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fMRI Modeling & Signal Characteristics



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fMRI Modeling & Signal Characteristics

Hall B Tuesday 13:30-15:30

1113. An EEG Homologue of the Negative BOLD Response as Measured at 7 Tesla

Wietske van der Zwaag1,2, Marzia De Lucia3, Nadine Graedel2, Micah M. Murray3, Rolf Gruetter1,2

1Radiologie, Université de Lausanne, Lausanne, Vaud, Switzerland; 2CIBM, EPFL, Lausanne, Vaud, Switzerland; 3Electroencephalography Brain Mapping core, CHUV, Lausanne, Vaud, Switzerland

The basis of fMRI experiments is a tight coupling of neural activity with the BOLD response in both space and time. However, cross-modal negative BOLD signal may also be caused by blood-steal effects. Here, we measure the negative BOLD signal using ultra-high field fMRI and the neuroelectrical activity as measured by EEG in the same subjects. Neural deactivation is found in the EEG-based electrical neuroimaging maps in regions partially overlapping with those where the negative BOLD signal is found, implying a possible neural basis for the negative BOLD response.



1114. Substantial Flow-Related Contribution in FMRI Signal Observed in Human Visual Cortex at 4T

Xiao Wang1, Wei Chen1

1Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, MN, United States

It is a common practice to apply a short repetition time (TR) for acquiring more fMRI volumes within a given total imaging time, thus gaining contrast-to-noise ratio (CNR). However, both the task-evoked BOLD (T2/T2*) effect and flow-related component (R1) increases could contribute to the total percentage change of fMRI signal. This study aims to quantitatively evaluate the BOLD and flow contributions in the fMRI signal detected by gradient echo EPI in the human visual cortex during visual stimulation at 4T. The results show a substantially large flow-related contribution in the measured fMRI signal when TR is short. The observed flow-related enhancement in fMRI signal is likely attributed by perfusion change, and it benefits fMRI mapping in two aspects: improved CNR and specificity. The finding also suggests that the flow-related component needs to be considered in BOLD quantification (e.g., calibration of CMRO2).



1115. Compromised Temporal Responsivity in Fusiform Areas by Aging

Makoto Miyakoshi1, Annabel Shen-Hsing Chen2, Kayako Matsuo3, Toshiharu Nakai

1National Center for Geriatrics and Gerontology, Ohbu, Aichi, Japan; 2Nangyang Technorogical University; 3National Taiwan Univsersity

To study the aging effect on neural mechanism of visual repetition, we performed an fMRI study. Participants saw inside and outside scenes repeatedly for five blocks, and the first two blocks (eight repetitions for each scene) were compared with the last two blocks for Young and Elderly groups. The results showed that the Elderly group has longer time-constant for the visual repetition effect to take place within fusiform areas and the occipital cortex. The results supported the conclusion that the aging effect on visual repetition is represented by the compromised ‘slew rate’ i.e., temporal responsivity in the fusiform gyri.



1116. Hemodynamic Response Function (HRF) Modulation by Inhaled CO2 Concentration Using Event-Related FMRI

Chao-Chun Lin1,2, Yi-Jui Liu3,4, Chien-Kuo Chen3, Hsiao-Wei Peng3, Kuo-Fang Shao4, Wu-Chung Shen1,5, Chang Hing-Chiu6

1Department of Radiology, China Medical University Hospital, Taichung, Taiwan, Taiwan; 2Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan, Taiwan; 3Department of Automatic Control Engineering, Feng Chia University, Taichung, Taiwan; 4Master's Program in Biomedical Informatics and Biomedical Engineering, Feng Chia University, Taichun, Taiwan; 5School of Medicine, China Medical University, Taichung, Taiwan; 6Applied Science Laboratory, GE Healthcare Taiwan, Taipei, Taiwan

The purpose of this study was to evaluate the hemodynamic response function (HRF) change after inhalation of different carbon dioxide concentrations. Using event-related method investigate the transient hemodynamic response function by short-time visual stimulus with different CO2 concentrations. Our results show that the peak of HRF curve is decreased and delayed with increased inhaled CO2 concentrations, and the width of HRF curve is wider with higher inhaled CO2 concentration.



1117. Increased Metabolic Activity, Not Preemptive Blood Flow Increase, Underlies Attentional Modulation in Primary Visual Cortex

Farshad Moradi1, Richard Buxton1

1Radiology, University of California, San Diego, San Diego, CA, United States

Previous studies found that attention produces robust BOLD modulation with only modest increase in firing activity in primary visual cortex. This could be due to a pure preemptive CBF increase with no relation to local neuronal firing. We tested the presence of such a mechanism using combined CBF/BOLD measurements to estimate relative CMRO2. Results show that attentional enhancement of V1 activity involves an increase of both metabolic activity and blood flow, rather than a preemptive increase in blood flow alone. The ratio of CBF to CMRO2 change appears to be higher when the stimulus is unattended than when attended.



1118. Uncoupled Couplings: Combined FMRI and 1H-MRS for the Study of the Neurovascular and Neurometabolic Coupling

Mauro DiNuzzo1, Federico Giove1,2, Bruno Maraviglia1,2

1Physics, Sapienza University of Rome, Rome, RM, Italy; 2MARBILab, "Enrico Fermi" Center, Rome, Italy

Functional magnetic resonance imaging (fMRI) is widely used to map brain function. Nevertheless, it does measure neural activity only indirectly via hemodynamic changes. Here we performed fMRI in combination with 1H-MRS in order to study the relationships between the vascular and metabolic response of the brain to a visual stimulation paradigm specifically designed to partly disentangle spiking and synaptic activity within the primary visual cortex. Our results, though preliminary, confirm that the energetics of the stimulated brain contains more information than that revealed by fMRI alone, thereby indicating an uncoupling between hemodynamics and metabolism upon brain activation.



1119. Decrease of Deoxy-Hemoglobin Containing Blood Volume in Activated Human Visual Cortex

Xiang He1, Dmitriy A. Yablonskiy1

1Mallinckrodt Institute of Radiology, Washington University in St Louis, School of Medicine, St. Louis, MO, United States

Quantification of brain hemodynamic parameters during functional activation is essential for understanding biophysical mechanisms behind blood oxygenation level depend (BOLD) phenomenon. Models of BOLD signal are often derived based on a relationship established by PET studies between cerebral blood volume (CBV) and cerebral blood flow (CBF), ignoring that only portion of CBV - deoxyhemoglobin-containing blood volume (DBV) affects BOLD signal. In this study, we directly measure DBV during visual activation in human visual cortex area using qBOLD-fMRI technique. We demonstrate for the first time that DBV decreases during functional activation – an effect opposite to well known increase in CBV.



1120. Investigating the Origins of the DfMRI Signal Using 4 Tesla

R.Allen Waggoner1, Keiji Tanaka1, Kang Cheng1,2

1Laboratory for Cognitive Brain Mapping, RIKEN-BSI, Wako-shi, Saitama, Japan; 2fMRI Support Unit, RIKEN-BSI, Wako-shi, Saitama, Japan

Recent DfMRI studies preformed at 3T have observed an increase in the fractional BOLD signal change with increasing b value during functional stimulation. The origin of this effect remains controversial with both cell swelling and vascular sources being offered as explanations. If this effect is truly due to cell swelling, increasing the static magnetic field will not alter the effect. We present DfMRI results obtained at 4T which shows a constant BOLD signal change with increasing b value. This result is consistent with a vascular source for a varying DfMRI response with diffusion weighting seen at 3T.



1121. Modeling The Non-Neuronal Contribution To The Blood Oxygenation Level Dependent Fmri Signal Oscillations

Mauro DiNuzzo1, Federico Giove1,2, Bruno Maraviglia1,2

1Physics, Sapienza University of Rome, Rome, RM, Italy; 2MARBILab, "Enrico Fermi" Center, Rome, RM, Italy

Resting oscillatory patterns in cortical activity can originate by both network- and metabolism-related mechanisms. In particular, recent evidences suggest that the cell metabolic state exert an indirect control over the intrinsic network responsivity of the brain, much likely via astrocytic intracellular calcium (Ca2+)-mediated gliotransmission. Here we examined theoretically the contribution of astrocytes in the generation of the fMRI signal changes in the absence of focal neuronal stimulations. We found that oscillations in brain electrical, metabolic and vascular activity, as revealed by BOLD fMRI, can be qualitatively and quantitatively explained by calcium-mediated coupling between neuroglial activation and metabolism.



1122. Diffusion Parameter Changes in White Matter Induced by Direct Intracortical Stimulation in Rats

Umesh Suryanarayana Rudrapatna1, Maurits P. van Meer1, Annette van der Toorn1, Rick M. Dijkhuizen1

1Image Sciences Institute, University Medical Center, Utrecht, Netherlands

While existing functional MRI techniques can reliably detect stimulus-induced activation in gray matter, activity in white matter regions has not been readily measured. A recent study has reported subtle increases

in fractional anisotropy (FA) in specific white matter pathways in response to motor or visual stimulation in human subjects. In the current study, we aimed to validate these findings with a direct cortical stimulation paradigm in rats. Our functional DTI approach revealed significant but variable FA changes in restricted corpus callosum regions, which demonstrates that functional DTI enables detection of white matter activity in response to cortical stimulation.
1123. Whole-Brain Mapping of Venous Vessel Size in Humans Using the Hypercapnia-Induced BOLD Effect

Thies Halvor Jochimsen1,2, Dimo Ivanov2, Derek V M Ott2, Wolfgang Heinke3, Robert Turner2, Harald E. Möller2, Jürgen R. Reichenbach1

1Medical Physics Group, Department of Diagnostic and Interventional Radiology, Jena University Hospital, Jena, Germany; 2Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany; 3Department of Anesthesiology and Intensive Care Medicine, University of Leipzig, Medical Faculty, Leipzig, Germany

It is demonstrated that non-invasive mapping of the venous microstructure (vessel radius) is possible by using the hypercapnia-induced BOLD effect. Furthermore, it is shown that maps of venous blood volume and vessel density can be obtained from the same experimental setup. These parameters are important for characterizing tumor angiogenesis and type.



1124. Characterization of the BOLD Hemodynamic Response Function at 7T: Towards Separation of Vasculature and Parenchyma

Jeroen Cornelis Siero1, Natalia Petridou2,3, Johannes Marinus Hoogduin2, Nick F. Ramsey1

1Rudolf Magnus Institute, University Medical Center Utrecht, Utrecht, Netherlands; 2Radiology, University Medical Center Utrecht, Utrecht, Netherlands; 3SPMMRC, University of Nottingam, Nottingam, United Kingdom

A limitation of T2*w BOLD fMRI is the confounding contribution of signal from the larger vasculature. Based on time-to-peak and full-width-at-half-maximum BOLD characteristics of different vascular compartments identified at 3T, we characterized the spatio-temporal properties of the BOLD response at 7T in the visual cortex using an event-related fMRI paradigm with short visual stimuli, high sampling rate, and multiple spatial resolutions. For the smallest voxelsize a high time-to-peak spatial heterogeneity of the BOLD response was observed with fast responses localized in parenchyma. This opens the possibility to use TTP to probe layer specific BOLD responses in the human brain.



1125. Linearity of Neural Responses in the Somatosensory Cortex and Their Relationship to BOLD FMRI.

Fan Wang1, Claire Stevenson1, Matthew Brookes1, Peter Morris1

1Physics, Sir Peter Mansfield Magnetic Resonance Centre, Nottingham, Nottinghamshire, United Kingdom

We use the combination of MEG and fMRI to study the neural basis for BOLD non-linearity. Both nonlinear neural responses to stimuli and nonlinear vascular responses to neural activity may contribute to BOLD non-linearity and the relative contribution of these two effects remains poorly understood. We extended the study of non-linear neural response to both phase locked evoked response and time related beta oscillations in somatosensory cortex. The N20 peak amplitudes show non-linearities with ISI of 0.25-2s, influenced by beta power at the time of stimulation, suggesting that best oscillation should also be considered for BOLD convolution.



1126. Simultaneous BOLD and NIRS Signal Correlation During Hypoxia

Matthew Borzage1,2, Marvin Nelson3, Istvan Seri1,4, Stefan Blüml3,5

1Neonatal Medicine, Childrens Hospital Los Angeles, Los Angeles, CA, United States; 2Viterbi School of Engineering, University of Southern California, Los Angeles, 90007, United States; 3Department of Radiology, Childrens Hospital Los Angeles, Los Angeles, CA, United States; 4Keck School of Medicine, University of Southern California, Los Angeles, CA, United States; 5Rudi Schulte Research Institute, Santa Barbara, CA, United States

Studying changes in cerebral hemodynamics is possible via MR, including blood oxygen level dependent (BOLD) imaging. We used near infrared spectroscopy (NIRS) to sample oxy- and deoxyhemoglobin directly, and utilized a nitrogen challenge to change FiO2 and thus cause measurable changes in blood oxygenation. We have observed good correlation between the BOLD and NIRS signals, with higher correlation in the gray matter than in the white matter. In the near future, we will use this paradigm to study the limited autoregulation of cerebral blood flow in preterm neonates.



1127. Cerebral Blood Volume Changes in Arterial and Post-Arterial Compartments and Their Relationship with Cerebral Blood Flow Alteration During Brief Breath-Holding and Visual Stimulation in Human Brain

Jun Hua1, Robert Stevens1, Manus J. Donahue1,2, Alan J. Huang1, James J. Pekar1, Peter C.M. van Zijl1

1Department of Radiology, The Johns Hopkins University, Baltimore, MD, United States; 2Department of Clinical Neurology, Oxford University, Oxford, United Kingdom

Changes in CBF/CBV/arterial-CBV(CBVa)/post-arterial-CBV(CBVpa) were measured in human brain during breath-hold and visual stimulation. δCBV/CBV was larger during breath-hold (54.9+/-5.8%) than visual stimulation (28.2+/-5.2%), a difference primarily originating from δCBVpa/CBVpa (54.5+/-4.9% vs. 22.2+/-3.8%); δCBVa/CBVa (53+/-6%) and δCBF/CBF (61+/-7%) were comparable in both tasks. During breath-hold, vasodilation distributed proportionally among arterial and post-arterial compartments, whereas, during visual stimulation, relative change in CBVa was greater than that in CBVpa. Our data indicate that the coupling between arterial-CBV and CBF was largely preserved during both tasks (rCBVa=rCBF0.86+/-0.05), while the relationship between total-CBV and CBF was substantially different between breath-hold (rCBV=rCBF0.90+/-0.05) and visual (rCBV=rCBF0.52+/-0.04) stimulation.



1128. Impact of the Mono-Exponential Signal Decay Approximation on the Numerically Predicted Spatial BOLD Specificity for Spin Echo Sequences

Daniel Pflugfelder1, Kaveh Vahedipour1, Kamil Uludag2, Nadim Jon Shah1,3, Tony Stöcker1

1Institute of Neuroscience and Medicine 4, Medical Imaging Physics, Forschungszentrum Jülich GmbH, Jülich, Germany; 2Max-Planck Institute for Biological Cybernetics, Tuebingen, Germany; 3Faculty of Medicine, Department of Neurology, RWTH Aachen University, Aachen, Germany

To increase the spatial specificity of the BOLD signal, a large ratio R of microvascular to macrovascular BOLD signal is desirable. This can be be achieved using spin echo sequences. To simplify the calculation the extravascular BOLD signal (EV) is often approximated by a mono-exponential decay (MEA). To investigate the effect of the MEA we calculated R for multiple B0 and TE without using this approximation. The parameter range for an optimal R was considerable different to the results obtained using the MEA. This is mainly due to an vessel radius dependent delay of the EV which is not reproduced by the MEA.



1129. A Realistic Vascular Model for BOLD Signal Up to 16.4 T.

Bernd Michael Müller-Bierl1, Verena Pawlak2, Jason Kerr2, Kamil Ugurbil3, Kamil Uludag1

1MRC, Max-Planck Institute for Biological Cybernetics, Tübingen, Germany; 2NWG, Max-Planck Institute for Biological Cybernetics, Tübingen, Germany; 3Center for Magnetic Resonance Research, University of Minnesota, Minnesota, Minneapolis, United States

We present a realistic vascular model based on Monte-Carlo modeling of diffusion and the finite element method to compute the background magnetic field of partly oxygenated finite venules exposed to up to 16.4 T. Our data show that the realistic vasculature data set is necessary to account for the effects due to finite-sized vessels. The venule data herein stems from 2 photon microscopy of the rat brain. Results show that the infinite vessel model is prone to error so that the use of realistic vascular data sets is necessary to get precise results. However, for a better understanding more realistic vascular data sets should be examined in future work.


1130. Relaxation of Blood at High Field: Another Exchange Regime

Ksenija Grgac1,2, Qin Qin1,3, Michael McMahon1,3, Jason Zhao1, Peter C.M. van Zijl1,3

1Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, United States; 2Department of Chemistry, Johns Hopkins University, Baltimore, MD, United States; 3F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States

To study the intravascular BOLD mechanism, we used a physiologically controlled blood perfusion system at 9.4T under oxygenated conditions for a series of hematocrits. Previous studies have shown that, at such high fields, the two-site (eryhtrocyte-plasma) fast exchange model can not describe oxygenation-based relaxation changes properly in that it gives incorrect lifetimes for water in erythrocytes (1-3ms). We show that, for the physiological range of hematocrits, a general two-site exchange model (including slow, fast and intermediate regimes) can appropriately describe blood relaxation in oxygenated blood and provides an erythrocyte lifetime of 12.2±3.7ms, in agreement with literature values



1131. Blood Longitudinal (T1) and Transverse (T2) Relaxation Times at 11.7 Tesla

Ai-Ling Lin1, Xia Zhao1, Peter T. Fox1, Timothy Q. Duong1

1Research Imaging Institute, University of Texas Health Science Center, San Antonio, TX, United States

Knowledge of blood T1 and T2 values are important for many MRI studies that include BOLD modeling, high spatial specificity BOLD fMRI, blood flow MRI using arterial spin labeling (ASL), and blood volume MRI using vascular space occupancy (VASO) techniques. The purpose of the present study was to determine blood T1 and T2 values at 11.7T as a function of oxygenation level (Y), temperature, hematocrit fraction (Hct) and field strength (B0).



1132. Maximal Accuracy and Precision of HRF Measurements in Rapid-Presentation ER-FMRI
Experimental Designs

Xiaopeng Zong1, Jie Huang1,2

1Department of Radiology, Michigan State University, East Lansing, MI, United States; 2Neuroscience Program, Michigan State University, East Lansing, MI, United States

A quantitative ER-fMRI study requires to measuring hemodynamic response function (HRF) both accurately and precisely. A periodic ER-fMRI design can produce a high accuracy of HRF measurement but a low precision. Utilizing the approximate linearity of the HRF, a rapid-presentation (RP) ER-fMRI design can improve the precision by shorting intersitimulus interval (ISI). Nevertheless, hemodynamic response is non-linear and its corresponding effect on the estimated HRF increases with decreasing ISI, rendering the estimated HRF inaccurate for small ISI values. Accordingly, as demonstrated in this preliminary study, an optimal RP ER-fMRI design should maximize both accuracy and precision of HRF measurements.



fMRI: Respiratory Calibrations

Hall B Wednesday 13:30-15:30

1133. Saturation of Visually Evoked BOLD Response During Carbogen Inhalation

Claudine J. Gauthier1,2, Cécile Madjar2, Richard D. Hoge1,2

1Physiology/Biomedical Engineering, Université de Montréal, Montréal, Quebec, Canada; 2CRIUGM, Montreal, Quebec, Canada

Oxidative metabolism can be estimated from the BOLD signal following a calibration manipulation to determine a factor M. M is the maximum possible BOLD signal change. Carbogen inhalation was used here with intense visual stimulation to test whether an asymptote in BOLD signal could be reached. Results show a convergence of percent BOLD changes around 9% in visual cortex for 10% carbogen alone, and 5-10% carbogen breathing plus visual stimulation. The diminishing incremental response from visual stimulation at high carbogen concentrations suggests that these manipulations approach BOLD levels close to the saturation plateau.



1134. Calibrated FMRI During a Cognitive Stroop Task in the Aging Brain

Rafat Saeed Mohtasib1,2, Vanessa Sluming1,2, Laura Parkes1,3

1Magnetic Resonance and Image Analysis Research Centre (MARIARC), The University of Liverpool, Liverpool, United Kingdom; 2Medical Imaging Department, The University of Liverpool, United Kingdom; 3Imaging Science and Biomedical Engineering, School of Cancer and Imaging Sciences, The University of Manchester, United Kingdom

Calibrated fMRI is a new technique that allows quantitative estimates of the relative changes in cerebral metabolic rate of oxygen (ÄCMRO2) and cerebral blood flow (ÄCBF) that accompany neural activation. In this research we extend our previous work to study changes in neurovascular coupling over an age range during a cognitive Stroop task.

37 volunteers (age range 20-70) were scanned using 3T MRI. We found BOLD response to the Stroop task increases with increasing age, calibration constant A was found to reduce with age, a trend to reduced ÄCMRO2 with increasing age, and globally ÄCBF did not change with age.
1135. Error Propagation in CMRO2 Derivations Using CBF and BOLD Imaging

Hsiao-Wen Chung1, Wen Chau Wu

1Electrical Engineering, National Taiwan University, Taipei, Taiwan, Taiwan

The purpose of this study is therefore to investigate the issues error propagation in CMRO2 estimations under different CNR. Results from our error propagation study suggest that CMRO2 estimations using CBF and BOLD are valid only when the CNR for CBF measurements is sufficiently large, or when the underlying changes in CMRO2 and CBF are sufficiently large as in hypercapnic experiments. Validity of current instantaneous CMRO2 measurements for resting-state brain functional studies is therefore in some doubt.



1136. Effects of the ValSalva Maneuver and Hypercapnia on the BOLD Signal

Daniel A. Handwerker1, Paula Wu1,2, Ronald M. Harper3, Peter A. Bandettini1,4

1Section on Functional Imaging Methods, National Institute of Mental Health, Bethesda, MD, United States; 2Neuroscience, University of California, Los Angeles, Los Angeles, CA, United States; 3Neurobiology, David Geffen School of Medicine, UCLA, Los Angeles, CA, United States; 4Functional MRI Facility, National Institute of Mental Health, Bethesda, MD, United States

Hypercapnia creates global changes in cerebral blood flow, volume, and oxygenation that can be measured with fMRI and used for calibration. Breath-holding is a simple way to induce hypercapnia, but it may alter thoracic chest pressure and include a ValSalva effect. We alter chest pressure while keeping the hold duration constant to see how the BOLD signal changes. The initial BOLD undershoot and following peak scale with pressure. Because the precise contrast mechanisms behind these changes are not fully understood, they may be a confound in calibration studies, or a novel way to rapidly induce calibration-useful global BOLD signal changes.



1137. Hypoxia and Hyperoxia Alter Brain Metabolism in Awake Human

Feng Xu1, Uma Yezhuvath1, Peiying Wang1, Hanzhang Lu1

1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States

Many studies tried to understand how neural activity change vascular parameters, but little attention was received to whether gas content changes in blood would reversely alter neural activity. To investigate such an effect, we used a recently developed MRI technique to quantify global cerebral metabolic rate of oxygen (CMRO2) under hypoxia and hyperoxia. Our data suggest that a change in arterial oxygen content can modulate brain metabolism in a dose-dependent manner, with hypoxia increasing CMRO2 and hyperoxia decreasing it. Therefore, in addition to the well-known “forward” neurovascular coupling, the “reverse” coupling may be important in the regulation of brain function.



1138. Hyperoxic (HO) Versus Hypercapnic (HC) BOLD Calibration Under Precise Control of End-Tidal Carbon Dioxide and Oxygen

Clarisse Ildiko Mark1, M. Slessarev2, S. Ito3, J. Han2, J. A. Fisher2, G. B. Pike1

1McConnell Brain Imaging Center, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; 2Department of Anaesthesiology, University Health Network, Univeristy of Toronto,, Toronto, Ontario, Canada; 3Department of Anaesthesiology and Medical Crisis Management, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

Manual HC calibration depends on intrinsically low signal-to-noise perfusion imaging and individual vascular architecture, with resulting calibration (M)-values prone to large intra- and inter-subject variations that may bias oxygen metabolism studies. We thereby sough to investigate HO as a calibration alternative under rigorous control of end-tidal partial pressures of CO2 (PetCO2) and O2 (PetO2). Our findings suggest the viability of precisely controlling HO stimulation to provide more precise per-subject and per-brain-region M-estimates, based on high SNR PaO2 measurements and the removal of the confound of vascular variation in population observed under HC-calibration.



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