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Biomedical subjects

Kamil Ugurbil

Publications and source records attributed to Kamil Ugurbil.

At least 19 recordsLinked to original sources

Motor control in basal ganglia circuits using fMRI and brain atlas approaches.

In this study, we examined how the motor, premotor and associative basal ganglia territories process movement parameters such as the complexity and the frequency of movement. Twelve right-handed volunteers were studied using EPI BOLD contrast (3 T) while performing audio-paced finger tapping tasks designed to differentiate basal ganglia territories. Tasks varied movement complexity (repetitive index tapping, simple sequence of finger movements and complex sequence of 10 moves) and frequency (from 0.5 to 3 Hz). Activation maps were coregistered onto a 3-D brain atlas derived from post-mortem brains. Three main patterns of activation were observed. In the posterior putamen and the sensorimotor cortex, signal increased with movement frequency but not with movement complexity. In premotor areas, the anterior putamen and the ventral posterolateral thalamus, signal increased regularly with increasing movement frequency and complexity. In rostral frontal areas, the caudate nucleus, the subthalamic nucleus and the ventral anterior/ventrolateral thalamus, signal increased mainly during the complex task and the high frequency task (3 Hz). These data show the different roles of motor, premotor and associative basal ganglia circuits in the processing of motor-related operations and suggest that activation can be precisely located within the entire circuitry of the basal ganglia.

Adolescent↗

In vivo 17O NMR approaches for brain study at high field.

17O is the only stable oxygen isotope that can be detected by NMR. The quadrupolar moment of 17O spin (I = 5/2) can interact with local electric field gradients, resulting in extremely short T1 and T2 relaxation times which are in the range of several milliseconds. One unique NMR property of 17O spin is the independence of 17O relaxation times on the magnetic field strength, and this makes it possible to achieve a large sensitivity gain for in vivo 17O NMR applications at high fields. In vivo 17O NMR has two major applications for studying brain function and cerebral bioenergetics. The first application is to measure the cerebral blood flow (CBF) through monitoring the washout of inert H2 17O tracer in the brain tissue following an intravascular bolus injection of the 17O-labeled water. The second application, perhaps the most important one, is to determine the cerebral metabolic rate of oxygen utilization (CMRO2) through monitoring the dynamic changes of metabolically generated H2 17O from inhaled 17O-labeled oxygen gas in the brain tissue. One great merit of in vivo 17O NMR for the determination of CMRO2 is that only the metabolic H2 17O is detectable. This merit dramatically simplifies both CMRO2 measurement and quantification compared to other established methods. There are two major NMR approaches for monitoring H2 17O in vivo, namely direct approach by using 17O NMR detection (referred as direct in vivo 17O NMR approach) and indirect approach by using 1H NMR detection for measuring the changes in T2- or T1rho-weighted proton NMR signals caused by the 17O-1H scalar coupling and proton chemical exchange (referred as indirect in vivo 17O NMR approach). Both approaches are suitable for CBF measurements. However, recent studies indicated that the direct in vivo 17O NMR approach at high/ultrahigh fields appears to offer significant advantages for quantifying and imaging CMRO2. New developments have further demonstrated the feasibility for establishing a completely noninvasive in vivo 17O NMR approach for imaging CMRO2 in a rat brain during a brief 17O2 inhalation. This approach should be promising for studying the central role of oxidative metabolism in brain function and neurological diseases. Finally, the similar approach could potentially be applied to image CMRO2 noninvasively in human brain.

Animals↗

An inverted-microstrip resonator for human head proton MR imaging at 7 tesla.

As an extension of the previously developed microstrip transmission line (MTL) RF coil design, a high-frequency RF volume coil using multiple inverted MTL (iMTL) resonators for human head imaging at high magnetic field strength of 7 tesla (T) is reported. Compared to conventional MTL resonators, iMTL resonators can operate at higher frequency with lower losses and, thus, are suitable for designs of high-frequency RF volume coils with large coil size for human MR imaging and spectroscopy at high fields. An approach using capacitive terminations was analyzed and applied to the design of the iMTL volume coil for improving RF field homogeneity and broadening frequency-tuning range. A performance-comparison study was conducted between the prototype iMTL volume coil and a custom-built TEM volume coil at 7 T. The iMTL volume coil presents a comparable SNR and intrinsic B1 homogeneity to the TEM volume coil. Phantom and the human head images acquired using the iMTL volume coil are also presented. The proposed iMTL volume coil provides an efficient and alternative solution to design high-frequency and large-size volume coils for human MR applications at very high fields.

Brain↗

Nitric oxide regulation of myocardial O2 consumption and HEP metabolism.

NO and O(2) compete at cytochrome-c oxidase, thus potentially allowing NO to modulate mitochondrial respiration. We previously observed a decrease of myocardial phosphocreatine (PCr)/ATP during very high cardiac work states, corresponding to an increase in cytosolic free ADP. This study tested the hypothesis that NO inhibition of respiration contributes to this increase of ADP. Infusion of dobutamine + dopamine (DbDp, each 20 microg.kg(-1).min(-1) iv) to more than double myocardial oxygen consumption (MVo(2)) in open-chest dogs caused a decrease of myocardial PCr/ATP measured with (31)P NMR from 2.04 +/- 0.09 to 1.85 +/- 0.08 (P < 0.05). Inhibition of NO synthesis with N(omega)-nitro-L-arginine (L-NNA), while catecholamine infusion continued, caused PCr/ATP to increase to the control value. In a second group of animals, L-NNA administered before catecholamine stimulation (reverse intervention of the first group) increased PCr/ATP during basal conditions. In these animals L-NNA did not prevent a decrease of PCr/ATP at the high cardiac work state but, relative to MVo(2), PCr/ATP was significantly higher after L-NNA. In a third group of animals, pharmacological coronary vasodilation with carbochromen was used to prevent changes in coronary flow that might alter endothelial NO production. In these animals L-NNA again restored depressed myocardial PCr/ATP during catecholamine infusion. The finding that inhibition of NO production increased PCr/ATP suggests that during very high work states NO inhibition of mitochondrial respiration requires ADP to increase to drive oxidative phosphorylation.

Adenosine Diphosphate↗

3-D diffusion tensor axonal tracking shows distinct SMA and pre-SMA projections to the human striatum.

Studies in non-human primates have shown that medial premotor projections to the striatum are characterized as a set of distinct circuits conveying different type of information. This study assesses the anatomical projections from the supplementary motor area (SMA), pre-SMA and motor cortex (MC) to the human striatum using diffusion tensor imaging (DTI) axonal tracking. Eight right-handed volunteers were studied at 1.5 T using DTI axonal tracking. A connectivity matrix was computed, which tested for connections between cortical areas (MC, SMA and pre-SMA) and subcortical areas (posterior, middle and anterior putamen and the head of the caudate nucleus) in each hemisphere. Pre-SMA projections to the striatum were located rostral to SMA projections to the striatum. The SMA and the MC were similarly connected to the posterior and middle putamen and not to the anterior striatum. These data show that the MC and SMA have connections with similar parts of the sensorimotor compartment of the human striatum, whereas the pre-SMA sends connections to more rostral parts of the striatum, including the associative compartment.

Adult↗

A comparison of hemodynamic and neural responses in cat visual cortex using complex stimuli.

We compare fMRI-BOLD responses in anesthetized cats with local field potentials (LFPs), aggregate high-frequency responses (analog-Mua) and spiking activity recorded in primary and higher visual cortex of alert animals. The similarity of the activations in these electrophysiological signals to those in the BOLD is quantified by counting recording sites where different stimuli elicit the same relative activation as in the imaging experiments. Using artificial stimuli, a comparison of BOLD and LFP strongly depends on the frequency range used. Stimulating with complex or natural stimuli reduces this frequency dependence and yields a good match of LFP and BOLD. In general, this match is best between 20 and 50 Hz. The measures of high-frequency activity behave qualitatively different: the responses of the analog-Mua match those of the LFP; the spiking activity shows a low concordance with the BOLD signal. This dissociation of BOLD and spiking activity is most prominent upon stimulation with natural stimuli.

Animals↗

Diffusion tensor fiber tracking shows distinct corticostriatal circuits in humans.

A landmark of corticostriatal connectivity in nonhuman primates is that cortical connections are organized into a set of discrete circuits. Each circuit is assumed to perform distinct behavioral functions. In animals, most connectivity studies are performed using invasive tracing methods, which are nonapplicable in humans. To test the proposal that corticostriatal connections are organized as multiple circuits in humans, we used diffusion tensor imaging axonal tracking, a new magnetic resonance technique that allows demonstration of fiber tracts in a noninvasive manner. Diffusion tensor imaging-based fiber tracking showed that the posterior (sensorimotor), anterior (associative), and ventral (limbic) compartments of the human striatum have specific connections with the cortex, and particularly the frontal lobes. These results provide the first direct demonstration of distinct corticostriatal connections in humans.

Adult↗

Temperature and SAR calculations for a human head within volume and surface coils at 64 and 300 MHz.

PURPOSE: To examine relationships between specific energy absorption rate (SAR) and temperature distributions in the human head during radio frequency energy deposition in MRI. MATERIALS AND METHODS: A multi-tissue numerical model of the head was developed that considered thermal conductivity, heat capacity, perfusion, heat of metabolism, electrical properties, and density. Calculations of SAR and the resulting temperature increase were performed for different coils at different frequencies. RESULTS: Because of tissue-dependent perfusion rates and thermal conduction, there is not a good overall spatial correlation between SAR and temperature increase. When a volume coil is driven to induce a head average SAR level of either 3.0 or 3.2 W/kg, it is unlikely that a significant temperature increase in the brain will occur due to its high rate of perfusion, although limits on SAR in any 1 g of tissue in the head may be exceeded. CONCLUSION: Attempts to ensure RF safety in MRI often rely on assumptions about local temperature from local SAR levels. The relationship between local SAR and local temperature is not, however, straightforward. In cases where high SAR levels are required due to pulse sequence demands, calculations of temperature may be preferable to calculations of SAR because of the more direct relationship between temperature and safety.

Equipment Safety↗

Phantom design method for high-field MRI human systems.

A phantom design method suitable for high-field MRI based on the RF field wave characteristics of sample and experimental validations at 7.0 T and 3.0 T are presented. The RF field distribution in a phantom with a given RF coil system is primarily determined by the sample size relative to the wavelength inside the sample, and the ratio between the displacement and conduction currents. Experimental results demonstrate that the MR image intensity patterns associated with wave behavior in human samples at a given field strength can be reproduced with a phantom at the same or different field strengths once the dimension and penetration constant are scaled by the corresponding wavelength in the sample medium.

Brain Mapping↗

Parallel imaging performance as a function of field strength--an experimental investigation using electrodynamic scaling.

In this work, the dependence of parallel MRI performance on main magnetic field strength is experimentally investigated. Using the general framework of electrodynamic scaling, the B0-dependent behavior of the relevant radiofrequency fields at a single physical field strength of 7 T is studied. In the chosen implementation this is accomplished by adjusting the permittivity and conductivity of a homogeneous spherical phantom. With different mixing ratios of decane, ethanol, purified water, N-methylformamide, and sodium chloride, field strengths in the range of 1.5 to 11.5 T are mimicked. Based on sensitivity maps of an eight-coil receiver array, the field-dependent performance of parallel imaging is assessed in terms of the geometry factor g, which reflects noise enhancement in parallel imaging reconstruction. At low field strengths the SNR penalty was nearly independent of B0 and favorably low for 1D reduction factors up to between 3 and 4. At higher field strengths the transition between favorable and prohibitive parallel imaging conditions was found to shift toward higher feasible reduction factors. These findings are in good agreement with previous theoretical predictions. From this agreement it is concluded that parallel MRI at high B0 benefits specifically from onsetting far-field behavior of the involved radiofrequency fields.

Electromagnetic Fields↗

Transverse relaxation in the rotating frame induced by chemical exchange.

In the presence of radiofrequency irradiation, relaxation of magnetization aligned with the effective magnetic field is characterized by the time constant T1rho. On the other hand, the time constant T2rho characterizes the relaxation of magnetization that is perpendicular to the effective field. Here, it is shown that T2rho can be measured directly with Carr-Purcell sequences composed of a train of adiabatic full-passage (AFP) pulses. During adiabatic rotation, T2rho characterizes the relaxation of the magnetization, which under adiabatic conditions remains approximately perpendicular to the time-dependent effective field. Theory is derived to describe the influence of chemical exchange on T2rho relaxation in the fast-exchange regime, with time constant defined as T2rho,ex. The derived theory predicts the rate constant R2rho,ex (= 1/T2rho,ex) to be dependent on the choice of amplitude- and frequency-modulation functions used in the AFP pulses. Measurements of R2rho,ex of the water/ethanol exchanging system confirm the predicted dependence on modulation functions. The described theoretical framework and adiabatic methods represent new tools to probe exchanging systems.

Algorithms↗

Spatial relationship between neuronal activity and BOLD functional MRI.

Despite the ubiquitous use of functional magnetic resonance imaging (fMRI), the extent to which the magnitude and spatial scale of the fMRI signal correlates with neuronal activity is poorly understood. In this study, we directly compared single and multiunit neuronal activity with blood oxygenation level-dependent (BOLD) fMRI responses across a large area of the cat area 18. Our data suggest that at the scale of several millimeters, the BOLD contrast correlates linearly with the underlying neuronal activity. At the level of individual electrode recording sites, however, the correlation between the two signals varied substantially. We conclude from our study that T(2)*-based positive BOLD signals are a robust predictor for neuronal activity only at supra-millimeter spatial scales.

Animals↗

Hypercapnic normalization of BOLD fMRI: comparison across field strengths and pulse sequences.

The blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signal response to neural stimulation is influenced by many factors that are unrelated to the stimulus. These factors are physiological, such as the resting venous cerebral blood volume (CBV(v)) and vessel size, as well as experimental, such as pulse sequence and static magnetic field strength (B(0)). Thus, it is difficult to compare task-induced fMRI signals across subjects, field strengths, and pulse sequences. This problem can be overcome by normalizing the neural activity-induced BOLD fMRI response by a global hypercapnia-induced BOLD signal. To demonstrate the effectiveness of the BOLD normalization approach, gradient-echo BOLD fMRI at 1.5, 4, and 7 T and spin-echo BOLD fMRI at 4 T were performed in human subjects. For neural stimulation, subjects performed sequential finger movements at 2 Hz, while for global stimulation, subjects breathed a 5% CO(2) gas mixture. Under all conditions, voxels containing primarily large veins and those containing primarily active tissue (i.e., capillaries and small veins) showed distinguishable behavior after hypercapnic normalization. This allowed functional activity to be more accurately localized and quantified based on changes in venous blood oxygenation alone. The normalized BOLD signal induced by the motor task was consistent across different magnetic fields and pulse sequences, and corresponded well with cerebral blood flow measurements. Our data suggest that the hypercapnic normalization approach can improve the spatial specificity and interpretation of BOLD signals, allowing comparison of BOLD signals across subjects, field strengths, and pulse sequences. A theoretical framework for this method is provided.

Adult↗

BOLD fMRI and psychophysical measurements of contrast response to broadband images.

We have measured the relationship between image contrast, perceived contrast, and BOLD fMRI activity in human early visual areas, for natural, whitened, pink noise, and white noise images. As root-mean-square contrast increases, BOLD response to natural images is stronger and saturates more rapidly than response to the whitened images. Perceived contrast and BOLD fMRI responses are higher for pink noise than for white noise patterns, by the same ratio as between natural and whitened images. Spatial phase structure has no measurable effect on perceived contrast or BOLD fMRI response. The fMRI and perceived contrast response results can be described by models of spatial frequency response in V1, that match the contrast sensitivity function at low contrasts, and have more uniform spatial frequency response at high contrasts.

Adult↗

Simplified methods for calculating cerebral metabolic rate of oxygen based on 17O magnetic resonance spectroscopic imaging measurement during a short 17O2 inhalation.

It has recently been shown that 17O magnetic resonance (MR) spectroscopic imaging at ultrahigh fields provides a reliable method for measuring CMRO2 during a short period of 17O2 gas inhalation. The mathematical (or complete) model used in the 17O MR method for calculating CMRO2 requires simultaneous measurements of multiple parameters including the concentration of H2 17O produced in the brain tissue from inhaled 17O2 gas (Cb), CBF, and the input function for the H2 17O concentration in the feeding artery (Ca). Both invasive and noninvasive measurements are involved in determining all of these parameters. In this article, two simplified methods are proposed and validated for calculating CMRO2 based on 17O MR measurement(s); the first method requires the measurements of Cb and CBF, but not Ca, and the second method only requires a single noninvasive measurement of Cb. The simplified methods were used to calculate CMRO2 in anesthetized rat brain, and the results were compared with those obtained using the complete model. The results from this work show (1) the validity of the simplified methods for quantifying CMRO2, and (2) the feasibility for establishing a completely noninvasive 17O MR approach for imaging CMRO2 in vivo.

Animals↗

Retinotopic mapping in cat visual cortex using high-field functional magnetic resonance imaging.

In the field of neuroscience, there has always been a need for imaging techniques that provide high-resolution, large field-of-view measurements of neural activity. Functional MRI has this capability, but the link between the blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) signal and neural activity is indirect. High magnetic field strengths (>3 T) improve the strength and specificity of the BOLD signal, but there are additional concerns about imaging artifacts at high field. We have tested the capabilities of ultra high field fMRI in the anesthetized juvenile cat, demonstrating rapid, non-invasive retinotopic mapping of early visual areas. Maps of topographic organization and measured cortical magnification factors are in good agreement with electrophysiological studies. Measurement precision was estimated at 1 mm. This mapping, performed with an MRI scanner at ultra high field (9.4 T), demonstrates the capabilities of high-resolution functional mapping of the visual system at ultra high field.

Animals↗

Mirror-symmetric tonotopic maps in human primary auditory cortex.

Understanding the functional organization of the human primary auditory cortex (PAC) is an essential step in elucidating the neural mechanisms underlying the perception of sound, including speech and music. Based on invasive research in animals, it is believed that neurons in human PAC that respond selectively with respect to the spectral content of a sound form one or more maps in which neighboring patches on the cortical surface respond to similar frequencies (tonotopic maps). The number and the cortical layout of such tonotopic maps in the human brain, however, remain unknown. Here we use silent, event-related functional magnetic resonance imaging at 7 Tesla and a cortex-based analysis of functional data to delineate with high spatial resolution the detailed topography of two tonotopic maps in two adjacent subdivisions of PAC. These maps share a low-frequency border, are mirror symmetric, and clearly resemble those of presumably homologous fields in the macaque monkey.

Acoustic Stimulation↗

Measurement of unidirectional Pi to ATP flux in human visual cortex at 7 T by using in vivo 31P magnetic resonance spectroscopy.

Taking advantage of the high NMR detection sensitivity and the large chemical shift dispersion offered by ultra-high field strength of 7 T, the effect of magnetization transfer on inorganic phosphate (Pi) resonance during saturation of gamma-ATP resonance, mediated by the ATP synthesis reaction, was observed noninvasively in the human primary visual cortex by using in vivo 31P magnetic resonance spectroscopy. The unidirectional flux from Pi to ATP was measured by using progressive saturation transfer experiments. The cerebral ATP synthesis rate in the human primary visual cortex measured by 31P magnetic resonance spectroscopy in this study was 12.1 +/- 2.8 micromol ATP/g per min, which agreed well with the value that was calculated indirectly from the cerebral metabolic rate of glucose consumption reported previously.

Adenosine Triphosphate↗