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Nanayakkara ND, Meusel LA, Anderson ND, Chen JJ. Estimation of cerebrovascular reactivity amplitude and lag using breath-holding fMRI and the global BOLD signal: Application in diabetes and hypertension. J Cereb Blood Flow Metab 2025; 45:459-475. [PMID: 39224949 PMCID: PMC11572012 DOI: 10.1177/0271678x241270420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2024] [Revised: 07/03/2024] [Accepted: 07/08/2024] [Indexed: 09/04/2024]
Abstract
In this work, we demonstrate a data-driven approach for estimating cerebrovascular reactivity (CVR) amplitude and lag from breathhold (BH) fMRI data alone. Our approach employs a frequency-domain approach that is independent of external recordings. CVR amplitude is estimated from the BOLD frequency spectrum and CVR lag is estimated from the Fourier phase using the global-mean BOLD signal as reference. Unlike referencing to external recordings, these lags are specific to the brain. We demonstrated our method in detecting regional CVR amplitude and lag differences across healthy (CTL), hypertensive (HT) and hypertension-plus-type-2-diabetes (HT + DM) groups of similar ages and sex ratios, with a total N of 49. We found CVR amplitude to be significantly higher in CTL compared to HT + DM, with minimal difference between CTL and HT. Also, voxelwise CVR lag estimated in the Fourier domain is a more sensitive marker of vascular dysfunction than CVR amplitude. CVR lag in HT is significantly shorter than in CTL, with minimal difference between CTL and HT + DM. Our results support the importance of joint CVR amplitude and lag assessments in clinical applications.
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Affiliation(s)
- Nuwan D Nanayakkara
- Rotman Research Institute, Baycrest Academy for Research and Education, Toronto, Canada
| | - Liesel-Ann Meusel
- Rotman Research Institute, Baycrest Academy for Research and Education, Toronto, Canada
| | - Nicole D Anderson
- Rotman Research Institute, Baycrest Academy for Research and Education, Toronto, Canada
- Departments of Psychology and Psychiatry, University of Toronto, Toronto, Canada
| | - J Jean Chen
- Rotman Research Institute, Baycrest Academy for Research and Education, Toronto, Canada
- Department of Medical Biophysics, University of Toronto, Toronto, Canada
- Department of Biomedical Engineering, University of Toronto, Toronto, Canada
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Agarwal S, Welker KM, Black DF, Little JT, DeLone DR, Messina SA, Passe TJ, Bettegowda C, Pillai JJ. Detection and Mitigation of Neurovascular Uncoupling in Brain Gliomas. Cancers (Basel) 2023; 15:4473. [PMID: 37760443 PMCID: PMC10527022 DOI: 10.3390/cancers15184473] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 08/28/2023] [Accepted: 09/01/2023] [Indexed: 09/29/2023] Open
Abstract
Functional magnetic resonance imaging (fMRI) with blood oxygen level-dependent (BOLD) technique is useful for preoperative mapping of brain functional networks in tumor patients, providing reliable in vivo detection of eloquent cortex to help reduce the risk of postsurgical morbidity. BOLD task-based fMRI (tb-fMRI) is the most often used noninvasive method that can reliably map cortical networks, including those associated with sensorimotor, language, and visual functions. BOLD resting-state fMRI (rs-fMRI) is emerging as a promising ancillary tool for visualization of diverse functional networks. Although fMRI is a powerful tool that can be used as an adjunct for brain tumor surgery planning, it has some constraints that should be taken into consideration for proper clinical interpretation. BOLD fMRI interpretation may be limited by neurovascular uncoupling (NVU) induced by brain tumors. Cerebrovascular reactivity (CVR) mapping obtained using breath-hold methods is an effective method for evaluating NVU potential.
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Affiliation(s)
- Shruti Agarwal
- Division of Neuroradiology, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA;
| | - Kirk M. Welker
- Division of Neuroradiology, Department of Radiology, Mayo Clinic Rochester & Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA; (K.M.W.); (D.F.B.); (J.T.L.); (D.R.D.); (S.A.M.); (T.J.P.)
| | - David F. Black
- Division of Neuroradiology, Department of Radiology, Mayo Clinic Rochester & Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA; (K.M.W.); (D.F.B.); (J.T.L.); (D.R.D.); (S.A.M.); (T.J.P.)
| | - Jason T. Little
- Division of Neuroradiology, Department of Radiology, Mayo Clinic Rochester & Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA; (K.M.W.); (D.F.B.); (J.T.L.); (D.R.D.); (S.A.M.); (T.J.P.)
| | - David R. DeLone
- Division of Neuroradiology, Department of Radiology, Mayo Clinic Rochester & Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA; (K.M.W.); (D.F.B.); (J.T.L.); (D.R.D.); (S.A.M.); (T.J.P.)
| | - Steven A. Messina
- Division of Neuroradiology, Department of Radiology, Mayo Clinic Rochester & Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA; (K.M.W.); (D.F.B.); (J.T.L.); (D.R.D.); (S.A.M.); (T.J.P.)
| | - Theodore J. Passe
- Division of Neuroradiology, Department of Radiology, Mayo Clinic Rochester & Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA; (K.M.W.); (D.F.B.); (J.T.L.); (D.R.D.); (S.A.M.); (T.J.P.)
| | - Chetan Bettegowda
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA;
| | - Jay J. Pillai
- Division of Neuroradiology, Department of Radiology, Mayo Clinic Rochester & Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA; (K.M.W.); (D.F.B.); (J.T.L.); (D.R.D.); (S.A.M.); (T.J.P.)
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA;
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Gong J, Stickland RC, Bright MG. Hemodynamic timing in resting-state and breathing-task BOLD fMRI. Neuroimage 2023; 274:120120. [PMID: 37072074 PMCID: PMC10208394 DOI: 10.1016/j.neuroimage.2023.120120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 04/06/2023] [Accepted: 04/15/2023] [Indexed: 04/20/2023] Open
Abstract
The blood flow response to a vasoactive stimulus demonstrates regional heterogeneity across both the healthy brain and in cerebrovascular pathology. The timing of a regional hemodynamic response is emerging as an important biomarker of cerebrovascular dysfunction, as well as a confound within fMRI analyses. Previous research demonstrated that hemodynamic timing is more robustly characterized when a larger systemic vascular response is evoked by a breathing challenge, compared to when only spontaneous fluctuations in vascular physiology are present (i.e., in resting-state data). However, it is not clear whether hemodynamic delays in these two conditions are physiologically interchangeable, and how methodological signal-to-noise factors may limit their agreement. To address this, we generated whole-brain maps of hemodynamic delays in nine healthy adults. We assessed the agreement of voxel-wise gray matter (GM) hemodynamic delays between two conditions: resting-state and breath-holding. We found that delay values demonstrated poor agreement when considering all GM voxels, but increasingly greater agreement when limiting analyses to voxels showing strong correlation with the GM mean time-series. Voxels showing the strongest agreement with the GM mean time-series were primarily located near large venous vessels, however these voxels explain some, but not all, of the observed agreement in timing. Increasing the degree of spatial smoothing of the fMRI data enhanced the correlation between individual voxel time-series and the GM mean time-series. These results suggest that signal-to-noise factors may be limiting the accuracy of voxel-wise timing estimates and hence their agreement between the two data segments. In conclusion, caution must be taken when using voxel-wise delay estimates from resting-state and breathing-task data interchangeably, and additional work is needed to evaluate their relative sensitivity and specificity to aspects of vascular physiology and pathology.
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Affiliation(s)
- Jingxuan Gong
- Department of Biomedical Engineering, McCormick School of Engineering and Applied Sciences, Northwestern University, Evanston, IL, United States of America.
| | - Rachael C Stickland
- Department of Physical Therapy and Human Movement Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States of America
| | - Molly G Bright
- Department of Biomedical Engineering, McCormick School of Engineering and Applied Sciences, Northwestern University, Evanston, IL, United States of America; Department of Physical Therapy and Human Movement Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States of America
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Pommy J, Smart CM, Bryant AM, Wang Y. Three potential neurovascular pathways driving the benefits of mindfulness meditation for older adults. Front Aging Neurosci 2023; 15:1207012. [PMID: 37455940 PMCID: PMC10340530 DOI: 10.3389/fnagi.2023.1207012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2023] [Accepted: 06/06/2023] [Indexed: 07/18/2023] Open
Abstract
Mindfulness meditation has been shown to be beneficial for a range of different health conditions, impacts brain function and structure relatively quickly, and has shown promise with aging samples. Functional magnetic resonance imaging metrics provide insight into neurovascular health which plays a key role in both normal and pathological aging processes. Experimental mindfulness meditation studies that included functional magnetic resonance metrics as an outcome measure may point to potential neurovascular mechanisms of action relevant for aging adults that have not yet been previously examined. We first review the resting-state magnetic resonance studies conducted in exclusively older adult age samples. Findings from older adult-only samples are then used to frame the findings of task magnetic resonance imaging studies conducted in both clinical and healthy adult samples. Based on the resting-state studies in older adults and the task magnetic resonance studies in adult samples, we propose three potential mechanisms by which mindfulness meditation may offer a neurovascular therapeutic benefit for older adults: (1) a direct neurovascular mechanism via increased resting-state cerebral blood flow; (2) an indirect anti-neuroinflammatory mechanism via increased functional connectivity within the default mode network, and (3) a top-down control mechanism that likely reflects both a direct and an indirect neurovascular pathway.
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Affiliation(s)
- Jessica Pommy
- Department of Neurology, Division of Neuropsychology, Medical College of Wisconsin, Milwaukee, WI, United States
| | - Colette M. Smart
- Department of Psychology, University of Victoria, Victoria, BC, Canada
| | - Andrew M. Bryant
- Department of Neurology, The Ohio State University, Columbus, OH, United States
| | - Yang Wang
- Department of Neurology, Division of Neuropsychology, Medical College of Wisconsin, Milwaukee, WI, United States
- Department of Radiology, Medical College of Wisconsin, Milwaukee, WI, United States
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Hsu AL, Li MK, Kung YC, Wang ZJ, Lee HC, Li CW, Huang CWC, Wu CW. Temporal consistency of neurovascular components on awakening: preliminary evidence from electroencephalography, cerebrovascular reactivity, and functional magnetic resonance imaging. Front Psychiatry 2023; 14:1058721. [PMID: 37215667 PMCID: PMC10196490 DOI: 10.3389/fpsyt.2023.1058721] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Accepted: 04/18/2023] [Indexed: 05/24/2023] Open
Abstract
Sleep inertia (SI) is a time period during the transition from sleep to wakefulness wherein individuals perceive low vigilance with cognitive impairments; SI is generally identified by longer reaction times (RTs) in attention tasks immediately after awakening followed by a gradual RT reduction along with waking time. The sluggish recovery of vigilance in SI involves a dynamic process of brain functions, as evidenced in recent functional magnetic resonance imaging (fMRI) studies in within-network and between-network connectivity. However, these fMRI findings were generally based on the presumption of unchanged neurovascular coupling (NVC) before and after sleep, which remains an uncertain factor to be investigated. Therefore, we recruited 12 young participants to perform a psychomotor vigilance task (PVT) and a breath-hold task of cerebrovascular reactivity (CVR) before sleep and thrice after awakening (A1, A2, and A3, with 20 min intervals in between) using simultaneous electroencephalography (EEG)-fMRI recordings. If the NVC were to hold in SI, we hypothesized that time-varying consistencies could be found between the fMRI response and EEG beta power, but not in neuron-irrelevant CVR. Results showed that the reduced accuracy and increased RT in the PVT upon awakening was consistent with the temporal patterns of the PVT-induced fMRI responses (thalamus, insula, and primary motor cortex) and the EEG beta power (Pz and CP1). The neuron-irrelevant CVR did not show the same time-varying pattern among the brain regions associated with PVT. Our findings imply that the temporal dynamics of fMRI indices upon awakening are dominated by neural activities. This is the first study to explore the temporal consistencies of neurovascular components on awakening, and the discovery provides a neurophysiological basis for further neuroimaging studies regarding SI.
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Affiliation(s)
- Ai-Ling Hsu
- Bachelor Program in Artificial Intelligence, Chang Gung University, Taoyuan, Taiwan
- Department of Psychiatry, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
| | - Ming-Kang Li
- Bachelor Program in Artificial Intelligence, Chang Gung University, Taoyuan, Taiwan
| | - Yi-Chia Kung
- Department of Radiology, Tri-Service General Hospital, Taipei, Taiwan
| | - Zhitong John Wang
- Graduate Institute of Mind, Brain and Consciousness, Taipei Medical University, Taipei, Taiwan
| | - Hsin-Chien Lee
- Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Research Center of Sleep Medicine, Taipei Medical University Hospital, Taipei, Taiwan
| | - Chia-Wei Li
- Department of Radiology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | | | - Changwei W. Wu
- Graduate Institute of Mind, Brain and Consciousness, Taipei Medical University, Taipei, Taiwan
- Brain and Consciousness Research Center, Taipei Medical University-Shuang Ho Hospital, New Taipei, Taiwan
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Zvolanek KM, Moia S, Dean JN, Stickland RC, Caballero-Gaudes C, Bright MG. Comparing end-tidal CO 2, respiration volume per time (RVT), and average gray matter signal for mapping cerebrovascular reactivity amplitude and delay with breath-hold task BOLD fMRI. Neuroimage 2023; 272:120038. [PMID: 36958618 DOI: 10.1016/j.neuroimage.2023.120038] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 02/27/2023] [Accepted: 03/14/2023] [Indexed: 03/25/2023] Open
Abstract
Cerebrovascular reactivity (CVR), defined as the cerebral blood flow response to a vasoactive stimulus, is an imaging biomarker with demonstrated utility in a range of diseases and in typical development and aging processes. A robust and widely implemented method to map CVR involves using a breath-hold task during a BOLD fMRI scan. Recording end-tidal CO2 (PETCO2) changes during the breath-hold task is recommended to be used as a reference signal for modeling CVR amplitude in standard units (%BOLD/mmHg) and CVR delay in seconds. However, obtaining reliable PETCO2 recordings requires equipment and task compliance that may not be achievable in all settings. To address this challenge, we investigated two alternative reference signals to map CVR amplitude and delay in a lagged general linear model (lagged-GLM) framework: respiration volume per time (RVT) and average gray matter BOLD response (GM-BOLD). In 8 healthy adults with multiple scan sessions, we compare spatial agreement of CVR maps from RVT and GM-BOLD to those generated with PETCO2. We define a threshold to determine whether a PETCO2 recording has "sufficient" quality for CVR mapping and perform these comparisons in 16 datasets with sufficient PETCO2 and 6 datasets with insufficient PETCO2. When PETCO2 quality is sufficient, both RVT and GM-BOLD produce CVR amplitude maps that are nearly identical to those from PETCO2 (after accounting for differences in scale), with the caveat they are not in standard units to facilitate between-group comparisons. CVR delays are comparable to PETCO2 with an RVT regressor but may be underestimated with the average GM-BOLD regressor. Importantly, when PETCO2 quality is insufficient, RVT and GM-BOLD CVR recover reasonable CVR amplitude and delay maps, provided the participant attempted the breath-hold task. Therefore, our framework offers a solution for achieving high quality CVR maps in both retrospective and prospective studies where sufficient PETCO2 recordings are not available and especially in populations where obtaining reliable measurements is a known challenge (e.g., children). Our results have the potential to improve the accessibility of CVR mapping and to increase the prevalence of this promising metric of vascular health.
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Affiliation(s)
- Kristina M Zvolanek
- Department of Physical Therapy and Human Movement Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Department of Biomedical Engineering, McCormick School of Engineering and Applied Sciences, Northwestern University, Evanston, IL, USA.
| | - Stefano Moia
- Basque Center on Cognition, Brain and Language, Donostia, Gipuzkoa, Spain; Medical Imaging Processing Lab (MIP:Lab), Neuro-X institute, EPFL, Geneva, Switzerland
| | - Joshua N Dean
- Department of Biomedical Engineering, McCormick School of Engineering and Applied Sciences, Northwestern University, Evanston, IL, USA
| | - Rachael C Stickland
- Department of Physical Therapy and Human Movement Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | | | - Molly G Bright
- Department of Physical Therapy and Human Movement Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Department of Biomedical Engineering, McCormick School of Engineering and Applied Sciences, Northwestern University, Evanston, IL, USA
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Ciumas C, Rheims S, Ryvlin P. fMRI studies evaluating central respiratory control in humans. Front Neural Circuits 2022; 16:982963. [PMID: 36213203 PMCID: PMC9537466 DOI: 10.3389/fncir.2022.982963] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 09/01/2022] [Indexed: 11/13/2022] Open
Abstract
A plethora of neural centers in the central nervous system control the fundamental respiratory pattern. This control is ensured by neurons that act as pacemakers, modulating activity through chemical control driven by changes in the O2/CO2 balance. Most of the respiratory neural centers are located in the brainstem, but difficult to localize on magnetic resonance imaging (MRI) due to their small size, lack of visually-detectable borders with neighboring areas, and significant physiological noise hampering detection of its activity with functional MRI (fMRI). Yet, several approaches make it possible to study the normal response to different abnormal stimuli or conditions such as CO2 inhalation, induced hypercapnia, volitional apnea, induced hypoxia etc. This review provides a comprehensive overview of the majority of available studies on central respiratory control in humans.
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Affiliation(s)
- Carolina Ciumas
- Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
- Lyon Neuroscience Research Center, Institut National de la Santé et de la Recherche Médicale U1028/CNRS UMR 5292 Lyon 1 University, Bron, France
- IDEE Epilepsy Institute, Lyon, France
| | - Sylvain Rheims
- Lyon Neuroscience Research Center, Institut National de la Santé et de la Recherche Médicale U1028/CNRS UMR 5292 Lyon 1 University, Bron, France
- IDEE Epilepsy Institute, Lyon, France
- Department of Functional Neurology and Epileptology, Hospices Civils de Lyon, Lyon, France
| | - Philippe Ryvlin
- Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
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8
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Zhao MY, Woodward A, Fan AP, Chen KT, Yu Y, Chen DY, Moseley ME, Zaharchuk G. Reproducibility of cerebrovascular reactivity measurements: A systematic review of neuroimaging techniques . J Cereb Blood Flow Metab 2022;42:700-717. [PMID: 34806918 PMCID: PMC9254040 DOI: 10.1177/0271678x211056702] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Cerebrovascular reactivity (CVR), the capacity of the brain to increase cerebral blood flow (CBF) to meet changes in physiological demand, is an important biomarker to evaluate brain health. Typically, this brain "stress test" is performed by using a medical imaging modality to measure the CBF change between two states: at baseline and after vasodilation. However, since there are many imaging modalities and many ways to augment CBF, a wide range of CVR values have been reported. An understanding of CVR reproducibility is critical to determine the most reliable methods to measure CVR as a clinical biomarker. This review focuses on CVR reproducibility studies using neuroimaging techniques in 32 articles comprising 427 total subjects. The literature search was performed in PubMed, Embase, and Scopus. The review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We identified 5 factors of the experimental subjects (such as sex, blood characteristics, and smoking) and 9 factors of the measuring technique (such as the imaging modality, the type of the vasodilator, and the quantification method) that have strong effects on CVR reproducibility. Based on this review, we recommend several best practices to improve the reproducibility of CVR quantification in neuroimaging studies.
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Affiliation(s)
- Moss Y Zhao
- Department of Radiology, Stanford University, Stanford, CA, USA
| | - Amanda Woodward
- Lane Medical Library, Stanford University, Stanford, CA, USA
| | - Audrey P Fan
- Department of Biomedical Engineering, University of California Davis, Davis, CA, USA.,Department of Neurology, University of California Davis, Davis, CA, USA
| | - Kevin T Chen
- Department of Radiology, Stanford University, Stanford, CA, USA
| | - Yannan Yu
- Department of Radiology, Stanford University, Stanford, CA, USA
| | - David Y Chen
- Department of Medical Imaging, Taipei Medical University - Shuan-Ho Hospital, New Taipei City.,Department of Radiology, School of Medicine, Taipei Medical University, Taipei *Research materials supporting this publication can be accessed at https://doi.org/10.25740/hd852bg4538
| | | | - Greg Zaharchuk
- Department of Radiology, Stanford University, Stanford, CA, USA
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Kucikova L, Goerdten J, Dounavi ME, Mak E, Su L, Waldman AD, Danso S, Muniz-Terrera G, Ritchie CW. Resting-state brain connectivity in healthy young and middle-aged adults at risk of progressive Alzheimer's disease. Neurosci Biobehav Rev 2021; 129:142-153. [PMID: 34310975 DOI: 10.1016/j.neubiorev.2021.07.024] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Revised: 05/18/2021] [Accepted: 07/21/2021] [Indexed: 11/15/2022]
Abstract
Functional brain connectivity of the resting-state networks has gained recent attention as a possible biomarker of Alzheimer's Disease (AD). In this paper, we review the literature of functional connectivity differences in young adults and middle-aged cognitively intact individuals with non-modifiable risk factors of AD (n = 17). We focus on three main intrinsic resting-state networks: The Default Mode network, Executive network, and the Salience network. Overall, the evidence from the literature indicated early vulnerability of functional connectivity across different at-risk groups, particularly in the Default Mode Network. While there was little consensus on the interpretation on directionality, the topography of the findings showed frequent overlap across studies, especially in regions that are characteristic of AD (i.e., precuneus, posterior cingulate cortex, and medial prefrontal cortex areas). We conclude that while resting-state functional connectivity markers have great potential to identify at-risk individuals, implementing more data-driven approaches, further longitudinal and cross-validation studies, and the analysis of greater sample sizes are likely to be necessary to fully establish the effectivity and utility of resting-state network-based analyses.
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Affiliation(s)
- Ludmila Kucikova
- Edinburgh Dementia Prevention and Centre for Clinical Brain Sciences, Edinburgh Medical School, University of Edinburgh, Edinburgh, United Kingdom.
| | - Jantje Goerdten
- Department of Epidemiological Methods and Etiological Research, Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany
| | - Maria-Eleni Dounavi
- Department of Psychiatry, School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom
| | - Elijah Mak
- Department of Psychiatry, School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom
| | - Li Su
- Department of Psychiatry, School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom
| | - Adam D Waldman
- Edinburgh Dementia Prevention and Centre for Clinical Brain Sciences, Edinburgh Medical School, University of Edinburgh, Edinburgh, United Kingdom
| | - Samuel Danso
- Edinburgh Dementia Prevention and Centre for Clinical Brain Sciences, Edinburgh Medical School, University of Edinburgh, Edinburgh, United Kingdom
| | - Graciela Muniz-Terrera
- Edinburgh Dementia Prevention and Centre for Clinical Brain Sciences, Edinburgh Medical School, University of Edinburgh, Edinburgh, United Kingdom
| | - Craig W Ritchie
- Edinburgh Dementia Prevention and Centre for Clinical Brain Sciences, Edinburgh Medical School, University of Edinburgh, Edinburgh, United Kingdom
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Tsvetanov KA, Henson RNA, Jones PS, Mutsaerts H, Fuhrmann D, Tyler LK, Cam‐CAN, Rowe JB. The effects of age on resting-state BOLD signal variability is explained by cardiovascular and cerebrovascular factors. Psychophysiology 2021; 58:e13714. [PMID: 33210312 PMCID: PMC8244027 DOI: 10.1111/psyp.13714] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2019] [Revised: 07/27/2020] [Accepted: 09/28/2020] [Indexed: 12/18/2022]
Abstract
Accurate identification of brain function is necessary to understand neurocognitive aging, and thereby promote health and well-being. Many studies of neurocognitive aging have investigated brain function with the blood-oxygen level-dependent (BOLD) signal measured by functional magnetic resonance imaging. However, the BOLD signal is a composite of neural and vascular signals, which are differentially affected by aging. It is, therefore, essential to distinguish the age effects on vascular versus neural function. The BOLD signal variability at rest (known as resting state fluctuation amplitude, RSFA), is a safe, scalable, and robust means to calibrate vascular responsivity, as an alternative to breath-holding and hypercapnia. However, the use of RSFA for normalization of BOLD imaging assumes that age differences in RSFA reflecting only vascular factors, rather than age-related differences in neural function (activity) or neuronal loss (atrophy). Previous studies indicate that two vascular factors, cardiovascular health (CVH) and cerebrovascular function, are insufficient when used alone to fully explain age-related differences in RSFA. It remains possible that their joint consideration is required to fully capture age differences in RSFA. We tested the hypothesis that RSFA no longer varies with age after adjusting for a combination of cardiovascular and cerebrovascular measures. We also tested the hypothesis that RSFA variation with age is not associated with atrophy. We used data from the population-based, lifespan Cam-CAN cohort. After controlling for cardiovascular and cerebrovascular estimates alone, the residual variance in RSFA across individuals was significantly associated with age. However, when controlling for both cardiovascular and cerebrovascular estimates, the variance in RSFA was no longer associated with age. Grey matter volumes did not explain age differences in RSFA, after controlling for CVH. The results were consistent between voxel-level analysis and independent component analysis. Our findings indicate that cardiovascular and cerebrovascular signals are together sufficient predictors of age differences in RSFA. We suggest that RSFA can be used to separate vascular from neuronal factors, to characterize neurocognitive aging. We discuss the implications and make recommendations for the use of RSFA in the research of aging.
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Affiliation(s)
- Kamen A. Tsvetanov
- Department of Clinical NeurosciencesUniversity of CambridgeCambridgeUK
- Department of PsychologyCentre for Speech, Language and the BrainUniversity of CambridgeCambridgeUK
| | - Richard N. A. Henson
- Medical Research Council Cognition and Brain Sciences UnitCambridgeUK
- Department of PsychiatryUniversity of CambridgeCambridgeUK
| | - P. Simon Jones
- Department of PsychologyCentre for Speech, Language and the BrainUniversity of CambridgeCambridgeUK
| | - Henk Mutsaerts
- Department of Radiology and Nuclear MedicineAmsterdam University Medical CenterAmsterdamthe Netherlands
| | - Delia Fuhrmann
- Medical Research Council Cognition and Brain Sciences UnitCambridgeUK
| | - Lorraine K. Tyler
- Department of PsychologyCentre for Speech, Language and the BrainUniversity of CambridgeCambridgeUK
| | - Cam‐CAN
- Department of Clinical NeurosciencesUniversity of CambridgeCambridgeUK
- Department of PsychologyCentre for Speech, Language and the BrainUniversity of CambridgeCambridgeUK
| | - James B. Rowe
- Department of Clinical NeurosciencesUniversity of CambridgeCambridgeUK
- Medical Research Council Cognition and Brain Sciences UnitCambridgeUK
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Stickland RC, Zvolanek KM, Moia S, Ayyagari A, Caballero-Gaudes C, Bright MG. A practical modification to a resting state fMRI protocol for improved characterization of cerebrovascular function. Neuroimage 2021; 239:118306. [PMID: 34175427 PMCID: PMC8552969 DOI: 10.1016/j.neuroimage.2021.118306] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 06/18/2021] [Accepted: 06/23/2021] [Indexed: 12/22/2022] Open
Abstract
Cerebrovascular reactivity (CVR), defined here as the Blood Oxygenation Level Dependent (BOLD) response to a CO2 pressure change, is a useful metric of cerebrovascular function. Both the amplitude and the timing (hemodynamic lag) of the CVR response can bring insight into the nature of a cerebrovascular pathology and aid in understanding noise confounds when using functional Magnetic Resonance Imaging (fMRI) to study neural activity. This research assessed a practical modification to a typical resting-state fMRI protocol, to improve the characterization of cerebrovascular function. In 9 healthy subjects, we modelled CVR and lag in three resting-state data segments, and in data segments which added a 2–3 minute breathing task to the start of a resting-state segment. Two different breathing tasks were used to induce fluctuations in arterial CO2 pressure: a breath-hold task to induce hypercapnia (CO2 increase) and a cued deep breathing task to induce hypocapnia (CO2 decrease). Our analysis produced voxel-wise estimates of the amplitude (CVR) and timing (lag) of the BOLD-fMRI response to CO2 by systematically shifting the CO2 regressor in time to optimize the model fit. This optimization inherently increases gray matter CVR values and fit statistics. The inclusion of a simple breathing task, compared to a resting-state scan only, increases the number of voxels in the brain that have a significant relationship between CO2 and BOLD-fMRI signals, and improves our confidence in the plausibility of voxel-wise CVR and hemodynamic lag estimates. We demonstrate the clinical utility and feasibility of this protocol in an incidental finding of Moyamoya disease, and explore the possibilities and challenges of using this protocol in younger populations. This hybrid protocol has direct applications for CVR mapping in both research and clinical settings and wider applications for fMRI denoising and interpretation.
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Affiliation(s)
- Rachael C Stickland
- Physical Therapy and Human Movement Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.
| | - Kristina M Zvolanek
- Physical Therapy and Human Movement Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States; Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL, United States
| | - Stefano Moia
- Basque Center on Cognition, Brain and Language, Donostia, Gipuzkoa, Spain; University of the Basque Country EHU/UPV, Donostia, Gipuzkoa, Spain
| | - Apoorva Ayyagari
- Physical Therapy and Human Movement Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States; Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL, United States
| | | | - Molly G Bright
- Physical Therapy and Human Movement Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States; Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL, United States
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12
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Moia S, Termenon M, Uruñuela E, Chen G, Stickland RC, Bright MG, Caballero-Gaudes C. ICA-based denoising strategies in breath-hold induced cerebrovascular reactivity mapping with multi echo BOLD fMRI. Neuroimage 2021; 233:117914. [PMID: 33684602 PMCID: PMC8351526 DOI: 10.1016/j.neuroimage.2021.117914] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Revised: 01/25/2021] [Accepted: 02/22/2021] [Indexed: 12/19/2022] Open
Abstract
Performing a BOLD functional MRI (fMRI) acquisition during breath-hold (BH) tasks is a non-invasive, robust method to estimate cerebrovascular reactivity (CVR). However, movement and breathing-related artefacts caused by the BH can substantially hinder CVR estimates due to their high temporal collinearity with the effect of interest, and attention has to be paid when choosing which analysis model should be applied to the data. In this study, we evaluate the performance of multiple analysis strategies based on lagged general linear models applied on multi-echo BOLD fMRI data, acquired in ten subjects performing a BH task during ten sessions, to obtain subject-specific CVR and haemodynamic lag estimates. The evaluated approaches range from conventional regression models, i.e. including drifts and motion timecourses as nuisance regressors, applied on single-echo or optimally-combined data, to more complex models including regressors obtained from multi-echo independent component analysis with different grades of orthogonalization in order to preserve the effect of interest, i.e. the CVR. We compare these models in terms of their ability to make signal intensity changes independent from motion, as well as the reliability as measured by voxelwise intraclass correlation coefficients of both CVR and lag maps over time. Our results reveal that a conservative independent component analysis model applied on the optimally-combined multi-echo fMRI signal offers the largest reduction of motion-related effects in the signal, while yielding reliable CVR amplitude and lag estimates, although a conventional regression model applied on the optimally-combined data results in similar estimates. This work demonstrates the usefulness of multi-echo based fMRI acquisitions and independent component analysis denoising for precision mapping of CVR in single subjects based on BH paradigms, fostering its potential as a clinically-viable neuroimaging tool for individual patients. It also proves that the way in which data-driven regressors should be incorporated in the analysis model is not straight-forward due to their complex interaction with the BH-induced BOLD response.
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Affiliation(s)
- Stefano Moia
- Basque Center on Cognition, Brain and Language, Donostia, Spain; University of the Basque Country UPV/EHU, Donostia, Spain.
| | - Maite Termenon
- Basque Center on Cognition, Brain and Language, Donostia, Spain
| | - Eneko Uruñuela
- Basque Center on Cognition, Brain and Language, Donostia, Spain; University of the Basque Country UPV/EHU, Donostia, Spain
| | - Gang Chen
- Scientific and Statistical Computing Core, NIMH/NIH/HHS, Bethesda, MD, United States
| | - Rachael C Stickland
- Physical Therapy and Human Movement Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
| | - Molly G Bright
- Physical Therapy and Human Movement Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States; Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL, United States
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13
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Cohen AD, Jagra AS, Visser NJ, Yang B, Fernandez B, Banerjee S, Wang Y. Improving the Breath-Holding CVR Measurement Using the Multiband Multi-Echo EPI Sequence. Front Physiol 2021; 12:619714. [PMID: 33716769 PMCID: PMC7953053 DOI: 10.3389/fphys.2021.619714] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Accepted: 01/20/2021] [Indexed: 02/04/2023] Open
Abstract
Blood oxygen level-dependent (BOLD) functional MRI (fMRI) is commonly used to measure cerebrovascular reactivity (CVR), which can convey insightful information about neurovascular health. Breath-holding (BH) has been shown to be a practical vasodilatory stimulus for measuring CVR in clinical settings. The conventional BOLD fMRI approach has some limitations, however, such as susceptibility-induced signal dropout at air tissue interfaces and low BOLD sensitivity especially in areas of low T 2 * . These drawbacks can potentially be mitigated with multi-echo sequences, which acquire several images at different echo times in one shot. When combined with multiband techniques, high temporal resolution images can be acquired. This study compared an advanced multiband multi-echo (MBME) echo planar imaging (EPI) sequence with an existing multiband single-echo (MB) sequence to evaluate the repeatability and sensitivity of BH activation and CVR mapping. Images were acquired from 28 healthy volunteers, of which 18 returned for repeat imaging. Both MBME and MB data were pre-processed using both standard and advanced denoising techniques. The MBME data was further processed by combining echoes using a T 2 * -weighted approach and denoising using multi-echo independent component analysis. BH activation was calculated using a general linear model and the respiration response function. CVR was computed as the percent change related to the activation. To account for differences in CVR related to TE, relative CVR (rCVR) was computed and normalized to the mean gray matter CVR. Test-retest metrics were assessed with the Dice coefficient, rCVR difference, within subject coefficient of variation, and the intraclass correlation coefficient. Our findings demonstrate that rCVR for MBME scans were significantly higher than for MB scans across most of the gray matter. In areas of high susceptibility-induced signal dropout, however, MBME rCVR was significantly less than MB rCVR due to artifactually high rCVR for MB scans in these regions. MBME rCVR showed improved test-retest metrics compared with MB. Overall, the MBME sequence displayed superior BOLD sensitivity, improved specificity in areas of signal dropout on MBME scans, enhanced reliability, and reduced variability across subjects compared with MB acquisitions. Our results suggest that the MBME EPI sequence is a promising tool for imaging CVR.
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Affiliation(s)
- Alexander D. Cohen
- Department of Radiology, Medical College of Wisconsin, Milwaukee, WI, United States
| | | | - Nicholas J. Visser
- Department of Radiology, Medical College of Wisconsin, Milwaukee, WI, United States
| | | | | | | | - Yang Wang
- Department of Radiology, Medical College of Wisconsin, Milwaukee, WI, United States,*Correspondence: Yang Wang,
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14
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Altered cerebrovascular reactivity due to respiratory rate and breath holding: a BOLD-fMRI study on healthy adults. Brain Struct Funct 2021; 226:1229-1239. [PMID: 33598760 DOI: 10.1007/s00429-021-02236-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Accepted: 02/05/2021] [Indexed: 01/22/2023]
Abstract
Cerebrovascular reactivity (CVR) is of great significance for the treatment and prevention of cerebrovascular diseases. CVR can be mapped using the blood oxygenation level-dependent (BOLD) signal of fMRI. Breath holding (BH) is a reliable method to produce the desired increase in arterial CO2, while its application in clinical research is limited due to subject's compliance and variability. BH task with variable respiratory rates could allow more flexibility in clinical populations. In this study, 50 healthy volunteers were scanned for end-inspiration BH tasks with three different respiration rates. For the three respiratory rates BH tasks, the CVR was estimated based on the BOLD signal and general linear model (GLM) separately. Specifically, the extra time delay was considered for the hemodynamic response function, and the optimal delay was estimated for each voxel. To measure CVR in grey matter, BOLD signals of end-inspiration BH were used as regressors in general linear models to quantify their impact on CVR. This was performed for regions and voxels. Systematic differences were observed between the three end-inspiratory breathing rates. The greatest increase in activation intensity was found in fast breathing followed by self-paced and slow breathing. We conclude that the BH task of variable respiratory rates allows for CVR measurement, making breath-holding challenges more flexible and appropriate for routine practice.
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15
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Solis-Barquero SM, Echeverria-Chasco R, Calvo-Imirizaldu M, Cacho-Asenjo E, Martinez-Simon A, Vidorreta M, Dominguez PD, García de Eulate R, Fernandez-Martinez M, Fernández-Seara MA. Breath-Hold Induced Cerebrovascular Reactivity Measurements Using Optimized Pseudocontinuous Arterial Spin Labeling. Front Physiol 2021; 12:621720. [PMID: 33679436 PMCID: PMC7925895 DOI: 10.3389/fphys.2021.621720] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Accepted: 01/26/2021] [Indexed: 11/13/2022] Open
Abstract
A pseudocontinuous arterial spin labeling (PCASL) sequence combined with background suppression and single-shot accelerated 3D RARE stack-of-spirals was used to evaluate cerebrovascular reactivity (CVR) induced by breath-holding (BH) in ten healthy volunteers. Four different models designed using the measured change in PETCO2 induced by BH were compared, for CVR quantification. The objective of this comparison was to understand which regressor offered a better physiological model to characterize the cerebral blood flow response under BH. The BH task started with free breathing of 42 s, followed by interleaved end-expiration BHs of 21 s, for ten cycles. The total scan time was 12 min and 20 s. The accelerated readout allowed the acquisition of PCASL data with better temporal resolution than previously used, without compromising the post-labeling delay. Elevated CBF was observed in most cerebral regions under hypercapnia, which was delayed with respect to the BH challenge. Significant statistical differences in CVR were obtained between the different models in GM (p < 0.0001), with ramp models yielding higher values than boxcar models and between the two tissues, GM and WM, with higher values in GM, in all the models (p < 0.0001). The adjustment of the ramp amplitude during each BH cycle did not improve the results compared with a ramp model with a constant amplitude equal to the mean PETCO2 change during the experiment.
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Affiliation(s)
| | - Rebeca Echeverria-Chasco
- Department of Radiology, Clínica Universidad de Navarra, Pamplona, Spain.,Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
| | | | - Elena Cacho-Asenjo
- Department of Anesthesia, Perioperative Medicine and Critical Care, Clínica Universidad de Navarra, Pamplona, Spain
| | - Antonio Martinez-Simon
- Department of Anesthesia, Perioperative Medicine and Critical Care, Clínica Universidad de Navarra, Pamplona, Spain
| | | | - Pablo D Dominguez
- Department of Radiology, Clínica Universidad de Navarra, Pamplona, Spain.,Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
| | | | | | - María A Fernández-Seara
- Department of Radiology, Clínica Universidad de Navarra, Pamplona, Spain.,Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
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16
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Kaczmarz S, Göttler J, Petr J, Hansen MB, Mouridsen K, Zimmer C, Hyder F, Preibisch C. Hemodynamic impairments within individual watershed areas in asymptomatic carotid artery stenosis by multimodal MRI. J Cereb Blood Flow Metab 2021; 41:380-396. [PMID: 32237952 PMCID: PMC7812517 DOI: 10.1177/0271678x20912364] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Improved understanding of complex hemodynamic impairments in asymptomatic internal carotid artery stenosis (ICAS) is crucial to better assess stroke risks. Multimodal MRI is ideal for measuring brain hemodynamics and has the potential to improve diagnostics and treatment selections. We applied MRI-based perfusion and oxygenation-sensitive imaging in ICAS with the hypothesis that the sensitivity to hemodynamic impairments will improve within individual watershed areas (iWSA). We studied cerebral blood flow (CBF), cerebrovascular reactivity (CVR), relative cerebral blood volume (rCBV), relative oxygen extraction fraction (rOEF), oxygen extraction capacity (OEC) and capillary transit-time heterogeneity (CTH) in 29 patients with asymptomatic, unilateral ICAS (age 70.3 ± 7.0 y) and 30 age-matched healthy controls. In ICAS, we found significant impairments of CBF, CVR, rCBV, OEC, and CTH (strongest lateralization ΔCVR = -24%), but not of rOEF. Although the spatial overlap of compromised hemodynamic parameters within each patient varied in a complex manner, most pronounced changes of CBF, CVR and rCBV were detected within iWSAs (strongest effect ΔCVR = +117%). At the same time, CTH impairments were iWSA independent, indicating widespread dysfunction of capillary-level oxygen diffusivity. In summary, complementary MRI-based perfusion and oxygenation parameters offer deeper perspectives on complex microvascular impairments in individual patients. Furthermore, knowledge about iWSAs improves the sensitivity to hemodynamic impairments.
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Affiliation(s)
- Stephan Kaczmarz
- Department of Neuroradiology, School of Medicine, Technical University of Munich (TUM), Munich, Germany.,TUM Neuroimaging Center (TUM-NIC), Technical University of Munich (TUM), Munich, Germany.,MRRC, Yale University, New Haven, CT, USA
| | - Jens Göttler
- Department of Neuroradiology, School of Medicine, Technical University of Munich (TUM), Munich, Germany.,TUM Neuroimaging Center (TUM-NIC), Technical University of Munich (TUM), Munich, Germany.,MRRC, Yale University, New Haven, CT, USA.,Department of Radiology, School of Medicine, Technical University of Munich (TUM), Munich, Germany
| | - Jan Petr
- PET Center, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany
| | - Mikkel Bo Hansen
- Center of Functionally Integrative Neuroscience, Aarhus University, Aarhus, Denmark
| | - Kim Mouridsen
- Center of Functionally Integrative Neuroscience, Aarhus University, Aarhus, Denmark
| | - Claus Zimmer
- Department of Neuroradiology, School of Medicine, Technical University of Munich (TUM), Munich, Germany
| | | | - Christine Preibisch
- Department of Neuroradiology, School of Medicine, Technical University of Munich (TUM), Munich, Germany.,TUM Neuroimaging Center (TUM-NIC), Technical University of Munich (TUM), Munich, Germany.,Clinic for Neurology, School of Medicine, Technical University of Munich (TUM), Munich, Germany
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17
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Pinto J, Bright MG, Bulte DP, Figueiredo P. Cerebrovascular Reactivity Mapping Without Gas Challenges: A Methodological Guide. Front Physiol 2021; 11:608475. [PMID: 33536935 PMCID: PMC7848198 DOI: 10.3389/fphys.2020.608475] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Accepted: 12/02/2020] [Indexed: 01/08/2023] Open
Abstract
Cerebrovascular reactivity (CVR) is defined as the ability of vessels to alter their caliber in response to vasoactive factors, by means of dilating or constricting, in order to increase or decrease regional cerebral blood flow (CBF). Importantly, CVR may provide a sensitive biomarker for pathologies where vasculature is compromised. Furthermore, the spatiotemporal dynamics of CVR observed in healthy subjects, reflecting regional differences in cerebral vascular tone and response, may also be important in functional MRI studies based on neurovascular coupling mechanisms. Assessment of CVR is usually based on the use of a vasoactive stimulus combined with a CBF measurement technique. Although transcranial Doppler ultrasound has been frequently used to obtain global flow velocity measurements, MRI techniques are being increasingly employed for obtaining CBF maps. For the vasoactive stimulus, vasodilatory hypercapnia is usually induced through the manipulation of respiratory gases, including the inhalation of increased concentrations of carbon dioxide. However, most of these methods require an additional apparatus and complex setups, which not only may not be well-tolerated by some populations but are also not widely available. For these reasons, strategies based on voluntary breathing fluctuations without the need for external gas challenges have been proposed. These include the task-based methodologies of breath holding and paced deep breathing, as well as a new generation of methods based on spontaneous breathing fluctuations during resting-state. Despite the multitude of alternatives to gas challenges, existing literature lacks definitive conclusions regarding the best practices for the vasoactive modulation and associated analysis protocols. In this work, we perform an extensive review of CVR mapping techniques based on MRI and CO2 variations without gas challenges, focusing on the methodological aspects of the breathing protocols and corresponding data analysis. Finally, we outline a set of practical guidelines based on generally accepted practices and available data, extending previous reports and encouraging the wider application of CVR mapping methodologies in both clinical and academic MRI settings.
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Affiliation(s)
- Joana Pinto
- Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, United Kingdom
- Institute for Systems and Robotics - Lisboa and Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal
| | - Molly G. Bright
- Physical Therapy and Human Movement Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
- Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL, United States
| | - Daniel P. Bulte
- Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, United Kingdom
| | - Patrícia Figueiredo
- Institute for Systems and Robotics - Lisboa and Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal
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18
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Tsvetanov KA, Henson RNA, Rowe JB. Separating vascular and neuronal effects of age on fMRI BOLD signals. Philos Trans R Soc Lond B Biol Sci 2021; 376:20190631. [PMID: 33190597 PMCID: PMC7741031 DOI: 10.1098/rstb.2019.0631] [Citation(s) in RCA: 70] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/19/2020] [Indexed: 12/14/2022] Open
Abstract
Accurate identification of brain function is necessary to understand the neurobiology of cognitive ageing, and thereby promote well-being across the lifespan. A common tool used to investigate neurocognitive ageing is functional magnetic resonance imaging (fMRI). However, although fMRI data are often interpreted in terms of neuronal activity, the blood oxygenation level-dependent (BOLD) signal measured by fMRI includes contributions of both vascular and neuronal factors, which change differentially with age. While some studies investigate vascular ageing factors, the results of these studies are not well known within the field of neurocognitive ageing and therefore vascular confounds in neurocognitive fMRI studies are common. Despite over 10 000 BOLD-fMRI papers on ageing, fewer than 20 have applied techniques to correct for vascular effects. However, neurovascular ageing is not only a confound in fMRI, but an important feature in its own right, to be assessed alongside measures of neuronal ageing. We review current approaches to dissociate neuronal and vascular components of BOLD-fMRI of regional activity and functional connectivity. We highlight emerging evidence that vascular mechanisms in the brain do not simply control blood flow to support the metabolic needs of neurons, but form complex neurovascular interactions that influence neuronal function in health and disease. This article is part of the theme issue 'Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity'.
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Affiliation(s)
- Kamen A. Tsvetanov
- Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0SZ, UK
- Department of Psychology, University of Cambridge, Cambridge CB2 3EB, UK
| | - Richard N. A. Henson
- Department of Psychiatry, University of Cambridge, Cambridge CB2 0SP, UK
- Medical Research Council Cognition and Brain Sciences Unit, University of Cambridge, Cambridge CB2 7EF, UK
| | - James B. Rowe
- Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0SZ, UK
- Medical Research Council Cognition and Brain Sciences Unit, University of Cambridge, Cambridge CB2 7EF, UK
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19
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Abstract
Neurovascular uncoupling (NVU) is one of the most important confounds of blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMR imaging) in the setting of focal brain lesions such as brain tumors. This article reviews the assessment of NVU related to focal brain lesions with emphasis on the use of cerebrovascular reactivity mapping measurement methods and resting state BOLD fMR imaging metrics in the detection of NVU, as well as the use of amplitude of low-frequency fluctuation metrics to mitigate the effects of NVU on clinical fMR imaging activation.
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Affiliation(s)
- Shruti Agarwal
- Division of Neuroradiology, The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA
| | - Haris I Sair
- Division of Neuroradiology, The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA; The Malone Center for Engineering in Healthcare, The Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA
| | - Jay J Pillai
- Division of Neuroradiology, The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA; Department of Neurosurgery, Johns Hopkins University School of Medicine, 1800 Orleans Street, Baltimore, MD 21287, USA.
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20
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Liu P, Xu C, Lin Z, Sur S, Li Y, Yasar S, Rosenberg P, Albert M, Lu H. Cerebrovascular reactivity mapping using intermittent breath modulation. Neuroimage 2020; 215:116787. [PMID: 32278094 DOI: 10.1016/j.neuroimage.2020.116787] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2019] [Revised: 03/24/2020] [Accepted: 03/30/2020] [Indexed: 01/28/2023] Open
Abstract
Cerebrovascular reactivity (CVR), an index of brain vessel's dilatory capacity, is typically measured using hypercapnic gas inhalation or breath-holding as a vasoactive challenge. However, these methods require considerable subject cooperation and could be challenging in clinical studies. More recently, there have been attempts to use resting-state BOLD data to map CVR by utilizing spontaneous changes in breathing pattern. However, in subjects who have small fluctuations in their spontaneous breathing pattern, the CVR results could be noisy and unreliable. In this study, we aim to develop a new method for CVR mapping that does not require gas-inhalation yet provides substantially higher sensitivity than resting-state CVR mapping. This new method is largely based on resting-state scan, but introduces intermittent modulation of breathing pattern in the subject to enhance fluctuations in their end-tidal CO2 (EtCO2) level. Here we examined the comfort level, sensitivity, and accuracy of this method in two studies. First, in 8 healthy young subjects, we developed the intermittent breath-modulation method using two different modulation frequencies, 6 s per breath and 12 s per breath, respectively, and compared the results to three existing CVR methods, specifically hypercapnic gas inhalation, breath-holding, and resting-state. Our results showed that the comfort level of the 6-s breath-modulation method was significantly higher than breath-holding (p = 0.007) and CO2-inhalation (p = 0.015) methods, while not different from the resting-state, i.e. free breathing method (p = 0.52). When comparing the sensitivity of CVR methods, the breath-modulation methods revealed higher Z-statistics compared to the resting-state scan (p < 0.008) and was comparable to breath-holding results. Next, we tested the feasibility of breath-modulation CVR mapping (6 s per breath) in 21 cognitively normal elderly participants and compared quantitative CVR values to that obtained with the CO2-inhalation method. Whole-brain CVR was found to be 0.150 ± 0.055 and 0.154 ± 0.032 %ΔBOLD/mmHg for the breath-modulation and CO2-inhalation method, respectively, with a significant correlation between them (y = 0.97x, p = 0.007). CVR mapping with intermittent breath modulation may be a useful method that combines the advantages of resting-state and CO2-inhalation based approaches.
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Affiliation(s)
- Peiying Liu
- Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
| | - Cuimei Xu
- Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Zixuan Lin
- Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Sandeepa Sur
- Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Yang Li
- Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Sevil Yasar
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Paul Rosenberg
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Marilyn Albert
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Hanzhang Lu
- Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, MD, USA
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21
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The Contribution of Functional Magnetic Resonance Imaging to the Understanding of the Effects of Acute Physical Exercise on Cognition. Brain Sci 2020; 10:brainsci10030175. [PMID: 32197357 PMCID: PMC7139910 DOI: 10.3390/brainsci10030175] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Revised: 03/04/2020] [Accepted: 03/13/2020] [Indexed: 02/06/2023] Open
Abstract
The fact that a single bout of acute physical exercise has a positive impact on cognition is well-established in the literature, but the neural correlates that underlie these cognitive improvements are not well understood. Here, the use of neuroimaging techniques, such as functional magnetic resonance imaging (fMRI), offers great potential, which is just starting to be recognized. This review aims at providing an overview of those studies that used fMRI to investigate the effects of acute physical exercises on cerebral hemodynamics and cognition. To this end, a systematic literature survey was conducted by two independent reviewers across five electronic databases. The search returned 668 studies, of which 14 studies met the inclusion criteria and were analyzed in this systematic review. Although the findings of the reviewed studies suggest that acute physical exercise (e.g., cycling) leads to profound changes in functional brain activation, the small number of available studies and the great variability in the study protocols limits the conclusions that can be drawn with certainty. In order to overcome these limitations, new, more well-designed trials are needed that (i) use a more rigorous study design, (ii) apply more sophisticated filter methods in fMRI data analysis, (iii) describe the applied processing steps of fMRI data analysis in more detail, and (iv) provide a more precise exercise prescription.
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22
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McIntosh RC, Hoshi RA, Timpano KR. Take my breath away: Neural activation at breath-hold differentiates individuals with panic disorder from healthy controls. Respir Physiol Neurobiol 2020; 277:103427. [PMID: 32120012 DOI: 10.1016/j.resp.2020.103427] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2019] [Revised: 02/12/2020] [Accepted: 02/24/2020] [Indexed: 01/04/2023]
Abstract
There is neuroanatomical evidence of an "extended fear network" of brain structures involved in the etiology of panic disorder (PD). Although ventilatory distrubance is a primary symptom of PD these sensations may also trigger onset of a panic attack (PA). Here, a voluntary breath-holding paradigm was used to mimic the hypercapnia state in order to compare blood oxygen level-dependent (BOLD) response, at the peak of a series of 18 s breath-holds, of 21 individuals with PD to 21 low anxiety matched controls. Compared to the rest condition, BOLD activity at the peak (12 - 18 s) of the breath-hold was greater for PD versus controls within a number of structures implicated in the extended fear network, including hippocampus, thalamus, and brainstem. Activation was also observed in cortical structures that are shown to be involved in interoceptive and self-referential processing, such as right insula, middle frontal gyrus, and precuneus/posterior cingulate. In lieu of amygdala activation, our findings show elevated activity throughout an extended network of cortical and subcortical structures involved in contextual, interoceptive and self-referential processing when individuals with PD engage in voluntary breath-holding.
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Affiliation(s)
- R C McIntosh
- Department of Psychology, University of Miami, 1120 NW 14th Street, Miami, FL, 33136, United States.
| | - R A Hoshi
- Clinical and Epidemiological Research Center, Sao Paulo University. 2565 Professor Lineu Prestes Ave, Sao Paulo, 05508-000, Brazil
| | - K R Timpano
- Department of Psychology, University of Miami, 1120 NW 14th Street, Miami, FL, 33136, United States
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23
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Peng SL, Yang HC, Chen CM, Shih CT. Short- and long-term reproducibility of BOLD signal change induced by breath-holding at 1.5 and 3 T. NMR IN BIOMEDICINE 2020; 33:e4195. [PMID: 31885110 DOI: 10.1002/nbm.4195] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/21/2019] [Revised: 09/09/2019] [Accepted: 09/09/2019] [Indexed: 06/10/2023]
Abstract
Cerebrovascular reactivity (CVR) can give insight into the cerebrovascular function. CVR can be estimated by measuring a blood-oxygen-level-dependent (BOLD) response combined with breath-holding (BH). The reproducibility of this technique has been addressed and existing studies have focused on short-term reproducibility using a 3 T magnetic resonance imaging (MRI) system. However, little is known about the long-term reproducibility of this procedure and the corresponding reproducibility using a 1.5 T MRI system. Here, we systematically examined the short- and long-term reproducibility of BOLD responses to BH across field strengths. Nine subjects participated in three MRI sessions separated by 30 minutes (sessions 1 and 2: short term) and 68-92 days (sessions 1 and 3, long term) at both 1.5 and 3 T MRI. Our findings revealed that significant differences between field strengths were detected in the activated gray matter volume and BOLD signal change (both P < 0.001), with smaller magnitudes at 1.5 T. However, activation patterns were reproducible, independent of the time interval, brain region or field strength. All interscan coefficient of variation values were below the 33% fiducial limit, and the intraclass correlation coefficient values were above 0.4, which is usually considered the acceptability limit in functional studies. These findings suggest that the response of BOLD signal to BH for assessing CVR is reproducible over time at 1.5 and 3 T. This technique can be considered a tool for monitoring longitudinal changes in patients with cerebrovascular diseases, and its use should be encouraged for clinical 1.5 T MRI systems.
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Affiliation(s)
- Shin-Lei Peng
- Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, Taiwan
| | - Hui-Chieh Yang
- Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, Taiwan
| | - Chun-Ming Chen
- Department of Radiology, China Medical University Hospital, Taichung, Taiwan
| | - Cheng-Ting Shih
- Department of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung, Taiwan
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24
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Raitamaa L, Korhonen V, Huotari N, Raatikainen V, Hautaniemi T, Kananen J, Rasila A, Helakari H, Zienkiewicz A, Myllylä T, Borchardt V, Kiviniemi V. Breath hold effect on cardiovascular brain pulsations - A multimodal magnetic resonance encephalography study. J Cereb Blood Flow Metab 2019; 39:2471-2485. [PMID: 30204040 PMCID: PMC6893986 DOI: 10.1177/0271678x18798441] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Ultra-fast functional magnetic resonance encephalography (MREG) enables separate assessment of cardiovascular, respiratory, and vasomotor waves from brain pulsations without temporal aliasing. We examined effects of breath hold- (BH) related changes on cardiovascular brain pulsations using MREG to study the physiological nature of cerebrovascular reactivity. We used alternating 32 s BH and 88 s resting normoventilation (NV) to change brain pulsations during MREG combined with simultaneously measured respiration, continuous non-invasive blood pressure, and cortical near-infrared spectroscopy (NIRS) in healthy volunteers. Changes in classical resting-state network BOLD-like signal and cortical blood oxygenation were reproduced based on MREG and NIRS signals. Cardiovascular pulsation amplitudes of MREG signal from anterior cerebral artery, oxygenated hemoglobin concentration in frontal cortex, and blood pressure decreased after BH. MREG cardiovascular pulse amplitudes in cortical areas and sagittal sinus increased, while cerebrospinal fluid and white matter remained unchanged. Respiratory centers in the brainstem - hypothalamus - thalamus - amygdala network showed strongest increases in cardiovascular pulsation amplitude. The spatial propagation of averaged cardiovascular impulses altered as a function of successive BH runs. The spread of cardiovascular pulse cycles exhibited a decreasing spatial similarity over time. MREG portrayed spatiotemporally accurate respiratory network activity and cardiovascular pulsation dynamics related to BH challenges at an unpreceded high temporal resolution.
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Affiliation(s)
- Lauri Raitamaa
- Oulu Functional Neuro Imaging Group, Research Unit of Medical Imaging Physics and Technology (MIPT), University of Oulu, Oulu, Finland
| | - Vesa Korhonen
- Oulu Functional Neuro Imaging Group, Research Unit of Medical Imaging Physics and Technology (MIPT), University of Oulu, Oulu, Finland.,Department of Diagnostic Radiology, Medical Research Center (MRC), Oulu University Hospital, Oulu, Finland
| | - Niko Huotari
- Oulu Functional Neuro Imaging Group, Research Unit of Medical Imaging Physics and Technology (MIPT), University of Oulu, Oulu, Finland
| | - Ville Raatikainen
- Oulu Functional Neuro Imaging Group, Research Unit of Medical Imaging Physics and Technology (MIPT), University of Oulu, Oulu, Finland
| | - Taneli Hautaniemi
- Oulu Functional Neuro Imaging Group, Research Unit of Medical Imaging Physics and Technology (MIPT), University of Oulu, Oulu, Finland
| | - Janne Kananen
- Oulu Functional Neuro Imaging Group, Research Unit of Medical Imaging Physics and Technology (MIPT), University of Oulu, Oulu, Finland
| | - Aleksi Rasila
- Oulu Functional Neuro Imaging Group, Research Unit of Medical Imaging Physics and Technology (MIPT), University of Oulu, Oulu, Finland
| | - Heta Helakari
- Oulu Functional Neuro Imaging Group, Research Unit of Medical Imaging Physics and Technology (MIPT), University of Oulu, Oulu, Finland
| | - Aleksandra Zienkiewicz
- Biomedical Sensors and Measurement Systems Group, Optoelectronics and Measurement Techniques Unit, University of Oulu, Oulu, Finland
| | - Teemu Myllylä
- Oulu Functional Neuro Imaging Group, Research Unit of Medical Imaging Physics and Technology (MIPT), University of Oulu, Oulu, Finland.,Biomedical Sensors and Measurement Systems Group, Optoelectronics and Measurement Techniques Unit, University of Oulu, Oulu, Finland
| | - Viola Borchardt
- Oulu Functional Neuro Imaging Group, Research Unit of Medical Imaging Physics and Technology (MIPT), University of Oulu, Oulu, Finland
| | - Vesa Kiviniemi
- Oulu Functional Neuro Imaging Group, Research Unit of Medical Imaging Physics and Technology (MIPT), University of Oulu, Oulu, Finland.,Department of Diagnostic Radiology, Medical Research Center (MRC), Oulu University Hospital, Oulu, Finland
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25
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Cohen AD, Wang Y. Improving the Assessment of Breath-Holding Induced Cerebral Vascular Reactivity Using a Multiband Multi-echo ASL/BOLD Sequence. Sci Rep 2019; 9:5079. [PMID: 30911056 PMCID: PMC6434035 DOI: 10.1038/s41598-019-41199-w] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Accepted: 02/28/2019] [Indexed: 01/18/2023] Open
Abstract
Breath holding (BH) is a viable vasodilatory stimulus for calculating functional MRI-derived cerebral vascular reactivity (CVR). The BH technique suffers from reduced repeatability compared with gas inhalation techniques; however, extra equipment is needed to perform gas inhalation techniques, and this equipment is not available at all institutions. This study aimed to determine the sensitivity and repeatability of BH activation and CVR using a multiband multi-echo simultaneous arterial spin labelling/blood oxygenation level dependent (ASL/BOLD) sequence. Whole-brain images were acquired in 14 volunteers. Ten subjects returned for repeat imaging. Each subject performed four cycles of 16 s BH on expiration interleaved with paced breathing. Following standard preprocessing, the echoes were combined using a T2*-weighted approach. BOLD and ASL BH activation was computed, and CVR was then determined as the percent signal change related to the activation. The "M" parameter from the Davis Model was also computed by incorporating the ASL signal. Our results showed higher BH activation strength, volume, and repeatability for the combined multi-echo (MEC) data compared with the single-echo data. MEC CVR also had higher repeatability, sensitivity, specificity, and reliability compared with the single-echo BOLD data. These data support the usefulness of an MBME ASL/BOLD acquisition for BH CVR and M measurements.
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Affiliation(s)
- Alexander D Cohen
- Medical College of Wisconsin, Department of Radiology, Milwaukee, WI, USA.
| | - Yang Wang
- Medical College of Wisconsin, Department of Radiology, Milwaukee, WI, USA.
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26
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Evaluation of cerebrovascular reserve in patients with cerebrovascular diseases using resting-state MRI: A feasibility study. Magn Reson Imaging 2019; 59:46-52. [PMID: 30849484 DOI: 10.1016/j.mri.2019.03.003] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2019] [Revised: 03/03/2019] [Accepted: 03/04/2019] [Indexed: 11/22/2022]
Abstract
PURPOSE To demonstrate the feasibility of mapping cerebrovascular reactivity (CVR) using resting-state functional MRI (fMRI) data without gas or other challenges in patients with cerebrovascular diseases and to show that brain regions affected by the diseases have diminished vascular reactivity. MATERIALS AND METHODS Two sub-studies were performed on patients with stroke and Moyamoya disease. In Study 1, 20 stroke patients (56.3 ± 9.7 years, 7 females) were enrolled and resting-state blood‑oxygenation-level-dependent (rs-BOLD) fMRI data were collected, from which CVR maps were computed. CVR values were compared across lesion, perilesional and control ROIs defined on anatomic images. Reproducibility of the CVR measurement was tested in 6 patients with follow-up scans. In Study 2, rs-BOLD fMRI and dynamic susceptibility contrast (DSC) MRI scans were collected in 5 patients with Moyamoya disease (32.4 ± 8.2 years, 4 females). Cerebral blood flow (CBF), cerebral blood volume (CBV), and time-to-peak (TTP) maps were obtained from the DSC MRI data. CVR values were compared between stenotic brain regions and control regions perfused by non-stenotic arteries. RESULTS In stroke patients, lesion CVR (0.250 ± 0.055 relative unit (r.u.)) was lower than control CVR (0.731 ± 0.088 r.u., p = 0.0002). CVR was also lower in the perilesional regions in a graded manner (perilesion 1 CVR = 0.422 ± 0.051 r.u., perilesion 2 CVR = 0.492 ± 0.046 r.u.), relative to that in the control regions (p = 0.005 and 0.036, respectively). In the repeatability analysis, a strong correlation was observed between lesion CVR (r2 = 0.91, p = 0.006) measured at two time points, as well as between control CVR (r2 = 0.79, p = 0.036) at two time points. In Moyamoya patients, CVR in the perfusion deficit regions delineated by DSC TTP maps (0.178 ± 0.189 r.u.) was lower than that in the control regions (0.868 ± 0.214 r.u., p = 0.013). Furthermore, the extent of reduction in CVR was significantly correlated with the extent of lengthening in TTP (r2 = 0.91, p = 0.033). CONCLUSION Our findings suggested that rs-BOLD data can be used to reproducibly evaluate CVR in patients with cerebrovascular diseases without the use of any vasoactive challenges.
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27
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Agarwal S, Sair HI, Gujar S, Hua J, Lu H, Pillai JJ. Functional Magnetic Resonance Imaging Activation Optimization in the Setting of Brain Tumor-Induced Neurovascular Uncoupling Using Resting-State Blood Oxygen Level-Dependent Amplitude of Low Frequency Fluctuations. Brain Connect 2019; 9:241-250. [PMID: 30547681 DOI: 10.1089/brain.2017.0562] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
The goal of this study was to demonstrate that a novel resting state BOLD ALFF (amplitude of low frequency fluctuations)-based correction method can substantially enhance the detectability of motor task activation in the presence of tumor-induced neurovascular uncoupling (NVU). Twelve de novo brain tumor patients who underwent comprehensive clinical BOLD fMRI exams including task fMRI and resting state fMRI (rsfMRI) were evaluated. Each patient displayed decreased/absent task fMRI activation in the ipsilesional primary motor cortex in the absence of corresponding motor deficit or suboptimal task performance, consistent with NVU. Z-score maps for the motor tasks were obtained from general linear model (GLM) analysis (reflecting motor activation vs. rest). ALFF maps were calculated from rsfMRI data. Precentral and postcentral gyri in contralesional (CL) and ipsilesional (IL) hemispheres were parcellated using an Automated Anatomical Labeling (AAL) template for each patient. A novel ALFF-based correction method was used to identify the NVU affected voxels in the ipsilesional primary motor cortex (PMC), and a correction factor was applied to normalize the baseline Z-scores for these voxels. In all cases, substantially greater activation was seen on post-ALFF correction motor activation maps within the ipsilesional precentral gyri than in the pre-ALFF correction activation maps. We have demonstrated the feasibility of a new resting state ALFF-based technique for effective correction of brain tumor-related NVU in the primary motor cortex.
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Affiliation(s)
- Shruti Agarwal
- 1 Divisions of Neuroradiology and Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Haris I Sair
- 1 Divisions of Neuroradiology and Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Sachin Gujar
- 1 Divisions of Neuroradiology and Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Jun Hua
- 2 Divisions of MR Research, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland.,3 F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland
| | - Hanzhang Lu
- 2 Divisions of MR Research, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland.,3 F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland
| | - Jay J Pillai
- 1 Divisions of Neuroradiology and Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland.,4 Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
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28
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Agarwal S, Sair HI, Pillai JJ. Limitations of Resting-State Functional MR Imaging in the Setting of Focal Brain Lesions. Neuroimaging Clin N Am 2018; 27:645-661. [PMID: 28985935 DOI: 10.1016/j.nic.2017.06.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Methods of image acquisition and analysis for resting-state functional MR imaging (rsfMR imaging) are still evolving. Neurovascular uncoupling and susceptibility artifact are important confounds of rsfMR imaging in the setting of focal brain lesions such as brain tumors. This article reviews the detection of these confounds using rsfMR imaging metrics in the setting of focal brain lesions. In the near future, with the wide range of ongoing research in rsfMR imaging, these issues likely will be overcome and will open new windows into brain function and connectivity.
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Affiliation(s)
- Shruti Agarwal
- Division of Neuroradiology, The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Phipps B-100, 1800 Orleans Street, Baltimore, MD 21287, USA
| | - Haris I Sair
- Division of Neuroradiology, The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Phipps B-100, 1800 Orleans Street, Baltimore, MD 21287, USA
| | - Jay J Pillai
- Division of Neuroradiology, The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Phipps B-100, 1800 Orleans Street, Baltimore, MD 21287, USA.
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29
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Liu P, De Vis JB, Lu H. Cerebrovascular reactivity (CVR) MRI with CO2 challenge: A technical review. Neuroimage 2018; 187:104-115. [PMID: 29574034 DOI: 10.1016/j.neuroimage.2018.03.047] [Citation(s) in RCA: 182] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2017] [Revised: 02/06/2018] [Accepted: 03/19/2018] [Indexed: 11/16/2022] Open
Abstract
Cerebrovascular reactivity (CVR) is an indicator of cerebrovascular reserve and provides important information about vascular health in a range of brain conditions and diseases. Unlike steady-state vascular parameters, such as cerebral blood flow (CBF) and cerebral blood volume (CBV), CVR measures the ability of cerebral vessels to dilate or constrict in response to challenges or maneuvers. Therefore, CVR mapping requires a physiological challenge while monitoring the corresponding hemodynamic changes in the brain. The present review primarily focuses on methods that use CO2 inhalation as a physiological challenge while monitoring changes in hemodynamic MRI signals. CO2 inhalation has been increasingly used in CVR mapping in recent literature due to its potency in causing vasodilation, rapid onset and cessation of the effect, as well as advances in MRI-compatible gas delivery apparatus. In this review, we first discuss the physiological basis of CVR mapping using CO2 inhalation. We then review the methodological aspects of CVR mapping, including gas delivery apparatus, the timing paradigm of the breathing challenge, the MRI imaging sequence, and data analysis. In addition, we review alternative approaches for CVR mapping that do not require CO2 inhalation.
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Affiliation(s)
- Peiying Liu
- Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, United States.
| | - Jill B De Vis
- Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, United States
| | - Hanzhang Lu
- Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, United States; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, 21287, United States; F.M. Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, 21205, United States
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30
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Rane S, Koh N, Boord P, Madhyastha T, Askren MK, Jayadev S, Cholerton B, Larson E, Grabowski TJ. Quantitative cerebrovascular pathology in a community-based cohort of older adults. Neurobiol Aging 2018; 65:77-85. [PMID: 29452984 DOI: 10.1016/j.neurobiolaging.2018.01.006] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2017] [Revised: 01/08/2018] [Accepted: 01/09/2018] [Indexed: 02/07/2023]
Abstract
Cerebrovascular disease, especially small vessel pathology, is the leading comorbidity in degenerative disorders. We applied arterial spin labeling and cerebrovascular reserve (CVR) imaging to quantify small vessel disease and study its effect on cognitive symptoms in nondemented older adults from a community-based cohort. We evaluated baseline cerebral blood flow (CBF) using arterial spin labeling and percent signal change as a marker of CVR using blood-oxygen level-dependent imaging following a breath-hold stimulus. Measurements were performed in and near white matter hyperintensities, which are currently the standard to assess severity of vascular pathology. We show that similar to other studies (1) CBF and CVR are markedly reduced in the hyperintensities as well as in the tissue surrounding them, indicating susceptibility to infarction; (2) low CBF and CVR are significantly correlated with poor cognitive performance; and (3) in addition, compared to a 58.4% reduction in CBF, larger exhaustion (79.3%) of CVR was observed in the hyperintensities with a faster, nonlinear rate of decline. We conclude that CVR may be a more sensitive biomarker of small vessel disease than CBF.
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Affiliation(s)
- Swati Rane
- Radiology, University of Washington Medical Center, Seattle, WA, USA.
| | - Natalie Koh
- Radiology, University of Washington Medical Center, Seattle, WA, USA
| | - Peter Boord
- Radiology, University of Washington Medical Center, Seattle, WA, USA
| | - Tara Madhyastha
- Radiology, University of Washington Medical Center, Seattle, WA, USA
| | - Mary K Askren
- Radiology, University of Washington Medical Center, Seattle, WA, USA
| | - Suman Jayadev
- Radiology, University of Washington Medical Center, Seattle, WA, USA
| | - Brenna Cholerton
- Department of Pathology, Stanford University School of Medicine, Palo Alto, CA, USA
| | - Eric Larson
- Group Health Research Institute, Seattle, WA, USA
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31
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van Oers CAMM, van der Worp HB, Kappelle LJ, Raemaekers MAH, Otte WM, Dijkhuizen RM. Etiology of language network changes during recovery of aphasia after stroke. Sci Rep 2018; 8:856. [PMID: 29339771 PMCID: PMC5770409 DOI: 10.1038/s41598-018-19302-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2017] [Accepted: 12/27/2017] [Indexed: 01/17/2023] Open
Abstract
Knowledge of spatiotemporal patterns of language network changes may help in predicting outcome in aphasic stroke patients. Here we assessed language function and performed functional MRI four times during one year to measure language network activation and cerebrovascular reactivity (with breath-holding) in twelve left-hemispheric stroke patients, of whom two dropped out before the final measurement, and eight age-matched controls. Language outcome was related to increase of activation in left and right posterior inferior temporal gyrus over the first year, while activation increase in right inferior frontal gyrus was inversely correlated to language recovery. Outcome prediction improved by addition of early language-induced activation of the left posterior inferior temporal gyrus to a regression model with baseline language performance as first predictor. Variations in language-induced activation in right inferior frontal gyrus were primarily related to differences in vascular reactivity. Furthermore, several language-activation changes could not be linked to alterations in language proficiency nor vascular reactivity, and were assumed to be caused by unspecified intersession variability. In conclusion, early functional neuroimaging improves outcome prediction of aphasia after stroke. Controlling for cerebrovascular reactivity and unspecified intersession variability may result in more accurate assessment of the relationship between activation pattern shifts and function after stroke.
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Affiliation(s)
- Casper A M M van Oers
- Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht and Utrecht University, 3584 CX, Utrecht, The Netherlands. .,Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences, University Medical Center Utrecht and Utrecht University, 3584 CX, Utrecht, The Netherlands. .,Department of Neurology, Amphia Hospital, 4818 CK, Breda, The Netherlands.
| | - H Bart van der Worp
- Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht and Utrecht University, 3584 CX, Utrecht, The Netherlands
| | - L Jaap Kappelle
- Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht and Utrecht University, 3584 CX, Utrecht, The Netherlands
| | - Mathijs A H Raemaekers
- Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht and Utrecht University, 3584 CX, Utrecht, The Netherlands
| | - Willem M Otte
- Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences, University Medical Center Utrecht and Utrecht University, 3584 CX, Utrecht, The Netherlands.,Department of Pediatric Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht and Utrecht University, 3584 CX, Utrecht, The Netherlands
| | - Rick M Dijkhuizen
- Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences, University Medical Center Utrecht and Utrecht University, 3584 CX, Utrecht, The Netherlands
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32
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Identifying and characterizing systematic temporally-lagged BOLD artifacts. Neuroimage 2017; 171:376-392. [PMID: 29288128 DOI: 10.1016/j.neuroimage.2017.12.082] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2017] [Revised: 12/20/2017] [Accepted: 12/22/2017] [Indexed: 01/08/2023] Open
Abstract
Residual noise in the BOLD signal remains problematic for fMRI - particularly for techniques such as functional connectivity, where findings can be spuriously influenced by noise sources that can covary with individual differences. Many such potential noise sources - for instance, motion and respiration - can have a temporally lagged effect on the BOLD signal. Thus, here we present a tool for assessing residual lagged structure in the BOLD signal that is associated with nuisance signals, using a construction similar to a peri-event time histogram. Using this method, we find that framewise displacements - both large and very small - were followed by structured, prolonged, and global changes in the BOLD signal that depend on the magnitude of the preceding displacement and extend for tens of seconds. This residual lagged BOLD structure was consistent across datasets, and independently predicted considerable variance in the global cortical signal (as much as 30-40% in some subjects). Mean functional connectivity estimates varied similarly as a function of displacements occurring many seconds in the past, even after strict censoring. Similar patterns of residual lagged BOLD structure were apparent following respiratory fluctuations (which covaried with framewise displacements), implicating respiration as one likely mechanism underlying the displacement-linked structure observed. Global signal regression largely attenuates this artifactual structure. These findings suggest the need for caution in interpreting results of individual difference studies where noise sources might covary with the individual differences of interest, and highlight the need for further development of preprocessing techniques for mitigating such structure in a more nuanced and targeted manner.
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33
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Black DF, Vachha B, Mian A, Faro SH, Maheshwari M, Sair HI, Petrella JR, Pillai JJ, Welker K. American Society of Functional Neuroradiology-Recommended fMRI Paradigm Algorithms for Presurgical Language Assessment. AJNR Am J Neuroradiol 2017; 38:E65-E73. [PMID: 28860215 DOI: 10.3174/ajnr.a5345] [Citation(s) in RCA: 98] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
INTRODUCTION Functional MR imaging is increasingly being used for presurgical language assessment in the treatment of patients with brain tumors, epilepsy, vascular malformations, and other conditions. The inherent complexity of fMRI, which includes numerous processing steps and selective analyses, is compounded by institution-unique approaches to patient training, paradigm choice, and an eclectic array of postprocessing options from various vendors. Consequently, institutions perform fMRI in such markedly different manners that data sharing, comparison, and generalization of results are difficult. The American Society of Functional Neuroradiology proposes widespread adoption of common fMRI language paradigms as the first step in countering this lost opportunity to advance our knowledge and improve patient care. LANGUAGE PARADIGM REVIEW PROCESS A taskforce of American Society of Functional Neuroradiology members from multiple institutions used a broad literature review, member polls, and expert opinion to converge on 2 sets of standard language paradigms that strike a balance between ease of application and clinical usefulness. ASFNR RECOMMENDATIONS The taskforce generated an adult language paradigm algorithm for presurgical language assessment including the following tasks: Sentence Completion, Silent Word Generation, Rhyming, Object Naming, and/or Passive Story Listening. The pediatric algorithm includes the following tasks: Sentence Completion, Rhyming, Antonym Generation, or Passive Story Listening. DISCUSSION Convergence of fMRI language paradigms across institutions offers the first step in providing a "Rosetta Stone" that provides a common reference point with which to compare and contrast the usefulness and reliability of fMRI data. From this common language task battery, future refinements and improvements are anticipated, particularly as objective measures of reliability become available. Some commonality of practice is a necessary first step to develop a foundation on which to improve the clinical utility of this field.
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Affiliation(s)
- D F Black
- From the Mayo Clinic (D.F.B., K.W.), Rochester Minnesota
| | - B Vachha
- Memorial Sloan Kettering Cancer Center (B.V.), New York, New York
| | - A Mian
- Boston University School of Medicine (A.M.), Boston, Massachusetts
| | - S H Faro
- Johns Hopkins University School of Medicine and the Johns Hopkins Hospital (S.H.F., H.I.S., J.J.P.), Baltimore, Maryland
| | - M Maheshwari
- Children's Hospital of Wisconsin (M.M.), Milwaukee, Wisconsin
| | - H I Sair
- Johns Hopkins University School of Medicine and the Johns Hopkins Hospital (S.H.F., H.I.S., J.J.P.), Baltimore, Maryland
| | - J R Petrella
- Duke University School of Medicine, (J.R.P.) Durham, North Carolina
| | - J J Pillai
- Johns Hopkins University School of Medicine and the Johns Hopkins Hospital (S.H.F., H.I.S., J.J.P.), Baltimore, Maryland
| | - K Welker
- From the Mayo Clinic (D.F.B., K.W.), Rochester Minnesota
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Urback AL, MacIntosh BJ, Goldstein BI. Cerebrovascular reactivity measured by functional magnetic resonance imaging during breath-hold challenge: A systematic review. Neurosci Biobehav Rev 2017; 79:27-47. [PMID: 28487157 DOI: 10.1016/j.neubiorev.2017.05.003] [Citation(s) in RCA: 58] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2016] [Revised: 04/05/2017] [Accepted: 05/02/2017] [Indexed: 10/19/2022]
Abstract
Cerebrovascular reactivity (CVR) is the cerebral hemodynamic response to a vasoactive substance. Breath-hold (BH) induced CVR has the advantage of being non-invasive and easy to implement during magnetic resonance imaging (MRI). We systematically reviewed the literature regarding MRI measurement of BH induced CVR. The literature was searched using MEDLINE with the search terms breath-hold; and MRI or cerebrovascular reactivity. The search yielded 2244 results and 54 articles were included. Between-group comparisons have found that CVR was higher among healthy controls than patients with various pathologies (e.g. sleep apnea, diabetes, hypertension etc.). However, counter-intuitive findings have also been reported, including higher CVR among smokers, sedentary individuals, and patients with schizophrenia vs. CONTROLS Methodological studies have highlighted important measurement characteristics (e.g. normalizing signal to end-tidal CO2), and comparisons of BH induced CVR to non-BH methods. Future studies are warranted to address questions about group differences, treatment response, disease progression, and other salient clinical themes. Standardization of CVR and BH designs is needed to fully exploit the potential of this practical non-invasive method.
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Affiliation(s)
- Adam L Urback
- Centre for Youth Bipolar Disorder, Sunnybrook Health Sciences Centre 2075 Bayview Ave., FG-53, Toronto, ON, M4N 3M5, Canada; Department of Pharmacology, University of Toronto, Medicine, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
| | - Bradley J MacIntosh
- University of Toronto, Department of Medical Biophysics, 101 College Street Suite 15-701, Toronto, ON, M5G 1L7, Canada; Canadian Partnership for Stroke Recovery, Sunnybrook Health Sciences Centre, 2075 Bayview Ave., Room M6 180, Toronto, ON, M4N 3M5, Canada.
| | - Benjamin I Goldstein
- Centre for Youth Bipolar Disorder, Sunnybrook Health Sciences Centre 2075 Bayview Ave., FG-53, Toronto, ON, M4N 3M5, Canada; Department of Pharmacology, University of Toronto, Medicine, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada; Department of Psychiatry, University of Toronto, Medicine,250 College Street, Room 835, Toronto, ON, M5T 1R8, Canada.
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35
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Tan CH, Low KA, Schneider-Garces N, Zimmerman B, Fletcher MA, Maclin EL, Chiarelli AM, Gratton G, Fabiani M. Optical measures of changes in cerebral vascular tone during voluntary breath holding and a Sternberg memory task. Biol Psychol 2016; 118:184-194. [PMID: 27235126 PMCID: PMC9906974 DOI: 10.1016/j.biopsycho.2016.05.008] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2015] [Revised: 05/20/2016] [Accepted: 05/20/2016] [Indexed: 12/24/2022]
Abstract
The human cerebral vasculature responds to changes in blood pressure and demands for oxygenation via cerebral autoregulation. Changes in cerebrovascular tone (vasoconstriction and vasodilation) also mediate the changes in blood flow measured by the BOLD fMRI signal. This cerebrovascular reactivity is known to vary with age. In two experiments, we demonstrate that cerebral pulse parameters measured using optical imaging can quantify changes in cerebral vascular tone, both globally and locally. In experiment 1, 51 older adults (age range=55-87) performed a voluntary breath-holding task while cerebral pulse amplitude measures were taken. We found significant pulse amplitude variations across breath-holding periods, indicating vasodilation during, and vasoconstriction after breath holding. The breath-holding index (BHI), a measure of cerebrovascular reactivity (CVR) was derived and found to correlate with age. BHI was also correlated with performance in the Modified Mini-Mental Status Examination, even after controlling for age and education. In experiment 2, the same participants performed a Sternberg task, and changes in regional pulse amplitude between high (set-size 6) and low (set-size 2) task loads were compared. Only task-related areas in the fronto-parietal network (FPN) showed significant reduction in pulse amplitude, indicating vasodilation. Non-task-related areas such as the somatosensory and auditory cortices did not show such reductions. Taken together, these experiments suggest that optical pulse parameters can index changes in brain vascular tone both globally and locally, using both physiological and cognitive load manipulations.
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Affiliation(s)
- Chin Hong Tan
- Department of Psychology, University of Illinois at Urbana-Champaign, United States,Beckman Institute, University of Illinois at Urbana-Champaign, United States
| | - Kathy A. Low
- Beckman Institute, University of Illinois at Urbana-Champaign, United States
| | | | - Benjamin Zimmerman
- Beckman Institute, University of Illinois at Urbana-Champaign, United States
| | - Mark A. Fletcher
- Beckman Institute, University of Illinois at Urbana-Champaign, United States
| | - Edward L. Maclin
- Beckman Institute, University of Illinois at Urbana-Champaign, United States
| | | | - Gabriele Gratton
- Department of Psychology, University of Illinois at Urbana-Champaign, United States,Beckman Institute, University of Illinois at Urbana-Champaign, United States
| | - Monica Fabiani
- Department of Psychology, University of Illinois at Urbana-Champaign, United States; Beckman Institute, University of Illinois at Urbana-Champaign, United States.
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36
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Quantitative mapping of cerebrovascular reactivity using resting-state BOLD fMRI: Validation in healthy adults. Neuroimage 2016; 138:147-163. [PMID: 27177763 DOI: 10.1016/j.neuroimage.2016.05.025] [Citation(s) in RCA: 68] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2016] [Revised: 05/04/2016] [Accepted: 05/07/2016] [Indexed: 11/23/2022] Open
Abstract
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 (CO2) modulations, in units of [%ΔBOLD/mmHg]. While this method has achieved wide appeal and clinical translation, the tolerability of CO2-related tasks amongst patients and the elderly remains a challenge in more routine and large-scale applications. In this work, we propose an improved method to quantify CVR by exploiting intrinsic fluctuations in CO2 and corresponding changes in the resting-state BOLD signal (rs-qCVR). Our rs-qCVR approach requires simultaneous monitoring of PETCO2, cardiac pulsation and respiratory volume. In 16 healthy adults, we compare our quantitative CVR estimation technique to the prospective CO2-targeting based CVR quantification approach (qCVR, the "standard"). We also compare our rs-CVR to non-quantitative alternatives including the resting-state fluctuation amplitude (RSFA), amplitude of low-frequency fluctuation (ALFF) and global-signal 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 PETCO2-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 within-subject 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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Fierstra J, Burkhardt JK, van Niftrik CHB, Piccirelli M, Pangalu A, Kocian R, Neidert MC, Valavanis A, Regli L, Bozinov O. Blood oxygen-level dependent functional assessment of cerebrovascular reactivity: Feasibility for intraoperative 3 Tesla MRI. Magn Reson Med 2016; 77:806-813. [PMID: 26918794 DOI: 10.1002/mrm.26135] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2015] [Revised: 11/29/2015] [Accepted: 12/26/2015] [Indexed: 11/10/2022]
Abstract
PURPOSE To assess the feasibility of functional blood oxygen-level dependent (BOLD) MRI to evaluate intraoperative cerebrovascular reactivity (CVR) at 3 Tesla field strength. METHODS Ten consecutive neurosurgical subjects scheduled for a clinical intraoperative MRI examination were enrolled in this study. In addition to the clinical protocol a BOLD sequence was implemented with three cycles of 44 s apnea to calculate CVR values on a voxel-by-voxel basis throughout the brain. The CVR range was then color-coded and superimposed on an anatomical volume to create high spatial resolution CVR maps. RESULTS Ten subjects (mean age 34.8 ± 13.4; 2 females) uneventfully underwent the intraoperative BOLD protocol, with no complications occurring. Whole-brain CVR for all subjects was (mean ± SD) 0.69 ± 0.42, whereas CVR was markedly higher for tumor subjects as compared to vascular subjects, 0.81 ± 0.44 versus 0.33 ± 0.10, respectively. Furthermore, color-coded functional maps could be robustly interpreted for a whole-brain assessment of CVR. CONCLUSION We demonstrate that intraoperative BOLD MRI is feasible in creating functional maps to assess cerebrovascular reactivity throughout the brain in subjects undergoing a neurosurgical procedure. Magn Reson Med 77:806-813, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
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Affiliation(s)
- Jorn Fierstra
- Department of Neurosurgery, Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Switzerland
| | - Jan-Karl Burkhardt
- Department of Neurosurgery, Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Switzerland
| | | | - Marco Piccirelli
- Department of Neuroradiology, Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Switzerland
| | - Athina Pangalu
- Department of Neuroradiology, Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Switzerland
| | - Roman Kocian
- Department of Neuro-anesthesia, Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Switzerland
| | - Marian Christoph Neidert
- Department of Neurosurgery, Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Switzerland
| | - Antonios Valavanis
- Department of Neuroradiology, Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Switzerland
| | - Luca Regli
- Department of Neurosurgery, Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Switzerland
| | - Oliver Bozinov
- Department of Neurosurgery, Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Switzerland
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38
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Pinto J, Jorge J, Sousa I, Vilela P, Figueiredo P. Fourier modeling of the BOLD response to a breath-hold task: Optimization and reproducibility. Neuroimage 2016; 135:223-31. [PMID: 26908316 DOI: 10.1016/j.neuroimage.2016.02.037] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2015] [Revised: 01/09/2016] [Accepted: 02/12/2016] [Indexed: 11/18/2022] Open
Abstract
Cerebrovascular reactivity (CVR) reflects the capacity of blood vessels to adjust their caliber in order to maintain a steady supply of brain perfusion, and it may provide a sensitive disease biomarker. Measurement of the blood oxygen level dependent (BOLD) response to a hypercapnia-inducing breath-hold (BH) task has been frequently used to map CVR noninvasively using functional magnetic resonance imaging (fMRI). However, the best modeling approach for the accurate quantification of CVR maps remains an open issue. Here, we compare and optimize Fourier models of the BOLD response to a BH task with a preparatory inspiration, and assess the test-retest reproducibility of the associated CVR measurements, in a group of 10 healthy volunteers studied over two fMRI sessions. Linear combinations of sine-cosine pairs at the BH task frequency and its successive harmonics were added sequentially in a nested models approach, and were compared in terms of the adjusted coefficient of determination and corresponding variance explained (VE) of the BOLD signal, as well as the number of voxels exhibiting significant BOLD responses, the estimated CVR values, and their test-retest reproducibility. The brain average VE increased significantly with the Fourier model order, up to the 3rd order. However, the number of responsive voxels increased significantly only up to the 2nd order, and started to decrease from the 3rd order onwards. Moreover, no significant relative underestimation of CVR values was observed beyond the 2nd order. Hence, the 2nd order model was concluded to be the optimal choice for the studied paradigm. This model also yielded the best test-retest reproducibility results, with intra-subject coefficients of variation of 12 and 16% and an intra-class correlation coefficient of 0.74. In conclusion, our results indicate that a Fourier series set consisting of a sine-cosine pair at the BH task frequency and its two harmonics is a suitable model for BOLD-fMRI CVR measurements based on a BH task with preparatory inspiration, yielding robust estimates of this important physiological parameter.
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Affiliation(s)
- Joana Pinto
- Institute for Systems and Robotics, Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal.
| | - João Jorge
- Institute for Systems and Robotics, Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal; Biomedical Imaging Research Center, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
| | - Inês Sousa
- Institute for Systems and Robotics, Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal; Healthcare Sector, Siemens, S.A., Portugal
| | - Pedro Vilela
- Imaging Department, Hospital da Luz, Lisbon, Portugal
| | - Patrícia Figueiredo
- Institute for Systems and Robotics, Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal
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van Niftrik CHB, Piccirelli M, Bozinov O, Pangalu A, Valavanis A, Regli L, Fierstra J. Fine tuning breath-hold-based cerebrovascular reactivity analysis models. Brain Behav 2016; 6:e00426. [PMID: 27110448 PMCID: PMC4834934 DOI: 10.1002/brb3.426] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2015] [Revised: 11/25/2015] [Accepted: 12/07/2015] [Indexed: 11/11/2022] Open
Abstract
INTRODUCTION We elaborate on existing analysis methods for breath-hold (BH)-derived cerebrovascular reactivity (CVR) measurements and describe novel insights and models toward more exact CVR interpretation. METHODS Five blood-oxygen-level-dependent (BOLD) fMRI datasets of neurovascular patients with unilateral hemispheric hemodynamic impairment were used to test various BH CVR analysis methods. Temporal lag (phase), percent BOLD signal change (CVR), and explained variance (coherence) maps were calculated using three different sine models and two novel "Optimal Signal" model-free methods based on the unaffected hemisphere and the sagittal sinus fMRI signal time series, respectively. RESULTS All models showed significant differences in CVR and coherence between the affected-hemodynamic impaired-and unaffected hemisphere. Voxel-wise phase determination significantly increases CVR (0.60 ± 0.18 vs. 0.82 ± 0.27; P < 0.05). Incorporating different durations of breath hold and resting period in one sine model (two-task) did increase coherence in the unaffected hemisphere, as well as eliminating negative phase commonly obtained by one-task frequency models. The novel model-free "optimal signal" methods both explained the BOLD MR data similar to the two task sine model. CONCLUSIONS Our CVR analysis demonstrates an improved CVR and coherence after implementation of voxel-wise phase and frequency adjustment. The novel "optimal signal" methods provide a robust and feasible alternative to the sine models, as both are model-free and independent of compliance. Here, the sagittal sinus model may be advantageous, as it is independent of hemispheric CVR impairment.
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Affiliation(s)
- Christiaan Hendrik Bas van Niftrik
- Department of Neurosurgery University Hospital Zurich University of Zurich Clinical Neuroscience Center Frauenklinikstrasse 10 8091 Zurich Switzerland
| | - Marco Piccirelli
- Department of Neuroradiology University Hospital Zurich University of Zurich Clinical Neuroscience Center Frauenklinikstrasse 10 8091 Zurich Switzerland
| | - Oliver Bozinov
- Department of Neurosurgery University Hospital Zurich University of Zurich Clinical Neuroscience Center Frauenklinikstrasse 10 8091 Zurich Switzerland
| | - Athina Pangalu
- Department of Neuroradiology University Hospital Zurich University of Zurich Clinical Neuroscience Center Frauenklinikstrasse 10 8091 Zurich Switzerland
| | - Antonios Valavanis
- Department of Neuroradiology University Hospital Zurich University of Zurich Clinical Neuroscience Center Frauenklinikstrasse 10 8091 Zurich Switzerland
| | - Luca Regli
- Department of Neurosurgery University Hospital Zurich University of Zurich Clinical Neuroscience Center Frauenklinikstrasse 10 8091 Zurich Switzerland
| | - Jorn Fierstra
- Department of Neurosurgery University Hospital Zurich University of Zurich Clinical Neuroscience Center Frauenklinikstrasse 10 8091 Zurich Switzerland
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40
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Agreement and repeatability of vascular reactivity estimates based on a breath-hold task and a resting state scan. Neuroimage 2015; 113:387-96. [PMID: 25795342 PMCID: PMC4441043 DOI: 10.1016/j.neuroimage.2015.03.004] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2014] [Revised: 02/27/2015] [Accepted: 03/03/2015] [Indexed: 12/02/2022] Open
Abstract
FMRI BOLD responses to changes in neural activity are influenced by the reactivity of the vasculature. By complementing a task-related BOLD acquisition with a vascular reactivity measure obtained through breath-holding or hypercapnia, this unwanted variance can be statistically reduced in the BOLD responses of interest. Recently, it has been suggested that vascular reactivity can also be estimated using a resting state scan. This study aimed to compare three breath-hold based analysis approaches (block design, sine–cosine regressor and CO2 regressor) and a resting state approach (CO2 regressor) to measure vascular reactivity. We tested BOLD variance explained by the model and repeatability of the measures. Fifteen healthy participants underwent a breath-hold task and a resting state scan with end-tidal CO2 being recorded during both. Vascular reactivity was defined as CO2-related BOLD percent signal change/mm Hg change in CO2. Maps and regional vascular reactivity estimates showed high repeatability when the breath-hold task was used. Repeatability and variance explained by the CO2 trace regressor were lower for the resting state data based approach, which resulted in highly variable measures of vascular reactivity. We conclude that breath-hold based vascular reactivity estimations are more repeatable than resting-based estimates, and that there are limitations with replacing breath-hold scans by resting state scans for vascular reactivity assessment.
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41
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Buterbaugh J, Wynstra C, Provencio N, Combs D, Gilbert M, Parthasarathy S. Cerebrovascular reactivity in young subjects with sleep apnea. Sleep 2015; 38:241-50. [PMID: 25409111 DOI: 10.5665/sleep.4406] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2014] [Accepted: 10/24/2014] [Indexed: 11/03/2022] Open
Abstract
STUDY OBJECTIVES Regional brain alterations may be involved in the pathogenesis and adverse consequences of obstructive sleep apnea (OSA). The objectives for the current study were to (1) determine cerebrovascular reactivity in the motor areas that control upper airway musculature in patients with OSA, and (2) determine whether young patients with OSA have decreased cerebrovascular reactivity in response to breath holding. DESIGN Case-control study. SETTING Academic center. PARTICIPANTS Twelve subjects with OSA (age 24-42 y; apnea-hypopnea index 17; interquartile range [IQR] 9, 69 per hour) and control subjects (n = 10; age 29-44 y; AHI 2; IQR 1, 3 per hour). MEASUREMENTS AND RESULTS Subjects underwent blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) while awake, swallowing, and breath holding. In subjects with OSA, during swallowing, there was less activity in the brainstem than in controls (P = 0.03) that remained reduced after adjusting for cortical motor strip activity (P = 0.036). In OSA subjects, brain regions of increased cerebrovascular reactivity (38; IQR 17, 96 cm(3)) was smaller than that in controls (199; IQR 5, 423 cm(3); P = 0.01). In OSA subjects, brain regions of decreased cerebrovascular reactivity during breath hold was greater (P = 0.01), and the ratio of increased-to-decreased brain regions was lower than that of controls (P = 0.006). Adjustment for cerebral volumes, body mass index, and white matter lesions did not change these results substantively. CONCLUSIONS In patients with obstructive sleep apnea (OSA), diminished change in brainstem activity during swallowing and reduced cerebrovascular reactivity may contribute to the etiopathogenesis and adverse cerebrovascular consequences, respectively. We speculate that decreased cerebral auto-regulation may be causative of gray matter loss in OSA.
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Affiliation(s)
- John Buterbaugh
- Southern Arizona Veterans Administration Health Care System, Tucson, AZ
| | - Charles Wynstra
- Southern Arizona Veterans Administration Health Care System, Tucson, AZ.,Arizona Respiratory Center, Tucson, AZ
| | - Natalie Provencio
- Southern Arizona Veterans Administration Health Care System, Tucson, AZ.,Arizona Respiratory Center, Tucson, AZ
| | - Daniel Combs
- Arizona Respiratory Center, Tucson, AZ.,Department of Medicine of University of Arizona, Tucson, AZ
| | - Michael Gilbert
- Southern Arizona Veterans Administration Health Care System, Tucson, AZ
| | - Sairam Parthasarathy
- Southern Arizona Veterans Administration Health Care System, Tucson, AZ.,Arizona Respiratory Center, Tucson, AZ.,Department of Medicine of University of Arizona, Tucson, AZ
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Reproducibility of hypocapnic cerebrovascular reactivity measurements using BOLD fMRI in combination with a paced deep breathing task. Neuroimage 2014; 98:31-41. [DOI: 10.1016/j.neuroimage.2014.04.049] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2013] [Revised: 04/14/2014] [Accepted: 04/16/2014] [Indexed: 11/23/2022] Open
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Pillai JJ, Mikulis DJ. Cerebrovascular reactivity mapping: an evolving standard for clinical functional imaging. AJNR Am J Neuroradiol 2014; 36:7-13. [PMID: 24788129 DOI: 10.3174/ajnr.a3941] [Citation(s) in RCA: 95] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
SUMMARY This review article explains the methodology of breath-hold cerebrovascular reactivity mapping, both in terms of acquisition and analysis, and reviews applications of this method to presurgical mapping, particularly with respect to blood oxygen level-dependent fMRI. Its main application in clinical fMRI is for the assessment of neurovascular uncoupling potential. Neurovascular uncoupling is potentially a major limitation of clinical fMRI, particularly in the setting of mass lesions in the brain such as brain tumors and intracranial vascular malformations that are associated with alterations in regional hemodynamics on either an acquired or congenital basis. As such, breath-hold cerebrovascular reactivity mapping constitutes an essential component of quality control analysis in clinical fMRI, particularly when performed for presurgical mapping of eloquent cortex. Exogenous carbon dioxide challenges used for cerebrovascular reactivity mapping will also be discussed, and their applications to the evaluation of cerebrovascular reserve and cerebrovascular disease will be described.
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Affiliation(s)
- J J Pillai
- From the Division of Neuroradiology (J.J.P.), Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - D J Mikulis
- Department of Medical Imaging (D.J.M.), The University of Toronto, The University Health Network, The Toronto Western Hospital, Toronto, Ontario, Canada
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44
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Zacà D, Jovicich J, Nadar SR, Voyvodic JT, Pillai JJ. Cerebrovascular reactivity mapping in patients with low grade gliomas undergoing presurgical sensorimotor mapping with BOLD fMRI. J Magn Reson Imaging 2013; 40:383-90. [PMID: 24338845 DOI: 10.1002/jmri.24406] [Citation(s) in RCA: 86] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2013] [Accepted: 08/05/2013] [Indexed: 11/11/2022] Open
Abstract
PURPOSE (i) to validate blood oxygenation level dependent (BOLD) breathhold cerebrovascular reactivity (BH CVR) mapping as an effective technique for potential detection of neurovascular uncoupling (NVU) in a cohort of patients with perirolandic low grade gliomas undergoing presurgical functional MRI (fMRI) for sensorimotor mapping, and (ii) to determine whether NVU potential, as assessed by BH CVR mapping, is prevalent in this tumor group. MATERIALS AND METHODS We retrospectively evaluated 12 patients, with histological diagnosis of grade II glioma, who performed multiple motor tasks and a BH task. Sensorimotor activation maps and BH CVR maps were compared in two automatically defined regions of interest (ROIs), ipsilateral to the lesion (i.e., ipsilesional) and contralateral to the lesion (i.e., contralesional). RESULTS Motor task mean T-value was significantly higher in the contralesional ROIs (6.00 ± 1.74 versus 4.34 ± 1.68; P = 0.00004) as well as the BH mean T-value (4.74 ± 2.30 versus 4.09 ± 2.50; P = 0.009). The number of active voxels was significantly higher in the contralesional ROIs (Z = 2.99; P = 0.03). Actual NVU prevalence was 75%. CONCLUSION Presurgical sensorimotor fMRI mapping can be affected by NVU-related false negative activation in low grade gliomas (76% of analyzed tasks).
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Affiliation(s)
- Domenico Zacà
- Division of Neuroradiology, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Center for Mind/Brain Sciences, University of Trento, Italy
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Blockley NP, Griffeth VEM, Simon AB, Buxton RB. A review of calibrated blood oxygenation level-dependent (BOLD) methods for the measurement of task-induced changes in brain oxygen metabolism. NMR IN BIOMEDICINE 2013; 26:987-1003. [PMID: 22945365 PMCID: PMC3639302 DOI: 10.1002/nbm.2847] [Citation(s) in RCA: 113] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/23/2012] [Revised: 07/17/2012] [Accepted: 08/02/2012] [Indexed: 05/23/2023]
Abstract
The dynamics of the blood oxygenation level-dependent (BOLD) response are dependent on changes in cerebral blood flow, cerebral blood volume and the cerebral metabolic rate of oxygen consumption. Furthermore, the amplitude of the response is dependent on the baseline physiological state, defined by the haematocrit, oxygen extraction fraction and cerebral blood volume. As a result of this complex dependence, the accurate interpretation of BOLD data and robust intersubject comparisons when the baseline physiology is varied are difficult. The calibrated BOLD technique was developed to address these issues. However, the methodology is complex and its full promise has not yet been realised. In this review, the theoretical underpinnings of calibrated BOLD, and issues regarding this theory that are still to be resolved, are discussed. Important aspects of practical implementation are reviewed and reported applications of this methodology are presented.
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Affiliation(s)
- Nicholas P Blockley
- Center for Functional Magnetic Resonance Imaging, Department of Radiology, University of California San Diego, La Jolla, CA, USA.
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46
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Bright MG, Murphy K. Reliable quantification of BOLD fMRI cerebrovascular reactivity despite poor breath-hold performance. Neuroimage 2013; 83:559-68. [PMID: 23845426 PMCID: PMC3899001 DOI: 10.1016/j.neuroimage.2013.07.007] [Citation(s) in RCA: 127] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2013] [Revised: 06/11/2013] [Accepted: 07/02/2013] [Indexed: 11/28/2022] Open
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 3 T. 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.
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Affiliation(s)
- Molly G Bright
- Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, Cardiff University, CF10 3AT Cardiff, UK.
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Wen X, Rangarajan G, Ding M. Is Granger causality a viable technique for analyzing fMRI data? PLoS One 2013; 8:e67428. [PMID: 23861763 PMCID: PMC3701552 DOI: 10.1371/journal.pone.0067428] [Citation(s) in RCA: 92] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2013] [Accepted: 05/17/2013] [Indexed: 01/19/2023] Open
Abstract
Multivariate neural data provide the basis for assessing interactions in brain networks. Among myriad connectivity measures, Granger causality (GC) has proven to be statistically intuitive, easy to implement, and generate meaningful results. Although its application to functional MRI (fMRI) data is increasing, several factors have been identified that appear to hinder its neural interpretability: (a) latency differences in hemodynamic response function (HRF) across different brain regions, (b) low-sampling rates, and (c) noise. Recognizing that in basic and clinical neuroscience, it is often the change of a dependent variable (e.g., GC) between experimental conditions and between normal and pathology that is of interest, we address the question of whether there exist systematic relationships between GC at the fMRI level and that at the neural level. Simulated neural signals were convolved with a canonical HRF, down-sampled, and noise-added to generate simulated fMRI data. As the coupling parameters in the model were varied, fMRI GC and neural GC were calculated, and their relationship examined. Three main results were found: (1) GC following HRF convolution is a monotonically increasing function of neural GC; (2) this monotonicity can be reliably detected as a positive correlation when realistic fMRI temporal resolution and noise level were used; and (3) although the detectability of monotonicity declined due to the presence of HRF latency differences, substantial recovery of detectability occurred after correcting for latency differences. These results suggest that Granger causality is a viable technique for analyzing fMRI data when the questions are appropriately formulated.
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Affiliation(s)
- Xiaotong Wen
- The J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, Florida, United State of America
| | - Govindan Rangarajan
- Department of Mathematics and Centre for Neuroscience, Indian Institute of Science, Bangalore, India
| | - Mingzhou Ding
- The J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, Florida, United State of America
- * E-mail:
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Pillai JJ, Zacá D. Clinical utility of cerebrovascular reactivity mapping in patients with low grade gliomas. World J Clin Oncol 2011; 2:397-403. [PMID: 22171282 PMCID: PMC3235658 DOI: 10.5306/wjco.v2.i12.397] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2011] [Revised: 11/24/2011] [Accepted: 12/01/2011] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate neurovascular uncoupling (NVU) associated with low grade gliomas (LGG) using blood oxygen level dependent (BOLD) cerebrovascular reactivity mapping.
METHODS: Seven patients with low grade gliomas referred by neurosurgeons for presurgical mapping were included in this pilot study. Cerebrovascular reactivity (CVR) mapping was performed by acquiring BOLD images while patients performed a block-design breath-hold (BH) hypercapnia task. CVR mapping was expressed as BOLD percentage signal change (PSC) from baseline associated with performance of the BH hypercapnia task. Standard T2* Dynamic Susceptibility Contrast perfusion imaging was performed and relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) maps were generated. Structural T1 weighted MR images were also acquired. A correlation analysis between intratumoral normalized (via ratio with contralateral homologous regions) BOLD BH PSC [referred to as (nCVR)] and intratumoral normalized resting state rCBV (rCBF) values (i.e., nCBV and nCBF, respectively) was performed.
RESULTS: No significant correlation was seen between the normalized BOLD BH PSC (i.e., nCBV) and nCBV or nCBF. However, the average nCVR (median = 0.50, z = -2.28, P = 0.01) was significantly less than 1.0, indicating abnormally reduced vascular responses in the tumor regions relative to normal contralesional homologous regions, whereas the average nCBV (median = 0.94, z = -0.92, P = 0.375) and nCBF (median = 0.93, z = -1.16, P = 0.25) were not significantly higher or lower than 1.0, indicating iso-perfusion in the tumor regions relative to normal contralesional homologous regions. These findings suggest that in LGG, hyperperfusion that is seen in high grade gliomas is not present, but, nevertheless, abnormally decreased regional CVR is present within and adjacent to LGG. Since the patients all demonstrated at least some residual function attributable to the cortical regions of impaired CVR, but were incapable of producing a BOLD response in these regions regardless of the tasks performed, such regionally decreased CVR is indicative of NVU. The low nCVR ratios indicate high prevalence of NVU in this LGG cohort, which is an important consideration in the interpretation of clinical presurgical mapping with functional magnetic resonance (MR) imaging.
CONCLUSION: Our preliminary study shows that BH CVR mapping is clinically feasible and demonstrates an unexpectedly high prevalence of NVU in patients with LGG.
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Affiliation(s)
- Jay J Pillai
- Jay J Pillai, Domenico Zacá, Neuroradiology Division, Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins University, School of Medicine and The Johns Hopkins Hospital, 600 N. Wolfe Street, Phipps B-100, Baltimore, MD 21287, United States
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Pimentel MAF, Vilela P, Sousa I, Figueiredo P. Localization of the hand motor area by arterial spin labeling and blood oxygen level-dependent functional magnetic resonance imaging. Hum Brain Mapp 2011; 34:96-108. [PMID: 22121040 DOI: 10.1002/hbm.21418] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2010] [Revised: 06/26/2011] [Accepted: 07/01/2011] [Indexed: 12/21/2022] Open
Abstract
The new clinically available arterial spin labeling (ASL) perfusion imaging sequences present some advantages relatively to the commonly used blood oxygen level-dependent (BOLD) method for functional brain studies using magnetic resonance imaging (MRI). In particular, regional cerebral blood flow (CBF) changes are thought to be more directly related with neuronal activation. In this study, we aimed to investigate the accuracy of the functional localization of the hand motor area obtained by simultaneous CBF and BOLD contrasts provided by ASL functional MRI (fMRI) and compare it with a standard BOLD fMRI protocol. For this purpose, we measured the distance between the center of gravity of the activation clusters obtained with each contrast (CBF, BOLD(ASL), and Standard BOLD) and 11 positions defined on a well-established anatomical landmark of the hand motor area (the omega in the axial plane of the precentral gyrus). We found that CBF measurements were significantly closer to the anatomical landmark than the ones obtained using either simultaneous BOLD(ASL) or standard BOLD contrasts. Moreover, we also observed reduced intersubject variability of the functional localization, as well as percent signal change, for CBF relative to both BOLD contrast measurements. In conclusion, our results add further evidence in support to the notion that CBF provides a more accurate localization of motor activation than BOLD contrast, indicating that ASL may be an appropriate technique for clinical fMRI studies.
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Affiliation(s)
- Marco A F Pimentel
- Institute for Systems and Robotics/Department of Bioengineering, Instituto Superior Técnico, Technical University of Lisbon, Lisbon, Portugal
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Santos N, Sanches JM, Sousa I, Figueiredo P. Optimal sampling and estimation in PASL perfusion imaging. IEEE Trans Biomed Eng 2011; 58:3165-74. [PMID: 21846602 DOI: 10.1109/tbme.2011.2164916] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Pulsed arterial spin labeling (PASL) techniques potentially allow the absolute, noninvasive quantification of brain perfusion using MRI. This can be achieved by fitting a kinetic model to the data acquired at a number of sampling times. However, the intrinsically low signal-to-noise ratio of PASL measurements usually requires substantial signal averaging, which may result in undesirably long scanning times. A judicious choice of the sampling points is, therefore, crucial in order to minimize scanning time, while optimizing estimation accuracy. On the other hand, a priori information regarding the model parameters may improve estimation performance. Here, we propose a Bayesian framework to determine an optimal sampling strategy and estimation method for the measurement of brain perfusion and arterial transit time (ATT). A Bayesian Fisher information criterion is used to determine the optimal sampling points and a MAP criterion is employed for the estimation of the model parameters, both taking into account the uncertainty in the model parameters as well as the amount of noise in the data. By Monte Carlo simulations, we show that using optimal compared to uniform sampling strategies, as well as the Bayesian estimator relative to a standard least squares approach, improves the accuracy of perfusion and ATT measurements. Moreover, we also demonstrate the applicability of the proposed approach to real data, with the advantage of reduced intersubject variability relative to conventional sampling and estimation approaches.
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Affiliation(s)
- Nuno Santos
- Institute for Systems and Robotics, Lisbon, Portugal.
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