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Biomedical subjects

M E Phelps

Publications and source records attributed to M E Phelps.

At least 289 records · Page 16Linked to original sources

The fluorodeoxyglucose 18F scan in Alzheimer's disease and multi-infarct dementia.

Patients with Alzheimer's disease and multi-infarct dementia were studied with scans using fluorodeoxyglucose tagged with fluorine 18. The rates of glucose metabolism were calculated. Patients with Alzheimer's dementia showed decreased metabolism in all areas of the brain but with preferential sparing of the primary motor and sensory cortex. Patients with multi-infarct dementia also had global reductions in glucose metabolic rates when compared with normal control subjects, but the areas of hypometabolism were focal and asymmetric.

Aged↗

Comparison of metabolic rates, language, and memory in subcortical aphasias.

Four patients with subcortical lesions and either aphasia or amnesia were compared to four patients with cortical lesions and aphasia. Each patient had [18F] fluorodeoxyglucose positron-emission computed tomography, language, and memory evaluations. Marked metabolic depression was found in the thalamus and caudate in all patients. The subcortical patients had only mild left-cortical changes, while the cortical patients showed marked cortical metabolic changes in the left hemisphere. Language changes were mild in the subcortical patients, while moderate to severe in the cortical patients. All patients showed severe verbal memory dysfunction. The only common abnormalities in the two groups were metabolic changes in the thalamus and severity of verbal memory dysfunction. These findings suggest a relationship between verbal memory and thalamic function.

Adult↗

Sister-chromatid exchange induction in peripheral blood lymphocytes of rats exposed to ethylene oxide by inhalation.

Male Fischer-344 rats were exposed to target concentrations of 0, 50, 150 or 450 ppm ethylene oxide (EO) for 6 h/day for 1 or 3 days. Blood was removed by cardiac puncture and cultured in the presence of 5-bromodeoxyuridine for sister-chromatid exchange (SCE) and chromosome-breakage analyses. EO caused a concentration-dependent increase in SCE following both 1 and 3 days of exposure, and the effects appeared to be additive. No significant dose-dependent increase in chromosome breakage was observed, and reasons for this apparent discrepancy with other published data are discussed. These findings are consistent with the occurrence of elevated SCE frequencies in occupationally-exposed workers, and the results demonstrate for the first time that SCE can be detected in cultured lymphocytes of rodents following inhalation exposures.

Animals↗

Quantitative measurement of local cerebral blood flow in humans by positron computed tomography and 15O-water.

A noninvasive method that employs 15O-water and positron-computed tomography (PCT) was used to measure quantitative local cerebral blood flow (lCBF) in man. 15O-Water (about 30-50 mCi) was introduced through a single-breath inhalation of 15O-carbon dioxide or through an intravenous bolus injection of 15O-water. A sequence of five 2-min PCT scans was initiated at the time of tracer administration. A series of 15-20 blood samples (1 ml each) was withdrawn from the radial artery of the subject over a period of 10 min. Oxygen-15 radioactivities in the blood samples were immediately counted in a well counter to give an input function, which together with the projection data collected by PCT were processed to provide images of 1CBF and local water distribution volume. The method was found to be convenient to use and gave good-quality images of 1CBF. Quantitative values of 1CBF in images were 59 +/- 11 and 20 +/- 4 ml/min/100 g for gray and white matter, respectively, with a gray-to-white matter ratio of 2.93 and a global flow value of 42 +/- 8 ml/min/100 g. Distribution volume of water was 0.85 +/- 0.03, 0.76 +/- 0.03, and 0.81 +/- 0.02 ml/g respectively, for gray matter, white matter, and whole brain.

Adult↗

Cerebral glucose metabolism as a function of age in man: influence of the rate constants in the fluorodeoxyglucose method.

Measurement of the local cerebral metabolic rate of glucose (LCMRGlc) with the fluorodeoxyglucose (FDG) method requires the utilization of appropriate values for the rate constants of the transport and phosphorylation processes. We measured these rate constants as a function of age to determine whether a decline in LCMRGlc as a function of age, in prior studies with the FDG method, actually represents changes in the rate constants. We found that measurements of LCMRGlc are not significantly affected by changes in rate constants as a function of aging, and that LCMRGlc did not change significantly with age.

Adolescent↗

Identification and differentiation of resting myocardial ischemia and infarction in man with positron computed tomography, 18F-labeled fluorodeoxyglucose and N-13 ammonia.

Studies have shown that the extraction of glucose per unit flow is increased in moderately ischemic myocardium primarily due to anaerobic glucose metabolism manifested as lactate production, whereas myocardial infarction is characterized by the loss of metabolically active myocardium. To determine the feasibility of demonstrating these metabolic abnormalities reflecting both ischemia and infarction, we used positron computed tomography (PCT) to evaluate relative regional myocardial exogenous glucose utilization and perfusion in 15 patients with recent myocardial infarction. The positron-emitting tracers of glucose metabolism and perfusion, 18F-2-fluoro-2-deoxyglucose (FDG) and N-13 ammonia, respectively, were used. Fourteen of 19 documented infarctions were demonstrated by PCT to have concordantly decreased glucose utilization and perfusion. However, in an additional 11 regions, glucose utilization was disproportionately increased relative to perfusion, consistent with ischemic glucose consumption. These findings correlated with the presence of postinfarction angina, the site of ischemic electrocardiographic changes during chest pain, and the presence of regional left ventricular dysfunction and severe coronary artery disease. Because three ECG infarct zones not detected by PCT demonstrated ischemic glucose utilization, only two of 19 electrocardiographically defined infarctions had no detectable metabolic abnormality. We conclude that the changes in regional FDG and N-13 ammonia concentrations detected with PCT in patients who had had a recent myocardial infarction are consistent with regional exogenous glucose utilization and perfusion in moderately ischemic and irreversibly infarcted myocardium. This approach has the potential to identify and differentiate resting myocardial ischemia from infarction and to assess tissue viability after an ischemic event.

Adult↗

Local cerebral metabolism during partial seizures.

Interictal and ictal fluorodeoxyglucose scans were obtained with positron CT from four patients with spontaneous recurrent partial seizures, one with epilepsia partialis continua, and one with a single partial seizure induced by electrical stimulation of the hippocampus. Ictal metabolic patterns were different for each patient studied. Focal and generalized increased and decreased metabolism were observed. Ictal hypermetabolism may exceed six times the interictal rate and could represent activation of excitatory or inhibitory synapses in the epileptogenic region and its projection fields. Hypometabolism seen on ictal scans most likely reflects postictal depression and may indicate projection fields of inhibited neurons. No quantitative relationship between alterations in metabolism and EEG or behavioral measurements of ictal events could be demonstrated.

Adolescent↗

Positron computed tomography for studies of myocardial and cerebral function.

Positron computed tomography is a noninvasive medical imaging technique. Biologically active, radiolabeled compounds are administered intravenously to patients and the distribution of the radioactivity is quantitatively measured. By using appropriate mathematical models and labeled compounds, quantitative measurements of local metabolism, blood flow and volume, protein synthesis, transport, receptor binding, drug kinetics, and concentrations can be obtained noninvasively. This technique goes beyond medical imaging; it allows local analytic assays of biochemical reactions. In the heart, the technique measures local blood flow as well as myocardial free fatty acid and glucose metabolism, and can clinically evaluate patients with ischemic heart disease or cardiomyopathies. In the brain, positron computed tomography can be used to examine alterations in blood flow and metabolism including ischemia and degenerative disorders (Huntington's disease and Alzheimer's disease), cerebral tumors, and epilepsy. In normal persons, positron computed tomography shows cerebral activations resulting from physiologic stimulation (auditory and visual).

Alzheimer Disease↗

[Positron computed tomography: a new method for quantitative determination of cardiac metabolism, blood circulation and function. I. Technical and experimental bases].

Positron computed tomography represents a new method which permits qualitative and quantitative assessment of physiologic processes in different organs on a molecular basis. Thus this 'physiologic imaging device' enables noninvasive detection of regional myocardial metabolism, perfusion and global as well as regional myocardial function. The unique capability of simultaneous measurement of the interdependent parameters perfusion, metabolism and function will provide new insights in physiologic and pathophysiologic processes of the heart and, hence, in the understanding of heart disease. Since a great number of cardiac disorders is related to disturbances at the cellular and metabolic level, this new method may contribute to the early detection and eventually to an early treatment of heart disease. With improvements in instrumentation as well as the development of new physiologic indicators and small generator-like cyclotrons, positron computed tomography will become clinically more widespread in various medical centers.

Amino Acids↗

Performance evaluation of a positron tomograph designed for brain imaging.

The NeuroECAT, a multiplane positron tomograph for imaging the brain, was characterized in terms of both quantitative performance and image quality. The tomograph has four modes of operation, defined by the placement of interplane septa and shadow shields. Each mode was fully characterized by measurement of image resolution, axial resolution, resolution uniformity, scatter, accidentals, and deadtime. Each measurement was performed with scattering media simulating the human head, and resolutions were obtained from images processed with reconstruction techniques actually used in patient imaging. The results for the most frequent mode of operation are: image resolution 9.8 +/- 0.2 mm (FWHM), axial resolution 12.4 +/- 0.4 mm, and scatter 8.1% +/- 0.6. At a count rate of 10,000 cps per image plane, accidentals are 9% and the deadtime 3%. Accidentals are measured and subtracted in hardware, and corrections for deadtime loss are calculated from the on-line measurement of triple-coincidence events. Scatter is estimated from the scan data and subtracted in software. Image quality is demonstrated by phantom studies and by the patient images obtained with [F-18] fluorodeoxyglucose and carbon-11 monoxide. The FDG images show clear delineation of the convolutions of the cortical ribbon, internal gray nuclei, internal and external capsules, and other substructures of the brain. The carbon monoxide images, in addition to visualizing the large vessels, clearly show the blood volumes of the cortex, the Sylvian fissure, and the circle of Willis.

Brain↗

L-[1-11C]leucine: routine synthesis by enzymatic resolution.

L-[1-11C]leucine, suitable for the determination of cerebral protein synthesis rates in man using positron emission tomography, has been synthesized using a modified Bucherer-Strecker reaction sequence. The isolation of the pure L-amino acid isomer from the enantiomeric mixture, initially obtained using either an open or closed reaction vessel, was achieved using a D-amino acid oxidase/catalase enzyme complex immobilized on a Sepharose support. The O2 required by the D-amino acid oxidase as the hydrogen acceptor was supplied by catalase. The L-[1-11C]leucine was obtained with a radiochemical purity of greater than 99% and with a radiochemical yield of 25%. Using a remote, semiautomated synthesis system, typical production time was 30-40 min after preparation of H11CN. The use of immobilized enzymes for rapid and effective resolution of amino acid enantiomers eliminates the possibility of protein contamination and assures the production of a sterile, pyrogen-free product.

Brain↗

Local cerebral glucose metabolic response to audiovisual stimulation and deprivation: studies in human subjects with positron CT.

Positron computed tomography (CT) and 18-F fluorodeoxyglucose (FDG) were used to measure local cerebral glucose metabolism (LCMRGlc) in patients and normal subjects during auditory and visual stimulation and deprivation. Sixty-six studies were performed in 42 individuals. In normal subjects metabolic left-right symmetry was found in states of partial (eyes patched or ears plugged) sensory deprivation. Visual stimuli of increasing complexity produced symmetric increases in LCMRGlc of the primary and associative visual cortices. Patients with lesions of the visual pathway but sparing the visual cortex demonstrated abnormalities in visual cortical LCMRGlc that correlated with clinical symptoms. Auditory stimulation studies in normal subjects demonstrated metabolic evidence of hemispheric specialization. The side (left versus right) and site of maximal metabolic response correlated with the type (verbal versus nonverbal) and content (factual story, chords, tone sequences) of the stimulus as well as the strategy used by the subject to solve the listening task. There was no correlation between the site of metabolic response and side of stimulus presentation. The results of these studies demonstrate that positron CT provides new and previously unattainable information about local human brain physiology in normal and pathological states. The limitations, advantages and future prospects of using these methods to study human brain function are discussed.

Aged↗

Measurements of regional tissue and blood-pool radiotracer concentrations from serial tomographic images of the heart.

Quantification of myocardial tissue kinetics from serial tomographic images is limited because of bidirectional cross-contamination of recorded counts between myocardium and blood for metabolic tracers with relative slow blood clearance. We have developed and validated a new deconvolution technique that permits calculation of spillover fractions derived from geometric measurements of the imaged cross section (wall thickness, chamber diameter) and the intrinsic resolution of the tomograph. Serial gated positron-emission computerized imaging (PCT) and a-v blood sampling across the heart were performed in five dogs for 45 min after i.v. C-11 palmitate (CPA) and in five dogs for 3 hr after i.v. F-18 deoxyglucose (FDG). Tracer concentrations in myocardial tissue and arterial blood were also measured in vitro. Uncorrected PCT tissue and blood concentrations correlated poorly with in vitro measurements. After correction for count crossover, the correlation for FDG in tissue was r = 0.99, for FDG in blood r = 0.97, and for CPA in blood r = 0.99. Deconvolution techniques applied to serial PCT images provide accurate noninvasive measurement of myocardial tracer concentrations and direct determination of the arterial input function required for measurements of myocardial metabolism.

Animals↗