Assessment Of Cerebrovascular Reactivity Research Articles

Increased Risk of Recurrent Stroke in Symptomatic Large Vessel Disease With Impaired BOLD Cerebrovascular Reactivity.

Impaired cerebrovascular reactivity (CVR) has been correlated with recurrent ischemic stroke. However, for clinical purposes, most CVR techniques are rather complex, time-consuming, and lack validation for quantitative measurements. The recent adaptation of a standardized hypercapnic stimulus in combination with a blood-oxygenation-level-dependent (BOLD) magnetic resonance imaging signal as a surrogate for cerebral blood flow offers a potential universally comparable CVR assessment. We investigated the association between impaired BOLD-CVR and risk for recurrent ischemic events. We conducted a retrospective analysis of patients with symptomatic cerebrovascular large vessel disease who had undergone a prospective hypercapnic-challenged BOLD-CVR protocol at a single tertiary stroke referral center between June 2014 and April 2020. These patients were followed up for recurrent acute ischemic events for up to 3 years. BOLD-CVR (%BOLD signal change per mm Hg CO2) was calculated on a voxel-by-voxel basis. Impaired BOLD-CVR of the affected (ipsilateral to the vascular pathology) hemisphere was defined as an average BOLD-CVR, falling 2 SD below the mean BOLD-CVR of the right hemisphere in a healthy age-matched reference cohort (n=20). Using a multivariate Cox proportional hazards model, the association between impaired BOLD-CVR and ischemic stroke recurrence was assessed and Kaplan-Meier survival curves to visualize the acute ischemic stroke event rate. Of 130 eligible patients, 28 experienced recurrent strokes (median, 85 days, interquartile range, 5-166 days). Risk factors associated with an increased recurrent stroke rate included impaired BOLD-CVR, a history of atrial fibrillation, and heart insufficiency. After adjusting for sex, age group, and atrial fibrillation, impaired BOLD-CVR exhibited a hazard ratio of 10.73 (95% CI, 4.14-27.81; P<0.001) for recurrent ischemic stroke. Among patients with symptomatic cerebrovascular large vessel disease, those exhibiting impaired BOLD-CVR in the affected hemisphere had a 10.7-fold higher risk of recurrent ischemic stroke events compared with individuals with nonimpaired BOLD-CVR.

Cerebrovascular Reactivity Is Not Associated With Therapeutic Intensity in Adult Traumatic Brain Injury: A Validation Study.

Within traumatic brain injury (TBI) care, there is growing interest in pathophysiological markers as surrogates of disease severity, which may be used to improve and individualize care. Of these, assessment of cerebrovascular reactivity (CVR) has been extensively studied given that it is a consistent, independent factor associated with mortality and functional outcome. However, to date, the literature supports little-to-no impact of current guideline-supported therapeutic interventions on continuously measured CVR. Previous work in this area has suffered from a lack of validation studies, given the rarity of time-matched high-frequency cerebral physiology with serially recorded therapeutic interventions; thus, we undertook a validation study. Utilizing the Winnipeg Acute TBI database, we evaluated the association between daily treatment intensity levels, as measured through the therapeutic intensity level (TIL) scoring system, and continuous multi-modal-derived CVR measures. CVR measures included the intracranial pressure (ICP)-derived pressure reactivity index, pulse amplitude index, and RAC index (a correlation between the pulse amplitude of ICP and cerebral perfusion pressure), as well as the cerebral autoregulation measure of near-infrared spectroscopy-based cerebral oximetry index. These measures were also derived over a key threshold for each day and were compared to the daily total TIL measure. In summary, we could not observe any overall relationship between TIL and these CVR measures. This validates previous findings and represents only the second such analysis to date. This helps to confirm that CVR appears to remain independent of current therapeutic interventions and is a potential unique physiological target for critical care. Further work into the high-frequency relationship between critical care and CVR is required.

Near-infrared spectroscopy monitoring of neonatal cerebrovascular reactivity: where are we now?

Cerebrovascular reactivity defines the ability of the cerebral vasculature to regulate its resistance in response to both local and systemic factors to ensure an adequate cerebral blood flow to meet the metabolic demands of the brain. The increasing adoption of near-infrared spectroscopy (NIRS) for non-invasive monitoring of cerebral oxygenation and perfusion allowed investigation of the mechanisms underlying cerebrovascular reactivity in the neonatal population, confirming important associations with pathological conditions including the development of brain injury and adverse neurodevelopmental outcomes. However, the current literature on neonatal cerebrovascular reactivity is mainly still based on small, observational studies and is characterised by methodological heterogeneity; this has hindered the routine application of NIRS-based monitoring of cerebrovascular reactivity to identify infants most at risk of brain injury. This review aims (1) to provide an updated review on neonatal cerebrovascular reactivity, assessed using NIRS; (2) to identify critical points that need to be addressed with targeted research; and (3) to propose feasibility trials in order to fill the current knowledge gaps and to possibly develop a preventive or curative approach for preterm brain injury. IMPACT: NIRS monitoring has been largely applied in neonatal research to assess cerebrovascular reactivity in response to blood pressure, PaCO2 and other biochemical or metabolic factors, providing novel insights into the pathophysiological mechanisms underlying cerebral blood flow regulation. Despite these insights, the current literature shows important pitfalls that would benefit to be addressed in a series of targeted trials, proposed in the present review, in order to translate the assessment of cerebrovascular reactivity into routine monitoring in neonatal clinical practice.

Magnetic resonance imaging for cerebrovascular reactivity assessment

Purpose. To analyze the publications related to the technique of MRI mapping of cerebrovascular reactivity.Materials and methods. We have analyzed 75 publications (4 Russian, 71 foreign), published in the period from 1960 to 2021 years. More than half of these articles were published in the last ten years, with 26 studies – in the period from 2016 to 2021 years.Results. The article systematizes methods for assessing cerebrovascular reactivity and approaches to assessing cerebrovascular reactivity by MRI. The technique of non-enhanced MRI mapping of cerebrovascular reactivity with a hypercapnic challenge is described in detail; alternative vasoactive stimuli are also considered. Issues related to data processing and evaluation of research results were discussed.Conclusion. Impairment of cerebrovascular reactivity plays an important role in the pathogenesis of cerebrovascular diseases. Over the past decades, various radionuclide and ultrasound methods have been widely used to assess cerebrovascular reactivity. In recent years the interest of researchers in MRI as a method of mapping cerebrovascular reactivity has increased significantly. Noninvasiveness, safety, absence of radiation exposure, and good tolerability are the absolute advantages of MRI mapping over other methods of assessing cerebrovascular reactivity. However, the variety of methodological approaches to MRI mapping of cerebrovascular reactivity causes significant variability in the results of the study. Standardization of the procedure should be the first step toward the introduction of MRI mapping of cerebrovascular reactivity into clinical practice.

Cerebrovascular Function, Vascular Risk, and Lifestyle Patterns in Resistant Hypertension.

Impaired cerebrovascular reactivity (CVR) and blunted cerebral hemodynamic recruitment are thought to be important mechanisms linking hypertension to cerebrovascular and cognitive outcomes. Few studies have examined cardiovascular or dietary correlates of CVR among hypertensives. To delineate associations between cardiometabolic risk, diet, and cerebrovascular functioning among individuals with resistant hypertension from the TRIUMPH trial (n = 140). CVR was assessed by examining changes in tissue oxygenation (tissue oxygenation index [TOI] and oxygenated hemoglobin [HBO2]) using functional near-infrared spectroscopy (fNIRS) during a breath holding test, a standardized CVR assessment to elicit a hypercapnic response. Participants also underwent fNIRS during three cognitive challenge tasks. Vascular function was assessed by measurement of brachial artery flow-mediated dilation and hyperemic flow response. Cardiometabolic fitness was assessed from peak VO2 on an exercise treadmill test and body mass index. Dietary patterns were quantified using the DASH eating score. Cognitive function was assessed using a 45-minute test battery assessing Executive Function, Processing Speed, and Memory. Greater levels fitness (B = 0.30, p = 0.011), DASH compliance (B = 0.19, p = 0.045), and lower obesity (B = -0.30, p = 0.004), associated with greater changes in TOI, whereas greater flow-mediated dilation (B = 0.19, p = 0.031) and lower stroke risk (B = -0.19, p = 0.049) associated with greater HBO2. Similar associations were found for cerebral hemodynamic recruitment, and associations between CVR and cognition were moderated by duration of hypertension. Impaired CVR elevated cardiometabolic risk, obesity, vascular function, and fitness among hypertensives.

Study of cerebrovascular reactivity to hypercapnia by imaging photoplethysmography to develop a method for intraoperative assessment of the brain functional reserve.

Intraoperative assessment of cerebrovascular reactivity is a relevant problem of neurosurgery. To assess the functional reserve of cerebral blood flow, we suggest using imaging photoplethysmography for measuring changes in cortical perfusion caused by CO2 inhalation. Feasibility of the technique was demonstrated in three groups of anesthetized rats (n=21) with opened and closed cranial windows. Our study for the first time revealed that the hemodynamic response to hypercapnia strongly depends on the cranial state. However, it was shown that regardless of the direction of changes in local and systemic hemodynamics, the ratio of normalized changes in arterial blood pressure and cortical perfusion could be used as a measure of the cerebrovascular functional reserve.

Transcranial color-coded duplex sonography assessment of cerebrovascular reactivity to carbon dioxide: an interventional study

BackgroundThe investigation of CO2 reactivity (CO2-CVR) is used in the setting of, e.g., traumatic brain injury (TBI). Transcranial color-coded duplex sonography (TCCD) is a promising bedside tool for monitoring cerebral hemodynamics. This study used TCCD to investigate CO2-CVR in volunteers, in sedated and mechanically ventilated patients without TBI and in sedated and mechanically ventilated patients in the acute phase after TBI.MethodsThis interventional investigation was performed between March 2013 and February 2016 at the surgical ICU of the University Hospital of Zurich. Ten volunteers (group 1), ten sedated and mechanically ventilated patients (group 2), and ten patients in the acute phase (12–36 h) after severe TBI (group 3) were included. CO2-CVR to moderate hyperventilation (∆ CO2 -5.5 mmHg) was assessed by TCCD.ResultsCO2-CVR was 2.14 (1.20–2.70) %/mmHg in group 1, 2.03 (0.15–3.98) %/mmHg in group 2, and 3.32 (1.18–4.48)%/mmHg in group 3, without significant differences among groups.ConclusionOur data did not yield evidence for altered CO2-CVR in the early phase after TBI examined by TCCD.Trial registrationPart of this trial was performed as preparation for the interventional trial in TBI patients (clinicaltrials.gov NCT03822026, 30.01.2019, retrospectively registered).

Arterial Spin Labeling Imaging Assessment of Cerebrovascular Reactivity in Hypertensive Small Vessel Disease.

Objective: Cerebrovascular reactivity (CVR) represents the phenomenon where cerebral vessels dilate or constrict in response to vasoactive stimuli. CVR impairment may contribute to brain injury due to cerebral small vessel disease (SVD). We aimed to determine the CVR in hypertensive intracerebral hemorrhage (ICH) and to identify its vascular dysfunction.Methods: A total of 21 patients with spontaneous hypertensive ICH (strictly deep or mixed deep and lobar hemorrhages, mean age 62.5 ± 11.3 years) and 10 control subjects (mean age 66.1 ± 6.0 years) were enrolled for CVR measurement at least 3 months after the symptomatic ICH event. Each participant underwent a brain MRI study, and CVR was calculated as the cerebral blood flow (CBF) reduction using arterial spin labeling (ASL) between baseline and 10 min after an intravenous dipyridamole injection (0.57 mg/kg). Traditional MRI markers for SVD were also evaluated, including cerebral microbleed, white matter hyperintensity, lacune, and MRI-visible enlarged perivascular space, which were used to determine the total small vessel disease score.Results: Compared to control subjects, hypertensive ICH patients showed reduced CVR in the basal ganglia (CBF reduction 22.4 ± 22.7% vs. 41.7 ± 18.3, p = 0.026), the frontal lobe (15.1 ± 11.9 vs. 26.6 ± 9.9, p = 0.013), and the temporal lobe (14.7 ± 11.1 vs. 26.2 ± 10.0, p = 0.010). These differences remained significant in multivariable models after adjusting for age and sex. Within ICH groups, the CBF reduction in the basal ganglia was significantly correlated with the total small vessel disease score (R = 0.58, p = 0.006), but not with individual MRI markers.Conclusion: Patients with advanced hypertensive SVD demonstrated impaired vasoconstriction after dipyridamole challenge in the basal ganglia and the frontal and temporal lobes. Our findings provide safe approaches for whole-brain CVR mapping in SVD and identify a potential physiological basis for vascular dysfunction in hypertensive SVD.

The Relationship Between Cognition and Cerebrovascular Reactivity: Implications for Task-Based fMRI

Elucidating the brain regions and networks associated with cognitive processes has been the mainstay of task-based fMRI, under the assumption that BOLD signals are uncompromised by vascular function. This is despite the plethora of research highlighting BOLD modulations due to vascular changes induced by disease, drugs, and aging. On the other hand, BOLD fMRI-based assessment of cerebrovascular reactivity (CVR) is often used as an indicator of the brain's vascular health and has been shown to be strongly associated with cognitive function. This review paper considers the relationship between BOLD-based assessments of CVR, cognition and task-based fMRI. How the BOLD response reflects both CVR and neural activity, and how findings of altered CVR in disease and in normal physiology are associated with cognition and BOLD signal changes are discussed. These are pertinent considerations for fMRI applications aiming to understand the biological basis of cognition. Therefore, a discussion of how the acquisition of BOLD-based CVR can enhance our ability to map human brain function, with limitations and potential future directions, is presented.

The value of assessing cerebrovascular reactivity in hypertension and comorbid pathology

The review presents the rationale for the importance of studies on the reactivity of cerebral vessels, the classification of cerebrovascular reactivity (CVR) and the threshold values of quantitative indicators of the reserve phase and autoregulation of cerebral blood flow in healthy volunteers. Features of CVR in hypertension are described depending on the clinical course, daily blood pressure profile, the presence of comorbid pathology, the treatment approaches in treatment CVR disorders. We discuss the evidence-based data on the role of CVR assessment in diagnosing latent cerebral circulation insufficiency, prediction of cerebrovascular complications, monitoring the effectiveness and safety of drug and devise-based therapy of hypertension associated with abnormal CVR.

Cerebrovascular reactivity measured in awake mice using diffuse correlation spectroscopy.

.Significance: Cerebrovascular reactivity (CVR), defined as the ability of the cerebral vasculature to dilate or constrict in response to a vasoactive stimulus, is an important indicator of the brain’s vascular health. However, mechanisms of cerebrovascular dysregulation are poorly understood, and no effective treatment strategies for impaired CVR exist. Preclinical murine models provide an excellent platform for interrogating mechanisms underlying CVR dysregulation and determining novel therapeutics that restore impaired CVR. However, quantification of CVR in mice is challenging.Aim: We present means of assessing CVR in awake mice using intraperitoneal injection of acetazolamide (ACZ) combined with continuous monitoring of cerebral blood flow.Approach: Measurements of cerebral blood flow were made with a minimally invasive diffuse correlation spectroscopy sensor that was secured to an optical window glued to the intact skull. Two source–detector separations (3 and 4.5 mm) per hemisphere were used to probe different depths. CVR was quantified as the relative increase in blood flow due to ACZ. CVR was assessed once daily for 5 days in 5 mice.Results: We found that CVR and the response half-time were remarkably similar across hemispheres and across 3- versus 4.5-mm separations, suggesting a homogenous, whole brain response to ACZ. Mean(std) intra- and intermouse coefficients of variations were 15(9)% and 19(10)%, respectively, for global CVR and 24(15)% and 27(11)%, respectively, for global response half-time.Conclusion: In sum, we report a repeatable method of measuring CVR in free-behaving mice which can be used to screen for impairments with disease and to track changes in CVR with therapeutic interventions.

Cerebrovascular Reactivity Assessment during Carbon Dioxide Inhalation Using SPECT

Background: Perfusion single-photon emission computed tomography (SPECT) using an acetazolamide is an important clinical tool used to assess cerebrovascular reactivity (CVR) in patients, but its use has been limited to clinical diagnostics. This study aimed to preliminarily evaluate the feasibility of perfusion SPECT using carbon dioxide (CO2). Methods: Ten healthy subjects participated in two consecutive SPECT scans using CO2 inhalation. To evaluate brain perfusion after preprocessing, the voxel-by-voxel CVR values were averaged in 13 subgroup regions of interest (ROIs) based on a template. Subsequently, averaged CVR values of each ROI were analyzed based on both cerebellar hemispheres. Results: CVR values in the eight subgroup ROIs, which included vermis, both insula/cingulate, and frontal cortices, showed significant changes (p &lt; 0.05). CVR values were higher in vermis and right insula/cingulate by 3.34% and 3.15%, respectively. Conclusions: This study showed that quantitative SPECT with CO2 inhalation could be used to evaluate the voxel-based CVR in healthy subjects, which could be beneficial for elucidating induced hypercapnic states and for longitudinally investigating the healthy aging in brain vessels. Furthermore, the cerebrovascular hemodynamic parameters induced by CO2 could play an important role as a biomarker to evaluate treatment progress in patients with cerebrovascular disease.

Cerebrovascular Reactivity Mapping Without Gas Challenges: A Methodological Guide.

Cerebrovascular reactivity (CVR) is defined as the ability of vessels to alter their caliber in response to vasoactive factors, by means of dilating or constricting, in order to increase or decrease regional cerebral blood flow (CBF). Importantly, CVR may provide a sensitive biomarker for pathologies where vasculature is compromised. Furthermore, the spatiotemporal dynamics of CVR observed in healthy subjects, reflecting regional differences in cerebral vascular tone and response, may also be important in functional MRI studies based on neurovascular coupling mechanisms. Assessment of CVR is usually based on the use of a vasoactive stimulus combined with a CBF measurement technique. Although transcranial Doppler ultrasound has been frequently used to obtain global flow velocity measurements, MRI techniques are being increasingly employed for obtaining CBF maps. For the vasoactive stimulus, vasodilatory hypercapnia is usually induced through the manipulation of respiratory gases, including the inhalation of increased concentrations of carbon dioxide. However, most of these methods require an additional apparatus and complex setups, which not only may not be well-tolerated by some populations but are also not widely available. For these reasons, strategies based on voluntary breathing fluctuations without the need for external gas challenges have been proposed. These include the task-based methodologies of breath holding and paced deep breathing, as well as a new generation of methods based on spontaneous breathing fluctuations during resting-state. Despite the multitude of alternatives to gas challenges, existing literature lacks definitive conclusions regarding the best practices for the vasoactive modulation and associated analysis protocols. In this work, we perform an extensive review of CVR mapping techniques based on MRI and CO2 variations without gas challenges, focusing on the methodological aspects of the breathing protocols and corresponding data analysis. Finally, we outline a set of practical guidelines based on generally accepted practices and available data, extending previous reports and encouraging the wider application of CVR mapping methodologies in both clinical and academic MRI settings.

A Promising Subject-Level Classification Model for Acute Concussion Based on Cerebrovascular Reactivity Metrics

Concussion imaging research has primarily focused on neuronal disruption with lesser emphasis directed toward vascular dysfunction. However, blood flow metrics may be more sensitive than measures of neuronal integrity. Vascular dysfunction can be assessed by measuring cerebrovascular reactivity (CVR)-the change in cerebral blood flow per unit change in vasodilatory stimulus. CVR metrics, including speed and magnitude of flow responses to a standardized well-controlled vasoactive stimulus, are potentially useful for assessing individual subjects following concussion given that blood flow dysregulation is known to occur with traumatic brain injury. We assessed changes in CVR metrics to a standardized vasodilatory stimulus during the acute phase of concussion. Using a case control design, 20 concussed participants and 20 healthy controls (HCs) underwent CVR assessment measuring blood oxygen-level dependent (BOLD) magnetic resonance imaging using precise changes in end-tidal partial pressure of CO2 (PETCO2). Metrics were calculated for the whole brain, gray matter (GM), and white matter (WM) using sex-stratification. A leave-one-out receiver operating characteristic (ROC) analysis classified concussed from HCs based on CVR metrics. CVR magnitude was greater and speed of response faster in concussed participants relative to HCs, with WM showing higher classification accuracy compared with GM. ROC analysis for WM-CVR metrics revealed an area under the curve of 0.94 in males and 0.90 in females for speed and magnitude of response respectively. These greater than normal responses to a vasodilatory stimulus warrant further investigation to compare the predictive ability of CVR metrics against structural injury metrics for diagnosis and prognosis in acute concussion.

Carotid occlusion: Impact of cerebral hemodynamic impairment on cognitive performances.

The aim of this study was to investigate whether the presence of carotid artery occlusion (CO) may be associated with different cognitive performances in relation to the side of the occlusion and its hemodynamic consequences. During a 12-month period, 61 asymptomatic patients, 32 with right and 29 with left CO, were enrolled. Each patient underwent an assessment of cerebrovascular reactivity (CVR) to hypercapnia with transcranial Doppler (TCD) ultrasonography using the breath-holding index (BHI). Neuropsychological assessment evaluating performances of the hemisphere ipsilateral to CO were administered at entry (T0 ) and then repeated after 2 years (T1 ). Scores obtained at colored progressive matrices (CPM) and Rey Complex Figure Copy Test were significantly lower at T0 in patients with reduced BHI values ipsilateral to CO. Multivariate models showed that reduced BHI values were also associated to a significant decrease from T0 to T1 in scores obtained for CPM and Categorical Verbal Fluency tests, respectively, in patients with right (P = 0.002) or left CO (P = 0.004). These findings suggest that hemodynamic alterations could be involved in the reduction in cognitive function regulated by the hemisphere ipsilateral to CO. The assessment of CVR with TCD ultrasonography may be a reliable approach for the individuation of asymptomatic patients with CO at increased risk of cognitive deterioration.

Integrated assessment of cerebral blood flow and cerebrovascular reactivity based on functional tests data in patients with Parkinson’s disease and vascular pathology

Objective. To evaluate cerebral blood flow parameters and cerebrovascular reactivity indices based on data of functional tests in patients with Parkinson’s disease (PD) and vascular pathology.Material and Methods. A total of 148 people were examined, divided into 4 groups: (1) main group comprised 24 patients with idiopathic PD; (2) comparison group 1 included 21 patients with vascular parkinsonism; (3) comparison group 2 included 26 patients with a diagnosis of chronic cerebral ischemia of severity degree 2 with no signs of parkinsonism; and (4) comparison group 3 included 77 patients with PD and cerebrovascular disease. All patients received transcranial duplex scanning of cerebral blood vessels (TCD) through the temporal window (Toshiba Aplio 500, Japan, 2–2.5 MHz sector probe) using standard protocols for the assessment of blood flow velocity characteristics. An assessment of cerebrovascular reactivity (reserve) was performed using the diagnostic and treatment complex “Carbonic”. The range of cerebrovascular and vasomotor hypercapnia reactivity to hypercapnia was evaluated in the “Testing of cerebrovascular reactivity” mode.Results. A comprehensive study of cerebral blood flow parameters using functional tests suggested that the absence of changes in the cerebrovascular reactivity index (VRhyperCO2 ) observed in patients with idiopathic PD may be considered a differential diagnostic criterion for Parkinson’s disease and cerebrovascular pathology with Parkinson’s symptoms.

Interpretive Complications Underlying Cerebrovascular Response To Hypercapnia; Significance Of The Central Respiratory Chemoreflex Transient

Cerebral blood flow (CBF) is sensitive to changes in the arterial partial pressure of carbon dioxide (CO2) with cerebrovascular reactivity an established risk factor for stroke and neurodegenerative disease. However, its interpretation can be complicated given subtle differences in cerebrovascular and central respiratory chemoreflex response transients. PURPOSE: To examine to what extent exposure time to CO2 influences CBF response. METHOD: We measured CBF response to hypercapnia (FICO2 = 5%) in five healthy participants for 10 min in the supine position. End-tidal partial pressures of CO2 (PETCO2), minute ventilation (VE), and middle cerebral artery blood velocity (MCAv) were assessed during both the early (3~4 min) and late phases (9~10 min) of exposure. RESULT: We observed elevated VE larger during the late compared to the early phase of exposure (from 11 ± 2 to 29 ± 8 vs. 23 ± 4 L/min, P = 0.047) despite no differences in PETCO2 (P = 0.304). The corresponding increase in MCAv during the late phase was suppressed compared to the early phase (from 48 ± 11 to 58 ± 14 vs. 63 ± 13 cm/sec, P = 0.029). Thus, the response of CBF to change in PETCO2 at late phase was lower than that of early phase (1.1 ± 1 %/mmHg vs. 1.7 ± 1 %/mmHg, P=0.07). CONCLUSION: These findings highlight the importance of considering the central respiratory chemoreflex transient during the clinical assessment of cerebrovascular reactivity.

The influence of age and sex on cerebrovascular reactivity and ventilatory response to hypercapnia in children and adults.

What is the central question of this study? In this study, we investigated intracranial cerebrovascular and ventilatory reactivity to 6% CO2 in children and adults and explored dynamic ventilatory and cerebrovascular onset responses. What is the main finding and its importance? We showed that cerebrovascular reactivity was similar in children and adults, but the intracranial blood velocity onset response was markedly attenuated in children. Sex differences were apparent, with greater increases in intracranial blood velocity in females and lower ventilatory reactivity in adult females. Our study confirms the importance of investigating dynamic onset responses when assessing the influence of development on cerebrovascular regulation. The purpose of this study was to compare the integrated intracranial cerebrovascular reactivity (CVR) and hypercapnic ventilatory response between children and adults and to explore the dynamic response of the middle cerebral artery mean velocity (MCAV ). Children (n=20; 9.9±0.7years of age) and adults (n=21; 24.4±2.0years of age) completed assessment of CVR over 240s using a fixed fraction of inspired CO2 (0.06). Baseline MCAV was higher in the adult females compared with the males (P≤0.05). The MCAV was greater in female children compared with male children (P≤0.05) and in female adults compared with male adults (P≤0.05) with hypercapnia. Relative CVR was similar in children and adults (3.71±1.06 versus 4.12±1.32%mmHg-1 ; P=0.098), with absolute CVR being higher in adult females than males (3.27±0.86 versus 2.53±0.70cms-1 mmHg-1 ; P≤0.001). Likewise, the hypercapnic ventilatory response did not differ between the children and adults (1.89±1.00 versus 1.77±1.34lmin-1 mmHg-1 ; P=0.597), but was lower in adult females than males (1.815±0.37 versus 2.33±1.66lmin-1 mmHg-1 ; P≤0.05). The heart rate response to hypercapnia was greater in children than in adults (P=0.001). A monoexponential regression model was used to characterize the dynamic onset, consisting of a delay term, amplitude and time constant (τ). The results revealed that MCAV τ was faster in adults than in children (34±18versus 74±28s; P=0.001). Our study provides new insight into the impact of age and sex on CVR and the dynamic response of the MCAV to hypercapnia.

Continuous and entirely non-invasive method for cerebrovascular reactivity assessment: technique and implications.

Continuous cerebrovascular reactivity assessment in traumatic brain injury (TBI) has been limited by the need for invasive monitoring of either cerebral physiology or arterial blood pressure (ABP). This restricts the application of continuous measures to the acute phase of care, typically in the intensive care unit. It remains unknown if ongoing impairment of cerebrovascular reactivity occurs in the subacute and long-term phase, and if it drives ongoing morbidity in TBI. We describe an entirely non-invasive method for continuous assessment of cerebrovascular reactivity. We describe the technique for entirely non-invasive continuous assessment of cerebrovascular reactivity utilizing near-infrared spectroscopy (NIRS) and robotic transcranial Doppler (rTCD) technology, with details provided for NIRS. Recent advances in continuous high-frequency non-invasive ABP measurement, combined with NIRS or rTCD, can be employed to derive continuous and entirely non-invasive cerebrovascular reactivity metrics. Such non-invasive measures can be obtained during any aspect of patient care post-TBI, and even during outpatient follow-up, avoiding classical intermittent techniques and costly neuroimaging based metrics obtained only at specialized centers. This combination of technology and signal analytic techniques creates avenues for future investigation of the long-term consequences of cerebrovascular reactivity, integrating high-frequency non-invasive cerebral physiology, neuroimaging, proteomics and clinical phenotype at various stages post-injury.

Predicting Ischemic Risk Using Blood Oxygen Level-Dependent MRI in Children with Moyamoya.

Moyamoya is a progressive steno-occlusive arteriopathy. MR imaging assessment of cerebrovascular reactivity can be performed by measuring the blood oxygen level-dependent cerebrovascular reactivity response to vasoactive stimuli. Our objective was to determine whether negative blood oxygen level-dependent cerebrovascular reactivity status is predictive of ischemic events in childhood moyamoya. We conducted a retrospective study of a consecutive cohort of children with moyamoya who underwent assessment of blood oxygen level-dependent cerebrovascular reactivity. The charts of patients with written informed consent were reviewed for the occurrence of arterial ischemic stroke, transient ischemic attack, or silent infarcts. We used logistic regression to calculate the OR and 95% CI for ischemic events based on steal status. Hazard ratios for ischemic events based on age at blood oxygen level-dependent cerebrovascular reactivity imaging, sex, and moyamoya etiology were calculated using Cox hazards models. Thirty-seven children (21 female; median age, 10.7 years; interquartile range, 7.5-14.7 years) were followed for a median of 28.8 months (interquartile range, 13.7-84.1 months). Eleven (30%) had ischemic events, 82% of which were TIA without infarcts. Steal was present in 15 of 16 (93.8%) hemispheres in which ischemic events occurred versus 25 of 58 (43.1%) ischemic-free hemispheres (OR = 19.8; 95% CI, 2.5-160; P = .005). Children with idiopathic moyamoya were at significantly greater risk of ischemic events (hazard ratio, 3.71; 95% CI, 1.1-12.8; P = .037). Our study demonstrates that idiopathic moyamoya and the presence of steal are independently associated with ischemic events. The use of blood oxygen level-dependent cerebrovascular reactivity could potentially assist in the selection of patients for revascularization surgery and the direction of therapy in children with moyamoya.