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Biomedical subjects

M Garwood

Publications and source records attributed to M Garwood.

At least 19 recordsLinked to original sources

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

An analysis of the intrinsic resonance offset dependence of magnetization generated by stimulated echo pulse sequences for noncoupled spins.

It is demonstrated that the basic radiofrequency pulse train used to generate stimulated echoes (90x-tau TE-90x-tau TM-90x-tau TE-Acq.) is in general characterized by strong amplitude and phase modulations of the transverse magnetization as a function of the resonance offset. Two dephasing techniques which eliminate the modulations are investigated both theoretically and experimentally, and a simple formula is derived for calculating the relative modulation across a spectrum as a function of gradient strength and duration, echo delay, and spectral linewidth.

Magnetic Resonance Spectroscopy

Transmural high energy phosphate distribution and response to alterations in workload in the normal canine myocardium as studied with spatially localized 31P NMR spectroscopy.

Spatially localized phosphorus-31 nuclear magnetic resonance (31P NMR) spectroscopy has been applied to the study of the normal canine myocardium to measure the relative content of high energy phosphates across the left ventricular wall. Transmural NMR data were acquired in five voxels spanning the wall of the left ventricle using the FLAX-ISIS technique. The validity of the FLAX-ISIS approach in acquiring localized spectra for transmural studies and in providing quantitative information from the localized spectra was examined rigorously by studies involving phantoms, intact rats, and the canine myocardium in vivo. The results indicated that (1) this technique yields spatially resolved spectra with partial overlap between adjacent voxels and virtually no overlap between every other voxel; (2) in the canine heart, signals from subepicardium, midwall, and subendocardium can be detected separately without cross contamination; and (3) relative metabolite contents within a voxel and among voxels can be quantitated. Transmural 31P NMR spectra were acquired with cardiac gating on 29 separate animals either at early systole or late diastole, and at three different workloads with the heart rate peak systolic pressure product (RPP) increasing from 6000 mmHg/min to 35,000 mmHg/min. The data revealed that in the normal canine myocardium, the creatine phosphate (CP) content and the CP/ATP ratio was significantly lower in the subendocardium than in the subepicardium. ATP levels were transmurally constant. Both the CP content and the CP/ATP ratio measured for each voxel remained unaltered in relation to either the phase of the cardiac cycle or approximately fourfold increase in workload. Free ADP levels calculated for each voxel showed that ADP was relatively higher in the subendocardium than the subepicardium, and in all transmural layers was higher than its apparent Km for oxidative phosphorylation. In this domain changes in ADP content with workload and MVO2 are not expected and were not observed.

Adenosine Diphosphate

3-D FLASH imaging using a single surface coil and a new adiabatic pulse, BIR-4.

A new adiabatic pulse, which can induce uniform and arbitrary flip angles despite the presence of transmitter coil magnetic field (B1) inhomogeneities, is employed for 3-D fast imaging using a single surface coil for pulse transmission and signal detection. Computer calculations and phantom, rat, and human surface coil imaging experiments demonstrate the utility of this adiabatic pulse for T1-weighted imaging with a transmitter coil which generates a highly inhomogeneous B1 field profile.

Animals

Correlation between transmural high energy phosphate levels and myocardial blood flow in the presence of graded coronary stenosis.

Spatially localized nuclear magnetic resonance spectroscopy was used to investigate with transmural differentiation the response of myocardial high energy phosphate compounds and inorganic orthophosphate (Pi) to graded reductions in coronary blood flow caused by sustained coronary stenosis. In an open-chest model, localized 31P nuclear magnetic resonance spectra from five layers across the left ventricular wall were obtained simultaneously with transmural blood flow measurements during control conditions and during sustained graded reductions in intracoronary pressure. Both the blood flow, and high energy phosphate and Pi contents displayed transmural heterogeneity in response to decreases in intracoronary pressure. The subendocardial creatine phosphate (CP) level remained unchanged as blood flow was reduced to approximately 0.7 ml/min/g wet wt and decreased precipitously beyond this critical flow level. The relation between CP and flow in the midmyocardium and especially in the subepicardium was more complex. Subepicardial CP content did not correlate well with blood flow; however, in cases in which a coronary stenosis resulted in subendocardial hypoperfusion but subepicardial flow was near or above normal, a close correlation was present between subepicardial and subendocardial CP levels. ATP levels in all layers remained unaltered until blood flow was severely reduced. These results demonstrate that 1) the myocardial high energy phosphate and Pi levels at any transmural layer are not generally determined by O2 and blood flow limitation under basal conditions; 2) during subtotal coronary occlusion, increased oxygen extraction is able to meet myocardial needs until a critical level of stenosis is reached; 3) below a critical flow level, subendocardial CP and Pi contents are closely correlated with absolute subendocardial blood flow; and 4) in the presence of a coronary stenosis, subepicardial CP and Pi contents may change even in the absence of perfusion deficit secondary to loss of subendocardial function.

Adenosine Triphosphate

Gas chromatographic-mass spectrometric analysis of hexose monophosphate shunt activity in cultured cells.

A GC/MS method is described for monitoring the relative amount of glucose degraded to lactate via the hexose monophosphate shunt (HMPS) in neoplastic cells. C6 glioma cells were incubated in medium supplemented with [1-13 C]glucose and medium containing [1-13C]glucose with 0.001 mM phenazine methosulfate (PMS). The ratio of the [13C]lactate to [12C]lactate determined from the measurement of the m/z 219/220 and 117/118 ions of the trimethyl silyl derivative, was used to calculate HMPS activity. PMS increased HMPS activity in C6 glioma cells by 3.2 and 4.8 fold at 2 and 12 hours of incubation respectively. GC/MS results were compared with 1H NMR measurements of the [3-13C]lactate/[3-12C]lactate ratio. The GC/MS method was found to require less sample size and yielded better sensitivity than the NMR method.

Animals

Magnetic resonance imaging with adiabatic pulses using a single surface coil for RF transmission and signal detection.

In order to overcome the problems that arise from nonuniform B1 fields, there has been interest in developing pulses that are insensitive to large variations in RF power. Pulses derived from adiabatic passage principles that can execute spin inversion, excitation, and 90 degrees and 180 degrees plane rotations in the presence of B1 inhomogeneities have recently been described. When driven with optimized modulation functions, these pulses can execute uniform excitation, refocusing, and slice-selective inversion over a 10-fold or greater variation in B1 magnitude. This insensitivity to B1 strength enables the execution of T1- and/or T2-weighted spin-echo imaging experiments using coils, such as the surface coil, with extremely inhomogeneous B1 profiles. We have successfully acquired images with these pulses at 200 MHz using a single surface coil as the transmitter and receiver. Images of the slice definition, the region over which the excitation and refocusing pulses operate with a surface coil, and brain images obtained with slice planes perpendicular to the plane of the surface coil are presented. Results demonstrate that these pulses can be transmitted with a surface coil to yield high-quality T1- and/or T2-weighted images without B1 artifacts.

Animals