Quantification of Cerebrovascular Reactivity by Blood Oxygen Level-Dependent MR Imaging and Correlation with Conventional Angiography in Patients with Moyamoya Disease

Departments of Medical Imaging, Toronto Western Hospital of the University Health Network, Toronto, Ontario, Canada.
American Journal of Neuroradiology (Impact Factor: 3.59). 05/2010; 31(5):862-7. DOI: 10.3174/ajnr.A1922
Source: PubMed


BOLD MR imaging combined with a technique for precision control of end-tidal pCO(2) was used to produce quantitative maps of CVR in patients with Moyamoya disease. The technique was validated against measures of disease severity by using conventional angiography; it then was used to study the relationship between CVR, vascular steal, and disease severity.
A retrospective analysis comparing conventional angiography with BOLD MR imaging was performed on 11 patients with Moyamoya disease. Iso-oxic cycling of end-tidal pCO(2) between 2 target values was performed during BOLD MR imaging. CVR was calculated as the BOLD signal difference per Delta pCO(2). CVR was correlated with the presence of Moyamoya or pial collaterals and the degree of Moyamoya disease as graded by using a modified Suzuki score.
A good correlation between mean CVR and Suzuki score was found for the MCA and ACA territories (Pearson correlation coefficient, -0.7560 and -0.6140, respectively; P < .0001). A similar correlation was found between mean CVR and the presence of pial and Moyamoya collateral vessels for combined MCA and ACA territories (Pearson correlation coefficient, -0.7466; P < .0001). On a voxel-for-voxel basis, there was a greater extent of steal within vascular territories with increasing disease severity (higher modified Suzuki score). Mean CVR was found to scale nonlinearly with the extent of vascular steal.
Quantitative measures of CVR show direct correlation with impaired vascular supply as measured by the modified Suzuki score and enable direct investigation of the physiology of autoregulatory reserve, including steal phenomenon, within a given vascular territory.

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    • "In many studies of clinical populations, an increase in arterial CO 2 levels is achieved using administration of a vasodilatory gas through a face mask during scanning [Heyn et al., 2010]. In patients with stroke, this may not always be desirable or feasible due to the discomfort of the experimental setup. "
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    ABSTRACT: Blood oxygenation level-dependent (BOLD) contrast functional magnetic resonance imaging (fMRI) is a widely used technique to map brain function, and to monitor its recovery after stroke. Since stroke has a vascular etiology, the neurovascular coupling between cerebral blood flow and neural activity may be altered, resulting in uncertainties when interpreting longitudinal BOLD signal changes. The purpose of this study was to demonstrate the feasibility of using a recently validated breath-hold task in patients with stroke, both to assess group level changes in cerebrovascular reactivity (CVR) and to determine if alterations in regional CVR over time will adversely affect interpretation of task-related BOLD signal changes. Three methods of analyzing the breath-hold data were evaluated. The CVR measures were compared over healthy tissue, infarcted tissue and the peri-infarct tissue, both sub-acutely (∼2 weeks) and chronically (∼4 months). In this cohort, a lack of CVR differences in healthy tissue between the patients and controls indicates that any group level BOLD signal change observed in these regions over time is unlikely to be related to vascular alterations. CVR was reduced in the peri-infarct tissue but remained unchanged over time. Therefore, although a lack of activation in this region compared with the controls may be confounded by a reduced CVR, longitudinal group-level BOLD changes may be more confidently attributed to neural activity changes in this cohort. By including this breath-hold-based CVR assessment protocol in future studies of stroke recovery, researchers can be more assured that longitudinal changes in BOLD signal reflect true alterations in neural activity. Hum Brain Mapp, 2015. © 2014 Wiley Periodicals, Inc. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.
    Human Brain Mapping 02/2015; 36(5). DOI:10.1002/hbm.22735 · 5.97 Impact Factor
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    • "Mapping of CVR has been used to identify neuro-vascular uncoupling for the purpose of pre-surgical planning in tumor resection procedures (Zaca et al., 2011). Furthermore, CVR maps have been used to evaluate clinical outcomes in patients following corrective cerebrovascular surgery (Han et al., 2011; Heyn et al., 2010; Mikulis et al., 2005). CVR also plays a role during the calibration process for quantitative functional Blood Oxygen Level Dependent (BOLD) imaging (Davis et al., 1998; Gauthier and Hoge, 2013; He and Yablonskiy, 2007; Hoge, 2012; Pike, 2012). "
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    ABSTRACT: Cerebrovascular reactivity (CVR) is a mechanism responsible for maintaining stable perfusion pressure within the brain via smooth muscle mediated modulations of vascular tone. The amplitude of cerebral blood flow (CBF) change in response to a stimulus has been evaluated using Blood Oxygen Level Dependent (BOLD) MRI, however the relationship between the stimulus and the measured signal remain unclear. CVR measured invasively in animal models and using blood-velocity based measurements in humans has demonstrated a sigmoidal relationship between Cerebral Blood Flow and CO2 partial pressure. Using an ultra-high magnetic field strength (7T) MRI scanner and a computer controlled gas delivery system, we examined the regional and voxel-wise CVR response in relation to a targeted progressively increasing hypo- to hypercapnic stimulus. The aim of this study was to assess the non-linearity/sigmoidal behavior of the CVR response at varying arterial CO2 (PaCO2) levels. We find that a sigmoidal model provides a better description of the BOLD signal response to increasing PaCO2 than a linear model. A distinct whole-brain and gray matter BOLD-CVR signal plateau was observed in both voxel-wise and regional analysis. Furthermore, we demonstrate that a progressively increasing stimulus in combination with a sigmoidal response model can be used to obtain CVR values and provides additional physiologically relevant information (such as linear and non-linear response domains, and maximum response amplitudes) that may be more difficult to obtain from blocked CVR experiments. Considering these results, we propose an alternative way in which to define CVR based on the derivative of the BOLD-CVR response curve, which can potentially be used to differentiate between healthy and diseased vascular states.
    NeuroImage 05/2014; 98. DOI:10.1016/j.neuroimage.2014.05.006 · 6.36 Impact Factor
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    • "These two examples used transcranial Doppler ultrasonography to measure CVR, whereas whole-brain BOLD fMRI can better localise the downstream effects of arterial stenosis and provide even more powerful diagnostic information . For example, CO 2 gas administration and BOLD CVR maps determine the location and extent of abnormal vascular reactivity secondary to proximal large-vessel stenoses, including steal phenomenon , in moyamoya patients (Heyn et al., 2010; Mikulis et al., 2005). Breath-holds have also been successfully used to measure BOLD CVR in patients with brain tumours; good agreement with the results of gadolinium contrast administration was observed, and the authors suggest that BOLD CVR may be more sensitive to certain types of vascular abnormalities than the DSC technique (Pillai and Zacá, 2011, 2012). "
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    ABSTRACT: Cerebrovascular reactivity (CVR) can be mapped using BOLD fMRI to provide a clinical insight into vascular health that can be used to diagnose cerebrovascular disease. Breath-holds are a readily accessible method for producing the required arterial CO2 increases but their implementation into clinical studies is limited by concerns that patients will demonstrate highly variable performance of breath-hold challenges. This study assesses the repeatability of CVR measurements despite poor task performance, to determine if and how robust results could be achieved with breath-holds in patients. Twelve healthy volunteers were scanned at 3T. Six functional scans were acquired, each consisting of 6 breath-hold challenges (10, 15, or 20 s duration) interleaved with periods of paced breathing. These scans simulated the varying breath-hold consistency and ability levels that may occur in patient data. Uniform ramps, time-scaled ramps, and end-tidal CO2 data were used as regressors in a general linear model in order to measure CVR at the grey matter, regional, and voxelwise level. The intraclass correlation coefficient (ICC) quantified the repeatability of the CVR measurement for each breath-hold regressor type and scale of interest across the variable task performances. The ramp regressors did not fully account for variability in breath-hold performance and did not achieve acceptable repeatability (ICC<0.4) in several regions analysed. In contrast, the End-tidal CO2 regressors resulted in "excellent" repeatability (ICC=0.82) in the average grey matter data, and resulted in acceptable repeatability in all smaller regions tested (ICC > 0.4). Further analysis of intra-subject CVR variability across the brain (ICCspatial and voxelwise correlation) supported the use of End-tidal CO2 data to extract robust whole-brain CVR maps, despite variability in breath-hold performance. We conclude that the incorporation of end-tidal CO2 monitoring into scanning enables robust, repeatable measurement of CVR that makes breath-hold challenges suitable for routine clinical practice.
    NeuroImage 07/2013; 83(100). DOI:10.1016/j.neuroimage.2013.07.007 · 6.36 Impact Factor
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