The Vascular Steal Phenomenon is an Incomplete Contributor to Negative Cerebrovascular Reactivity in Patients with Symptomatic Intracranial Stenosis

‘Vascular steal’ has been proposed as a compensatory mechanism in hemodynamically compromised ischemic parenchyma. Here, independent measures of cerebral blood flow (CBF) and blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) responses to a vascular stimulus in patients with ischemic cerebrovascular disease are recorded. Symptomatic intracranial stenosis patients ( n = 40) underwent a multimodal 3.0T MRI protocol including structural (T1-weighted and T2-weighted fluid-attenuated inversion recovery) and hemodynamic (BOLD and CBF-weighted arterial spin labeling) functional MRI during room air and hypercarbic gas administration. CBF changes in regions demonstrating negative BOLD reactivity were recorded, as well as clinical correlates including symptomatic hemisphere by infarct and lateralizing symptoms. Fifteen out of forty participants exhibited negative BOLD reactivity. Of these, a positive relationship was found between BOLD and CBF reactivity in unaffected (stenosis degree <50%) cortex. In negative BOLD cerebrovascular reactivity regions, three patients exhibited significant ( P < 0.01) reductions in CBF consistent with vascular steal; six exhibited increases in CBF; and the remaining exhibited no statistical change in CBF. Secondary findings were that negative BOLD reactivity correlated with symptomatic hemisphere by lateralizing clinical symptoms and prior infarcts(s). These data support the conclusion that negative hypercarbia-induced BOLD responses, frequently assigned to vascular steal, are heterogeneous in origin with possible contributions from autoregulation and/or metabolism.

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Hemodynamic and metabolic changes during hypercapnia with normoxia and hyperoxia using pCASL and TRUST MRI in healthy adults

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x211064572 ◽

2021 ◽

pp. 0271678X2110645

Author(s):

Pieter T Deckers ◽

Alex A Bhogal ◽

Mathijs BJ Dijsselhof ◽

Carlos C Faraco ◽

Peiying Liu ◽

...

Keyword(s):

Arterial Spin Labeling ◽

Oxygen Metabolism ◽

Blood Oxygenation Level Dependent ◽

Blood Oxygenation ◽

Cerebrovascular Reactivity ◽

Oxygen Extraction Fraction ◽

Mixed Effect ◽

Cerebral Oxygen Metabolism ◽

Extraction Fraction ◽

Oxygenation Level

Blood oxygenation level-dependent (BOLD) or arterial spin labeling (ASL) MRI with hypercapnic stimuli allow for measuring cerebrovascular reactivity (CVR). Hypercapnic stimuli are also employed in calibrated BOLD functional MRI for quantifying neuronally-evoked changes in cerebral oxygen metabolism (CMRO2). It is often assumed that hypercapnic stimuli (with or without hyperoxia) are iso-metabolic; increasing arterial CO2 or O2 does not affect CMRO2. We evaluated the null hypothesis that two common hypercapnic stimuli, ‘CO2 in air’ and carbogen, are iso-metabolic. TRUST and ASL MRI were used to measure the cerebral venous oxygenation and cerebral blood flow (CBF), from which the oxygen extraction fraction (OEF) and CMRO2 were calculated for room-air, ‘CO2 in air’ and carbogen. As expected, CBF significantly increased (9.9% ± 9.3% and 12.1% ± 8.8% for ‘CO2 in air’ and carbogen, respectively). CMRO2 decreased for ‘CO2 in air’ (−13.4% ± 13.0%, p < 0.01) compared to room-air, while the CMRO2 during carbogen did not significantly change. Our findings indicate that ‘CO2 in air’ is not iso-metabolic, while carbogen appears to elicit a mixed effect; the CMRO2 reduction during hypercapnia is mitigated when including hyperoxia. These findings can be important for interpreting measurements using hypercapnic or hypercapnic-hyperoxic (carbogen) stimuli.

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

Magnetic Resonance Imaging ◽

10.1016/j.mri.2020.03.012 ◽

2020 ◽

Vol 70 ◽

pp. 50-56

Author(s):

Giovanni Muscas ◽

Christiaan Hendrik Bas van Niftrik ◽

Martina Sebök ◽

Katharina Seystahl ◽

Marco Piccirelli ◽

...

Keyword(s):

Blood Oxygenation Level Dependent ◽

Blood Oxygenation ◽

Cerebrovascular Reactivity ◽

Diffuse Glioma ◽

Blood Oxygenation Level ◽

Oxygenation Level

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The Cumulative Influence of Hyperoxia and Hypercapnia on Blood Oxygenation and R2*

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2015.168 ◽

2015 ◽

Vol 35 (12) ◽

pp. 2032-2042 ◽

Cited By ~ 9

Author(s):

Carlos C Faraco ◽

Megan K Strother ◽

Jeroen CW Siero ◽

Daniel F Arteaga ◽

Allison O Scott ◽

...

Keyword(s):

Venous Blood ◽

Quantitative Information ◽

Blood Oxygenation ◽

Cerebrovascular Reactivity ◽

Resonance Imaging ◽

Tissue Water ◽

Bold Mri ◽

Bold Imaging ◽

Complex Interactions ◽

Oxygenation Level

Cerebrovascular reactivity (CVR)-weighted blood-oxygenation-level-dependent magnetic resonance imaging (BOLD-MRI) experiments are frequently used in conjunction with hyperoxia. Owing to complex interactions between hyperoxia and hypercapnia, quantitative effects of these gas mixtures on BOLD responses, blood and tissue R2∗, and blood oxygenation are incompletely understood. Here we performed BOLD imaging (3T; TE/TR = 35/2,000 ms; spatial resolution = 3×3×3.5 mm3) in healthy volunteers ( n = 12; age = 29±4.1 years) breathing (i) room air (RA), (ii) normocapnic-hyperoxia (95% O2/5% N2, HO), (iii) hypercapnic-normoxia (5% CO2/21% O2/74% N2, HC-NO), and (iv) hypercapnic-hyperoxia (5% CO2/95% O2, HC-HO). For HC-HO, experiments were performed with separate RA and HO baselines to control for changes in O2. T2-relaxation-under-spin-tagging MRI was used to calculate basal venous oxygenation. Signal changes were quantified and established hemodynamic models were applied to quantify vasoactive blood oxygenation, blood–water R∗2, and tissue-water R∗2. In the cortex, fractional BOLD changes (stimulus/baseline) were HO/RA = 0.011 ± 0.007; HC-NO/RA = 0.014±0.004; HC-HO/HO = 0.020±0.008; and HC-HO/RA = 0.035 ±0.010; for the measured basal venous oxygenation level of 0.632, this led to venous blood oxygenation levels of 0.660 (HO), 0.665 (HC-NO), and 0.712 (HC-HO). Interleaving a HC-HO stimulus with HO baseline provided a smaller but significantly elevated BOLD response compared with a HC-NO stimulus. Results provide an outline for how blood oxygenation differs for several gas stimuli and provides quantitative information on how hypercapnic BOLD CVR and R∗2 are altered during hyperoxia.

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Impact of baseline CO 2 on Blood-Oxygenation-Level-Dependent MRI measurements of cerebrovascular reactivity and task-evoked signal activation

Magnetic Resonance Imaging ◽

10.1016/j.mri.2018.02.002 ◽

2018 ◽

Vol 49 ◽

pp. 123-130 ◽

Cited By ~ 5

Author(s):

Christiaan Hendrik Bas van Niftrik ◽

Marco Piccirelli ◽

Oliver Bozinov ◽

Nicolai Maldaner ◽

Catherine Strittmatter ◽

...

Keyword(s):

Blood Oxygenation Level Dependent ◽

Blood Oxygenation ◽

Cerebrovascular Reactivity ◽

Blood Oxygenation Level ◽

Oxygenation Level ◽

Mri Measurements ◽

Signal Activation ◽

And Task

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Origin of Negative Blood Oxygenation Level—Dependent fMRI Signals

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-200208000-00002 ◽

2002 ◽

Vol 22 (8) ◽

pp. 908-917 ◽

Cited By ~ 231

Author(s):

Noam Harel ◽

Sang-Pil Lee ◽

Tsukasa Nagaoka ◽

Dae-Shik Kim ◽

Seong-Gi Kim

Keyword(s):

Neural Activity ◽

Spike Activity ◽

Visual Stimulation ◽

Blood Oxygenation Level Dependent ◽

Blood Oxygenation ◽

Bold Signal ◽

Area 18 ◽

Blood Oxygenation Level ◽

Oxygenation Level ◽

Negative Bold

Functional magnetic resonance imaging (fMRI) techniques are based on the assumption that changes in spike activity are accompanied by modulation in the blood oxygenation level—dependent (BOLD) signal. In addition to conventional increases in BOLD signals, sustained negative BOLD signal changes are occasionally observed and are thought to reflect a decrease in neural activity. In this study, the source of the negative BOLD signal was investigated using T2*-weighted BOLD and cerebral blood volume (CBV) techniques in isoflurane-anesthetized cats. A positive BOLD signal change was observed in the primary visual cortex (area 18) during visual stimulation, while a prolonged negative BOLD change was detected in the adjacent suprasylvian gyrus containing higher-order visual areas. However, in both regions neurons are known to increase spike activity during visual stimulation. The positive and negative BOLD amplitudes obtained at six spatial-frequency stimuli were highly correlated, and negative BOLD percent changes were approximately one third of the postitive changes. Area 18 with positive BOLD signals experienced an increase in CBV, while regions exhibiting the prolonged negative BOLD signal underwent a decrease in CBV. The CBV changes in area 18 were faster than the BOLD signals from the same corresponding region and the CBV changes in the suprasylvian gyrus. The results support the notion that reallocation of cortical blood resources could overcome a local demand for increased cerebral blood flow induced by increased neural activity. The findings of this study imply that caution should be taken when interpreting the negative BOLD signals as a decrease in neuronal activity.

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Assessing Cerebrovascular Reactivity in Carotid Steno-Occlusive Disease Using MRI BOLD and ASL Techniques

Radiology Research and Practice ◽

10.1155/2012/268483 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 5

Author(s):

Renata F. Leoni ◽

Kelley C. Mazzetto-Betti ◽

Afonso C. Silva ◽

Antonio C. dos Santos ◽

Draulio B. de Araujo ◽

...

Keyword(s):

Cerebrovascular Diseases ◽

Blood Oxygenation ◽

Occlusive Disease ◽

Cerebrovascular Reactivity ◽

Vascular Regulation ◽

Oxygenation Level ◽

Biochemical Mechanisms ◽

Magnetic Resonance Imaging Mri ◽

Source Of Information ◽

Reliable Methods

Impaired cerebrovascular reactivity (CVR), a predictive factor of imminent stroke, has been shown to be associated with carotid steno-occlusive disease. Magnetic resonance imaging (MRI) techniques, such as blood oxygenation level-dependent (BOLD) and arterial spin labeling (ASL), have emerged as promising noninvasive tools to evaluate altered CVR with whole-brain coverage, when combined with a vasoactive stimulus, such as respiratory task or injection of acetazolamide. Under normal cerebrovascular conditions, CVR has been shown to be globally and homogenously distributed between hemispheres, but with differences among cerebral regions. Such differences can be explained by anatomical specificities and different biochemical mechanisms responsible for vascular regulation. In patients with carotid steno-occlusive disease, studies have shown that MRI techniques can detect impaired CVR in brain tissue supplied by the affected artery. Moreover, resulting CVR estimations have been well correlated to those obtained with more established techniques, indicating that BOLD and ASL are robust and reliable methods to assess CVR in patients with cerebrovascular diseases. Therefore, the present paper aims to review recent studies which use BOLD and ASL to evaluate CVR, in healthy individuals and in patients with carotid steno-occlusive disease, providing a source of information regarding the obtained results and the methodological difficulties.

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Distinct Cerebrovascular Reactivity Patterns for Brain Radiation Necrosis

Cancers ◽

10.3390/cancers13081840 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1840

Author(s):

Giovanni Muscas ◽

Christiaan Hendrik Bas van Niftrik ◽

Martina Sebök ◽

Alessandro Della Puppa ◽

Katharina Seystahl ◽

...

Keyword(s):

Radiation Necrosis ◽

Area Under The Curve ◽

Recurrent Glioblastoma ◽

Blood Oxygenation ◽

Cerebrovascular Reactivity ◽

Receiver Operating Characteristic Curves ◽

Volume Of Interest ◽

Oxygenation Level ◽

Newly Diagnosed Glioblastoma ◽

Two Parameters

Background: Current imaging-based discrimination between radiation necrosis versus recurrent glioblastoma contrast-enhancing lesions remains imprecise but is paramount for prognostic and therapeutic evaluation. We examined whether patients with radiation necrosis exhibit distinct patterns of blood oxygenation-level dependent fMRI cerebrovascular reactivity (BOLD-CVR) as the first step to better distinguishing patients with radiation necrosis from recurrent glioblastoma compared with patients with newly diagnosed glioblastoma before surgery and radiotherapy. Methods: Eight consecutive patients with primary and secondary brain tumors and a multidisciplinary clinical and radiological diagnosis of radiation necrosis, and fourteen patients with a first diagnosis of glioblastoma underwent BOLD-CVR mapping. For all these patients, the contrast-enhancing lesion was derived from high-resolution T1-weighted MRI and rendered the volume-of-interest (VOI). From this primary VOI, additional 3 mm concentric expanding VOIs up to 30 mm were created for a detailed perilesional BOLD-CVR tissue analysis between the two groups. Receiver operating characteristic curves assessed the discriminative properties of BOLD-CVR for both groups. Results: Mean intralesional BOLD-CVR values were markedly lower in radiation necrosis than in glioblastoma contrast-enhancing lesions (0.001 ± 0.06 vs. 0.057 ± 0.05; p = 0.04). Perilesionally, a characteristic BOLD-CVR pattern was observed for radiation necrosis and glioblastoma patients, with an improvement of BOLD-CVR values in the radiation necrosis group and persisting lower perilesional BOLD-CVR values in glioblastoma patients. The ROC analysis discriminated against both groups when these two parameters were analyzed together (area under the curve: 0.85, 95% CI: 0.65–1.00). Conclusions: In this preliminary analysis, distinctive intralesional and perilesional BOLD-cerebrovascular reactivity patterns are found for radiation necrosis.

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Intraoperative BOLD-fMRI Cerebrovascular Reactivity Assessment

Acta Neurochirurgica Supplement - Trends in Cerebrovascular Surgery and Interventions ◽

10.1007/978-3-030-63453-7_20 ◽

2021 ◽

pp. 139-143

Author(s):

Giovanni Muscas ◽

Christiaan Hendrik Bas van Niftrik ◽

Martina Sebök ◽

Giuseppe Esposito ◽

Luca Regli ◽

...

Keyword(s):

Cerebrovascular Diseases ◽

Blood Oxygenation ◽

Cerebrovascular Reactivity ◽

Hemodynamic State ◽

Neurosurgical Patients ◽

Blood Oxygenation Level ◽

Oxygenation Level ◽

Ischemic Cerebrovascular Diseases ◽

Brain Gliomas ◽

The Brain

AbstractBlood 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.

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Abstract 167: Noninvasive MRI Measurement of Cerebrovascular Reactivity Enables Evaluation of Surgical Revascularization Response in Moyamoya

Stroke ◽

10.1161/str.45.suppl_1.167 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Travis R Ladner ◽

Carlos Faraco ◽

Manus J Donahue ◽

Daniel Arteaga ◽

Lori C Jordan ◽

...

Keyword(s):

Tissue Level ◽

Blood Oxygenation ◽

Cerebrovascular Reactivity ◽

Clinical Severity ◽

Atmospheric Air ◽

Bold Mri ◽

Oxygenation Level ◽

Hemodynamic Improvement ◽

Mri Changes ◽

Mri Measurements

Introduction: Frequent dissociation between clinical severity and angiographic grading of moyamoya supports a role for alternative tissue-level hemodynamic measures. Here, angiography is complemented with noninvasive MRI measurements of parenchymal impairment to assess changes in cerebrovascular reactivity (CVR) after extracranial-intracranial bypass in moyamoya. Hypothesis: CVR is regionally impaired pre-operatively, yet increases after surgery. This can be visualized noninvasively by assessing blood oxygenation level-dependent (BOLD) MRI changes with safe, mildly hypercarbic gas. Methods: Using a block MRI paradigm, carbogen (5% CO 2 ; 95% O 2 3 min) was interleaved with atmospheric air (<1% CO 2 ; 3 min) administration during BOLD MRI in intracranial stenosis patients (n=70), a subset of which (n=9; age=35.7+/-10.8; 7F/2M) underwent indirect (n=8) or direct (n=1) revascularization for moyamoya. Five patients had both pre-operative and post-operative hemodynamic imaging, with post-operative scans performed after 7.3+/-4.1 months. CVR, calculated as a z-statistic in response to hypercarbia vs. atmospheric air, was compared (two-tailed t-test) for each patient between the two time points to correlate CVR changes with surgery. Results: Fig. 1 shows BOLD MRI on a patient scanned before and 2 years after right-sided indirect bypass, with significant (t=79.29, p<0.01) right-sided hemodynamic improvement. Cohort analyses of patients with pre/post-operative scans revealed significant interhemispheric CVR differences prior to surgery (t=3.48, p<0.01), which resolved after bypass (t=0.88, p=0.20). Additionally, CVR increased significantly in the operative hemisphere (t=4.50, p<0.01). Conclusions: CVR-weighted hemodynamic MRI can be implemented into routine clinical protocols, corresponds well with revascularization response, and has potential as a noninvasive complement to angiography for serial monitoring of moyamoya patients.

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The Role of Cerebrovascular-Reactivity Mapping in Functional MRI: Calibrated fMRI and Resting-State fMRI

Frontiers in Physiology ◽

10.3389/fphys.2021.657362 ◽

2021 ◽

Vol 12 ◽

Author(s):

J. Jean Chen ◽

Claudine J. Gauthier

Keyword(s):

Functional Mri ◽

Resting State ◽

Resting State Fmri ◽

Blood Oxygenation ◽

Cerebrovascular Reactivity ◽

Resting State Functional Connectivity ◽

Non Invasive ◽

Oxygenation Level ◽

Calibrated Fmri

Task and resting-state functional MRI (fMRI) is primarily based on the same blood-oxygenation level-dependent (BOLD) phenomenon that MRI-based cerebrovascular reactivity (CVR) mapping has most commonly relied upon. This technique is finding an ever-increasing role in neuroscience and clinical research as well as treatment planning. The estimation of CVR has unique applications in and associations with fMRI. In particular, CVR estimation is part of a family of techniques called calibrated BOLD fMRI, the purpose of which is to allow the mapping of cerebral oxidative metabolism (CMRO2) using a combination of BOLD and cerebral-blood flow (CBF) measurements. Moreover, CVR has recently been shown to be a major source of vascular bias in computing resting-state functional connectivity, in much the same way that it is used to neutralize the vascular contribution in calibrated fMRI. Furthermore, due to the obvious challenges in estimating CVR using gas challenges, a rapidly growing field of study is the estimation of CVR without any form of challenge, including the use of resting-state fMRI for that purpose. This review addresses all of these aspects in which CVR interacts with fMRI and the role of CVR in calibrated fMRI, provides an overview of the physiological biases and assumptions underlying hypercapnia-based CVR and calibrated fMRI, and provides a view into the future of non-invasive CVR measurement.

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