Reduced cerebrovascular reactivity (CVR) with steal phenomenon is an independent predictor for stroke and may indicate tissue exposed to episodic low-grade ischemia. The apparent diffusion coefficient (ADC) calculated using diffusion-weighted MRI is effective in characterizing focal brain ischemia and subtle structural changes in normal-appearing white matter (WM). We hypothesized that regions of steal phenomenon are associated with increased ADC in normal-appearing WM of patients with Moyamoya disease.
Twenty-two patients with unilateral CVR impairment secondary to Moyamoya disease and 12 healthy control subjects underwent diffusion-weighted MRI and functional MRI mapping of the cerebrovascular response to hypercapnia. Parametric maps of ADC and CVR were calculated, coregistered, and segmented using automated image processing methods. ADC of normal-appearing WM was compared between hemispheres, and between WM with negative CVR (ie, steal phenomenon) and WM with positive CVR.
In patients, ADC of normal-appearing WM was elevated in the hemisphere ipsilateral to the CVR impairment compared with the contralateral hemisphere (P<0.005) and in WM with negative CVR compared with WM with positive CVR (P<0.001). WM in regions of steal phenomenon within the affected hemisphere had higher ADC than homologous contralateral WM (P<0.005). In control subjects, negative CVR in WM was not associated with elevated ADC.
Regions of steal phenomenon are spatially correlated with elevated ADC in normal-appearing WM of patients with Moyamoya disease. This structural abnormality may reflect low-grade ischemic injury after exhaustion of the cerebrovascular reserve capacity.
"TFA provides the estimates of both the magnitude of the response to CO 2 as well as the phase relationship to the stimulus, which would reflect the speed of the response. Measuring not only the magnitude of the response but also an indication of its speed may be of clinical benefit (Conklin et al. 2010; Regan et al. 2013). Our aim in these experiments was, therefore, to investigate how changes in MAP, and different body positions, stimulus patterns and analysis techniques affect the calculation of CVR. "
[Show abstract][Hide abstract] ABSTRACT: Background and PurposeCerebrovascular reactivity (CVR), measures the ability of the cerebrovasculature to respond to vasoactive stimuli such as CO2. CVR is often expressed as the ratio of cerebral blood flow change to CO2 change. We examine several factors affecting this measurement: blood pressure, stimulus pattern, response analysis and subject position.Methods
Step and ramp increases in CO2 were implemented in nine subjects, seated and supine. Middle cerebral artery blood flow velocity (MCAv), and mean arterial pressure (MAP) were determined breath-by-breath. Cerebrovascular conductance (MCAc) was estimated as MCAv/MAP. CVR was calculated from both the relative and absolute measures of MCAc and MCAv responses.ResultsMAP increased with CO2 in some subjects so that relative CVR calculated from conductance responses were less than those calculated from CVR calculated from velocity responses. CVR measured from step responses were affected by the response dynamics, and were less than those calculated from CVR measured from ramp responses. Subject position did not affect CVR.Conclusions(1) MAP increases with CO2 and acts as a confounding factor for CVR measurement; (2) CVR depends on the stimulus pattern used; (3) CVR did not differ from the sitting versus supine in these experiments; (4) CVR calculated from absolute changes of MCAv was less than that calculated from relative changes.
Brain and Behavior 09/2014; 4(5). DOI:10.1002/brb3.275 · 2.24 Impact Factor
"Although the majority of the CVR literature has focused on BOLD signal increases with CO 2 , observations of negative CVR have also been noted. For example, negative CVR has been reported in Moyamoya disease and other types of steno-occlusive diseases (Conklin et al., 2010; Mandell et al., 2008b; Mikulis et al., 2005). "
[Show abstract][Hide abstract] ABSTRACT: With a growing need for specific biomarkers in vascular diseases, there has been a surging interest in mapping cerebrovascular reactivity (CVR) of the brain. This index can be measured by conducting a hypercapnia challenge while acquiring Blood-oxygenation-level-dependent (BOLD) signals. A BOLD signal increase with hypercapnia is the expected outcome and represents the majority of literature reports; in this work we report an intriguing observation of an apparently negative BOLD CVR response at 3 Tesla, during inhalation of 5% CO2 with balance medical air. These "negative-CVR" clusters were specifically located in the ventricular regions of the brain, where CSF is abundant and results in an intense baseline signal. The amplitude of the CVR response was -0.51±0.44% (N=14, age 26±4years). We hypothesized that this observation might not be due to a decrease in oxygenation but rather a volume effect in which bright CSF signal is replaced by a less intensive blood signal as a result of vasodilation. To test this, we performed an inversion-recovery (IR) experiment to suppress the CSF signal (N=10, age 27±5years). This maneuver in imaging sequence reversed the sign of the signal response (to 0.66±0.25%), suggesting that the volume change was the predominant reason for the apparently negative CVR in the BOLD experiment. Further support of this hypothesis was provided by a BOLD hyperoxia experiment, in which no voxels showed a negative response, presumably because vasodilation is not usually associated with this challenge. Absolute CBF response to hypercapnia was measured in a new group of subjects (N=8, age 29±7years) and it was found that CBF in ventricular regions increased by 48% upon CO2 inhalation, suggesting that blood oxygenation most likely increased rather than decreased. The findings from this study suggest that CO2 inhalation results in the dilation of ventricular vessels accompanied by shrinkage in CSF space, which is responsible for the apparently negative CVR in brain ventricles.
"Increased water random motion may derive from a degeneration of microstructural barriers, e.g., loss of membrane integrity and myelin and decreased cellular density. Higher water apparent diffusion coefficient values were also related to a disturbance of cerebral hemodynamics in patients with carotid disease . The LADIS study  showed that an increase in apparent diffusion coefficient values within the NAWM is related to WMH severity and has per se a negative effect on cognitive functions that is independent from WMH. "
[Show abstract][Hide abstract] ABSTRACT: Increasing evidence is emerging that vascular disease and its risk factors play a role in the development of Alzheimer's disease (AD) and affect the probability of an adverse outcome. The aims of this review are to explore the relationship between vascular risk factors and AD and to discuss the potential use of vascular markers in the clinical approach to cognitive impairment. Moreover, we present evidence about the potential use of ultrasonographic and neuroradiologic markers of cognitive impairment in order to establish possible treatment strategies in subjects with a clinical profile at risk of developing AD.
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