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Journal articles on the topic 'Hypercapnia fMRI'

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Author: Grafiati
Published: 10 December 2022
Last updated: 28 January 2023

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1

Cohen, Eric R., Kamil Ugurbil, and Seong-Gi Kim. "Effect of Basal Conditions on the Magnitude and Dynamics of the Blood Oxygenation Level-Dependent fMRI Response." Journal of Cerebral Blood Flow & Metabolism 22, no. 9 (September 2002): 1042–53. http://dx.doi.org/10.1097/00004647-200209000-00002.

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The effect of the basal cerebral blood flow (CBF) on both the magnitude and dynamics of the functional hemodynamic response in humans has not been fully investigated. Thus, the hemodynamic response to visual stimulation was measured using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in human subjects in a 7-T magnetic field under different basal conditions: hypocapnia, normocapnia, and hypercapnia. Hypercapnia was induced by inhalation of a 5% carbon dioxide gas mixture and hypocapnia was produced by hyperventilation. As the fMRI baseline signal increased linearly with expired CO2 from hypocapnic to hypercapnic levels, the magnitude of the BOLD response to visual stimulation decreased linearly. Measures of the dynamics of the visually evoked BOLD response (onset time, full-width-at-half-maximum, and time-to-peak) increased linearly with the basal fMRI signal and the end-tidal CO2 level. The basal CBF level, modulated by the arterial partial pressure of CO2, significantly affects both the magnitude and dynamics of the BOLD response induced by neural activity. These results suggest that caution should be exercised when comparing stimulus-induced fMRI responses under different physiologic or pharmacologic states.
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2

Peng, Shin-Lei, Harshan Ravi, Min Sheng, Binu P. Thomas, and Hanzhang Lu. "Searching for a truly “iso-metabolic” gas challenge in physiological MRI." Journal of Cerebral Blood Flow & Metabolism 37, no. 2 (July 20, 2016): 715–25. http://dx.doi.org/10.1177/0271678x16638103.

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Hypercapnia challenge (e.g. inhalation of CO2) has been used in calibrated fMRI as well as in the mapping of vascular reactivity in cerebrovascular diseases. An important assumption underlying these measurements is that CO2 is a pure vascular challenge but does not alter neural activity. However, recent reports have suggested that CO2 inhalation may suppress neural activity and brain metabolic rate. Therefore, the goal of this study is to propose and test a gas challenge that is truly “iso-metabolic,” by adding a hypoxic component to the hypercapnic challenge, since hypoxia has been shown to enhance cerebral metabolic rate of oxygen (CMRO2). Measurement of global CMRO2 under various gas challenge conditions revealed that, while hypercapnia (P = 0.002) and hypoxia (P = 0.002) individually altered CMRO2 (by −7.6 ± 1.7% and 16.7 ± 4.1%, respectively), inhalation of hypercapnic-hypoxia gas (5% CO2/13% O2) did not change brain metabolism (CMRO2 change: 1.5 ± 3.9%, P = 0.92). Moreover, cerebral blood flow response to the hypercapnic-hypoxia challenge (in terms of % change per mmHg CO2 change) was even greater than that to hypercapnia alone (P = 0.007). Findings in this study suggest that hypercapnic-hypoxia gas challenge may be a useful maneuver in physiological MRI as it preserves vasodilatory response yet does not alter brain metabolism.
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3

Basile, Miriam, Simone Cauzzo, Alejandro Luis Callara, Domenico Montanaro, Valentina Hartwig, Maria Sole Morelli, Francesca Frijia, et al. "mICA-Based fMRI Analysis of Specific CO2-Level-Dependent BOLD Signal Changes in the Human Brainstem." Electronics 12, no. 2 (January 6, 2023): 290. http://dx.doi.org/10.3390/electronics12020290.

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Noninvasive studies of the central respiratory control are of key importance to understanding the physiopathology of central apneas and periodic breathing. The study of the brainstem and cortical-subcortical centers may be achieved by using functional magnetic resonance imaging (fMRI) during gas challenges (hypercapnia). Nonetheless, disentangling specific from non-specific effects of hypercapnia in fMRI is a major methodological challenge, as CO2 vasodilatory effects and physiological noise do strongly impact the BOLD signal. This is particularly true in deep brainstem regions where chemoreceptors and rhythm pattern generators are located. One possibility to detect the true neural-related activation is given by the presence of a supralinear relation between CO2 changes and BOLD signal related to neurovascular coupling in overactive neural areas. Here, we test this hypothesis of a supralinear relationship between CO2 and BOLD signal, as a marker of specificity. We employed a group-masked Independent Component Analysis (mICA) approach and we compared activation levels across different mixtures of inspired CO2 using polynomial regression. Our results highlight key nodes of the central breathing control network, also including dorsal pontine and medullary regions. The suggested methodology allows a voxel-wise parametrization of the response, targeting an issue that affects many fMRI studies employing hypercapnic challenges.
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4

Englund, Erin K., Maria A. Fernández-Seara, Ana E. Rodríguez-Soto, Hyunyeol Lee, Zachary B. Rodgers, Marta Vidorreta, John A. Detre, and Felix W. Wehrli. "Calibrated fMRI for dynamic mapping of CMRO2 responses using MR-based measurements of whole-brain venous oxygen saturation." Journal of Cerebral Blood Flow & Metabolism 40, no. 7 (August 8, 2019): 1501–16. http://dx.doi.org/10.1177/0271678x19867276.

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Functional MRI (fMRI) can identify active foci in response to stimuli through BOLD signal fluctuations, which represent a complex interplay between blood flow and cerebral metabolic rate of oxygen (CMRO2) changes. Calibrated fMRI can disentangle the underlying contributions, allowing quantification of the CMRO2 response. Here, whole-brain venous oxygen saturation ( Y v) was computed alongside ASL-measured CBF and BOLD-weighted data to derive the calibration constant, M, using the proposed Y v-based calibration. Data were collected from 10 subjects at 3T with a three-part interleaved sequence comprising background-suppressed 3D-pCASL, 2D BOLD-weighted, and single-slice dual-echo GRE (to measure Y v via susceptometry-based oximetry) acquisitions while subjects breathed normocapnic/normoxic, hyperoxic, and hypercapnic gases, and during a motor task. M was computed via Y v-based calibration from both hypercapnia and hyperoxia stimulus data, and results were compared to conventional hypercapnia or hyperoxia calibration methods. Mean M in gray matter did not significantly differ between calibration methods, ranging from 8.5 ± 2.8% (conventional hyperoxia calibration) to 11.7 ± 4.5% (Yv-based calibration in response to hyperoxia), with hypercapnia-based M values between ( p = 0.56). Relative CMRO2 changes from finger tapping were computed from each M map. CMRO2 increased by ∼20% in the motor cortex, and good agreement was observed between the conventional and proposed calibration methods.
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5

Uh, J., F. Xu, U. Yezhuvath, Y. Cheng, H. Gu, Y. Yang, and H. Lu. "The Effect of Hypercapnia on Resting State fMRI." NeuroImage 47 (July 2009): S185. http://dx.doi.org/10.1016/s1053-8119(09)72046-4.

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6

Andrade, Katia C., Octavio M. Pontes-Neto, Joao P. Leite, Antonio Carlos Santos, Oswaldo Baffa, and Draulio B. de Araujo. "Quantitative aspects of brain perfusion dynamic induced by BOLD fMRI." Arquivos de Neuro-Psiquiatria 64, no. 4 (December 2006): 895–98. http://dx.doi.org/10.1590/s0004-282x2006000600001.

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The increase of relative cerebral blood flow (rCBF) may contribute for a change in blood oxygenation level dependent signal (BOLD). The main purpose of this study is to investigate some aspects of perfusional alterations in the human brain in response to a uniform stimulation: hypercapnia induced by breath holding. It was observed that the BOLD signal increased globally during hypercapnia and that it is correlated with the time of breath holding. This signal increase shows a clear distinction between gray and white matter, being greater in the grey matter.
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7

Kruuse, Christina, Adam E. Hansen, Henrik BW Larsson, Martin Lauritzen, and Egill Rostrup. "Cerebral Haemodynamic Response or Excitability is not Affected by Sildenafil." Journal of Cerebral Blood Flow & Metabolism 29, no. 4 (February 11, 2009): 830–39. http://dx.doi.org/10.1038/jcbfm.2009.10.

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Sildenafil (Viagra®), a cyclic guanosine monophosphate-degrading phosphodiesterase 5 inhibitor, induces headache and migraine. Such headache induction may be caused by an increased neuronal excitability, as no concurrent effect on cerebral arteries is found. In 13 healthy females (23±3 years, 70.3±6.6 kg), the effect of sildenafil on a visual (reversing checkerboard) and a hypercapnic (6% CO2 inhalation) response was evaluated using functional magnetic resonance imaging (fMRI, 3 T MR scanner). On separate occasions, visual-evoked potential (VEP) measurements (latency (P100) and maximal amplitude) were performed. The measurements were applied at baseline and at both 1 and 2 h after ingestion of 100mg of sildenafil. Blood pressure, heart rate and side effects, including headache, were obtained. Headache was induced in all but one subject on both study days. Sildenafil did not affect VEP amplitude or latency (P100). The fMRI response to visual stimulation or hypercapnia was unchanged by sildenafil. In conclusion, sildenafil induces mild headache without potentiating a neuronal or local cerebrovascular visual response or a global cerebrovascular hypercapnic response. The implication is that sildenafil-induced headache does not include a general lowering of threshold for a neuronal or cerebrovascular response, and that sildenafil does not modulate the hypercapnic response in healthy subjects.
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8

Xu, Feng, Jinsoo Uh, Matthew R. Brier, John Hart, Uma S. Yezhuvath, Hong Gu, Yihong Yang, and Hanzhang Lu. "The Influence of Carbon Dioxide on Brain Activity and Metabolism in Conscious Humans." Journal of Cerebral Blood Flow & Metabolism 31, no. 1 (September 15, 2010): 58–67. http://dx.doi.org/10.1038/jcbfm.2010.153.

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A better understanding of carbon dioxide (CO2) effect on brain activity may have a profound impact on clinical studies using CO2 manipulation to assess cerebrovascular reserve and on the use of hypercapnia as a means to calibrate functional magnetic resonance imaging (fMRI) signal. This study investigates how an increase in blood CO2, via inhalation of 5% CO2, may alter brain activity in humans. Dynamic measurement of brain metabolism revealed that mild hypercapnia resulted in a suppression of cerebral metabolic rate of oxygen ( CMRO 2) by 13.4%±2.3% ( N=14) and, furthermore, the CMRO 2 change was proportional to the subject's end-tidal CO2 (Et-CO2) change. When using functional connectivity MRI (fcMRI) to assess the changes in resting-state neural activity, it was found that hypercapnia resulted in a reduction in all fcMRI indices assessed including cluster volume, cross-correlation coefficient, and amplitude of the fcMRI signal in the default-mode network (DMN). The extent of the reduction was more pronounced than similar indices obtained in visual-evoked fMRI, suggesting a selective suppression effect on resting-state neural activity. Scalp electroencephalogram (EEG) studies comparing hypercapnia with normocapnia conditions showed a relative increase in low frequency power in the EEG spectra, suggesting that the brain is entering a low arousal state on CO2 inhalation.
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9

Wang, Xiao, Xiao-Hong Zhu, Yi Zhang, and Wei Chen. "Large Enhancement of Perfusion Contribution on fMRI Signal." Journal of Cerebral Blood Flow & Metabolism 32, no. 5 (March 7, 2012): 907–18. http://dx.doi.org/10.1038/jcbfm.2012.26.

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The perfusion contribution to the total functional magnetic resonance imaging (fMRI) signal was investigated using a rat model with mild hypercapnia at 9.4 T, and human subjects with visual stimulation at 4 T. It was found that the total fMRI signal change could be approximated as a linear superposition of ‘true’ blood oxygenation level-dependent (BOLD; T2/T2*) effect and the blood flow-related ( T1) effect. The latter effect was significantly enhanced by using short repetition time and large radiofrequency pulse flip angle and became comparable to the ‘true’ BOLD signal in response to a mild hypercapnia in the rat brain, resulting in an improved contrast-to-noise ratio (CNR). Bipolar diffusion gradients suppressed the intravascular signals but had no significant effect on the flow-related signal. Similar results of enhanced fMRI signal were observed in the human study. The overall results suggest that the observed flow-related signal enhancement is likely originated from perfusion, and this enhancement can improve CNR and the spatial specificity for mapping brain activity and physiology changes. The nature of mixed BOLD and perfusion-related contributions in the total fMRI signal also has implication on BOLD quantification, in particular, the BOLD calibration model commonly used to estimate the change of cerebral metabolic rate of oxygen.
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10

Chen, J. Jean, and G. Bruce Pike. "Global Cerebral Oxidative Metabolism during Hypercapnia and Hypocapnia in Humans: Implications for BOLD fMRI." Journal of Cerebral Blood Flow & Metabolism 30, no. 6 (April 7, 2010): 1094–99. http://dx.doi.org/10.1038/jcbfm.2010.42.

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The effect of carbon dioxide (CO2) on cerebral metabolism is of tremendous interest to functional imaging. In particular, mild-to-moderate hypercapnia is routinely used in calibrated blood oxygen-level dependent (BOLD)-functional magnetic resonance imaging (fMRI)-based quantification of cerebral oxidative metabolism changes (ΔCMRO2), and relies on the assumption of a stable CMRO2 during CO2 challenges. However, this assumption has been challenged by certain animal studies, necessitating its verification in humans and under conditions customary to fMRI. We report, for the first time, on global ΔCMRO2 measurements made noninvasively in humans during graded hypercapnia and hypocapnia. We used computerized end-tidal CO2 modulation to minimize undesired concurrent changes in oxygen pressure, and our findings suggest that no significant change in global CMRO2 is expected at the levels of end-tidal CO2 changes customary to calibrated BOLD.
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11

Bendell, Caroline, Shakeeb H. Moosavi, and Mari Herigstad. "Low-level carbon monoxide exposure affects BOLD fMRI response." Journal of Cerebral Blood Flow & Metabolism 40, no. 11 (November 11, 2019): 2215–24. http://dx.doi.org/10.1177/0271678x19887358.

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Blood oxygen level dependent (BOLD) fMRI is a common technique for measuring brain activation that could be affected by low-level carbon monoxide (CO) exposure from, e.g. smoking. This study aimed to probe the vulnerability of BOLD fMRI to CO and determine whether it may constitute a significant neuroimaging confound. Low-level (6 ppm exhaled) CO effects on BOLD response were assessed in 12 healthy never-smokers on two separate experimental days (CO and air control). fMRI tasks were breath-holds (hypercapnia), visual stimulation and fingertapping. BOLD fMRI response was lower during breath holds, visual stimulation and fingertapping in the CO protocol compared to the air control protocol. Behavioural and physiological measures remained unchanged. We conclude that BOLD fMRI might be vulnerable to changes in baseline CO, and suggest exercising caution when imaging populations exposed to elevated CO levels. Further work is required to fully elucidate the impact on CO on fMRI and its underlying mechanisms.
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12

Li, Baoqiang, Jonghwan Lee, David A. Boas, and Frederic Lesage. "Contribution of low- and high-flux capillaries to slow hemodynamic fluctuations in the cerebral cortex of mice." Journal of Cerebral Blood Flow & Metabolism 36, no. 8 (May 10, 2016): 1351–56. http://dx.doi.org/10.1177/0271678x16649195.

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We employed optical coherence tomography to measure cerebral cortical capillary red blood cell (RBC) flux in mice. The results suggest that baseline-flux weakly depends on cortical depth. Furthermore, under hypercapnia, low baseline-flux capillaries exhibit greater flux increases while the higher ones saturate, resulting in RBC-flux homogenization. Power-spectrum analysis indicates that higher flux capillaries saw greater flux variability in the low-frequency range (0.01–0.1 Hz) both at baseline and during hypercapnia. These results suggest that lower baseline-flux capillaries have more reserve to deliver oxygen with increased blood flow; but higher ones more strongly impact the low-frequency fluctuations associated with BOLD fMRI measurements of resting state functional connectivity.
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13

Pattinson, Kyle TS, Richard Rogers, Stephen D. Mayhew, Irene Tracey, and Richard G. Wise. "Pharmacological FMRI: Measuring Opioid Effects on the BOLD Response to Hypercapnia." Journal of Cerebral Blood Flow & Metabolism 27, no. 2 (May 31, 2006): 414–23. http://dx.doi.org/10.1038/sj.jcbfm.9600347.

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14

Tak, Sungho, Jaeduck Jang, Kangjoo Lee, and Jong Chul Ye. "Quantification of CMRO2without hypercapnia using simultaneous near-infrared spectroscopy and fMRI measurements." Physics in Medicine and Biology 55, no. 11 (May 17, 2010): 3249–69. http://dx.doi.org/10.1088/0031-9155/55/11/017.

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15

Wey, Hsiao-Ying, Danny J. Wang, and Timothy Q. Duong. "Baseline CBF, and BOLD, CBF, and CMRO2 fMRI of Visual and Vibrotactile Stimulations in Baboons." Journal of Cerebral Blood Flow & Metabolism 31, no. 2 (September 8, 2010): 715–24. http://dx.doi.org/10.1038/jcbfm.2010.154.

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Neurovascular coupling associated with visual and vibrotactile stimulations in baboons anesthetized sequentially with isoflurane and ketamine was evaluated using multimodal functional magnetic resonance imaging (fMRI) on a clinical 3-Tesla scanner. Basal cerebral blood flow ( CBF), and combined blood-oxygenation-level-dependent ( BOLD) and CBF fMRI of visual and somatosensory stimulations were measured using pseudo-continuous arterial spin labeling. Changes in stimulus-evoked cerebral metabolic rate of oxygen ( CMRO2) were estimated using calibrated fMRI. Arterial transit time for vessel, gray matter (GM), and white matter (WM) were 250, 570, and 823 ms, respectively. Gray matter and WM CBF, respectively, were 107.8 ± 7.9 and 47.8 ± 3.8 mL per 100 g per minute under isoflurane, and 108.8 ± 10.3 and 48.7 ± 4.2 mL per 100 g per minute under ketamine (mean ± s.e.m., N = 8 sessions, five baboons). The GM/WM CBF ratio was not statistically different between the two anesthetics, averaging 2.3 ± 0.1. Hypercapnia evoked global BOLD and CBF increases. Blood-oxygenation-level-dependent, CBF, and CMRO2 signal changes by visual and vibrotactile stimulations were 0.19% to 0.22%, 18% to 23%, and 4.9% to 6.7%, respectively. The CBF/CMRO2 ratio was 2.9 to 4.7. Basal CBF and fMRI responses were not statistically different between the two anesthetics. This study establishes a multimodal fMRI protocol to probe clinically relevant functional, physiological and metabolic information in large nonhuman primates.
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16

Leoni, R. F., K. C. Mazzeto-Betti, K. C. Andrade, and D. B. de Araujo. "Quantitative evaluation of hemodynamic response after hypercapnia among different brain territories by fMRI." NeuroImage 41, no. 4 (July 2008): 1192–98. http://dx.doi.org/10.1016/j.neuroimage.2008.03.035.

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17

Bandettini, Peter A., and Eric C. Wong. "A hypercapnia-based normalization method for improved spatial localization of human brain activation with fMRI." NMR in Biomedicine 10, no. 4-5 (June 1997): 197–203. http://dx.doi.org/10.1002/(sici)1099-1492(199706/08)10:4/5<197::aid-nbm466>3.0.co;2-s.

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18

Kannurpatti, Sridhar S., Bharat B. Biswal, and A. G. Hudetz. "Regional dynamics of the fMRI-BOLD signal response to hypoxia-hypercapnia in the rat brain." Journal of Magnetic Resonance Imaging 17, no. 6 (May 19, 2003): 641–47. http://dx.doi.org/10.1002/jmri.10311.

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19

Rostrup, E., I. Law, M. Blinkenberg, H. B. W. Larsson, A. P. Born, S. Holm, and O. B. Paulson. "Regional Differences in the CBF and BOLD Responses to Hypercapnia: A Combined PET and fMRI Study." NeuroImage 11, no. 2 (February 2000): 87–97. http://dx.doi.org/10.1006/nimg.1999.0526.

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20

Chen, Jean J., Marguerite Wieckowska, Ernst Meyer, and G. Bruce Pike. "Cerebral Blood Flow Measurement Using fMRI and PET: A Cross-Validation Study." International Journal of Biomedical Imaging 2008 (2008): 1–12. http://dx.doi.org/10.1155/2008/516359.

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An important aspect of functional magnetic resonance imaging (fMRI) is the study of brain hemodynamics, and MR arterial spin labeling (ASL) perfusion imaging has gained wide acceptance as a robust and noninvasive technique. However, the cerebral blood flow (CBF) measurements obtained with ASL fMRI have not been fully validated, particularly during global CBF modulations. We present a comparison of cerebral blood flow changes (ΔCBF) measured using a flow-sensitive alternating inversion recovery (FAIR) ASL perfusion method to those obtained usingH2O15PET, which is the current gold standard for in vivo imaging of CBF. To study regional and global CBF changes, a group of 10 healthy volunteers were imaged under identical experimental conditions during presentation of 5 levels of visual stimulation and one level of hypercapnia. The CBF changes were compared using 3 types of region-of-interest (ROI) masks. FAIR measurements of CBF changes were found to be slightly lower than those measured with PET (averageΔCBF of21.5±8.2% for FAIR versus28.2±12.8% for PET at maximum stimulation intensity). Nonetheless, there was a strong correlation between measurements of the two modalities. Finally, at-test comparison of the slopes of the linear fits of PET versus ASLΔCBF for all 3 ROI types indicated no significant difference from unity (P>.05).
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21

Goode, S. D., N. Altaf, S. Munshi, S. T. R. MacSweeney, and D. P. Auer. "Impaired Cerebrovascular Reactivity Predicts Recurrent Symptoms in Patients with Carotid Artery Occlusion: A Hypercapnia BOLD fMRI Study." American Journal of Neuroradiology 37, no. 5 (March 24, 2016): 904–9. http://dx.doi.org/10.3174/ajnr.a4739.

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22

Posse, Stefan, Lars J. Kemna, Barbara Elghahwagi, Stefan Wiese, and Valerij G. Kiselev. "Effect of graded hypo- and hypercapnia on fMRI contrast in visual cortex: Quantification ofT*2 changes by multiecho EPI." Magnetic Resonance in Medicine 46, no. 2 (2001): 264–71. http://dx.doi.org/10.1002/mrm.1187.

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23

Lajoie, Isabelle, Felipe B. Tancredi, and Richard D. Hoge. "The impact of inspired oxygen levels on calibrated fMRI measurements of M, OEF and resting CMRO2 using combined hypercapnia and hyperoxia." PLOS ONE 12, no. 3 (March 31, 2017): e0174932. http://dx.doi.org/10.1371/journal.pone.0174932.

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24

Krieger, Steffen Norbert, Markus Nikolar Streicher, Robert Trampel, and Robert Turner. "Cerebral Blood Volume Changes during Brain Activation." Journal of Cerebral Blood Flow & Metabolism 32, no. 8 (May 9, 2012): 1618–31. http://dx.doi.org/10.1038/jcbfm.2012.63.

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Cerebral blood volume (CBV) changes significantly with brain activation, whether measured using positron emission tomography, functional magnetic resonance imaging (fMRI), or optical microscopy. If cerebral vessels are considered to be impermeable, the contents of the skull incompressible, and the skull itself inextensible, task- and hypercapnia-related changes of CBV could produce intolerable changes of intracranial pressure. Because it is becoming clear that CBV may be useful as a well-localized marker of neural activity changes, a resolution of this apparent paradox is needed. We have explored the idea that much of the change in CBV is facilitated by exchange of water between capillaries and surrounding tissue. To this end, we developed a novel hemodynamic boundary-value model and found approximate solutions using a numerical algorithm. We also constructed a macroscopic experimental model of a single capillary to provide biophysical insight. Both experiment and theory model capillary membranes as elastic and permeable. For a realistic change of input pressure, a relative pipe volume change of 21±5% was observed when using the experimental setup, compared with the value of approximately 17±1% when this quantity was calculated from the mathematical model. Volume, axial flow, and pressure changes are in the expected range.
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Yücel, Meryem A., Karleyton C. Evans, Juliette Selb, Theodore J. Huppert, David A. Boas, and Louis Gagnon. "Validation of the hypercapnic calibrated fMRI method using DOT–fMRI fusion imaging." NeuroImage 102 (November 2014): 729–35. http://dx.doi.org/10.1016/j.neuroimage.2014.08.052.

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26

Mark, Clarisse I., Joseph A. Fisher, and G. Bruce Pike. "Improved fMRI calibration: Precisely controlled hyperoxic versus hypercapnic stimuli." NeuroImage 54, no. 2 (January 2011): 1102–11. http://dx.doi.org/10.1016/j.neuroimage.2010.08.070.

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27

Liau, Joy, and Thomas T. Liu. "Inter-subject variability in hypercapnic normalization of the BOLD fMRI response." NeuroImage 45, no. 2 (April 2009): 420–30. http://dx.doi.org/10.1016/j.neuroimage.2008.11.032.

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28

Cohen, Eric R., Egill Rostrup, Karam Sidaros, Torben E. Lund, Olaf B. Paulson, Kamil Ugurbil, and Seong-Gi Kim. "Hypercapnic normalization of BOLD fMRI: comparison across field strengths and pulse sequences." NeuroImage 23, no. 2 (October 2004): 613–24. http://dx.doi.org/10.1016/j.neuroimage.2004.06.021.

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29

Gagnon, Louis, Sava Sakadžić, Frédéric Lesage, Philippe Pouliot, Anders M. Dale, Anna Devor, Richard B. Buxton, and David A. Boas. "Validation and optimization of hypercapnic-calibrated fMRI from oxygen-sensitive two-photon microscopy." Philosophical Transactions of the Royal Society B: Biological Sciences 371, no. 1705 (October 5, 2016): 20150359. http://dx.doi.org/10.1098/rstb.2015.0359.

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Hypercapnic-calibrated fMRI allows the estimation of the relative changes in the cerebral metabolic rate of oxygen (rCMRO 2 ) from combined BOLD and arterial spin labelling measurements during a functional task, and promises to permit more quantitative analyses of brain activity patterns. The estimation relies on a macroscopic model of the BOLD effect that balances oxygen delivery and consumption to predict haemoglobin oxygenation and the BOLD signal. The accuracy of calibrated fMRI approaches has not been firmly established, which is limiting their broader adoption. We use our recently developed microscopic vascular anatomical network model in mice as a ground truth simulator to test the accuracy of macroscopic, lumped-parameter BOLD models. In particular, we investigate the original Davis model and a more recent heuristic simplification. We find that these macroscopic models are inaccurate using the originally defined parameters, but that the accuracy can be significantly improved by redefining the model parameters to take on new values. In particular, we find that the parameter α that relates cerebral blood-volume changes to cerebral blood-flow changes is significantly smaller than typically assumed and that the optimal value changes with magnetic field strength. The results are encouraging in that they support the use of simple BOLD models to quantify BOLD signals, but further work is needed to understand the physiological interpretation of the redefined model parameters. This article is part of the themed issue ‘Interpreting BOLD: a dialogue between cognitive and cellular neuroscience’.
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30

Jung, Won Beom, Geun Ho Im, Haiyan Jiang, and Seong-Gi Kim. "Early fMRI responses to somatosensory and optogenetic stimulation reflect neural information flow." Proceedings of the National Academy of Sciences 118, no. 11 (March 8, 2021): e2023265118. http://dx.doi.org/10.1073/pnas.2023265118.

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Blood oxygenation level–dependent (BOLD) functional magnetic resonance imaging (fMRI) has been widely used to localize brain functions. To further advance understanding of brain functions, it is critical to understand the direction of information flow, such as thalamocortical versus corticothalamic projections. For this work, we performed ultrahigh spatiotemporal resolution fMRI at 15.2 T of the mouse somatosensory network during forepaw somatosensory stimulation and optogenetic stimulation of the primary motor cortex (M1). Somatosensory stimulation induced the earliest BOLD response in the ventral posterolateral nucleus (VPL), followed by the primary somatosensory cortex (S1) and then M1 and posterior thalamic nucleus. Optogenetic stimulation of excitatory neurons in M1 induced the earliest BOLD response in M1, followed by S1 and then VPL. Within S1, the middle cortical layers responded to somatosensory stimulation earlier than the upper or lower layers, whereas the upper cortical layers responded earlier than the other two layers to optogenetic stimulation in M1. The order of early BOLD responses was consistent with the canonical understanding of somatosensory network connections and cannot be explained by regional variabilities in the hemodynamic response functions measured using hypercapnic stimulation. Our data demonstrate that early BOLD responses reflect the information flow in the mouse somatosensory network, suggesting that high-field fMRI can be used for systems-level network analyses.
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31

Donahue, Manus J., Megan K. Strother, Kimberly P. Lindsey, Lia M. Hocke, Yunjie Tong, and Blaise deB Frederick. "Time delay processing of hypercapnic fMRI allows quantitative parameterization of cerebrovascular reactivity and blood flow delays." Journal of Cerebral Blood Flow & Metabolism 36, no. 10 (July 22, 2016): 1767–79. http://dx.doi.org/10.1177/0271678x15608643.

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Blood oxygenation level-dependent fMRI contrast depends on the volume and oxygenation of blood flowing through the circulatory system. The effects on image intensity depend temporally on the arrival of blood within a voxel, and signal can be monitored during the time course of such blood flow. It has been previously shown that the passage of global endogenous variations in blood volume and oxygenation can be tracked as blood passes through the brain by determining the strength and peak time lag of their cross-correlation with blood oxygenation level-dependent data. By manipulating blood composition using transient hypercarbia and hyperoxia, we can induce much larger oxygenation and volume changes in the blood oxygenation level-dependent signal than result from natural endogenous fluctuations. This technique was used to examine cerebrovascular parameters in healthy subjects (n = 8) and subjects with intracranial stenosis (n = 22), with a subgroup of intracranial stenosis subjects scanned before and after surgical revascularization (n = 6). The halfwidth of cross-correlation lag times in the brain was larger in IC stenosis subjects (21.21 ± 14.22 s) than in healthy control subjects (8.03 ± 3.67), p < 0.001, and was subsequently reduced in regions that co-localized with surgical revascularization. These data show that blood circulatory timing can be measured robustly and longitudinally throughout the brain using simple respiratory challenges.
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32

Sivakolundu, Dinesh K., Kathryn L. West, Gayathri B. Maruthy, Mark Zuppichini, Monroe P. Turner, Dema Abdelkarim, Yuguang Zhao, et al. "Reduced arterial compliance along the cerebrovascular tree predicts cognitive slowing in multiple sclerosis: Evidence for a neurovascular uncoupling hypothesis." Multiple Sclerosis Journal 26, no. 12 (August 2, 2019): 1486–96. http://dx.doi.org/10.1177/1352458519866605.

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Background: Cognitive slowing occurs in ~70% of multiple sclerosis (MS) patients. The pathophysiology of this slowing is unknown. Neurovascular coupling, acute localized blood flow increases following neural activity, is essential for efficient cognition. Loss of vascular compliance along the cerebrovascular tree would result in suboptimal vasodilation, neurovascular uncoupling, and cognitive slowing. Objective: To assess vascular compliance along the cerebrovascular tree and its relationship to MS-related cognition. Methods: We tested vascular compliance along the cerebrovascular tree by dividing cerebral cortex into nested layers. MS patients and healthy controls were scanned using a dual-echo functional magnetic resonance imaging (fMRI) sequence while they periodically inhaled room air and hypercapnic gas mixture. Cerebrovascular reactivity was calculated from both cerebral blood flow (arterial) and blood-oxygen-level-dependent signal (venous) increases per unit increase in end-tidal CO2. Results: Arterial cerebrovascular reactivity changes along the cerebrovascular tree were reduced in cognitively slow MS compared to cognitively normal MS and healthy controls. These changes were fit to exponential functions, the decay constant (arterial compliance index; ACI) of which was associated with individual subjects’ reaction time and predicted reaction time after controlling for disease processes. Conclusion: Such associations suggest prospects for utility of ACI in predicting future cognitive disturbances, monitoring cognitive deficiencies and therapeutic responses, and implicates neurovascular uncoupling as a mechanism of cognitive slowing in MS.
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Wise, Richard G., Kyle TS Pattinson, Daniel P. Bulte, Peter A. Chiarelli, Stephen D. Mayhew, George M. Balanos, David F. O'Connor, et al. "Dynamic Forcing of End-Tidal Carbon Dioxide and Oxygen Applied to Functional Magnetic Resonance Imaging." Journal of Cerebral Blood Flow & Metabolism 27, no. 8 (April 4, 2007): 1521–32. http://dx.doi.org/10.1038/sj.jcbfm.9600465.

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Investigations into the blood oxygenation level-dependent (BOLD) functional MRI signal have used respiratory challenges with the aim of probing cerebrovascular physiology. Such challenges have altered the inspired partial pressures of either carbon dioxide or oxygen, typically to a fixed and constant level (fixed inspired challenge (FIC)). The resulting end-tidal gas partial pressures then depend on the subject's metabolism and ventilatory responses. In contrast, dynamic end-tidal forcing (DEF) rapidly and independently sets end-tidal oxygen and carbon dioxide to desired levels by altering the inspired gas partial pressures on a breath-by-breath basis using computer-controlled feedback. This study implements DEF in the MRI environment to map BOLD signal reactivity to CO2. We performed BOLD (T2*) contrast FMRI in four healthy male volunteers, while using DEF to provide a cyclic normocapnichypercapnic challenge, with each cycle lasting 4 mins (PetCO2 mean±s.d., from 40.9 ± 1.8 to 46.4 ± 1.6 mm Hg). This was compared with a traditional fixed-inspired (FiCO2 = 5%) hypercapnic challenge (PetCO2 mean±s.d., from 38.2 ± 2.1 to 45.6 ± 1.4 mm Hg). Dynamic end-tidal forcing achieved the desired target PetCO2 for each subject while maintaining PetCO2 constant. As a result of CO2-induced increases in ventilation, the FIC showed a greater cyclic fluctuation in PetCO2. These were associated with spatially widespread fluctuations in BOLD signal that were eliminated largely by the control of PetCO2 during DEF. The DEF system can provide flexible, convenient, and physiologically well-controlled respiratory challenges in the MRI environment for mapping dynamic responses of the cerebrovasculature.
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Chiarelli, Antonio M., Michael Germuska, Hannah Chandler, Rachael Stickland, Eleonora Patitucci, Emma Biondetti, Daniele Mascali, et al. "A flow-diffusion model of oxygen transport for quantitative mapping of cerebral metabolic rate of oxygen (CMRO2) with single gas calibrated fMRI." Journal of Cerebral Blood Flow & Metabolism, February 2, 2022, 0271678X2210773. http://dx.doi.org/10.1177/0271678x221077332.

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One promising approach for mapping CMRO2 is dual-calibrated functional MRI (dc-fMRI). This method exploits the Fick Principle to combine estimates of CBF from ASL, and OEF derived from BOLD-ASL measurements during arterial O2 and CO2 modulations. Multiple gas modulations are required to decouple OEF and deoxyhemoglobin-sensitive blood volume. We propose an alternative single gas calibrated fMRI framework, integrating a model of oxygen transport, that links blood volume and CBF to OEF and creates a mapping between the maximum BOLD signal, CBF and OEF (and CMRO2). Simulations demonstrated the method’s viability within physiological ranges of mitochondrial oxygen pressure, PmO2, and mean capillary transit time. A dc-fMRI experiment, performed on 20 healthy subjects using O2 and CO2 challenges, was used to validate the approach. The validation conveyed expected estimates of model parameters (e.g., low PmO2), with spatially uniform OEF maps (grey matter, GM, OEF spatial standard deviation ≈ 0.13). GM OEF estimates obtained with hypercapnia calibrated fMRI correlated with dc-fMRI (r = 0.65, p = 2·10−3). For 12 subjects, OEF measured with dc-fMRI and the single gas calibration method were correlated with whole-brain OEF derived from phase measures in the superior sagittal sinus (r = 0.58, p = 0.048; r = 0.64, p = 0.025 respectively). Simplified calibrated fMRI using hypercapnia holds promise for clinical application.
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Tip, Liesbeth Muriel. "Breathing patterns in psychopathology and blood oxygen levels - Risk factor for cognitive decline?" Journal of Clinical Images and Medical Case Reports 3, no. 5 (May 17, 2022). http://dx.doi.org/10.52768/2766-7820/1838.

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Neuronal brain activity is assumed to be reflected by blood level oxygenation levels, also known as BOLD signal, measured with fMRI. A scan of the literature points to both oxygen and carbon dioxide blood levels effects on BOLD fMRI. The roles of oxygen (O2 ; hypoxia/hypoxemia, hyperoxia) and carbon dioxide (CO2 ; hypocapnia, hypercapnia) in neuronal activity and BOLD signal are complex and still under investigation [1,2]. Inspiration while varying levels of O2 and CO2 in the air have been used to investigate resting state fMRI [3].
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36

Hampson, Johnson P., Nuria Lacuey, MRS Sandhya Rani, Jaison S. Hampson, Kristina A. Simeone, Timothy A. Simeone, Ponnada A. Narayana, Louis Lemieux, and Samden D. Lhatoo. "Functional MRI Correlates of Carbon Dioxide Chemosensing in Persons With Epilepsy." Frontiers in Neurology 13 (July 7, 2022). http://dx.doi.org/10.3389/fneur.2022.896204.

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ObjectivesSudden unexpected death in epilepsy (SUDEP) is a catastrophic epilepsy outcome for which there are no reliable premortem imaging biomarkers of risk. Percival respiratory depression is seen in monitored SUDEP and near SUDEP cases, and abnormal chemosensing of raised blood carbon dioxide (CO2) is thought to contribute. Damage to brainstem respiratory control and chemosensing structures has been demonstrated in structural imaging and neuropathological studies of SUDEP. We hypothesized that functional MRI (fMRI) correlates of abnormal chemosensing are detectable in brainstems of persons with epilepsy (PWE) and are different from healthy controls (HC).MethodsWe analyzed fMRI BOLD activation and brain connectivity in 10 PWE and 10 age- and sex-matched HCs during precisely metered iso-oxic, hypercapnic breathing challenges. Segmented brainstem responses were of particular interest, along with characterization of functional connectivity metrics between these structures. Regional BOLD activations during hypercapnic challenges were convolved with hemodynamic responses, and the resulting activation maps were passed on to group-level analyses. For the functional connectivity analysis, significant clusters from BOLD results were used as seeds. Each individual seed time-series activation map was extracted for bivariate correlation coefficient analyses to study changes in brain connectivity between PWE and HCs.Results(1) Greater brainstem BOLD activations in PWE were observed compared to HC during hypercapnic challenges in several structures with respiratory/chemosensing properties. Group comparison between PWE vs. HC showed significantly greater activation in the dorsal raphe among PWE (p &lt; 0.05) compared to HCs. (2) PWE had significantly greater seed-seed connectivity and recruited more structures during hypercapnia compared to HC.SignificanceThe results of this study show that BOLD responses to hypercapnia in human brainstem are detectable and different in PWE compared to HC. Increased dorsal raphe BOLD activation in PWE and increased seed-seed connectivity between brainstem and adjacent subcortical areas may indicate abnormal chemosensing in these individuals. Imaging investigation of brainstem respiratory centers involved in respiratory regulation in PWE is an important step toward identifying suspected dysfunction of brainstem breathing control that culminates in SUDEP and deserve further study as potential imaging SUDEP biomarkers.
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37

Mazzetto-Betti, Kelley C., Luis H. Castro-Afonso, Pedro T. Pinto, Antonio C. dos Santos, Daniel Abud, Draulio B. de Araujo, João P. Leite, and Octavio M. Pontes Neto. "Abstract 2762: Asymmetry of The Blood Oxygen Level-Dependent fMRI Response During Hypercapnia Is Reliable to Evaluate Cerebrovascular Reactivity in Patients with Severe Unilateral Carotid Stenosis." Stroke 43, suppl_1 (February 2012). http://dx.doi.org/10.1161/str.43.suppl_1.a2762.

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Background and Purpose: Previous transcranial Doppler studies have suggested that, in patients with severe carotid stenosis, the lack of cerebrovascular reactivity (CVR) is an independent predictor of ipsilateral stroke. The BOLD (Blood Oxygenation Level-Dependent) fMRI contrast can be used to assess the CVR during normal condition and during hemodynamic stress, like hypercapnia. The purpose of this study is to evaluate the BOLD signal parameters on the Middle Cerebral Artery (MCA) territory, induced by auditory stimulus, during different levels of hypercapnia in patients with severe unilateral carotid stenosis, comparing the ipsilateral hemisphere (IH) to the contralateral hemisphere (CH). Methods: The images were obtained from 16 patients with severe unilateral carotid stenosis. Patients were submitted to an auditory stimulus (3s) in three different conditions: normocapnia and at EtCO2 increase of 5 and 10mmHg. The images were acquired with a 3T Philips MR, preprocessed and analyzed using an autoregressive method. Results: The BOLD signal from the IH was different from the CH during the basal condition and at 5mmHg (p<0.0001), but not at the 10mmHg ETCO2 increase. For each BOLD parameter, the major differences between the hemispheres were seen on the onset time (p<0.0001) and amplitude of BOLD signal (p<0.0001). The width difference was significant between the basal and 10mmhHg increase (p<0.01). In these three parameters, the BOLD signal of the IH presented no significant variations with the CO2 increment. However, the BOLD signal for CH showed an increase on the time-to-onset and width and amplitude decrease. The time to peak parameters of the BOLD signal showed no differences between the hemispheres and at hypercapnic conditions. Conclusion: In our results the IH did not respond to the hypercapnic stress as the CH. Therefore, among patients with severe carotid stenosis, BOLD can reliably identify some that have an exhausted CVR, which cannot respond to a vasodilatory stress like hypercapnia. Future studies using this technique may help to select patients for recanalization procedures.
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38

Mazzetto-Betti, Kelley C., Luis H. Castro-Affonso, Renata F. Leoni, Antonio C. dos Santos, Daniel G. Abud, JoãP Leite, and Octavio M. Pontes Neto. "Abstract WP137: Improvement of Cerebrovascular Reactivity After Carotid Stenting is Greater in Non-Diabetic than in Diabetic Patients: a Bold-FMRI Study." Stroke 44, suppl_1 (February 2013). http://dx.doi.org/10.1161/str.44.suppl_1.awp137.

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Background: Cerebrovascular reactivity (CVR) has been suggested as an independent predictor of stroke in patients with severe carotid stenosis. Functional-MRI (fMRI) can be used to assess CVR by comparing latency parameters of the neurovascular coupling, i.e. BOLD response at baseline and during hypercarbic challenge. We aim to compare BOLD amplitude and latency parameters in the ipsilateral (IH) and contralateral hemispheres (CH) induced by auditory stimulus, under different hypercapnia levels in diabetic and non-diabetic patients with symptomatic carotid stenosis, before and after carotid stenting. Methods: seven diabetic and eight non-diabetic patients with unilateral severe symptomatic carotid stenosis and similar clinical characteristics were evaluated. The protocol was undertaken one week before and three months after the endovascular intervention. Subjects were submitted to auditory stimulus (3s) under normocapnia and EtCO2 increase of 5 and 10mmHg. The images were acquired with a 3T MRI-scanner, preprocessed and BOLD response amplitude and latency parameters were analyzed. Results: We observed decreased BOLD amplitude in the IH compared to the CH (p<0.05) in non-diabetic patients in hypercapnic conditions, and was compromised bilaterally in diabetic patients before the stenting. In diabetic patients the mean change on BOLD latency parameters were not significant with CO2 increment. After carotid stenting, BOLD amplitude (p<0.05) under hypercapnic conditions and area under the curve (P<0.05) were increased for non-diabetic patients but not for diabetic patients. Conclusions: diabetic patients have diffuse baseline compromise of CVR and their cerebrovascular reactivity measured on BOLD fMRI does not respond to carotid stenting as non-diabetic patients.
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39

Chen, J. Jean, and Claudine J. Gauthier. "The Role of Cerebrovascular-Reactivity Mapping in Functional MRI: Calibrated fMRI and Resting-State fMRI." Frontiers in Physiology 12 (March 25, 2021). http://dx.doi.org/10.3389/fphys.2021.657362.

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Task and resting-state functional MRI (fMRI) is primarily based on the same blood-oxygenation level-dependent (BOLD) phenomenon that MRI-based cerebrovascular reactivity (CVR) mapping has most commonly relied upon. This technique is finding an ever-increasing role in neuroscience and clinical research as well as treatment planning. The estimation of CVR has unique applications in and associations with fMRI. In particular, CVR estimation is part of a family of techniques called calibrated BOLD fMRI, the purpose of which is to allow the mapping of cerebral oxidative metabolism (CMRO2) using a combination of BOLD and cerebral-blood flow (CBF) measurements. Moreover, CVR has recently been shown to be a major source of vascular bias in computing resting-state functional connectivity, in much the same way that it is used to neutralize the vascular contribution in calibrated fMRI. Furthermore, due to the obvious challenges in estimating CVR using gas challenges, a rapidly growing field of study is the estimation of CVR without any form of challenge, including the use of resting-state fMRI for that purpose. This review addresses all of these aspects in which CVR interacts with fMRI and the role of CVR in calibrated fMRI, provides an overview of the physiological biases and assumptions underlying hypercapnia-based CVR and calibrated fMRI, and provides a view into the future of non-invasive CVR measurement.
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40

Ciumas, Carolina, Sylvain Rheims, and Philippe Ryvlin. "fMRI studies evaluating central respiratory control in humans." Frontiers in Neural Circuits 16 (September 23, 2022). http://dx.doi.org/10.3389/fncir.2022.982963.

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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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41

Zerweck, Leonie, Till-Karsten Hauser, Constantin Roder, Ganna Blazhenets, Nadia Khan, Ulrike Ernemann, Philipp T. Meyer, and Uwe Klose. "Evaluation of the cerebrovascular reactivity in patients with Moyamoya Angiopathy by use of breath-hold fMRI: investigation of voxel-wise hemodynamic delay correction in comparison to [15O]water PET." Neuroradiology, November 25, 2022. http://dx.doi.org/10.1007/s00234-022-03088-4.

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Abstract Purpose Patients with Moyamoya Angiopathy (MMA) require hemodynamic assessment to evaluate the risk of stroke. Hemodynamic evaluation by use of breath-hold-triggered fMRI (bh-fMRI) was proposed as a readily available alternative to the diagnostic standard [15O]water PET. Recent studies suggest voxel-wise hemodynamic delay correction in hypercapnia-triggered fMRI. The aim of this study was to evaluate the effect of delay correction of bh-fMRI in patients with MMA and to compare the results with [15O]water PET. Methods bh-fMRI data sets of 22 patients with MMA were evaluated without and with voxel-wise delay correction within different shift ranges and compared to the corresponding [15O]water PET data sets. The effects were evaluated combined and in subgroups of data sets with most severely impaired CVR (apparent steal phenomenon), data sets with territorial time delay, and data sets with neither steal phenomenon nor delay between vascular territories. Results The study revealed a high mean cross-correlation (r = 0.79, p < 0.001) between bh-fMRI and [15O]water PET. The correlation was strongly dependent on the choice of the shift range. Overall, no shift range revealed a significantly improved correlation between bh-fMRI and [15O]water PET compared to the correlation without delay correction. Delay correction within shift ranges with positive high high cutoff revealed a lower agreement between bh-fMRI and PET overall and in all subgroups. Conclusion Voxel-wise delay correction, in particular with shift ranges with high cutoff, should be used critically as it can lead to false-negative results in regions with impaired CVR and a lower correlation to the diagnostic standard [15O]water PET.
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42

You, Taeyi, Geun Ho Im, and Seong-Gi Kim. "Characterization of brain-wide somatosensory BOLD fMRI in mice under dexmedetomidine/isoflurane and ketamine/xylazine." Scientific Reports 11, no. 1 (June 23, 2021). http://dx.doi.org/10.1038/s41598-021-92582-5.

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AbstractMouse fMRI under anesthesia has become increasingly popular due to improvement in obtaining brain-wide BOLD response. Medetomidine with isoflurane has become well-accepted for resting-state fMRI, but whether this combination allows for stable, expected, and robust brain-wide evoked response in mice has yet to be validated. We thus utilized intravenous infusion of dexmedetomidine with inhaled isoflurane and intravenous infusion of ketamine/xylazine to elucidate whether stable mouse physiology and BOLD response are obtainable in response to simultaneous forepaw and whisker-pad stimulation throughout 8 h. We found both anesthetics result in hypercapnia with depressed heart rate and respiration due to self-breathing, but these values were stable throughout 8 h. Regardless of the mouse condition, brain-wide, robust, and stable BOLD response throughout the somatosensory axis was observed with differences in sensitivity and dynamics. Dexmedetomidine/isoflurane resulted in fast, boxcar-like, BOLD response with consistent hemodynamic shapes throughout the brain. Ketamine/xylazine response showed higher sensitivity, prolonged BOLD response, and evidence for cortical disinhibition as significant bilateral cortical response was observed. In addition, differing hemodynamic shapes were observed between cortical and subcortical areas. Overall, we found both anesthetics are applicable for evoked mouse fMRI studies.
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43

Amyot, Franck, Cillian E. Lynch, John Ollinger, J. Kent Werner, E. Silverman, Carol Moore, Cora Davis, L. Christine Turtzo, Ramon Diaz-Arrastia, and Kimbra Kenney. "Cerebrovascular Reactivity Measures Are Associated With Post-traumatic Headache Severity in Chronic TBI; A Retrospective Analysis." Frontiers in Physiology 12 (May 13, 2021). http://dx.doi.org/10.3389/fphys.2021.649901.

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ObjectiveTo characterize the relationship between persistent post-traumatic headache (pPTH) and traumatic cerebrovascular injury (TCVI) in chronic traumatic brain injury (TBI). Cerebrovascular reactivity (CVR), a measure of the cerebral microvasculature and endothelial cell function, is altered both in individuals with chronic TBI and migraine headache disorder (Amyot et al., 2017; Lee et al., 2019b). The pathophysiologies of pPTH and migraine are believed to be associated with chronic microvascular dysfunction. We therefore hypothesize that TCVI may contribute to the underlying migraine-like mechanism(s) of pPTH.Materials and Methods22 moderate/severe TBI participants in the chronic stage (&gt;6 months) underwent anatomic and functional magnetic resonance imaging (fMRI) scanning with hypercapnia gas challenge to measure CVR as well as the change in CVR (ΔCVR) after single-dose treatment of a specific phosphodiesterase-5 (PDE-5) inhibitor, sildenafil, which potentiates vasodilation in response to hypercapnia in impaired endothelium, as part of a Phase2a RCT of sildenafil in chronic TBI (NCT01762475). CVR and ΔCVR measures of each participant were compared with the individual’s pPTH severity measured by the headache impact test-6 (HIT-6) survey.ResultsThere was a moderate correlation between HIT-6 and both CVR and ΔCVR scores [Spearman’s correlation = –0.50 (p = 0.018) and = 0.46 (p = 0.03), respectively], indicating that a higher headache burden is associated with decreased endothelial function in our chronic TBI population.ConclusionThere is a correlation between PTH and CVR in chronic moderate-severe TBI. This relationship suggests that chronic TCVI may underlie the pathobiology of pPTH. Further, our results suggest that novel treatment strategies that target endothelial function and vascular health may be beneficial in refractory pPTH.
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44

Yao, Jinxia (Fiona), Ho-Ching (Shawn) Yang, James H. Wang, Zhenhu Liang, Thomas M. Talavage, Gregory G. Tamer, Ikbeom Jang, and Yunjie Tong. "A novel method of quantifying hemodynamic delays to improve hemodynamic response, and CVR estimates in CO2 challenge fMRI." Journal of Cerebral Blood Flow & Metabolism, January 14, 2021, 0271678X2097858. http://dx.doi.org/10.1177/0271678x20978582.

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Elevated carbon dioxide (CO2) in breathing air is widely used as a vasoactive stimulus to assess cerebrovascular functions under hypercapnia (i.e., “stress test” for the brain). Blood-oxygen-level-dependent (BOLD) is a contrast mechanism used in functional magnetic resonance imaging (fMRI). BOLD is used to study CO2-induced cerebrovascular reactivity (CVR), which is defined as the voxel-wise percentage BOLD signal change per mmHg change in the arterial partial pressure of CO2 (PaCO2). Besides the CVR, two additional important parameters reflecting the cerebrovascular functions are the arrival time of arterial CO2 at each voxel, and the waveform of the local BOLD signal. In this study, we developed a novel analytical method to accurately calculate the arrival time of elevated CO2 at each voxel using the systemic low frequency oscillations (sLFO: 0.01-0.1 Hz) extracted from the CO2 challenge data. In addition, 26 candidate hemodynamic response functions (HRF) were used to quantitatively describe the temporal brain reactions to a CO2 stimulus. We demonstrated that our approach improved the traditional method by allowing us to accurately map three perfusion-related parameters: the relative arrival time of blood, the hemodynamic response function, and CVR during a CO2 challenge.
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45

Schellekens, Wouter, Alex A. Bhogal, Emiel CA Roefs, Mario G. Báez-Yáñez, Jeroen CW Siero, and Natalia Petridou. "The many layers of BOLD. The effect of hypercapnic and hyperoxic stimuli on macro- and micro-vascular compartments quantified by CVR, M, and CBV across cortical depth." Journal of Cerebral Blood Flow & Metabolism, October 19, 2022, 0271678X2211339. http://dx.doi.org/10.1177/0271678x221133972.

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Ultra-high field functional magnetic resonance imaging (fMRI) offers the spatial resolution to measure neuronal activity at the scale of cortical layers. However, cortical depth dependent vascularization differences, such as a higher prevalence of macro-vascular compartments near the pial surface, have a confounding effect on depth-resolved blood-oxygen-level dependent (BOLD) fMRI signals. In the current study, we use hypercapnic and hyperoxic breathing conditions to quantify the influence of all venous vascular and micro-vascular compartments on laminar BOLD fMRI, as measured with gradient-echo (GE) and spin-echo (SE) scan sequences, respectively. We find that all venous vascular and micro-vascular compartments are capable of comparable theoretical maximum signal intensities, as represented by the M-value parameter. However, the capacity for vessel dilation, as reflected by the cerebrovascular reactivity (CVR), is approximately two and a half times larger for all venous vascular compartments combined compared to the micro-vasculature at superficial layers. Finally, there is roughly a 35% difference in estimates of CBV changes between all venous vascular and micro-vascular compartments, although this relative difference was approximately uniform across cortical depth. Thus, our results suggest that fMRI BOLD signal differences across cortical depth are likely caused by differences in dilation properties between macro- and micro-vascular compartments.
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46

Hays Weeks, Chelsea C., Zvinka Z. Zlatar, M. J. Meloy, David D. Shin, Liu Thomas, and Christina E. Wierenga. "APOE Genotype Modifies the Association of Fusiform Gyrus Cerebral Metabolic Rate of Oxygen Consumption and Object Naming Performance." Journal of Alzheimer's Disease, January 7, 2023, 1–13. http://dx.doi.org/10.3233/jad-220749.

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Background: The apolipoprotein E (APOE) ɛ4 allele confers risk for age and Alzheimer’s disease related cognitive decline but the mechanistic link remains poorly understood. Blood oxygenation level dependent (BOLD) response in the fusiform gyrus (FG) during object naming appears greater among APOE ɛ4 carriers even in the face of equivalent cognitive performance, suggesting neural compensation. However, BOLD is susceptible to known age and APOE-related vascular changes that could confound its interpretation. Objective: To address this limitation, we used calibrated fMRI during an object naming task and a hypercapnic challenge to obtain a more direct measure of neural function – percent change cerebral metabolic rate of oxygen consumption (%ΔCMRO2). Methods: Participants were 45 older adults without dementia (28 ɛ4– , 17 ɛ4+) between the ages of 65 and 85. We examined APOE-related differences in %ΔCMRO2 in the FG during object naming and the extent to which APOE modified associations between FG %ΔCMRO2 and object naming accuracy. Exploratory analyses also tested the hypothesis that %ΔCMRO2 is less susceptible to vascular compromise than are measures of %ΔCBF and %ΔBOLD. Results: We observed a modifying role of APOE on associations between FG %ΔCMRO2 and cognition, with ɛ4 carriers (but not non-carriers) demonstrating a positive association between right FG %ΔCMRO2 and object naming accuracy. Conclusion: Results suggest that the relationship between neural function and cognition is altered among older adult APOE ɛ4 carriers prior to the onset of dementia, implicating CMRO2 response as a potential mechanism to support cognition in APOE-related AD risk.
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