Cerebrovascular Reactivity Measurements Research Articles

120 Outcome Related Thresholds of Near Infrared Spectroscopy Based Cerebrovascular Reactivity Metrics in Moderate Severe TBI: A Canadian High Resolution-TBI (CAHR-TBI) Cohort Study

INTRODUCTION: Dysfunctional cerebrovascular reactivity (CVR)/autoregulation contributes to secondary injury following traumatic brain injury (TBI). Currently, monitoring of CVR relies on intracranial pressure (ICP) monitoring and has known thresholds at which outcomes worsen. Interest has shifted to less invasive near infrared spectroscopic (NIRS) regional cerebral oxygen saturation (rSO2) based measures of CVR. However, threshold levels at which outcomes worsen have not yet been determined for these indices. METHODS: A retrospective multi-institutional cohort study utilizing the CAnadian High Resolution TBI (CAHR-TBI) Research Collaborative database was performed. The cohort included TBI patients with ICP, arterial blood pressure (ABP), and rSO2 monitoring treated in adult intensive care units (ICU). COx (using rSO2 and cerebral perfusion pressure) as well as COx_a (using rSO2 and ABP) were calculated for each subject as the rSO2 based indices of CVR. 2 x 2 tables were created grouping patients by alive/dead and favorable/unfavorable outcomes at various thresholds of COx and COx_a as well as rSO2 itself. Chi-square values were calculated and the threshold producing the highest value was identified as providing the best discriminative value. RESULTS: A total of 129 patients were included. For both COx and COx_a an optimal threshold value of 0.2 was identified for both survival (χ2 = 9.57, p = 0.0020; χ2 = 13.04, p = 0.0003 respectively) and favorable outcomes (χ2 = 5.98, p = 0.0145; χ2 = 8.94, p = 0.0028 respectively) with values above this associated with worse outcomes. Notably, there was no identifiable threshold for raw rSO2 values at which outcomes were identified to worsen. CONCLUSIONS: In this multi-institutional cohort study, COx and COx_a were found to have a uniform threshold of 0.2, above which clinical outcomes worsened. This study lays the groundwork to transition to less invasive means of continuously measuring CVR.

Advances in Cerebral Small Vessel Disease: Sandra E. Black Lecture to the Canadian Neurological Sciences Federation.

Cerebral small vessel diseases (CSVDs) are among the most common age-related pathologies of the brain. Arteriolosclerosis and cerebral amyloid angiopathy (CAA) are the most common CSVDs. In addition to causing stroke and dementia, CSVDs can have diverse covert radiological manifestations on computed tomography and magnetic resonance imaging including lacunes, T2-weighted white matter hyperintensities, increased density of visible perivascular spaces, microbleeds and cortical superficial siderosis. Because they cannot be visualized directly, research on the pathophysiology of CSVD has been difficult. However, advances in quantitative imaging methods, including physiological imaging such as measurement of cerebrovascular reactivity and increased vascular permeability, are beginning to allow investigation of the early effects of CSVD in living people. Furthermore, genomics, metabolomics and proteomics have the potential to illuminate previously unrecognized pathways to CSVD that could be important targets for new clinical trials.

Abstract TP139: Revascularization Improves Vascular Hemodynamics in Pediatric Moyamoya Patients

Introduction: Cerebrovascular reactivity (CVR) reflects the change in cerebral blood flow (CBF) in response to vasodilation. Studies have demonstrated that impaired CVR was associated with a higher risk of acute stroke in patients with intracranial vasculopathy and that bypass surgeries can reduce the risk of strokes. Moyamoya disease is a progress cerebrovascular disorder that begins during childhood. Arterial spin labeling (ASL) is a quantitative MRI technique for non-invasive CBF and CVR measurement; ASL with multiple delays can also measure arterial transit time (ATT). Here, we compare the CBF, CVR, and ATT in pediatric Moyamoya patients before and after bypass using multi-delay ASL. Hypothesis: CVR will increase significantly after bypass surgeries. Methods: Imaging data were acquired from 22 Moyamoya patients (11 months - 18 years, 14 females) using a 3T MRI system. All patients had unilateral or bilateral occlusion at ACA, MCA and/or PCA. Multi-delay ASL data (7 delays) were acquired at baseline and 15 minutes after acetazolamide administration. CBF and ATT were computed using the general kinetic model. CVR was computed as the percentage of CBF change compared with baseline CBF. Flow territories (right and left ACA, MCA, and PCA) were defined using the Harvard-Oxford atlases. Paired t-tests were conducted to compare the mean CVR, CBF, and ATT changes before and after bypass surgeries. Results: The figure shows the hemodynamic maps of an example patients. Overall, CVR and CBF in the affected regions increased after bypass; ATT in these regions decreased after bypass. For this cohort, our analysis showed that CVR of the affected regions increased significantly by 68% and ATT reduced significantly by 10.7% measured by multi-delay ASL, implying improved circulation and lower risk for strokes. Discussion: Multi-delay ASL was effective to detect improved CVR and reduced ATT in pediatric Moyamoya patients after bypass surgeries.

Baseline cerebrovascular reactivity predicts longitudinal enlarged perivascular space burden in the basal ganglia among cognitively normal older adults

AbstractBackgroundIncreasing evidence suggests that enlarged perivascular spaces (ePVS) on magnetic resonance images (MRIs) are associated with cognitive dysfunction in aging. However, the etiology of ePVS remains unknown. Here we tested the possibility that cerebrovascular dysfunction, as assessed by an MRI measure of cerebrovascular reactivity (CVR), may contribute to ePVS development.Method79 cognitively normal, older adults (46 women, age range 60‐84) were recruited to undergo baseline MRI scanning and follow‐up scanning approximately 2.5 years later. Of the 79 participants scanned at baseline, 50 returned for follow‐up. Participants were scanned on a 3T Siemens Prisma scanner with a 64‐channel head coil. All scanning methods were identical across time points and included collection of T1‐weighted, T2‐weighted FLAIR, and quantitative susceptibility mapping (QSM) images. Cerebrovascular dysfunction was assessed using CVR, a measure of the ability of cerebrovasculature to dilate in response to vasoactive stimuli. Participants underwent blocked administration of breathing either room air or hypercapnic gas, while blood‐oxygen‐level‐dependent (BOLD) functional magnetic resonance imaging (fMRI) was performed. CVR values were computed for baseline scans in specific regions by dividing change in BOLD signal by change in end‐tidal CO2. Baseline and follow‐up ePVS counts were performed by a single rater who was blinded to participant demographics. ePVS were individually and manually counted using STRIVE criteria in a representative, axial slice of the basal ganglia (BGePVS) and centrum semiovale (CSePVS).ResultBGePVS and CSePVS significantly increased during the follow‐up period. Mixed effects models indicated that baseline basal ganglia CVR values significantly predicted increased BGePVS counts after controlling for age, sex, education, and time point (p = <0.001). Furthermore, this effect was present bilaterally: Baseline CVR in the left hemisphere predicted increased BGePVS in the left hemisphere (p = <0.001) and baseline CVR in the right hemisphere predicted increased BGePVS in the right hemisphere (p = <0.001). Conversely, there was no longitudinal relationship between baseline CVR and increased CSePVS (p = 0.449).ConclusionThese results demonstrate that low baseline CVR is a risk factor for later development of ePVS. Localization of these findings to the basal ganglia suggests that it is particularly vulnerable to cerebrovascular dysfunction.

Progressive Cerebrovascular Reactivity Reduction Occurs in Parkinson's Disease: A Longitudinal Study.

The change of microvascular function over the course of Parkinson's disease (PD) remains unclear. We aimed to ascertain regional cerebrovascular reactivity (CVR) changes in the patients with PD at baseline (V0) and during a 2-year follow-up period (V1). We further investigated whether alterations in CVR were linked to cognitive decline and brain functional connectivity (FC). We recruited 90 PD patients and 51 matched healthy controls (HCs). PD patients underwent clinical evaluations, neuropsychological assessments, and magnetic resonance (MR) scanning at V0 and V1, whereas HCs completed neuropsychological assessments and MR at baseline. The analysis included evaluating CVR and FC maps derived from resting-state functional magnetic resonance imaging and investigating CVR measurement reproducibility. Compared with HCs, CVR reduction in left inferior occipital gyrus and right superior temporal cortex at V0 persisted at V1, with larger clusters. Longitudinal reduction in CVR of the left posterior cingulate cortex correlated with decline in Trail Making Test B performance within PD patients. Reproducibility validation further confirmed these findings. In addition, the results also showed that there was a tendency for FC to be weakened from posterior to anterior with the progression of the disease. Microvascular dysfunction might be involved in disease progression, subsequently weaken brain FC, and partly contribute to executive function deficits in early PD. © 2023 International Parkinson and Movement Disorder Society.

Abstract 12782: Serial Cerebral Hemodynamic Monitoring in Patients With HeartMate 3 Left Ventricular Assist Devices

Introduction: Left ventricular assist device (LVAD) implantation improves cardiopulmonary hemodynamics and vital organ perfusion, but cerebral blood flow is not routinely measured despite the clinical significance of neurologic complications. We aimed to quantify the short and long-term impact of LVAD on cerebral hemodynamics by serially monitoring patients before and after LVAD implantation. Hypothesis: We hypothesize that LVAD implantation improves dynamic measures of cerebral blood flow: cerebral autoregulation (CA) and cerebrovascular reactivity (CVR). Methods: 20 patients with advanced heart failure with planned LVAD implantation participated in serial cerebral hemodynamic monitoring: (1) <72-hours pre-implant, (2) <72-hours post-implant, (3) 14-days post-implant, and (4) 90-days post-implant. Cerebral blood flow velocity was measured at each visit by transcranial Doppler. CA, quantified by Mx index , characterized the relationship between blood pressure and cerebral blood flow. CVR quantified the cerebral hemodynamic reserve, based on the response to a hypercapnic stimulus (5% inhaled CO 2 ). Results: As compared to the pre-implant assessment, no change was noted in absolute cerebral blood flow velocity ( Figure 1a ). However, CA improved immediately post-implant (0.47 vs 0.26; p=0.0007), at 14-days (0.47 vs 0.33; p=0.007), and at 90-days (0.47 vs 0.31; p=0.03), Figure 1b . Pre-implant CVR was not significantly altered at 14-days (1.14 vs 1.70, p=0.25) but improved at 90-days (1.14 vs 2.11, p=0.03), Figure 1c . Conclusions: Despite no change in cerebral blood flow velocity, LVAD implantation improves dynamic measures of cerebral blood flow, CA and CVR. Future studies should include longer follow-up and correlate post-LVAD cerebral hemodynamics with clinically meaningful neurologic endpoints such as stroke and cognitive decline.

25 Delayed Cerebrovascular Response in Parkinson's Disease

Objective:Cardiovascular risk factors and white matter hyperintensities predict the progression and severity of cognitive symptoms in PD. While controversial, emerging evidence suggests that cerebrovascular dysfunction is an etiological driver of protein aggregation in neurodegenerative conditions, highlighting a need to understand how cerebrovascular function impacts cognitive function in PD. MRI cerebrovascular reactivity (CVR) paradigms provide an opportunity to measure the ability of the cerebral vessels to dilate or constrict in response to challenges. The current study evaluates whether whole brain CVR measures, degree of response (fit) and delay differ in PD with normal cognition (PD-NC) and PD with mild cognitive impairment (PD-MCI) relative to healthy controls (HC). Additionally, we evaluate if these metrics are associated with cognitive performance.Participants and Methods:8 PD-NC, 11 PD-MCI and 11 age and sex-matched healthy controls (HC) participated in the study. PD participants were diagnosed with MCI based on the Movement Disorders Society Task force, Level II assessment (comprehensive assessment). Participants were asked to inhale gas enriched in CO2 to elicit a vasodilatory response while undergoing bold oxygen level-dependent magnetic resonance image (MRI). Whole brain fit to an end-tidal CO2 regressor and delay were used to quantify CVR in each participant. An analysis of covariance (ANCOVA) was used to evaluate group differences between HC, PD-NC, and PD-MCI in the whole brain fit and delay CVR measures accounting for age, sex, and education. Multiple regressions were conducted for each cognitive variable with whole brain fit and delay as the dependent variables adjusting for age, sex, and education.Results:A significant main effect of group was observed for whole brain CVR latency (F(2, 23) = 4.227; p = 0.027). Post hoc tests were not significant, though indicated a trend that PD-NC (18.14 ±1.94) and PD-MCI (18.15 ± 1.55) patients exhibited longer delays relative to HC (15.84 ± 2.37). Regression results indicated limited relationships between CVR measures and cognitive functioning.Conclusions:PD patients (PD-NC and PD-MCI) exhibited longer CVR delays relative to HC, suggesting a delayed vasodilatory response in PD. Examination of the association between CVR metrics and cognition were not significant, though these results should be interpreted with caution given the small sample size.

Cerebrovascular Pressure Reactivity Measures: Index Comparison and Clinical Outcome in Patients With Traumatic Brain Injury Treated According to an Intracranial Pressure-Focused Management: Rejection of the Null Hypothesis.

The aim was to investigate whether the pressure reactivity indices PRx, long-PRx (L-PRx), and pressure reactivity (PR) are interchangeable as measures of vascular reactivity, and whether they correlate with clinical outcome when an intracranial pressure (ICP)-targeted treatment regimen is applied in patients with traumatic brain injury (TBI). Patients with TBI (n = 29) that arrived at the hospital within 24 h of injury were included. PRx and L-PRx were derived from Pearson correlations between mean arterial pressure (MAP) and ICP over a short- and long-time interval. PR was the regression coefficient between the hourly mean values of ICP and MAP. Indices were compared to each other, parameters at admission, and outcome assessed by the extended Glasgow Outcome Scale-Extended (GOSE) at 6 and 12 months. PRx and L-PRx had the strongest correlation with each other (R = 0.536, p < 0.01). A correlation was also noted between L-PRx and PR (R = 0.475, p < 0.01), but not between PRx and PR. A correlation was found between age and PRx (R = 0.482, p = 0.01). No association with outcome for any of the indices was found. PRx/L-PRx and L-PRx/PR were moderately correlated with each other. Age was associated with PRx. None of the indices correlated with outcome when our ICP treatment regime was applied. Part of our null hypothesis, that the three indices are associated with outcome, must be rejected. There was, however, an association between some of the indices. To further understand the relation of treatment regimes and pressure reactivity indices, a larger, randomized study is warranted.

Association of Baseline Cerebrovascular Reactivity and Longitudinal Development of Enlarged Perivascular Spaces in the Basal Ganglia.

Increasing evidence suggests that enlarged perivascular spaces (ePVS) are associated with cognitive dysfunction in aging. However, the pathogenesis of ePVS remains unknown. Here, we tested the possibility that baseline cerebrovascular dysfunction, as measured by a magnetic resonance imaging measure of cerebrovascular reactivity, contributes to the later development of ePVS. Fifty cognitively unimpaired, older adults (31 women; age range, 60-84 years) underwent magnetic resonance imaging scanning at baseline and follow-up separated by ≈2.5 years. ePVS were counted in the basal ganglia, centrum semiovale, midbrain, and hippocampus. Cerebrovascular reactivity, an index of the vasodilatory capacity of cerebral small vessels, was assessed using carbon dioxide inhalation while acquiring blood oxygen level-dependent magnetic resonance images. Low baseline cerebrovascular reactivity values in the basal ganglia were associated with increased follow-up ePVS counts in the basal ganglia after controlling for age, sex, and baseline ePVS values (estimate [SE]=-3.18 [0.96]; P=0.002; [95% CI, -5.11 to -1.24]). This effect remained significant after accounting for self-reported risk factors of cerebral small vessel disease (estimate [SE]=-3.10 [1.00]; P=0.003; [CI, -5.11 to -1.09]) and neuroimaging markers of cerebral small vessel disease (estimate [SE]=-2.72 [0.99]; P=0.009; [CI, -4.71 to -0.73]). Our results demonstrate that low baseline cerebrovascular reactivity is a risk factor for later development of ePVS.

Regional differences in the link between water exchange rate across the blood–brain barrier and cognitive performance in normal aging

The blood–brain barrier (BBB) undergoes functional changes with aging which may contribute to cognitive decline. A novel, diffusion prepared arterial spin labeling-based MRI technique can measure the rate of water exchange across the BBB (kw) and may thus be sensitive to age-related alterations in water exchange at the BBB. However, studies investigating relationships between kw and cognition have reported different directions of association. Here, we begin to investigate the direction of associations between kw and cognition in different brain regions, and their possible underpinnings, by evaluating links between kw, cognitive performance, and MRI markers of cerebrovascular dysfunction and/or damage. Forty-seven healthy older adults (age range 61–84) underwent neuroimaging to obtain whole-brain measures of kw, cerebrovascular reactivity (CVR), and white matter hyperintensity (WMH) volumes. Additionally, participants completed uniform data set (Version 3) neuropsychological tests of executive function (EF) and episodic memory (MEM). Voxel-wise linear regressions were conducted to test associations between kw and cognitive performance, CVR, and WMH volumes. We found that kw in the frontoparietal brain regions was positively associated with cognitive performance but not with CVR or WMH volumes. Conversely, kw in the basal ganglia was negatively associated with cognitive performance and CVR and positively associated with regional, periventricular WMH volume. These regionally dependent associations may relate to different physiological underpinnings in the relationships between kw and cognition in neocortical versus subcortical brain regions in older adults.

Statistical properties of cerebral near infrared and intracranial pressure-based cerebrovascular reactivity metrics in moderate and severe neural injury: a machine learning and time-series analysis

BackgroundCerebrovascular reactivity has been identified as a key contributor to secondary injury following traumatic brain injury (TBI). Prevalent intracranial pressure (ICP) based indices of cerebrovascular reactivity are limited by their invasive nature and poor spatial resolution. Fortunately, interest has been building around near infrared spectroscopy (NIRS) based measures of cerebrovascular reactivity that utilize regional cerebral oxygen saturation (rSO2) as a surrogate for pulsatile cerebral blood volume (CBV). In this study, the relationship between ICP- and rSO2-based indices of cerebrovascular reactivity, in a cohort of critically ill TBI patients, is explored using classical machine learning clustering techniques and multivariate time-series analysis.MethodsHigh-resolution physiologic data were collected in a cohort of adult moderate to severe TBI patients at a single quaternary care site. From this data both ICP- and rSO2-based indices of cerebrovascular reactivity were derived. Utilizing agglomerative hierarchical clustering and principal component analysis, the relationship between these indices in higher dimensional physiologic space was examined. Additionally, using vector autoregressive modeling, the response of change in ICP and rSO2 (ΔICP and ΔrSO2, respectively) to an impulse in change in arterial blood pressure (ΔABP) was also examined for similarities.ResultsA total of 83 patients with 428,775 min of unique and complete physiologic data were obtained. Through agglomerative hierarchical clustering and principal component analysis, there was higher order clustering between rSO2- and ICP-based indices, separate from other physiologic parameters. Additionally, modeled responses of ΔICP and ΔrSO2 to impulses in ΔABP were similar, indicating that ΔrSO2 may be a valid surrogate for pulsatile CBV.ConclusionsrSO2- and ICP-based indices of cerebrovascular reactivity relate to one another in higher dimensional physiologic space. ΔICP and ΔrSO2 behave similar in modeled responses to impulses in ΔABP. This work strengthens the body of evidence supporting the similarities between ICP-based and rSO2-based indices of cerebrovascular reactivity and opens the door to cerebrovascular reactivity monitoring in settings where invasive ICP monitoring is not feasible.

Hemodynamic imaging parameters in brain metastases patients – Agreement between multi-delay ASL and hypercapnic BOLD

Arterial spin labeling (ASL) MRI is a routine clinical imaging technique that provides quantitative cerebral blood flow (CBF) information. A related technique is blood oxygenation level-dependent (BOLD) MRI during hypercapnia, which can assess cerebrovascular reactivity (CVR). ASL is weighted towards arteries, whereas BOLD is weighted towards veins. Their associated parameters in heterogeneous tissue types or under different hemodynamic conditions remains unclear. Baseline multi-delay ASL MRI and BOLD MRI during hypercapnia were performed in fourteen patients with brain metastases. In the ROI analysis, the CBF and CVR values were positively correlated in regions showing sufficient reserve capacity (i.e. non-steal regions, rrm = 0.792). Additionally, longer hemodynamic lag times were related to lower baseline CBF (rrm = −0.822) and longer arterial arrival time (AAT; rrm = 0.712). In contrast, in regions exhibiting vascular steal an inverse relationship was found with higher baseline CBF related to more negative CVR (rrm = −0.273). These associations were confirmed in voxelwise analyses. The relationship between CBF, AAT and CVR measures seems to be dependent on the vascular status of the underlying tissue. Healthy tissue relationships do not hold in tissues experiencing impaired or exhausted autoregulation. CVR metrics can possibly identify at-risk areas before perfusion deficiencies become visible on ASL MRI, specifically within vascular steal regions.

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.

Reproducibility and diurnal variation in middle cerebral artery blood velocity in healthy humans.

What is the central question of this study? We sought to establish between-day reproducibility in estimates of middle cerebral artery blood velocity (MCAv) and cerebrovascular reactivity (CVR) in young, healthy male and female adults in tightly controlled experimental conditions. What is the main finding and its importance? Measures of MCAv assessed during morning, afternoon and evening hours are reproducible between days. There is diurnal variation in CVR, with values being highest during the evening compared with the morning. Greater diurnal variation in CVR is associated with more efficient sleep and greater nocturnal blood pressure dipping. These data enhance our understanding of modulators of MCAv and CVR. Transcranial Doppler (TCD) is used to assess cerebral blood velocity (CBV) and cerebrovascular reactivity (CVR). Assessments of TCD reproducibility are limited, and few include multiple within-day measurements. We sought to establish reproducibility of CBV and CVR in healthy adults during three time periods (morning, afternoon and evening). We hypothesized that CBV and CVR measured at the same time of day are reproducible between days. We also hypothesized that CBV and CVR exhibit diurnal variation, with measurements being higher in the evening compared with morning/afternoon hours. Twelve adults [six male and six female, 27 years (95% CI, 22-31 years)] completed three measurements (morning, afternoon and evening) on two separate days in controlled conditions (e.g., meals, activity and sleep). Middle cerebral artery blood velocity (MCAv, TCD) was measured continuously at rest and during two CVR tests (end-expiratory apnoea and carbogen inhalation). Intraclass correlation coefficients for resting MCAv showed moderate to good reproducibility, which did not differ between morning, afternoon and evening (0.87, 0.56 and 0.67, respectively; P>0.05). Intraclass correlation coefficients for peak MCAv during apnoea (0.80, 0.46 and 0.65, respectively; P>0.05) and minute 2 of carbogen inhalation (0.81, 0.74 and 0.73, respectively; P>0.05) were also not different from morning compared with afternoon/evening. Time of day had no effect on resting MCAv (F=0.69, P=0.51, ƞp 2 =0.06) or the peak response to apnoea (F=1.00, P=0.39, ƞp 2 =0.08); however, peak MCAv during carbogen breathing exhibited diurnal variation, with highest values in the evening (F=3.41, P=0.05, ƞp 2 =0.24). Measures of CBV and CVR assessed via TCD during morning, afternoon and evening hours are reproducible between days. There is diurnal variation in the MCAv response to carbogen exposure, with CVR being highest during evening compared with morning hours.

Acetazolamide-augmented BOLD MRI to Assess Whole-Brain Cerebrovascular Reactivity in Chronic Steno-occlusive Disease Using Principal Component Analysis.

Background Exhaustion of cerebrovascular reactivity (CVR) portends increased stroke risk. Acetazolamide-augmented blood oxygenation level-dependent (BOLD) MRI has been used to estimate CVR, but low signal-to-noise conditions relegate its use to terminal CVR (CVRend) measurements that neglect dynamic features of CVR. Purpose To demonstrate comprehensive characterization of acetazolamide-augmented BOLD MRI response in chronic steno-occlusive disease using a computational framework to precondition signal time courses for dynamic whole-brain CVR analysis. Materials and Methods This study focused on retrospective analysis of consecutive patients with unilateral chronic steno-occlusive disease who underwent acetazolamide-augmented BOLD imaging for recurrent minor stroke or transient ischemic attack at an academic medical center between May 2017 and October 2020. A custom principal component analysis-based denoising pipeline was used to correct spatially varying non-signal-bearing contributions obtained by a local principal component analysis of the MRI time series. Standard voxelwise CVRend maps representing terminal responses were produced and compared with maximal CVR (CVRmax) as isolated from binned (per-repetition time) denoised BOLD time course. A linear mixed-effects model was used to compare CVRmax and CVRend in healthy and diseased hemispheres. Results A total of 23 patients (median age, 51 years; IQR, 42-61, 13 men) who underwent 32 BOLD examinations were included. Processed MRI data showed twofold improvement in signal-to-noise ratio, allowing improved isolation of dynamic characteristics in signal time course for sliding window CVRmax analysis to the level of each BOLD repetition time (approximately 2 seconds). Mean CVRmax was significantly higher than mean CVRend in diseased (5.2% vs 3.8%, P < .01) and healthy (5.5% vs 4.0%, P < .01) hemispheres. Several distinct time-signal signatures were observed, including nonresponsive; delayed/blunted; brisk; and occasionally nonmonotonic time courses with paradoxical features in normal and abnormal tissues (ie, steal and reverse-steal patterns). Conclusion A principal component analysis-based computational framework for analysis of acetazolamide-augmented BOLD imaging can be used to measure unsustained CVRmax through twofold improvements in signal-to-noise ratio. © RSNA, 2023 Supplemental material is available for this article.

Cerebrovascular reactivity measurements using 3T BOLD MRI and a fixed inhaled CO2 gas challenge: Repeatability and impact of processing strategy.

Introduction: Cerebrovascular reactivity (CVR) measurements using blood oxygen level dependent (BOLD) magnetic resonance imaging (MRI) are commonly used to assess the health of cerebral blood vessels, including in patients with cerebrovascular diseases; however, evidence and consensus regarding reliability and optimal processing are lacking. We aimed to assess the repeatability, accuracy and precision of voxel- and region-based CVR measurements at 3 T using a fixed inhaled (FI) CO2 stimulus in a healthy cohort. Methods: We simulated the effect of noise, delay constraints and voxel- versus region-based analysis on CVR parameters. Results were verified in 15 healthy volunteers (28.1±5.5years, female: 53%) with a test-retest MRI experiment consisting of two CVR scans. CVR magnitude and delay in grey matter (GM) and white matter were computed for both analyses assuming a linear relationship between the BOLD signal and time-shifted end-tidal CO2 (EtCO2) profile. Results: Test-retest repeatability was high [mean (95% CI) inter-scan difference: -0.01 (-0.03, -0.00) %/mmHg for GM CVR magnitude; -0.3 (-1.2,0.6) s for GM CVR delay], but we detected a small systematic reduction in CVR magnitude at scan 2 versus scan 1, accompanied by a greater EtCO2 change [±1.0 (0.4,1.5) mmHg] and lower heart rate [-5.5 (-8.6,-2.4] bpm]. CVR magnitude estimates were higher for voxel- versus region-based analysis [difference in GM: ±0.02 (0.01,0.03) %/mmHg]. Findings were supported by simulation results, predicting a positive bias for voxel-based CVR estimates dependent on temporal contrast-to-noise ratio and delay fitting constraints and an underestimation for region-based CVR estimates. Discussion: BOLD CVR measurements using FI stimulus have good within-day repeatability in healthy volunteers. However, measurements may be influenced by physiological effects and the analysis protocol. Voxel-based analyses should be undertaken with care due to potential for systematic bias; region-based analyses are more reliable in such cases.

Cerebrovascular pulsatility index is higher in chronic kidney disease.

Patients with chronic kidney disease (CKD) are more likely to die of cardiovascular diseases, including cerebrovascular disease, than to progress to end-stage kidney disease. Cerebrovascular dysfunction, characterized by reduced cerebrovascular reactivity, cerebral hypoperfusion, and increased pulsatile flow within the brain, precedes the onset of dementia and is linked to cognitive dysfunction. However, whether impaired cerebrovascular function is present in non-dialysis dependent CKD is largely unknown. Using transcranial Doppler, we compared middle cerebral artery (MCA) blood velocity response to hypercapnia (normalized for blood pressure and end-tidal CO2 ; a measure of cerebrovascular reactivity) and MCA pulsatility index (PI; a measure of cerebrovascular stiffness) in patients with stage 3-4 CKD vs. age-matched healthy controls. We also administered the NIH cognitive toolbox (cognitive function), measured carotid-femoral pulse-wave velocity (PWV; aortic stiffness), and assessed ex vivo nitric oxide (NO) and reactive oxygen species (ROS) production from human brain endothelial cells incubated with serum obtained from study participants. MCA PI was higher in patients with CKD vs. controls; however, normalized MCA blood velocity response to hypercapnia did not differ between groups. Similar results were observed in a validation cohort of midlife and older adults divided by the median estimated glomerular filtration rate (eGFR). MCA PI was associated with greater large-elastic artery stiffness (carotid-femoral PWV), worse executive function (trails B time), lower eGFR, and higher ex vivo ROS production. These data suggest that impaired kidney function is associated with greater cerebrovascular stiffness, which may contribute to the known increased risk for cognitive impairment in patients with CKD.

CVR-MRICloud: An online processing tool for CO2-inhalation and resting-state cerebrovascular reactivity (CVR) MRI data.

Cerebrovascular Reactivity (CVR) provides an assessment of the brain's vascular reserve and has been postulated to be a sensitive marker in cerebrovascular diseases. MRI-based CVR measurement typically employs alterations in arterial carbon dioxide (CO2) level while continuously acquiring Blood-Oxygenation-Level-Dependent (BOLD) images. CO2-inhalation and resting-state methods are two commonly used approaches for CVR MRI. However, processing of CVR MRI data often requires special expertise and may become an obstacle in broad utilization of this promising technique. The aim of this work was to develop CVR-MRICloud, a cloud-based CVR processing pipeline, to enable automated processing of CVR MRI data. The CVR-MRICloud consists of several major steps including extraction of end-tidal CO2 (EtCO2) curve from raw CO2 recording, alignment of EtCO2 curve with BOLD time course, computation of CVR value on a whole-brain, regional, and voxel-wise basis. The pipeline also includes standard BOLD image processing steps such as motion correction, registration between functional and anatomic images, and transformation of the CVR images to canonical space. This paper describes these algorithms and demonstrates the performance of the CVR-MRICloud in lifespan healthy subjects and patients with clinical conditions such as stroke, brain tumor, and Moyamoya disease. CVR-MRICloud has potential to be used as a data processing tool for a variety of basic science and clinical applications.

Optimal bispectral index level of sedation and cerebral oximetry in traumatic brain injury: a non-invasive individualized approach in critical care?

BackgroundImpaired cerebral autoregulation has been linked with worse outcomes, with literature suggesting that current therapy guidelines fail to significantly impact cerebrovascular reactivity. The cerebral oximetry index (COx_a) is a surrogate measure of cerebrovascular reactivity which can in theory be obtained non-invasively using regional brain tissue oxygen saturation and arterial blood pressure. The goal of this study was to assess the relationship between objectively measured depth of sedation through BIS and autoregulatory capacity measured through COx_a.MethodsIn a prospectively maintained observational study, we collected continuous regional brain tissue oxygen saturation, intracranial pressure, arterial blood pressure and BIS in traumatic brain injury patients. COx_a was obtained using the Pearson’s correlation between regional brain tissue oxygen saturation and arterial blood pressure and ranges from − 1 to 1 with higher values indicating impairment of cerebrovascular reactivity. Using BIS values and COx_a, a curve-fitting method was applied to determine the minimum value for the COx_a. The associated BIS value with the minimum COx_a is called BISopt. This BISopt was both visually and algorithmically determined, which were compared and assessed over the whole dataset.ResultsOf the 42 patients, we observed that most had a parabolic relationship between BIS and COx_a. This suggests a potential “optimal” depth of sedation where COx_a is the most intact. Furthermore, when comparing the BISopt algorithm with visual inspection of BISopt, we obtained similar results. Finally, BISopt % yield (determined algorithmically) appeared to be independent from any individual sedative or vasopressor agent, and there was agreement between BISopt found with COx_a and the pressure reactivity index (another surrogate for cerebrovascular reactivity).ConclusionsThis study suggests that COx_a is capable of detecting disruption in cerebrovascular reactivity which occurs with over-/under-sedation, utilizing a non-invasive measure of determination and assessment. This technique may carry implications for tailoring sedation in patients, focusing on individualized neuroprotection.

More pronounced hemodynamic alterations in patients with brain arteriovenous malformation-associated epilepsy.

Epileptic seizures in patients with brain arteriovenous malformations (bAVMs) may be caused by hemodynamic alterations due to the complex angioarchitecture of bAVMs. In particular, an arterial steal phenomenon and venous outflow disruption may play an etiological role in seizure development but remain challenging to demonstrate quantitatively. Blood oxygenation level-dependent (BOLD) cerebrovascular reactivity (CVR) imaging is an emerging technique that can measure both arterial steal phenomenon (as a paradoxical BOLD signal decrease during a vasodilatory stimulus) and impaired perinidal BOLD-CVR (which has been found in the presence of venous congestion on conventional angiography in bAVM patients with epilepsy). By applying this innovative BOLD-CVR technique, the aim is to better study CVR patterns and their correlation with morphological features on conventional angiography in patients with bAVM with and without epilepsy. Twenty-two patients with unruptured and previously untreated bAVMs (8 with and 14 without epilepsy) were included in this case-control study. Quantitative CVR measurements were derived from BOLD functional MRI volumes using a novel standardized and precise hypercapnic stimulus (i.e., % BOLD/mm Hg CO2). In addition, 22 matched healthy controls underwent an identical BOLD-CVR study. Evaluation of venous congestion was performed on conventional angiography for all patients with bAVM. Patients with bAVM-associated epilepsy showed impaired whole-brain BOLD-CVR compared to those in the nonepilepsy group, even after correction for AVM volume and AVM grade (epilepsy vs nonepilepsy group: 0.17 ± 0.07 vs 0.25 ± 0.07, p = 0.04). A BOLD-CVR-derived arterial steal phenomenon was observed in 2 patients with epilepsy (25%). Venous congestion was noted in 3 patients with epilepsy (38%) and in 1 patient without epilepsy (7%; p = 0.08). These data suggest that whole-brain CVR impairment, and more pronounced hemodynamic alterations (i.e., arterial steal phenomenon and venous outflow restriction), may be more present in patients with bAVM-associated epilepsy. The association of impaired BOLD-CVR and bAVM-associated epilepsy will need further investigation in a larger patient cohort.