Cerebrovascular Reactivity Mapping: An Evolving Standard for Clinical Functional Imaging

Pillai, Jay J.; Mikulis, David J.

doi:10.3174/ajnr.a3941

Cited by 131 publications

(173 citation statements)

References 31 publications

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“…A significant limitation of task-based fMRI, however, is false negative activation, termed neurovascular uncoupling. [13,14] Here, the neurons are indeed signaling (ie. the subject performs a task, such as fingertapping), resulting in a BOLD signal change.…”

Section: Discussionmentioning

confidence: 99%

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Altered intraoperative cerebrovascular reactivity in brain areas of high-grade glioma recurrence

Fierstra

Niftrik

Piccirelli

et al. 2016

Magnetic Resonance Imaging

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INTRODUCTION: Current MRI sequences are limited in identifying brain areas at risk for high grade glioma recurrence. We employed intraoperative 3-Tesla functional MRI to assess cerebrovascular reactivity (CVR) after high-grade glioma resection and analyzed regional CVR responses in areas of tumor recurrence on clinical follow-up imaging. METHODS: Five subjects with high-grade glioma that underwent an intraoperative Blood Oxygen-Level Dependent (BOLD) MRI CVR examination and had a clinical follow-up of at least 18 months were selected from a prospective database. For this study, location of tumor recurrence was spatially matched to the intraoperative imaging to assess CVR response in that particular area. CVR is defined as the percent BOLD signal change during repeated cycles of apnea. RESULTS: Of the 5 subjects (mean age 44, 2 females), 4 were diagnosed with a WHO grade III and 1 subject with a WHO grade IV glioma. Three subjects exhibited a tumor recurrence on clinical follow-up MRI (mean: 15 months). BOLD CVR measured in the spatially matched area of tumor recurrence was on average 94% increased (range -32% to 183%) as compared to contralateral hemisphere CVR response, 1.50±0.81 versus 1.03±0.46 respectively (p=0.31). CONCLUSION: For this first analysis in a small cohort, we found altered intraoperative CVR in brain areas exhibiting high grade glioma recurrence on clinical follow-up imaging. Methods: Five subjects with high-grade glioma that underwent an intraoperative BloodOxygen-Level Dependent (BOLD) MRI CVR examination and had a clinical follow-up of at least 18 months were selected from a prospective database. For this study, location of tumor recurrence was spatially matched to the intraoperative imaging to assess CVR response in that particular area. CVR is defined as the percent BOLD signal change during repeated cycles of apnea.Results: Of the 5 subjects (mean age 44, 2 females), 4 were diagnosed with a WHO grade III and 1 subject with a WHO grade IV glioma. Three subjects exhibited a tumor recurrence on clinical follow-up MRI (mean: 15 months). BOLD CVR measured in the spatially matched area of tumor recurrence was on average 64% increased (range -29% to 123%) as compared to whole brain CVR response, 1.50±0.81 versus 1.09±0.37 respectively. Conclusion:For this first analysis in a small cohort, we found altered intraoperative CVR in brain areas exhibiting high grade glioma recurrence on clinical follow-up imaging.

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Section: Discussionmentioning

confidence: 99%

“…6 Improvements of BOLD CVR methodologies have been proposed [13,15] and may increase sensitivity and quantification of (regional) CVR measurements in subjects with high-grade cerebral glioma.…”

Section: Limitations and Future Considerationsmentioning

confidence: 99%

Altered intraoperative cerebrovascular reactivity in brain areas of high-grade glioma recurrence

Fierstra

Niftrik

Piccirelli

et al. 2016

Magnetic Resonance Imaging

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“…This method was chosen to maximize steadystate PETCO 2 -targetting accuracy and stability while minimizing PETO 2 confounds during CO 2 -based CVR measurements (Chen and Pike, 2010b;Halani et al, 2015;Mark et al, 2010;Prisman et al, 2008), and is the most established method clinically (Pillai and Mikulis, 2015).…”

Section: Bmentioning

confidence: 99%

Quantitative mapping of cerebrovascular reactivity using resting-state BOLD fMRI: Validation in healthy adults

2016

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In conventional neuroimaging, cerebrovascular reactivity (CVR) is quantified primarily using the blood-oxygenation level-dependent (BOLD) functional MRI (fMRI) signal, specifically, as the BOLD response to intravascular carbon dioxide (CO 2 ) modulations, in units of [%ΔBOLD/ mmHg]. While this method has achieved wide appeal and clinical translation, the tolerability of CO 2 -related tasks amongst patients and the elderly remains a challenge in more routine and largescale applications. In this work, we propose an improved method to quantify CVR by exploiting intrinsic fluctuations in CO 2 and corresponding changes in the resting-state BOLD signal (rsqCVR). Our rs-qCVR approach requires simultaneous monitoring of PETCO 2 , cardiac pulsation and respiratory volume. In 16 healthy adults, we compare our quantitative CVR estimation technique to the prospective CO 2 -targeting based CVR quantification approach (qCVR, the "standard"). We also compare our rs-CVR to non-quantitative alternatives including the restingstate fluctuation amplitude (RSFA), amplitude of low-frequency fluctuation (ALFF) and globalsignal regression. When all subjects were pooled, only RSFA and ALFF were significantly associated with qCVR. However, for characterizing regional CVR variations within each subject, only the PETCO 2 -based rs-qCVR measure is strongly associated with standard qCVR in 100% of the subjects (p<=0.1). In contrast, for the more qualitative CVR measures, significant withinsubject association with qCVR was only achieved in 50-70% of the subjects. Our work establishes the feasibility of extracting quantitative CVR maps using rs-fMRI, opening the possibility of mapping functional connectivity and qCVR simultaneously.

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“…Moreover, the relationship between fMRI signals, neurovascular coupling and neuronal activity is not fully understood 113 . Furthermore, some inherent assumptions about the haemodynamic response and vascular reactivity might be violated for some people, owing to age, obesity, stroke and other neurovascular complications [114][115][116] . The haemodynamic ceiling effect and baseline blood flow both affect the magnitude of stimulus-evoked fMRI responses, and should be considered when using fMRI to assess the magnitude of evoked responses and analyse connectivity.…”

Section: Haemodynamic Ceiling Effectmentioning

confidence: 99%

Brain imaging tests for chronic pain: medical, legal and ethical issues and recommendations

et al. 2017

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624 | OCTOBER 2017 | VOLUME 13 www.nature.com/nrneurol CONSENSUS STATEMENT © 2 0 1 7 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d . NeuroethicsA field that studies the implications of neuroscience for human self-understanding, ethics, and policy. Arterial spin labellingAn MRI-based brain imaging technique that detects cerebral blood flow based on magnetic tagging of blood.Nevertheless, diverse groups -including patients, researchers, clinicians, pharmaceutical and medical device companies, insurers and the legal communityseek methods for evaluating chronic pain besides selfreporting. Patients seek objective testing to demonstrate the reality of an invisible condition that is sometimes subject to doubt, researchers seek brain imaging markers that provide scientific, diagnostic and prognostic information that cannot be provided by patient self-reporting, and legal representatives and officials seek techniques to supplement self-reporting and objectively support or challenge claims related to chronic pain. Brain imaging technologies, including functional MRI (fMRI), PET, EEG and magnetoencephalography (MEG), have the potential to provide objective measurements of patterns of brain activity that underlie perceptual experiences (BOX 1). Consequently, some people are looking to brain imaging to provide a window into the experience of chronic pain, particularly because testimony based on fMRI was deemed to be admissible as evidence of pain in a 2015 state trial court in the USA 10,11 . This case was highly publicized, although the judgement was not published so no legal precedent was set, and the grounds on which the fMRI evidence was admitted were criticized by established experts in brain imaging studies of pain 10,11 . In this context, the development of a brain imaging test for chronic pain [12][13][14] has real-world consequences, so appropriate criteria for the use of such a test must be defined. Importantly, the way in which brain imaging evidence might be implemented in legal cases strongly depends on laws that vary greatly between countries. Therefore, examination of the capability of so-called 'pain-o-meter' brain imaging tests is critical, as is consideration of the use of such technology in light of societal views, neuroethics and legal issues. Thus, the aims of this Consensus Statement are to recommend criteria for the evaluation of neuroimaging measures of chronic pain, and to discuss the technical, biological, neuroethical and legal challenges related to establishing brain-based tests for chronic pain. MethodsA presidential task force of the International Association for the Study of Pain (IASP) was established in 2015 to examine the feasibility of a brain-imaging-based diagnostic test for chronic pain. The task force had three purposes: to consider the capacity of brain imaging (in particular fMRI), on the basis of its technical and physiological constraints, to detect whether an individual has chronic pain; to place th...

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Cerebrovascular Reactivity Mapping: An Evolving Standard for Clinical Functional Imaging

Cited by 131 publications

References 31 publications

Altered intraoperative cerebrovascular reactivity in brain areas of high-grade glioma recurrence

Altered intraoperative cerebrovascular reactivity in brain areas of high-grade glioma recurrence

Quantitative mapping of cerebrovascular reactivity using resting-state BOLD fMRI: Validation in healthy adults

Brain imaging tests for chronic pain: medical, legal and ethical issues and recommendations

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