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The Gordon coupler was introduced for use in EPR experiments at liquid helium temperatures. It provides an evanescent wave incident on the iris of a microwave resonator. Match of power incident on the coupler to the resonator is obtained by variation of the amplitude of an evanescent wave that arises from displacement of a dielectric wedge in a tapered waveguide. Reduced microphonics from helium bubbling was reported. The Gordon coupler was subsequently extended from cavity resonators to loop-gap resonators, initially at helium temperatures but later for aqueous samples. Plastics with low dielectric constants, usually Teflon, were used. Here, we extend the Gordon coupler for application in X-band five-loop-four-gap resonators using fused quartz, sapphire, or rutile dielectrics, noting that the size of the coupler can then be commensurate with dimensions of dielectric loop-gap resonators as well as dielectric tube resonators. Finite element modeling of electromagnetic fields has been carried out, and use of a capacitive iris that interfaces with the Gordon coupler reduces pulling of the resonant frequency when matching the resonator.

The stretched exponential function (SEF) was used to analyze and interpret saturation recovery (SR) electron paramagnetic resonance (EPR) data obtained from spin-labeled porcine eye-lens membranes. This function has two fitting parameters: the characteristic spin–lattice relaxation rate (T1str−1) and the stretching parameter (β), which ranges between zero and one. When β =1, the function is a single exponential. It is assumed that the SEF arises from a distribution of single exponential functions, each described by a T1 value. Because T 1 −1 s are determined primarily by the rotational diffusion of spin labels, they are a measure of membrane fluidity. Since β describes the distribution of T 1 −1 s, it can be interpreted as a measure of membrane heterogeneity. The SEF was used to analyze SR data obtained from intact cortical and nuclear fiber cell plasma membranes extracted from the eye lenses of 2-year-old animals and spin labeled with phospholipid and cholesterol analogs. The lipid environment sensed by these probe molecules was found to be less fluid and more heterogeneous in nuclear membranes than in cortical membranes. Parameters T 1str −1 and β were also used for a multivariate K-means cluster analysis of stretched exponential data. This analysis indicates that SEF data can be assigned accurately to clusters in nuclear or cortical membranes. In future work, the SEF will be applied to analyze data from human eye lenses of donors with differing health histories.

The hypothesis is made that the dispersion electron paramagnetic resonance (EPR) spectrum can yield a higher signal-to-noise ratio than the absorption spectrum in diagnostic examinations if phase noise in the bridge is under control. The rationale for this hypothesis is based on the observation that the dispersion spectrum becomes more intense than the absorption spectrum at high incident powers. The rationale is dependent on optimization of high microwave efficiency (Λ; mT/W1/2) and low-quality factor (Q-value) sample resonators as well as the use of microwave sources with reduced phase noise. Microwave frequencies from 1.2 to 94 GHz are considered. Although the dispersion display appears to be observable with an adequate signal-to-noise ratio for most EPR research initiatives, a weakness of microwave bridges for studies at high incident microwave power was identified. Spurious leakage of incident microwave power through the circulator, thereby bypassing the probe leading to the resonator, can result in a decreased signal-to-noise ratio in both absorption and dispersion because of phase noise. For dispersion EPR with low Q-value sample resonators, this leakage is the primary contributor to phase noise at the receiver. In this work, we focus on the design of microwave reflection bridges and discuss possible methods to ameliorate this source of noise.

The papers, book chapters, reviews, and patents by James S. Hyde in the bibliography of this document have been separated into EPR and MRI sections, and within each section by topics. Within each topic, publications are listed chronologically. A brief summary is provided for each patent listed. A few publications and patents that do not fit this schema have been omitted. This list of publications is preceded by a scientific autobiography that focuses on selected topics that are judged to have been of most scientific importance. References to many of the publications and patents in the bibliography are made in the autobiography.

The dielectric tube resonator (DTR) for electron paramagnetic resonance spectroscopy is introduced. It is defined as a metallic cylindrical TE011 microwave cavity that contains a dielectric tube centered on the axis of the cylinder. Contour plots of dimensions of the metallic cylinder to achieve resonance at 9.5 GHz are shown for quartz, sapphire, and rutile tubes as a function of wall thickness and average radius. These contour plots were developed using analytical equations and confirmed by finite-element modeling. They can be used in two ways: design of the metallic cylinder for use at 9.5 GHz that incorporates a readily available tube such as a sapphire tube intended for NMR and design of a custom procured tube for optimized performance for specific sample-size constraints. The charts extend to the limiting condition where the dielectric fills the tube. However, the structure at this limit is not a dielectric resonator due to the metal wall and does not radiate. In addition, the uniform field (UF) DTR is introduced. Development of the UF resonator starting with a DTR is shown. The diameter of the tube remains constant along the cavity axis, and the diameter of the cylindrical metallic enclosure increases at the ends of the cavity to satisfy the uniform field condition. This structure has advantages over the previously developed UF TE011 resonators: higher resonator efficiency parameter Λ, convenient overall size when using sapphire tubes, and higher quality data for small samples. The DTR and UF DTR structures fill the gap between free space and dielectric resonator limits in a continuous manner.

In this work we present the design and implementation of two uniform-field resonators: a seven-loop-six-gap loop-gap resonator (LGR) and a rectangular TEU02 cavity resonator. Each resonator has uniform-field-producing end-sections. These resonators have been designed for electron paramagnetic resonance (EPR) of aqueous samples at 94GHz. The LGR geometry employs low-loss Rexolite end-sections to improve the field homogeneity over a 3mm sample region-of-interest from near-cosine distribution to 90% uniform. The LGR was designed to accommodate large degassable Polytetrafluorethylen (PTFE) tubes (0.81mm O.D.; 0.25mm I.D.) for aqueous samples. Additionally, field modulation slots are designed for uniform 100kHz field modulation incident at the sample. Experiments using a point sample of lithium phthalocyanine (LiPC) were performed to measure both the uniformity of the microwave magnetic field and 100kHz field modulation, and confirm simulations. The rectangular TEU02 cavity resonator employs over-sized end-sections with sample shielding to provide an 87% uniform field for a 0.1×2×6mm3 sample geometry. An evanescent slotted window was designed for light access to irradiate 90% of the sample volume. A novel dual-slot iris was used to minimize microwave magnetic field perturbations and maintain cross-sectional uniformity. Practical EPR experiments using the application of light irradiated rose bengal (4,5,6,7-tetrachloro-2',4',5',7'-tetraiodofluorescein) were performed in the TEU02 cavity. The implementation of these geometries providing a practical designs for uniform field resonators that continue resonator advancements towards quantitative EPR spectroscopy.

This paper builds on the work of Mett and Hyde [J. Magn. Reson. 165 (2003) p.137] and Sidabras, Mett, and Hyde [J. Magn. Reson. 172 (2005) p.333] where multiple flat aqueous sample cells placed perpendicular to electric fields in microwave cavities were used to reduce the rf losses and increase the EPR signal. In this work, we present three novel sample holders for loop-gap resonators (LGRs) and cylindrical cavity geometries. Two sample holders have been commissioned and built by polytetrafluoroethylene (PTFE) extrusion techniques: a 1 mm O.D. capillary with a septum down the middle, named DoubleDee, and a 3.5 mm O.D. star shaped sample holder, named AquaStar. Simulations and experimental results at X-band show that the EPR signal intensity increases by factors of 1.43 and 3.87 in the DoubleDee and AquaStar respectively, over the current TPX 0.9 mm O.D. sample tube in a two-loop–one-gap LGR. Finally, combining the insight gained from the constructed sample holders and finite-element solutions, a third multi-lumen sample holder for a cylindrical TE011 cavity is optimized, named AquaSun, where simulations show an EPR signal intensity increase by a factor of 8.2 over a standard 1 mm capillary.

In continuous-wave (CW) Electron Paramagnetic Resonance (EPR) a low-frequency time-harmonic magnetic field, called field modulation, is applied parallel to the static magnetic field and incident on the sample. Varying amplitude of the field modulation incident on the sample has consequences on spectral line-shape and line-height over the axis of the sample. Here we present a method of coupling magnetic field into the cavity using slots perpendicular to the sample axis where the slot depths are designed in such a way to produce an axially uniform magnetic field along the sample. Previous literature typically assumes a uniform cross-section and axial excitation due to the wavelength of the field modulation being much larger than the cavity. Through numerical analysis and insights obtained from the eigenfunction expansion of dyadic Green’s functions, it is shown that evanescent standing-wave modes with complex cross-sections are formed within the cavity. From this analysis, a W-band (94 GHz) cylindrical cavity is designed where modulation slots are optimized to present a uniform 100 kHz field modulation over the length of the sample.

Non-adiabatic rapid passage (NARS) electron paramagnetic resonance (EPR) spectroscopy was introduced by Kittell, A.W., Camenisch, T.G., Ratke, J.J. Sidabras, J.W., Hyde, J.S., 2011 as a general purpose technique to collect the pure absorption response. The technique has been used to improve sensitivity relative to sinusoidal magnetic field modulation, increase the range of inter-spin distances that can be measured under near physiological conditions, and enhance spectral resolution in copper (II) spectra. In the present work, the method is extended to CW microwave power saturation of spin-labeled T4 Lysozyme (T4L). As in the cited papers, rapid triangular sweep of the polarizing magnetic field was superimposed on slow sweep across the spectrum. Adiabatic rapid passage (ARP) effects were encountered in samples undergoing very slow rotational diffusion as the triangular magnetic field sweep rate was increased. The paper reports results of variation of experimental parameters at the interface of adiabatic and non-adiabatic rapid sweep conditions. Comparison of the forward (up) and reverse (down) triangular sweeps is shown to be a good indicator of the presence of rapid passage effects. Spectral turning points can be distinguished from spectral regions between turning points in two ways: differential microwave power saturation and differential passage effects. Oxygen accessibility data are shown under NARS conditions that appear similar to conventional field modulation data. However, the sensitivity is much higher, permitting, in principle, experiments at substantially lower protein concentrations. Spectral displays were obtained that appear sensitive to rotational diffusion in the range of rotational correlation times of 10−3 to 10−7 s in a manner that is analogous to saturation transfer spectroscopy.

This study validated the use of small unilamellar vesicles (SUVs) made of 1-palmitoyl-2-oleoylphosphatidylcholine with 1 mol % spin label of 1-palmitoyl-2-(16-doxylstearoyl)phosphatidylcholine (16-PC) as an oxygen-sensitive analyte to study cellular respiration. In the analyte, the hydrocarbon environment surrounds the nitroxide moiety of 16-PC. This ensures high oxygen concentration and oxygen diffusion at the location of the nitroxide as well as isolation of the nitroxide moiety from cellular reductants and paramagnetic ions that might interfere with spin-label oximetry measurements. The saturation-recovery electron paramagnetic resonance approach was applied in the analysis since this approach is the most direct method to carry out oximetric studies. It was shown that this display (spin–lattice relaxation rate) is linear in oxygen partial pressure up to 100 % air (159 mmHg). Experiments using a neuronal cell line in suspension were carried out at X-band for closed-chamber geometry. Oxygen consumption rates showed a linear dependence on the number of cells. Other significant benefits of the analyte are: the fast effective rotational diffusion and slow translational diffusion of the spin-probe is favorable for the measurements, and there is no cross-reactivity between oxygen and paramagnetic ions in the lipid bilayer.

The presence of integral membrane proteins induces the formation of distinct domains in the lipid bilayer portion of biological membranes. Qualitative application of both continuous wave (CW) and saturation recovery (SR) electron paramagnetic resonance (EPR) spin-labeling methods allowed discrimination of the bulk, boundary, and trapped lipid domains. A recently developed method, which is based on the CW EPR spectra of phospholipid (PL) and cholesterol (Chol) analog spin labels, allows evaluation of the relative amount of PLs (% of total PLs) in the boundary plus trapped lipid domain and the relative amount of Chol (% of total Chol) in the trapped lipid domain [M. Raguz, L. Mainali, W. J. O'Brien, and W. K. Subczynski (2015), Exp. Eye Res., 140:179-186]. Here, a new method is presented that, based on SR EPR spin-labeling, allows quantitative evaluation of the relative amounts of PLs and Chol in the trapped lipid domain of intact membranes. This new method complements the existing one, allowing acquisition of more detailed information about the distribution of lipids between domains in intact membranes. The methodological transition of the SR EPR spin-labeling approach from qualitative to quantitative is demonstrated. The abilities of this method are illustrated for intact cortical and nuclear fiber cell plasma membranes from porcine eye lenses. Statistical analysis (Student's t-test) of the data allowed determination of the separations of mean values above which differences can be treated as statistically significant (P ≤ 0.05) and can be attributed to sources other than preparation/technique.

In this work we present the design and implementation of two uniform-field resonators: a seven-loop–six-gap loop-gap resonator (LGR) and a rectangular TEU02 cavity resonator. Each resonator has uniform-field-producing end-sections. These resonators have been designed for electron paramagnetic resonance (EPR) of aqueous samples at 94 GHz. The LGR geometry employs low-loss Rexolite end-sections to improve the field homogeneity over a 3 mm sample region-of-interest from near-cosine distribution to 90% uniform. The LGR was designed to accommodate large degassable Polytetrafluorethylen (PTFE) tubes (0.81 mm O.D.; 0.25 mm I.D.) for aqueous samples. Additionally, field modulation slots are designed for uniform 100 kHz field modulation incident at the sample. Experiments using a point sample of lithium phthalocyanine (LiPC) were performed to measure both the uniformity of the microwave magnetic field and 100 kHz field modulation, and confirm simulations. The rectangular TEU02 cavity resonator employs over-sized end-sections with sample shielding to provide an 87% uniform field for a 0.1 × 2 × 6 mm3 sample geometry. An evanescent slotted window was designed for light access to irradiate 90% of the sample volume. A novel dual-slot iris was used to minimize microwave magnetic field perturbations and maintain cross-sectional uniformity. Practical EPR experiments using the application of light irradiated rose bengal (4,5,6,7-tetrachloro-2′,4′,5′,7′-tetraiodofluorescein) were performed in the TEU02 cavity. The implementation of these geometries providing a practical designs for uniform field resonators that continue resonator advancements towards quantitative EPR spectroscopy.

Experimental results have been reported on an oversize rectangular waveguide assembly operating nominally at 94 GHz. It was formed using commercially available WR28 waveguide as well as a pair of specially designed tapers with a hyperbolic-cosine shape from WR28 to WR10 waveguide [R. R. Mett et al., Rev. Sci. Instrum. 82, 074704 (2011)]. The oversize section reduces broadband insertion loss for an Electron Paramagnetic Resonance (EPR) probe placed in a 3.36 T magnet. Hyperbolic-cosine tapers minimize reflection of the main mode and the excitation of unwanted propagating waveguide modes. Oversize waveguide is distinguished from corrugated waveguide, overmoded waveguide, or quasi-optic techniques by minimal coupling to higher-order modes. Only the TE10 mode of the parent WR10 waveguide is propagated. In the present work, a new oversize assembly with a gradual 90° twist was implemented. Microwave power measurements show that the twisted oversize waveguide assembly reduces the power loss in the observe and pump arms of a W-band bridge by an average of 2.35 dB and 2.41 dB, respectively, over a measured 1.25 GHz bandwidth relative to a straight length of WR10 waveguide. Network analyzer measurements confirm a decrease in insertion loss of 2.37 dB over a 4 GHz bandwidth and show minimal amplitude distortion of approximately 0.15 dB. Continuous wave EPR experiments confirm these results. The measured phase variations of the twisted oversize waveguide assembly, relative to an ideal distortionless transmission line, are reduced by a factor of two compared to a straight length of WR10 waveguide. Oversize waveguide with proper transitions is demonstrated as an effective way to increase incident power and the return signal for broadband EPR experiments. Detailed performance characteristics, including continuous wave experiment using 1 μM 2,2,6,6-tetramethylpiperidine-1-oxyl in aqueous solution, provided here serve as a benchmark for other broadband low-loss probes in millimeter-wave EPR bridges.

The somatosensory functional magnetic resonance imaging (fMRI) response to electrical stimulation of the middle phalange of the second digit of four rats at a spatial resolution of 200 μm cubic at 9.4 T is reported. At high threshold (p

Resting state functional connectivity magnetic resonance imaging studies in rat brain show brain reorganization caused by nerve injury and repair. In this study, distinguishable differences were found in healthy, nerve transection without repair (R−) and nerve transection with repair (R+) groups in the subacute stage (2 weeks after initial injury). Only forepaw on the healthy side was used to determine seed voxel regions in this study. Disturbance of neuronal network in the primary sensory region of cortex occurs within two hours after initial injury, and the network pattern was restored in R+ group in subacute stage, while the disturbed pattern remained in R− group. These are the central findings of the study. This technique provides a novel way of detecting and monitoring the effectiveness of peripheral nerve injury treatment in the early stage and potentially offers a tool for clinicians to avoid poor clinical outcomes.

A novel inductively coupled coil pair was used to obtain magnetic resonance phantom images. Rationale for using such a structure is described in R. R. Mett et al. [Rev. Sci. Instrum. 87, 084703 (2016)]. The original rationale was to increase the Q-value of a small diameter surface coil in order to achieve dominant loading by the sample. A significant improvement in the vector reception field (VRF) is also seen. The coil assembly consists of a 3-turn 10 mm tall meta-metallic self-resonant spiral (SRS) of inner diameter 10.4 mm and outer diameter 15.1 mm and a single-loop equalization coil of 25 mm diameter and 2 mm tall. The low-frequency parallel mode was used in which the rf currents on each coil produce magnetic fields that add constructively. The SRS coil assembly was fabricated and data were collected using a tissue-equivalent 30% polyacrylamide phantom. The large inductive coupling of the coils produces phase-coherency of the rf currents and magnetic fields. Finite-element simulations indicate that the VRF of the coil pair is about 4.4 times larger than for a single-loop coil of 15 mm diameter. The mutual coupling between coils influences the current ratio between the coils, which in turn influences the VRF and the signal-to-noise ratio (SNR). Data on a tissue-equivalent phantom at 9.4 T show a total SNR increase of 8.8 over the 15 mm loop averaged over a 25 mm depth and diameter. The experimental results are shown to be consistent with the magnetic resonance theory of the emf induced by spins in a coil, the theory of inductively coupled resonant circuits, and the superposition principle. The methods are general for magnetic resonance and other types of signal detection and can be used over a wide range of operating frequencies.

The performance of a metallic microwave resonator that contains a dielectric depends on the separation between metallic and dielectric surfaces, which affects radio frequency currents, evanescent waves, and polarization charges. The problem has previously been discussed for an X-band TE(011) cylindrical cavity resonator that contains an axial dielectric tube [J. S. Hyde and R. R. Mett, Appl. Magn. Reson. 48, 1185–1204 (2017)]. Here, a short rutile dielectric tube inserted into a loop-gap resonator (LGR) at X-band, which is called a dielectric LGR (dLGR), is considered. The theory is developed and experimental results are presented. It was found that a central sample loop surrounded by four “flux-return” loops (i.e., 5-loop–4-gap) is preferable to a 3-loop–2-gap configuration. For sufficiently small samples (less than 1 μL), a rutile dLGR is preferred relative to an LGR both at constant Λ ([Formula: see text]) and at constant incident power. Introduction of LGR technology to X-band EPR was a significant advance for site-directed spin labeling because of small sample size and high Λ. The rutile dLGR introduced in this work offers further extension to samples that can be as small as 50 nLwhen using typical EPR acquisition times.

Non-adiabatic rapid sweep (NARS) EPR spectroscopy has been introduced for application to nitroxide-labeled biological samples (Kittell et al., 2011) [1] . Displays are pure absorption, and are built up by acquiring data in spectral segments that are concatenated. In this paper we extend the method to frozen solutions of copper-imidazole, a square planar copper complex with four in-plane nitrogen ligands. Pure absorption spectra are created from concatenation of 170 5-gauss segments spanning 850 G at 1.9 GHz. These spectra, however, are not directly useful since nitrogen superhyperfine couplings are barely visible. Application of the moving difference (MDIFF) algorithm to the digitized NARS pure absorption spectrum is used to produce spectra that are analogous to the first harmonic EPR. The signal intensity is about four times higher than when using conventional 100 kHz field modulation, depending on line shape. MDIFF not only filters the spectrum, but also the noise, resulting in further improvement of the SNR for the same signal acquisition time. The MDIFF amplitude can be optimized retrospectively, different spectral regions can be examined at different amplitudes, and an amplitude can be used that is substantially greater than the upper limit of the field modulation amplitude of a conventional EPR spectrometer, which improves the signal-to-noise ratio of broad lines.

The goal of this work was to increase the level of acceleration using multiband excitation pulses as described in Refs. (1) and (2). These pulses reduce the time needed to acquire a single volumetric gradient-recalled echo-planar image of the brain. Multichannel coils are used to separate overlapping slices as described in Refs. (3–5). In an abstract in 2009 (1), we showed that the number of receivers can be reduced when the relative phases of excited slices are set properly. In addition, it was shown that a single receiver channel is sufficient for 2-fold acceleration when the relative phase of slices is set to 90°. The thrust of this paper is improved formation of multiband excitation pulses, which has not been explicitly considered in previous publications in the field. The standard gradient-echo (GE) eight-channel receive-only high-resolution brain array coil was used for publications (1) and (2). Accelerations greater than two were reported in Ref. (1), but separated images were of lower quality. In this work, the presence of ghost slices of low amplitude for spectral separations larger than 50 kHz was observed. Ghosts were visible on images of a ball-shaped phantom due to different diameters of cross sections. It was concluded that the limit of the eight-channel system had been reached. After updating the acquisition system to 32 channels, these experiments were repeated. Two different 32-channel receive-only coils were evaluated. To our surprise, at 4-fold acceleration the separated images with 32 and eight channels showed similar poor quality. Ghost slices remained visible. Development of a different method of radiofrequency (RF) pulse creation rather than the Fourier transform approximation was considered (6). First, however, RF pulses were produced and observed with a pickup loop placed in the magnet, which immediately revealed the source of the problem. Figure 1a shows a spectral profile of a pulse created by the standard modulator of the GE Signa EXCITE 3T scanner. The two main ghost slices on either side of four prescribed slices have amplitudes of 36%. These cause significant interference in the separated images because reference slices that are used in the separation algorithm do not include these ghosts. There are other ghosts of lower amplitudes in the spectrum, which also disrupt the separation. The spectrum of the same pulse played on the GE MR750 3T scanner is shown in Figure 1b. It is better but two main ghosts exhibit amplitudes of 9% and several lower amplitude ghosts are also visible. FIG. 1 Four-fold multiband spectral profiles created by: (a) the GE 3-T Signa EXCITE original modulator; (b) the GE 3-T MRI750 original modulator; and (c) the Pentek 78621 16-bit digital waveform synthesizer. The algorithm used to create tailored pulses produces two digital arrays, one with amplitude data (14 bits) and one with phase (12 bits) data, which are loaded to a transceiver processor and storage exciter in 2-μs increments in the GE Signa EXCITE system. A pulse simulation program showed that even when applying high nonlinearities to the amplitude and phase, distortions as seen in Figure 1a cannot be obtained. However, when phase data were shifted by 3 μs against the amplitude data, the simulator replicated the pattern of Figure 1a. Correction of this behavior requires a shift of digital phase data by 3 μs on hardware with 2-μs update time only. The Fourier transform shift theorem was implemented in the magnetic resonance imaging (MRI) sequence and artifacts were minimized when using a 3-μs shift. The same sequence when played on the MR750 system showed the best result at a 0-μs shift, which leads to the conclusion that although the MR750 is improved, a flaw remains in the system. In spite of the fact that the spectrum is better than the corrected one on the EXCITE system, as seen in Figure 1b, it was still judged to be inadequate. To improve the spectral quality of RF pulses, a Pentek Waveform Playback PCIe card model 78621 (Upper Saddle River, NJ), which is based on the Texas Instrument DAC5688 chip, was evaluated. This card is controlled by a Virtex-6 FPGA (field-programmable gate array) and is mainly intended to produce radar beams. This card can be synchronized with others of the same type. It has absolute phase accuracy and timing required for varying radar beams without the need for antenna rotation. In the interpolate mode, the D/A converter of this card creates RF pulses with a 2-ns sampling time as well as smooth, stair-step-less modulation of the I and Q channels at a 16-bit resolution. As a result, the spectral quality of an RF pulse created with the same algorithm as pulses in Figure 1a is better as shown in Figure 1c. The same power transmitter and pickup loop were used to acquire RF pulses for all images. Figure 2 shows several excerpts of RF pulses produced by different modulators and acquired by an Agilent digital oscilloscope DOS6104A. Figure 2a shows the central 1.2-ms region of a 6.4-ms RF pulse. Three other frames: b, c, and d show the short part of the pulse in frame 1 marked by green color. Stair steps of RF modulation are clearly visible for both 3-T Signa EXCITE and MR750 scanners. There are no such steps in the pulse created by the Pentek 78621 card. The spectrum of the pulse created by the DAC5688 chip as seen in Figure 1c has at least two orders of magnitude lower out-of-slice excitations compared with the spectrum of Figure 1a. Ghost slices are not evident. For comparison, the simulation of an ideal stair-step modulation showed harmonics far away from the central spectrum, which do not excite protons inside the imaging object. It is hypothesized that the rounding of steps, as seen in Figure 2d, is the source of the ghost artifacts seen in Figure 1b. FIG. 2 Oscillograms of RF pulses obtained by different modulators: (a) the central region of a 6.4-ms long RF pulse at a resolution of 200 μs/cm. The 12-μs segment marked by green is expanded in other windows at a resolution of 2 μs/cm; ... The unprecedented spectral phase quality and time-course stability of pulses obtained using the DAC5688 chip have another benefit. The 90° RF pulses used in standard two-dimensional MRI methods were programmed to achieve interslice phase coherency that is usually lost because of frequency offsets from the central Larmor frequency. The benefit of this technology becomes more important with increase in the magnetic field of whole-body MRI scanners where phase images of the brain (7,8) carry more information than amplitude images. With phase alignment between all two-dimensional slices, consistent phase analysis in three dimensions can be carried out without the need for additional (and rather long) three-dimensional acquisition. Moreover, in the realm of echo-planar imaging, especially at high resolution, phase contrast in an arbitrary oblique plane can be obtained by postprocessing the full set of phase coherent slices. Another benefit of the DAC5688 chip was discovered. The phase stability is so high that it is no longer necessary to use a phase reference in the receiver. This was an incidental finding that is not central to the paper. Images with and without a reference were compared.

Conventional and saturation-recovery (SR) EPR at W-band (94GHz) using phosphatidylcholine spin labels (labeled at the alkyl chain [n-PC] and headgroup [T-PC]) to obtain profiles of membrane fluidity has been demonstrated. Dimyristoylphosphatidylcholine (DMPC) membranes with and without 50 mol% cholesterol have been studied, and the results have been compared with similar studies at X-band (9.4 GHz) (L. Mainali, J.B. Feix, J.S. Hyde, W.K. Subczynski, J. Magn. Reson. 212 (2011) 418-425). Profiles of the spin-lattice relaxation rate (T(1)(-1)) obtained from SR EPR measurements for n-PCs and T-PC were used as a convenient quantitative measure of membrane fluidity. Additionally, spectral analysis using Freed's MOMD (microscopic-order macroscopic-disorder) model (E. Meirovitch, J.H. Freed J. Phys. Chem. 88 (1984) 4995-5004) provided rotational diffusion coefficients (R(perpendicular) and R(||)) and order parameters (S(0)). Spectral analysis at X-band provided one rotational diffusion coefficient, R(perpendicular). T(1)(-1), R(perpendicular), and R(||) profiles reflect local membrane dynamics of the lipid alkyl chain, while the order parameter shows only the amplitude of the wobbling motion of the lipid alkyl chain. Using these dynamic parameters, namely T(1)(-1), R(perpendicular), and R(||), one can discriminate the different effects of cholesterol at different depths, showing that cholesterol has a rigidifying effect on alkyl chains to the depth occupied by the rigid steroid ring structure and a fluidizing effect at deeper locations. The nondynamic parameter, S(0), shows that cholesterol has an ordering effect on alkyl chains at all depths. Conventional and SR EPR measurements with T-PC indicate that cholesterol has a fluidizing effect on phospholipid headgroups. EPR at W-band provides more detailed information about the depth-dependent dynamic organization of the membrane compared with information obtained at X-band. EPR at W-band has the potential to be a powerful tool for studying membrane fluidity in samples of small volume, ~30 nL, compared with a representative sample volume of ~3 μL at X-band.

Functional MRI (fMRI) studies have demonstrated that a number of brain regions (cingulate, insula, prefrontal, and sensory/motor cortices) display blood oxygen level-dependent (BOLD) positive activity during swallow. Negative BOLD activations and reproducibility of these activations have not been systematically studied. The aim of our study was to investigate the reproducibility of swallow-related cortical positive and negative BOLD activity across different fMRI sessions. We studied 16 healthy volunteers utilizing an fMRI event-related analysis. Individual analysis using a general linear model was used to remove undesirable signal changes correlated with motion, white matter, and cerebrospinal fluid. The group analysis used a mixed-effects multilevel model to identify active cortical regions. The volume and magnitude of a BOLD signal within each cluster was compared between the two study sessions. All subjects showed significant clustered BOLD activity within the known areas of cortical swallowing network across both sessions. The cross-correlation coefficient of percent fMRI signal change and the number of activated voxels across both positive and negative BOLD networks were similar between the two studies ( r ≥ 0.87, P < 0.0001). Swallow-associated negative BOLD activity was comparable to the well-defined “default-mode” network, and positive BOLD activity had noticeable overlap with the previously described “task-positive” network. Swallow activates two parallel cortical networks. These include a positive and a negative BOLD network, respectively, correlated and anticorrelated with swallow stimulus. Group cortical activity maps, as well as extent and amplitude of activity induced by volitional swallowing in the cortical swallowing network, are reproducible between study sessions.

Site-directed spin-labeling electron paramagnetic resonance (SDSL EPR) provides insight into the local structure and motion of a spin probe strategically attached to a molecule. When a second spin is introduced to the system, macromolecular information can be obtained through measurement of inter-spin distances either by continuous wave (CW) or pulsed electron double resonance (ELDOR) techniques. If both methodologies are considered, inter-spin distances of 8–80 A can be experimentally determined. However, there exists a region at the upper limit of the conventional X-band (9.5 GHz) CW technique and the lower limit of the four-pulse double electron–electron resonance (DEER) experiment where neither method is particularly reliable. The work presented here utilizes L-band (1.9 GHz) in combination with non-adiabatic rapid sweep (NARS) EPR to address this opportunity by increasing the upper limit of the CW technique. Because L-band linewidths are three to seven times narrower than those at X-band, dipolar broadenings that are small relative to the X-band inhomogeneous linewidth become observable, but the signal loss, due to the frequency dependence of the Boltzmann factor, has made L-band especially challenging. NARS has been shown to increase sensitivity by a factor of five, and overcomes much of this loss, making L-band distance determination more feasible [1] . Two different systems are presented, and distances of 18–30 A have been experimentally determined at physiologically relevant temperatures. Measurements are in excellent agreement with a helical model and values determined by DEER.

The purpose of this study is to develop a rodent functional magnetic resonance imaging (fMRI) survival model with the use of heparin-coated vascular access devices. Such a model would ease the administration of sedative agents, reduce the number of animals required in a survival experiment, and eliminate animal-to-animal variability seen in previous designs. Seven male Sprague-Dawley rats underwent surgical placement of an MRI-compatible vascular access port, followed by implantable electrode placement on the right median nerve. Functional MRI during nerve stimulation and resting-state functional connectivity MRI (fcMRI) were performed at times 0, 2, 4, 8, and 12 weeks postoperatively using a 9.4 T scanner. Anesthesia was maintained using intravenous dexmedetomidine and reversed using atipamezole. There were no fatalities or infectious complications during this study. All vascular access ports remained patent. Blood oxygen level dependent (BOLD) activation by electrical stimulation of the median nerve using implanted electrodes was seen within the forelimb sensory region (S1FL) for all animals at all time points. The number of activated voxels decreased at time points 4 and 8 weeks, returning to a normal level at 12 weeks, which is attributed to scar tissue formation and resolution around the embedded electrode. The applications of this experiment extend far beyond the scope of peripheral nerve experimentation. These vascular access ports can be applied to any survival MRI study requiring repeated medication administration, intravenous contrast, or blood sampling.

Spin-lattice relaxation times (T1s) of both small water-soluble spin labels in the aqueous phase as well as lipid-type spin labels in membranes increase when the microwave frequency increases from 2 to 35 GHz (Hyde et al., J. Phys. Chem. B 108 [2004] 9524–9529). The T1 measured at W-band (94 GHz) for the water-soluble spin labels CTPO and TEMPONE (Froncisz et al., J. Magn. Reson. 193 [2008] 297–304) is, however, shorter than when measured at Q-band (35 GHz). In this paper, the decreasing trends at W-band have been confirmed for commonly used lipid-type spin labels in model membranes. It is concluded that the longest values of T1 will generally be found at Q-band, noting that long values are advantageous for measurement of bimolecular collisions with oxygen. The contribution of dissolved molecular oxygen to the relaxation rate was found to be independent of microwave frequency up to 94 GHz for lipid-type spin labels in membranes. This contribution is expressed in terms of the oxygen transport parameter W = T1−1(Air) − T1−1(N2), which is a function of both concentration and translational diffusion of oxygen in the local environment of a spin label. The new capabilities in measurement of the oxygen transport parameter using saturation-recovery (SR) EPR at Q- and W-band have been demonstrated in saturated (DMPC) and unsaturated (POPC) lipid bilayer membranes with the use of stearic acid (n-SASL) and phosphatidylcholine (n-PC) spin labels, and compared with results obtained earlier at X-band. SR EPR spin-label oximetry at Q- and W-band has the potential to be a powerful tool for studying samples of small volume, ~30 nL. These benefits, together with other factors such as a higher resonator efficiency parameter and a new technique for canceling free induction decay signals, are discussed.

Background Since the 1980s, the C7 nerve root has gained clinical relevance as a donor nerve in severe brachial plexus root avulsion injuries. Despite success with the cross-chest C7 nerve transfer, inducing injury on an otherwise normal side hinders global acceptance. By sacrificing the C7 nerve root, a predictable pattern of transient sequelae is seen, including extensor weakness and index and middle finger anesthesia. The purpose of this study is to observe cortical activity during direct stimulation of the C7 nerve root using blood oxygen level dependent functional magnetic resonance imaging (fMRI) in a rat model. Methods A total of 12 male Sprague-Dawley rats, weighing 200–250 g, were used in this study. Following an acclimation period of 1 week, 12 rats underwent exposure and dissection of the brachial plexus. Seven rats underwent placement of an implantable electrode (AISI 304, Plastics1, Roanoke, VA, USA) on the C7 nerve root, while five rats underwent electrode placement on the radial nerve. All animals then underwent fMRI during direct nerve stimulation. Ten consecutive coronal images were obtained during nerve stimulation, using a 9.4-T small-animal MRI scanner. Results Cortical activation is seen within a very specific area of the primary sensory region of the forelimb during C7 nerve root stimulation. The cortical activation seen during radial nerve stimulation includes that seen during C7 stimulation but extends several slices caudally. Conclusions The sensory representation of the C7 nerve root is seen in only a small area in the S1FL region compared to that seen in the terminal branches of the brachial plexus. However, this area shows a significant overlap with the S1FL area of activation seen during radial nerve stimulation. This makes sense as the C7 nerve root contributes some, but not all, sensory axons to the radial nerve. Mapping of the C7 cortical representation in the rat brain not only adds to the ongoing development of the motor and sensory ratunculus but also provides an important foundation to study subsequent C7 donor nerve models.

Whole brain functional connectivity magnetic resonance imaging requires acquisition of a time course of gradient-recalled (GR) volumetric images. A method is developed to accelerate this acquisition using GR echo-planar imaging and radio frequency (RF) slice phase tagging. For N-fold acceleration, a tailored RF pulse excites N slices using a uniform-field transmit coil. This pulse is the Fourier transform of the profile for the N slices with a predetermined RF phase tag on each slice. A multichannel RF receive coil is used for detection. For n slices, there are n/N groups of slices. Signal-averaged reference images are created for each slice within each slice group for each member of the coil array and used to separate overlapping images that are simultaneously received. The time-overhead for collection of reference images is small relative to the acquisition time of a complete volumetric time course. A least-squares singular value decomposition method allows image separation on a pixel-by-pixel basis. Twofold slice acceleration is demonstrated using an eight-channel RF receive coil, with application to resting-state functional magnetic resonance imaging in the human brain. Data from six subjects at 3 T are reported. The method has been extended to half k-space acquisition, which not only provides additional acceleration, but also facilitates slice separation because of increased signal intensity of the central lines of k-space coupled with reduced susceptibility effects.

A better understanding of the central control of the physiology of deglutition is necessary for devising interventions aimed at correcting pathophysiological conditions of swallowing. Positive modulation of the cortical swallowing network can have clinical ramifications in dysphagia due to central nervous system deficits. Our aim was to determine the effect of nutritive sensory input on the cortical swallowing network. In 14 healthy right-handed volunteers, we utilized a paradigm-driven protocol to quantify the number of activated voxels and their signal intensity within the left hemispheric cortical swallowing network by high-resolution functional MRI (fMRI) during five different swallowing conditions. Swallowing conditions included a dry swallow (saliva) and natural water-, lemon-, popcorn-, and chocolate-flavored liquid swallows. Each flavored liquid was presented simultaneously by its image, scent, and taste in random order and tested over three runs. fMRIs were analyzed in a blinded fashion. Average fMRI blood oxygenation level-dependent signal intensity and number of activated voxels during swallowing concurrent with nutritive gustatory, olfactory, and visual stimulations were significantly increased compared with dry/natural water swallows throughout the cortical swallowing network ( P < 0.001 and P < 0.05, respectively). Subregion analysis showed the increased activity for flavored liquids in prefrontal, cingulate gyrus, and sensory/motor cortex, but not in precuneus and insula. Concurrent gustatory, olfactory, and visual nutritive stimulation enhances the activity of the cortical swallowing network. This finding may have clinical implications in management of swallowing disorders due to cortical lesions.

Functional connectivity magnetic resonance imaging (fcMRI) studies in rat brain show brain reorganization following peripheral nerve injury. Subacute neuroplasticity was observed two weeks following transection of the four major nerves of the brachial plexus. Direct functional magnetic resonance imaging (fMRI) stimulation of the intact radial nerve reveals an activation pattern in the forelimb regions of the sensory and motor cortices that is significantly different from that observed in normal rats. Results of this fMRI experiment were used to determine seed voxel regions for fcMRI analysis. Intrahemispheric connectivities in the sensorimotor forelimb representations in both hemispheres are largely unaffected by deafferentation, whereas substantial disruption of interhemispheric sensorimotor cortical connectivity occurs. In addition, significant intra- and interhemispheric changes in connectivities of thalamic nuclei were found. These are the central findings of the study. They could not have been obtained from fMRI studies alone—both fMRI and fcMRI are needed. The combination provides a general marker for brain plasticity. The rat visual system was studied in the same animals as a control. No neuroplastic changes in connectivities were found in the primary visual cortex upon forelimb deafferentation. Differences were noted in regions responsible for processing multisensory visual-motor information. This incidental discovery is considered to be significant. It may provide insight into phantom limb epiphenomena.

A double octarepeat prion protein construct, which has two histidines, mixed with copper sulfate in a 3:2 molar ratio provides at most three imidazole ligands to each copper ion to form a square-planar Cu2+ complex. This work is concerned with identification of the fourth ligand. A new (to our knowledge) electron paramagnetic resonance method based on analysis of the intense features of the electron paramagnetic resonance spectrum in the g⊥ region at 2 GHz is introduced to distinguish between three and four nitrogen ligands. The methodology was established by studies of a model system consisting of histidine imidazole ligation to Cu2+. In this spectral region at 2 GHz (S-band), g-strain and broadening from the possible rhombic character of the Zeeman interaction are small. The most intense line is identified with the MI = +1/2 extra absorption peak. Spectral simulation demonstrated that this peak is insensitive to cupric Ax and Ay hyperfine interaction. The spectral region to the high-field side of this peak is uncluttered and suitable for analysis of nitrogen superhyperfine couplings to determine the number of nitrogens. The spectral region to the low-field side of the intense extra absorption peak in the g⊥ part of the spectrum is sensitive to the rhombic distortion parameters Ax and Ay. Application of the method to the prion protein system indicates that two species are present and that the dominant species contains four nitrogen ligands. A new loop-gap microwave resonator is described that contains ∼1 mL of frozen sample.

The regions of the body have cortical and subcortical representation in proportion to their degree of innervation. The rat forepaw has been studied extensively in recent years using functional magnetic resonance imaging (fMRI), typically by stimulation using electrodes directly inserted into the skin of the forepaw. Here we stimulate the nerve directly using surgically implanted electrodes. A major distinction is that stimulation of the skin of the forepaw is mostly sensory, whereas direct nerve stimulation reveals not only the sensory system but also deep brain structures associated with motor activity. In this article, we seek to define both the motor and sensory cortical and subcortical representations associated with the four major nerves of the rodent upper extremity. We electrically stimulated each nerve (median, ulnar, radial, and musculocutaneous) during fMRI acquisition using a 9.4-T Bruker scanner (Bruker BioSpin, Billerica, MA). A current level of 0.5 to 1.0 mA and a frequency of 5 Hz were used while keeping the duration constant. A distinct pattern of cortical activation was found for each nerve that can be correlated with known sensorimotor afferent and efferent pathways to the rat forepaw. This direct nerve stimulation rat model can provide insight into peripheral nerve injury.

Velopharyngeal incompetence is a complication following cleft palate surgery, with an incidence ranging from 5 to 38 percent following palatoplasty.1 It occurs when the velopharyngeal valving mechanism is incapable of complete closure to isolate the oropharynx from the nasopharynx during speech production. The anatomical components of the velopharynx are the velum (soft palate) and the three pharyngeal walls: posterior, right lateral, and left lateral. Velopharyngeal closure depends on three basic factors: (1) superior and posterior movement of the soft palate produced by the contraction of the levator veli palatini muscle, (2) medial movement of the lateral pharyngeal walls, and (3) bulging forward of the posterior pharyngeal wall, creating a Passavant's ridge to facilitate velopharyngeal closure. Both the levator veli palatini muscle and the soft palate play a major role in the pathogenesis of velopharyngeal incompetence. Dysfunction of the levator veli palatini muscle or shortness of the soft palate may cause velopharyngeal incompetence, yet treatment options are quite different. Therefore, accurate diagnosis is crucial. Procedures that rely on restoration of a functional levator sling require the presence of adequate levator musculature for reconstruction of the levator sling. When the diagnosis of velopharyngeal incompetence is confirmed, speech therapy is initiated. Should the patient fail to demonstrate sufficient improvement in nasality despite speech therapy, secondary surgical management to restore a competent velopharyngeal valving mechanism may be indicated. If it is possible to do so by restoration of the levator muscular sling, this may obviate the need for surgical alteration of the posterior or lateral pharyngeal walls as occurs during a pharyngeal flap or sphincter pharyngoplasty. Dynamic reconstruction of the levator sling can be accomplished using either a Furlow palatoplasty in patients with submucous cleft palate or postpalatoplasty velopharyngeal incompetence,2 or by palate re-repair in patients with postpalatoplasty velopharyngeal incompetence as advocated by Sommerlad and colleagues.3 However, should the levator mechanism be negligible or replaced with scar following prior surgery, attempting dynamic levator reconstruction would not result in a competent velopharyngeal valving mechanism, and pharyngeal flap or sphincter pharyngoplasty should be considered. Therefore, the ability to visualize different soft-tissue planes of the velopharynx and to visualize the muscular anatomy preoperatively become crucial when planning secondary surgical management of velopharyngeal incompetence. Current methods for functional visualization of the velopharynx are either invasive (nasendoscopy) or impart ionizing radiation (speech videofluoroscopy), and do not provide anatomical definition of palatal soft-tissue planes. In addition to its invasiveness, nasendoscopy allows only a single viewpoint (from a ventral and cephalad observation point) of the velum. Furthermore, both the passage of the endoscope itself and the local anesthetic agent used during scoping may affect speech. In contrast, although speech videofluoroscopy allows visualization of dynamic interaction (i.e., functional evaluation) of velopharyngeal structures from different angles, interpretation is difficult because of shadows introduced by the overlying structures. Moreover, relative proportion distortion is inevitable in speech videofluoroscopy because three-dimensional structures are converted into two-dimensional images. An ideal test that is noninvasive and does not impart ionizing radiation is not in widespread use for preoperative assessment of the velopharyngeal mechanism in children. Magnetic resonance imaging is noninvasive and poses no ionizing radiation hazard, and allows imaging of the velopharyngeal mechanism during limited speech production. Magnetic resonance imaging also allows anatomical assessment of soft-tissue planes involved in the velopharyngeal valving mechanism, which is not possible with other techniques currently in use. The major hurdle that prevents the widespread application of magnetic resonance imaging for functional evaluation of the velopharyngeal mechanism is poor image quality. To examine the function of the velopharyngeal mechanism during active phonation using magnetic resonance imaging, patients are instructed to sustain phonation of a chosen vowel or consonant during the image-acquisition process. Because most patients, especially children, are only able to sustain phonation for 15 to 20 seconds comfortably, image-acquisition time is limited. This in turn limits the resolution of the acquired image. Fortunately, magnetic resonance image quality is dependent not only on the length of acquisition time but also on the magnetic field strength and head coil design. By using more powerful magnetic resonance imaging scanners and better head coil design, improvement in magnetic resonance images is possible without increasing image-acquisition time. Previous magnetic resonance imaging studies involving functional evaluation of the velopharyngeal valving mechanism in children used magnetic resonance imaging scanners with a strength up to only 1.5 T.4–7 By using a 3.0-T magnetic resonance imaging scanner with a multichannel head coil, we hypothesize that the quality of the images acquired will be sufficient to allow functional evaluation of the velopharyngeal valving mechanism in children. Moreover, resolution of the images will allow delineation of palatal soft-tissue planes for surgical planning.

The response of the rat visual system to flashes of blue light has been studied by blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI). The BOLD temporal response is dependent on the number of flashes presented and demonstrates a refractory period that depends on flash frequency. Activated brain regions included the primary and secondary visual cortex, superior colliculus (SC), dorsal lateral geniculate (DLG), and lateral posterior nucleus (LP), which were found to exhibit differing temporal responses. To explain these differences, the BOLD neurovascular response function was modeled. A second-order differential equation was developed and solved numerically to arrive at region-specific response functions. Included in the model are the light input from the diode (duty cycle), a refractory period, a transient response following onset and cessation of stimulus, and a slow adjustment to changes in the average level of the signal. Constants in the differential equation were evaluated for each region by fitting the model to the experimental BOLD response from a single flash, and the equation was then solved for multiple flashes. The simulation mimics the major features of the data; however, remaining differences in the frequency dependence of the response between the cortical and subcortical regions were unexplained. We hypothesized that these discrepancies were due to regional-specific differences in neuronal response to flash frequency. To test this hypothesis, cortical visual evoked potentials (VEPs) were recorded using the same stimulation protocol as the fMRI. Cortical VEPs were more suppressed than subcortical VEPs as flash frequency increased, supporting our hypothesis. This is the first report that regional differences in neuronal activation to the same stimulus lead to differential BOLD activation.

Functional MRI (fMRI) studies of tasks involving orofacial motion, such as speech, are prone to problems related to motion-induced magnetic field variations. Orofacial motion perturbs the static magnetic field, leading to signal changes that correlate with the task and corrupt activation maps with false positives or signal loss. These motion-induced signal changes represent a contraindication for the implementation of fMRI to study the neurophysiology of orofacial motion. An fMRI experiment of a structured, non-semantic vowel production task was performed using four different voxel volumes and three different slice orientations in an attempt to find a set of acquisition parameters leading to activation maps with maximum specificity. Results indicate that the use of small voxel volumes (2 × 2 × 3 mm 3 ) yielded a significantly higher percentage of true positive activation compared to the use of larger voxel volumes. Slice orientation did not have as great an impact as spatial resolution, although coronal slices appeared superior at high spatial resolutions. Furthermore, it was found that combining the strategy of high spatial resolution with an optimum task duration and post-processing methods for separating true and false positives greatly improved the specificity of single-subject, block-design fMRI studies of structured, overt vowel production.

Regional-specific average time courses of spontaneous fluctuations in blood oxygen level dependent (BOLD) MRI contrast at 9.4T in lightly anesthetized resting rat brain are formed, and correlation coefficients between time course pairs are interpreted as measures of connectivity. A hierarchy of regional pairwise correlation coefficients (RPCCs) is observed, with the highest values found in the thalamus and cortex, both intra- and interhemisphere, and lower values between the cortex and thalamus. Independent sensory networks are distinguished by two methods: data driven, where task activation defines regions of interest (ROI), and hypothesis driven, where regions are defined by the rat histological atlas. Success in these studies is attributed in part to the use of medetomidine hydrochloride (Domitor) for anesthesia. Consistent results in two different rat-brain systems, the sensorimotor and visual, strongly support the hypothesis that resting-state BOLD fluctuations are conserved across mammalian species and can be used to map brain systems.

At high frequencies, e.g., Q- and W-bands, it is advantageous to make the axial length of loop-gap resonators (LGRs) at least as long as a free-space wavelength. The opposite scaling of capacitance and inductance with LGR length suggests that the length of an LGR can be increased without limit, with the axial radio frequency (rf) field profiles and resonance frequency independent of length. This scaling is accurate for resonator dimensions much less than one free-space wavelength. When the resonator length approaches one-tenth of a free-space wavelength, the rf field uniformity degrades. From one-tenth to one free-space wavelength, computer simulations and experimental measurements show that the axial magnetic field energy density profile is peaked in the center of the LGR, gradually decreases from 25 to 50% at a distance one radius from the end, and rapidly there-after. The nonuniformity is of two types. One type, in the vicinity of one radius of the end, is caused by the flaring of the field as it curves from the central loop to the end region, into the larger return loop(s). The other type, in the central part of the resonator, is caused by impedance mismatch at the ends of the LGR. The LGR may be viewed as a strongly reentrant (ridge) waveguide nearly open at both ends and supporting a standing wave. A transmission line model relates the central nonuniformity to the fringing capacitance and inductance at the ends of the resonator. This nonuniformity can be eliminated in several ways including modifying the ends of the LGR by adding a small metal bridge or a dielectric ring. These uniformity trimming elements increase the fringing capacitance and/or decrease the fringing inductance. With trimmed ends, LGRs can be made many free-space wavelengths long. The maximum resonator length is determined by the proximity in frequency of the fundamental LGR mode to the next highest frequency mode as well as the quality factor. Results of this theory are compared and conformed with finite-element simulations. This theory connects the uniform LGR with the uniform field cavity resonators previously introduced by this laboratory.

Purpose Achieving a reduction in scan time with minimal inter-slice signal leakage is one of the significant obstacles in parallel MR imaging. In fMRI, multiband-imaging techniques accelerate data acquisition by simultaneously magnetizing the spatial frequency spectrum of multiple slices. The SPECS model eliminates the consequential inter-slice signal leakage from the slice unaliasing, while maintaining an optimal reduction in scan time and activation statistics in fMRI studies. Materials and methods When the combined k -space array is inverse Fourier reconstructed, the resulting aliased image is separated into the un-aliased slices through a least squares estimator. Without the additional spatial information from a phased array of receiver coils, slice separation in SPECS is accomplished with acquired aliased images in shifted FOV aliasing pattern, and a bootstrapping approach of incorporating reference calibration images in an orthogonal Hadamard pattern. Result The aliased slices are effectively separated with minimal expense to the spatial and temporal resolution. Functional activation is observed in the motor cortex, as the number of aliased slices is increased, in a bilateral finger tapping fMRI experiment. Conclusion The SPECS model incorporates calibration reference images together with coefficients of orthogonal polynomials into an un-aliasing estimator to achieve separated images, with virtually no residual artifacts and functional activation detection in separated images.

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 10 s 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 1 s, peaked at 11 ± 0.5% (S.E.M.) above baseline within 2–3 s, decreased to a plateau of 5 ± 0.3% for the duration of the stimulation, and returned to baseline within 5–10 s 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 ± 0.2 ms, 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.

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.

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.

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.

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.

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 μl) compared with submaximal effort contractions (2,558 ± 306 μl). 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.

Although symptoms arising from the esophagus such as heartburn and pain can at times become challenging clinical problems, esophageal viscerosensation, especially with regard to chemical stimulation in humans, is incompletely understood. Our aims were 1) to characterize and ascertain the reproducibility of cerebral cortical registration of heartburn and 2) to elucidate the differences between these findings and those of esophageal subliminal acid stimulation in asymptomatic controls. We studied 11 gastroesophageal reflux disease (GERD) patients (9 males, 30–55 yr) and 15 healthy controls (8 males, 21–49 yr). Cerebral cortical functional magnetic resonance imaging (fMRI) activity was recorded twice in each subject, during two 5-min intervals of 0.1 N HCl, separated by 5 min of NaCl perfusion. Time from onset of acid perfusion to instant of fMRI signal increase and first report of heartburn averaged 1.60 ± 0.80 and 1.85 ± 0.60 min, respectively. Average maximum percent signal increase in the GERD patients (16.3 ± 3.5%) was significantly greater than that of healthy controls (3.8 ± 0.9%; P < 0.01). Temporal fMRI signal characteristics during heartburn were significantly different from those of subliminal acid stimulation in controls ( P < 0.01). Activated cortical regions included sensory/motor, parieto-occipital, cingulate and prefrontal regions, and the insula. There was 92% concordance between the activated Brodmann areas in repeated studies of GERD patients. Cortical activity associated with perceived and unperceived esophageal acid exposure in GERD patients and healthy controls, respectively, involves multiple brain regions but occurs more rapidly and with greater intensity in GERD patients than the activity in response to subliminal acid exposure in healthy controls. The cortical pain-processing pathway seems to be involved in perception of esophageal acid exposure and could explain the variations encountered in clinical practice defining this sensation.