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M E Phelps

Publications and source records attributed to M E Phelps.

At least 163 records · Page 9Linked to original sources
PubMed1992

Use of the abdominal aorta for arterial input function determination in hepatic and renal PET studies.

A method using the activity in the abdominal aorta of human and animal subjects to noninvasively estimate blood-pool input function in dynamic, abdominal PET scans is proposed and validated in this paper. Partial volume effects due to the aorta's dimensions are corrected by a semi-automated algorithm based on the transaxial resolution in the reconstructed images. The technique was validated by comparing PET measurements of abdominal aortic activity to well counter measurements of arterial blood samples (eight canine renal studies) and to PET measurements of left ventricular cavity activity (eight human hepatic studies). In renal studies, correlation analysis of the areas subtended by the two input functions yielded an essentially unitary slope (1.03 +/- 0.09), with high correlation (R2 greater than 0.95, p less than 0.001). In hepatic studies, similar values (0.99 +/- 0.03 and R2 greater than 0.85, p less than 0.001) were found. Correlation of the blood flow estimates based on the two input functions and a two-compartment model produced slopes of 1.07 +/- 0.16 and 1.03 +/- 0.07, and correlations of (R2 greater than 0.98, p less than 0.001) and (R2 greater than 0.97, p less than 0.001) for the renal and hepatic studies, respectively. We conclude that noninvasive, accurate measurements of the arterial input function by dynamic PET imaging are possible and represent a clinically viable alternative to arterial blood sampling.

Animals↗
PubMed1992

Evaluation of the skeletal kinetics of fluorine-18-fluoride ion with PET.

To evaluate the feasibility of quantitatively assessing regional skeletal fluoride uptake in humans in focal and generalized bone disease, we investigated the skeletal kinetics of [18F]fluoride ion with dynamic PET imaging. Dynamic image sets were acquired over a 60-min interval in a multiplane PET device, and input functions (plasma 18F time-activity curves) were measured directly from arterialized blood and, in some cases, determined from image-derived left ventricular cavity activity measurements. Our results indicate: 1. A steady-state ratio of [18F]fluoride ion concentration in plasma to whole blood greater than unity (1.23 for plasma to directly assayed whole blood and 1.44 for plasma to left ventricular cavity imaged concentrations. This concentration difference produces a scaling factor that must be considered when using image derived or directly measured input functions. 2. The preferred tracer kinetic model configuration for [18F]fluoride ion skeletal kinetics is a three compartment model that includes a "bound" and "unbound" bone [18F]fluoride ion compartment. 3. The rate constant for forward transport of [18F]fluoride ion from plasma to the extravascular space of bone (K1) and the regional blood volume parameter generate estimates of bone blood flow and vascular volume, respectively, that are in the physiologic range of reported for mammals. Estimates of the uptake constant for fluoride in bone, using nonlinear regression (KNLR = 0.0360 +/- 0.0064 ml/min/ml), are in very good agreement with an estimate of the same parameter obtained with Patlak graphical analysis (KPAT = 0.0355 +/- 0.0061 ml/min/ml). 4. Generating parametric images of KPAT facilitates quantification of regional bone [18F]fluoride ion kinetics. The method is computationally practical, and, with either the parametric imaging approach or with standard region of interest analysis, can be used to generate quantitative estimates of fluoride uptake (a "bone metabolic index") in focal skeletal regions or in more generalized distributions.

Adult↗
PubMed1992

Whole-body positron emission tomography: Part I. Methods and performance characteristics.

Methods for whole-body PET imaging have been developed to provide a clinical tool for the detection and evaluation of primary and metastatic cancers. The axial FOV of the PET system is extended by imaging at multiple bed positions to cover the whole body. In typical rectilinear PET scans, only a small fraction of the data is collected to form two-dimensional projection images. In this work, 100% of the projection data was collected to form the two-dimensional projection images. These projection images were generated for continuous angles over 180 degrees by resorting sinogram data. In addition, tomographic images were formed by using filtered backprojection reconstruction without attenuation correction. Coronal and sagittal cuts were then extracted from the three-dimensional data set. The tomographic images were reconstructed to a resolution of 10.8 mm in all dimensions because of statistical limitations of the data. Both methods of image formation resulted in images of high quality with the tomographic reconstruction providing the highest contrast and resolution. An acquisition time of 1-2 min/bed position after a 10-mCi injection of [18F]fluoride ion or [18F]FDG was found to give a sufficient number of counts for producing images of good resolution and contrast, from a total scanning time of 32-64 min.

Deoxyglucose↗
PubMed1992

Issues in the quantitation of reoriented cardiac PET images.

Reorientation of transaxial cardiac PET images into short-axis images has been shown by other investigators to improve visual identifiability of defects in myocardial tracer uptake. However, quantification of physiologic processes from such reoriented images may be complicated by errors introduced during the reorientation process. Therefore, a quantitative characterization of these errors is necessary. An annular phantom of human cardiac dimensions was imaged in a 15-plane positron emission tomograph at six angles (0 degrees, 5 degrees, 25 degrees, 45 degrees, 65 degrees, 85 degrees) and at two different axial sampling densities. In addition, two different reorientation interpolators were employed, one using three-dimensional linear interpolation and the other using a "hybrid" interpolation algorithm. Distortion of linear distances was variable but was minimized with denser axial sampling and the use of hybrid interpolation. Circumferential profile analysis, corrected for inhomogeneities in reoriented image spatial resolution, revealed a maximal loss of region of interest counts at 65 degrees of at least 14.4%. Reorientation errors were minimized by use of dense axial sampling, low angles of reorientation and use of the hybrid interpolation algorithm.

Deoxyglucose↗
PubMed1992

Functional anatomy of human procedural learning determined with regional cerebral blood flow and PET.

The functional anatomy of motor skill acquisition was investigated in six normal human subjects who learned to perform a pursuit rotor task with their dominant right hand during serial positron emission tomography (PET) imaging of relative cerebral blood flow (relCBF). The effect of motor execution, rather than learning, was identified by a comparison of four motor performance scans with two control scans (eye movements only). Motor execution was associated with activation of a distributed network involving cortical, striatonigral, and cerebellar sites. Second, the effect of early motor learning was examined. Performance improved from 17% to 66% mean time on target across the four PET scans obtained during pursuit rotor performance. Across the same scans, significant longitudinal increases of relCBF were located in the left primary motor cortex, the left supplementary motor area, and the left pulvinar thalamus. The results demonstrate that changes of regional cerebral activity associated with early learning of skilled movements occur in sites that are a subset of a more widely distributed network that is active during motor execution.

Adult↗
PubMed1992

The effects of carbidopa administration on 6-[18F]fluoro-L-dopa kinetics in positron emission tomography.

Carbidopa (L-alpha-hydrazino-alpha-methyl-b-(3,4-dihydroxyphenyl) propionic acid is a known inhibitor of aromatic amino acid decarboxylase. In both humans and monkeys, we studied the effects of carbidopa on plasma and brain kinetics of 6-[18F]fluoro-L-DOPA (FDOPA), an analog of L-DOPA used for PET studies of the central dopaminergic system. Pretreatment with carbidopa resulted in increases in the plasma levels of FDOPA and 3-O-methyl-6-[18F]fluoro-L-DOPA (3-OMFD). Total striatal and cerebellar activities measured with PET were also increased. Furthermore, increases observed in the specific striatal activity (striatum minus cerebellum total activity) were correlated with increases in the plasma FDOPA curve. Carbidopa pretreatment did not affect the influx rate constant (K) for FDOPA from plasma to striatum in humans as determined by Patlak graphical analysis. Thus, an increase in measured striatal tomographic activity was secondary to the increase in plasma FDOPA levels rather than as a result of changes in the FDOPA influx rate constant.

Adult↗
PubMed1991

6-[18F]fluoro-L-dopa metabolism in MPTP-treated monkeys: assessment of tracer methodologies for positron emission tomography.

6-[18F]Fluoro-L-DOPA (FDOPA) is an L-DOPA analog that is used to assess the functional integrity of central dopaminergic systems in vivo with positron emission tomography (PET). FDOPA metabolites from putamen of normal and MPTP-treated monkeys were characterized to correlate FDOPA metabolism changes with those of the endogenous dopamine system. In MPTP-lesioned putamen, 6-[18F]fluorodopamine and dopamine levels were less than 2% those of controls. Increases in endogenous dopamine metabolism were reflected by similar increases in 6-[18F]fluorodopamine metabolites. These results suggest that changes in the central dopamine system biochemistry can be monitored in vivo with FDOPA and PET.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1991

PET: a biological imaging technique.

Like in vivo autoradiography, PET provides a means to image and measure rates of biological processes throughout the distributed and interrelated systems of the entire living brain. In addition, both techniques can track and image the functional interactions of the brain with other systems throughout the entire body. Technological advances are yielding higher image spatial resolution and "Electronic generators" for automated synthesis of positron labeled compounds. The expanding number of labeled compounds (greater than 500) is providing a growing number of biological assays (i.e., substrate metabolism, pre and post synaptic processes, enzyme activity, interaction of medical and illicit drugs with biological systems of the brain, immune system, membrane processes). Studies of normal cerebral function focus on mapping evoked responses of various components of motor, visual, somatosensory, memory and cognitive functions. Cerebral development, neuronal plasticity, and compensatory reorganization to lesions or surgery are active areas of investigation. Various types of assays have been used to identify specific biological alterations, map progression and determine therapeutic responses in a wide variety of neuropsychiatric disorders and drug abuse.

Autoradiography↗
PubMed1991

A quantitative index of regional blood flow in canine myocardium derived noninvasively with N-13 ammonia and dynamic positron emission tomography.

To derive a quantitative index of regional myocardial blood flow, the arterial input function of the flow tracer N-13 ammonia and the regional myocardial N-13 activity concentrations were noninvasively determined in 29 experiments in eight dogs. N-13 ammonia was administered intravenously and cross-sectional images were acquired dynamically using an ECAT III positron emission tomograph with an effective in-plane resolution of 13.46 mm full-width half-maximum. Time-activity curves were derived from the serial images by assigning regions of interest to the left ventricular myocardium and left ventricular blood pool. Tracer net extractions were estimated from the myocardial time-activity concentrations at various times after tracer injection and the integral of the arterial input function. Myocardial blood flow was altered by intravenous dipyridamole, morphine, propranolol and partial or complete occlusion of the left anterior descending coronary artery, and ranged from 9 to 860 ml/min per 100 g. Estimates of tracer net extractions were most accurate when determined from the myocardial N-13 activity concentrations at 60 s divided by the integral of the arterial input function to that time. These estimates correlated with regional myocardial blood flows determined independently by the microsphere technique by y = x (1 - 0.64(e-114/x); SEE = 22.9; r = 0.94). First pass extraction fractions of N-13 ammonia determined noninvasively with this approach declined with higher flows in a nonlinear fashion and were similar to those determined invasively by direct intracoronary N-13 ammonia injections. The findings indicate that an accurate index of regional myocardial blood flow can be obtained noninvasively by high temporal sampling of arterial and myocardial tracer activity concentrations with positron emission tomography. They also provide a basis for the in vivo application of tracer kinetic principles to derive quantitatively and noninvasively regional rates of functional processes in human myocardium.

Ammonia↗
PubMed1991

Metabolic and functional recovery of ischemic human myocardium after coronary angioplasty.

Although revascularization of hypoperfused but metabolically active human myocardium improves segmental function, the temporal relations among restoration of blood flow, normalization of tissue metabolism and recovery of segmental function have not been determined. To examine the effects of coronary angioplasty on 13 asynergic vascular territories in 12 patients, positron emission tomography and two-dimensional echocardiography were performed before and within 72 h of revascularization. Ten patients underwent late echocardiography (67 +/- 19 days) and eight underwent a late positron emission tomographic study (68 +/- 19 days). The extent and severity of abnormalities of wall motion, perfusion and glucose metabolism were expressed as wall motion scores, perfusion defect scores and perfusion-metabolism mismatch scores. Angioplasty significantly increased mean stenosis cross-sectional area (from 0.95 +/- 0.9 to 2.7 +/- 1.4 mm2) and mean cross-sectional luminal diameter (from 0.9 +/- 0.6 to 1.9 +/- 0.5 mm) (both p less than 0.001). Perfusion defect scores in dependent vascular territories improved early after angioplasty (from 116 +/- 166 to 31 +/- 51, p less than 0.002) with no further improvement on the late follow-up study. The mean perfusion-metabolism mismatch score decreased from 159 +/- 175 to 65 +/- 117 early after angioplasty (p less than 0.01) and to 26 +/- 29 at late follow-up (p less than 0.001 vs. before angioplasty; p = NS vs. early after angioplasty). However, absolute rates of glucose utilization remained elevated early after revascularization, normalizing only at late follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗
PubMed1991

Changes in glucose metabolism in dementia of the Alzheimer type compared with depression: a preliminary report.

We evaluated positron emission tomography (PET) in the differential diagnosis of depression and Alzheimer's disease. The local cerebral metabolic rate for glucose (LCMRGlc) in the parahippocampal gyrus-hippocampus and the dorsolateral prefrontal cortex were determined. The ratio of the LCMRGlc in those two regions was examined in patients with unipolar depression, bipolar depression, and Alzheimer's dementia. An analysis of variance revealed significant overall intergroup differences in values for both hemispheres. Student's t test showed significant differences in LCMRGlc for both unipolar and bipolar depression as compared with Alzheimer's dementia. These data indicate that PET may be useful in the differential diagnosis of dementia vs. depression.

Aged↗
PubMed1991

Differentiating cardiomyopathy of coronary artery disease from nonischemic dilated cardiomyopathy utilizing positron emission tomography.

To determine if imaging of blood flow (using N-13 ammonia) and glucose metabolism (using F-18 2-deoxyglucose) with positron emission tomography can distinguish cardiomyopathy of coronary artery disease from nonischemic dilated cardiomyopathy, 21 patients with severe left ventricular dysfunction who were evaluated for cardiac transplantation were studied. The origin of left ventricular dysfunction had been previously determined by coronary angiography to be ischemic (11 patients) or nonischemic (10 patients). Images were visually analyzed by three observers on a graded scale in seven left ventricular segments and revealed fewer defects in dilated cardiomyopathy compared with ischemic cardiomyopathy for N-13 ammonia (2.7 +/- 1.6 versus 5 +/- 0.6; p less than 0.03) and F-18 deoxyglucose (2.8 +/- 2.1 versus 4.6 +/- 1.1; p less than 0.03). An index incorporating extent and severity of defects revealed more homogeneity with fewer and less severe defects in subjects with nonischemic than in those with ischemic cardiomyopathy as assessed by imaging of flow (2.8 +/- 1.8 versus 9.2 +/- 3; p less than 0.001) and metabolism (3.8 +/- 3.3 versus 8.5 +/- 3.6; p less than 0.005). Diagnostic accuracy for distinguishing the two subgroups by visual image analysis was 85%. Using previously published circumferential count profile criteria, patients with dilated cardiomyopathy had fewer ischemic segments (0.4 +/- 0.8 versus 2.5 +/- 2 per patient; p less than 0.01) and infarcted segments (0.1 +/- 0.3 versus 2.4 +/- 1.4 per patient; p less than 0.001) than did patients with cardiomyopathy of coronary artery disease. The sensitivity for differentiating the two clinical subgroups using circumferential profile analysis was 100% and the specificity 80%. An index incorporating both number and severity of defects derived from circumferential profile analysis was significantly lower in subjects with dilated cardiomyopathy than in ischemic cardiomyopathy (0.3 +/- 0.8 versus 2.7 +/- 2.4; p less than 0.005). Thus, noninvasive positron emission tomographic imaging with N-13 ammonia and F-18 deoxyglucose is helpful in distinguishing patients with severe left ventricular dysfunction secondary to coronary artery disease from those with nonischemic cardiomyopathy, and a semiquantitative index such as circumferential profile analysis is superior to that of visual analysis alone.

Adult↗
PubMed1991

L-6-[18F]fluoro-dopa metabolism in monkeys and humans: biochemical parameters for the formulation of tracer kinetic models with positron emission tomography.

Characterization of peripheral and cerebral L-3,4-dihydroxy-6-[18F]fluorophenylalanine (FDOPA) metabolism in humans and monkeys has shown FDOPA to be an analogue of L-DOPA for the study of the dopaminergic system with positron emission tomography (PET). In human studies with carbidopa pretreatment, L-3,4-dihydroxy-6-[18F]fluoro-3-O-methylphenylalanine (3-OMFD) was the only FDOPA metabolite detected in plasma. FDOPA administration in monkeys resulted in selective accumulation of FDOPA metabolites in central dopaminergic regions, whereas 3-OMFD of peripheral origin was uniformly distributed among putamen, caudate, frontal cortex, and cerebellum. At 60 min, 3-OMFD and 6-[18F]fluorodopamine (FDA) each represented approximately 35% of the total activity, the remainder being FDOPA and FDA metabolites. These data on monkey and human FDOPA metabolism provide the basis for the configuration of an FDOPA tracer kinetic model with PET.

Adult↗
PubMed1991

Kinetics and modeling of L-6-[18F]fluoro-dopa in human positron emission tomographic studies.

Kinetics of L-3,4-dihydroxy-6-[18F]fluorophenylalanine (FDOPA) in striatum and cerebellum were measured in 10 normal human subjects with positron emission tomography (PET) from 0 to 120 min after an intravenous bolus injection of the tracer. The time course of the arterial plasma concentrations of the tracer and its metabolites was also assayed biochemically. FDOPA compartmental models that are based on biochemical information were investigated for their consistency with the measured striatal and cerebellar tissue kinetics. A modeling approach was also developed for separating plasma FDOPA and metabolite time-activity curves from the measured total 18F time-activity curve in plasma. Results showed that a model consisting of three separate compartments for tissue FDOPA, tissue 6-[18F]fluorodopamine (FDA) and its metabolites, and tissue L-3,4-dihydroxy-6-[18F]fluoro-3-O-methylphenylalanine (3-OMFD) could describe adequately the striatal kinetics in humans. Based on this model, the FDOPA transport constant across the blood-brain barrier (BBB) (K1), the FDOPA decarboxylation rate constant (k3), and the turn-over rate constant of FDA and its metabolites (k4) could be estimated by model fitting to the tissue kinetics and were found for the normal subjects to be 0.031 +/- 0.006 ml/min/g (mean +/- SD), 0.041 +/- 0.015/min, and 0.004 +/- 0.002/min, respectively. About 50% of the FDOPA that crossed the BBB from plasma to striatum was decarboxylated. The decarboxylation constant with respect to plasma FDOPA (K3) was 0.015 +/- 0.003 ml/min/g. The BBB transport corresponded to a permeability-surface area product of 0.032 ml/min/g for FDOPA. For 3-OMFD, the BBB transport was 1.7 times faster. The effects of tissue heterogeneity on the FDOPA kinetics and on the estimated model parameters were also investigated. The usefulness and implications of these findings for interpretation of PET FDOPA studies are discussed.

Adult↗
PubMed1991

Metabolic maturation of the brain: a study of local cerebral glucose utilization in the developing cat.

Previously, using positron emission tomography (PET), we showed that local cerebral metabolic rates for glucose (lCMRglc) in children undergo dynamic maturational trends before reaching adult values. In order to develop an animal model that can be used to explore the biological significance of the different segments of the lCMRglc maturational curve, we measured lCMRglc in kittens at various stages of postnatal development and in adult cats using quantitative [14C]2-deoxyglucose autoradiography. In the kitten, very low lCMRglc levels (0.14 to 0.53 mumol min-1 g-1) were seen during the first 15 days of life, with phylogenetically older brain regions being generally more metabolically mature than newer structures. After 15 days of age, many brain regions (particularly telencephalic structures) underwent sharp increases of lCMRglc to reach, or exceed, adult rates by 60 days. This developmental period (15 to 60 days) corresponds to the time of rapid synaptic proliferation known to occur in the cat. At 90 and 120 days, a slight decline in lCMRglc was observed, but this was followed by a second, larger peak occurring at about 180 days, when sexual maturation occurs in the cat. Only after 180 days did lCMRglc decrease to reach final adult values (0.21 to 2.04 mumol min-1 g-1). In general, there was good correlation between the metabolic maturation of various neuroanatomical regions and the emergence of behaviors mediated by the specific region. At least in the kitten visual cortex, which has been extensively studied with respect to developmental plasticity, the "critical period" corresponded to that portion of the lCMRglc maturational curve surrounding the 60-day metabolic peak. These normal maturational lCMRglc data will serve as baseline values with which to compare anatomical and metabolic plasticity changes induced by age-related lesions in the cat.

3-Hydroxybutyric Acid↗
PubMed1991

Modelling approach for separating blood time-activity curves in positron emission tomographic studies.

A modelling approach is developed to generate the full time course of an injected radiotracer and its labelled metabolites in plasma/blood, based on measurements of the total radioactivities in withdrawn plasma/blood samples. A compartmental model is used to describe the conversion of an injected tracer to its metabolites in the body. The model equation is formulated with the total radioactivity concentration curve as the input function. The utility and characteristics of the approach in quantitative positron emission tomographic (PET) studies are shown with two examples. In the first example, using the tracer 6-[18F]fluoro-L-dopa (FDOPA), the approach is shown to derive the full time course of plasma FDOPA and its metabolites. In the second example of dynamic 15O oxygen PET, the approach is used to solve a deconvolution problem to give separated time-activity curves of 15O oxygen and 15O water in blood. The modelling approach improves the separation of blood/plasma time-activity curves and leads to better quantitative interpretation of PET results.

Dihydroxyphenylalanine↗
PubMed1991

Functional brain imaging and Alzheimer-type dementia.

Alzheimer disease is a common neurodegenerative disorder consisting of memory impairment and intellectual function that produces not only profound disabilities in the patient, but a significant cost to society as well. The biochemical basis for Alzheimer disease is not completely understood, but both positron-emission tomography and single-photon-emission computed tomography provide insights into the in vivo biochemistry associated with this disease. Both techniques show characteristic brain abnormalities, which consist of reductions in temporal-parietal metabolism that progress in severity and extent as the disease itself shows clinical progression. Such noninvasive biochemical assays may ultimately prove to be of assistance in clinical management, and are clearly helpful in understanding the pathophysiologic mechanisms associated with the production of this disease.

Alzheimer Disease↗