Richard b. Buxton
University of California, San Diego, Radiology, Faculty Member
Several techniques have been proposed to estimate relative changes in cerebral metabolic rate of oxygen consumption (CMRO2) by exploiting combined BOLD fMRI and cerebral blood flow data in conjunction with hypercapnic or hyperoxic... more
Several techniques have been proposed to estimate relative changes in cerebral metabolic rate of oxygen consumption (CMRO2) by exploiting combined BOLD fMRI and cerebral blood flow data in conjunction with hypercapnic or hyperoxic respiratory challenges. More recently, methods based on respiratory challenges that include both hypercapnia and hyperoxia have been developed to assess absolute CMRO2, an important parameter for understanding brain energetics. In this paper, we empirically optimize a previously presented "original calibration model" relating BOLD and blood flow signals specifically for the estimation of oxygen extraction fraction (OEF) and absolute CMRO2. To do so, we have created a set of synthetic BOLD signals using a detailed BOLD signal model to reproduce experiments incorporating hypercapnic and hyperoxic respiratory challenges at 3T. A wide range of physiological conditions was simulated by varying input parameter values (baseline cerebral blood volume (CB...
Research Interests: Mathematics, Computer Science, Magnetic Resonance Imaging, Medicine, Brain, and 12 moreHumans, Computer Simulation, Calibration, Neuroimage, Theoretical Models, Oxygen, Cerebral Blood Flow, Hyperoxia, Oxygen Consumption, Hypercapnia, Psychology and Cognitive Sciences, and Medical and Health Sciences
Human immunodeficiency virus (HIV) and methamphetamine (METH) dependence are independently associated with neuronal dysfunction. The coupling between cerebral blood flow (CBF) and neuronal activity is the basis of many task-based... more
Human immunodeficiency virus (HIV) and methamphetamine (METH) dependence are independently associated with neuronal dysfunction. The coupling between cerebral blood flow (CBF) and neuronal activity is the basis of many task-based functional neuroimaging techniques. We examined the interaction between HIV infection and a previous history of METH dependence on CBF within the lenticular nuclei (LN). Twenty-four HIV-/METH-, eight HIV-/METH+, 24 HIV+/METH-, and 15 HIV+/METH+ participants performed a finger tapping paradigm. A multiple regression analysis of covariance assessed associations and two-way interactions between CBF and HIV serostatus and/or previous history of METH dependence. HIV+ individuals had a trend towards a lower baseline CBF (-10%, p = 0.07) and greater CBF changes for the functional task (+32%, p = 0.01) than HIV- subjects. Individuals with a previous history of METH dependence had a lower baseline CBF (-16%, p = 0.007) and greater CBF changes for a functional task (...
Research Interests: Magnetic Resonance Imaging, Medicine, Humans, Female, Methamphetamine, and 15 moreMale, Hiv Infection, Aged, Middle Aged, Human immunodeficiency virus, Meth, Adult, Highly Active Antiretroviral Therapy, Multiple regression analysis, Functional Neuroimaging, Brain Function, Cerebral Blood Flow, Corpus striatum, Central nervous system stimulants, and HIV infections
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Research Interests: Neuroscience, Psychology, Computer Science, Magnetic Resonance Imaging, Attention, and 15 moreMedicine, Visual Cortex, Brain Mapping, Humans, Female, Neuroimage, Male, Young Adult, Neural Activity, Oxygen, Adult, Oxidative Metabolism, Psychology and Cognitive Sciences, Metabolic Activity, and Medical and Health Sciences
Research Interests: Computer Science, Chemistry, Magnetic Resonance Imaging, Medicine, Brain Mapping, and 15 moreHumans, Hemodynamics, Female, Neuroimage, Male, Oxygen, Adult, Blood Flow, Stimulation, Cerebral Blood Flow, Oxygen Consumption, Oxygenation, photic stimulation, Psychology and Cognitive Sciences, and Medical and Health Sciences
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Functional magnetic resonance imaging is widely used to map patterns of brain activation based on blood oxygenation level dependent (BOLD) signal changes associated with changes in neural activity. However, because oxygenation changes... more
Functional magnetic resonance imaging is widely used to map patterns of brain activation based on blood oxygenation level dependent (BOLD) signal changes associated with changes in neural activity. However, because oxygenation changes depend on the relative changes in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO(2)), a quantitative interpretation of BOLD signals, and also other functional neuroimaging signals related to blood or tissue oxygenation, is fundamentally limited until we better understand brain oxygen metabolism and how it is related to blood flow. However, the positive side of the complexity of oxygenation signals is that when combined with dynamic CBF measurements they potentially provide the best tool currently available for investigating the dynamics of CMRO(2). This review focuses on the problem of interpreting oxygenation-based signals, the challenges involved in measuring CMRO(2) in general, and what is needed to put oxygenation-based estim...
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SummarySeveral current functional neuroimaging methods are sensitive to cerebral metabolism and cerebral blood flow (CBF) rather than the underlying neural activity itself. Empirically, the connections between metabolism, flow and neural... more
SummarySeveral current functional neuroimaging methods are sensitive to cerebral metabolism and cerebral blood flow (CBF) rather than the underlying neural activity itself. Empirically, the connections between metabolism, flow and neural activity are complex and somewhat counterintuitive: CBF and glycolysis increase more than seems to be needed to provide oxygen and pyruvate for oxidative metabolism, and the oxygen extraction fraction is relatively low in the brain anddecreaseswhen oxygen metabolism increases. This work lays a foundation for the idea that this unexpected pattern of physiological changes is consistent with basic thermodynamic considerations related to metabolism. In the context of this thermodynamic framework, the apparent mismatches in metabolic rates and CBF are related to preserving the entropy change of oxidative metabolism, specifically the O2/CO2ratio in the mitochondria. However, the mechanism supporting this CBF response is likely not due to feedback from a h...
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Functional magnetic resonance imaging (fMRI) using the blood oxygenation level dependent (BOLD) signal is a standard tool in human neuroscience studies. However, the BOLD signal is physiologically complex, depending on the baseline state... more
Functional magnetic resonance imaging (fMRI) using the blood oxygenation level dependent (BOLD) signal is a standard tool in human neuroscience studies. However, the BOLD signal is physiologically complex, depending on the baseline state of the brain and the balance of changes in blood flow and oxygen metabolism in response to a change in neural activity. Interpretation of the magnitude of the BOLD response is thus problematic; specifically, group differences of the BOLD response to a standard task or stimulus, or a change after administration of a drug, could be due to a change in the neural response, neurovascular coupling, or the baseline state. While changes in oxygen metabolism can serve as a biomarker of neural activity change, reflecting the energy cost of activity, oxygen metabolism cannot be estimated from BOLD measurements alone. Here we used the effects of caffeine as a test case to show that a suite of additional noninvasive measurements, requiring no manipulation of inh...
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Quantitative functional magnetic resonance imaging methods make it possible to measure cerebral oxygen metabolism (CMRO2) in the human brain. Current methods require the subject to breathe special gas mixtures (hypercapnia and hyperoxia).... more
Quantitative functional magnetic resonance imaging methods make it possible to measure cerebral oxygen metabolism (CMRO2) in the human brain. Current methods require the subject to breathe special gas mixtures (hypercapnia and hyperoxia). We tested a noninvasive suite of methods to measure absolute CMRO2in both baseline and dynamic activation states without the use of special gases: arterial spin labeling (ASL) to measure baseline and activation cerebral blood flow (CBF), with concurrent measurement of the blood oxygenation level dependent (BOLD) signal as a dynamic change in tissue R2*; VSEAN to estimate baseline O2extraction fraction (OEF) from a measurement of venous blood R2, which in combination with the baseline CBF measurement yields an estimate of baseline CMRO2; and FLAIR-GESSE to measure tissue R2′to estimate the scaling parameter needed for calculating the change in CMRO2in response to a stimulus with the calibrated BOLD method. Here we describe results for a study sample...
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The computational properties of the human brain arise from an intricate interplay between billions of neurons connected in complex networks. However, our ability to study these networks in healthy human brain is limited by the necessity... more
The computational properties of the human brain arise from an intricate interplay between billions of neurons connected in complex networks. However, our ability to study these networks in healthy human brain is limited by the necessity to use non-invasive technologies. This is in contrast to animal models where a rich, detailed view of cellular-level brain function with cell-type-specific molecular identity has become available due to recent advances in microscopic optical imaging and genetics. Thus, a central challenge facing neuroscience today is leveraging these mechanistic insights from animal studies to accurately draw physiological inferences from non-invasive signals in humans. On the essential path towards this goal is the development of a detailed 'bottom-up' forward model bridging neuronal activity at the level of cell-type-specific populations to non-invasive imaging signals. The general idea is that specific neuronal cell types have identifiable signatures in th...
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Identification of the cellular players and molecular messengers that communicate neuronal activity to the vasculature driving cerebral hemodynamics is important for (1) the basic understanding of cerebrovascular regulation and (2)... more
Identification of the cellular players and molecular messengers that communicate neuronal activity to the vasculature driving cerebral hemodynamics is important for (1) the basic understanding of cerebrovascular regulation and (2) interpretation of functional Magnetic Resonance Imaging (fMRI) signals. Using a combination of optogenetic stimulation and 2-photon imaging in mice, we demonstrate that selective activation of cortical excitation and inhibition elicits distinct vascular responses and identify the vasoconstrictive mechanism as Neuropeptide Y (NPY) acting on Y1 receptors. The latter implies that task-related negative Blood Oxygenation Level Dependent (BOLD) fMRI signals in the cerebral cortex under normal physiological conditions may be mainly driven by the NPY-positive inhibitory neurons. Further, the NPY-Y1 pathway may offer a potential therapeutic target in cerebrovascular disease.
Research Interests: Neuroscience, Magnetic Resonance Imaging, Biology, Medicine, Gene expression, and 15 moreCerebral Cortex, Mice, Mouse, Animals, Male, Neurons, Diagnostic Imaging, Neurological, Neuropeptide Y, Cerebrovascular Disorders, Elife, Biochemistry and cell biology, Dilation, Constriction, and Brain Disorders
Calibrated BOLD imaging, in which traditional measurements of the BOLD signal are combined with measurements of cerebral blood flow (CBF) within a BOLD biophysical model to estimate changes in oxygen metabolism (CMRO2), has been a... more
Calibrated BOLD imaging, in which traditional measurements of the BOLD signal are combined with measurements of cerebral blood flow (CBF) within a BOLD biophysical model to estimate changes in oxygen metabolism (CMRO2), has been a valuable tool for untangling the physiological processes associated with neural stimulus-induced BOLD activation. However, to date this technique has largely been applied to the study of essentially steady-state physiological changes (baseline to activation) associated with block-design stimuli, and it is unclear whether this approach may be directly extended to the study of more dynamic, naturalistic experimental designs. In this study we tested an assumption underlying this technique whose validity is critical to the application of calibrated BOLD to the study of more dynamic stimuli, that information about fluctuations in venous cerebral blood volume (CBVv) can be captured indirectly by measuring fluctuations in CBF, making the independent measurement o...
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Functional magnetic resonance imaging (fMRI) based on blood oxygenation level dependent (BOLD) signal changes is a sensitive tool for mapping brain activation, but quantitative interpretation of the BOLD response is problematic. The BOLD... more
Functional magnetic resonance imaging (fMRI) based on blood oxygenation level dependent (BOLD) signal changes is a sensitive tool for mapping brain activation, but quantitative interpretation of the BOLD response is problematic. The BOLD response is primarily driven by cerebral blood flow (CBF) changes, but is moderated by M, a scaling parameter reflecting baseline deoxyhemoglobin, and n, the ratio of fractional changes in CBF to cerebral metabolic rate of oxygen consumption (CMRO(2)). We compared M and n between cortical (visual cortex, VC) and subcortical (lentiform nuclei, LN) regions using a quantitative approach based on calibrating the BOLD response with a hypercapnia experiment. Although M was similar in both regions (~5.8%), differences in n (2.21+/-0.03 in VC and 1.58+/-0.03 in LN; Cohen d=1.71) produced substantially weaker (~3.7x) subcortical than cortical BOLD responses relative to CMRO(2) changes. Because of this strong sensitivity to n, BOLD response amplitudes cannot ...
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ABSTRACT With the growing recognition of the complexity of neurovascular coupling, research has focused on the “neurovascular unit”, a close association between neurons, astrocytes and blood vessels. A number of experimental tools have... more
ABSTRACT With the growing recognition of the complexity of neurovascular coupling, research has focused on the “neurovascular unit”, a close association between neurons, astrocytes and blood vessels. A number of experimental tools have been developed for probing the neurovascular unit in animal models, providing the potential for a much deeper understanding of these fundamental physiological mechanisms. In this chapter, we review some of the available experimental and computational methods and present a multi-level conceptual framework for analyzing and interpreting a wide range of experimental measurements. We then discuss our working hypotheses regarding the regulation of blood flow and neurophysiological correlates of fMRI signals. Finally, we discuss how multimodal imaging, along with valid physiological models, can ultimately be used to obtain quantitative estimates of physiological parameters in health and disease and provide an outlook for the future directions in neurovascular research.
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The blood oxygenation level-dependent (BOLD) contrast is widely used in functional magnetic resonance imaging (fMRI) studies aimed at investigating neuronal activity. However, the BOLD signal reflects changes in blood volume and... more
The blood oxygenation level-dependent (BOLD) contrast is widely used in functional magnetic resonance imaging (fMRI) studies aimed at investigating neuronal activity. However, the BOLD signal reflects changes in blood volume and oxygenation rather than neuronal activity per se. Therefore, understanding the transformation of microscopic vascular behavior into macroscopic BOLD signals is at the foundation of physiologically informed noninvasive neuroimaging. Here, we use oxygen-sensitive two-photon microscopy to measure the BOLD-relevant microvascular physiology occurring within a typical rodent fMRI voxel and predict the BOLD signal from first principles using those measurements. The predictive power of the approach is illustrated by quantifying variations in the BOLD signal induced by the morphological folding of the human cortex. This framework is then used to quantify the contribution of individual vascular compartments and other factors to the BOLD signal for different magnet str...
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Research Interests: Computer Science, Kinetics, Magnetic Resonance Imaging, Functional MRI, Medicine, and 15 moreLinear models, Neuroimmunology, Humans, Caffeine, Calibration, Neuroimage, Male, Metabolic rate, Oxygen, Adult, Brain Function, Cerebral Blood Flow, Hypercapnia, Central nervous system stimulants, and Medical and Health Sciences
ABSTRACT Elasticity imaging is based on two processes. The first is the evaluation of the mechanical response of a stressed tissue using imaging modalities, e.g. ultrasound, magnetic resonance imaging (MRI), computed tomography (CT) scans... more
ABSTRACT Elasticity imaging is based on two processes. The first is the evaluation of the mechanical response of a stressed tissue using imaging modalities, e.g. ultrasound, magnetic resonance imaging (MRI), computed tomography (CT) scans and Doppler ultrasound. The second step is depiction of the elastic properties of internal tissue structures by mathematical solution of the inverse mechanical problem. The evaluation of elastic properties of tissues has the potential for being an important diagnostic tool in the detection of cancer as well as other injuries and diseases. The success of breast self-examination in conjunction with mammography for detection and continuous monitoring of lesions has resulted in early diagnosis and institution of therapy. Self-examination is based on the manually palpable texture difference of the lesion relative to adjacent tissue and, as such, is limited to lesions located relatively near the skin surface and increased lesion hardness with respect to the surrounding tissue. Imaging of tissue “hardness” should allow more sensitive detection of abnormal structures deeper within tissue. Tissue hardness can actually be quantified in terms of the tissue elastic moduli and may provide good contrast between normal and abnormal tissues based on the large relative variation in shear (or Young’s) elastic modulus.
Simultaneous implementation of magnetic resonance imaging methods for Arterial Spin Labeling (ASL) and Blood Oxygenation Level Dependent (BOLD) imaging makes it possible to quantitatively measure the changes in cerebral blood flow (CBF)... more
Simultaneous implementation of magnetic resonance imaging methods for Arterial Spin Labeling (ASL) and Blood Oxygenation Level Dependent (BOLD) imaging makes it possible to quantitatively measure the changes in cerebral blood flow (CBF) and cerebral oxygen metabolism (CMRO(2)) that occur in response to neural stimuli. To date, however, the range of neural stimuli amenable to quantitative analysis is limited to those that may be presented in a simple block or event related design such that measurements may be repeated and averaged to improve precision. Here we examined the feasibility of using the relationship between cerebral blood flow and the BOLD signal to improve dynamic estimates of blood flow fluctuations as well as to estimate metabolic-hemodynamic coupling under conditions where a stimulus pattern is unknown. We found that by combining the information contained in simultaneously acquired BOLD and ASL signals through a method we term BOLD Constrained Perfusion (BCP) estimatio...
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A variety of biological evidence has identified a frontal-parietal circuit underlying spatial working memory for visual stimuli. But the question remains, how do these neural regions accomplish the goal of maintaining location information... more
A variety of biological evidence has identified a frontal-parietal circuit underlying spatial working memory for visual stimuli. But the question remains, how do these neural regions accomplish the goal of maintaining location information on-line? We tested the hypothesis that the active rehearsal of spatial information in working memory is accomplished by means of focal shifts of spatial selective attention to memorized locations. Spatial selective attention has been shown to cause changes in the early visual processing of stimuli that appear in attended locations. Thus, the hypothesis of attention-based rehearsal predicts similar modulations of visual processing at memorized locations. We used functional magnetic resonance imaging to observe posterior visual activations during the performance of a spatial working memory task. In line with the hypothesis, spatial rehearsal led to enhanced activation in the early visual areas contralateral to the memorized locations.
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Research Interests: Psychology, Cognitive Science, Neuropsychology, Cognition, Magnetic Resonance Imaging, and 15 moreMedicine, Energy Metabolism, Brain Mapping, Brain, Humans, Arousal, Sensitivity and Specificity, Cerebral Blood Flow, Reference Values, ASL (Arterial Spin Labeling), Oxygen Consumption, Neurosciences, Brain Diseases, Magnetic resonance image, and Relaxation Time
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Research Interests: Psychology, Computer Science, Magnetic Resonance Imaging, Medicine, Neuroimmunology, and 15 moreEnergy Metabolism, Brain Mapping, Humans, Neuroimage, Motor Cortex, Metabolic rate, Image Enhancement, Oxygen, Adult, Cerebral Blood Flow, Oxygen Consumption, Hemoglobins, Motor activity, Cerebral Blood Volume, and Medical and Health Sciences
Research Interests: Psychology, Algorithms, Nonlinear dynamics, Magnetic Resonance Imaging, Medicine, and 15 moreFMRI, Neuroimmunology, Brain, Humans, Hemodynamics, Neuroimage, Neurons, Mathematical Model, Metabolic rate, Oxygen, Blood Vessels, Brain Function, Cerebral Blood Flow, Experimental Data, and Medical and Health Sciences
Research Interests: Psychology, Computer Science, Algorithms, Magnetic Resonance Imaging, Stability, and 15 moreMedicine, Humans, Calibration, Female, Neuroimage, Male, Metabolic rate, Intraclass Correlation Coefficient, Oxygen, Adult, Reproducibility of Results, Hiv seropositivity, Cerebral Blood Flow, Psychology and Cognitive Sciences, and Medical and Health Sciences
Research Interests: Magnetic Resonance Imaging, Functional MRI, Brain Mapping, Brain, Humans, and 13 moreCaffeine, Neuroimage, Metabolic rate, Oxygen, Adult, Blood Flow, Cerebral Blood Flow, Human Subjects, ASL (Arterial Spin Labeling), photic stimulation, Psychology and Cognitive Sciences, Central nervous system stimulants, and Medical and Health Sciences
Research Interests: Psychology, Computer Science, Carbon Dioxide, Magnetic Resonance Imaging, Medicine, and 15 moreEnergy Metabolism, Brain Mapping, Humans, Female, Neuroimage, Male, Artifacts, Experimental Evaluation, Metabolic rate, Oxygen, Indexation, Cerebral Blood Flow, photic stimulation, Measurement technique, and Medical and Health Sciences
Research Interests: Computer Science, Chemistry, Magnetic Resonance Imaging, Medicine, Neuroimmunology, and 15 moreHumans, Neuroimage, Metabolic rate, Adult, Neural pathways, Cerebral Blood Flow, Human Subjects, Oxygen Extraction Fraction, Blood Flow Velocity, Oxygen Consumption, Block Design, Occipital Lobe, photic stimulation, Medical and Health Sciences, and Feed Forward
Research Interests: Computer Science, Algorithms, Chemistry, Magnetic Resonance Imaging, Energy Metabolism, and 15 moreBrain Mapping, Humans, Calibration, Functional Magnetic Resonance Imaging, Female, Male, Coefficient of Variation, Adult, Blood Flow, Indexation, Cerebral Blood Flow, Brain Chemistry, Block Design, Hypercapnia, and Medical and Health Sciences
The authors studied the effects of altering global cerebral blood flow on both blood oxygen level–dependent (BOLD) response and perfusion response to finger-thumb apposition. A PICORE/QUIPSS II protocol was used to collect interleaved... more
The authors studied the effects of altering global cerebral blood flow on both blood oxygen level–dependent (BOLD) response and perfusion response to finger-thumb apposition. A PICORE/QUIPSS II protocol was used to collect interleaved BOLD-weighted and perfusion-weighted images on eight finger-thumb apposition trials. Subjects were studied on a drug-free day and on a day when acetazolamide was administered between the second and third trials. After acetazolamide administration, resting cortical perfusion increased an average of 20% from preadministration levels, whereas the BOLD response to finger-thumb apposition decreased by an average of 35% in the S1M1 hand area. Contrary to predictions from the exhausted cerebrovascular reserve hypothesis and the oxygen limitation model, an effect of acetazolamide on cerebral blood flow response in the S1M1 hand area was not observed. Across the acetazolamide trials, BOLD response was inversely correlated with resting cortical perfusion for ind...
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Research Interests: Speech perception, Magnetic Resonance Imaging, Attention, Experimental Design, Brain Mapping, and 12 moreBrain, Humans, Cerebral Cortex, Female, Lexical Decision, Arousal, Adult, Auditory evoked Potentials, Auditory Cortex, Mr Imaging, Psychology and Cognitive Sciences, and Medical and Health Sciences
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Research Interests: Psychology, Computer Science, Magnetic Resonance Imaging, Medicine, Brain Mapping, and 14 moreBrain, Humans, Female, Neuroimage, Male, Young Adult, Oxygen, Adult, Reproducibility of Results, Sensitivity and Specificity, Oxygen Consumption, photic stimulation, Psychology and Cognitive Sciences, and Medical and Health Sciences
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Research Interests: Functional Analysis, Algorithms, Electrophysiology, Visual attention, Magnetic Resonance Imaging, and 16 moreAdolescent, Visual Cortex, Spatial Attention, Vision, Humans, Female, Male, Vigilance, Primary visual cortex, Adult, Time Factors, Visual Field, Visual Evoked Potentials, Nuclear Magnetic Resonance Imaging, Time Course, and Visual Pathway
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Research Interests: Algorithms, Kinetics, Magnetic Resonance Imaging, Functional MRI, Mathematical Modeling, and 14 moreHumans, Computer Simulation, Calibration, Neuroimage, Mathematical Model, Metabolic rate, Oxygen, Theoretical Framework, Cerebral Blood Flow, Oxygen Extraction Fraction, Oxygen Consumption, Hematocrit, Hemoglobins, and Hypercapnia
Some of the important features of how pulsatile flow generates artifacts in three-dimensional magnetic resonance imaging are analyzed and demonstrated. Time variations in the magnetic resonance signal during the heart cycle lead to more... more
Some of the important features of how pulsatile flow generates artifacts in three-dimensional magnetic resonance imaging are analyzed and demonstrated. Time variations in the magnetic resonance signal during the heart cycle lead to more complex patterns of artifacts in 3D imaging than in 2D imaging. The appearance and location of these artifacts within the image volume are shown to be describable as displacements along a line in a plane parallel to that defined by the phase and volume encode directions. The angle of the line in the plane depends solely upon the imaging parameters while the ghost displacement along the line is proportional to the signal modulation frequency. Aliasing of these ghosts leads to a variety of artifact patterns which are sensitive to the pulsation period and repetition time of the pulse sequence. Numerical simulations of these effects were found to be in good agreement with experimental images of an elastic model of a human carotid artery under simulated physiological conditions and with images of two human subjects.