Biomedical subjects

James S Hyde

Publications and source records attributed to James S Hyde.

18 recordsLinked to original sources

PubMed2006

Three-dimensional dynamic structure of the liquid-ordered domain in lipid membranes as examined by pulse-EPR oxygen probing.

Membranes made of dimyristoylphosphatidylcholine and cholesterol, one of the simplest paradigms for the study of liquid ordered-disordered phase separation, were investigated using a pulse-EPR spin-labeling method in which bimolecular collision of molecular oxygen with the nitroxide spin label is measured. This method allowed discrimination of liquid-ordered, liquid-disordered, and solid-ordered domains because the collision rates (OTP) differ in these domains. Furthermore, the oxygen transport parameter (OTP) profile across the bilayer provides unique information about the three-dimensional dynamic organization of the membrane domains. First, the OTP in the bilayer center in the liquid-ordered domain was comparable to that in the liquid-disordered domain without cholesterol, but the OTP near the membrane surface (up to carbon 9) was substantially smaller in the ordered domain, i.e., the cholesterol-based liquid-ordered domain is ordered only near the membrane surface, still retaining high levels of disorder in the bilayer center. This property may facilitate lateral mobility in ordered domains. Second, in the liquid-disordered domain, the domains with approximately 5 mol % cholesterol exhibited higher OTP than those without cholesterol, everywhere across the membrane. Third, the transmembrane OTP profile in the liquid-ordered domain that contained 50 mol % cholesterol dramatically differed from that which contained 27 mol % cholesterol.

Cholesterol↗

PubMed2006

Measurements of tissue T1 spin-lattice relaxation time and discrimination of large draining veins using transient EPI data sets in BOLD-weighted fMRI acquisitions.

The signal intensity during the dynamic approach to the equilibrium state of longitudinal magnetization is a function of sequence parameters, such as repetition time and flip angle, and depends on tissue characteristics, including longitudinal relaxation time of stationary tissue and the rate of blood inflow. A method is presented to extract information from data acquired during the transient state prior to T1 equilibrium using echo-planar acquisitions in T2*-weighted functional magnetic resonance imaging (fMRI) experiments. A voxel in a single slice acquisition is assumed to contain either stationary tissue or large vessels with flowing blood. Models are presented to characterize longitudinal magnetization relaxation of heterogeneous stationary tissue and blood inflow. The data were fitted to theoretical models for longitudinal relaxation of stationary tissue and inflowing blood assuming no residual signal prior to each RF excitation. Parameters were estimated at 3 T for each model using least squares estimation. A goodness-of-fit criterion was applied to exclude voxels that have transient data that does not fit the selected (best fit) model. Voxels that best fit the inflow model, measured at various TR and flip angles, were assumed to contain large draining veins and were excluded from functional maps. Histogram analysis of T1 distributions for activated voxels in a visual paradigm demonstrated the distributions are centered at T1 values of gray matter with tails at both sides of the center due to partial voluming of gray matter with white matter and CSF respectively. The mean gray matter volume fraction in activated voxels was about 0.9. The results indicate that transient data sets can provide additional information that is useful for both localization and characterization of the functionally relevant BOLD response.

Adult↗

PubMed2006

Digit tapping model of functional activation in the rat somatosensory cortex.

To establish a non-invasive model for functional activation of the rat somatosensory cortex, the forepaw digits of halothane-anesthetized rats were tapped while the blood flow (laser-Doppler flow, LDF) and somatosensory evoked potential (SSEP) responses in the forelimb area of the somatosensory cortex (S1FL) were measured. The distal phalanges of the forepaw digits were lightly tapped for 10s with an aluminum bar at frequencies between 1 and 40 Hz, with 0.4 cm total bar displacement. The LDF signal was normalized to the baseline preceding each stimulus block and averaged. The LDF response to digit tapping in the contralateral, but not ipsilateral S1FL, commenced within 1s, peaked at 11+/-0.5% (S.E.M.) above baseline within 2-3s, decreased to a plateau of 5+/-0.3% for the duration of the stimulation, and returned to baseline within 5-10s following tapping cessation. The LDF peak and plateau were not significantly different at different tapping frequencies. In the contralateral, but not ipsilateral, S1FLs, tapping produced an SSEP with positive (P1) and negative (N1) peaks at 27+/-0.5 and 47+/-0.2m s, respectively, after onset of the tap stimulation. As the tapping frequency increased from 1 to 20 Hz, the P1-N1 peak-to-peak amplitude decreased. At 30 and 40 Hz, the shortened interstimulus interval entrained the individual SSEPs into a steady-state evoked response. This study demonstrates that a robust functional activation of the forelimb region of primary somatosensory cortex of halothane-anesthetized rats can be produced by non-invasively tapping the forepaw digits and quantified with LDF and SSEP.

Analysis of Variance↗

PubMed2006

Water diffusion heterogeneity index in the human brain is insensitive to the orientation of applied magnetic field gradients.

The alpha diffusion-weighted imaging (DWI) method was developed to study heterogeneous water diffusion in the human brain using magnetic resonance imaging (MRI). An advantage of this model is that it does not require an assumption about the shape of the intravoxel distribution of apparent diffusion rates, and it has a calculable relationship to this distribution. The alpha-DWI technique is useful for detecting microstructural tissue changes associated with brain tumor invasion, and may be useful for directing therapy to invading tumor cells. In previous work, alpha-DWI was performed with magnetic field gradients applied along a single direction in order to avoid artificially introducing a source of heterogeneity to the decay. However, it is known that restricted diffusion is anisotropic in the brain, and the alpha-DWI method must take this into account to be complete. In this work the relationship between the applied magnetic field gradients and the fitted stretched-exponential model parameters was studied in the human brain. It was found the distributed diffusion coefficient (DDC) varies with the direction of applied gradients, while the heterogeneity index alpha is relatively direction-insensitive. It is proposed that in clinical use, maps of alpha can be created using diffusion-weighting gradients applied in a single direction that reflect the tissue heterogeneity.

Algorithms↗

PubMed2005

Strategies for block-design fMRI experiments during task-related motion of structures of the oral cavity.

Functional MRI (fMRI) studies of jaw motion, speech, and swallowing disorders have been hampered by motion artifacts. Tissue motion perturbs the static magnetic field, creating geometric distortions in echo-planar images that lead to many false positives in activation maps. These problems have restricted blood oxygenation level-dependent (BOLD) fMRI studies involving orofacial muscles to event-related designs, which offer weak contrast-to-noise ratios when compared to block designs. Two new approaches are described that greatly reduce false positives in the activation maps created by the distortions in block-design fMRI studies involving jaw and tongue motion during chewing. First, an appropriate task duration of 10-14 s was found to maximize functional contrast while minimizing motion artifacts. Second, three motion-sensitive postprocessing methods were applied successively to examine the temporal and spatial characteristics of responses and identify and remove false positives caused by motion artifacts. These techniques are shown to allow the use of block design in an fMRI study of a jaw motion task. Extension to speech and swallowing tasks is discussed.

Adult↗

PubMed2005

Temporal evolution of the CBV-fMRI signal to rat whisker stimulation of variable duration and intensity: a linearity analysis.

Cerebral blood volume functional magnetic resonance imaging (CBV-fMRI) experiments employing iron oxide contrast agent were conducted in rat whisker barrel cortex at 3 Tesla. Stimuli of constant frequency (12 Hz) but variable duration and intensity were delivered separately using a homemade whisker stimulator. The temporal behavior of CBV-fMRI signals was investigated using a linearity analysis method. Both superposition and scaling tests show that CBV-fMRI responses are generally consistent with a linear time-invariant (LTI) model. In particular, the response to a stimulus of higher intensity can be linearly scaled from that of lower intensity. However, significant deviations exist when the stimulus duration is manipulated, particularly in the trailing edge of the CBV-fMRI response curves.

Animals↗

PubMed2005

Multiquantum EPR spectroscopy of spin-labeled arrestin K267C at 35 GHz.

Three- and five-quantum absorption and dispersion multiquantum electron paramagnetic resonance spectra of a spin-labeled protein have been obtained for the first time at Q-band (35 GHz). Spectra of arrestin spin-labeled at site 267 were recorded at room temperature as a function of microwave power. The separation of irradiating microwave frequencies, Deltaf, was 10 kHz, and a newly-designed multiquantum Q-band electron paramagnetic resonance bridge was utilized, operating in a superheterodyne detection mode. The sample volume was 30 nL using a 3-loop-2-gap resonator. Most spectra were obtained at a 300 microM concentration in single, 2-min scans, but spectra were also successfully obtained at 30 microM, corresponding to one picomole of protein. Enhanced sensitivity to T(1) and T(2) was evident in the spectra, and linewidths varied considerably across the spectra. The pure absorption displays are beneficial relative to field modulation methods for spectral characterization. The presence of two states of the nitroxide spin-label with different relaxation times is evident, particularly in the dispersion spectra, which are expected to exhibit enhanced sensitivity to lineshape variation relative to absorption. Feasibility has been established for the use of this technique for site-directed spin-labeling studies of biologically relevant samples, particularly the study of protein structure and dynamics.

Absorption↗

PubMed2005

Aqueous flat-cells perpendicular to the electric field for use in electron paramagnetic resonance spectroscopy, II: design.

This paper builds on the work of Mett and Hyde [J. Magn. Reson. 165 (2003) 137]. Various aqueous flat-cell geometries in the perpendicular orientation have been studied using Ansoft High Frequency Structure Simulator (version 9.0, Pittsburgh, PA) and Computer Simulation Technology Microwave Studio (version 5.0, Wellesley Hills, MA). The analytic theory of Mett and Hyde has been refined to predict optimum dimensions of multiple sample cell structures including the effect of the sample holder dielectric properties and the interaction of the cells with each other on EPR signal strength. From these calculations and simulations we propose a practical multiple cell sample structure for use in commercial rectangular TE102 cavities that yields 2.0-2.3 times higher sensitivity relative to a single flat-cell in the nodal orientation. We also describe a modified TE102 resonator design with square rather than cylindrical sample-access stacks that is predicted to give a factor of 2.2-2.7 enhancement in EPR signal strength of a single flat-cell in the nodal orientation. These signal enhancements are predicted with sample holders fabricated from polytetrafluoroethylene. Additional improvement in EPR signal of up to 75% can be achieved by using sample holder materials with lower dielectric constants.

Computer-Aided Design↗

PubMed2005

Concentration by centrifugation for gas exchange EPR oximetry measurements with loop-gap resonators.

Measurement of the bimolecular collision rate between a spin label and oxygen is conveniently carried out using a gas permeable plastic sample tube of small diameter that fits a loop-gap resonator. It is often desirable to concentrate the sample by centrifugation in order to improve the signal-to-noise ratio (SNR), but the deformable nature of small plastic sample tubes presents technical problems. Solutions to these problems are described. Two geometries were considered: (i) a methylpentene polymer, TPX, from Mitsui Chemicals, at X-band and (ii) Teflon tubing with 0.075 mm wall thickness at Q-band. Sample holders were fabricated from Delrin that fit the Eppendorf microcentrifuge tubes and support the sample capillaries. For TPX, pressure of the sealant at the end of the sample tube against the Delrin sample holder provided an adequate seal. For Teflon, the holder permitted introduction of water around the tube in order to equalize pressures across the sealant during centrifugation. Typically, the SNR was improved by a factor of five to eight. Oxygen accessibility applications in site-directed spin labeling studies are discussed.

Centrifugation↗

PubMed2004

Momentum-weighted conjugate gradient descent algorithm for gradient coil optimization.

MRI gradient coil design is a type of nonlinear constrained optimization. A practical problem in transverse gradient coil design using the conjugate gradient descent (CGD) method is that wire elements move at different rates along orthogonal directions (r, phi, z), and tend to cross, breaking the constraints. A momentum-weighted conjugate gradient descent (MW-CGD) method is presented to overcome this problem. This method takes advantage of the efficiency of the CGD method combined with momentum weighting, which is also an intrinsic property of the Levenberg-Marquardt algorithm, to adjust step sizes along the three orthogonal directions. A water-cooled, 12.8 cm inner diameter, three axis torque-balanced gradient coil for rat imaging was developed based on this method, with an efficiency of 2.13, 2.08, and 4.12 mT.m(-1).A(-1) along X, Y, and Z, respectively. Experimental data demonstrate that this method can improve efficiency by 40% and field uniformity by 27%. This method has also been applied to the design of a gradient coil for the human brain, employing remote current return paths. The benefits of this design include improved gradient field uniformity and efficiency, with a shorter length than gradient coil designs using coaxial return paths.

Algorithms↗

PubMed2004

Spatial correlations of laminar BOLD and CBV responses to rat whisker stimulation with neuronal activity localized by Fos expression.

The spatial relationship between a measured fMRI signal and its underlying neuronal activity remains unclear. One obstacle is the localization of neuronal activity; another is the spatial resolution of fMRI. In the present study, high-resolution BOLD and CBV fMRI experiments (voxel size: 156 x 156 x 2000 microm3) were conducted in the rat whisker barrel cortex at 3 T; neuronal activity across cortical layers was mapped using the Fos expression technique. Results show that BOLD response is weighted by blood volume and that pixels with high BOLD response can be located at the cortical surface or in deep layers, depending on local vasculature. In contrast to BOLD response, the pixels with high CBV response were consistently clustered in the deep cortical layers. Percentage-CBV change in cortical layers IV-V was 7.3 +/- 1.5%, which was significantly higher than in layers I-III (4.1 +/- 0.9%) and VI (4.3 +/- 0.7%) (mean +/- SEM). The laminar distribution of CBV response correlates well with neuronal activity localized by Fos expression. We conclude that neuronal activity can be inferred from CBV fMRI data with high spatial accuracy. The data indicate that both intracolumn functional connectivity and neurovascular coupling can be studied using CBV fMRI.

Animals↗

PubMed2004

Intravoxel distribution of DWI decay rates reveals C6 glioma invasion in rat brain.

The hypothesis was tested that the intravoxel distribution of water diffusion rates, as measured with a stretched-exponential model of diffusion-weighted imaging (DWI), is a marker of brain tumor invasion. Eight rats underwent intracerebral inoculation of C6 glioma cells. In three rats, cells were labeled with a fluorescent dye for microscopy. One rat was inoculated with a saline solution, and five more rats were imaged without inoculation as controls. Five healthy uninoculated rats were also imaged. DWI was performed 14-15 days after inoculation, with diffusion-weighting factor b = 500 to 6500 sec/mm2, and the resulting signal attenuation was fitted with the stretched-exponential model. The heterogeneity index values were significantly lower (P < 0.05) in the peritumor ROI than in normal gray matter and significantly higher than in normal white matter. The distributed diffusion coefficient values were significantly lower than in normal white matter or normal gray matter. Fluorescence microscopy confirmed the presence of tumors in the peritumor region that could be histologically distinguished from the main tumor mass. There was no change in proton density or T2-weighted images in the peritumor region, making vasogenic edema unlikely as a source of contrast. It is therefore thought that the heterogeneity parameter alpha is a marker of brain tumor invasion.

Animals↗

PubMed2003

Cerebral cortical representation of external anal sphincter contraction: effect of effort.

The external anal sphincter (EAS) plays a critical role in maintaining fecal continence; however, cerebral cortical control of voluntary EAS contraction is not completely understood. Our aims were to determine the cortical areas associated with voluntary EAS contraction and to determine the effect of two levels of sphincter contraction effort on brain activity. Seventeen asymptomatic adults (ages 21-48, 9 male) were studied using functional magnetic resonance imaging (fMRI) to detect brain activity. Studies were done in two stages. In stage 1 (10 subjects, 5 male), anal sphincter pressure was monitored from a catheter-affixed bag. Subjects performed maximal and submaximal EAS contractions during two fMRI scanning sessions consisting of alternating 10-s intervals of sustained contraction and rest. In stage 2 studies, seven subjects (4 male) performed only maximum effort sphincter contractions without a catheter. EAS contraction was associated with multifocal fMRI activity in sensory/motor, anterior cingulate, prefrontal, parietal, occipital, and insular regions. Total cortical activity volume was significantly larger (P < 0.05) for maximal (5,175 +/- 720 microl) compared with submaximal effort contractions (2,558 +/- 306 microl). Similarly, percent fMRI signal change was significantly higher (P < 0.05) for maximal (4.8 +/- 0.1%) compared with submaximal effort contractions (2.2 +/- 0.1%). Cortical region-of-interest analysis showed the incidence of insular activation to be more common in women compared with men. Other cortical regions showed no such gender differences. fMRI activity detected in stage 2 showed similar regions of cortical activation to those of the stage 1 study. Willful contraction of the EAS is associated with multifocal cerebral cortical activity. The volume and intensity of cerebral cortical activation is commensurate with the level of contractile effort.

Adult↗

PubMed2003

Molecular dynamics of 1-palmitoyl-2-oleoylphosphatidylcholine membranes containing transmembrane alpha-helical peptides with alternating leucine and alanine residues.

The effects of the transmembrane alpha-helical peptide Ac-K(2)(LA)(12)K(2)-amide [(LA)(12)] on the molecular organization and dynamics of 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) membranes were investigated using conventional and saturation-recovery EPR observations of phosphatidylcholine spin labels, and the results were compared with our earlier, similar study of Ac-K(2)L(24)K(2)-amide (L(24)) [Subczynski, W. K., Lewis, R. N. A. H., McElhaney, R. N., Hodges, R. S., Hyde, J. S., and Kusumi, A. (1998) Biochemistry 37, 3156-3164]. At peptide-to-POPC ratios between 1/10 and 1/40, both methods (covering a time scale of 100 ps-10 micros) detect the presence of a single homogeneous membrane environment for both peptides, suggesting that these peptides are both well dispersed and that POPC is exchanging rapidly between the boundary and the bulk domains. The local diffusion-solubility product of oxygen molecules (oxygen transport parameter) in the membrane, studied by saturation-recovery EPR, decreases by a factor of about 2 by including 10 mol % (LA)(12) whereas incorporating L(24) has practically no effect. (LA)(12) increases the alkyl chain order of POPC more than L(24). L(24) increases hydrophobicity (decreases the degree of water penetration into the hydrophobic region of the membrane) more than does (LA)(12). We ascribe the much stronger effects of (LA)(12) on membrane order and dynamics to the increased roughness of its hydrophobic surface and also to the increased motional freedom of its leucine side chains. In L(24), the leucine side chains are packed tightly, giving a smooth hydrophobic surface. In (LA)(12), they are separated by the small methyl groups of the alanine side chains, giving them additional motional freedom and the ability to protrude between the phospholipid hydrocarbon chains. The frequency of gauche-trans isomerization of hydrocarbon chains and concentration of vacant pockets (voids) in the lipid bilayer are thus reduced, which decreases oxygen transport. This explanation was confirmed by calculating the orientational order of leucine side chains in (LA)(12) and L(24) from molecular dynamics simulation studies.

Alanine↗

PubMed2003

Characterization of continuously distributed cortical water diffusion rates with a stretched-exponential model.

Experience with diffusion-weighted imaging (DWI) shows that signal attenuation is consistent with a multicompartmental theory of water diffusion in the brain. The source of this so-called nonexponential behavior is a topic of debate, because the cerebral cortex contains considerable microscopic heterogeneity and is therefore difficult to model. To account for this heterogeneity and understand its implications for current models of diffusion, a stretched-exponential function was developed to describe diffusion-related signal decay as a continuous distribution of sources decaying at different rates, with no assumptions made about the number of participating sources. DWI experiments were performed using a spin-echo diffusion-weighted pulse sequence with b-values of 500-6500 s/mm(2) in six rats. Signal attenuation curves were fit to a stretched-exponential function, and 20% of the voxels were better fit to the stretched-exponential model than to a biexponential model, even though the latter model had one more adjustable parameter. Based on the calculated intravoxel heterogeneity measure, the cerebral cortex contains considerable heterogeneity in diffusion. The use of a distributed diffusion coefficient (DDC) is suggested to measure mean intravoxel diffusion rates in the presence of such heterogeneity.

Animals↗

PubMed2003

Single-shot magnetic field mapping embedded in echo-planar time-course imaging.

A technique for acquiring magnetic field maps simultaneously with gradient-recalled echo-planar time-course data is described. This technique uses a trajectory in which the central part of k-space is collected twice. For a 64 x 64 image acquired with a 125-kHz bandwidth, a field map suitable for geometric correction can be collected simultaneously with the echo-planar time-course data in <70 ms. The field maps generated by this technique are registered with the magnitude images because they are calculated using the same data. They do not suffer from errors due to subject motion, or from different geometric distortions that can result from using different pulse sequences. In addition to correcting geometric distortions that resulted from dynamic magnetic field perturbations, this method was used to measure field shifts arising from respiration and jaw motion across five subjects. Values ranged from 0.035 to 0.165 parts per million (ppm).

Brain↗

PubMed2003

Multishot partial-k-space EPI for high-resolution fMRI demonstrated in a rat whisker barrel stimulation model at 3T.

A multishot partial-k-space EPI technique is presented and validated by fMRI at high spatial resolution. High-resolution phase maps corrected by phase-encoded reference scans have less off-resonance effects. Phantom studies demonstrate that this method can substantially improve partial-k-space EPI image formation. BOLD fMRI at submillimeter spatial resolution (156 x 156 x 2000 microm(3), 0.049 microl) was achieved in a rat whisker barrel stimulation model using this technique. The study included eight rats, five of which were administered an intravascular contrast agent (monocrystalline iron oxide nanocolloid (MION)) after the BOLD experiments. In two rats the highest BOLD responses were in the deep layers (IV-VI), and in six rats the highest responses were on the surface and in the deep cortical layers. Most of the pixels that exhibited high BOLD responses had high blood volume weightings. The benefits of this technique are expected to increase for high-resolution fMRI at higher magnetic fields, where T(2) (*) is shorter.

Animals↗

PubMed2003

Aqueous flat cells perpendicular to the electric field for use in electron paramagnetic resonance spectroscopy.

An analytic solution of the Maxwell equations for aqueous flat cells in rectangular TE(102) cavities has led to the prediction of significant (3-6 times) X-band EPR signal improvement over the standard flat cell for a new sample configuration consisting of many flat cells oriented perpendicular to the electric field nodal plane. Analytic full wave solutions in the presence of sample and wall losses have been obtained and numerically evaluated. Observation of the predicted fields led to a classification of three distinct types of sample loss mechanisms, which, in turn inspired sample designs that minimize each loss type. The resulting EPR signal enhancement is due to the presence and centering of a tangential electric field node within each individual sample region. Samples that saturate with the available RF magnetic field and those that do not are considered. Signal enhancement appears in both types. These observations, done for the TE(102) mode, carry over to the uniform field (UF) modes, a relatively new class of microwave cavities for use in EPR spectroscopy developed in this laboratory. Rectangular UF modes have an RF magnetic field magnitude that is uniform in a plane. Based on this analysis, a practical multiple flat-cell design is proposed.

Computer-Aided Design↗