Assessment Of Cerebrovascular Reserve Research Articles

Abstract TP95: Utility Of Automated Artificial Intelligence Software In The Analysis Of Ct Perfusion With Acetazolamide Challenge For The Assessment Of Cerebrovascular Reserve In Patients With Cervico-cranial Arterial Stenoses And Occlusions

Background: Cerebrovascular reserve (CVR) assessment is valuable in predicting stroke risk in patients with cranio-cervical stenoses and occlusions. CTP with Acetazolamide challenge (AC) allows a qualitative and quantitative assessment of CVR but is limited by ROI positioning, motion and software. Artificial intelligence (AI) automated software with delay in arrival correction has been validated for the processing of CTP data for acute stroke and may more easily detect abnormal CVR. We sought to compare the results of image-processing with a standard platform (Vitrea™) and AI platform (RAPID™). Methods: Retrospective analysis of an IRB approved prospective database of patients who had CTP with acetazolamide (1g IV) who also had a stenosis/occlusion of the internal carotid or middle cerebral arteries was performed. Symptomatic status was defined as recurrent symptoms related to the vessel of interest within 6 months of scan. Two readers, blinded to the clinical scenario, independently reviewed the CTP datasets and identified CBF regional abnormalities and changes post AC using the 2 different platforms. Abnormal CVR was defined as an increase of CBF post AC of <25% of the baseline in the region of interest with Vitrea™, and an expansion of the volume of tissue with CBF<30% using RAPID™. CTP analyses were correlated with the clinical presentation. Results: Thirty patients fulfilling criteria received CTP before and after AC. 24 patients (80%) were symptomatic. Vitrea™ detected decrease in CBF pre-AC in 27 patients and worsening CBF value post-AC in 19 patients. 10 Patients had an increase >25% in CBF post AC. Rapid™ detected 5 patients with CBF lesion <30% pre-AC. Expansion of the CBF lesion occurred in 8 patients post-AC with a mean change in volume of 7.7 ml (P-value=0.002). The sensitivity for the detection of poor CVR in patients with recurrent symptoms was 80% (95% CI 59.30 - 93.17) with Vitrea™ and 45% (95% CI 25.55%-67.18%) with RAPID™. Conclusion: Automated post processing software with delay in arrival correction algorithm is less sensitive to abnormal CVR and has lower correlation with clinical presentation in this small cohort. Further study is warranted to identify thresholds that may better correlate.

Assessment of Cerebrovascular Reserve in the Setting of Moyamoya Disease Using Arterial Spin-Labeling and Acetazolamide Challenge

Arterial spin-labeling is a safe, noninvasive, contrast-free MR imaging technique that can be used to assess CBF. In this review, we will briefly discuss the advantages and disadvantages of arterial spin-labeling juxtaposed to previously established modalities of cerebral perfusion imaging, summarize the materials and methods required for arterial spin-labeling, and provide clinical case examples in which application of arterial spin-labeling combined with an acetazolamide challenge was used safely to improve patient outcomes in the setting of Moyamoya disease. Arterial spin-labeling takes advantage of the directionality of arterial blood flow by labeling the patient's own endogenous water within the neck via radiofrequency pulse and imaging of the downstream brain after an appropriate delay. This tool allows repeatable intra- and intersession estimation of CBF to better assess postinterventional outcomes in patients with cerebrovascular dysfunction. One specific example of the utility of arterial spin-labeling is its application in patients with Moyamoya disease by selection and stratification of those most likely to benefit from surgical intervention. The combination of arterial spin-labeling with acetazolamide challenge is an effective way to assess cerebrovascular reserve in Moyamoya disease and is easily adaptable on a clinical 3T MR imaging scanner using a commercially available arterial spin-labeling pulse sequence to generate augmentation and steal maps. The entire study can be completed in only 20 minutes in a routine clinical setting.Learning Objective: To describe the implementation and interpretation of arterial spin-labeling combined with an acetazolamide challenge

Abstract TP97: White Matter And Deep Grey Matter Structural Variations In Childhood Moyamoya Disease

Background: Moyamoya disease is a progressive steno-occlusive arteriopathy that increases stroke risk. Clinically, cognitive decline is known to occur over time, even in the absence of stroke. MRI measures of cerebrovascular reactivity (CVR) provide an in vivo assessment of cerebrovascular reserve and stroke risk. Typically, in normal-appearing white matter (WM) lower (quantified as negative) CVR is associated with increased apparent diffusion coefficient (ADC). However, the association between negative CVR and ADC in children is not well understood. Objectives: To determine (i) whether negative CVR is associated with changes in ADC in normal-appearing WM of children with Moyamoya, ii) whether there is an association between CVR and ADC with structural damage to the brain (by measuring the volume of subcortical structures). Methods: Retrospective analysis of a consecutive cohort of nine children with Moyamoya (male = 4, median age = 12.1) with no history of stroke, and seven age and sex-matched controls. ADC values and fractional negativity (fneg), calculated from CVR parametric maps as the fraction of negative CVR voxels within a region of interest (ROI), were extracted from WM and subcortical GM ROIs. Volumes from the subcortical GM regions were extracted and normalized for head size. Analyses of differences was calculated per hemisphere (n=18, bilateral disease n = 4, unilateral n=5) and categorized as affected and unaffected and compared to controls. Results: Mean (m) ADC in WM of affected hemispheres (m=807.05, p<0.01) and unaffected (m=814.68, p<0.05) hemispheres were significantly larger compared to controls (m=761.04). A positive relationship was found between fneg and ADC in affected (r=0.37, p=0.24) and unaffected (r=0.26, p=0.62) hemispheres, but with no statistical significance. Increased ADC in the caudate was associated with smaller volume in the affected hemisphere of patients (r =-0.83, p=0.02). Conclusions: ADC in normal appearing WM in children with Moyamoya is elevated, and is associated with volume of the caudate in this cohort demonstrating the association between abnormal CVR, perfusion and structural damage in children with Moyamoya and no stroke.

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 <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, >0.74) in 7 (21.9%), fair (≤0.41, >0.59) in 6 (18.8%) and poor (<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.

Characterization of regional differences in cerebral vascular response to breath holding usingBOLD fMRI

AbstractCerebrovascular reactivity (CVR) is a specific indicator of autoregulatory efficiency. Studies have demonstrated that CVR depends on the baseline vascular dilation status between groups. Within the brain, there also exist spatial variations in both the resting cerebral blood flow (CBF) and CVR across different cerebral regions. However, the relationship between the regional CBF and CVR remains unclear. Hence, the primary goal of this study was to investigate the relationship between the resting CBF using pseudocontinuous arterial spin labeling (pCASL) technique and CVR using blood oxygenation level‐dependent (BOLD) technique across different cerebral regions. Eleven male and 14 female young volunteers were recruited in this study. Each subject was asked to perform the breath‐holding challenge to evaluate CVR at 3 T. The resting CBF was measured using pCASL in each subject. The relationships between CBF and CVR across the lobes were evaluated using the Spearman's rank test. The results showed that, for both sexes, the frontal lobe had the maximal resting perfusion but minimal vascular response to hypercapnia, whereas the occipital lobe had the lowest baseline CBF but maximal reactivity to hypercapnia, suggesting low and high autoregulatory efficiencies at high and low resting CBF in the brain, respectively. Sex‐related differences were observed in CBF but not in CVR. These findings may be of clinical interest in the assessment of cerebrovascular reserve and regional‐dependent vascular diseases.

Assessment of Cerebrovascular Reserve in the Heart Failure Patients Supported with the HeartMate3

We previously showed that cerebrovascular reactivity (CVR) is reduced in heart failure (HF) patients and does not improve after left ventricular assist device (LVAD) HeartMate II (HMII) implantation, possibly because of low pulsatile physiology. Therefore, it is possible that the artificial pulse of the latest generation LVAD, the HeartMate3 (HM3), restores normal CVR. HM3 patients will have an increased CVR to a CO2-retention challenge compared with HF and HMII. A total of 79 subjects (17 healthy, 30 HF, 15 HMII and 17 HM3) underwent angle-corrected transcranial Doppler sonography. Middle cerebral artery (MCA) velocity profiles were recorded before and at the end of a 30s breath hold. Mean flow velocity (MFV), peak flow velocity (Vmax), minimal flow velocity (Vmin), Pulsatility Index (PI) and Resistance Index (RI) were quantified. Statistical differences were determined using 2-way ANOVA (Breathhold x group). At baseline, HF patients with and without LVAD implantation had a decreased Vmax, MFV, PI and RI compared to healthy (all P < 0.05). With CO2-retention the absolute and relative increase in MFV was highest in the HM3 group significantly compared with HMII (7.8±2.4 vs 1.6±2.1 cm/s; +16% vs +3%, p<0.01). HM3 and HF subjects exhibited similar absolute and relative changes in MFV and both were lower than health controls. Similar results were seen for Vmax and Vmin, however, there was no change PI or RI in any groups (Fig. 1). The change with MFV with breath-holding was not different when considering HF subjects on inotropes, or when comparing beats with and without artificial pulse in HM3 patients. HM3 patients have a significantly improved CVR to a CO2-retention challenge compared with HMII patients. However, the acute CVR is not altered by the artificial pulse. Since CVR of HM3 patients remains reduced compared with healthy controls, further research is needed to understand the pathophysiology of cerebrovascular complications in LVAD.

Assessment of cerebrovascular reserve in unilateral middle cerebral artery stenosis using perfusion CT and CO2 inhalation tests

Purpose/Aim of the study: Cerebrovascular reactivity (CVR) is an important marker for assessing cerebrovascular disease. This study assessed the CVR by perfusion computed tomography (CT) and CO2 inhalation tests in patients with unilateral middle cerebral artery (MCA) stenosis disease. Materials and Methods: Thirty-one patients with unilateral MCA stenosis disease diagnosed by digital subtraction angiography were studied. Patients were divided into two groups according to the degree of stenosis: severe and moderate. The regional cerebral blood flow (CBF) before and after CO2 inhalation was determined by perfusion CT. Regional CVR values were obtained by the following formula: increase (%) = (post-CBF) − (pre-CBF)/(pre-CBF) × 100%. Results: No significant differences in the mean CBF in the MCA stenosis region were found between the affected and contralateral sides before the CO2 inhalation test; after the test, CBF was more significantly decreased on the affected side than on the contralateral side. The changes in CBF on the affected side were categorized into three types: increased CBF (17 cases), decreased CBF (12 cases) and no change in CBF (2 cases). The rate of CVR impairment among severe stenosis patients (13/19) was higher than that among moderate stenosis patients (3/12). CVR was significantly correlated with the degree of stenosis (r = 0.423, P = 0.018). Conclusion: CVR impairment was found in approximately half of patients with unilateral MCA stenosis. Along with an increase in the degree of stenosis, patients with unilateral MCA stenosis were more likely to exhibit CVR impairment. It is important to assess the CVR in patients with unilateral MCA stenosis, especially those with severe stenosis.

Evaluation of cerebrovascular reserve in patients undergoing carotid artery stenting and its usefulness in predicting significant hemodynamic changes during temporary carotid occlusion.

We investigated the usefulness of cerebrovascular reserve (CVR) testing to predict severe hemodynamic changes during proximally protected carotid artery stenting. Of 90 patients referred, 63 eligible underwent complete evaluation of the extent of carotid artery disease and transcranial Doppler ultrasound (TCD) assessment of CVR by means of a breath-holding test and ophthalmic artery flow pattern evaluation. Periprocedural TCD monitoring of the ipsilateral middle cerebral artery flow was performed in 24 patients undergoing proximally protected procedure (requiring induction of flow arrest within internal carotid artery). Abnormal CVR was significantly less common in patients with unilateral compared to bilateral carotid artery disease (26.3 % vs. 76.9 %, p=0.02), while ophthalmic artery flow reversal was rare in patients with unilateral carotid artery disease (2.5 % vs. 42.9 %, p<0.01). During the induction of carotid flow arrest, the average mean flow velocity drop following external carotid artery occlusion was low (3.5 %, p=0.67) compared to the induction of complete flow arrest (32.8 %, p<0.01). Six patients had a total mean flow velocity drop >50 %, including 2 patients with normal pre-procedural CVR. Our results suggest that TCD evaluation of CVR is not a reliable predictor of hemodynamic changes induced during proximally protected carotid artery stenting in patients with unilateral carotid artery disease.

CO2BOLD assessment of moyamoya syndrome: Validation with single photon emission computed tomography and positron emission tomography imaging.

AIMTo compare the assessment of cerebrovascular reserve (CVR) using CO2BOLD magnetic resonance imaging (MRI) vs positron emission tomography (PET) and single photon emission computed tomography (SPECT) as reference standard.METHODSTen consecutive patients (8 women, mean age of 41 ± 26 years) with moyamoya syndrome underwent 14 pre-surgical evaluations for external-internal carotid artery bypass surgery. CVR was assessed using CO2BOLD and PET (4)/SPECT (11) with a maximum interval of 36 d, and evaluated by two experienced neuroradiologists.RESULTSThe inter-rater agreement was 0.81 for SPECT (excellent), 0.43 for PET (fair) and 0.7 for CO2BOLD (good). In 9/14 cases, there was a correspondence between CO2BOLD and PET/SPECT. In 4/14 cases, CVR was over-estimated in CO2BOLD, while in 1/14 case, CVR was underestimated in CO2BOLD. The sensitivity of CO2BOLD was 86% and a specificity of 43%.CONCLUSIONCO2BOLD can be used for pre-surgical assessment of CVR in patients with moyamoya syndrome and combines the advantages of absent irradiation, high availability of MRI and assessment of brain parenchyma, cerebral vessels and surrogate CVR in one stop.

BOLD MRI and early impairment of cerebrovascular reserve after aneurysmal subarachnoid hemorrhage

Currently no biological or radiological marker is available to identify patients at risk of delayed ischemic deficit (DIND) after aneurysmal subarachnoid hemorrhage (aSAH). We hypothesized whether MR-based quantitative assessment of cerebrovascular reserve (CVR) would detect early radiological markers of vasospasm and DIND. This manuscript describes our initial experience with this population. Five patients with aSAH underwent blood-oxygen level dependent-MRI (BOLD-MRI) with CO2 challenge for assessment of whole brain CVR. Patients were examined as soon as possible after aneurysm treatment. We obtained good quality anatomical and functional images without complications. Initial anatomical cerebrovascular imaging showed no vasospasm in all patients. Two patients had abnormal CVR-MRI tests and both developed DIND. Of the 3 others with normal CVR-MRI, one developed posterior circulation DIND. One patient with a normal CVR-MRI developed angiographic vasospasm but no DIND. Changes in CVR maps as early as 36 h after hemorrhage had good spatial correlation with delayed ischemia during short-term follow-up. Our series shows that MRI with CO2 challenge is feasible in this difficult population. Further developments might allow BOLD-MRI with CO2 challenge to identify patients at risk and provide anatomical correlation with future DIND, opening a new venue for prophylactic treatments. Further study is warranted in a larger patient cohort.

Comparison of Perfusion Weighted Magnetic Resonance Imaging and Single Photon Emission Computed Tomography for Assessment of Cerebrovascular Reserve in Symptomatic Carotid Territory Stenosis

Background: Perfusion Weighted Magnetic Resonance Imaging (PW-MRI) and HMPAO Single Photon Emission Computed Tomography (SPECT) are both cerebral perfusion measurement techniques. Imaging before and after acetazolamide administration can assess cerebrovascular reserve in symptomatic haemodynamic cerebrovascular disease. We compared SPECT and PW-MRI parameters in this patient group. Methods: We identified 10 patients with haemody-namically induced symptoms and intra- or extra-cranial arterial stenoses with back-to-back acetazolamide challenge SPECT and PW-MRI, 4 of whom had resting studies. Regions of interest (ROIs) were applied to parameter maps using an ASPECTS template and perfusion parameters expressed relative to contralateral ROIs, giving 118 challenge and 48 resting ROIs. Results: SPECT relative cerebral blood flow (rCBF) correlated with PW-MRI time to peak (TTP) (r = ?0.568), mean transit time (MTT) (r = ?0.317), regional cerebral blood flow (rCBF) (r = 0.299) and cerebral blood volume (CBV) (r = 0.224). Bias between SPECT and PW-MRI rCBF was small (?0.018) with wide limits of agreement and a systematic measurement error. Pre- to post-acetazolamide PW-MRI rCBF change showed poor sensitivity and specificity for detecting change in SPECT rCBF. SPECT and PW-MRI rCBF had stronger correlation and smaller bias in unilateral stenosis than with bilateral stenosis. Conclusion: Systematic bias between techniques limits interchange- ability in cerebrovascular reserve measurement in patients with cerebrovascular stenosis.

Assessment of cerebrovascular reserve before and after STA-MCA bypass surgery by SPECT and SPM analysis

ObjectiveThe purpose of this study was to objectively assess the efficacy of superficial temporal artery to middle cerebral artery (STA-MCA) bypass surgery using Technetium (Tc)-99m-ethyl cysteinate dimer (ECD) single photon emission computed tomography (SPECT) in patients who underwent STA-MCA bypass surgery.Materials and MethodsBrain perfusion SPECT images obtained at baseline and after the administration of acetazolamide were reconstructed using statistical parametric mapping in 23 patients, both before and after STA-MCA bypass surgery. The clinical outcomes of the surgery were also recorded and compared with the hemodynamic changes. A voxel with an uncorrected p-value of less than 0.001 was considered to be statistically significant.ResultsSPECT images of the territory supplied by the bypass graft showed an increase in both cerebrovascular flow and reserve at baseline, and the increase was significantly higher following the administration of acetazolamide. All patients showed improvement of clinical symptoms and increased blood flow to the left temporal, parietal, and frontal cortices as well as the thalamus.ConclusionBrain SPECT effectively and objectively demonstrated the improved outcomes of STA-MCA bypass surgery, and thus may be used in postoperative analyses.

Serial imaging of the carotid bifurcation and cerebrovascular reserve after carotid endarterectomy.

A radioisotopic method of quantifying mean cerebral transit time was used to assess the immediate effects of carotid endarterectomy on cerebrovascular reserve (CVR) in 69 patients. In addition, serial postoperative data were acquired on CVR, clinical status and non-invasive imaging of the internal carotid arteries in 56 patients over a period of 6-48 (median 24) months. Twenty-one patients (30 per cent) had preoperative evidence of impaired CVR in the symptomatic hemisphere. Within 4 days of surgery, however, reserve had returned to normal in 17 of the 21 patients. During follow-up, four of the 56 patients developed recurrent stenosis (> 50 per cent) or occlusion of the artery operated on but only two of these had impairment of CVR and none was symptomatic. Three patients suffered recurrent transient ischaemic attacks (TIAs) but none had recurrent internal carotid artery disease or impaired CVR. One patient suffered a TIA in the territory of the non-operated artery during follow-up in association with disease progression and CVR impairment. However, the TIA preceded recognition of either of these changes. Twelve other patients had (or developed) stenosis (> 50 per cent) in the non-operated artery during follow-up but none was symptomatic or developed impairment of CVR. Although assessment of CVR provided useful information on the frequency of haemodynamic compromise before carotid endarterectomy and on the natural history of disease progression, neither serial assessment of reserve nor non-invasive imaging of the carotid bifurcation influenced clinical practice during follow-up.

Diagnosis of stroke with advanced CT and MR imaging.

There have been important advances in stroke imaging, including CT perfusion imaging, xenon-CT, CT angiography, MR diffusion imaging, MR perfusion imaging, MR angiography and haemorrhage-sensitive gradient echo MR sequences. The technical principles and clinical applications of these methods are explained. An emphasis is made on the diagnosis of hyperacute cerebral ischaemia and issues surrounding the differentiation of reversible from irreversible ischaemic damage with modern imaging modalities, which has implications for thrombolytic therapy. This is followed by an overview of the role of imaging in patients with chronic stroke and transient ischaemic attack. In these patients, the diagnostic contribution of MRI in detecting the underlying pathology and the assessment of cerebrovascular reserve with perfusion imaging from an important part in the secondary prevention of stroke.