanistically, carotid arterial stenosis or occlusion may decrease CPP distal to the lesions and exhaust the autoregulatory vasodilatory reserve; therefore, additional stimuli such as hypercapnia may not further vasodilate the cerebral arteries (Gupta et al 2012). In addition to stroke, attenuated hypercapnic CVMR has been shown to correlate with cognitive decline in AD patients (Silvestrini et al 2006), microstructural damage of the cerebral white matter (Sam et al 2016), and increased mortality (Portegies et al 2014).…”

The efficiency of the brain connectome is associated with cerebrovascular reactivity in persons with white matter hyperintensities

“…Prior studies showed impaired white matter CVR is associated with disruption of white matter at the microstructural scale in participants with WMH (Sam, Conklin, Holmes, et al, 2016;Sam, Peltenburg, Conklin, et al, 2016). Prior studies showed impaired white matter CVR is associated with disruption of white matter at the microstructural scale in participants with WMH (Sam, Conklin, Holmes, et al, 2016;Sam, Peltenburg, Conklin, et al, 2016).…”

“…Impaired cerebrovascular autoregulation may also be contributing to chronic ischemia (Mikulis, 2013). Exhaustion of cerebrovascular reserve and the associated chronic ischemic injury to gray matter and white matter is hypothesized as the cause of disruption of both the network nodes and edges of the connectome respectively (Sam, Conklin, Holmes, et al, 2016;Sam, Peltenburg, Conklin, et al, 2016). Exhaustion of cerebrovascular reserve and the associated chronic ischemic injury to gray matter and white matter is hypothesized as the cause of disruption of both the network nodes and edges of the connectome respectively (Sam, Conklin, Holmes, et al, 2016;Sam, Peltenburg, Conklin, et al, 2016).…”

“…Impaired CVR is implicated in disruption of gray matter and cortical thinning (Fierstra et al, 2010). Also in normal appearing white matter, impaired CVR is associated with worse fractional anisotropy (FA), mean diffusivity (MD), cerebral blood flow and blood volume and the development of new WMH (Sam, Peltenburg, Conklin, et al, 2016). Impaired CVR has been associated with WMH lesions .…”