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Biomedical subjects

J W Prichard

Publications and source records attributed to J W Prichard.

At least 19 recordsLinked to original sources
PubMed1992

1H-[13C] NMR measurements of [4-13C]glutamate turnover in human brain.

A limitation of previous methods for studying human brain glucose metabolism, such as positron emission tomography, is that metabolic steps beyond glucose uptake cannot be studied. Nuclear magnetic resonance (NMR) has the advantage of allowing the nondestructive measurement of 13C distribution in specific carbon positions of metabolites. In this study 1H-[13C] NMR spectroscopy in conjunction with volume localization was used to measure the rate of incorporation of 13C isotope from infused enriched [1-13C]glucose to human brain [4-13C]glutamate. In three studies C4 glutamate turnover time constants of 25, 20, and 17 min were measured in a 21-cm3 volume centered in the region of the visual cortex. Based on an analysis of spectrometer sensitivity the spatial resolution of the method can be improved to < 4 cm3. In conjunction with metabolic modeling and other NMR measurements this method can provide a measure of regional rates of the brain tricarboxylic acid cycle and other metabolic pathways.

Brain↗
PubMed1992

Magnetic resonance spectroscopy of the brain.

Magnetic resonance spectroscopy of the living brain is described. It is based on the same physics as magnetic resonance imaging, but instead of images based on the signal from tissue water, it measures specific compounds in the brain, currently numbering some two dozen. Being almost entirely non-invasive, it is well-suited for longitudinal and human studies of both normal function and disease processes.

Animals↗
PubMed1992

Quantitative analysis of rat synaptosomes and cerebrum using high-resolution 1H magnetic resonance spectroscopy.

This study explored the utility of 1H magnetic resonance spectroscopy to study a standard synaptosomally enriched preparation (P2 pellet) made from rat cerebrum. The preparation contained high concentrations of N-acetylaspartate and gamma-aminobutyric acid and low concentrations of glutamine, indicating that they were in fact rich in neuronal cytosol. Synaptosomes contained half the lactate and glutamine of cerebrum. Alanine, aspartate, glutamate, and succinate had the same concentrations in synaptosomes and cerebrum.

Amino Acids↗
PubMed1992

New anatomical and functional imaging methods.

Powerful new methods for imaging both brain anatomy and brain function are appearing at an increasing rate. The modern era of minimally invasive, highly informative, neurological diagnostic imaging methods began with the introduction of x-ray computed tomography in the 1970s. More recently, positron emission tomography and single-photon emission computed tomography have been used extensively in research on normal and pathological brain function, and they are finding specific medical applications. Nuclear magnetic resonance methods are in widespread use for neurological diagnosis only a decade after they became available. Rapid development of new techniques based on the same principles, and implementable on clinical instruments with relatively minor modifications, will expand the range of nuclear magnetic resonance measurement capabilities considerably in the near future. These technological innovations and others yet to come have major implications for the practice of neurology. The most important one is an increase in relative value among clinical diagnostic skills of history taking and mental status examination, which will remain largely beyond the reach of technology.

Brain↗
PubMed1992

Localized 1H NMR spectra of glutamate in the human brain.

Localized 1H NMR spectra at TE = 12 ms were obtained from cerebral cortex of human subjects using ISIS with surface suppression. The 2.29-ppm resonance was assigned to C4 glutamate with contributions from C4 glutamine and GABA using in vivo spectral editing and comparison of chemical shift with pure compounds. The measured intensity ratio between the 2.29 resonance and the creatine resonance at 3.03 ppm was in good agreement with the ratio predicted from previously reported measurements of glutamate, glutamine, and GABA concentrations in biopsied human brain tissue.

Aspartic Acid↗
PubMed1992

Cerebral lactate turnover after electroshock: in vivo measurements by 1H/13C magnetic resonance spectroscopy.

We reported earlier that brain activation by 10 s of cortical electroshock caused prolonged elevation of brain lactate without significant change in intracellular pH, brain high-energy phosphorylated metabolites, or blood gases. The metabolic state of the elevated lactate has been investigated in further experiments using combined, in vivo 1H-observed 13C-edited nuclear magnetic resonance spectroscopy (NMRS), homonuclear J-edited 1H-NMRS, and high-resolution 1H-NMRS of perchloric acid extracts to monitor concentrations and 13C-isotopic fractions of brain and blood lactate and glucose. We now report that electroshock-elevated lactate pool in rabbit brain approaches equilibrium with blood glucose within 1 h. There was nearly complete turnover of the raised lactate pool in brain; any pool of metabolically inactive lactate could not have been > 5% of the total. In the same experiments, blood lactate underwent < 50% turnover in 1 h. The new 1H-spectroscopic methods used for these experiments are readily adaptable for the study of human brain and may be useful in characterizing the metabolic state of elevated lactate pools associated with epilepsy, stroke, trauma, tumors, and other pathological conditions.

Animals↗
PubMed1992

Proton magnetic resonance spectroscopy of cerebral lactate and other metabolites in stroke patients.

BACKGROUND AND PURPOSE: Proton magnetic resonance spectroscopy can measure in vivo brain lactate and other metabolites noninvasively. We measured the biochemical changes accompanying stroke in 16 human subjects with cortical or deep cerebral infarcts within the first 3 weeks after symptom onset, and performed follow-up studies on six. METHODS: One-dimensional proton spectroscopic imaging encompassing the infarct region was performed with a 2.1-T whole-body magnet using the stimulated echo pulse sequence and an echo time of 270 msec. RESULTS: All but one of the cortical stroke patients had increased lactate within or near the infarct. Persistently elevated cerebral lactate was documented in five of six cases studied serially as long as 251 days after infarction. N-acetylaspartate levels were decreased in most cortical strokes. Elevated lactate, accompanied by minimal reduction in N-acetylaspartate, was recorded in two of four patients in the first week following a small subcortical infarct. CONCLUSIONS: Long-term elevation of lactate commonly occurs after stroke. This lactate may arise from ongoing ischemia or infiltrating leukocytes, or it may be a residual of the lactate formed during the initial insult. The ability to observe stroke-elevated lactate pools at any time after lesion onset provides an approach to distinguishing among these possibilities in the future.

Aspartic Acid↗
PubMed1992

Spectroscopic imaging of stroke in humans: histopathology correlates of spectral changes.

Previous studies of human stroke by 1H nuclear magnetic resonance spectroscopy have shown elevation of lactate lasting 3 to 6 months. Complete metabolic turnover of the elevated lactate pool has been demonstrated 5 weeks after a stroke. Its cellular localization is among the first questions requiring clarification. Information pertinent to this question came to us from a patient with a 2-week-old stroke by 1H nuclear magnetic resonance spectroscopic imaging 1 week before his death led to neuropathologic examination of the brain. 1H spectra from voxels including the infarcts showed increased lactate and decreased N-acetylaspartate. Histopathology showed sheets of foamy macrophages in the infarct, but few neurons. Macrophage density ranged from 196 cells/mm2 near the surface of the infarct to 788 near its medial margin. Glial density was 500 to 800 cells/mm2. Lactate concentration in voxels including portions of the infarct was estimated at 7 to 14 mM. Voxels showing low N-acetylaspartate and high lactate on spectroscopic imaging were associated with histopathologic sections containing foamy macrophages. Brain macrophages--which begin to appear 3 days after infarction and gradually disappear over several months--could be a major source of elevated lactate signals that persist for months after stroke.

Brain↗
PubMed1991

Localized proton NMR observation of [3-13C]lactate in stroke after [1-13C]glucose infusion.

To assess whether elevated lactate in stable stroke is being actively produced from blood glucose localized 1H NMR stimulated echo spectra were obtained from a patient in the region of a 32-day-old cortical infarct before and 60-100 min after infusion of [1-13C]glucose. Prior to the infusion the spectrum from the region of the infarct contained an elevated resonance from C3 lactate and a greatly reduced resonance from N-acetyl groups relative to an unaffected contralateral region. After the infusion two additional resonances were observed at 62 and -64 Hz relative to the unlabeled resonance of C3 lactate which were assigned on the basis of chemical shift and relative intensity to [3-13C]lactate. The [3-13C]lactate fractional enrichment in the infarct region was measured to be 32% which is within error one-half the average [1-13C]plasma glucose enrichment during the postinfusion NMR measurement. The result suggests that the stroke lactate pool was completely derived from infused glucose.

Blood Glucose↗
PubMed1991

What the clinician can learn from MRS lactate measurements.

Lactate is of special importance in brain metabolism. In the 1980s, noninvasive methods for measurement of lactate concentration and turnover rate in living brain by 1H and 13C NMR spectroscopy were implemented in both animals and humans, opening the way to innovative examination of lactate's role in normal and deranged brain function. Early data on elevation of lactate in human visual cortex by physiologic stimulation and turnover of pathologically elevated brain lactate pools in animals and humans suggest that the new methods are likely to benefit clinical practice both directly--by providing information useful in management of individual patients--and indirectly--through improved understanding of disease processes.

Brain↗
PubMed1991

Metabolism of [1-13C]glucose in a synaptosomally enriched fraction of rat cerebrum studied by 1H/13C magnetic resonance spectroscopy.

This study explored the utility of 1H and 13C magnetic resonance spectroscopy to study a standard synaptosomally enriched fraction (P2 pellet) made from rat cerebrum. The preparations contained high concentrations of N-acetylaspartate and gamma-aminobutyric acid and low concentrations of glutamine, indicating that they were in fact rich in neuronal cytosol. The metabolic competence of the preparation was assessed by quantitative measurements of its ability to convert [1-13C]glucose into lactate, glutamate, aspartate, and other metabolites under well oxygenated conditions in 30 minutes. The minimum mean glycolytic rate was 0.8 mM glucose/min and the flow through the tricarboxylic acid cycle was equivalent to 0.2 mM glucose/min.

Animals↗
PubMed1990

Direct carbon versus proton heteronuclear editing of 2-13C ethanol in rabbit brain in vivo: a sensitivity comparison.

Proton NMR editing techniques were utilized to study the pharmacology of 13C-labeled ethanol in the cerebrum of the living rabbit at 4.7 T. The sensitivity of these proton spectroscopic methods was compared to direct carbon spectroscopy and a 14-fold improvement in sensitivity of 1H over 13C NMR spectroscopy was observed in vivo. This increase in sensitivity permitted the observation of the time course of the influx and afflux of this 13C-labeled compound with a time resolution of approximately 2 min per spectrum.

Animals↗
PubMed1990

In vivo measurements of ethanol concentration in rabbit brain by 1H magnetic resonance spectroscopy.

In vivo 1H magnetic resonance spectroscopy was used to measure the cerebral ethanol concentration in the rabbit after both intraarterial and intragastric administration. There was good agreement between cerebral and blood ethanol concentrations at all times after administration by either route. Cerebral ethanol levels, measured using in vivo 1H spectroscopy, agreed well with those measured in perchloric acid extracts of brain, analyzed by both high-resolution 1H spectroscopy and gas chromatography. Ethanol may be useful as an indicator to measure cerebral blood flow by 1H spectroscopy and chemical shift-selective magnetic resonance imaging.

Animals↗
PubMed1990

Proton NMR observation of phenylalanine and an aromatic metabolite in the rabbit brain in vivo.

1H nuclear magnetic resonance (NMR) was used to detect directly the signal from the aromatic protons of phenylalanine (phe) in the brains of rabbits made hyperphenylalaninemic by administration of a diet high in phe and containing 0.4% alpha-methylphenylalanine. In addition to those resonances found in the region between 6.5 and 8.5 ppm in the 1H NMR spectra of control rabbits, a resonance centered at 7.37 ppm was observed in the spectra obtained from the brains of hyperphenylalaninemic rabbits in vivo or in situ postmortem. The chemical shift of this additional resonance was that expected for protons of the phenyl ring of phe. Its intensity correlated well with measurements of brain phe levels made on postmortem samples by amino acid analyzer. Both of these measurements correlated poorly with amino acid analyzer measurements of serum phe, especially at high values of the latter. High-resolution 1H NMR spectra of the brain extracts showed that in most animals an unidentified aromatic compound, possibly gamma-glutamyl-phe, was present in addition to phe. This study demonstrates the feasibility of measuring the concentration of brain phenyl and its metabolites noninvasively by 1H NMR. The method can be used for similar measurements in human brain.

Animals↗
PubMed1990

Measurement of ethanol in the human brain using NMR spectroscopy.

Ethanol in the human brain is readily observable by noninvasive 1H NMR spectroscopy. We have made such observations in a human subject with a time resolution per measurement of 6.5 min and volume resolution of 16 cc. The ethanol methyl proton signal is well separated from signals of other metabolites in 1H spectra from human brain and it is one of the most intense signals in such spectra when blood ethanol concentration is 0.1% (21.7 mM)--the legal definition of alcoholic intoxication in many jurisdictions. These properties, plus the fact that the ethanol signal can be further isolated from other resonances by spectral editing, open several possibilities for further investigation.

Alcoholic Intoxication↗
PubMed1989

High-field proton magnetic resonance spectroscopy of human cerebrum obtained during surgery for epilepsy.

We analyzed specimens of histologically normal human cerebrum obtained at surgery for medically refractory epilepsy using proton magnetic resonance spectroscopy. Perchloric acid extracts of anterolateral temporal lobe cortex contained greater concentrations of creatine, N-acetylaspartate, gamma-aminobutyric acid, alanine, and glutamate than the under lying white matter, which contained more acetate. Frontal and temporal lobe specimens composed of both gray and white matter failed to show statistically significant differences in the concentrations of creatine, N-acetylaspartate, alanine, aspartate gamma-aminobutyric acid, glutamate, glycine, taurine, threonine, valine, acetate, choline, beta-hydroxybutyric acid, inositols, lactate pyruvate, or succinate.

Adult↗