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Biomedical subjects

G M Pohost

Publications and source records attributed to G M Pohost.

At least 19 recordsLinked to original sources

The evolving role of MRI in the assessment of coronary artery disease.

Magnetic resonance imaging (MRI) methods are positioned to make a major impact in the care of patients with ischemic heart disease. Further advances are to be expected in the area of myocardial perfusion imaging and noninvasive MRI coronary "angiography." Work also continues in determining quantitative flow via MRI. Although expensive, the unique ability of MRI methods to provide multiple pieces of information in a single examination may make this technology cost effective. The concept of a "one-step shop" is progressing steadily toward a clinical reality.

Coronary Disease

Block regional interpolation scheme for k-space (BRISK): a rapid cardiac imaging technique.

We introduce an acquisition method, "block regional interpolation scheme for k-space" (BRISK), to reduce the acquisition time for cardiac imaging. The method exploits the high degree of correlation that exists between time-resolved cardiac images. For representative k-space data sets, Fourier analysis was applied along the cardiac phase dimension to reveal that different regions of k-space can be effectively sampled at different rates. A reduced sampling strategy was implemented, and unsampled points were generated by Fourier interpolation. Time savings of up to 75% are quite feasible and 25% BRISK scans compare well with 100% scans. Simulations and acquisitions using a normal volunteer and patients are presented.

Aortic Valve Insufficiency

3D 31P spectroscopic imaging of the human heart at 4.1 T.

High field (4 Tesla) spectroscopic imaging offers the advantages of increased signal-to-noise ratio and the possibility of acquiring high resolution metabolite images. We have applied a three dimensional spectroscopic imaging sequence using a sparse Gaussian sampling method to acquire phosphocreatine (PCr) images of the human heart with 8-cc voxels. PCr images enabled observation of the septum, left ventricular free wall, apex, and skeletal muscle. Quantitative evaluation of the 50 myocardial voxels acquired from 10 studies of healthy adults revealed a PCr/adenosine triphosphate (ATP) ratio of 1.80 +/- 0.32 after correction for saturation effects. Due to the small size of the voxels and the ability to choose the location of the volumes to minimize inclusion of blood, no correction for blood pool ATP was required. The calculated PCr/ATP ratio is in agreement with other studies at 1.5 and 4.0 T.

Adenosine Triphosphate

Multislice first-pass myocardial perfusion imaging on a conventional clinical scanner.

A technique is demonstrated for the acquisition and processing of multislice, first-pass contrast-enhanced perfusion images in the myocardium. The acquisition is a modification of "keyhole" imaging in which time series images are acquired by sampling a limited segment of k-space, corresponding to the low spatial frequencies. In the modification demonstrated here, keyhole samples are divided into two groups that are sampled on alternate cardiac cycles. The alternate "missing" k-space portions are synthesized by Fourier interpolation. Visualization of contrast agent accumulation by image subtraction is demonstrated. A motion artifact reduction process using time domain Fourier filtering is used to reduce artifacts from respiration. Studies were performed on 46 patients at 1.5 T using gadoteridol (0.05-0.1 mmol/kg) injected into the right antecubital vein in conjunction with radionuclide imaging. Fully concordant studies were noted in 27 of these patients. Remaining studies were either partially or completely discordant for reasons relating to the differing natures of radionuclide versus MR contrast agent characteristics.

Artifacts

MR imaging of regional cardiac function: low-pass filtering of wall thickness curves.

Wall thickness curves (WTCs) derived from MR images are subject to considerable measurement error. This study determines the effects of low-pass Fourier filtering of WTCs on functional parameters derived from the curve: peak rate of wall thinning (PRWT) and time to PRWT (TPRWT). The inter-subject standard deviation (SD) of PRWT changed from 0.35 to 0.18, and the SD of TPRWT from 34.3 to 29.5. Differences between neighboring segments decreased from 0.31 to 0.15% mean thickness/ms for PRWT (P = 0.012), and from 35.0 to 19.0 ms for TPRWT (P = 0.005). It is concluded that filtering of MR imaging-derived WTCs contributes to a better representation of myocardial wall motion.

Adult

Water-suppressed one-dimensional 1H NMR chemical shift imaging of the heart before and after regional ischemia.

This study tests the hypothesis that brief periods of ischemia result in an increase in myocardial lipids during early reperfusion. We conducted 1H NMR spectroscopy to serially measure myocardial lipids before and after regional ischemia. Localized 1H NMR spectra (spatial resolution of 1.25 mm) were obtained using a one-dimensional chemical shift imaging technique. Two regions, the subendocardium and the subepicardium, were estimated by summing spectral areas from three slices (3.75 mm). Two groups of dogs that underwent a 45 min ischemia and 4 h reperfusion were studied: a group in which the myocardium beneath the surface coil underwent ischemia and reperfusion; and a group in which the ischemic event was distant from the tissue under the surface coil. Microsphere measurements showed significant blood flow reductions in the subepicardium and subendocardium in the ischemic zones during coronary occlusion. Flow returned to baseline values during reperfusion. In the ischemic zone group, the subendocardium, the triglyceride resonance areas decreased by 24% (p < 0.05) during reperfusion. However, subepicardial triglyceride areas were unchanged. Subendocardial creatine areas were also unchanged. The non-ischemic zone group subendocardial triglycerides decreased by 33% (p < 0.05) following ischemia and reperfusion in the remote region. In contrast to the ischemic group, the subepicardial triglyceride resonance areas decreased by 42% (p < 0.05). Subendocardial creatine areas were unchanged. These data show that triglycerides of the ischemic-reperfused subendocardium do not increase during 4 h of reperfusion. Furthermore, they show that the triglycerides resonance areas of the non-ischemic region decrease following remote ischemia and reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Numerically optimized experiment design for measurement of grey/white matter metabolite T2 in high-resolution spectroscopic images of brain.

T2 relaxation measurements for choline (Cho), total creatine (Cr = creatine + phosphocreatine), and N-acetylaspartate (NAA) were made separately in eight healthy volunteers using an average of forty 0.5 cc volumes (20 from grey matter and 20 from white matter) in spectroscopic images with a 32 x 32 resolution and a 240 mm field of view. In grey matter, the means and standard deviations of the T2 values were 186 +/- 23, 149 +/- 10, and 232 +/- 15 ms for Cho, Cr, and NAA, respectively, and in white matter, the mean T2 values were 178 +/- 16, 143 +/- 8, and 228 +/- 16 ms, respectively, with no significant differences between grey and white matter. The high-resolution measurements of T2 values were possible because of experimental planning based on the minimization of predicted fitting uncertainties. Explicit expressions were derived to estimate the uncertainties in T2 values, and it was found that two spectroscopic images with echo times of 50 and 250 ms, respectively, would yield sufficient precision for T2 measurements. The derivation of the expressions, a discussion of their behavior, and the experimental planning and verification are presented.

Aspartic Acid

Concomitant EEG, lactate, and phosphorus changes by 1H and 31P NMR spectroscopy during repeated brief cerebral ischemia.

Pilots of high-performance aircraft are subject to transient loss of consciousness due to cerebral ischemia resulting from sudden high gravitational stress. To assess the effects of gravitational stress-induced blackout on cerebral metabolism and electrical function, we developed an animal model in which global cerebral ischemia is produced repeatedly at short intervals. Rats were prepared by ligation of subclavian and external carotid arteries and the right carotid artery was cannulated bidirectionally to measure circle of Willis and systemic pressures. Ischemia was induced by inflation of an occluder about the left carotid artery. Interleaved 31P and 1H NMR spectra were acquired on a 4.7-T Biospec system simultaneously with EEG recordings. We report results from 20 experiments of 30-min duration in which rats were subject to 30 1-min ischemia:reflow cycles of 10I:50R, 20I:40R, 30I:30R, and 40I:20R [numbers are seconds of ischemia (I) and reflow (R) during each 1-min cycle]. During ischemia the graded delivery of the ischemic insult permitted direct correlations between 2- to 5- and 7- to 20-Hz EEG activity and progressive changes in pH, lactate, ATP, phosphocreatine (PCr) and Pi. The best correlations were found between EEG activity and pH and PCr; correlation coefficients ranged from 0.93 to 0.95. A loss of EEG activity was observed without significant sustained energy loss in all but the most severe cycle.

Adenosine Triphosphate

Acylcarnitine accumulation does not correlate with reperfusion recovery in palmitate-perfused rat hearts.

Carnitine palmitoyltransferase-I (CPT-I) inhibitors improve postischemic myocardial function either by decreasing muscle long-chain acylcarnitines (LCAC) during ischemia or by increasing oxidation of alternate substrates such as glucose during reperfusion. These possibilities were evaluated using oxfenicine, a CPT-I inhibitor, and alternate substrates that bypass carnitine-dependent metabolism. Isolated rat hearts subjected to 20 min of ischemia followed by 40 min of reperfusion with 1.8 mM palmitate as exogenous substrate recovered little function during reperfusion. Hearts made ischemic and reperfused with palmitate and 2.4 mM hexanoate as exogenous substrates had significantly improved reperfusion function compared to palmitate-perfused hearts. Addition of 2 mM oxfenicine to palmitate-hexanoate-perfused hearts gave an additional small improvement in reperfusion function. At the end of ischemia, the LCAC content of hearts perfused with palmitate or hexanoate and palmitate was identical. Palmitate-, hexanoate, and oxfenicine-perfused hearts had significantly decreased LCAC content at the end of ischemia compared with hexanoate-palmitate-perfused hearts. Therefore, depressed reperfusion function in long-chain fatty acid-perfused hearts can be ameliorated by alternate substrates, including medium-chain fatty acids. LCAC accumulation during ischemia apparently plays only a minor role in the postischemic dysfunction of long-chain fatty acid-perfused hearts.

Acylation

Right and left ventricular volumes and function after acute pulmonary hypertension in intact dogs.

A canine model was developed to record right (RV) and left ventricular (LV) volumes and high-fidelity pressures during acute pulmonary hypertension without the need for major surgery. In this study, new methodology was applied to record high-fidelity RV and LV pressures during cinemagnetic resonance imaging of the heart before and after acute pulmonary hypertension in six anesthetized intact dogs in which the pericardium and thorax were never disturbed by any surgical procedure. After pulmonary embolus, RV systolic pressure increased from 27 + 2 (SD) to 43 +/- 8 mmHg (P < 0.01) as LV systolic pressure decreased (97 +/- 17 to 76 +/- 3 mmHg; P < 0.05). Stroke volume (26 +/- 7 to 21 +/- 5 ml; P < 0.05) and RV ejection fraction (45 +/- 9 to 28 +/- 3%; P < 0.01) decreased as LV ejection fraction was unchanged (50 +/- 5 to 52 +/- 5%; P = NS). LV end-diastolic pressure decreased from 11 +/- 4 to 7 +/- 3 mmHg (P < 0.05), and RV end-diastolic pressure increased from 6 +/- 3 to 11 +/- 3 mmHg (P < 0.01). RV end-diastolic volume increased from 57 +/- 14 to 75 +/- 20 ml (P < 0.01) as LV end-diastolic volumes decreased from 53 +/- 11 to 42 +/- 10 ml (P < 0.01), resulting in no change in total ventricular volume at end diastole (111 +/- 24 to 116 +/- 28 ml). The observed mean decrease of 4.0 mmHg and 11 ml in LV end-diastolic pressure and volume, respectively, was associated with no change in total ventricular volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Nuclear magnetic resonance studies of cationic and energetic alterations with oxidant stress in the perfused heart. Modulation with pyruvate and lactate.

The postischemic generation of oxygen-derived free radicals may contribute to myocardial reperfusion injury by affecting sarcolemmal ion transport. Recent evidence indicates that exposure to reactive oxygen intermediates induces rapid increases in myocardial cytosolic free Ca2+ (Ca2+i). The mechanism is undetermined but may involve disturbances in Na+ homeostasis. We tested this hypothesis by interleaving 23Na and 31P nuclear magnetic resonance (NMR) measurements of Na+i and high-energy phosphates in glucose-perfused rat hearts exposed to hydroxyl radicals generated from H2O2 and Fe3+. In separate experiments, K+i and Ca2+i were measured with 39K and 19F NMR, respectively. The hearts rapidly exhibited contracture. Threefold Na+i increases and substantial K+i depletion were observed. Glycolytic inhibition was indicated by rapid sugar phosphate accumulation and cellular energy depletion. Notably, however, severe functional and energetic deterioration and substantial elevation of Ca2+i occurred before substantial Na+i accumulation or K+i depletion was observed. Further experiments investigated the ability of pyruvate to scavenge H2O2 and to protect the myocardium from oxidant stress. Pyruvate (1 or 2.5 mmol/L) dramatically attenuated functional and energetic alterations and alterations in Na+i and K+i, whereas acetate (2.5 mmol/L) offered no protection. Unlike pyruvate, lactate (5 mmol/L) has little or no capacity to scavenge H2O2 but has similar protective effects. In conclusion, pyruvate effectively protects against H2O2/Fe3+, largely by direct H2O2 scavenging. Protection with lactate may involve intracellular pyruvate augmentation. Without exogenous pyruvate or lactate, myocardial Na+ homeostasis can be substantially altered by oxidant stress, possibly via cellular energy depletion. Excess Na+i accumulation may, in turn, hasten metabolic and functional deterioration, but a causal link with the initial alterations in function or Ca2+i was not supported.

Animals

Detection of brain glutamate and glutamine in spectroscopic images at 4.1 T.

Brain glutamate and glutamine were detected in healthy human volunteers in spectroscopic images with a nominal voxel size of 2.25 cm3 at an echo time of 15 ms. Due to the increased frequency separation and simplification of J-coupling patterns, the separate detection of brain glutamate and glutamine at short echo times was possible. Creatine, choline, and N-acetylaspartate with other N-acetylated compounds were also detected. The ratios of the metabolite resonance intensities were in agreement with previously published values.

Brain

Observation of cardiac lipids in humans by localized 1H magnetic resonance spectroscopic imaging.

Different approaches are being explored for the noninvasive observation of myocardial lipids in the human heart by in vivo 1H NMR spectroscopy. One approach is to measure cardiac lipids using a combination of volume selection and 2D gradient phase encoding. From these data sets lipid images can be reconstructed. By comparing these lipid images with 1H MR scout images, it is demonstrated that these signals represent epicardial and pericardial lipid. By selecting a smaller bar-shaped volume combined with 1D phase encoding or by using single volume techniques, it is possible to avoid most of the pericardial and epicardial lipid to obtain myocardial 1H NMR spectra of the human heart showing lipid signals, as well as trimethylamine and (phospho)creatine signals. These measurements demonstrate the feasibility of obtaining 1H NMR spectra of the human myocardium.

Humans

High frequency volume coils for clinical NMR imaging and spectroscopy.

A tuned transmission line resonator has been developed in theory and in practical design for the clinical NMR volume coil application at 4.1 tesla. The distributed circuit transmission line resonator was designed for high frequency, large conductive volume applications where conventional lumped element coil designs perform less efficiently. The resonator design has made use of a resonant coaxial cavity, which could be variably tuned to the Larmor frequency of interest by tunable transmission line elements. Large head- and body-sized volumes, high efficiencies, and broad tuning ranges have been shown to be characteristic of the transmission line resonator to frequencies of 500 MHz. The B1 homogeneity of the resonator has been demonstrated to be a function of the electromagnetic properties of the load itself. By numerically solving Maxwell's equations for the fully time-dependent B1 field, coil homogeneity was predicted with finite-element models of anatomic structure, and inhomogeneities corrected for. A how-to exposition of coil design and construction has been included. Simple methods of quadrature driving and double tuning the transmission line resonator have also been presented. Human head images obtained with a tuned transmission line resonator at 175 MHz have clearly demonstrated uncompromised high field advantages of signal-to-noise and spatial resolution.

Brain

2D 1H spectroscopic imaging of the human brain at 4.1 T.

A two-dimensional spectroscopic imaging sequence consisting of an inversion recovery pulse, a plane selective prefocused pulse, and a semiselective water suppression pulse has been used to create 1H spectroscopic images of the human brain with nominal voxels of 0.5 cc. Due to the excellent lipid suppression provided by the inversion recovery pulse and subsequent delay, only planar volume selection is required enabling the entire brain within the slice to be imaged without contamination from extracerebral lipids in the brain voxels. The use of a semiselective refocusing pulse for water suppression permits any echo evolution time to be used, minimizing J-modulation and T2 losses, while retaining full sensitivity in the lactate resonance. Using this sequence we have visualized the lactate elevation in the peri-infarct region about a 6-week-old stroke.

Brain

Evaluation of cerebral gray and white matter metabolite differences by spectroscopic imaging at 4.1T.

Using a 4.1T whole body system, we have acquired 1H spectroscopic imaging (SI) data of N-acetyl (NA) compounds, creatine (CR), and choline (CH) with nominal voxel sizes of 0.5 cc (1.15 cc after filtering). We have used the SI data to estimate differences in cerebral metabolites of human gray and white matter. To evaluate the origin of an increased CR/NA and CH/NA ratios in gray matter relative to white matter, we measured the T1 and T2 of CR, NA, and CH in gray and white matter using moderate resolution SI imaging. In white matter the T2s of NA, CR, and CH were 233 +/- 27, 141 +/- 18, and 167 +/- 20 ms, respectively, and 227 +/- 27, 140 +/- 16, and 189 +/- 25 ms in gray matter. The T1 values for NA, CR, and CH were 1267 +/- 141, 1487 +/- 146, and 1111 +/- 136 ms in gray matter and 1260 +/- 154, 1429 +/- 233, and 1074 +/- 146 ms in white matter. After correcting for T1 and T2 losses, creatine content was significantly lower in white matter than gray (P < 0.01, t-test), with a white/gray content ratio of 0.8, in agreement with biopsy and in vivo measurements at 1.5 and 2.0T.

Aspartic Acid

Structural studies of NMR detected lipids in myocardial ischemia.

Lipid-induced abnormalities in myocardial function have been implicated in a number of ischemic events including the accumulation of lipids in human myocardium following myocardial infarction. Although animal models have shown the source of these lipids to be triglycerides, the specific species involved has not been identified. In order to better understand the mechanism(s) defining this lipid accumulation, it follows that the identification of the lipids involved may be important in achieving this aim. Therefore, this study examined the use of NMR probes for delineating the biochemical makeup of the increased 1H NMR observed lipid signal following myocardial infarction. Specifically, the present study demonstrated the utility of the spin-echo pulse sequence for the study of alterations in myocardial lipids following ischemic injury. Spin-echo spectra allowed the analysis of subsets of lipids within the large lipid pool inherent in most myocardium. The analyses of the chemical shifts of the lipid resonances provided a simple yet powerful means for deducing lipid class associated with the ischemic injury and suggested the species arises predominantly from saturated lipids. The examination of the CH2/CH3 NMR ratio provided additional information regarding the species involved, however, because the spin-echo technique was utilized, which may distort certain signal intensities, caution must be exercised in interpreting the specific species involved. With this in mind, a tentative assignment has been given to octanoic acid. Finally, a temperature dependence of the lipid signals was noted and determined to be unique for spin-echo lipid.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals