We define cerebral vascular reactivity (CVR) as the ratio of the change in blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) signal (S) to an increase in blood partial pressure of CO2 (PCO2): % Δ S/Δ PCO2 mm Hg. Our aim was to further characterize CVR into dynamic and static components and then study 46 healthy subjects collated into a reference atlas and 20 patients with unilateral carotid artery stenosis. We applied an abrupt boxcar change in PCO2 and monitored S. We convolved the PCO2 with a set of first-order exponential functions whose time constant τ was increased in 2-second intervals between 2 and 100 seconds. The τ corresponding to the best fit between S and the convolved PCO2 was used to score the speed of response. Additionally, the slope of the regression between S and the convolved PCO2 represents the steady-state CVR (ssCVR). We found that both prolongations of τ and reductions in ssCVR (compared with the reference atlas) were associated with the reductions in CVR on the side of the lesion. τ and ssCVR are respectively the dynamic and static components of measured CVR.

CVR mapping by using a prospectively targeted CO(2) stimulus and BOLD MR imaging is safe, well tolerated, and technically feasible in a clinical patient population.

Attribution of vascular pathophysiology to reductions in cerebrovascular reactivity (CVR) is confounded by subjective assessment and the normal variation between anatomic regions. This study aimed to develop an objective scoring assessment of abnormality. CVR was measured as the ratio of the blood-oxygen-level-dependent magnetic resonance signal response divided by an increase in CO 2 , standardized to eliminate variability. A reference normal atlas was generated by coregistering the CVR maps from 46 healthy subjects into a standard space and calculating the mean and standard deviation (s.d.) of CVR for each voxel. Example CVR studies from 10 patients with cerebral vasculopathy were assessed for abnormality, by normalizing each patient's CVR to the same standard space as the atlas, and assigning a z-score to each voxel relative to the mean and s.d. of the corresponding atlas voxel. Z-scores were color coded and superimposed on their anatomic scans to form CVR z-maps. We found the CVR z-maps provided an objective evaluation of abnormality, enhancing our appreciation of the extent and distribution of pathophysiology compared with CVR maps alone. We concluded that CVR z-maps provide an objective, improved form of evaluation for comparisons of voxel-specific CVR between subjects, and across tests sites.

Areas of reduced CVR precede the progression from NAWM to WMH, suggesting that hemodynamic impairment may contribute to the pathogenesis and progression of age-related white matter disease. Ann Neurol 2016;80:277-285.

PurposeTo evaluate the relationship between both dynamic and steady-state measures of cerebrovascular reactivity (CVR) and the progression of age-related white matter disease.MethodsBlood oxygen level-dependent (BOLD) MRI CVR scans were acquired from forty-five subjects (age range: 50–90 years, 25 males) with moderate to severe white matter disease, at baseline and one-year follow-up. To calculate the dynamic (τ) and steady-state (ssCVR) components of the BOLD signal response, the PETCO2 signal waveform was convolved with an exponential decay function. The τ corresponding to the best fit between the convolved PETCO2 and BOLD signal defined the speed of response, and the slope of the regression between the convolved PETCO2 and BOLD signal defined ssCVR. ssCVR and τ were compared between normal-appearing white matter (NAWM) that remains stable over time and NAWM that progresses to white matter hyperintensities (WMHs).ResultsIn comparison to contralateral NAWM, NAWM that progressed to WMH had significantly lower ssCVR values by mean (SD) 46.5 (7.6)%, and higher τ values by 31.9 (9.6)% (both P < 0.01).ConclusionsVascular impairment in regions of NAWM that progresses to WMH consists not only of decreased magnitude of ssCVR, but also a pathological decrease in the speed of vascular response. These findings support the association between cerebrovascular dysregulation and the development of WMH.

Background and Purpose— Cerebral small vessel disease (SVD) is associated with increased stroke risk and poor stroke outcomes. We aimed to evaluate whether chronic SVD burden is associated with poor recruitment of collaterals in large-vessel occlusive stroke. Methods— Consecutive patients with middle cerebral artery or internal carotid artery occlusion presenting within 6 hours after stroke symptom onset who underwent thrombectomy from 2012 to 2017 were included. The prespecified primary outcome was poor collateral flow, which was assessed on baseline computed tomographic angiography (poor, ≤50% filling; good, >50% filling). Markers of chronic SVD on brain magnetic resonance imaging were rated for the extent of white matter hyperintensities, enlarged perivascular spaces, chronic lacunar infarctions and cerebral microbleeds using the Standards for Reporting Vascular Changes on Neuroimaging criteria. Severity of SVD was quantified by adding the presence of each SVD feature, with a total possible score of 0 to 4; each SVD type was also evaluated separately. Multivariable logistic regression analyses were performed to evaluate the relationships between SVD and poor collaterals, with adjustment for potential confounders. Results— Of the 100 eligible patients, the mean age was 65±16 years, median National Institutes of Health Stroke Scale score was 15, and 68% had any SVD. Poor collaterals were observed in 46%, and those with SVD were more likely to have poor collaterals than patients without SVD (aOR, 1.9 [95% CI, 1.1–3.2]). Of the SVD types, poor collaterals were significantly associated with white matter hyperintensities (aOR, 2.9 per Fazekas increment [95% CI, 1.6–5.3]) but not with enlarged perivascular spaces (adjusted odds ratio [aOR], 1.3 [95% CI, 0.4–4.0]), lacunae (aOR, 2.1 [95% CI, 0.6–7.1]), or cerebral microbleeds (aOR, 2.1 [95% CI, 0.6–7.8]). Having a greater number of different SVD markers was associated with a higher odds of poor collaterals (crude trend P <0.001; adjusted P =0.056). There was a dose-dependent relationship between white matter hyperintensity burden and poor collaterals: adjusted odds of poor collaterals were 1.5, 3.0, and 9.7 across Fazekas scores of 1 to 3 ( P trend=0.015). No patient with an SVD score of 4 had good collaterals. Conclusions— Chronic cerebral SVD is associated with poor recruitment of collaterals in large vessel occlusive stroke. A prospective study to elucidate the potential mechanism of how SVD may impair the recruitment of collaterals is ongoing.

Cerebral blood flow responds to a carbon dioxide challenge, and is often assessed as cerebrovascular reactivity, assuming a linear response over a limited stimulus range or a sigmoidal response over a wider range. However, these assumed response patterns may not necessarily apply to regions with pathophysiology. Deviations from sigmoidal responses are hypothesised to result from upstream flow limitations causing competition for blood flow between downstream regions, particularly with vasodilatory stimulation; flow is preferentially distributed to regions with more reactive vessels. Under these conditions, linear or sigmoidal fitting may not fairly describe the relationship between stimulus and flow. To assess the range of response patterns and their prevalence a survey of healthy control subjects and patients with cerebrovascular disease was conducted. We used a ramp carbon dioxide challenge from hypo- to hypercapnia as the stimulus, and magnetic resonance imaging to measure the flow responses. We categorized BOLD response patterns into four types based on the signs of their linear slopes in the hypo- and hypercapnic ranges, color coded and mapped them onto their respective anatomical scans. We suggest that these type maps complement maps of linear cerebrovascular reactivity by providing a better indication of the actual response patterns. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

No abstract