Blood Oxygen Level-dependent Cerebrovascular Reactivity Research Articles

BOLD Cerebrovascular Reactivity and NOVA Quantitative MR Angiography in Adult Patients with Moyamoya Vasculopathy Undergoing Cerebral Bypass Surgery

Revascularization surgery for the symptomatic hemisphere with hemodynamic impairment is effective for Moyamoya vasculopathy patients. However, careful patient selection is crucial and ideally supported by advanced quantitative hemodynamic imaging. Recently, blood oxygenation level-dependent cerebrovascular reactivity (BOLD-CVR) and quantitative magnetic resonance angiography with non-invasive optimal vessel analysis (qMRA-NOVA) have gained prominence in assessing these patients. This study aims to present the results of BOLD-CVR and qMRA-NOVA imaging along with the changes in cerebral hemodynamics and flow status following flow augmentation with superficial temporal artery–middle cerebral artery (STA-MCA) bypass in our Moyamoya vasculopathy patient cohort. Symptomatic patients with Moyamoya vasculopathy treated at the Clinical Neuroscience Center of the University Hospital Zurich who underwent hemodynamic and flow imaging (BOLD-CVR and qMRA-NOVA) before and after bypass were included in the analysis. Reduced hemispheric volume flow rates, as well as impaired BOLD-CVR, were measured in all 12 patients with Moyamoya vasculopathy before STA-MCA bypass surgery. Following the surgical procedure, post-operative BOLD-CVR demonstrated a non-significant increase in BOLD-CVR values within the revascularized, symptomatic middle cerebral artery territory and cerebral hemisphere. The results of the statistical tests should be viewed as indicative due to the small sample size. Additionally, post-operative qMRA-NOVA revealed a significant improvement in the hemispheric volume flow rate of the affected hemisphere due to the additional bypass flow rate. Our findings affirm the presence of hemodynamic and flow impairments in the symptomatic hemisphere of the Moyamoya vasculopathy patients. Bypass surgery proves effective in improving both BOLD-CVR impairment and the hemispheric volume flow rate in our patient cohort.

The volume of steal phenomenon is associated with neurological deterioration in patients with large-vessel occlusion minor stroke not eligible for thrombectomy.

A significant number of patients who present with mild symptoms following large-vessel occlusion acute ischemic stroke (LVO-AIS) are currently considered ineligible for EVT. However, they frequently experience neurological deterioration during hospitalization. This study aimed to investigate the association between neurological deterioration and hemodynamic impairment by assessing steal phenomenon derived from blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) in this specific patient cohort. From the database of our single-center BOLD-CVR observational cohort study (June 2015-October 2023) we retrospectively identified acute ischemic stroke patients with admission NIHSS < 6, a newly detected large vessel occlusion of the anterior circulation and ineligible for EVT. Neurological deterioration during hospitalization as well as outcome at hospital discharge were rated with NIHSS score. We analyzed the association between these two outcomes and BOLD-CVR-derived steal phenomenon volume through regression analysis. Additionally, we investigated the discriminatory accuracy of steal phenomenon volume for predicting neurological deterioration. Forty patients were included in the final analysis. Neurological deterioration occurred in 35% of patients. In the regression analysis, a strong association between steal phenomenon volume and neurological deterioration (OR 4.80, 95% CI 1.32-31.04, p = 0.04) as well as poorer NIHSS score at hospital discharge (OR 3.73, 95% CI 1.52-10.78, p = 0.007) was found. The discriminatory accuracy of steal phenomenon for neurological deterioration prediction had an AUC of 0.791 (95% CI 0.653-0.930). Based on our results we may distinguish two groups of patients with minor stroke currently ineligible for EVT, however, showing hemodynamic impairment and exhibiting neurological deterioration during hospitalization: (1) patients exhibiting steal phenomenon on BOLD-CVR imaging as well as hemodynamic impairment on resting perfusion imaging; (2) patients exhibiting steal phenomenon on BOLD-CVR imaging, however, no relevant hemodynamic impairment on resting perfusion imaging. The presence of BOLD-CVR derived steal phenomenon may aid to further study hemodynamic impairment in patients with minor LVO-AIS not eligible for EVT.

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.

Hemodynamic Failure Staging With Blood Oxygenation Level-Dependent Cerebrovascular Reactivity and Acetazolamide-Challenged (15O-)H2O-Positron Emission Tomography Across Individual Cerebrovascular Territories.

Staging of hemodynamic failure (HF) in symptomatic patients with cerebrovascular steno-occlusive disease is required to assess the risk of ischemic stroke. Since the gold standard positron emission tomography-based perfusion reserve is unsuitable as a routine clinical imaging tool, blood oxygenation level-dependent cerebrovascular reactivity (BOLD-CVR) with CO2 is a promising surrogate imaging approach. We investigated the accuracy of standardized BOLD-CVR to classify the extent of HF. Patients with symptomatic unilateral cerebrovascular steno-occlusive disease, who underwent both an acetazolamide challenge (15O-)H2O-positron emission tomography and BOLD-CVR examination, were included. HF staging of vascular territories was assessed using qualitative inspection of the positron emission tomography perfusion reserve images. The optimum BOLD-CVR cutoff points between HF stages 0-1-2 were determined by comparing the quantitative BOLD-CVR data to the qualitative (15O-)H2O-positron emission tomography classification using the 3-dimensional accuracy index to the randomly assigned training and test data sets with the following determination of a single cutoff for clinical application. In the 2-case scenario, classifying data points as HF 0 or 1-2 and HF 0-1 or 2, BOLD-CVR showed an accuracy of >0.7 for all vascular territories for HF 1 and HF 2 cutoff points. In particular, the middle cerebral artery territory had an accuracy of 0.79 for HF 1 and 0.83 for HF 2, whereas the anterior cerebral artery had an accuracy of 0.78 for HF 1 and 0.82 for HF 2. Standardized and clinically accessible BOLD-CVR examinations harbor sufficient data to provide specific cerebrovascular reactivity cutoff points for HF staging across individual vascular territories in symptomatic patients with unilateral cerebrovascular steno-occlusive disease.

Blood Oxygenation Level-Dependent Cerebrovascular Reactivity-Derived Steal Phenomenon May Indicate Tissue Reperfusion Failure After Successful Endovascular Thrombectomy.

In acute ischemic stroke due to large-vessel occlusion (LVO), the clinical outcome after endovascular thrombectomy (EVT) is influenced by the extent of autoregulatory hemodynamic impairment, which can be derived from blood oxygenation level-dependent cerebrovascular reactivity (BOLD-CVR). BOLD-CVR imaging identifies brain areas influenced by hemodynamic steal. We sought to investigate the presence of steal phenomenon and its relationship to DWI lesions and clinical deficit in the acute phase of ischemic stroke following successful vessel recanalization.From the prospective longitudinal IMPreST (Interplay of Microcirculation and Plasticity after ischemic Stroke) cohort study, patients with acute ischemic unilateral LVO stroke of the anterior circulation with successful endovascular thrombectomy (EVT; mTICI scale ≥ 2b) and subsequent BOLD-CVR examination were included for this analysis. We analyzed the spatial correlation between brain areas exhibiting BOLD-CVR-associated steal phenomenon and DWI infarct lesion as well as the relationship between steal phenomenon and NIHSS score at hospital discharge.Included patients (n = 21) exhibited steal phenomenon to different extents, whereas there was only a partial spatial overlap with the DWI lesion (median 19%; IQR, 8-59). The volume of steal phenomenon outside the DWI lesion showed a positive correlation with overall DWI lesion volume and was a significant predictor for the NIHSS score at hospital discharge.Patients with acute ischemic unilateral LVO stroke exhibited hemodynamic steal identified by BOLD-CVR after successful EVT. Steal volume was associated with DWI infarct lesion size and with poor clinical outcome at hospital discharge. BOLD-CVR may further aid in better understanding persisting hemodynamic impairment following reperfusion therapy.

Dynamic Magnetic Resonance Vascular Fingerprinting During Hypercapnia for Quantitative and Multiparametric Cerebrovascular Reactivity Measures.

Magnetic resonance fingerprinting (MRF) represents a potential paradigm shift in MR image acquisition, reconstruction, and analysis using computational biophysical modelling in parallel to image acquisition. Its flexibility allows for examination of cerebrovascular metrics through MR vascular fingerprinting (MRvF), and this has been extended even further to produce quantitative cerebral blood volume (CBV), microvascular vessel radius, and tissue oxygen saturation (SO2) maps of the whole brain simultaneously every few seconds. This allows for observation of rapid physiological changes like cerebrovascular reactivity (CVR), which is the ability of vessels to dilate in response to a vasoactive stimulus. Here we demonstrated a novel protocol in which a rapid, spin- and gradient-echo pulse sequence allowed for dynamic, and simultaneous acquisition of MRvF and blood oxygen level dependent (BOLD) measures. By combining this with a tailored hypercapnic (5% CO2) breathing paradigm we were able to show how these quantitative CBV, radius, and SO2 parameters changed in response to a stimulus and directly compare those to a colocalized, traditionally used BOLD CVR. We also compared these measures to another traditionally utilized technique in cerebral blood flow CVR from an arterial spin labelling sequence. These imaging, processing, and analysis techniques will allow for further investigation into the magnitude and rate of CVR based on BOLD and MRvF-based metrics and enable investigations to better understand vascular function in healthy aging and cerebrovascular diseases.Clinical Relevance- The development of dynamic magnetic resonance vascular fingerprinting has the potential to enable rapid, quantitative, and multiparametric functional imaging biomarkers of cerebrovascular diseases like vascular cognitive impairment, dementia, and Alzheimer's disease.

Heterogeneous motor BOLD-fMRI responses in brain areas exhibiting negative BOLD cerebrovascular reactivity indicate that steal phenomenon does not always result from exhausted cerebrovascular reserve capacity

IntroductionBrain areas exhibiting negative blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) responses to carbon dioxide (CO2) are thought to suffer from a completely exhausted autoregulatory cerebrovascular reserve capacity and exhibit vascular steal phenomenon. If this assumption is correct, the presence of vascular steal phenomenon should subsequently result in an equal negative fMRI signal response during a motor-task based BOLD-fMRI study (increase in metabolism without an increase in cerebral blood flow due to exhausted reserve capacity) in otherwise functional brain tissue. To investigate this premise, the aim of this study was to further investigate motor-task based BOLD-fMRI signal responses in brain areas exhibiting negative BOLD-CVR. Material and methodsSeventy-one datasets of patients with cerebrovascular steno-occlusive disease without motor defects, who underwent a CO2-calibrated motor task-based BOLD-fMRI study with a fingertapping paradigm and a subsequent BOLD-CVR study with a precisely controlled CO2-challenge during the same MRI examination, were included. We compared BOLD-fMRI signal responses in the bilateral pre- and postcentral gyri – i.e. Region of Interest (ROI) with the corresponding BOLD-CVR in this ROI. The ROI was determined using a second level group analysis of the BOLD-fMRI task study of 42 healthy individuals undergoing the same study protocol. ResultsAn overall decrease in BOLD-CVR was associated with a decrease in BOLD-fMRI signal response within the ROI. For patients exhibiting negative BOLD-CVR, we found both positive and negative motor-task based BOLD-fMRI signal responses. ConclusionWe show that the presence of negative BOLD-CVR responses to CO2 is associated with heterogeneous motor task-based BOLD-fMRI signal responses, where some patients show -more presumed- negative BOLD-fMRI signal responses, while other patient showed positive BOLD-fMRI signal responses. This finding may indicate that the autoregulatory vasodilatory reserve capacity does not always need to be completely exhausted for vascular steal phenomenon to occur.

A dual-center validation of the PIRAMD scoring system for assessing the severity of ischemic Moyamoya disease.

Prior Infarcts, Reactivity, and Angiography in Moyamoya Disease (PIRAMD) is a recently proposed imaging-based scoring system that incorporates the severity of disease and its impact on parenchymal hemodynamics in order to better support clinical management and evaluate response to intervention. In particular, PIRAMD may have merit in identifying symptomatic patients that may benefit most from revascularization. Our aim was to validate the PIRAMD scoring system. Patients with ischemic Moyamoya disease, who underwent catheter angiographic [modified Suzuki Score (mSS) and collateralization status], morphological MRI and a parenchymal hemodynamic evaluation with blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) at two transatlantic centers, were retrospectively included. The primary outcome was the presence of neurological symptoms. The diagnostic capacity of each PIRAMD feature alone was evaluated, as well as combined and the inter-institutional differences of each parameter were evaluated. Seventy-two hemispheres of 38 patients were considered for analysis, of which 39 (54%) were classified as symptomatic. The presence of a prior infarct had the highest odds ratio [odds ratio (OR) =24; 95% CI: 6.7-87.2] for having neurological symptoms, followed by impaired CVR (OR =17; 95% CI: 5-62). No inter-institutional differences in the odds ratios or area under the curve (AUC) were found for any study parameter. The PIRAMD score had an AUC of 0.88 (95% CI: 0.80-0.96) with a similar AUC for the PIRAMD grading score. Our multicentric validation of the recently published PIRAMD scoring system was highly effective in rating the severity of ischemic Moyamoya disease with excellent inter-institutional agreement. Future studies should investigate the prognostic value of this novel imaging-based score in symptomatic patients with Moyamoya disease.

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.

Blood oxygenation-level dependent cerebrovascular reactivity imaging as strategy to monitor CSF-hemoglobin toxicity

ObjectivesCell-free hemoglobin in the cerebrospinal fluid (CSF-Hb) may be one of the main drivers of secondary brain injury after aneurysmal subarachnoid hemorrhage (aSAH). Haptoglobin scavenging of CSF-Hb has been shown to mitigate cerebrovascular disruption. Using digital subtraction angiography (DSA) and blood oxygenation-level dependent cerebrovascular reactivity imaging (BOLD-CVR) the aim was to assess the acute toxic effect of CSF-Hb on cerebral blood flow and autoregulation, as well as to test the protective effects of haptoglobin. MethodsDSA imaging was performed in eight anesthetized and ventilated sheep (mean weight: 80.4 kg) at baseline, 15, 30, 45 and 60 minutes after infusion of hemoglobin (Hb) or co-infusion with haptoglobin (Hb:Haptoglobin) into the left lateral ventricle. Additionally, 10 ventilated sheep (mean weight: 79.8 kg) underwent BOLD-CVR imaging to assess the cerebrovascular reserve capacity. ResultsDSA imaging did not show a difference in mean transit time or cerebral blood flow. Whole-brain BOLD-CVR compared to baseline decreased more in the Hb group after 15 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.01 vs -0.01 ± 0.02) and remained diminished compared to Hb:Haptoglobin group after 30 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.01 vs 0.0 ± 0.01), 45 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.01 vs 0.01 ± 0.02) and 60 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.02 vs 0.01 ± 0.01). ConclusionIt is demonstrated that CSF-Hb toxicity leads to rapid cerebrovascular reactivity impairment, which is blunted by haptoglobin co-infusion. BOLD-CVR may therefore be further evaluated as a monitoring strategy for CSF-Hb toxicity after aSAH.

Blood oxygenation level dependent cerebrovascular reactivity (BOLD-CVR) recovery following STA-MCA bypass flow augmentation surgery in acute and recurrent symptomatic patients with cerebrovascular atherosclerotic steno-occlusive disease

Blood oxygenation level dependent cerebrovascular reactivity (BOLD-CVR) recovery following STA-MCA bypass flow augmentation surgery in acute and recurrent symptomatic patients with cerebrovascular atherosclerotic steno-occlusive disease

Vascular and neuronal effects of general anesthesia on the brain: An fMRI study.

A number of functional magnetic resonance imaging (fMRI) studies rely on application of anesthetic agents during scanning that can modulate and complicate interpretation of the measured hemodynamic blood oxygenation level-dependent (BOLD) response. The purpose of the present study was to investigate the effect of general anesthesia on two main components of BOLD signal including neuronal activity and vascular response. Breath-holding (BH) fMRI was conducted in wakefulness and under anesthesia states in 9 patients with drug-resistant epilepsy who needed to get scanned under anesthesia during laser interstitial thermal therapy. BOLD and BOLD cerebrovascular reactivity (BOLD-CVR) maps were compared using t-test between two states to assess the effect of anesthesia on neuronal activity and vascular factors (p<.05). Overall, our findings revealed an increase in BOLD-CVR and decrease in BOLD response under anesthesia in several brain regions. The results proposed that the modulatory mechanism of anesthetics on neuronal and vascular components of BOLD signal may work in different ways. This experiment for the first human study showed that anesthesia may play an important role in dissociation between neuronal and vascular responses contributed to hemodynamic BOLD signal using BH fMRI imaging that may assist the implication of general anesthesia and interpretation of outcomes in clinical setting.

Abstract 65: Assessment Of MR Blood-Oxygen-Level-Dependent Cerebrovascular Reactivity Under General Anaesthesia In Children With Moyamoya

Background: Moyamoya is a progressive arteriopathy condition characterized by steno-occlusion of the arteries of the circle of Willis. MRI performed with hypercapnic challenge can image blood-oxygen-level-dependent cerebrovascular reactivity (BOLD-CVR) thereby assessing cerebrovascular reserve. MRI studies of children &lt;7 years of age, or with significant behavioural challenges require anesthesia. The purpose of this study was to validate the use of ventilator-induced hypercapnic challenge under general anaesthesia (GA). Methods: Children with moyamoya underwent two BOLD-CVR imaging in the same session under GA (GA-CVR). Differences in CVR estimates and intraclass correlation coefficient (ICC) between repeated scans were examined to determine repeatability across grey and white matter tissue and vascular territories. Bland-Altman plots were used to visulaize the overall variation between the scans. The associations with age, moyamoya types, and stroke presentation were also examined. Qualitative scoring by visual inspection was also conducted by trained neurologists. Results: Thirty-two paired GA-CVR studies (sixty-four scans in total) were analyzed (mean age: 7.07 (2.74 -17.95) years, 13 females). Forty-one percent (41%) were under 7 and 77%, under 10. No significant differences between repeated scans were found for any of the CVR estimates, when summarized by tissue and vascular territory. Of the paired studies, repeatability (ICC) for the whole-brain CVR estimates was excellent (≥0.74) in 14 (43.8%), good (≤0.59, &gt;0.74) in 7 (21.9%), fair (≤0.41, &gt;0.59) in 6 (18.8%) and poor (&lt;0.41) in 5 (15.6%). Bland-Altman plots illustrated the overall variation of whole-brain CVR within 95% confidence interval level. Repeatability indices were not affected by children’s age and other clinical factors. On qualitative scoring, the Cohen weighted kappa showed substantial agreement in both right (0.75) and left (0.81) hemispheres. Conclusion: Our study support the clinical use of GA-CVR across all ages and disease conditions. The GA-CVR provides a feasible, repeatable, and reliably interpretable tool for the assessment of cerebrovascular reserve of very young and behaviourally challenged children with moyamoya.

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

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

Agreement of novel hemodynamic imaging parameters for the acute and chronic stages of ischemic stroke: a matched-pair cohort study.

In symptomatic patients with cerebrovascular steno-occlusive disease, impaired blood oxygenation level-dependent cerebrovascular reactivity (BOLD-CVR) and increased flow velocity of the P2 segment of the posterior cerebral artery (PCA-P2) on transcranial Doppler (TCD) ultrasonography have been introduced as emerging clinical imaging parameters to identify patients at high risk for recurrent ischemic events. Since hemodynamic physiology differs between the acute and chronic stages of ischemic stroke, the authors sought to investigate whether those parameters have merit for both the acute and chronic stages of ischemic stroke. From a prospective database, patients who underwent BOLD-CVR and TCD examinations in the acute stroke stage (< 10 days) were matched to patients in the chronic stroke stage (> 3 months). A linear regression analysis for both groups was performed between ipsilateral PCA-P2 systolic flow velocity and BOLD-CVR of the ipsilateral (affected) hemisphere, the ipsilateral middle cerebral artery (MCA) territory, and the ipsilateral steal volume (i.e., paradoxical BOLD-CVR response). The resulting slopes and intercepts were statistically compared to evaluate differences between groups. Forty matched patient pairs were included. Regression analysis showed no significant difference for either the intercept (p = 0.84) or the slope (p = 0.85) between PCA-P2 flow velocity and BOLD-CVR as measured for the ipsilateral (affected) hemisphere. Similarly, no significant difference was seen between PCA-P2 flow velocity and BOLD-CVR of the ipsilateral MCA territory (intercept, p = 0.72; slope, p = 0.36) or between PCA-P2 flow velocity and steal volume (intercept, p = 0.59; slope, p = 0.34). The study results indicated that the relationship between ipsilateral PCA-P2 systolic flow velocity and BOLD-CVR remains the same during the acute and chronic stages of ischemic stroke. This provides further support that these novel hemodynamic imaging parameters may have merit to assess the risk for recurrent ischemic events for a wide ischemic stroke population. PCA-P2 systolic flow velocity, in particular, may be a highly practical screening tool, independent of ischemic stroke stage.

Investigating the Association of Wallerian Degeneration and Diaschisis After Ischemic Stroke With BOLD Cerebrovascular Reactivity.

IntroductionWallerian degeneration and diaschisis are considered separate remote entities following ischemic stroke. They may, however, share common neurophysiological denominators, since they are both related to disruption of fiber tracts and brain atrophy over time. Therefore, with advanced multimodal neuroimaging, we investigate Wallerian degeneration and its association with diaschisis.MethodsIn order to determine different characteristics of Wallerian degeneration, we conducted examinations on seventeen patients with chronic unilateral ischemic stroke and persisting large vessel occlusion, conducting high-resolution anatomical magnetic resonance imaging (MRI) and blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) tests, as well as Diamox 15(O)–H2O–PET hemodynamic examinations. Wallerian degeneration was determined using a cerebral peduncle asymmetry index (% difference of volume of ipsilateral and contralateral cerebral peduncle) of more than two standard deviations away from the average of age-matched, healthy subjects (Here a cerebral peduncle asymmetry index > 11%). Diaschisis was derived from BOLD-CVR to assess the presence of ipsilateral thalamus diaschisis and/or crossed cerebellar diaschisis.ResultsWallerian degeneration, found in 8 (47%) subjects, had a strong association with ipsilateral thalamic volume reduction (r2 = 0.60) and corticospinal-tract involvement of stroke (p < 0.001). It was also associated with ipsilateral thalamic diaschisis (p = 0.021), No cerebral peduncular hemodynamic differences were found in patients with Wallerian degeneration. In particular, no CBF decrease or BOLD-CVR impairment was found.ConclusionWe show a strong association between Wallerian degeneration and ipsilateral thalamic diaschisis, indicating a structural pathophysiological relationship.

Increased Ipsilateral Posterior Cerebral Artery P2-Segment Flow Velocity Predicts Hemodynamic Impairment.

Increased Transcranial Doppler flow velocity in the ipsilateral P2-segment of the posterior cerebral artery (PCA-P2: cm/second) is associated with recurrent cerebrovascular events in patients with unilateral internal carotid artery occlusion. However, its predictive value and correlation with hemodynamic impairment in an overall stroke patient cohort remains to be determined. Transcranial doppler PCA-P2 flow velocity was measured in 88 patients with symptomatic unilateral steno-occlusive disease who also underwent blood oxygenation-level dependent cerebrovascular reactivity imaging (blood oxygenation-level dependent [BOLD]-cerebrovascular reactivity [CVR]). A multivariate linear regression was used to evaluate the independent correlation between the ipsilateral PCA-P2 flow velocity measurements and hemispheric BOLD-CVR. Follow-up BOLD-CVR imaging data, available in 25 patients, were used to evaluate the temporal evolution of the BOLD-CVR and PCA-P2 flow velocity association using a mixed-effect model. Furthermore, a transcranial doppler cutoff for hemodynamic failure stage 2 was determined. The ipsilateral systolic PCA-P2 flow velocity strongly correlated with hemispheric BOLD-CVR (R=0.79; R2=0.61), which remained unchanged when evaluating the follow-up data. Using a PCA-P2 systolic flow velocity cutoff value of 85 cm/second, patients with BOLD-CVR based hemodynamic failure stage 2 were diagnosed with an area under the curve of 95. In patients with symptomatic unilateral steno-occlusive disease, increased ipsilateral transcranial doppler PCA-P2 systolic flow velocity independently correlates with BOLD-CVR based hemodynamic failure. A cutoff value of 85 cm/second appears to indicate hemodynamic failure stage 2, but this finding needs to be validated in an independent patient cohort.

Intraoperative BOLD-fMRI Cerebrovascular Reactivity Assessment.

Blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) has gained attention in recent years as an effective way to investigate CVR, a measure of the hemodynamic state of the brain, with high spatial and temporal resolution. An association between impaired CVR and diverse pathologies has been observed, especially in ischemic cerebrovascular diseases and brain gliomas. The ability to obtain this information intraoperatively is novel and has not been widely tested. We report our first experience with this intraoperative technique in vascular and oncologic neurosurgical patients, discuss the results of its feasibility, and the possible developments of the intraoperative employment of BOLD-CVR.

Crossed Cerebellar Diaschisis in Patients With Symptomatic Unilateral Anterior Circulation Stroke Is Associated With Hemodynamic Impairment in the Ipsilateral MCA Territory.

In patients with steno-occlusive disease, recent findings suggest that hemodynamic alterations may also be associated with crossed cerebellar diaschisis (CCD) rather than a functional disruption alone. To use a quantitative multiparametric hemodynamic MRI to gain a better understanding of hemodynamic changes related to CCD in patients with unilateral anterior circulation stroke. Prospective cohort study. Twenty-four patients (25 datasets) with symptomatic unilateral anterior circulation stroke. 3T/two sequences: single-shot (echo-planar imaging) EPI sequence and T2* gradient echo perfusion-weighted imaging study. The presence of CCD was inferred from the cerebellar asymmetry index (CAI) of the blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) exam, which was calculated from the mean BOLD-CVR and standard deviation of the CAI of the healthy control group. For all perfusion-weighted (PW)-MRI parameters, the cerebellar and middle cerebral artery (MCA) territory asymmetry indices were calculated. Independent Student's t-test to compare the variables from the CCD positive(+) and CCD negative(-) groups and analysis of covariance (ANCOVA) to statistically control the effect of covariates (infarct volume and time since ischemia onset). CCD was present in 33% of patients. In the MCA territory of the affected hemisphere, BOLD-CVR was significantly more impaired in the CCD(+) group as compared to the CCD(-) group (mean BOLD-CVR ± SD [%BOLD signal/ΔmmHgCO2 ]: -0.03 ± 0.12 vs. 0.11 ± 0.13, P < 0.05). Moreover, the mean transit time (MTT) (asymmetry index (%) CCD(+) vs. CCD(-): 28 ± 23 vs. 4 ± 11, P < 0.05) and time to peak (TTP) (10 ± 10 vs. 2 ± 5, P < 0.05) in the MCA territory of the affected hemisphere were significantly prolonged, while cerebral blood volume was, on average, increased in the CCD(+) group (25 ± 15 vs. 4 ± 19, P < 0.05). Our findings show that, in patients with symptomatic unilateral anterior circulation stroke, CCD is associated with hemodynamic impairment in the ipsilateral MCA territory, which further supports the concept of a vascular component of CCD. 3 TECHNICAL EFFICACY STAGE: 3.

Hemodynamic investigation of peritumoral impaired blood oxygenation-level dependent cerebrovascular reactivity in patients with diffuse glioma

IntroductionThe presence of peritumorally impaired blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) has been unequivocally demonstrated in patients with diffuse glioma, and may have value to better identify tumor infiltration zone. Since BOLD-CVR does not measure hemodynamic changes directly, we performed additional MR perfusion studies to better characterize the peritumoral hemodynamic environment. MethodsSeventeen patients with WHO grade III and IV diffuse glioma underwent high resolution advanced hemodynamic MR imaging including BOLD-CVR and MR perfusion. The obtained multiparametric hemodynamic factors (i.e., regional cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), mean transit time (MTT), time-to-peak (TTP) and BOLD-CVR, were analyzed within 10 concentric expanding 3 mm volumes of interest (VOIs) up to 30 mm from the tumor tissue mask. ResultsBOLD-CVR impairment was found within the tumor tissue mask and the peritumoral VOIs up to 21 mm as compared to the contralateral flipped CVR analysis (p<0.05). In the affected hemisphere, we observed positive spatial correlations including all VOIs between BOLD-CVR and rCBV values (r=0.27; p<0.001), rCBF (r=0.42; p<0.001) and a negative correlation between BOLD-CVR and TTP (r=-0.47; p<0.001). ConclusionsPeritumorally impaired BOLD-CVR is associated with concomitant hemodynamic alterations with severity correlating to tumor volume. The distribution of these multiparametric hemodynamic MRI patterns may be considered for future studies characterizing the hemodynamic peritumoral environment, thereby better identifying the extent of tumor infiltration.