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Biomedical subjects

M E Phelps

Publications and source records attributed to M E Phelps.

At least 253 records · Page 14Linked to original sources
PubMed1986

Model dependency and estimation reliability in measurement of cerebral oxygen utilization rate with oxygen-15 and dynamic positron emission tomography.

The use of oxygen-15 and dynamic positron emission tomography (PET) for the measurement of CMRO was investigated in terms of the achievable accuracy of CMRO and its sensitivity to model configuration assumed in the estimation. Three models of different descriptions for the vascular radioactivity in tissue were examined by computer simulation. By simulating the tracer kinetics with one model and curve fitting them with another, it was found that the CMRO measurement was very sensitive to the model configuration used and it needed kinetic data of low noise level to determine the correct model to use. The approach of sensitivity functions and covariance matrices was used to examine the estimation reliability and error propagation of the model parameters. It was found that for all three model configurations examined the reliability of the CMRO estimate was dependent on the blood flow and oxygen extraction fraction in tissue (approximately 2% in tissues of high blood flow and normal extraction and 10% in tissues of low blood flow and low extraction fraction, in a study of 1 X 10(6) counts/brain slice in 3 min). The estimation reliability is drastically decreased if the total data collection time is reduced to 1 min but is not critically sensitive to the scan sampling interval used. Estimating blood flow or vascular volume simultaneously with CMRO will reduce the reliability of the CMRO estimate by approximately 50%. Propagation of parameter error from blood flow or vascular volume to CMRO is dependent on the model configuration as well as the scanning schedule and estimation procedure used. Results from the study provide useful information for improving the study procedure of CMRO measurements. The present study also illustrates a general representation of PET measurements and an approach that can be applied to other tracer techniques in PET for selecting appropriate model configurations and for designing proper experimental procedures.

Brain↗
PubMed1986

Effects of temporal sampling, glucose metabolic rates, and disruptions of the blood-brain barrier on the FDG model with and without a vascular compartment: studies in human brain tumors with PET.

The addition of a cerebral blood volume (CBV) compartment in the [18F]2-fluoro-2-deoxy-D-glucose (FDG) model produces estimates of local CBV simultaneously with glucose metabolic rates when kinetic FDG studies are performed. We investigated the influence of this term upon CMRglc values in a series of brain tumor patients and found that significant overestimations of CMRglc are possible if the effect of CBV upon the model is ignored. The magnitude of this potential overestimation is directly related to the absolute value of CBV locally and inversely related to the CMRglc value. The kinetic estimates also permitted an evaluation of the FDG model in an environment with a variable disruption of the blood-brain barrier. Incorporating the vascular compartment in the FDG model also frequently improved the statistical accuracy of model fits to tissue kinetic data. The sampling requirements for this model configuration were also investigated in a series of computer simulations.

Blood Glucose↗
PubMed1986

Regional perfusion, glucose metabolism, and wall motion in patients with chronic electrocardiographic Q wave infarctions: evidence for persistence of viable tissue in some infarct regions by positron emission tomography.

Positron-emission tomography with 13N-ammonia and 18F-2-deoxyglucose was used to assess regional perfusion and glucose utilization in 31 chronic electrocardiographic Q wave regions in 20 patients. With previously published criteria, regions of infarction were identified by a concordant reduction in regional perfusion and glucose utilization, and regions of ischemia were identified by preservation of glucose utilization in regions of diminished perfusion. Only 10 of the 31 regions (32%) exhibited myocardial infarction tomographically. In contrast, positron tomography revealed ischemia in six regions (20%) and was normal in 15 regions (48%). Even when Q wave regions were reassigned and consolidated to enhance the specificity of the electrocardiogram, uptake of 18F-2-deoxyglucose was noted in the majority (54%) of the regions. Neither electrocardiographic ST-T changes nor severity of associated wall motion abnormality reliably distinguished tomographically identified regions of ischemia from infarction. Thus positron tomography reveals evidence of persistent tissue metabolism in a high proportion of chronic electrocardiographic Q wave regions, and commonly used clinical tests do not reliably distinguish hypoperfused but viable regions from tomographically defined regions of myocardial infarction.

Adult↗
PubMed1986

Identification of impaired metabolic reserve by atrial pacing in patients with significant coronary artery stenosis.

We investigated myocardial 11C-palmitate clearance kinetics at a resting heart rate (control) and during pacing using positron-emission tomography in 10 patients with significant coronary artery stenosis (greater than 70%) and evidence of exercise-induced ischemia. Serial 11C-palmitate images acquired at control and during pacing revealed biexponential myocardial 11C clearance both in myocardium supplied by a stenotic coronary artery (myocardium "at risk") and in myocardium supplied by a normal coronary artery (normal myocardium). At control, the average rate of myocardial 11C clearance from the early rapid curve component (the clearance half-time) was similar in normal myocardium and in that at risk (22.2 +/- 5.2 vs 21.0 +/- 5.4 min, NS), as was the amount of myocardial 11C activity at the end of the early rapid phase (residual fraction 56.3 +/- 7.2% vs 54.7 +/- 7.3%, NS). Thus, myocardial clearance was homogeneous at control, suggesting a similar rate and amount of 11C-palmitate oxidation in normal myocardium and in that at risk. Pacing shortened clearance half-times and decreased residual fraction in both normal myocardium and that at risk compared with control. However, clearance half-times were 17% longer and residual fractions 14% higher in myocardium at risk compared with normal myocardium (p less than .005 and p less than .01, respectively). Therefore, during pacing myocardial 11C clearance became heterogeneous, suggesting impaired 11C-palmitate oxidation in myocardium at risk compared with normal myocardium. Increased substrate utilization in response to increased workload can be thought of as a measure of metabolic reserve. Our data suggest metabolic reserve for free fatty acid oxidation is impaired in myocardium supplied by a significantly stenosed coronary artery and that this impairment can be detected by analysis of myocardial 11C-palmitate clearance.

Adult↗
PubMed1986

Left hemisphere intracerebral hemorrhages studied by ( (F-18)-fluorodeoxyglucose PET.

We used PET to study patients with intracerebral hemorrhages in the left hemisphere. Three anatomic and physiologic patterns were observed. Patients 1 and 2 had midputamen hemorrhages with diffuse left less than right hemispheric metabolic asymmetry most prominent in temporal and parietal regions. Patients 3 and 4 had posterior putamen-insula-temporal hemorrhages with left less than right metabolic asymmetry in temporoparietal cortex and thalamus. Patients 5, 6, and 7 had smaller posterior hemorrhages. Left cortical metabolism was little affected in these three cases. Persistent aphasia was associated with severe metabolic left less than right asymmetry in posterior middle temporal regions.

Adult↗
PubMed1986

Identification of seizure-mediating brain structures with the deoxyglucose method: studies of human epilepsy with positron emission tomography, and animal seizure models with contact autoradiography.

This chapter describes tomographic and autoradiographic studies of human and animal seizure syndromes employing Sokoloff's deoxyglucose method. The method's rationale rests on two principal facts: that adult brains normally utilize glucose almost exclusively as their exogenous energy source, and that deoxyglucose, a glucose analog, accumulates in brain cells in proportion to their activity level. Thus, computed tomography or contact autoradiography allows visualization and indirect measurement of changes in the activity of different brain structures under specified conditions, such as between, during, or immediately following seizures. In humans, partial seizures have been the most extensively studied, with 18F-fluorodeoxyglucose and positron emission tomography. Interictally, the brains of patients with partial seizures are characterized by hypometabolism that is particularly severe in the vicinity of seizure foci. In many cases, these focal hypometabolic zones become hypermetabolic ictally. Other brain areas may also become hypermetabolic ictally, or they may instead become hypometabolic. Often the physical extent of interictal hypometabolic zones is substantially greater than the extent of overt pathology. This indicates that hypometabolism can result from subtle, presently undescribed, structural or functional derangements, as well as from frank neuronal loss. A variety of animal seizure "models" have also been studied, with 14C-2-deoxyglucose and contact autoradiography. Each model has produced a unique deoxyglucose and contact autoradiography. Each model has produced a unique deoxyglucose utilization pattern, but thus far none that closely resembles any of the human seizure patterns. This probably reflects true differences between the mechanisms mediating different types of animal seizures and those mediating human seizures. Although in widespread use for only a few years, the Sokoloff method has already demonstrated its ability to distinguish among a variety of seizure types in both humans and animals, and to correctly identify those structures most involved in focal seizures. Thus, the method can be of great aid in narrowing the search for seizure-mediating mechanisms.

Animals↗
PubMed1985

Positron emission tomography: human brain function and biochemistry.

Positron emission tomography (PET) is an analytical imaging technique that provides a way of making in vivo measurements of the anatomical distribution and rates of specific biochemical reactions. This ability of PET to measure and image dynamic biochemistry builds a bridge between the basic and clinical neurosciences founded on the commonality of the types of measurements made. Clinical findings with PET in humans are suggesting hypotheses that can be tested rigorously in the basic science laboratory.

Acoustic Stimulation↗
PubMed1985

Cerebral metabolic rates for glucose in mood disorders. Studies with positron emission tomography and fluorodeoxyglucose F 18.

Cerebral metabolic rates for glucose were examined in patients with unipolar depression (N = 11), bipolar depression (N = 5), mania (N = 5), bipolar mixed states (N = 3), and in normal controls (N = 9) using positron emission tomography and fluorodeoxyglucose F 18. All subjects were studied supine under ambient room conditions with eyes open. Bipolar depressed and mixed patients had supratentorial whole brain glucose metabolic rates that were significantly lower than those of the other comparison groups. The whole brain metabolic rates for patients with bipolar depression increased going from depression or a mixed state to a euthymic or manic state. Patients with unipolar depression showed a significantly lower ratio of the metabolic rate of the caudate nucleus, divided by that of the hemisphere as a whole, when compared with normal controls and patients with bipolar depression.

Adult↗
PubMed1985

Local cerebral metabolic rate for glucose during petit mal absences.

Four patients with primary generalized or true petit mal epilepsy were studied with positron emission tomography using [18F]fluorodeoxyglucose (FDG). FDG studies were carried out during 10 minutes of hyperventilation before and again after medical control of spontaneous absences. Before seizures were controlled all 4 patients demonstrated frequent bilaterally synchronous three-per-second spike-and-wave discharges associated with altered consciousness. After spontaneous seizures were controlled, hyperventilation produced only electroencephalographic slowing without clinical symptoms in 3; the fourth patient had absences less frequently. Patterns of local cerebral metabolic rate for glucose (CMRGlc) were normal and identical for ictal and interictal scans; there was, however, a 2.5- to 3.5-fold diffuse ictal increase in global CMRGlc evident when ictal studies were compared with hyperventilation control studies in which no seizures occurred. The CMRGlc was similar in the two scans obtained from the patient who had absences during both studies. No anatomical substrate of petit mal epilepsy was identified. The CMRGlc in these patients during petit mal absences was higher than that recorded in other patients during partial or generalized convulsive seizures. This difference may reflect the fact that petit mal absences are not associated with postictal depression.

Brain↗
PubMed1985

Positron computed tomography and its applications in the young.

Positron computed tomography is a new method for the external quantification of regional myocardial blood flow, substrate fluxes and biochemical reaction rates. It takes advantage of positron emitting tracers, metabolically active tracers, tracer kinetic principles and the quantitative imaging capabilities of the tomograph. To date, the technique has been used primarily for the study of ischemic heart disease and cardiomyopathies in adults. However, initial studies in infants and adolescents with regional cardiomyopathies provide evidence for its potential value in detecting disease at the biochemical level or at a stage that antedates clinical manifestations and cardiac dysfunction. Positron computed tomography is likely to contribute to our understanding of metabolic abnormalities associated with cyanotic or congenital heart disease and of the heart's maturation, and may become useful for optimal timing of corrective surgery. It allows the study of intrinsic myocardial disease in children, clarification of disease mechanisms and diagnosis of congenital metabolic disorders. It also might become useful for detecting disease when it is still confined to biochemical derangements and permit institution of therapy that may halt progression or even reversal of disease before irreversible morphologic changes develop. The high cost of equipment purchase and operation has precluded widespread use, but new technologic developments may make it possible to perform these studies at a cost comparable with that of other noninvasive procedures. Positron computed tomography may then become available as a routine diagnostic tool for studying pediatric cardiac disorders.

Cardiomyopathies↗
PubMed1985

Retention and clearance of C-11 palmitic acid in ischemic and reperfused canine myocardium.

Free fatty acids are the major energy source for cardiac muscle. Oxidation of fatty acid decreases or even ceases during ischemia. Its recovery after transient ischemia remains largely unexplored. Using intracoronary carbon-11 palmitic acid as a tracer of myocardial fatty acid metabolism in an open chest dog model, retention and clearance of tracer in myocardium were evaluated at control, during ischemia and after reperfusion following a 20 minute occlusion of the left anterior descending coronary artery. Myocardial C-11 time-activity curves were analyzed with biexponential curve-fitting routines yielding fractional distribution and clearance half-times of C-11 palmitic acid in myocardial tissue. In animals with permanent occlusion and intracoronary injection of C-11 palmitic acid distal to the occlusion site, the relative size and half-time of the early clearance curve component differed markedly from control values and did not change with ongoing ischemia. Conversely, in animals with only 20 minutes of coronary occlusion, the relative size of the early C-11 clearance phase was still significantly depressed at 20 and 90 minutes of reperfusion but returned to control level at 180 minutes. Tissue C-11 clearance half-times remained significantly prolonged throughout the reperfusion period. Regional function in reperfused myocardium monitored with ultrasonic crystals recovered slowly and was still less than control after 3 hours of reperfusion. The data indicate that after transient ischemia, myocardial fatty acid metabolism fails to recover immediately. Because the metabolic recovery occurs in parallel with recovery of regional function, C-11 palmitic acid in conjunction with positron tomography may be useful for studying regional fatty acid metabolism noninvasively after an ischemic injury, and may be helpful in identifying reversible tissue injury.

Animals↗
PubMed1985

Sustained regional abnormalities in cardiac metabolism after transient ischemia in the chronic dog model.

Positron emission tomography allows noninvasive assessment of myocardial blood flow and metabolism, and may aid in defining the extent and severity of an ischemic injury. This hypothesis was tested by studying, in chronically instrumented dogs, regional blood flow and metabolism during and after a 3 hour balloon occlusion of the left anterior descending coronary artery. The metabolic findings after ischemia were compared with the recovery of regional function over a 4 week period. N-13 ammonia was used as a blood flow tracer, and C-11 palmitic acid and F-18 deoxyglucose as tracers of fatty acid and glucose metabolism, respectively. Regional myocardial function was monitored with ultrasonic crystals implanted subendocardially. Regional function improved most between 24 hours and 1 week after reperfusion, but was still attenuated at 4 weeks. The slow functional recovery was paralleled by sustained metabolic abnormalities, reflected by segmentally delayed clearance of C-11 activity from myocardium and increased uptake of F-18 deoxyglucose. Absence of blood flow and C-11 palmitic acid uptake at 24 hours of reperfusion correlated with extensive necrosis as evidenced by histologic examination. Conversely, uptake of C-11 palmitic acid with delayed C-11 clearance and increased F-18 deoxyglucose accumulation identified reversibly injured tissue that subsequently recovered functionally and revealed little necrosis. Thus, recovery of metabolism after 3 hours of ischemia is slow in canine myocardium and paralleled by slow recovery of function. Metabolic indexes by positron tomography early after reperfusion can identify necrotic and reversibly injured tissue. Positron tomography may therefore aid in defining the extent and prognosis of an ischemic injury in patients undergoing reperfusion during evolving myocardial infarction.

Animals↗
PubMed1985

A noninvasive positron computed tomography technique using oxygen-15--labeled water for the evaluation of neurobehavioral task batteries.

A technique is described that provides information about relative cerebral responses to differing neurobehavioral tasks in normal subjects studied with positron computed tomography and oxygen-15-labeled water. Simulation studies demonstrate that this technique is sensitive to changes in true local CBF within a physiological range and tends to underestimate relative flow changes at high flow values (greater than 30 ml min-1 100 g-1) and to overestimate these changes for flow values of less than 25 ml min-1 100 g-1. Image acquisition times of 60 s following the arrival of oxygen-15-labeled water in the brain were the most accurate for identifying such relative changes between radioisotope administrations and were not limited by statistical noise from total image counts. Studies in normal volunteers indicate that the technique is highly reproducible, demonstrating a coefficient of variation for small (less than 2 cm2) regions of 2.98 between studies in the same state. Visual stimulation studies in normal volunteers demonstrated relative radioisotope concentration changes between control and stimulated states that are in good agreement with similar results obtained using the same stimulation paradigm but with the use of fluorodeoxyglucose to determine cerebral glucose metabolism.

Adult↗
PubMed1985

Brain glucose metabolism and memory functions: age decrease in factor scores.

The F-18 fluorodeoxyglucose (FDG) scan method with positron emission tomography was used to determine age differences in factors underlying both the performances on 18 multivariate memory tests and the rates of cerebral glucose utilization in nine left and nine right hemispheric regions of 23 healthy adults aged 27 to 78 years. Two of the five derived factors separated persons below age 42 from those above age 48 years, one reflecting secondary memory for material verbally processed together with Broca's metabolic ratio, the other defined by tests requiring sequential or organizational coding of information and metabolic measures of thalamic regions. Education did not override their parallel age decrease. Several regional metabolic measures covaried with distinct memory measures. Persons with high superior frontal and low caudate-thalamic metabolic measures were those who performed well in tests of memory for sentences, story, designs, and complex patterns, suggesting a frontal-subcortical interaction in age-dependent memory processing.

Adult↗
PubMed1985

Comparison of glucose metabolism, x-ray CT, and postmortem data in a patient with multiple cerebral infarcts.

We studied a 69-year-old man with multiple brain infarcts who died 8 days after being studied with positron emission tomography and (F-18)-fluorodeoxyglucose. Metabolic abnormalities were greater than structural changes in size and extent. They were found in areas with no gross pathologic abnormalities. Remote metabolic effects were attributed both to degeneration of fiber tracts with disconnection of remote structures, as demonstrated by hypometabolism in the left frontal cortex associated with an infarct in the genu of the left internal capsule, and to microscopic infarcts not apparent on gross examination but manifested as hypometabolic regions.

Aged↗
PubMed1985

Local cerebral glucose utilization in symptomatic and presymptomatic Huntington's disease.

Patterns of local cerebral glucose utilization were measured with positron emission CT using the 18F-fluorodeoxyglucose method in 13 patients with HD, 15 subjects at risk for HD, and control subjects. These data were compared with CT measures of cerebral atrophy, age, and 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 demented patients with Alzheimer's disease or Parkinson's disease, 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 indicate that the caudate is hypometabolic in some asymptomatic persons who are carriers of the autosomal-dominant gene for HD.

Adolescent↗
PubMed1985

Quantitative measurement of myocardial blood flow with oxygen-15 water and positron computed tomography: an assessment of potential and problems.

An in vivo measurement technique using 15O water and positron CT for quantitation of myocardial blood flow (MBF) was investigated. A closed-chest dog model and NeuroECAT scanner were used in the study. The in vivo technique involves i.v. infusion of 15O water for a duration of 2-3 min. Oxygen-15 water radioactivity in myocardium was imaged with a NeuroECAT scanner for 10 min, starting at the time of tracer infusion. A separate scan following inhalation of 15O CO was obtained to label the blood pool and to help remove the contribution of radioactivity in the blood pool during the 15O water scans. The integrated projection technique was used for calculating MBF. The quantitative microsphere technique for measurement of MBF was performed along with the 15O water study to provide reference values, with which the MBF values by the in vivo technique was compared. Results of 12 experimental runs (in seven animals) show the in vivo technique with 15O water and positron CT can give quantitative flow images of myocardium. The in vivo positron CT measurement was found to correlate well (r = 0.93) with the in vitro values (by microspheres) over the flow range of 40 to 150 ml/min/100 g.

Animals↗