Biomedical subjects

M E Phelps

Publications and source records attributed to M E Phelps.

At least 325 records · Page 18Linked to original sources

PubMed1982

Quantitation in positron emission computed tomography: 6. effect of nonuniform resolution.

The intrinsic resolution (FWHM) of coincident bismuth germanate detector pairs was measured for geometries consistent with positron emission computed tomography systems designed for brain imaging. The resolutions were measured as a function of the position in the field of view (FOV) for single slice and multislice configurations for both the image and axial resolutions. System diameters of 66 to 42 cm were simulated, and intrinsic resolution variation for image and axial dimensions for a 24 cm FOV were 14 and 32% and 24 and 39%, respectively. Measurement of axial resolutions of interplane slices of multiplane systems employing interplane septa showed resolution variations for the 24 cm FOV of as large as a factor of three. A simple model was shown to predict the dominant features of the line shapes. Images of phantoms with small axial dimensions indicate that the variations in resolution, particularly in interplane data, seriously compromise the validity of point to point comparison of information within an image or between single plane and interplane images. Serious variations in axial resolution were shown to create artifacts and degrade the image resolution. Index Terms: Emission computed tomography--Image quality.

Tomography, Emission-Computed↗

PubMed1982

Dependence of 13NH3 myocardial extraction and clearance on flow and metabolism.

The isolated arterially perfused rabbit interventricular septum was used to study the relationship between flow (F) and myocardial uptake and subsequent clearance of bolus injections of 13N-labeled ammonia (13NH3). Multiple 13NH3 injections were delivered to a total of 19 septa at perfusion rates (F/g) ranging from 0.2-4.0 ml.min-1.g-1. Ten septa were studied at 37 degrees C and nine were studied at 28 degrees C to obtain uptake and clearance data at different metabolic rates. The septa were perfused without recirculation with a modified Tyrode solution. Analysis of the time-activity curves generated by the injections of 13NH3 revealed that the data was best described by three components. The first two components exhibited short clearance times (t1/2s less than 7 min) in contrast to prolonged clearance times (30-500 min) for component 3. Component 1 was consistent with a freely diffusible 13NH3 compartment. Component 3 persists and permits myocardial imaging 15 min or more after 13NH3 injection. At each perfusion rate the extraction fraction of component 3 was twice as large, and the clearance time of component 3 was twice as fast at 37 as at 28 degrees C, implying that the extraction and washout of this third component are dependent on enzymatic reactions. The total myocardial extraction into component 3 from a systemic injection is determined by multiplying the extraction fraction by the perfusion rate (EF(3) X F/g) and was directly related to the perfusion rate at both 28 and 37 degrees C.

Ammonia↗

PubMed1982

Estimation of rabbit myocardial metabolic rate for glucose using fluorodeoxyglucose.

The isolated arterially perfused rabbit interventricular septum was used to determine the feasibility of using the glucose analogue 18F-2-deoxy-2-fluoro-d-glucose (DG) with a tracer kinetic model to estimate the rate of exogenous glucose utilization. FDG was delivered to the septum by constant infusion, and tissue 18F radioactivity was measured as a function of time by external coincidence counting. The following four conditions were studied: flow rates of 0.5, 1.0, and 1.5 ml/min with a heart rate of 72 beats/min and flow at 1.5 ml/min with 96 beats/min. The rate constants for FDG forward and reverse transport between the vascular and extravascular compartments (k*1, k*2, respectively), phosphorylation of FDG (k*3), and dephosphorylation of FDG-6-phosphate (FDG-6-P) (k*4) were determined from the tissue curves using a tracer kinetic model. The lumped constant (LC) of the deoxyglucose model calculated using Fick-derived myocardial metabolic rates of glucose (MMRGlc), was 0.60 +/- 0.10 and was stable over the range of conditions studied. Average k*'s and LC were used to calculate MMRGlc's employing the model and were not significantly (P greater than 0.05) different from those determined by the Fick method. Tissue analyses using high-pressure liquid chromatography documented that tissue 18F radioactivity wa due to FDG and FDG-6-P, and their relative fractions agreed well with the values predicted from the tracer kinetic model. Only FDG was detected in the effluent. These studies also indicate the presence of a myocardial enzyme that can hydrolyze FDG-6-P to FDG. Thus our results support the use of the FDG method with positron-computed tomography for the in vivo determination of the myocardial rate of exogenous glucose utilization.

Animals↗

PubMed1982

Tomographic mapping of human cerebral metabolism: auditory stimulation.

Cerebral metabolic responses to verbal and nonverbal auditory stimuli were examined, using 18F-fluorodeoxyglucose and positron CT. Twenty right-handed subjects were studied in both control and stimulated states. Monaural verbal stimuli produced diffuse metabolic changes in the left hemisphere and bilateral activation of the transverse and posterior temporal lobes. Monaural nonverbal stimulation with chords demonstrated bilateral parietotemporal activations and diffuse right greater than left frontotemporal asymmetries. Tone sequence pairs presented monaurally produced asymmetries that differed by the subject's analysis strategy. Nonanalytical, musically naive subjects had right greater than left frontotemporal asymmetries, whereas analytic or musically sophisticated subjects had an absence of right greater than left relative hypermetabolism and demonstrated left greater than right temporal asymmetries. Binaural presentation of a factual story and music produced diffuse bilateral activations of the temporal and frontal cortex. Known anatomic asymmetries of the perisylvian cortex were revealed by high-resolution tomography. These results demonstrate that metabolic responses to auditory stimuli are determined by the content of the stimulus and the analysis strategy of the subject rather than the side of stimulation. The results also demonstrate the capacity of functional imaging techniques to study the physiologic cerebral mechanisms underlying auditory processing.

Acoustic Stimulation↗

PubMed1982

Quantifying local cerebral blood flow by N-isopropyl-p-[123I]iodoamphetamine (IMP) tomography.

A model was validated wherein local cerebral blood flow (LCBF) in humans was quantified by single-photon emission computed tomography (SPECT) with intravenously injected N-isopropyl-p-[123I]iodoamphetamine (IMP) combined with a modification of the classic method of arterial input sampling. After intravenous injection of IMP in rat, autoradiograms of the brain showed activity distributions in the pattern of LCBF. IMP was nearly completely removed on first pass through monkey brain after intracarotid injection (CBF=33 ml/100 g/min) and washed out with a half-time of approximately 1 hr. When the modified method of arterial input and tissue-sample counting applied to dog brain, there was good correspondence between LCBF based on IMP and on that by microsphere injection over a wide flow range. In applying the method to human subjects using SPECT, whole-brain CBF measured 47.2 +/- 5.4 ml/100 g/min (mean +/- s.d., N=5), stable gray-white distinction persisted for over 1 hr, and the half-time for brain washout was approximately 1 hr. Perfusion deficits in patients were clearly demonstrated and quantified, comparing well with results now available from positron ECT.

Adolescent↗

PubMed1982

Performance of the rotating slant-hole collimator for the detection of myocardial perfusion abnormalities.

To determine the usefulness of the rotating slant-hole (RSH) collimator, a new imaging device for tomographic myocardial imaging, we evaluated its performance in phantom studies. Perfusion defects of variable size, location, and tracer concentration were simulated and imaging was performed with a conventional parallel-hole collimator and the RSH collimator. Planar and depth resolutions assessed with a line source compared favorably with those reported previously for the seven-pinhole collimator. The results also showed RSH tomography to be more sensitive than planar imaging in detecting simulated myocardial defects but indicated some limitations, especially the occurrence of artifactual defects that may reduce the specificity of the imaging device for the detection of perfusion abnormalities.

Coronary Disease↗

PubMed1982

Positron tomography with deoxyglucose for estimating local myocardial glucose metabolism.

The deoxyglucose method originally developed for measurements of the local cerebral metabolic rate for glucose has been investigated in terms of its application to cardiac studies with positron computed tomography (PCT) and fluorodeoxyglucose (FDG). Studies were performed in dogs to measure the tissue kinetics of FDG with PCT and by arterial and venous sampling. The operational equation developed in our laboratory as an extension of the Sokoloff model was used to analyze the data. Error propagation, primarily from corrections applied to remove spillover of activity from the myocardial blood pool to tissue and from partial-volume effects in the PCT images, limited accuracy in the estimation of the individual rate constants for transport, phosphorylation, and dephosphorylation. However, a constant representing the combination of transport and phosphorylation was accurately determined and yielded measured values of the myocardial metabolic rate for glucose (MMRGlc) that were in good agreement with direct determinations using the Fick method over a wide range of glucose metabolic rates (from 1.7 to 21.1 mg/min-100 g). The lumped constant (0.67 +/- 0.10) was also found accurate and stable over this range of metabolism. The FDG method accurately predicted the true MMRGlc even when the glucose metabolic rate was normal but myocardial blood flow (MBF) was five times the control value, or when metabolism was reduced to 10% of normal and MBF increased to five times normal. Improvements of PCT resolution are required to improve the accuracy of the estimates of the rate constant and the MMRGlc.

Animals↗

PubMed1982

Evaluation of myocardial metabolism, with N-13- and C-11-labeled amino acids and positron computed tomography.

To evaluate the utility of labeled L-amino acids (AA) for imaging regional myocardial AA metabolism by positron computed tomography (PCT), the myocardial uptake and clearance of Ala,* Glu, Gln, Asp, Leu tagged with N-13, and of C-11-tagged Asp, and oxaloacetate (Oxal), were examined in 44 experiments at control, during ischemia, and after transaminase inhibition. The myocardial time-activity curves recorded after intracoronary tracer injection had two clearance phases (an early and a late) for all N-13 AA, and three (early, intermediate, late) for the two C-11 compounds, with significantly different clearance half-times of 18.7 +/- 8.0 (s.d.) sec for the early phase, 141.7 +/- 56.5 sec for the intermediate, and 61.2 +/- 43.5 min for the late phase. The residual fractions ranged from 0.07 to 0.23 in normal myocardium, and consistently increased with ischemia by 0.01-0.07 for N-13-labeled Ala, Glu, Asp, and Leu, but not for N-13 Gln and C-11 compounds. Transaminase inhibition shortened the half-times of the late phases of N-13-labeled Ala, Glu, Asp, and Leu; had no effect on t1/2 of N-13 Gln and C-11 Oxal; and resulted in a loss of C-11 CO2 production and of the intermediate phase for C-11 Asp. On the PCT images, N-13 activity from labeled Ala and Glu was not decreased in an ischemic segment despite a significant flow reduction, as demonstrated by N-13 NH3 imaging and labeled microspheres. From the results, a three-compartment tracer kinetic model is proposed for the noninvasive quantification of Krebscycle activity, protein synthesis, and metabolic derangements related to ischemia.

Amino Acids↗

PubMed1982

An investigation of a double-tracer technique for positron computerized tomography.

We describe a double-tracer technique for positron computed tomography (PCT) that utilizes the differences in physical decay rates to distinguish between two positron emitters. The technique is applied to PCT studies on phantoms (a) to separate two tracers with different half-lives, and (b) to measure simultaneously the attenuation coefficients and the tracer concentrations in a phantom. Results from these experiments are encouraging, but they also reveal a major limitation of the technique, namely, noise enhancement that is related to the relative half-lives of the two tracers and the time duration of the PCT scans, as well as to the relative concentrations of the two tracers. If these parameters are carefully selected, the double-tracer technique will have high potential for examining simultaneously two different biological processes with PCT and for measuring tracer concentrations and attenuation correction factors at the same time.

Copper↗

PubMed1982

The unit operations approach applied to the synthesis of [1(-11)C]2-deoxy-D-glucose for routine clinical applications.

An approach to the design of remote semiautomated chemical processing systems has been developed and tested in more than 750 production runs. This design stresses the idea of unit operations, which allows maximum flexibility while maintaining the highest possible standards regarding safety, reliability, efficiency, and practicality. Application of this approach has resulted in the development of a simple and reliable remote semiautomated synthesis system for the routine production of [1(-11)C]2-deoxy-D-glucose. Use of this system results in the preparation of a sterile, pyrogen-free product suitable for human injection after a synthesis time of 50 min, with radiochemical purity of greater than 98% and yields (25-30%) permitting quantitative measurements using positron computed tomography.

Carbon Radioisotopes↗

PubMed1981

Metabolic mapping of the brain's response to visual stimulation: studies in humans.

These studies demonstrated increasing glucose metabolic rates in the human primary (PVC) and associative (AVC) visual cortex as the complexity of visual scenes increased. The metabolic response of the AVC increased more rapidly with scene complexity than that of the PVC, indicating the greater involvement of the higher order AVC for complex visual interpretations. Increases in local metabolic activity by as much as a factor of 2 above that of control subjects with eyes closed indicate the wide range and metabolic reserve of the visual cortex.

Adult↗

PubMed1981

FDG positron emission computed tomography in a study of aphasia.

Positron emission computed tomography (PECT) using 18F-2-fluoro-2-deoxy-D-glucose (FDG) was used to investigate the correlations between clinical status, anatomy (as described by CT), and metabolism in five patients with stable aphasia resulting from ischemic cerebral infarction. Local cerebral metabolic activity was diminished in an area larger than the area of infarction demonstrated by CT. In one patient, FDG PECT revealed a metabolic lesion that probably caused the aphasic syndrome and was not apparent by CT. The data suggest that reliance on CT in delineating the extent of the brain lesion in aphasia or other neuropsychological defects can be misleading; FDG PECT may provide important additional information. Two patients with similar metabolic lesions had very different clinical syndromes, showing that even when currently available methods are combined, major gaps remain in clinicoanatomical correlations in aphasia.

Aged↗

PubMed1981

Positron computed tomography studies of cerebral glucose metabolism in man: theory and application in nuclear medicine.

The capability of positron computed tomography (PCT) to delineate the substructures of the brain and its facility for accurately measuring the local tissue radioactivity concentration allow the application of tracer kinetic models for the study of local cerebral function in man. This principle and an adaptation of the 14C-deoxyglucose (DG) model of Sokoloff et al. with 18F-2-fluoro-deoxy-D-glucose (FDG) is being used at UCLA. Brookhaven National Laboratory, University of Pennsylvania, NIH, and the Massachusetts General Hospital to determine the local cerebral glucose metabolic rate (LCMRGIc) in normal man at rest and during sensory activation and the changes that occur in patients with a variety of cerebral disorders. Kinetic studies with PCT have been employed to measure the rate constants of the model in different gray and white matter structures of the brain in both normal and ischemic states. The precision of the method in normals has been shown to be about +/- 5% for 1.5-2.0 sq cm regions of the brain. Studies in normals have yielded values for hemispheric CMRGIc that are in agreement with measurement using the Kety-Schmidt technique and LCMRGIc values in agreement with values in monkeys using DG autoradiography. Studies in volunteers subjected to visual and auditory stimulation are demonstrating the potential of this technique for investigating the human brain's response to different stimuli. STudies in patients with stroke show excellent correlation between the degree, extent, and particular structures involved and the clinical symptoms. The method consistently detected hypometabolism in cortical, thalamic, and striatal tissues that were dysfunctional due to deactivation or damage but which appeared normal on x-ray CT. Studies in patients with partial epilepsy have shown hypometabolic zones that highly correlated anatomically with interictal EEG spike foci and were associated with normal x-ray CT studies in 77% of the patients studied. The studies on epilepsy at UCLA have resulted in the integration of the LCMRGIc study into the clinical workup of patients with partial epilepsy that are candidates for surgical resection of their epileptogenic focus (effective June 1979). Studies on Huntington's chorea, Parkinson's disease, aphasia, dementia, schizophrenia, and tumors are in early stage of investigation but also are providing exciting new results. Further studies are needed to determine the role of the local function information obtained with the PCT-FDG method in elucidating the basic mechanism and the potential to aid in improving the approach to medical therapy.

Brain↗

PubMed1981

13N-labeled L-amino acids for in vivo assessment of local myocardial metabolism.

The hot cell synthesis of sterile, pyrogen-free 13N-labeled L-amino acids was accomplished by employing the appropriate immobilized enzymes on a CNBr-activated Sepharose support and using remote, semiautomated systems. The syntheses were completed 6-12 min after cyclotron production of [13N]ammonia. Myocardial time-activity curves after intracoronary injection of 13N-labeled L-amino acids in dogs were triexponential in both normal and ischemic myocardium. Higher retention of 13N activity was observed in ischemic segments. Positron computed tomography imaging also showed increased uptake of 13N-labeled L-glutamate and L-alanine in ischemic segments compared with normal myocardium when blood flow corrections were made. Myocardial transaminases are primarily responsible for the observed retention fractions. It suggests the participation of the carbon skeletons of these amino acids in the Krebs cycle.

Amino Acids↗

PubMed1981

Error sensitivity of fluorodeoxyglucose method for measurement of cerebral metabolic rate of glucose.

The fluorodeoxyglucose (FDG) method for the measurement of local cerebral metabolic rate of glucose (LCMRGlc) employs typical values of the FDG transport rate constants that have been obtained by kinetic measurements on an appropriate control group. Discrepancies between the true values of the rate constants in tissue and the typical values used in the operational equation of the FDG method will introduce error in the estimate of LCMRGlc. Computer simulations were used to evaluate the accuracy of the FDG method in cases where (1) the tissue LCMRGlc deviates greatly from the normal values (e.g., stroke) or (2) the tissue LCMRGlc changes during the experiment (e.g., epileptic seizure). The effects of the magnitude and duration of metabolic changes were studied. The results indicate that if tissue LCMRGlc differs greatly from the normal value, the error in the estimated LCMRGlc at a scan time of 60 min is less than 20% of the difference between the true and normal values. In the non-steady-state cases, the estimated LCMRGlc was found to be a weighted average of the metabolic rates during the experiments, with the weightings approximately proportional to the plasma FDG concentration at the corresponding times. For example, if LCMRGlc in tissue was 5 times the normal values for the first 10 min but then returned to normal state, the LCMRGlc measured by the FDG method at a scan time of 60 min would be about only 2-3 times the normal value. The results of this study provide a better understanding of the accuracy of the FDG method under various tissue metabolic conditions and is useful for interpreting metabolic values obtained with the FDG method.

Biological Transport↗

PubMed1981

Effect of ischemia on quantification of local cerebral glucose metabolic rate in man.

The model for quantifying local cerebral glucose metabolic rates originally developed by Sokoloff et al. and modified by Phelps. Huang and co-workers was applied to humans with cerebral ischemia (i.e., stroke). Rate constants for fluorodeoxyglucose were measured in ischemic and nonischemic regions with position computed tomography. Using measured rate constants for ischemia, the model generate more accurate estimates of local cerebral glucose metabolism as compared to the use constants from normal young adults, because the local metabolic rate is significantly underestimated, and temporal instability of the model is observed when normal values are applied to ischemic regions. A method was also developed to test the stability of the local lumped constant. The estimates of the lumped constant showed no or only small variations between ischemic and nonischemic types. Thus, errors introduced in the calculated local cerebral glucose metabolism by inappropriate rate constants appear to be more significant than those caused by any potential change in the lumped constant in ischemia.

Aged↗

PubMed1981

Quantitation in positron emission computed tomography: 4. Effect of accidental coincidences.

Accidental coincidences (ACs) and methods of compensation for ACs were investigated in terms of their effect on quantitation in positron emission computed tomography (ECT). Formulations of basic expressions describing the physical factors, which cause true coincidences or ACs, are presented to provide a framework of contrasting the two phenomena. Correction of image data for attenuation of the annihilation radiation or nonuniformities in detector efficiency is shown to amplify errors caused by the presence of ACs in the data. It was shown that failure to compensate for ACs caused overestimates in measurements of isotope concentrations from image data and that in many cases the overestimate was significant for relatively modest percentages of ACs in the data. Three methods of compensation for ACs were evaluated as to their accuracy and effect on statistical noise in images. It was found that nonuniform detector efficiencies could cause prominent image artifacts if an inadequate method was employed in the determination and subtraction of ACs from image data. The additional statistical noise produced in images by subtraction of ACs from total coincidence data demonstrates the advisability of minimizing AC rates in spite of an ability to adequately measure and compensate for their presence in the data.

Copper↗

PubMed1981

Quantitation in positron emission computed tomography: 5. Physical--anatomical effects.

The effect of neuroanatomical structure size, shape, and position versus spatial tomographic resolution on quantitation in positron computed tomography was investigated. For neuroanatomical structures, voxel sizes in excess of 3 ml exceeded the volume of most structures examined. When the voxel size exceeded structure volume, calculated recovery coefficient (fraction of the true isotope concentration measured in the image) fell to less than or equal to 42%. Partial volume effects in the plane of section analyzed by computer simulation produced errors that were largest for small, thin, irregularly shaped structures whose averaged pixel values were most different from neighboring structures. Smallest errors occurred in large, circular structures surrounded by regions of similar pixel values. Computer simulation of regional cerebral asymmetries of pixel values demonstrated that the measurement of these asymmetries was often predominated (enhanced or obliterated) by partial volume effects related to structure size and shape. Large, circular, and widely separated regional asymmetries were more easily detected at a given spatial resolution than small, thin, adjacent regions. Recommendations for error reduction and possible correction factors are provided and discussed.

Brain↗