PubMed Health⌕ Search

Biomedical subjects

M E Phelps

Publications and source records attributed to M E Phelps.

At least 217 records · Page 12Linked to original sources
PubMed1989

Simple noninvasive quantification method for measuring myocardial glucose utilization in humans employing positron emission tomography and fluorine-18 deoxyglucose.

To estimate regional myocardial glucose utilization (rMGU) with positron emission tomography (PET) and 2-[18F]fluoro-2-deoxy-D-glucose (FDG) in humans, we studied a method which simplifies the experimental procedure and is computationally efficient. This imaging approach uses a blood time-activity curve derived from a region of interest (ROI) drawn over dynamic PET images of the left ventricle (LV), and a Patlak graphic analysis. The spillover of radioactivity from the cardiac chambers to the myocardium is automatically removed by this analysis. Estimates of rMGU were obtained from FDG PET cardiac studies of six normal human subjects. Results from this study indicate that the FDG time-activity curve obtained from the LV ROI matched well with the arterial plasma curve. The rMGU obtained by Patlak graphic analysis was in good agreement with direct curve fitting results (r = 0.90). The average standard error of the estimate of the Patlak rMGU was low (3%). These results demonstrate the practical usefulness of a simplified method for the estimation of rMGU in humans by PET. This approach is noninvasive, computationally fast, and highly suited for developing parametric images of myocardial glucose utilization rate.

Adult↗
PubMed1988

Disconnection and cerebral metabolism. The case of conduction aphasia.

Ten patients with conduction aphasia were studied with computed tomography and 18-F-fluorodeoxyglucose positron emission tomography to examine glucose metabolism. Computed tomographic results identified a postrolandic structural locus for conduction aphasia. All patients demonstrated resting glucose hypometabolism throughout the parietal and temporal regions, and half of the patients also demonstrated reduced metabolic rates in the posterior, inferior, frontal (Broca's) regions. These data suggest that disconnection between posterior and anterior language areas may not be the best anatomical explanation for conduction aphasia.

Adult↗
PubMed1988

PET in clinical oncology.

Positron Emission Tomography (PET) is an imaging technique that produces cross sectional images based on tissue biochemical and physiological processes. PET complements other anatomic imaging techniques such as x-ray CT and magnetic resonance imaging (MRI). Fundamental processes such as glucose metabolism, oxygen metabolism, and blood flow can be imaged and quantified with PET, in addition to many other processes of both clinical and investigative interest. PET is now emerging as a clinical tool in oncology and is useful in noninvasively grading tumors, in determining tumor activity and recurrence, and in monitoring the effects of a variety of therapeutic interventions with tumors. While most of the applications of PET in oncology to date have been in brain tumors, the technique is now being applied in tumor evaluations outside of the central nervous system.

Neoplasms↗
PubMed1988

Radionuclide evaluation of liver transplants.

Orthotopic liver transplantation is now an established technique for treating patients with various forms of end stage liver disease. The number of centers performing the procedure is increasing and, as the number of transplant recipients in the population increases, many institutions performing nuclear medicine studies will be confronted with requests to evaluate these patients. While a variety of radionuclides are proving useful in this evaluation, the 99mTc iminodiacetic acid (IDA) compounds, particularly 99mTc diisopropyl IDA (DISIDA), will probably account for the majority of radionuclide evaluations of these patients because they are well suited to monitor both structural and functional changes of the graft. The primary application of radionuclide studies is focused in the postoperative period, when problems with the vascular and biliary anastomoses, rejection, infections, and bile leaks all produce alterations in radionuclide hepatobiliary studies. Abnormalities such as rejection and infection produce primarily functional, rather than structural changes and are not easily differentiated based upon the kinetics of 99mTc-DISIDA extraction and excretion by the liver, serial imaging and correlation with clinical data is necessary in such situations. Quantitative analyses of kinetic 99mTc IDA (DISIDA) studies and quantitative approaches with other compounds such as 99mTc galactosyl-neoglycoalbumin (NGA) may permit better assessments of relatively subtle changes in liver function in the posttransplant period.

Bile Duct Diseases↗
PubMed1988

In vivo [3H]spiperone binding: evidence for accumulation in corpus striatum by agonist-mediated receptor internalization.

The processes of receptor internalization and recycling have been well-documented for receptors for hormones, growth factors, lysosomal enzymes, and cellular substrates. Evidence also exists that these processes also occur for beta-adrenergic, muscarinic cholinergic, and delta-opiate receptors in frog erythrocytes or cultured nervous tissue. In this study, evidence is presented that agonist-mediated receptor internalization and recycling occurs at the dopamine receptor in rat corpus striatum. First, the in vivo binding of the dopamine antagonist [3H]spiperone was increased by both electrical stimulation and pharmacologically induced increases of dopamine release. Conversely, depletion of dopamine with reserpine decreased in vivo [3H]spiperone binding, but the same reserpine treatment did not alter its in vitro binding. Second, the rate of dissociation of [3H]spiperone from microsomal membranes prepared from rat striatum following in vivo binding was fivefold slower than its dissociation following in vitro equilibrium binding. Mild detergent treatment, employed to disrupt endocytic vesicle membranes, increased the rate of dissociation of in vivo bound [3H]spiperone from microsomal membranes to values not significantly different from its in vitro bound dissociation rate. Third, treatment of rats with chloroquine, a drug that prevents receptor recycling but not internalization, prior to [3H]spiperone injection resulted in a selective increase of in vivo [3H]spiperone binding in the light microsome membranes. The existence of mechanisms that rapidly alter the number of neurotransmitter receptors at synapses provides dynamic regulation of receptors in response to varied acute stimulation states.

Animals↗
PubMed1988

Radiolabeled acetate as a tracer of myocardial tricarboxylic acid cycle flux.

The kinetics of [1-14C]acetate oxidation in isolated perfused rat hearts have been determined over a range of perfusion conditions. Effluent measurements demonstrated that 14CO2 cleared biexponentially over 50 minutes after bolus injection of [1-14C]acetate into normoxic hearts perfused with 5 mM glucose and 10 mU/ml insulin. The clearance half-time (t1/2) for the predominant initial clearance phase was 3.1 +/- 0.5 minutes (n = 4). MVO2 was varied over a fourfold range by hypoxia and phenylephrine stimulation (t1/2, 7.2 +/- 1.2 and 2.2 +/- 0.2 minutes, respectively) and in the presence of alternate substrates (lactate, 2 mM; DL-3-hydroxybutyrate, 20 mM; and palmitate, 0.1 mM), which did not modify either tricarboxylic acid (TCA) cycle flux or acetate kinetics. A good correlation (r = 0.93) was observed between k, the rate constant for the initial phase of 14CO2 clearance, and TCA cycle flux, estimated from oxygen consumption. In contrast to results with [1-14C]acetate, lactate (2 mM) increased t1/2 for 14CO2 clearance from a bolus injection of [1-14C]palmitate from 3.0 +/- 0.4 minutes (n = 3) at control to 4.3 +/- 0.2 minutes (n = 3, p less than 0.01). Addition of acetate in nontracer amounts (0.5 or 5 mM) caused significant underestimation of TCA cycle flux when estimated with [1-14C]acetate. 14CO2 clearance accounted for 88-98% of total effluent 14C between 10 and 20 minutes after [1-14C]acetate bolus injection; rate constants for clearance of 14CO2 and total 14C clearance were very similar during this period, and these two rate constants did not differ significantly from each other under any conditions tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗
PubMed1988

Cerebral glucose metabolic rates in nondepressed patients with obsessive-compulsive disorder.

The authors compared 10 nondepressed patients with obsessive-compulsive disorder with 10 normal control subjects of the same sex and similar age for cerebral glucose metabolic rates obtained using positron emission tomography. Obsessive-compulsive patients showed significantly elevated metabolic rates in the whole cerebral hemispheres, heads of the caudate nuclei, orbital gyri, and the orbital gyri relative to the ipsilateral hemisphere (the orbital-hemisphere ratio). These results are similar to those the authors reported previously for another group of obsessive-compulsive patients and normal control subjects.

Adult↗
PubMed1988

Surgical treatment of intractable neonatal-onset seizures: the role of positron emission tomography.

We have performed positron emission tomography (PET) with 2-deoxy-2[18F]fluoro-D-glucose (FDG) in eight infants and children (aged 18 days to 5 years) with medically refractory epilepsy of neonatal onset. It was hypothesized that in at least some of these infants a surgical approach (focal resection, cerebral hemispherectomy) might be of benefit in achieving seizure control, and that PET might assist in surgical selection. In three of the eight subjects, interictal PET revealed unilateral diffuse hypometabolism; following cerebral hemispherectomy in these three patients, all seizures ceased and there were no adverse effects. In one child, ictal PET showed hypermetabolism in the left frontal cortex, left striatum, and right cerebellum; a partial left cerebral hemispherectomy guided by intraoperative electrocorticography was performed, following which all seizures ceased. One infant had relative hypermetabolism in the right temporal and occipital lobes, right thalamus, and left frontal lobe on ictal PET, and EEG telemetry revealed a right occipitotemporal epileptic focus; this infant died from anesthetic complications following right occipitotemporal cortical resection. Of the three unoperated patients, one is a potential candidate for right frontal lobectomy, but the other two were not considered to be surgical candidates due to bilateral epileptogenicity. Neuropathologic correlation in our series revealed that PET is a sensitive test capable of detecting cytoarchitectural disturbances whereas CT and MRI failed in this regard. In addition, PET provides a very unique and important assessment of the functional integrity of brain regions outside the area of potential resection.

Brain↗
PubMed1988

Localization of neurochemical effects of cocaine and other stimulants in the human brain.

The cocaine epidemic is a complex problem that has defied conventional medical, psychological, and legal interventions. A better understanding of the brain mechanisms that lead to cocaine's unsurpassed euphoric and reinforcing effects, as well as to associated physical brain damage, will be needed to develop new treatment strategies. Although much work has been done on cocaine's effects in the brains of animals, most techniques used have not been safe for human subjects. Positron emission tomography (PET) offers a unique opportunity for studying the cerebral biochemistry of cocaine abuse in humans. The authors present preliminary data from their ongoing studies of the effects of cocaine and related psychostimulants on the brain's energy requirements and on catecholamine neurotransmitter systems.

Bipolar Disorder↗
PubMed1988

Vitamin D metabolites and bioactive parathyroid hormone levels during Spacelab 2.

The purpose of this study was to determine whether plasma levels of the vitamin D hormone and parathyroid hormone (PTH), two potent activators of bone remodeling sites, were altered in four astronauts during the 8-day (d) Spacelab 2 mission (SL2). Increased circulating levels of either hormone could change calcium homeostasis and bone cell activity and, thus, contribute to bone loss in crewmembers in space. The vitamin D hormone was elevated in all astronauts at the end of the first inflight day but returned to normal by the seventh day. Biologically active PTH tended to be normal throughout the mission. Both hormones were within the normal range by the end of the 8-d flight of this SL2 crew. Plasma levels of 25OHD, 24,25(OH)2D, calcium, phosphorus, and albumin were essentially normal during the mission.

24,25-Dihydroxyvitamin D 3↗
PubMed1987

Measurement of glucose and 2-deoxy-2-[18F]fluoro-D-glucose transport and phosphorylation rates in myocardium using dual-tracer kinetic experiments.

To examine the use of 2-deoxy-2-[18F]fluoro-D-glucose (2-FDG) as a glucose analog for measuring glucose utilization rate in myocardium, dual-tracer kinetic experiments with 2-FDG and 2-[3H]glucose were performed in the perfused, isolated rabbit interventricular septum to measure simultaneously the transport and phosphorylation rates of glucose and 2-FDG. Results of the present study indicated that, in the septum, the transport rate constants of 2-FDG and glucose were similar in magnitude, the phosphorylation rate constant for 2-FDG was about 60% of that of glucose, hypoxia caused an increase in phosphorylation rates of glucose and 2-FDG without affecting transport.

Animals↗
PubMed1987

Reduced cerebral glucose metabolism in asymptomatic subjects at risk for Huntington's disease.

Symptomatic patients with Huntington's disease may have reduced glucose metabolism in the caudate nuclei. We used positron emission tomography and [18F]fluorodeoxyglucose to study cerebral glucose metabolism in 95 subjects: 58 clinically asymptomatic (chorea-free) subjects at risk for Huntington's disease, 10 symptomatic patients with the disease, and 27 controls. All the symptomatic patients had marked reductions in caudate glucose metabolism. Despite a normal structural appearance on computed tomography, caudate glucose metabolism was bilaterally reduced in 31 percent of the subjects at risk (18 of 58). Using each at-risk subject's age and the sex of the affected parent, we averaged individual risk estimates for the development of Huntington's disease for this group and predicted that the probability of having the clinically unexpressed Huntington's disease gene should be 33.9 +/- 6.0 percent for the group. Thus, there was excellent agreement between the predicted percentage of carriers of the Huntington's disease gene (33.9 +/- 6.0 percent) and the percentage with metabolic abnormalities of the caudate nuclei (31 percent). These results indicate that the measurement of glucose metabolism may allow the observation of the pathophysiologic effects of the Huntington's disease gene during the natural development of the disease. It may also provide a direct means to monitor the response to experimental treatments during both the clinically asymptomatic and the symptomatic phases of the disorder.

Adult↗
PubMed1987

Local cerebral glucose metabolic rates in obsessive-compulsive disorder. A comparison with rates in unipolar depression and in normal controls.

We studied 14 patients with obsessive-compulsive disorder (OCD) by positron emission tomography and the fluorodeoxyglucose method, looking for abnormalities in local cerebral metabolic rates for glucose in brain structures that have been hypothesized to function abnormally in OCD. These patients were compared with 14 normal controls and 14 patients with unipolar depression. The patients with unipolar depression and OCD did not differ in levels of anxiety, tension, or depression. In OCD, metabolic rates were significantly increased in the left orbital gyrus and bilaterally in the caudate nuclei. This was apparent on all statistical comparisons with both controls and unipolar depression. The right orbital gyrus showed at least a trend to an increased metabolic rate in all comparisons. The metabolic rate in the left orbital gyrus, relative to that in the ipsilateral hemisphere (orbital gyrus/hemisphere ratio), was significantly elevated compared to controls and subjects with unipolar depression, and stayed high even with successful drug treatment. Though it was in the normal range in the morbid state, with improvement in OCD symptoms after drug treatment, the caudate/hemisphere metabolic ratio increased uniformly and significantly bilaterally. This ratio did not increase in patients who did not respond to treatment. Thus, OCD showed cerebral glucose metabolic patterns that differed from controls in both the symptomatic and recovered states.

Adult↗
PubMed1987

The Lennox-Gastaut syndrome: metabolic subtypes determined by 2-deoxy-2[18F]fluoro-D-glucose positron emission tomography.

We employed positron emission tomography (PET) with 2-deoxy-2[18F]fluoro-D-glucose (FDG) to study local cerebral glucose utilization in 15 children who had Lennox-Gastaut syndrome. Our results show that LGS can be classified into four predominant subtypes, each with a distinct metabolic pattern: unilateral focal hypometabolism, unilateral diffuse hypometabolism, bilateral diffuse hypometabolism, and normal. Functional disturbances seen on FDG-PET did not always correlate with abnormalities revealed by x-ray computed tomographic scan. This classification of Lennox-Gastaut syndrome into four major metabolic subtypes not only provides a new perspective toward understanding cerebral function in this complex syndrome, but may also prove useful in the clinical management of these patients.

Brain↗
PubMed1987

Positron emission tomography study of human brain functional development.

From over 100 children studied with 2-deoxy-2[18F]fluoro-D-glucose and positron emission tomography we selected 29 children (aged 5 days to 15.1 years) who had suffered transient neurological events not significantly affecting normal neurodevelopment. These 29 children were reasonably representative of normal children and provided an otherwise unobtainable population in which to study developmental changes in local cerebral metabolic rates for glucose (lCMRGlc). In infants less than 5 weeks old lCMRGlc was highest in sensorimotor cortex, thalamus, brainstem, and cerebellar vermis. By 3 months, lCMRGlc had increased in parietal, temporal, and occipital cortices; basal ganglia; and cerebellar cortex. Frontal and dorsolateral occipital cortical regions displayed a maturational rise in lCMRGlc by approximately 6 to 8 months. Absolute values of lCMRGlc for various grey matter regions were low at birth (13 to 25 mumol/min/100 gm), and rapidly rose to reach adult values (19 to 33 mumol/min/100 gm) by 2 years. lCMRGlc continued to rise until, by 3 to 4 years, it reached values of 49 to 65 mumol/min/100 gm in most regions. These high rates were maintained until approximately 9 years, when they began to decline, and reached adult rates again by the latter part of the second decade. The highest increases of lCMRGlc over adult values occurred in cerebral cortical structures; lesser increases were seen in subcortical structures and in the cerebellum. This time course of lCMRGlc changes matches that describing the process of initial overproduction and subsequent elimination of excessive neurons, synapses, and dendritic spines known to occur in the developing brain. The determination of changing metabolic patterns accompanying normal brain development is a necessary prelude to the study of abnormal brain development with positron emission tomography.

Adolescent↗
PubMed1987

Relationship between Tl-201, Tc-99m (Sn) pyrophosphate and F-18 2-deoxyglucose uptake in ischemically injured dog myocardium.

We have previously demonstrated that enhanced glucose utilization in reperfused myocardium as assessed by F-18 2-deoxyglucose (FDG) and positron tomography predicts functional recovery. In this study, we compared segmental uptake of F-18 FDG with that of Tl-201 and Tc-99m (Sn) pyrophosphate (Tc-99m PPi) as conventional markers of tissue viability in seven dogs after a 3-hour intracoronary balloon occlusion and 20 hours of reperfusion. Myocardial blood flow was determined with microspheres. Regional retention fractions were calculated from tracer tissue concentrations, the arterial input function, and blood flow. Ischemic injury was assessed by triphenyltetrazolium chloride (TTC) staining and histologic analysis. At 24 hours, blood flow was 22% lower in reperfused than in control myocardium (p less than 0.05). Uptake of Tl-201 was related linearly to blood flow (r = 0.92), while glucose utilization and Tc-99m PPi were 2.9 (p less than 0.01) and 4.7 (p less than 0.05) times higher in reperfused than in control myocardium. Retention fractions of Tc-99m PPi increased with the degree of ischemic injury, while F-18 FDG uptake was highest in segments with mild cell injury. Thus, in ischemically injured myocardium, Tl-201 primarily reflects blood flow. F-18 FDG as a marker of glucose utilization identifies ischemically injured but viable tissue. The admixture of necrotic cells can be determined with Tc-99m PPi. Our results indicate that a dual tracer approach might best characterize the presence and extent of reversibly and of irreversibly injured tissue in a given myocardial region.

Animals↗