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Biomedical subjects

M Garwood

Publications and source records attributed to M Garwood.

At least 37 records · Page 2Linked to original sources

Adiabatic pulses.

Adiabatic pulses are sometimes considered to be mysterious and exotic entities which are difficult to understand, complex to generate and impractical to implement. This work is an attempt to bring familiarity and to fulfill the preliminary needs of anyone interested in learning more about this subject. The response of magnetization to stimuli produced by adiabatic pulses is analyzed using vector representations in a frequency modulated rotating frame. The first section deals with basic principles of amplitude and frequency modulated pulses and a vector representation in a second rotating frame is used to explain how the adiabatic condition can be satisfied. The subsequent section explains the principles of offset independent adiabaticity. These principles are then used to design optimal functions for the amplitude, frequency, and magnetic field gradient modulations for adiabatic inversion pulses. The last section considers some practical aspects for those who want to develop methodologies involving adiabatic pulses.

Electromagnetic Fields↗

Relationships among lactate concentration, blood flow and histopathologic profiles in rat C6 glioma.

Increased capacity for glycolytic metabolism is a well-known characteristic of neoplastic cells. Because lactic acid is the end product of glycolysis, in vivo MRS measurements of tumor lactate concentration ([lac]t) may provide valuable information about tumor metabolism, which will aid the development of therapies and the clinical diagnosis and treatment of tumors. In the present study, several hemodynamic and histologic parameters were evaluated with respect to their influence on [lac]t. Pronounced differences in [lac]t in two distinct populations of tumors suggested a putative perfusion threshold. Above this threshold, [lac]t was independent of hemodynamic and histologic factors including tumor blood flow (measured using MRS and the method of D2O washout), extent of necrosis and inflammatory cell infiltrate. Thus, for most tumors, [lac]t was not determined by any one single factor such as hypoxia, venous clearance, glucose supply, extent of necrosis or degree of inflammatory cell infiltrate. Rather, [lac]t may be equilibrated, at least in part, by an interplay of forces involving hemodynamics and substrate supply. In general, the data are consistent with the hypothesis that elevated lactate in most tumors is related to the high glycolytic activity of adequately perfused, viable neoplastic cells.

Animals↗

Single-shot, B1-insensitive slice selection with a gradient-modulated adiabatic pulse, BISS-8.

An adiabatic pulse has been developed to accomplish uniform slice-selective excitation with a spatially inhomogeneous B1. This new pulse can generate a uniform, arbitrary flip angle that is determined by four adjustable phase shifts in the pulse. Self-refocused slice selection is achieved by modulating a B(O) gradient in concert with the pulse frequency (or phase) modulation. B1-compensated, self-refocused slice selection is demonstrated in computer simulations and phantom experiments using a surface transmitter/receiver coil. This adiabatic pulse can provide optimal performance in multislice MRI and localized spectroscopy when transmitting with an inhomogeneous B1.

Computer Simulation↗

Observation of resolved glucose signals in 1H NMR spectra of the human brain at 4 Tesla.

Measurement of the resonances of glucose between 3.2 and 3.9 ppm in 1H NMR spectra from the human brain is difficult due to spectral overlap with peaks from more concentrated metabolites. The H1 resonance of alpha-D-glucose at 5.23 ppm is resolved from other metabolite peaks, but potentially overlaps with the intense water signal at 4.72 ppm. This paper demonstrates that the increased resolution at 4 Tesla permits to suppress the water signal sufficiently to reliably detect glucose directly at 5.23 ppm by 1H MRS and the estimated peak intensity is consistent with previous 13C NMR quantification.

Blood Glucose↗

B1-insensitive, single-shot localization and water suppression.

A technique for single-shot, localized, water-suppressed in vivo 1H NMR with high immunity to B1 inhomogeneities is described. The single-shot localization is based on complete outer-volume suppression which is achieved with optimized, adiabatic BIR-4 pulses in combination with BO gradient modulation. B1-insensitive water suppression is achieved with BISTRO, a train of selective adiabatic full-passage pulses interleaved with BO gradient crushers. Computer simulations based on the Bloch equations, experimental images of the localized volume, and in vivo 1H spectroscopy experiments demonstrate the excellent spatial localization and water suppression.

Artifacts↗

High contrast and fast three-dimensional magnetic resonance imaging at high fields.

A new three-dimensional imaging strategy based on magnetization prepared ultrafast gradient recalled echo technique that demonstrates pronounced T1 contrast at high fields is introduced. High-resolution three-dimensional image sets of human brain showing high contrast between white and gray matter areas are presented. The ratio of contrast-to-noise was examined as a function of the relevant parameters in the imaging sequence; calculations based on high-field T1 values as well as the experimental data demonstrated that maximal contrast-to-noise ratio is attained under the same magnetization preparation conditions both for cortical and subcortical gray matter relative to white matter, leading to approximately equivalent appearance of all gray matter areas in the same image. In addition, the images displayed clear visualization of subtle anatomical structures such as the subthalamic nuclei (ventral tier nuclei, dorsomedial nucleus, and pulvinar) and mammillothalamic tracts.

Brain↗

Myocardial tagging with B1 insensitive adiabatic DANTE inversion sequences.

A new technique, based on adiabatic delays alternating with mutations for tailored excitation (DANTE) inversion sequences, is presented for generating uniform contrast tags across the myocardial wall even in the presence of B1 inhomogeneities. The utility of this pulse was demonstrated using a surface coil for both transmission and signal reception in phantom and animal heart tagging studies. The experimental data demonstrated uniform grid contrast over a sixfold variation of B1 magnitude, sharp tagging profiles, and the ability to follow the cardiac wall motion through the deformation of the fine rectangular tagging grid at different phases throughout the cardiac cycle.

Animals↗

Transmural distribution of 2-deoxyglucose uptake in normal and post-ischemic canine myocardium.

This investigation was performed to determine (i) whether 31P spatially localized 31P NMR spectroscopy could be utilized to determine the transmural distribution of 2-deoxyglucose (2DG) uptake in the in vivo canine heart and (ii) whether transmural 2DG uptake would be affected by a preceding ischemic insult. 2DG was infused and the accumulation of 2-deoxyglucose-6-phosphate (2DGP) was monitored (by means of spatially localized 31P NMR) in control hearts, in pharmacologically hyperperfused hearts, and in hearts subjected to four (5 min) occlusions of the left anterior descending coronary artery. Myocardial blood flow was measured with radioactive microspheres. In control hearts, subendocardial (ENDO) 2DGP contents were significantly higher than those in the subepicardium (EPI) being 3.8 +/- 0.3 and 2.2 +/- 0.2 mumol/g, respectively; the ENDO/EPI ratio of 2DGP was 1.70 +/- 0.21. During hyperperfusion blood flow increased approximately four-fold but 2DGP accumulation was not altered. ATP levels in post-ischemic myocardium were significantly decreased (ENDO more than EPI) and 2DGP accumulation in each layer was increased (p < 0.01 vs control); however, the ENDO/EPI ratio of 2DGP was not altered. 2DG infusion induced a marked elevation of blood insulin and norepinephrine levels. These data demonstrate that in the presence of high blood levels of 2DG and insulin: (i) 2DGP accumulation can be measured in the in vivo canine heart; (ii) in normal hearts 2DG uptake is more pronounced in the inner layers of the left ventricular wall (this transmural 2DG uptake gradient is not due to subendocardial hypoperfusion); and (iii) 2DG uptake is greater in the post-ischemic heart but the ENDO/EPI gradient of 2DG uptake is not altered indicating that the more severe ischemic insult in the subendocardium does not result in a disproportionate increase in 2DG uptake in that region of the myocardium. Although 2DG uptake patterns in this model most probably reflect those of glucose (at comparable glucose and insulin levels), quantitative extrapolations with regard to the rate of glucose uptake are not possible from the present data.

Animals↗

Spectral editing with adiabatic pulses.

Amplitude- and frequency-modulated pulses, known as adiabatic pulses, can induce uniform flip angles in the presence of extreme B1 inhomogeneity, which makes them advantageous for in vivo surface-coil studies. This paper describes the conversion of conventional (square pulse-based) spectral-editing sequences into their adiabatic counterparts. Eight adiabatic homo- and heteronuclear sequences are experimentally evaluated for lactate editing. For homonuclear lactate editing, gradient-enhanced multiple-quantum-coherence filtering provides the best overall performance (100% signal recovery with excellent water and lipid suppression in a single acquisition). For heteronuclear [3-(13)C]lactate editing, gradient-enhanced heteronuclear multiple-quantum-coherence filtering provides the best suppression of unwanted signals in a single acquisition, whereas J-modulated spin-echo sequences yield maximum sensitivity.

Animals↗

A new localization method using an adiabatic pulse, BIR-4.

A new method is described for accomplishing localized spectroscopy with an adiabatic pulse, BIR-4. The method has advantages similar to previously described combinations of outer-volume suppression (OVS) and ISIS, with the additional advantages that localization is achieved with only three radiofrequency pulses and the localization remains accurate even in the presence of intense signals with short relaxation times. This new localization pulse sequence is referred to as integrated OVS-ISIS. Computer simulations, experimental images of the localized volumes, and in vivo 1H spectroscopy measurements demonstrate the high degree of localization achievable with integrated OVS-ISIS.

Animals↗

Hyperperfusion and cardioplegia effects on myocardial high-energy phosphate distribution and energy expenditure.

This study examines the hypothesis that high-energy phosphate (HEP) compound levels in unstimulated in vivo myocardium are defined by 1) the level of perfusion and 2) non-perfusion-dependent metabolic characteristics. This hypothesis was tested by determining 1) the effects of pharmacological hyperperfusion of functioning myocardium on transmural HEP compound distribution, contractile function, and myocardial oxygen consumption rate (MVO2) as well as 2) the effect of KCl cardioplegia on transmural myocardial HEP compound distribution. Creatine phosphate (CP) and ATP were measured across the anterior left ventricular wall using spatially localized 31P-nuclear magnetic resonance (NMR). At baseline, the CP-to-ATP (CP/ATP) ratio was significantly lower in the subendocardium than in the subepicardium. This transmural HEP gradient was abolished by hyperperfusion without significant effects on contractile function or MVO2. Similarly, KCl arrest significantly increased CP and CP/ATP in all myocardial layers, and the transmural gradient of CP/ATP was abolished again. These studies indicate that in present experimental model 1) myocardial performance is not constrained by inadequate perfusion in any myocardial layer although modest oxygen limitation affects the kinetics of oxidative phosphorylation in the inner myocardial layers and 2) in all myocardial layers, submaximal activation of intermediary metabolism and oxidative phosphorylation reactions results in lower steady-state CP and higher ADP levels relative to their respective values when energy expenditure is markedly reduced by KCl arrest.

Adenosine Triphosphate↗

Localized detection of glioma glycolysis using edited 1H MRS.

In vivo 1H MRS can be used to detect and quantify the lactate resonance at 1.3 ppm provided that overlapping lipid resonances are eliminated. A homonuclear spectral editing method was developed to acquire uncontaminated 1H spectra of lactate with adiabatic pulses. An advantage of the adiabatic pulse sequence is the ability to induce uniform flip angles and to maximize sensitivity in applications employing surface coil transmitters which produce highly inhomogeneous B1. Glycolytic activity in an intracerebral C6 glioma in rats was monitored by using adiabatic editing sequences to observe [3-13C]lactate produced from infused [1-13C]glucose. Acute hyperglycemia (serum glucose > 22 mM, n = 10) had no significant effect (P = 0.08) on the total ([12C] + [13C]) tumor lactate signal intensity.

Animals↗

Bioenergetic abnormalities associated with severe left ventricular hypertrophy.

Transmurally localized 31P-nuclear magnetic resonance spectroscopy (NMR) was used to study the effect of severe pressure overload left ventricular hypertrophy (LVH) on myocardial high energy phosphate content. Studies were performed on 8 normal dogs and 12 dogs with severe left ventricular hypertrophy produced by banding the ascending aorta at 8 wk of age. Spatially localized 31P-NMR spectroscopy provided measurements of the transmural distribution of myocardial ATP, phosphocreatine (CP), and inorganic phosphate (Pi); spectra were calibrated from measurements of ATP content in myocardial biopsies using HPLC. Blood flow was measured with microspheres. In hypertrophied hearts during basal conditions, ATP was decreased by 42%, CP by 58%, and the CP/ATP ratio by 32% in comparison with normal. Increasing myocardial blood flow with adenosine did not correct these abnormalities, indicating that they were not the result of persistent hypoperfusion. Atrial pacing at 200 and 240 beats per min caused no change in high energy phosphate content in normal hearts but resulted in further CP depletion with Pi accumulation in the inner left ventricular layers of the hypertrophied hearts. These changes were correlated with redistribution of blood flow away from the subendocardium in LVH hearts. These findings demonstrate that high energy phosphate levels and the CP/ATP ratio are significantly decreased in severe LVH. These abnormalities are proportional to the degree of hypertrophy but are not the result of persistent abnormalities of myocardial perfusion. In contrast, depletion of CP and accumulation of Pi during tachycardia in LVH are closely related to the pacing-induced perfusion abnormalities and likely reflect subendocardial ischemia.

Adenosine↗

Imaging at high magnetic fields: initial experiences at 4 T.

This article reviews the preliminary experiences and the results obtained on the human brain at 4 T at the University of Minnesota. Anatomical and functional images are presented. Contrary to initial expectations and the early results, it is possible to obtain high-resolution images of the human brain with exquisite T1 contrast, delineating structures especially in the basal ganglia and thalamus, which were not observed clearly in 1.5-T images until now. These 4-T images are possible using a new approach that achieves maximal contrast for different T1 values at approximately the same repetition time and has built-in tolerance to variations in B1 magnitude. For functional images, the high field provides increased contribution from the venuoles and the capillary bed because the susceptibility-induced alterations in 1/T2* from these small-diameter vessels increase quadratically with the magnitude of the main field. Images obtained with short echo times at 4 T, and by implication at lower fields with correspondingly longer echo times, are expected to be dominated by contributions from large venous vessel or in-flow effects from the large arteries; such images are undesirable because of their poor spatial correspondence with actual sites of neuronal activity.

Brain↗

Spatially localized in vivo 1H magnetic resonance spectroscopy of an intracerebral rat glioma.

Surface coil MRI combined with spatially localized spectroscopy was used to noninvasively detect 1H signals from metabolites within an intracerebral malignant glioma in rats. The MRS pulse sequence was based upon two-dimensional ISIS, which restricted 1H signals to a column-shaped volume, combined with one-dimensional spectroscopic imaging, which further resolved the signals into 8 or 16 slices along the major axis of the column. All experiments were executed with adiabatic pulses which induced uniform spin excitation despite the inhomogeneous radiofrequency field distribution produced by the surface coil transmitter. Surface coil MRI and MRS experiments were performed on phantom samples, normal rat brains, and rat brains harboring malignant gliomas. Spatially resolved in vivo 1H spectra of intracerebral gliomas revealed significantly decreased concentrations of N-acetyl-aspartate and creatine and increased lactic acid (or lipids) as compared to the contralateral hemisphere. These results demonstrate that metabolic abnormalities in intracerebral rat gliomas can be spatially resolved in a noninvasive manner using localized in vivo 1H MRS.

Animals↗

Hepatic D-galactosamine toxicity studied with localized in vivo 31P magnetic resonance spectroscopy in intact rats.

Spatially resolved 31P magnetic resonance spectroscopy (MRS) at 4.7 T was applied to noninvasively assess liver phosphorus metabolites in a biochemically well-characterized model of hepatotoxicity induced by injection of a sublethal dose of D-galactosamine (galN). A newly developed hybrid method based on spectral localization with B0 and B1 gradients was employed to obtain multivoxel spectra in intact anesthesized rats. Spatially localized in vivo spectra were recorded 0 to 26 h after galN injection of female rats. In response to galN exposure, diphosphodiester peaks ascribed to UDP-hexosamines became detectable by 4 h and persisted up to 26 h. A metabolite coresonating with inorganic phosphate increased rapidly in intensity by 2 h after galN and returned to baseline by 18 h; this resonance was shown not to be Pi and was assigned to galN-1-phosphate by subsequent high resolution MRS experiments on extracts prepared from these livers. These results confirmed in vivo the metabolic perturbations described previously for this model of hepatotoxicity following biochemical studies based on classical extraction methods. Unlike the in vitro studies, however, these noninvasive experiments provided additional information on the time course of metabolic alterations on the same animal.

Adenosine Triphosphate↗