Changes In Cerebrovascular Reactivity Research Articles

Delayed cerebrovascular reactivity in individuals with spinal cord injury in the right inferior parietal lobe: a breath-hold functional near-infrared spectroscopy study.

Cerebrovascular reactivity (CVR) reflects the ability of blood vessels to dilate or constrict in response to a vasoactive stimulus, and allows researchers to assess the brain's vascular health. Individuals with spinal cord injury (SCI) are at an increased risk for autonomic dysfunction in addition to cognitive impairments, which have been linked to a decline in CVR; however, there is currently a lack of brain-imaging studies that investigate how CVR is altered after SCI. In this study, we used a breath-holding hypercapnic stimulus and functional near-infrared spectroscopy (fNIRS) to investigate CVR alterations in individuals with SCI (n = 20, 14M, 6F, mean age = 46.3 ± 10.2 years) as compared to age- and sex-matched able-bodied (AB) controls (n = 25, 19M, 6F, mean age = 43.2 ± 12.28 years). CVR was evaluated by its amplitude and delay components separately by using principal component analysis and cross-correlation analysis, respectively. We observed significantly delayed CVR in the right inferior parietal lobe in individuals with SCI compared to AB controls (linear mixed-effects model, fixed-effects estimate = 6.565, Satterthwaite's t-test, t = 2.663, p = 0.008), while the amplitude of CVR was not significantly different. The average CVR delay in the SCI group in the right inferior parietal lobe was 14.21 s (sd: 6.60 s), and for the AB group, the average delay in the right inferior parietal lobe was 7.08 s (sd: 7.39 s). CVR delays were also associated with the duration since injury in individuals with SCI, in which a longer duration since injury was associated with a shortened delay in CVR in the right inferior parietal region (Pearson's r-correlation, r = -0.59, p = 0.04). This study shows that fNIRS can be used to quantify changes in CVR in individuals with SCI, and may be further used in rehabilitative settings to monitor the cerebrovascular health of individuals with SCI.

Amelioration of gait and balance disorders by rosuvastatin is associated with changes in cerebrovascular reactivity in older patients with hypertensive treatment.

To investigate the effect of rosuvastatin on gait and balance disorder progression and elucidate the role of cerebrovascular reactivity (CVR) on this effect. From April 2008 to November 2010, 943 hypertensive patients aged ≥60 years were enrolled from the Shandong area of China. Patients were randomized into rosuvastatin and placebo groups. Gait, balance, CVR, fall and stroke were assessed. During an average 72 months of follow-up, the decreasing trends for step length, step speed, and Berg balance scale scores and the increasing trends for step width and chair rising test were slower in the rosuvastatin group when compared to the placebo group. The hazard ratio of incident balance impairment and falls was 0.542 [95% confidence interval (CI) 0.442-0.663] and 0.532 (95% CI 0.408-0.694), respectively, in the rosuvastatin group compared with placebo group. For CVR progression, the cerebrovascular reserve capacity and breath-holding index were increased and the pulsatility index decreased in the rosuvastatin group, while the cerebrovascular reserve capacity and breath-holding index were decreased, and pulsatility index increased in the placebo group. The changes in gait stability and balance function were independently associated with the changes in the CVR. The odds risks of balance impairment and falls were 2.178 (95% CI: 1.491-3.181) and 3.227 (95% CI: 1.634-6.373), respectively, in the patients with CVR impairment and patients without CVR impairment. Rosuvastatin ameliorated gait and balance disorder progression in older patients with hypertension. This effect might result from the improvement in the CVR. This double-blind clinical trial recruited 943 hypertensive patients aged ≥60 years who were randomly administered rosuvastatin and placebo interventions. The data indicates that rosuvastatin significantly ameliorated the progressions of gait and balance disorders in older hypertensive patients. The cerebrovascular reactivity might play an important mediating role in this amelioration.

Heme oxidation of NO-receptor soluble guanylyl cyclase is an important contributor to cerebrovascular and cognitive dysfunctions

Introduction: Decreased cerebral blood flow (CBF) is one of the major hemodynamic alterations leading to neurodegeneration and age-related cognitive decline. Nitric Oxide (NO)-dependent vasomotor reactivity is central in regulating cerebrovascular hemodynamics and adequate brain blood perfusion. NO receptor Soluble Guanylyl Cyclase (sGC) is the primary mediator of NO-dependent vasodilation. Oxidative stress, often persisting in diseased vasculature, renders sGC insensitive to NO and impairs the NO signaling. The objective of our study was to investigate the role of sGC oxidation in regulation CBF and brain function. Hypothesis: Oxidative stress disrupts NO/cGMP signaling in brain by decreasing sGC activity via oxidation of sGC heme. Approach: To assess causal effect of sGC oxidation on NO signaling function we administered ODQ, a sGC-specific heme oxidizing agent, to simulate long-term effect of sGC oxidation in cerebral vasculature. Two groups of young wild-type male and female mice (4 months old C57BL/6) were treated intraperitoneally (IP) twice a week for one month with ODQ (20 mg/kg) or a solvent as control. Changes in cerebrovascular reactivity and memory function were assessed and compared in treated and control groups. Using a non-invasive pulsed Doppler ultrasound-based system we assessed the changes in blood flow velocity (PVF, % of baseline) in the mouse middle cerebral artery (MCA) of male and female groups. MCA vasodilation was induced by bolus IP injection of NO-donor sodium nitroprusside (SNP) or BAY 58-2667, an allosteric NO-independent sGC activator. Memory function was assessed by the Novel Object Recognition Task (NORT, RI, recognition index) in all experimental groups. Western blotting and densitometry assessed the expression of major sGC subunits (α1, α2 and β1) in cleared brain lysates from ODQ-treated and control groups. Results: We observed a significantly blunted vasodilative response to SNP (1 mg/kg) in ODQ-treated mice vs controls of both genders (PVF, max response at 2 min post-injection, males 73.9 ± 10.4% (n=7/7) vs 58.5 ± 8.6 %, p=0.01; females (n=6/6) 77.4 ± 10.6 % vs 61.9 ± 5.4 %, p=0.01). Changes in response to NO-donor were more pronounced in males than females. The difference in BAY 58-2667 response between ODQ-treated and control groups was not statistically significant. ODQ significantly reduced the long-term memory in males but not female, according to NORT (RI, males (n=7/7) 0.58 ± 0.13 vs 0.69 ± 0.05; p=0.01; females (n=6/6) ODQ 0.59 ± 0.17 vs 0.73 ± 0.1, p=0.13). No statistically significant difference in expression of sGC subunits between control and ODQ-treated (n= 4/4) of male and female groups was determined. Conclusions: ODQ treatment significantly impairs vasodilation response to NO-donor but not to NO-independent sGC activator in mice MCA. ODQ treatment negatively affects long-term memory function in male, but not female mice. ODQ treatment does not significantly affect the expression of sGC subunits. Together our data suggest that the oxidation of sGC heme moiety impairs the regulation of cerebral blood flow of both genders and impairs long-term memory function gender-specifically in young mice. This research was supported by National Institute of Health grants RAG071999A (Iraida Sharina), HL139838, and American Heart Association 23TPA1070711 (Emil Martin). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Analyzing the hemodynamic basis of post-stroke epilepsy: impact of BOLD cerebrovascular reactivity changes and the role of STA-MCA bypass

Analyzing the hemodynamic basis of post-stroke epilepsy: impact of BOLD cerebrovascular reactivity changes and the role of STA-MCA bypass

The impact of sedative and vasopressor agents on cerebrovascular reactivity in severe traumatic brain injury

BackgroundThe aim of this study is to evaluate the impact of commonly administered sedatives (Propofol, Alfentanil, Fentanyl, and Midazolam) and vasopressor (Dobutamine, Ephedrine, Noradrenaline and Vasopressin) agents on cerebrovascular reactivity in moderate/severe TBI patients. Cerebrovascular reactivity, as a surrogate for cerebral autoregulation was assessed using the long pressure reactivity index (LPRx). We evaluated the data in two phases, first we assessed the minute-by-minute data relationships between different dosing amounts of continuous infusion agents and physiological variables using boxplots, multiple linear regression and ANOVA. Next, we assessed the relationship between continuous/bolus infusion agents and physiological variables, assessing pre-/post- dose of medication change in physiology using a Wilcoxon signed-ranked test. Finally, we evaluated sub-groups of data for each individual dose change per medication, focusing on key physiological thresholds and demographics.ResultsOf the 475 patients with an average stay of 10 days resulting in over 3000 days of recorded information 367 (77.3%) were male with a median Glasgow coma score of 7 (4–9). The results of this retrospective observational study confirmed that the infusion of most administered agents do not impact cerebrovascular reactivity, which is confirmed by the multiple linear regression components having p value > 0.05. Incremental dose changes or bolus doses in these medications in general do not lead to significant changes in cerebrovascular reactivity (confirm by Wilcoxon signed-ranked p value > 0.05 for nearly all assessed relationships). Within the sub-group analysis that separated the data based on LPRx pre-dose, a significance between pre-/post-drug change in LPRx was seen, however this may be more of a result from patient state than drug impact.ConclusionsOverall, this study indicates that commonly administered agents with incremental dosing changes have no clinically significant influence on cerebrovascular reactivity in TBI (nor do they impair cerebrovascular reactivity). Though further investigation in a larger and more diverse TBI patient population is required.

Understanding recovery of language after stroke: insights from neurovascular MRI studies.

Stroke causes a disruption in blood flow to the brain that can lead to profound language impairments. Understanding the mechanisms of language recovery after stroke is crucial for the prognosis and effective rehabilitation of people with aphasia. While the role of injured brain structures and disruptions in functional connectivity have been extensively explored, the relationship between neurovascular measures and language recovery in both early and later stages has not received sufficient attention in the field. Fully functioning healthy brain tissue requires oxygen and nutrients to be delivered promptly via its blood supply. Persistent decreases in blood flow after a stroke to the remaining non-lesioned tissue have been shown to contribute to poor language recovery. The goal of the current paper is to critically examine stroke studies looking at the relationship between different neurovascular measures and language deficits and mechanisms of language recovery via changes in neurovascular metrics. Measures of perfusion or cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) provide complementary approaches to understanding neurovascular mechanisms post stroke by capturing both cerebral metabolic demands and mechanical vascular properties. While CBF measures indicate the amount of blood delivered to a certain region and serve as a proxy for metabolic demands of that area, CVR indices reflect the ability of the vasculature to recruit blood flow in response to a shortage of oxygen, such as when one is holding their breath. Increases in CBF during recovery beyond the site of the lesion have been shown to promote language gains. Similarly, CVR changes, when collateral vessels are recruited to help reorganize the flow of blood in hypoperfused regions, have been related to functional recovery post stroke. In the current review, we highlight the main findings in the literature investigating neurovascular changes in stroke recovery with a particular emphasis on how language abilities can be affected by changes in CBF and CVR. We conclude by summarizing existing methodological challenges and knowledge gaps that need to be addressed in future work in this area, outlining a promising avenue of research.

Clinical Outcome, Cognition, and Cerebrovascular Reactivity after Surgical Treatment for Moyamoya Vasculopathy: A Dutch Prospective, Single-Center Cohort Study.

Background: It remains unclear whether revascularization of moyamoya vasculopathy (MMV) has a positive effect on cognitive function. In this prospective, single-center study, we investigated the effect of revascularization on cognitive function in patients with MMV. We report clinical and radiological outcome parameters and the associations between clinical determinants and change in neurocognitive functioning. Methods: We consecutively included all MMV patients at a Dutch tertiary referral hospital who underwent pre- and postoperative standardized neuropsychological evaluation, [15O]H2O-PET (including cerebrovascular reactivity (CVR)), MRI, cerebral angiography, and completed standardized questionnaires on clinical outcome and quality of life (QOL). To explore the association between patient characteristics, imaging findings, and change in the z-scores of the cognitive domains, we used multivariable linear- and Bayesian regression analysis. Results: We included 40 patients of whom 35 (27 females, 21 children) were treated surgically. One patient died after surgery, and two withdrew from the study. TIA- and headache frequency and modified Rankin scale (mRS) improved (resp. p = 0.001, 0.019, 0.039). Eleven patients (seven children) developed a new infarct during follow-up (31%), five of which were symptomatic. CVR-scores improved significantly (p < 0.0005). The language domain improved (p = 0.029); other domains remained stable. In adults, there was an improvement in QOL. We could not find an association between change in imaging and cognitive scores. Conclusion: In this cohort of Western MMV patients, TIA frequency, headache, CVR, and mRS improved significantly after revascularization. The language domain significantly improved, while others remained stable. We could not find an association between changes in CVR and cognitive scores.

Cerebrovascular reactivity deficits in cognitively unimpaired older adults: vasodilatory versus vasoconstrictive responses

Cerebrovascular reactivity (CVR) deficits may index vulnerability to vascular brain injury and cognitive impairment, but findings on age-related changes in CVR have been mixed, and no studies to date have directly compared age-related changes in CVR to hypercapnia versus hypocapnia. The present study compared CVR in 31 cognitively unimpaired older adults (ages 55–87) and 30 healthy younger adults (ages 18–28). Breath control tasks induced CVR to hypocapnia (0.1 Hz paced breathing) and hypercapnia (15s breath holds) during pseudo-continuous arterial spin labeling MRI. Relative to younger adults, cognitively unimpaired older adults displayed lower levels of global CVR under both hypocapnia and hypercapnia. In region-of-interest analyses, older adults exhibited attenuated CVR to hypocapnia in select frontal and temporal regions, and lower CVR to hypercapnia in all cortical, limbic, and subcortical regions examined, relative to younger adults. Results indicate age-related deficits in CVR are detectible even in cognitively unimpaired older adults and are disproportionately related to vasodilatory (hypercapnia) responses relative to vasoconstrictive (hypocapnia) responses. Findings may offer means for early detection of cerebrovascular dysfunction.

Abstract TP168: Quantitative Cerebrovascular Reactivity Atlas In Children

Introduction: Cerebrovascular reactivity (CVR) can be measured by inducing carbon dioxide (CO 2 ) changes in the circulation and measuring subsequent changes in blood flow with functional MRI blood oxygen level dependent sequences (BOLD). In clinical practice, abnormalities in CVR imaging can serve as a biomarker of ischemic risk. To characterize pathological aberrations in CVR, it is essential to have quantitative reference data as to what constitutes normal CVR across brain regions at various stages of development. Methods: Prospective enrollment of healthy children ages 6 to 18. Target N of 40. Two datasets are being generated within the atlas using two different methods of administering the vasoactive stimulus (CO 2 ): a breath-hold CVR dataset (endogenous stimulus) and a RespirAct TM CVR dataset (exogenous). A test of normality is performed on CVR values for each voxel across subjects, with mean and standard deviation calculations. This will allow for generation of a Z-score for each CVR value per voxel in any clinical CVR study. Voxel-wide validation of breath-hold CVR values against the gold standard RespirAct TM CVR values will be performed using within subject t-test and between group comparisons. Subgroup analysis based on gender and age will also be performed. Results: Preliminary CVR data for 8 healthy right-handed children is presented (4 female, median age 13, range 9 -14 years). All participants tolerated CVR studies well and no side effects were reported. Group datasets acquired to date passed tests of normality with no significant differences in CVR values between the two methods found. Conclusions: This study will generate the first atlas of quantitative CVR-fMRI data in healthy children. Normative physiological data on CVR changes throughout childhood, and associations between CVR, blood pressure, age, and gender will be obtained. CVR imaging is performed clinically in patients with a risk of recurrent arterial ischemic stroke such as those with intracranial arteriopathies, sickle cell disease and other genetic and metabolic disorders. Our atlas can provide clinicians with objective measures regarding extent and distribution of CVR abnormalities, allow for stroke risk stratification, and aid in determining the optimal time for intervention.

Medullary vein architecture modulates the white matter BOLD cerebrovascular reactivity signal response to CO2: Observations from high-resolution T2* weighted imaging at 7T

Brain stress testing using blood oxygenation level-dependent (BOLD) MRI to evaluate changes in cerebrovascular reactivity (CVR) is of growing interest for evaluating white matter integrity. However, even under healthy conditions, the white matter BOLD-CVR response differs notably from that observed in the gray matter. In addition to actual arterial vascular control, the venous draining topology may influence the WM-CVR response leading to signal delays and dispersions. These types of alterations in hemodynamic parameters are sometimes linked with pathology, but may also arise from differences in normal venous architecture. In this work, high-resolution T2*weighted anatomical images combined with BOLD imaging during a hypercapnic breathing protocol were acquired using a 7 tesla MRI system. Hemodynamic parameters including base CVR, hemodynamic lag, lag-corrected CVR, response onset and signal dispersion, and finally ΔCVR (corrected CVR minus base CVR) were calculated in 8 subjects. Parameter maps were spatially normalized and correlated against an MNI-registered white matter medullary vein atlas. Moderate correlations (Pearson's rho) were observed between medullary vessel frequency (MVF) and ΔCVR (0.52; 0.58 for total WM), MVF and hemodynamic lag (0.42; 0.54 for total WM), MVF and signal dispersion (0.44; 0.53 for total WM), and finally MVF and signal onset (0.43; 0.52 for total WM). Results indicate that, when assessed in the context of the WM venous architecture, changes in the response shape may only be partially reflective of the actual vascular reactivity response occurring further upstream by control vessels. This finding may have implications when attributing diseases mechanisms and/or progression to presumed impaired WM BOLD-CVR.

Cerebrovascular reactivity changes in acute concussion: a controlled cohort study.

Evidence suggests that cerebrovascular reactivity (CVR) increases within the first week after the incidence of concussion, indicating a disruption of normal autoregulation. We sought to extend these findings by investigating the effects of acute concussion on the speed of CVR response and by visualizing global and regional impairments in individual patients with acute concussion. Twelve patients aged 18-40 years who experienced concussion less than a week before this prospective study were included. Twelve age and sex-matched healthy subjects constituted the control group. In all subjects, CVR was assessed using blood oxygenation level-dependent (BOLD) echo-planar imaging with a 3.0T MRI scanner, in combination with changes in end-tidal partial pressure of CO2 (PETCO2). In each subject, we calculated the CVR amplitude and CVR response time in the gray and white matter using a step and ramp PETCO2 challenge. In addition, a separate group of 39 healthy controls who underwent the same evaluation was used to create atlases with voxel-wise mean and standard deviation of CVR amplitude and CVR response time. This allowed us to convert each metric of the 12 patients with concussion and the 12 healthy controls into z-score maps. These maps were then used to generate and compare z-scores for each of the two groups. Group differences were calculated using an unpaired t-test. All studies were well tolerated without any serious adverse events. Anatomical MRI was normal in all study subjects. No differences in CO2 stimulus and O2 targeting were observed between the two participant groups during BOLD MRI. With regard to the gray matter, the CVR magnitude step (P=0.117) and ramp + 10 (P=0.085) were not significantly different between patients with concussion and healthy controls. However, the tau value was significantly lower in patients with concussion than in the healthy controls (P=0.04). With regard to the white matter, the CVR magnitude step (P=0.003) and ramp + 10 (P=0.031) were significantly higher and the tau value (P=0.024) was significantly shorter in patients with concussion than in healthy controls. After z-score transformation, the z tau value was significantly lower in patients with concussion than in healthy controls (Grey matter P=0.021, White matter P=0.003). Comparison of the three parameters, z ramp + 10, z step, and z tau, between the two groups showed that z step (Grey matter P=0.035, White matter P=0.005) was the most sensitive parameter and that z ramp + 10 (Grey matter P=0.073, White matter P=0.126) was the least sensitive parameter. Concussion is associated with patient-specific abnormalities in BOLD cerebrovascular responsiveness that occur in the setting of normal global CVR. This study demonstrates that the measurement of CVR using BOLD MRI and precise CO2 control is a safe, reliable, reproducible, and clinically useful method for evaluating the state of patients with concussion. It has the potential to be an important tool for assessing the severity and duration of symptoms after concussion.

Sex moderations in the relationship between aortic stiffness, cognition, and cerebrovascular reactivity in healthy older adults.

It is well established that sex differences exist in the manifestation of vascular diseases. Arterial stiffness (AS) has been associated with changes in cerebrovascular reactivity (CVR) and cognitive decline in aging. Specifically, older adults with increased AS show a decline on executive function (EF) tasks. Interestingly, the relationship between AS and CVR is more complex, where some studies show decreased CVR with increased AS, and others demonstrate preserved CVR despite higher AS. Here, we investigated the possible role of sex on these hemodynamic relationships. Acquisitions were completed in 48 older adults. Pseudo-continuous arterial spin labeling (pCASL) data were collected during a hypercapnia challenge. Aortic pulse wave velocity (PWV) data was acquired using cine phase contrast velocity series. Cognitive function was assessed with a comprehensive neuropsychological battery, and a composite score for EF was calculated using four cognitive tests from the neuropsychological battery. A moderation model test revealed that sex moderated the relationship between PWV and CVR and PWV and EF, but not between CVR and EF. Together, our results indicate that the relationships between central stiffness, cerebral hemodynamics and cognition are in part mediated by sex.

Insights Into Cerebral Tissue-Specific Response to Respiratory Challenges at 7T: Evidence for Combined Blood Flow and CO2-Mediated Effects

Cerebrovascular reactivity (CVR) mapping is finding increasing clinical applications as a non-invasive probe for vascular health. Further analysis extracting temporal delay information from the CVR response provide additional insight that reflect arterial transit time, blood redistribution, and vascular response speed. Untangling these factors can help better understand the (patho)physiology and improve diagnosis/prognosis associated with vascular impairments. Here, we use hypercapnic (HC) and hyperoxic (HO) challenges to gather insight about factors driving temporal delays between gray-matter (GM) and white-matter (WM). Blood Oxygen Level Dependent (BOLD) datasets were acquired at 7T in nine healthy subjects throughout BLOCK- and RAMP-HC paradigms. In a subset of seven participants, a combined HC+HO block, referred as the “BOOST” protocol, was also acquired. Tissue-based differences in Rapid Interpolation at Progressive Time Delays (RIPTiDe) were compared across stimulus to explore dynamic (BLOCK-HC) versus progressive (RAMP-HC) changes in CO2, as well as the effect of bolus arrival time on CVR delays (BLOCK-HC versus BOOST). While GM delays were similar between the BLOCK- (21.80 ± 10.17 s) and RAMP-HC (24.29 ± 14.64 s), longer WM lag times were observed during the RAMP-HC (42.66 ± 17.79 s), compared to the BLOCK-HC (34.15 ± 10.72 s), suggesting that the progressive stimulus may predispose WM vasculature to longer delays due to the smaller arterial content of CO2 delivered to WM tissues, which in turn, decreases intravascular CO2 gradients modulating CO2 diffusion into WM tissues. This was supported by a maintained ∼10 s offset in GM (11.66 ± 9.54 s) versus WM (21.40 ± 11.17 s) BOOST-delays with respect to the BLOCK-HC, suggesting that the vasoactive effect of CO2 remains constant and that shortening of BOOST delays was be driven by blood arrival reflected through the non-vasodilatory HO contrast. These findings support that differences in temporal and magnitude aspects of CVR between vascular networks reflect a component of CO2 sensitivity, in addition to redistribution and steal blood flow effects. Moreover, these results emphasize that the addition of a BOOST paradigm may provide clinical insights into whether vascular diseases causing changes in CVR do so by way of severe blood flow redistribution effects, alterations in vascular properties associated with CO2 diffusion, or changes in blood arrival time.

Contralateral improvement of cerebrovascular reactivity and TIA frequency after unilateral revascularization surgery in moyamoya vasculopathy

ObjectiveMoyamoya vasculopathy is a rare, often bilateral disease characterized by progressive stenosis and occlusion of the distal internal carotid artery, leading to a progressive deterioration of cerebrovascular reactivity (CVR) and increased risk of transient ischemic attacks (TIAs), infarction and hemorrhage. Surgical revascularization is a widely accepted symptomatic treatment, often performed bilaterally in one or two stages. To possibly further optimize treatment strategy, we investigated the effect of unilateral revascularization surgery on the CVR of, and TIA frequency originating from, the contralateral hemisphere. MethodsFrom our database of 143 moyamoya vasculopathy patients we selected those with bilateral disease, who underwent hemodynamic imaging ([15O]H2O positron emission tomography (PET)-CT with acetazolamide challenge) before and 14 months (median) after unilateral revascularization. We evaluated CVR in three regions per hemisphere, and averaged these per hemisphere for statistical comparison. Conservatively treated patients were showed as a comparison group. To examine TIA frequency, we selected patients who presented with TIAs that (also) originated from the contralateral – not to be operated – hemisphere. We scored changes in CVR and TIA frequency of the ipsilateral and contralateral hemisphere over time. ResultsSeven surgical and seven conservative patients were included for CVR comparison. Of the 20 scored contralateral regions in the surgical group, 15 showed improved CVR after unilateral revascularization, while 5 remained stable. The averaged scores improved significantly for both hemispheres. In conservatively treated patients, however, only 3 of the 20 scored regions improved in the least-affected (contralateral) hemispheres, and 9 deteriorated. From the 6 patients with contralateral TIAs at presentation, 4 had a decreased TIA frequency originating from the contralateral hemisphere after unilateral surgery, while 2 patients remained stable. ConclusionBoth CVR and TIA frequency in the contralateral hemisphere can improve after unilateral revascularization surgery in bilateral MMV.

Incomplete circle of Willis and cerebrovascular reactivity in asymptomatic patients before and after carotid endarterectomy

Introduction/Objective. Circle of Willis (CoW) provides the most significant collateral flow in the presence of significant stenosis or occlusion of internal carotid artery. In terms of collateral flow ?incomplete? type and ?complete? type of CoW can be recognized. Patients with carotid artery disease with incomplete CoW have lower cerebrovascular reactivity and higher risk for stroke. Cerebrovascular reactivity refers to the residual capacity of dilatation of cerebral blood vessels in the condition of insufficient blood flow. In this study we analyzed changes in cerebrovascular reactivity after carotid endarterectomy in asymptomatic patients with respect to complete and incomplete CoW morphology. Methods. In this study in 97 patients with asymptomatic carotid artery disease we measured cerebrovascular reactivity before and after carotid endarterectomy by using method of ?apnea test? and ?breathholding index? (BHI). Patients were divided into two following groups: patients with ?complete? CoW and ?incomplete? CoW based on non-contrast magnetic resonance angio performed previously to the operation. Descriptive statistics, univariate analysis, and ANOVA for comparison of BHI values between groups were used. Results. The results showed significant increase in cerebrovascular reactivity at the side of stenosis in both groups of patients with complete CoW (BHI value increased from 0.897 to 1.090; F (1.65) = 30.788, p &lt; 0.0005, parc. ?2 = 0.321) and incomplete CoW (BHI value increased from 0.690 to 1.010; F (1.27) = 62.318, p &lt; 0.0005, parc. ?2 = 0.698) and the more significant increase in the group of incomplete CoW compared to the group with complete CoW (F (1.92) = 4.557, p = 0.035, parc. ?2 = 0.047) Conclusion. In most asymptomatic patients, cerebrovascular reactivity restores to normal following carotid endarterectomy. Parameters of cerebrovascular reactivity are lower in patients with incomplete CoW and the increase after carotid endarterectomy is more significant in such patients.

Alterations in resting cerebrovascular regulation do not affect reactivity to hypoxia, hyperoxia or neurovascular coupling following a SCUBA dive.

What is the central question of this study? What are the characteristics of cerebral blood flow (CBF) regulation following a single SCUBA dive to a depth of 18m sea water with a 47min bottom time. What is the main finding and its importance? Acute alterations in CBF regulation at rest, including extra-cranial vasodilatation, reductions in shear patterns and elevations in intra-cranial blood velocity were observed at rest following a single SCUBA dive. These subtle changes in CBF regulation did not translate into any functional changes in cerebrovascular reactivity to hypoxia or hyperoxia, or neurovascular coupling following a single SCUBA dive. Reductions in vascular function during a SCUBA dive - due to hyperoxia-induced oxidative stress, arterial and venous gas emboli and altered endothelial integrity - may also extend to the cerebrovasculature following return to the surface. This study aimed to characterize cerebral blood flow (CBF) regulation following a single SCUBA dive to a depth of 18m sea water with a 47min bottom time. Prior to and following the dive, participants (n=11) completed (1) resting CBF in the internal carotid (ICA) and vertebral (VA) arteries (duplex ultrasound) and intra-cranial blood velocity (v) of the middle and posterior cerebral arteries (MCAv and PCAv, respectively) (transcranial Doppler ultrasound); (2) cerebrovascular reactivity to acute poikilocapnic hypoxia (i.e. , 0.10) and hyperoxia (i.e. , 1.0); and (3) neurovascular coupling (NVC; regional CBF response to local increases in cerebral metabolism). Global CBF, cerebrovascular reactivity to hypoxia and hyperoxia, and NVC were unaltered following a SCUBA dive (all P>0.05); however, there were subtle changes in other cerebrovascular metrics post-dive, including reductions in ICA (-13±8%, P=0.003) and VA (-11±14%, P=0.021) shear rate, lower ICAv (-10±9%, P=0.008) and VAv (-9±14%, P=0.028), increases in ICA diameter (+4±5%, P=0.017) and elevations in PCAv (+10±19%, P=0.047). Although we observed subtle alterations in CBF regulation at rest, these changes did not translate into any functional changes in cerebrovascular reactivity to hypoxia or hyperoxia, or NVC. Whether prolonged exposure to hyperoxia and hyperbaria during longer, deeper, colder and/or repetitive SCUBA dives would provoke changes to the cerebrovasculature requires further investigation.

The Impact of Vasopressor and Sedative Agents on Cerebrovascular Reactivity and Compensatory Reserve in Traumatic Brain Injury: An Exploratory Analysis.

The impact of vasopressor and sedative drugs on cerebrovascular reactivity in traumatic brain injury (TBI) remains unclear. The aim of this study was to evaluate the impact of changes of doses of commonly administered sedation (i.e., propofol, fentanyl, and ketamine) and vasopressor agents (i.e., norepinephrine [NE], phenylephrine [PE], and vasopressin[VSP]) on cerebrovascular reactivity and compensatory reserve in patients with moderate/severe TBI. Using the Winnipeg Acute TBI Database, we identified 38 patients with more than 1000 distinct changes of infusion rates and more than 500 h of paired drug infusion/physiology data. Cerebrovascular reactivity was assessed using pressure reactivity index (PRx) and cerebral compensatory reserve was assessed using RAP (the correlation [R] between pulse amplitude of intracranial pressure [ICP; A] and ICP [P]). We evaluated the data in two phases. First, we assessed the relationship between mean hourly dose of medication and its relation to both mean hourly index values, and time spent above a given index threshold. Second, we evaluated time-series data for each individual dose change per medication, assessing for a statistically significant change in PRx and RAP metrics. The results of the analysis confirmed that, overall, the mean hourly dose of sedative (propofol, fentanyl, and ketamine) and vasopressor (NE, PE, and VSP) agents does not impact hourly cerebrovascular reactivity or compensatory reserve measures. Similarly, incremental dose changes in these medications in general do not lead to significant changes in cerebrovascular reactivity or compensatory reserve. For propofol with incremental dose increases, in situations where PRx is intact (i.e., PRx <0 prior), a statistically significant increase in PRx was seen. However, this may not indicate deteriorating cerebrovascular reactivity as the final PRx (∼0.05) may still be considered to be intact cerebrovascular reactivity. As such, this finding with regards to propofol remains “weak.” This study indicates that commonly administered sedative and vasopressor agents with incremental dosing changes have no clinically significant influence on cerebrovascular reactivity or compensatory reserve in TBI. These results should be considered preliminary, requiring further investigation.

Cerebrovascular reactivity mapping without hypercapnic challenge in patients with carotid artery stenosis

Vascular reactivity represents the ability of the vascular smooth muscle to dilate or contract in response to changes in metabolic demand or vasoactive stimulus. More specifically, the cerebrovascular reactivity (CVR) has raised interest in several studies that point to its potential to predict stroke risk in patients with cerebrovascular disease. CVR mapping is typically performed using carbon dioxide (CO2) inhalation, breath-holding, or acetazolamide injection as vasoactive challenges, while magnetic resonance imaging (MRI) based on the blood oxygenation level-dependent (BOLD) contrast is acquired. However, such challenges of hypercapnia depend on additional equipment and cooperation of the subjects, limiting their applications, especially in elderly patients. Therefore, the objective of the present study was to map the CVR using resting-state MRI-BOLD, with no hypercapnic challenge, considering the variations in BOLD signal associated with variations in the arterial partial pressure of CO2. The CVR maps obtained with resting data showed a high correlation with those obtained by the conventional experiment with CO2 inhalation (r &gt; 0.70). In addition, the CVR changes observed for the patients were consistent with their clinical reports. These results show that the mapping of CVR obtained with resting-state data may become a useful alternative in the detection of perfusion changes in clinical applications when the hypercapnic challenge is not feasible.

Cerebral Vascular Reactivity in Frail Older Adults with Vascular Cognitive Impairment.

Background: Frailty, a state of increased vulnerability, could play a role in the progression of vascular dementia. We aim to describe the changes in cerebrovascular reactivity of older adults with frailty and vascular-type mild cognitive impairment (MCIv). Methods: This was a cross-sectional study. A comprehensive geriatric assessment, neuropsychological evaluation, and transcranial Doppler ultrasound (TCD) was performed on 180 participants who were allocated into four groups: healthy (n = 74), frail (n = 40), MCIv (n = 35), and mixed (frail + MCIv) (n = 31). ANOVA and Kruskal–Wallis tests were used for the analysis of continuous variables with and without normal distribution. Multinomial logistic regression was constructed to identify associated covariates. Results: Subjects in the mixed group, compared to healthy group, were older (75.0 ± 5.9 vs 70.3 ± 5.9 years; p < 0.001), showed lower education (9.3 ± 6.4 vs 12.2 ± 4.0 years; p = 0.054), greater frequency of diabetes (42% vs 12%; p = 0.005), worse cognitive performance (z = −0.81 ± 0.94), and reduced left medial-cerebral artery cerebrovascular reactivity (0.43 ± 0.42 cm/s). The mixed group was associated with age (odds ratio (OR) 1.16, 95% Confidence Interval (CI) = 1.06–1.27; p < 0.001), diabetes (OR 6.28, 1.81–21.84; p = 0.004), and Geriatric Depression Scale (GDS) score (OR 1.34, 95% CI = 1.09–1.67; p = 0.007). Conclusions: Frailty among older adults was associated with worse cognitive performance, diabetes, and decreased cerebral blood flow.

Reduced arterial compliance along the cerebrovascular tree predicts cognitive slowing in multiple sclerosis: Evidence for a neurovascular uncoupling hypothesis

Background: Cognitive slowing occurs in ~70% of multiple sclerosis (MS) patients. The pathophysiology of this slowing is unknown. Neurovascular coupling, acute localized blood flow increases following neural activity, is essential for efficient cognition. Loss of vascular compliance along the cerebrovascular tree would result in suboptimal vasodilation, neurovascular uncoupling, and cognitive slowing. Objective: To assess vascular compliance along the cerebrovascular tree and its relationship to MS-related cognition. Methods: We tested vascular compliance along the cerebrovascular tree by dividing cerebral cortex into nested layers. MS patients and healthy controls were scanned using a dual-echo functional magnetic resonance imaging (fMRI) sequence while they periodically inhaled room air and hypercapnic gas mixture. Cerebrovascular reactivity was calculated from both cerebral blood flow (arterial) and blood-oxygen-level-dependent signal (venous) increases per unit increase in end-tidal CO2. Results: Arterial cerebrovascular reactivity changes along the cerebrovascular tree were reduced in cognitively slow MS compared to cognitively normal MS and healthy controls. These changes were fit to exponential functions, the decay constant (arterial compliance index; ACI) of which was associated with individual subjects’ reaction time and predicted reaction time after controlling for disease processes. Conclusion: Such associations suggest prospects for utility of ACI in predicting future cognitive disturbances, monitoring cognitive deficiencies and therapeutic responses, and implicates neurovascular uncoupling as a mechanism of cognitive slowing in MS.