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Biomedical subjects

M E Phelps

Publications and source records attributed to M E Phelps.

At least 145 records · Page 8Linked to original sources
PubMed1993

A refined method for quantification of myocardial oxygen consumption rate using mean transit time with carbon-11-acetate and dynamic PET.

The utility of the mean transit time equation was investigated for estimation of the myocardial clearance rate constant of 11C-acetate, which is proportional to myocardial oxygen consumption rates. The mean transit time approach was also employed to generate parametric images of the clearance rate constant of 11C-acetate with dynamic PET imaging in 20 normal human studies. Input function delays and cutoff errors due to the truncation of the myocardial tissue time-activity curve at a finite time were corrected. The clearance rate constants estimated by mean transit time correlated well with the estimates by conventional monoexponential fitting (15 min (truncation time): Y = 0.01 + 0.94X, correlated coefficient (r) = 0.99; 16 min: Y = 0.03 + 0.94X, r = 0.98; 20 min: Y = 0.03 + 0.84X, r = 0.99). The clearance rate constants estimated by the mean transit time approach also correlated well (r = 0.94) with the measured rate-pressure products. The quality and noise level of parametric images of the clearance rate constants generated by mean transit time are improved over those generated by monoexponential fitting. Additional advantages of the mean transit time approach compared to the standard monoexponential fitting method for estimating myocardial clearance rate constant of 11C-acetate include ease of input function delay correction, less sensitivity to the shape of the input function and elimination of subjective data selection of the linear portion of the clearance data on a semilog plot. Thus, this approach is expected to facilitate objective quantitative analysis of indices of myocardial oxygen consumption.

Acetates↗
PubMed1993

A simplified method for quantification of myocardial blood flow using nitrogen-13-ammonia and dynamic PET.

The utility of Patlak graphical analysis was investigated for quantification of regional myocardial blood flow (MBF) and for generating parametric images of MBF with 13N-ammonia and dynamic PET imaging in dogs and humans. MBF was estimated by a two-compartment model fit of the initial 2 min of the kinetic data and by Patlak graphical analysis of the initial 2, 3, or 4 min of data. In 11 dog studies, MBF by compartmental model fitting linearly correlated with MBF by microspheres (correlation coefficient (r) = 0.99, slope = 0.92) and by Patlak graphical analysis (r = 0.99, slope = 0.90). In 10 normal human studies, MBF obtained by the Patlak graphical analysis agreed well with MBF obtained by the compartmental model fitting (r = 0.96, slope = 1.04). Good agreement of the MBF estimates was also observed in 10 coronary artery disease patient studies (r = 0.96). Patlak graphical analysis permitted generation of parametric images of MBF. The parametric images of MBF, in units of ml/min/g, are of good image quality and have relatively low noise levels. We conclude that regional MBF can be noninvasively and conveniently measured with dynamic 13N-ammonia PET using either a two-compartment model or Patlak graphical analysis. MBF parametric images generated with the Patlak graphical analysis both map the distribution and quantitate the magnitude of myocardial perfusion abnormalities.

Adult↗
PubMed1993

Use of positron emission tomography in oncology.

Positron emission tomography is an imaging technique that produces images reflective of tissue biochemistry rather than anatomy. Utilizing different isotopes, many biochemical processes can be studied repetitively and non-invasively in cancers in vivo. Malignant tissue is characterized by an accelerated rate of glycolysis. This biochemical characteristic of malignancy can be exploited by PET imaging with the radiopharmaceutical FDG. PET with FDG has been successful in imaging primary and metastatic cancer of the breast, colon, lung, head and neck, as well as sarcomas and lymphomas. PET FDG imaging has potential as a screening, diagnostic and staging tool in cancer. Recently, whole body PET techniques have been developed which permit imaging of the entire body during a single scanning session. PET also has tremendous potential as a cancer research tool to study serial estimates of tumor glycolysis, DNA turnover, oxygen metabolism, protein synthesis, and blood.

Brain Neoplasms↗
PubMed1993

Methods for improving quantitation of putamen uptake constant of FDOPA in PET studies.

To estimate the striatal uptake constant of [18F]-L-6-fluorodopa (FDOPA) in humans, we studied two methods that can account for the image resolution and the background level of FDOPA. These two methods utilize information obtained from multiple ROIs varying in size around the putamen and from profiles crossing the middle of the putamen. The estimation of the uptake constant was based on a model of one-dimensional activity variation. Simulated data were used to evaluate the adequacy of these two methods. Parametric images of FDOPA uptake constants were generated using Patlak analysis for five studies in normals and were then analyzed with the two methods. Results from the simulated data indicated a good agreement between the estimated values and the true simulated values. Results from studies in normals show stable estimates of the FDOPA uptake constant that are not affected by image resolution. The two methods were not sensitive to the misplacement of ROIs and profiles.

Computer Simulation↗
PubMed1992

Serial changes of cerebral glucose metabolism and caudate size in persons at risk for Huntington's disease.

OBJECTIVE: To determine the rate of change of glucose metabolism and caudate size in persons at risk for Huntington's disease. DESIGN: Eighteen persons at risk for Huntington's disease had two positron emission tomographic glucose metabolic studies and two magnetic resonance imaging scans separated by 42 (+/- 9) months. SETTING: Ambulatory research subjects at a teaching hospital with magnetic resonance imaging and positron emission tomographic technology. SUBJECTS: Seven of the individuals were Huntington' disease gene negative by testing at the polymorphic DNA loci D4S10, D4S43, and D4S125; the remainder were gene positive by genetic testing or onset of chorea after study entry. INTERVENTIONS: None. OUTCOME MEASURES: Onset of chorea and imaging results. RESULTS: The gene-positive group demonstrated a significant 3.1% loss of glucose metabolic rate per year in the caudate nucleus (95% confidence interval [CI], -4.64, -1.48) compared with the gene-negative group. There was a 3.6% per year increase in the magnetic resonance imaging bicaudate ratio (95% CI, 1.81, 5.37), a linear measure of caudate atrophy. The rate of change in caudate size did not correlate with the rate of change in caudate metabolism, suggesting that metabolic loss and atrophy may develop independently. CONCLUSIONS: The results suggest that a reduction in caudate glucose metabolism and atrophy develop rapidly in Huntington's disease. The findings establish a strategy for using serial positron emission tomographic imaging to monitor experimental pharmacologic interventions in presymptomatic individuals who have developed caudate hypometabolism.

Adult↗
PubMed1992

Infantile spasms: II. Lenticular nuclei and brain stem activation on positron emission tomography.

Infantile spasms are generalized seizures specific to early infancy, and are believed to result from complex cortical-subcortical interactions during a critical period of development. We used positron emission tomography (PET) to determine local cerebral metabolic rates for glucose (1CMRG1c) in 44 infants with spasms, in an attempt to define the neuroanatomical substrates that mediate these seizures. All infants were studied in the awake state during continuous electroencephalographic monitoring. The most consistent abnormality on PET, seen in 32 infants, was the symmetrical increase in 1CMRG1c in the lenticular nuclei, compared to age-matched normal infants (p less than 0.05). In 21 infants, even though the brain stem appeared to be visually more prominent compared to normal infants, statistically significant differences could not be demonstrated. Relative hypermetabolism of the lenticular nuclei (1) occurred irrespective of whether the spasms were cryptogenic or symptomatic, (2) was associated with focal cortical hypometabolism in 22 and focal cortical hypermetabolism in 5 of the 44 infants, and (3) was not characterized by any specific electroencephalographic abnormality during PET. These findings suggest that the lenticular nuclei may contribute to the pathophysiological state that predisposes to infantile spasms, and is consistent with the observation that spasms are clinically symmetrical even when focal cortical lesions are present. A scheme describing the neuronal circuitry likely to be involved in the generation of infantile spasms is proposed.

Brain Stem↗
PubMed1992

Comparison of maximal myocardial blood flow during adenosine infusion with that of intravenous dipyridamole in normal men.

OBJECTIVE: This study compared quantitatively the efficacy of intravenous adenosine and dipyridamole for pharmacologic induction of myocardial hyperemia. BACKGROUND: Pharmacologic vasodilation is used increasingly for induction of myocardial hyperemia in conjunction with radionuclide imaging of myocardial blood flow. Although both intravenous dipyridamole and adenosine have been used, the magnitude of hyperemia induced by these agents and the hyperemia to baseline blood flow ratios have not been quantified and compared. METHODS: Twenty normal volunteers were studied with dynamic positron emission tomography (PET) and intravenous nitrogen-13 ammonia. Myocardial blood flow was quantified with a two-compartment tracer kinetic model. RESULTS: Myocardial blood flow at rest averaged 1.1 +/- 0.2 ml/min per g and increased significantly to 4.4 +/- 0.9 ml/min per g during adenosine and 4.3 +/- 1.3 ml/min per g after dipyridamole administration. Hyperemia to baseline flow ratios averaged 4.3 +/- 1.6 for adenosine and 4.0 +/- 1.3 for dipyridamole. The average flow ratios and the maximal flows achieved were similar for both agents, but there was considerable variation in the individual response to these agents, as indicated by the range of hyperemia to baseline flow ratios (from 2.0 to 8.4 for adenosine and from 1.5 to 5.8 for dipyridamole). In addition, the hyperemic responses to dipyridamole and to adenosine differed by greater than 1 ml/min per g in nine subjects. CONCLUSIONS: Despite these inter- and intraindividual differences, we conclude that both agents are equally effective in producing myocardial hyperemia.

Adenosine↗
PubMed1992

The use of positron emission tomography in the clinical assessment of dementia.

A number of reasons can be cited for performing a test that identifies patients early in their course who have fatal and currently untreatable neurological disorders. At this stage of illness there is clinical ambiguity. The patient, family, and physician are typically faced with a battery of negative test results and an ambiguous clinical impression that can lead to periodic repetition of tests that involve cost, inconvenience, potential morbidity to the patient, and lack of definitive diagnosis. An accurate test would lead to the avoidance of these low-yield, repetitive, and costly evaluations. In addition, such studies can identify homogeneous groups of individuals with degenerative disorders leading to dementia who could be enrolled in experimental therapeutic programs. In these programs therapies could be monitored in an objective and noninvasive fashion using positron emission tomography (PET). The magnitude of the health problems resulting from the dementing illnesses is great in terms of medical practice, economics, and family hardship. The number of individuals with these disorders is predicted to increase dramatically in the future. The ability to provide an accurate diagnosis and more clear prognosis early in the disease course should diminish ambiguity for patients, families, and physicians. Ample evidence is cited in this article to show that PET has the ability to provide such information objectively and noninvasively.

Alzheimer Disease↗
PubMed1992

Human functional anatomy of visually guided finger movements.

The functional anatomy of visually guided movement was investigated in 18 normal subjects performing visuomotor tracking tasks during positron emission tomography imaging. Tracking a moving target with the index finger defined a network of focal responses of relative cerebral blood flow (relCBF) located in the primary motor cortex, dorsal parietal cortex, precuneate cortex, supplementary motor area (SMA) and ipsilateral anterior cerebellum relative to visual tracking alone. When the temporal complexity of the tracking task was altered by introducing a 'no go' contingency that allowed for greater time for movement preparation, there was a significant increase of relCBF in the SMA (P less than 0.0001). When the spatial complexity was augmented by adding a secondary target that provided directional cues for the primary target, there were additional significant increases of relCBF in bilateral dorsal parietal cortex (P less than 0.05) and precuneate cortex (P less than 0.05). Although the cued 'no go' task was subjectively easier, relCBF responses were similar to the uncued 'no go' task in motor areas. Performing the tracking task with different body parts produced somatotopically distributed responses in only the motor cortex. The findings are concordant with clinical reports of patients with brain lesions and physiological evidence that identifies this distributed network for performing visually guided movement. The results provide direct human evidence in the normal brain that the supplementary motor area contributes in part to the sequencing of movements and the medial and dorsal parietal cortex participates in the integration of spatial attributes during selection of movements.

Adult↗
PubMed1992

The application of positron emission tomographic imaging with fluorodeoxyglucose to the evaluation of breast disease.

Positron emission tomography (PET) is a computer-aided tomographic imaging technique that uses positron-emitting compounds to trace biochemical processes of tissue, and construct images based on them. The authors applied a whole-body PET imaging technique to patients with breast masses or mammographic abnormalities using the isotope 2-[F-18]-fluoro-2-deoxy-D-glucose (FDG), in a clinical trial to evaluate the feasibility of using PET to identify primary breast cancer, axillary lymph node involvement, and systemic metastases, before surgical resection. Fourteen patients have been entered on this study, 10 of whom proved to have breast cancer. Positron emission tomography correctly predicted the nature of 12 of the 14 primary breast lesions, and correctly determined the lymph node status of 11 of the 14 patients. The authors conclude that PET with FDG has potential as a diagnostic modality for detection of primary breast cancer, particularly in the patient with radiodense breasts by conventional mammography, and that it has potential for the preoperative identification of axillary lymph node metastases.

Adolescent↗
PubMed1992

Positron emission tomography and familial Alzheimer's disease: a pilot study.

OBJECTIVE: Local cerebral metabolic rates for glucose were compared between patients with familial Alzheimer's disease (FAD), sporadic Alzheimer's Disease (SAD), and normal controls (NC) to determine if FAD is associated with a unique pattern of brain metabolism. DESIGN: Case-control study matched to convenience sample of FAD. METHODS: Subjects in the three diagnostic groups were scanned using fluorodeoxyglucose and the Positron Emission Tomographic (PET) technique. The criterion standard of a detailed clinical history and examination were compared to scan results. SETTING: Patients in a university hospital. SUBJECTS: Ambulatory controls and Alzheimer's patients, both sporadic (n = 8) and familial (n = 7). The two groups were similar in severity of cognitive dysfunction. RESULTS: FAD and SAD patients did not significantly differ in terms of local cerebral metabolic rates for glucose.

Aged↗
PubMed1992

Quantitative assessment of prolonged metabolic abnormalities in reperfused canine myocardium.

BACKGROUND: Prolonged metabolic abnormalities have been demonstrated previously in postischemic myocardium, including relative increases in glucose uptake and abnormal fatty acid kinetics. However, quantitative metabolic information is limited, and the time course of changes in MVO2 in postischemic myocardium is unknown. To address these issues, chronically instrumented dogs were studied serially over 1 month after transient left anterior descending coronary artery (LAD) occlusion, using positron emission tomography. METHODS AND RESULTS: Dynamic imaging protocols were used in conjunction with tracer kinetic models to quantify blood flow and metabolic rates. Myocardial sectors were defined as normal, predominantly reversibly injured, and infarct-containing, based on occlusion blood flow images and postmortem histochemistry. Myocardial blood flow and metabolism were homogeneous at baseline. During LAD occlusion for 3 hours, myocardial blood flow in reversibly injured and infarct-containing sectors (determined with 13NH3) was decreased to 46% and 23%, respectively, of blood flow in normal tissue. MVO2, determined with [1-11C]acetate, was decreased less than myocardial blood flow, consistent with increased oxygen extraction in the ischemic tissue. After reperfusion, blood flow normalized rapidly in reversibly injured tissue but remained depressed in infarct-containing sectors. Regional myocardial function, assessed by two-dimensional echocardiography, was severely depressed during occlusion and did not improve significantly until 1 week after reperfusion. MVO2 remained depressed after reperfusion in both reversibly injured and infarct-containing sectors, did not improve from occlusion levels until 1 week after reperfusion, and remained significantly depressed 1 month after reperfusion even in reversibly injured sectors; [1-11C]palmitate kinetics were also abnormal in postischemic tissue. As reported previously, glucose metabolic rates were increased relative to baseline in normal but not in postischemic tissue 3 hours after reperfusion. Subsequently, glucose metabolism tended to be higher in postischemic relative to normal myocardium. CONCLUSIONS: The results demonstrate decreased oxidative metabolism in postischemic tissue, with concomitant abnormalities in palmitate kinetics and glucose metabolism. Oxidative metabolism and regional function demonstrated a parallel recovery with time.

Acetates↗
PubMed1992

Quantification of regional myocardial blood flow using 13N-ammonia and reoriented dynamic positron emission tomographic imaging.

BACKGROUND: Regional myocardial blood flow has been quantified using transaxial positron emission tomographic (PET) imaging and tracer kinetic modeling. However, the use of transaxial images limits the accuracy of regional partial volume corrections and the localization of the quantified regional flow values. The purpose of the present study was to overcome both problems by calculating regional flows from reoriented short-axis PET images. METHODS AND RESULTS: Twelve experiments were performed in four dogs. 13N-ammonia was injected intravenously while microspheres were administered into the left atrium during baseline, hyperemic, and low-flow conditions. Serial transaxial frames were acquired with a 15-plane PET scanner and reoriented into short-axis frames. The arterial input function and eight regional myocardial tissue activity curves were derived from the reoriented frames. The arterial input functions were corrected for ammonia metabolites, and the myocardial tissue curves were corrected for spillover of activity, partial volume effects, and heterogeneities in the image's spatial resolution introduced during reorientation. Corrections for regional partial volume were based on estimates of the regional myocardial activity thickness derived from reoriented diastolic images of the heart. The myocardial 13N-ammonia kinetics were described with a two-pool compartmental model. Values of regional myocardial blood flow by PET correlated linearly with those by microspheres (slope, 0.94; y intercept, 0.06 ml/min/g; r = 0.93) over a wide range of flows. CONCLUSIONS: Regional myocardial blood flow can be measured accurately and noninvasively from serially acquired and reoriented short-axis 13N-ammonia images, thus overcoming limitations inherent to the use of transaxially acquired images and permitting a more complete evaluation of regional blood flows throughout the left ventricular myocardium.

Ammonia↗
PubMed1992

Positron emission tomography detects metabolic viability in myocardium with persistent 24-hour single-photon emission computed tomography 201Tl defects.

BACKGROUND: Four-hour 201Tl redistribution images underestimate myocardial viability in patients with coronary artery disease (CAD). Because 4-hour defects often redistribute late, delayed imaging may enhance assessment of tissue viability. Myocardial metabolic activity was therefore assessed with positron emission tomography (PET) in 26 CAD patients with impaired ventricular function (ejection fraction, 32.1 +/- 13.9%) and 24-hour single-photon emission computed tomography (SPECT) 201Tl defects. METHODS AND RESULTS: On circumferential profile analysis, PET ischemia was defined by preserved glucose metabolism in hypoperfused myocardium, and PET infarction was defined by concordant reductions in perfusion and metabolism. On 19 stress-redistribution and seven rest-redistribution SPECT studies, four observers visually scored 201Tl activity in eight segments on a scale from 0 (normal) to 3 (complete defect). Using an improvement in visual score > or = 0.75 to define redistribution, there were 100 fixed, 17 partially reversible, and 12 completely reversible defects. PET identified tissue metabolic activity in 51 (51%) segments with fixed defects (21 PET ischemia, 30 PET normal) and nine (53%) segments with partially reversible defects (five PET ischemia, four PET normal). When grouped by 24-hour score, the proportion of fixed defects with metabolic activity varied from 84% (scores < or = 1.4) to 15% (scores > 2.6). For partially reversible defects, only 53% with scores < 2.0 and one of two with scores > or = 2.0 were considered metabolically viable on PET. Of 12 completely reversible defects, six (50%) were normal, five (42%) had PET ischemia, and one (8%) had PET infarction. The proportion of fixed defects with metabolic activity did not depend on whether a rest or stress study was performed or on the change in visual score used to define 201Tl redistribution (0.25, 0.50, 0.75, and 1.00). CONCLUSIONS: In CAD patients, PET identifies glucose metabolic activity in the majority of fixed 24-hour 201Tl defects. However, very severe (near-complete) 24-hour 201Tl defects are less likely to exhibit metabolic activity on PET imaging than are defects with less-pronounced reductions in segmental 201Tl activity.

Coronary Angiography↗
PubMed1992

A new noninvasive quantification of renal blood flow with N-13 ammonia, dynamic positron emission tomography, and a two-compartment model.

In order to determine if dynamic positron emission tomography (PET) and N-13 ammonia can be used to quantitate regional RBF (rRBF) noninvasively, six anesthetized dogs were examined with PET imaging after an iv bolus administration of 5 mCi of N-13 ammonia. Renal time activity curves and the arterial input function were derived from regions of interest drawn over the renal cortex and abdominal aorta, respectively. For calculation of rRBF, less than 120 s of the initial data were used to minimize contamination by plasma metabolites of N-13 radioactivity. rRBF was quantitated with a two-compartment model, and the results were compared with simultaneously acquired microsphere blood flow measurement. Fourteen experiments were performed in six dogs, and four regions of interest on renal cortex were selected on each PET image. RBF derived from dynamic PET imaging with N-13 ammonia was linearly related to microsphere (MS) values (rRBF = 1.06 x MS - 0.17; r = 0.91). Mean rRBF in the canine experiments was 4.0 mL/min/g. The results indicate that dynamic N-13 ammonia renal PET can provide noninvasively quantitative rRBF.

Ammonia↗
PubMed1992

Semiquantitative assessment of myocardial blood flow and viability using polar map displays of cardiac PET images.

Preserved glucose metabolism in ischemically injured, dysfunctional myocardial tissue as demonstrated on PET imaging predicts functional improvement after revascularization. To characterize more precisely the relationship between regional myocardial blood flow, viability and extent and severity of flow and metabolism abnormalities, we developed a PC-based semiquantitative analysis technique using 13N-ammonia and 18F-deoxyglucose polar map displays. A data base for mean values (m) and standard deviations (s.d.) for relative 13N activities reflecting regional myocardial blood flow, relative 18F activities normalized to normal flow regions reflecting regional glucose utilization and the difference of normalized 18F and 13N activities as an index of a flow-metabolism mismatch was established in 11 normals. Parametric polar maps were derived by comparing patient data to a normal range defined as greater than m - 2 s.d. for relative myocardial blood flow and less than m + 2 s.d. for both relative glucose utilization and the difference between normalized 18F and 13N activities. Semiquantitative indices of extent and severity of blood flow defects, of relative increases in glucose utilization and of flow-metabolism mismatch areas are generated for the entire myocardium and the three coronary territories. The approach promises to be clinically useful to confirm presence and absence of flow and metabolic abnormalities and to assess their extent as a potential predictor of functional outcome after therapy.

Adult↗
PubMed1992

Design features and performance of a PET system for animal research.

The design features of a PET system designed for animal studies are described and its performance evaluated. The system employs a two-dimensional modular detector array consisting of bismuth germanate detector elements that are 3.5 mm (transaxially) by 6.25 mm (axially) by 30 mm (deep). These arrays are optically coupled to a pair of dual-photo-multiplier tubes (PMT). The detector ring is 64 cm in diameter with a field of view (FOV) of 40 cm by 5.4 cm axially, acquiring 15 slices at 3.4 mm spacing. These features include: (1) digitization of PMT signals from each block for improved position and energy discrimination of coincident events and (2) dual-window energy discrimination for simultaneous but separate acquisition of photopeak and scatter data. Intrinsic resolution averages 3.5 mm at the center of the FOV, while reconstructed resolution (ramp filter) ranges from 3.8 mm at the center of the FOV to 4.6 mm at an 8 cm radius. Axial resolution averages 4.4 and 4.9 mm and sensitivity averages 4.2 and 6.1 kcps/microCi/cc for cross planes and enhanced direct planes, respectively. Randoms fraction is high due to reduced interplane shielding, giving a peak true count rate of 103 kcps for a 10 cm cylinder. Scatter as a fraction of trues is 16% for a 10 cm cylinder at a lower energy threshold of 350 keV. All parameters are sensitive to energy threshold. Spatial resolution improves by 11% transaxially and 9% axially, scatter fraction drops to 10%, and overall sensitivity drops by 48% when the threshold value is increased from 350 keV to 450 keV.

Animals↗