Cerebrovascular dysfunction following mild traumatic brain injury (mTBI) is understudied relative to other microstructural injuries, especially during neurodevelopment. The blood-oxygen level dependent response was used to investigate cerebrovascular reactivity (CVR) in response to hypercapnia following pediatric mTBI (pmTBI; ages 8-18 years), as well as pseudocontinuous arterial spin labeling to measure cerebral blood flow (CBF). Data were collected ∼1-week (N = 107) and 4 months (N = 73) post-injury. Sex- and age-matched healthy controls (HC) underwent identical examinations at comparable time points (N = 110 and N = 91). Subtle clinical and cognitive deficits existed at ∼1 week that resolved for some, but not all domains at 4 months post-injury. At both visits, pmTBI showed an increased maximal fit between end-tidal CO2 regressor and the cerebrovascular response across multiple regions (primarily fronto-temporal), as well as increased latency to maximal fit in independent regions (primarily posterior). Hypoperfusion was also noted within the bilateral cerebellum. A biphasic relationship existed between CVR amplitude and age (i.e., positive until 14.5 years, negative thereafter) in both gray and white matter, but these neurodevelopment effects did not moderate injury effects. CVR metrics were not associated with post-concussive symptoms or cognitive deficits. In conclusion, cerebrovascular dysfunction may persist for up to four months following pmTBI.

Face masks are crucial parts of personal protective equipment (PPE) to reduce the risk of respiratory infections. The COVID-19 outbreak has increased healthcare workers’ use of face masks. This study aimed to evaluate changes in cerebrovascular response among healthcare workers using surgical and N95 respirator masks. 

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90 healthcare workers: 30 wearing surgical masks, 30 wearing N95 respirators, and 30 without masks were included. After two-hour of face mask use, the baseline mean flow velocity (MFV) and the mean breath-holding index (BHI) of the bilateral middle cerebral arteries (MCAs) were evaluated with transcranial Doppler ultrasound. The presence of de-novo headache was recorded. BHI values ​​below 0.69 were evaluated as a sign of impaired cerebrovascular reactivity (CVR). 

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The rate of de-novo headache was significantly higher in the N95 respirator mask group (p = 0.004). Compared to the control and surgical mask groups, the N95 respirator mask group had significantly lower values of the baseline MFV of the right MCA (p = 0.003 and p = 0.021, respectively) and mean BHI (p = 0.003 and p = 0.012, respectively). Still, only one N95 respirator mask user had a mean BHI value below 0.69.

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Surgical masks did not signi­fi­cantly affect cerebral hemodynamics. Although N95 respirator mask use significantly decreased BHI values, the CVR is still within normal limits, and the development of de-novo headache is not directly associated with low CVR. 

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Az arcmaszkok a légzőszervi fertőzések kockázatának csökkentésére alkalmazott személyes védőfelszerelés (PPE) elengedhetetlen részét képezik. A Covid-19-járvány hatására fokozódott az egészségügyi dolgozók arcmaszkhasználata. Tanulmányunk célja az volt, hogy értékeljük a sebészeti és az N95 respirátor maszkot viselő egészségügyi dolgozók körében bekövetkező cerebrovascularis válasz változásait.

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Összesen 90 egészségügyi dolgozót vontunk be a tanulmányba: 30-an sebészeti maszkot és 30-an N95 respirátor maszkot viseltek, míg 30-an nem viseltek maszkot. Kétórás maszkhasználat után trans­cranialis Doppler-ultrahanggal értékeltük a bilaterális középagyi artériák (MCA) átlagos áramlási sebességét (MFV) és átlagos légzéstartási indexét (BHI). Rögzítettük a de novo fejfájás jelenlétét. A 0,69 alatti BHI-értékeket a károsodott cerebrovascularis reaktivitás (CVR) jelének tekintettük. 

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A de novo fejfájás előfor­dulási aránya szignifikánsan magasabb volt az N95 légzőmaszkot viselő csoportban (p = 0,004). Az N95 légzőmaszkot viselő csoportban a jobb MCA átlagos áramlási sebességének kiindulási értéke (p = 0,003, illetve p = 0,021) és az átlagos BHI-értékek (p = 0,003 és p = 0,012) szignifikánsan alacsonyabbak voltak a kontroll- és a sebészeti maszkot viselő csoportok értékeihez képest. Mindazonáltal, csak egy N95 légzőmaszkot viselő személy esetében volt az átlagos BHI-érték 0,69 alatt.

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A sebészeti maszk hasz­nálata nem befolyásolta szignifikánsan a ce­rebralis hemodinamikát. Habár az N95 lég­zőmaszk használata szignifikánsan csökkentette a BHI-értékeket, a CVR-értékek továbbra is a normáltartományban voltak, és a de novo fejfájás kialakulása nem volt közvetlen összefüggésben az alacsony CVR-rel.

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OBJECTIVE: The aim of this study was to investigate whether the spatial coefficient of variation of arterial spin labeling (ASL-CoV) acquired in clinical settings can be used to estimate decreased cerebrovascular reactivity (CVR) measured with single-photon emission computed tomography (SPECT) and acetazolamide challenge in patients with atherosclerotic stenosis of intra- or extracranial arteries.
METHODS: We evaluated the data of 27 atherosclerotic stenosis patients who underwent pseudocontinuous ASL and SPECT. After spatial normalization, regional values were measured using the distributed middle cerebral artery territorial atlas of each patient. We performed comparisons, correlations, and receiver operating characteristic (ROC) curve analyses between ASL-cerebral blood blow (CBF), ASL-CoV, SPECT-CBF and SPECT-CVR.
RESULTS: Although the ASL-CBF values were positively correlated with SPECT-CBF values (r = 0.48, 95% confidence interval (CI) = 0.28-0.64), no significant difference in ASL-CBF values was detected between regions with and without decreased CVR. However, regions with decreased CVR had significantly greater ASL-CoV values than regions without decreased CVR. SPECT-CVR was negatively correlated with ASL-CoV (ρ = -0.29, 95% CI = -0.49 - -0.06). The area under the ROC curve of ASL-CoV in predicting decreased CVR (0.66, 95% CI = 0.51-0.81) was greater than that of ASL-CBF (0.51, 95% CI = 0.34-0.68). An ASL-CoV threshold value of 42% achieved a high specificity of 0.93 (sensitivity = 0.42, positive predictive value = 0.77, and negative predictive value = 0.75).
CONCLUSIONS: ASL-CoV acquired by single postlabeling delay without an acetazolamide challenge may aid in the identification of patients with decreased CVR on SPECT.

Cerebrovascular pressure reactivity plays a key role in maintaining constant cerebral blood flow. Unfortunately, this mechanism is often impaired in acute traumatic neural injury states, exposing the already injured brain to further pressure-passive insults. While there has been much work on the association between impaired cerebrovascular reactivity following moderate/severe traumatic brain injury (TBI) and worse long-term outcomes, there is yet to be a comprehensive review on the association between cerebrovascular pressure reactivity and intracranial pressure (ICP) extremes. Therefore, we conducted a systematic review of the literature for all studies presenting a quantifiable statistical association between a continuous measure of cerebrovascular pressure reactivity and ICP in a human TBI cohort. The methodology described in the Cochrane Handbook for Systematic Reviews was used. BIOSIS, Cochrane Library, EMBASE, Global Health, MEDLINE, and SCOPUS were all searched from their inceptions to March of 2023 for relevant articles. Full-length original works with a sample size of ≥10 patients with moderate/severe TBI were included in this review. Data were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A total of 16 articles were included in this review. Studies varied in population characteristics and statistical tests used. Five studies looked at transcranial Doppler-based indices and 13 looked at ICP-based indices. All but two studies were able to present a statistically significant association between cerebrovascular pressure reactivity and ICP. Based on the findings of this review, impaired reactivity seems to be associated with elevated ICP and reduced ICP waveform complexity. This relationship may allow for the calculation of patient-specific ICP thresholds, past which cerebrovascular reactivity becomes persistently deranged. However, further work is required to better understand this relationship and improve algorithmic derivation of such individualized ICP thresholds.

Pencil-beam presaturation (BeamSAT) magnetic resonance imaging (MRI) produces selective magnetic resonance angiography (MRA) images of specific arteries, including the unilateral internal carotid artery (ICA-selective MRA) or vertebral artery (VA-selective MRA). We evaluate the influence of flow pattern, visualized using BeamSAT MRI, on preoperative cerebral hemodynamic status and postoperative hyperperfusion syndrome (HPS). Patients undergoing carotid artery stenting or carotid endarterectomy were categorized into two groups to evaluate flow pattern. Patients with neither crossflow on BeamSAT MRI nor mismatch in middle cerebral artery (MCA) signal intensity between ICA-selective and conventional MRA were classified into Group I, comprising 29 patients. Group II included all other patients comprising 19 patients, who were suspected of experiencing changes in intracranial flow patterns. Cerebral blood flow and cerebrovascular reactivity (CVR) were assessed using single-photon emission computed tomography, and potential HPS symptoms were retrospectively assessed by chart review. Preoperative ipsilateral CVR was significantly lower in Group II than in Group I (18.0% ± 20.0% vs. 48.3% ± 19.5%; P < 0.0001). Group II showed significantly impaired CVR (odds ratio 17.7, 95% confidence interval 1.82-171; P = 0.013) in multivariate analysis. The partial areas under the curve of the BeamSAT logistic model (0.843) were significantly larger than those of the conventional logistic model (0.626) over the range of high sensitivity (0.6-1) (P = 0.04). The incidence of postoperative HPS symptoms was significantly higher in Group II than in Group I (8/19 vs. 1/29; P = 0.001). BeamSAT MRI may be a valuable and non-invasive tool for assessing cerebral hemodynamics and predicting postoperative HPS.

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BACKGROUND: The study investigated the effectiveness of low-frequency sampling in detecting alterations in cerebrovascular reactivity (CVR) associated with changes in intracranial pressure (ICP) in patients with traumatic brain injury (TBI) across different age groups. The primary objective was to investigate an ICP threshold that indicates a decrease in CVR as evidenced by a significant increase in the ultra-low-frequency pressure reactivity index (UL-PRx). Additionally, the study aimed to develop an age-based categorization method for patients with TBI to investigate the differences between these ICP thresholds in different age groups.
METHODS: In this retrospective analysis, data from 263 patients with TBI were prospectively collected. ICP and mean arterial pressure were extracted from the hospital database at 5-min intervals. Demographic details, clinical presentation, computed tomography scans, neurosurgical interventions, and 12-months outcome were recorded. ICP versus UL-PRx values were categorized into ICP bins and graphically represented with boxplots for each age group, illustrating how as ICP values rise, there is a bin (age-tailored ICP [AT-ICP]) beyond which UL-PRx shows a sudden increase, indicating CVR loss. Homogeneous age groups were established to obtain a consistent AT-ICP threshold. The discriminatory ability of the AT-ICP thresholds was compared with the guideline-recommended thresholds by calculating the area under the Receiver Operating Characteristic curve of the ICP-derived indices (dose above threshold, and the hourly dosage above threshold).
RESULTS: Age groups 0-5, 6-20, 21-60, 61-70, and 71-85 years were the best age subdivisions, corresponding to AT-ICP thresholds of 20, 30, 35, 25, and 30 mmHg, respectively. The AT-ICP thresholds exhibited better discriminative ability compared with the guideline-recommended thresholds.
CONCLUSIONS: The AT-ICP thresholds offer a novel approach for estimating CVR impairment and the developed method represents an alternative solution to address the age stratification issue in patients with TBI.

Introduction  Controlling the partial pressure of carbon dioxide (PaCO 2 ) is an important consideration in patients with intracranial steno-occlusive disease to avoid reductions in critical perfusion from vasoconstriction due to hypocapnia, or reductions in blood flow due to steal physiology during hypercapnia. However, the normal range for resting PCO 2 in this patient population is not known. Therefore, we investigated the variability in resting end-tidal PCO 2 (P ET CO 2 ) in patients with intracranial steno-occlusive disease and the impact of revascularization on resting P ET CO 2 in these patients. Setting and Design  Tertiary care center, retrospective chart review Materials and   Methods We collected resting P ET CO 2 values in adult patients with intracranial steno-occlusive disease who presented to our institution between January 2010 and June 2021. We also explored postrevascularization changes in resting P ET CO 2 in a subset of patients. Results  Two hundred and twenty-seven patients were included [moyamoya vasculopathy ( n  = 98) and intracranial atherosclerotic disease ( n  = 129)]. In the whole cohort, mean ± standard deviation resting P ET CO 2 was 37.8 ± 3.9 mm Hg (range: 26-47). In patients with moyamoya vasculopathy and intracranial atherosclerotic disease, resting P ET CO 2 was 38.4 ± 3.6 mm Hg (range: 28-47) and 37.4 ± 4.1 mm Hg (range: 26-46), respectively. A trend was identified suggesting increasing resting P ET CO 2 after revascularization in patients with low preoperative resting P ET CO 2 (<38 mm Hg) and decreasing resting P ET CO 2 after revascularization in patients with high preoperative resting P ET CO 2 (>38 mm Hg). Conclusion  This study demonstrates that resting P ET CO 2 in patients with intracranial steno-occlusive disease is highly variable. In some patients, there was a change in resting P ET CO 2 after a revascularization procedure.

BACKGROUND: Vascular contributions to cognitive impairment and dementia (VCID) represent a major factor in cognitive decline in older adults. The present study examined the relationship between cerebrovascular reactivity (CVR) measured by magnetic resonance imaging (MRI) and cognitive function in a multi-site study, using a predefined hypothesis.
METHODS: We conducted the study in a total of three analysis sites and 263 subjects. Each site performed an identical CVR MRI procedure using 5% carbon dioxide inhalation. A global cognitive measure of Montreal Cognitive Assessment (MoCA) and an executive function measure of item response theory (IRT) score were used as outcomes.
RESULTS: CVR and MoCA were positively associated, and this relationship was reproduced at all analysis sites. CVR was found to be positively associated with executive function.
CONCLUSIONS: The predefined hypothesis on the association between CVR and a global cognitive score was validated in three independent analysis sites, providing support for CVR as a biomarker in VCID.
CONCLUSIONS: This study measured a novel functional index of small arteries referred to as cerebrovascular reactivity (CVR). CVR was positively associated with global cognition in older adults. This finding was observed in three independent cohorts at three sites. Our statistical analysis plan was predefined before beginning data collection.

Studying brain-wide hemodynamic responses to different stimuli at high spatiotemporal resolutions can help gain new insights into the mechanisms of neuro- diseases and -disorders. Nonetheless, this task is challenging, primarily due to the complexity of neurovascular coupling, which encompasses interdependent hemodynamic parameters including cerebral blood volume (CBV), cerebral blood flow (CBF), and cerebral oxygen saturation (SO2). The current brain imaging technologies exhibit inherent limitations in resolution, sensitivity, and imaging depth, restricting their capacity to comprehensively capture the intricacies of cerebral functions. To address this, a multimodal functional ultrasound and photoacoustic (fUSPA) imaging platform is reported, which integrates ultrafast ultrasound and multispectral photoacoustic imaging methods in a compact head-mountable device, to quantitatively map individual dynamics of CBV, CBF, and SO2 as well as contrast agent enhanced brain imaging at high spatiotemporal resolutions. Following systematic characterization, the fUSPA system is applied to study brain-wide cerebrovascular reactivity (CVR) at single-vessel resolution via relative changes in CBV, CBF, and SO2 in response to hypercapnia stimulation. These results show that cortical veins and arteries exhibit differences in CVR in the stimulated state and consistent anti-correlation in CBV oscillations during the resting state, demonstrating the multiparametric fUSPA system\'s unique capabilities in investigating complex mechanisms of brain functions.