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Biomedical subjects

M E Phelps

Publications and source records attributed to M E Phelps.

At least 307 records · Page 17Linked to original sources
PubMed1983

Synthesis and myocardial kinetics of N-13 and C-11 labeled branched-chain L-amino acids.

Glutamate dehydrogenase (GDH), immobilized on CNBr-activated Sepharose supports, was used with N-13 ammonia to aminate alpha-ketoisocaproic acid (KIC), and alpha-ketoisovaleric acid (KIV) to produce N-13-labeled branched-chain L-amino acids with radiochemical yields ranging from 29% to 35%. From kinetic and practical considerations, pH 7.5-8.0 was established to be optimal for the synthesis of N-13-labeled branched-chain-L-amino acids. Myocardial time-activity curves in dogs at control, during low-flow ischemia, reperfusion, and after transaminase inhibition following intracoronary bolus injection of the N-13-labeled amino acids were biexponential. Higher retention of N-13 activity was observed in ischemic segments both during low-flow ischemia (29.2%) and reperfusion (23.2%) when compared with controls (20.0%), (n = 4). On the other hand, transaminase inhibition decreased residue fractions from 21.0% at control to 13.9% (n = 4). The residual activity with L-[1-11C]leucine allows for the calculation of protein synthesis rates.

Amino Acids, Branched-Chain↗
PubMed1983

Assessment of the [18F]fluorodeoxyglucose kinetic model in calculations of myocardial glucose metabolism during ischemia.

The lumped constant--a term in the operational equation of the Sokoloff tracer kinetic model for deoxyglucose that accounts for the difference in transport and phosphorylation between glucose and its analog, deoxyglucose--could potentially vary from normal to ischemic conditions in the heart. To test the stability of the lumped constant during ischemia, we evaluated the ratio of the extraction fraction for (F-18)-fluorodeoxyglucose (FDG) to that for glucose (a measure of the lumped constant if there is no significant dephosphorylation of FDG-6-PO4) and the rate constant for dephosphorylation of FDG-6-PO4 (k4*) in the isolated, arterially perfused interventricular septum of the rabbit during moderate and severe demand-induced and reduced-flow ischemias. The lumped constant and k4* in each of the four ischemic experimental conditions were found not to be significantly different from the value obtained from the nonischemic controls.

Animals↗
PubMed1982

Patterns of human local cerebral glucose metabolism during epileptic seizures.

Ictal patterns of local cerebral metabolic rate have been studied in epileptic patients by positron computed tomography with 18F-labeled 2-fluoro-2-deoxy-D-glucose. Partial seizures were associated with activation of anatomic structures unique to each patient studied. Ictal increases and decreases in local cerebral metabolism were observed. Scans performed during generalized convulsions induced by electroshock demonstrated a diffuse ictal increase and postictal decrease in cerebral metabolism. Petit mal absences were associated with a diffuse increase in cerebral metabolic rate. The ictal fluorodeoxyglucose patterns obtained from patients do not resemble autoradiographic patterns obtained from common experimental animal models of epilepsy.

Brain↗
PubMed1982

Noninvasive assessment of coronary stenoses by myocardial imaging during pharmacologic coronary vasodilation. VI. Detection of coronary artery disease in human beings with intravenous N-13 ammonia and positron computed tomography.

The possibility of detecting mild coronary stenoses with positron computed tomography and nitrogen (N-13) ammonia administered during pharmacologic coronary vasodilation was previously demonstrated in chronically instrumented dogs. The feasibility of using this technique in human beings and its sensitivity in determining the degree and extent of coronary artery disease were examined in 13 young normal healthy volunteers and 32 patients with angiographically documented coronary artery disease. N-13 ammonia was administered intravenously and its distribution in the left ventricular myocardium recorded at rest and during dipyridamole-induced coronary hyperemia. In the 13 volunteers, N-13 activity was homogeneous at rest and during hyperemia, whereas 31 of the 32 patients had regional defects on the hyperemic images not present during rest. All six patients with double, all 10 with triple and 15 of 16 patients with single vessel disease (97 percent) were correctly identified with the technique. Two vessel involvement was correctly identified in five of the six patients with double vessel disease and three vessel disease in six of 10 patients. Of all 58 coronary stenoses, 52 (90 percent) were correctly identified. In a subgroup of 11 patients, the technique was compared with exercise thallium-201 planar images, which were abnormal in 10 (91 percent) whereas N-13 images were abnormal in all 11. Of the 19 stenosed coronary arteries in this subgroup, 11 (58 percent) were correctly identified with thallium-201 and 17 (89 percent) with tomography (p less than 0.01). It is concluded that cross-sectional imaging of the myocardial distribution of N-13 ammonia administered during pharmacologic coronary vasodilation is a highly sensitive and accurate means for noninvasive detection of coronary stenoses in human beings and for estimating the extent of coronary artery disease.

Adolescent↗
PubMed1982

Cerebral metabolism and atrophy in Huntington's disease determined by 18FDG and computed tomographic scan.

Patterns of local cerebral glucose utilization were measured with positron emission, computed tomography using the 18F-fluorodeoxyglucose method in 13 patients with Huntington's disease (HD), 15 subjects at risk for HD, and 40 normal control subjects. These data were compared with computed tomographic measures of cerebral atrophy, with age, and with duration and severity of symptoms. The results indicate that in HD there is a characteristic decrease in glucose utilization in the caudate and putamen and that this local hypometabolism appears early and precedes bulk tissue loss. In contrast to patients with senile dementia, in these HD patients glucose utilization typically was normal throughout the rest of the brain, regardless of the severity of symptoms and despite apparent shrinkage of brain tissue. Our results suggest the possibility that the caudate may be hypometabolic in some asymptomatic subjects who are potential carriers of the autosomal dominant gene for HD.

Adolescent↗
PubMed1982

Tomographic mapping of human cerebral metabolism: sensory deprivation.

Local cerebral glucose metabolism was measured in 22 right-handed, normal volunteers using 18F-fluorodeoxy-glucose and positron computed tomography. Three states consisting of selective or combined auditory or visual deprivation were examined. Results demonstrated a progressive decline in overall glucose metabolism with reduced sensory inputs. The relative metabolism of the frontal cortex compared to that of the parietal and occipital cortex progressively increased from the eyes-closed to the both-closed states. Left-right symmetry was found throughout the distribution of structures within the region of brain samples for both the selective auditory and visual deprivation test conditions, but a relative decrease in right-sided metabolism occurred in the combined audiovisual deprivation state. The most significant metabolic asymmetries occurred in the perisylvian, inferior prefrontal, and lateral occipital cortex. The relative metabolic rates of the medial occipital cortex, measured as a percentage of the hemispheric mean, doubled bilaterally with eye opening. The results demonstrate the difficulties inherent in defining a stable and reproducible "resting" state for the human brain.

Adult↗
PubMed1982

Interictal cerebral glucose metabolism in partial epilepsy and its relation to EEG changes.

Interictal positron computed tomography (PCT) with 18F-fluorodeoxyglucose was performed on 50 patients with partial seizures disorders. Electroencephalographic (EEG) monitoring was carried out during the metabolic studies using scalp and sphenoidal electrodes in 33 patients and stereotaxically implanted depth electrodes in 17. Four patients in this series had focal abnormalities on x-ray computed tomographic scans, but these were at the site of the presumed epileptogenic lesion in only 2. One or more discrete zones of hypometabolism were identified in 35 patients, and only 1 patient appeared to show focal interictal hypermetabolism. No quantitative relationship could be demonstrated between the degree of focal hypometabolism and either the frequency of interictal EEG spikes of the presence of focal nonepileptiform EEG changes. It was concluded that metabolic and electrophysiological techniques measure different aspects of cerebral dysfunction in seizure disorders. Although interictal PCT in patients with partial epilepsy usually demonstrates zones of hypometabolism this finding, per se, does not reveal the epileptic nature of the abnormality.

Adolescent↗
PubMed1982

Pathological findings underlying focal temporal lobe hypometabolism in partial epilepsy.

Histopathological studies were carried out on temporal lobe tissue from 25 patients with partial complex seizures who were studied by interictal positron computed tomography (PCT) with 18F-fluorodeoxyglucose and subsequently underwent anterior temporal lobe resection. Abnormalities were identified on x-ray computed tomographic scans in 7 patients, but none indicated the site of a pathologically confirmed structural lesion. Hypometabolic zones were observed on PCT scans of 22 patients and corresponded to focal pathological abnormalities in 19 (15 mesial temporal sclerosis, 2 small neoplasms, 1 angioma, 1 heterotopia). In 1 patient with a focally abnormal PCT scan and no pathological changes, the lesion may have been located posterior to the resection. In the remaining 2 patients, the hypometabolic zones later disappeared and may have represented a transient response induced by depth electrode implantation. Three patients with normal PCT scans had no pathological abnormalities in their resected tissue. The degree of relative hypometabolism measured by PCT correlated well with the severity of the pathological lesion, but the size of the hypometabolic zone was generally much larger than the area of pathological involvement. This discrepancy could not be considered an artifact of technique and must represent either structural abnormalities below the resolution of routine histopathological studies (e.g., loss of synapses) or functional inactivation of neuronal elements associated with the epileptogenic lesion.

Adolescent↗
PubMed1982

Comparative localization of epileptic foci in partial epilepsy by PCT and EEG.

One or more interictal positron computed tomograms of 18F-fluorodeoxyglucose were obtained on 50 patients with partial seizure disorders. Ictal as well as interictal electroencephalographic (EEG) data were available for all 50 patients, with scalp, sphenoidal, and depth electrode recordings done on 27 and scalp and sphenoidal recordings alone on 23. Thirty-five patients demonstrated one or more abnormal interictal zones of hypometabolism, while combined EEG studies were localizing for 36. There were considerable disagreements between the location of metabolic deficits and the epileptic focus revealed by individual scalp and depth EEG recorded ictal and interictal epileptiform activity; however, there was good correlation between the site of focal hypometabolism and the epileptic focus determined by the combined results of all electrophysiological studies. When focal hypometabolism and focal nonepileptiform EEG abnormalities (i.e., slow waves and attenuation of fast rhythms) were both present in the same patient, their localization agreed completely. Metabolic and combined electrophysiological techniques both occasionally produced false positive as well as false negative results. When used together, the EEG can confirm that a hypometabolic zone is epileptogenic, while FDG scans may indicate whether an epileptic EEG focus represents a lesion or propagation from a distant site.

Adolescent↗
PubMed1982

Assessment of regional myocardial ischemia by positron-emission computed tomography.

Positron-emission computed tomography (PCT) is a new means of studying regional myocardial metabolism. This new device permits quantitative, cross-sectional imaging of the tissue concentrations of positron-emitting tracers of blood flow and metabolism in the myocardium. To examine the potential value of PCT for evaluating regional alterations in myocardial metabolism, acute myocardial ischemia was induced by rapid atrial pacing in open-chest dogs with partial coronary stenoses. Regional myocardial glucose uptake and utilization of free fatty acids were examined with the glucose analog F-18 2-fluoro-2-deoxyglucose (FDG) and C-11-labeled palmitic acid. Myocardial blood flow was evaluated with N-13 ammonia. In the ischemic segment, uptake of C-11 palmitic acid was reduced in proportion to blood flow and its rate of clearance as an index of beta oxidation was delayed. There was a relative or absolute increase in FDG uptake (depending on the uptake of FDG in the normal myocardium). Similar observations were made in patients with ischemic heart disease and anginal symptoms at the time study. The observed alterations in the regional distribution of positron-emitting tracers of metabolic substrates in ischemic myocardium are in agreement with previously reported animal experimental studies in which a fall in free fatty acid utilization associated with an increase in glycolytic flux was observed. These studies indicate that metabolic alterations associated with acute myocardial ischemia observed previously in destructive animal experiments do indeed occur in humans and can now be demonstrated noninvasively in humans by PCT.

Adult↗
PubMed1982

Measurement of local blood flow and distribution volume with short-lived isotopes: a general input technique.

A new technique for measuring local blood flow and distribution volume is proposed. The technique uses short-lived isotopes but is different from the equilibrium method in that no constant input is necessary, and no assumption about distribution volume is needed. The theoretical basis of the technique is developed, and the results of a computer-simulation study are presented to show the potential of the technique. The technique is expected to be easier to perform and to give more accurate flow values than the equilibrium method.

Blood Volume Determination↗
PubMed1982

Effects of human aging on patterns of local cerebral glucose utilization determined by the [18F]fluorodeoxyglucose method.

The [18F]fluorodeoxyglucose (FDG) scan method with positron emission computed tomography was used to determine patterns of local cerebral glucose utilization (LCMRglu) in 40 normal volunteer subjects aged 18 to 78 years. Throughout all the studies, each subject was quiet, without movement, with eyes open and ears unplugged, exposed only to ambient room light and sound. For the entire group, whole brain mean CMRglu was 26.1 +/- 6.1 mumol 100 g-1 min-1 (mean +/- SD, n = 40). At age 78, mean CMRglu was, on the average, 26% less than at age 18, an alteration of the same order as the variance among subjects at any age. The gradual decline of mean CMRglu with advancing age occurred at a faster rate than was reported for mean cerebral oxygen utilization, possibly due to increasingly altered pathways for glucose utilization, or to increasing oxidation of ketone bodies or other alternative substrates. Glucose utilization in the hemispheres was symmetrical and mean CMRglu of overall cortex, caudate, and thalamus was equal in individuals at all ages. The slopes of decline with age were similar when LCMRglu was averaged over zones corresponding to centrum semiovale, caudate, putamen, and frontal, temporal, parietal, occipital, and primary visual cortex. However, the metabolic ratio of superior frontal cortex to superior parietal cortex declined with age, possibly due to selective degeneration of superior frontal cortex or to differences between age groups in the sensory and cognitive response to the study. These results should be useful in distinguishing age from disease effects when the FDG scan method is used.

Adolescent↗
PubMed1982

An analysis of signal amplification using small detectors in positron emission tomography.

Spatial resolution in computed tomography (CT) has been limited because of the excessive increases in statistical noise associated with increasing resolution. Reconstruction filter functions have been designed to produce tomographic images with resolution as close as possible to the intrinsic detector resolution. Since these filter functions apply an increasing weight to increasing spatial frequencies in the measured data, this produces a large amplification of noise at the upper end of the spatial frequency band of the filter function where the signal from the detector has a low amplitude. This mathematical approach to spatial frequency amplification cannot distinguish between signal and noise and thus both are amplified equally. An approach for improving tomographic resolution is the use of very small detectors to selectively amplify the signal but not noise. This signal amplification technique (SAT) can provide improvements in image resolution without increases in the cutoff frequency of the reconstruction algorithm. Alternatively, in cases in which image counts are low, statistical noise can be reduced by lowering the cutoff frequency. A possible system design for a positron CT system with SAT is described.

Animals↗
PubMed1982

Anatomical localization schemes for use in positron computed tomography using a specially designed headholder.

A headholder system is described for use in the correlation of images obtained with positron computed tomography (PCT) and other neuroradiological imaging modalities. Methods are described for defining brain anatomy from PCT images by the use of projection schemes from tomographic data. Cross-correlation of images between positron CT and standard lateral skull films, X-ray computed tomography (XCT), and two-dimensional rectilinear positron images are discussed. Such methods allow for improved reproducibility of head positioning and more precise cortical localization necessary in studies of normal brain function as well as in neuropathological conditions.

Brain↗