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Biomedical subjects

M Garwood

Publications and source records attributed to M Garwood.

At least 19 recordsLinked to original sources

Detunable transverse electromagnetic (TEM) volume coil for high-field NMR.

Most high-field MRI systems do not have the actively detuned body coils that are integral to clinical systems operating at 1.5T and lower field strengths. Therefore, many clinical applications requiring homogeneous volume excitation in combination with local surface coil reception are not easily implemented at high fields. To solve this problem for neuroimaging applications, actively detunable transverse electromagnetic (TEM) head coils were developed to be used with receive-only surface coils for signal-to-noise ratio (SNR) gains and improved spatial coverage from homogeneously excited regions. These SNR and field of view (FOV) gains were achieved by application of a detunable TEM volume coil to human brain imaging at 4T.

Brain↗

BISTRO: an outer-volume suppression method that tolerates RF field inhomogeneity.

A technique is described for performing frequency-selective signal suppression with a high degree of tolerance to RF field inhomogeneity. The method is called B1-insensitive train to obliterate signal (BISTRO). BISTRO consists of multiple amplitude- and frequency-modulated (FM) pulses interleaved with spoiler gradients. BISTRO was developed for the purpose of accomplishing band-selective signal removal, as in water suppression and outer-volume suppression (OVS), in applications requiring the use of an inhomogeneous RF transmitter, such as a surface coil. In the present work, Bloch simulations were used to illustrate the principles and theoretical performance of BISTRO. Its performance for OVS was evaluated experimentally using MRI and spectroscopic imaging of phantoms and in vivo animal and human brain. By using FM pulses featuring offset-independent adiabaticity, BISTRO permitted high-quality, broadband suppression with one (or two) discrete borders demarcating the edge(s) of the suppression band. Simulations and experiments demonstrated the ability to operate BISTRO with reasonably attainable peak RF power levels and with average RF energy deposition similar to other multipulse OVS techniques.

Animals↗

7T vs. 4T: RF power, homogeneity, and signal-to-noise comparison in head images.

Signal-to-noise ratio (SNR), RF field (B(1)), and RF power requirement for human head imaging were examined at 7T and 4T magnetic field strengths. The variation in B(1) magnitude was nearly twofold higher at 7T than at 4T ( approximately 42% compared to approximately 23%). The power required for a 90 degrees pulse in the center of the head at 7T was approximately twice that at 4T. The SNR averaged over the brain was at least 1.6 times higher at 7T compared to 4T. These experimental results were consistent with calculations performed using a human head model and Maxwell's equations. Magn Reson Med 46:24-30, 2001.

Brain↗

The return of the frequency sweep: designing adiabatic pulses for contemporary NMR.

Frequency-modulated (FM) pulses that function according to adiabatic principles are becoming increasingly popular in many areas of NMR. Often adiabatic pulses can extend experimental capabilities and minimize annoying experimental imperfections. Here, adiabatic principles and some of the current methods used to create these pulses are considered. The classical adiabatic rapid passage, which is a fundamental element upon which all adiabatic pulses and sequences are based, is analyzed using vector models in different rotating frames of reference. Two methods to optimize adiabaticity are described, and ways to tailor modulation functions to best satisfy specific experimental needs are demonstrated. Finally, adiabatic plane rotation pulses and frequency-selective multiple spin-echo sequences are considered.

Brain↗

The effect of leucocyte depletion on the quality of fresh-frozen plasma.

The aim of this study was to evaluate the quality of leucodepleted (LD) fresh-frozen plasma (FFP) produced using one of five whole blood filters (Baxter RS2000 & RZ2000, NPBI T2926, Macopharma LST1 and Terumo WBSP) or two plasma filters (Pall LPS1 and Baxter FGR7014). Whole blood or plasma was filtered within 8 h of collection at an ambient temperature. Samples were taken pre- and post filtration for analysis of coagulation factors and complement activation (n = 7--12 for each type of filter). All filtered units (209--286 ml) contained < 5 x 10(6) residual leucocytes and < 30 x 10(9)/l platelets. Statistically significant losses of factors V, VIII, IX, XI and XII and increases in markers of coagulation activation were observed (0--21%), which were dependent on filter type. None of the filters had a significant effect on von Willebrand factor (VWF) multimeric distribution or the activity of VWF and factors II, VII or X. The effect on levels of C3a appeared to be related to the filter surface charge: positively charged filters resulted in C3a generation, whereas negatively charged resulted in C3a removal. None of the observed changes are likely to be clinically significant unless subsequent processing of plasma (such as pathogen inactivation) results in further losses of coagulation factors.

Blood Coagulation Factors↗

Subchronic in vivo effects of a high static magnetic field (9.4 T) in rats.

The potential adverse biologic effects of sub chronic (cumulatively 10 weeks) exposure to a high magnetic field (9.4 T) were evaluated in young adult male and female Fischer rats as well as in their progeny. Biologic end points in adult rats included changes in daily clinical observations; spatial memory tests; weekly heart rates, body weights, food and water consumption, and the feed efficiency ratio; terminal hematologic, blood biochemical and urinary parameter changes; gross pathologic findings; and major organ weights. In offspring, biologic end points included the gestation period, number of live births, number of pups, ratio of male to female pups/litter; postnatal time period of eye opening; birth and weekly body weights, behavioral changes, central nervous system responses, as well as hematologic, blood biochemistry, and urinary parameter changes; and gross pathologic findings. Findings from this study showed that there were no adverse biologic effects in male and female adult rats or their progeny that could be attributed to 10-week exposure to a 9.4-T static magnetic field.

Age Factors↗

Imaging blood flow in brain tumors using arterial spin labeling.

Measurements of tumor blood flow (TBF) are important for understanding tumor physiology and can be valuable in selecting and evaluating therapies. Brain tumors typically present reduced blood flows compared to normal brain tissue. This study shows that the arterial spin labeling (ASL) technique can be used to measure TBF non-invasively in a rat glioma model. Results show that TBF in the core (36.3 +/- 18.9 ml/100g/min, n=4) and peripheral regions (85.3 +/- 26.9 ml/100g/min, n=4) of the tumor are significantly reduced and show considerable heterogeneity compared to cerebral blood flow (CBF) of normal brain tissue (147.7 +/- 31.1 ml/100g/min, n=4), while T(1) in the tumor (2.6 +/- 0.1 sec) is significantly elevated compared to normal tissue T(1) (2.0 +/- 0.0 sec). These results strongly support the feasibility of using the ASL technique to evaluate different cancer treatment strategies, to monitor the effects of agents designed to modulate TBF and oxygenation (e.g., carbogen gas), and to assess and guide the use of anti-angiogenic agents. Magn Reson Med 44:169-173, 2000.

Animals↗

In vivo observation of lactate methyl proton magnetization transfer in rat C6 glioma.

Magnetic resonance spectroscopy (MRS) measurements of the lactate methyl proton in rat brain C6 glioma tissue acquired in the presence of an off-resonance irradiation field, analyzed using coupled Bloch equation formalism assuming two spin pools, demonstrated the occurrence of magnetization transfer. Quantitative analysis revealed that a very small fraction of lactate (f = 0.0012) is rotationally immobilized despite a large magnetization transfer effect. Off-resonance rotating frame spin-lattice relaxation studies demonstrated that deuterated lactate binds to bovine serum albumin and the proteins present in human plasma, thereby providing a possible physical basis for the observed magnetization transfer effect. These results demonstrate that partial or complete saturation of the motionally restricted lactate pool (as well as other metabolites) by the application of an off-resonance irradiation field, such as that used for water presaturation, can lead to a substantial decrease in resonance intensity by way of magnetization transfer effects, resulting in quantitation errors.

Animals↗

Localized in vivo 1H NMR detection of neurotransmitter labeling in rat brain during infusion of [1-13C] D-glucose.

Resolved localized nuclear magnetic resonance (NMR) signals of 1H bound to 13C label in the carbon positions of glutamate C4, C3 and glutamine C4, C3, as well as in aspartate C3, lactate C3, alanine C3, gamma-aminobutyric acid C3, and glucose C1 were simultaneously observed in spectra obtained from rat brain in vivo. Time-resolved label incorporation was measured with a new adiabatic carbon editing and decoupling (ACED) single-voxel stimulated echo acquisition mode (STEAM) sequence. Adiabatic carbon broadband decoupling of 12 kHz bandwidth was achieved in vivo, which decoupled the entire 13C spectrum at 9.4 T. Resonances from N-acetyl-aspartate and creatine were also detected, consistent with natural-abundance 13C levels. These results emphasize the potential of 1H NMR for following complex biochemical pathways in localized areas of resting rat brain as well as during focal activation using infusions of 13C-labeled glucose.

Animals↗

Asymmetric adiabatic pulses for NH selection.

Many types of NMR experiments demand the use of frequency-selective pulses to invert magnetization within discrete frequency limits. For certain experiments, only one side of the inversion band must be sharply demarcated, in which case this transition bandwidth can be narrowed when using an asymmetric adiabatic full passage. In the present study, a highly efficient asymmetric adiabatic full passage was created from a combination of two adiabatic half passages which used different modulation functions (HS12 and tanh/tan). Each adiabatic half passage occupied a different amount of time in the total pulse and performed one-half of the inversion. On one side, HS12 produced a sharp transition between inverted and noninverted states which was approximately 2.5 times narrower than the transition bandwidth afforded by a symmetric hyperbolic secant pulse of equal length. On the other side of the narrow transition band, the tanh/tan pulse achieved broadband inversion. These asymmetric pulses were applied to select NH groups immediately adjacent to the water signal in water-flip-back HSQC experiments using a double spin echo for the reverse INEPT step.

Fourier Analysis↗

Spatial assessment of the dynamics of lactate formation in focal ischemic rat brain.

Early identification of the potentially salvageable penumbra is critical for the determination of therapeutic intervention strategies in acute focal cerebral ischemia. This study differentiates the ischemic penumbra from the core on the basis of the dynamics of lactate formation. This was tested in a rat model of focal cerebral ischemia by infusion of [1-13C]-glucose, using lactate-edited magnetic resonance spectroscopic imaging techniques. The authors detected essentially no enrichment of lactate with 13C-label from the infused 13C-glucose in the ischemic core. However, in borderzone areas, 13C was incorporated into lactate, which could point toward compromised but potentially viable tissue. The authors' findings suggest that this combination of 13C-glucose infusion with the proposed magnetic resonance methods may aid in differentiating the penumbra from the core in cerebral ischemia.

Animals↗

Effects of continuous localized infusion of granulocyte-macrophage colony-stimulating factor and inoculations of irradiated glioma cells on tumor regression.

OBJECT: Glioblastoma multiforme (GBM) is a malignant tumor of the central nervous system that directly suppresses immunological defenses in vitro and in vivo. The authors used the peripheral delivery of continuously infused granulocyte-macrophage colony-stimulating factor (GM-CSF) in the presence of irradiated tumor antigens as a tumor-specific stimulant to dendritic cells to initiate an immune response to GBM in rats. METHODS: The 9L gliosarcoma tumors were established in the flanks of syngeneic Fischer 344 rats. Osmotic minipumps implanted in the animals' contralateral flanks continuously delivered recombinant GM-CSF (0, 0.1, 1, or 10 ng/day) for 28 days. Irradiated gliosarcoma cells were intermittently injected at the site of the GM-CSF infusion. Animals in the saline control group (0 ng/day GM-CSF) died on Day 59 with average tumor volumes greater than 30,000 mm3. This control group was significantly different from the GM-CSF-treated animals, which all survived with average tumor volumes that peaked on Day 23 and later regressed completely. Tumor growth as well as peak tumor volumes (5833+/-2284 mm3, 3294+/-1632 mm3, and 1979+/-1142 mm3 for 0.1, 1, and 10 ng/day GM-CSF, respectively) in the different treatment groups reflected a significant dose-response relationship with the GM-CSF concentrations. All animals treated with GM-CSF and irradiated cells were resistant to additional challenges of peripheral and intracerebral gliosarcoma, even when they were inoculated 8 months after initial immunotherapy. The colocalization of GM-CSF and inactivated tumor antigens was required to stimulate immunoprotection. To test the efficacy of a peripherally administered immunological therapy on intracerebral brain tumors the authors transplanted 10(6) gliosarcoma cells into the striatum of treated and control animals. Subcutaneous pumps that released GM-CSF (10 ng/day) and irradiated gliosarcoma cells were placed in the treated animals. The control animals all died within 31 days after intracerebral tumor implantation. In contrast, 40% of the animals receiving GM-CSF-irradiated cell vaccinations survived beyond 300 days. These long-term survivors showed no evidence of gliosarcoma at the injection site on evaluation by magnetic resonance imaging. CONCLUSIONS: These results suggest that the continuous localized delivery of subcutaneous GM-CSF in conjunction with inactivated tumor antigens can initiate a systemic response that leads to the regression of distant peripheral and intracerebral tumors. The success of this treatment illustrates the feasibility of tumor-specific peripheral immunological stimulation after tumor resection to prevent the recurrence of malignant brain tumors.

Animals↗

Lactate turnover in rat glioma measured by in vivo nuclear magnetic resonance spectroscopy.

Elevated tissue lactate concentrations typically found in tumors can be measured by in vivo nuclear magnetic resonance (NMR) spectroscopy. In this study, lactate turnover in rat C6 glioma was determined from in vivo 1H NMR measurements of [3-13C]lactate buildup during steady-state hyperglycemia with [1-13C]glucose. With this tumor model, a narrow range of values was observed for the first-order rate constant that describes lactate efflux, k2 = 0.043 +/- 0.007 (n = 12) SD min-1. For individual animals, the standard error in k2 was small (< 18%), which indicated that the NMR data fit the kinetic model well. Lactate measurements before and after infusing [1-13C]glucose showed that the majority of the tumor lactate pool was metabolically active. Signals from 13C-labeled glutamate in tumors were at least 10-fold smaller than the [3-13C]lactate signal, whereas spectra of the contralateral hemispheres revealed the expected labeling of [4-13C]glutamate, as well as [2-13C] and [3-13C]glutamate, which indicates that label cycled through the tricarboxylic acid cycle in the brain tissue. Lack of significant 13C labeling of glutamate was consistent with low respiratory metabolism in this glioma. It is concluded that lactate in rat C6 glioma is actively turning over and that the kinetics of lactate efflux can be quantified noninvasively by 1H NMR detection of 13C label. This noninvasive NMR approach may offer a valuable tool to help evaluate tumor growth and metabolic responsiveness to therapies.

Animals↗

MR imaging contrast enhancement based on intermolecular zero quantum coherences.

A new method for magnetic resonance imaging (MRI) based on the detection of relatively strong signal from intermolecular zero-quantum coherences (iZQCs) is reported. Such a signal would not be observable in the conventional framework of magnetic resonance; it originates in long-range dipolar couplings (10 micrometers to 1 millimeter) that are traditionally ignored. Unlike conventional MRI, where image contrast is based on variations in spin density and relaxation times (often with injected contrast agents), contrast with iZQC images comes from variations in the susceptibility over a distance dictated by gradient strength. Phantom and in vivo (rat brain) data confirm that iZQC images give contrast enhancement. This contrast might be useful in the detection of small tumors, in that susceptibility correlates with oxygen concentration and in functional MRI.

Animals↗

Simultaneous in vivo spectral editing and water suppression.

Water suppression is typically performed in vivo by exciting the longitudinal magnetization in combination with dephasing, or by using frequency-selective coherence generation. MEGA, a frequency-selective refocusing technique, can be placed into any pulse sequence element designed to generate a Hahn spin-echo or stimulated echo, to dephase transverse water coherences with minimal spectral distortions. Water suppression performance was verified in vivo using stimulated echo acquisition mode (STEAM) localization, which provided water suppression comparable with that achieved with four selective pulses in 3,1-DRYSTEAM. The advantage of the proposed method was exploited for editing J-coupled resonances. Using a double-banded pulse that selectively inverts a J-coupling partner and simultaneously suppresses water, efficient metabolite editing was achieved in the point resolved spectroscopy (PRESS) and STEAM sequences in which MEGA was incorporated. To illustrate the efficiency of the method, the detection of gamma-aminobutyric acid (GABA) was demonstrated, with minimal contributions from macromolecules and overlying singlet peaks at 4 T. The estimated occipital GABA concentration was consistent with previous reports, suggesting that editing for GABA is efficient when based on MEGA at high field strengths.

Brain Chemistry↗

Fast broadband inversion by adiabatic pulses.

Despite the advantages of compensation for resonance offset and B1 inhomogeneity, adiabatic pulses are not yet in general use in high-resolution NMR, often because of the conception that these pulses require longer time or increased power to perform. We show that adiabatic pulses with tangential frequency sweeps and other frequency-modulation functions can be optimized to accomplish 13C and 1H broadband inversion using pulse lengths of 192 and 64 micro(s), respectively, at B1 strengths available with modern high-resolution probes.

Algorithms↗

Resolution improvements in in vivo 1H NMR spectra with increased magnetic field strength.

The measurement of cerebral metabolites using highly homologous localization techniques and similar shimming methods was performed in the human brain at 1.5 and 4 T as well as in the dog and rat brain at 9.4 T. In rat brain, improved resolution was achieved by shimming all first- and second-order shim coils using a fully adiabatic FASTMAP sequence. The spectra showed a clear improvement in spectral resolution for all metabolite resonances with increased field strength. Changes in cerebral glutamine content were clearly observed at 4 T compared to 1.5 T in patients with hepatic encephalopathy. At 9.4 T, glutamine H4 at 2.46 ppm was fully resolved from glutamate H4 at 2.37 ppm, as was the potential resonance from gamma-amino-butyric acid at 2.30 ppm and N-acetyl-aspartyl-glutamate at 2.05 ppm. Singlet linewidths were found to be as low as 6 Hz (0.015 ppm) at 9.4 T, indicating a substantial decrease in ppm linewidth with field strength. Furthermore, the methylene peak of creatine was partially resolved from phosphocreatine, indicating a close to 1:1 relationship in gray matter. We conclude that increasing the magnetic field strength increases spectral resolution also for 1H NMR, which can lead to more than linear sensitivity gains.

Adult↗

Retrospective correction of surface coil MR images using an automatic segmentation and modeling approach.

The use of surface coils in magnetic resonance imaging offers significant improvements in the signal-to-noise ratio over volume coils for many applications. However, the inhomogeneous reception profile of surface coils hampers their usefulness by introducing significant nonuniformities or intensity variations which can vary by greater than six-fold across the sample. In this study, we evaluated an automatic technique for retrospective correction of intensity variations observed in a high-resolution surface coil MR image of the rat brain obtained using an adiabatic magnetic resonance imaging sequence. The images are shown to have a coefficient of variation less than 12% following application of this correction algorithm. This image intensity correction technique can be applied retrospectively to all data sets and corrects both sample/patient dependent effects (e.g. attenuation of overlying tissue) or sample independent effects (e.g. coil geometry or position). This approach should also prove valuable in improving regions of interest analysis, volume histograms and thresholding techniques.

Animals↗