The prognostic significance of indium-111-capromab penetide.
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Antibodies, Monoclonal↗
Biomedical subjects
A D Nelson
Publications and source records attributed to A D Nelson.
The effect of scatter and attenuation on aerosol deposition as determined by gamma scintigraphy.
Gamma scintigraphy is often used to quantify deposition patterns from aerosol inhalers. The errors caused by scatter and tissue attenuation in planar Tc-99m gamma scintigraphy were investigated based on the data collected from four subjects in this study. Several error correction methods were tested. The results from two scatter correction methods, Jaszczak's method and factor analysis of dynamic sequences (FADS), were similar. Scatter accounted for 20% of raw data in the whole lung, 20% in the oropharynx, and 43% in the central airways and esophagus. Three attenuation correction methods were investigated and compared. These were: uniform attenuation correction (UAC), a known method used for inhalation drug imaging work; the broad-beam attenuation correction used for organ imaging in nuclear medicine; and a narrow-beam inhomogeneous tissue attenuation correction proposed in this study. The three methods differed significantly (p < 0.05), but all indicated that attenuation is a severe quantification problem. The narrow beam attenuation correction with scatter correction, showed that raw data underestimated tracer deposition by 44% in the lung, 137% in the oropharynx, and 153% in the trachea/esophageal region. To quantify aerosol lung deposition using planar scintigraphy even in relative terms, corrections are necessary. Much of the literature concerning quantified aerosol dose distributions measured by gamma scintigraphy needs to be interpreted carefully.
Administration, Inhalation↗
Iterative optimal design of PET experiments for estimating beta-adrenergic receptor concentration.
To estimate in vivo myocardial beta-adrenergic receptor concentration with sufficient precision and to reduce the experimental complexities in positron emission tomography (PET), an iterative optimal design method is applied. An initial three-injection protocol, utilising [F-18]-labelled (R)- and (S)-fluorocarazolol and unlabelled (S)-fluorocarazolol, is optimised for ligand dosages and administration times to maximise the precision of all model parameters using the D-optimal criterion. Using this experimental protocol, PET data are collected in porcine studies, and model parameters are estimated. All model parameters are identified with satisfactory precision. The in vivo myocardial beta-receptor concentration is 7.5+/-0.6 pmol x ml(-1), which corresponds to the in vitro result of 10.1+/-1.3 pmol x ml(-1). With more accurate parameter values, a simplified two-injection protocol is optimally designed, utilising only radiolabelled and unlabelled (S)-fluorocarazolol, based on a new criterion to maximise the precision of the beta-receptor concentration. This revised optimum design predicts that the in vivo beta-receptor concentration can be estimated with good precision but reduced experiment complexity.
Adrenergic beta-Antagonists↗
Polyploid evolution and biogeography in Chelone (Scrophulariaceae): morphological and isozyme evidence.
Chelone is a genus of perennial herbs comprising three diploid species (C. cuthbertii, C. glabra, and C. lyonii) and a fourth species (C. obliqua) that occurs as tetraploid and hexaploid races. To assess patterns of isozyme and morphological variation, and to test hypotheses of hybridization and allopolyploidy, we analyzed variation among 16 isozyme loci from 61 populations and 16 morphological characters from 33 populations representing all taxa and ploidy levels. Based on morphological analyses using clustering (unweighted pair group method using an arithmetic average) and ordination (principal components analysis and canonical variance analysis) methods, we recognize three diploid species without infraspecific taxa. Polyploids in the C. obliqua complex were most similar morphologically to diploid populations of C. glabra and C. lyonii. Patterns of isozyme variation among polyploids, which included fixed heterozygosity and recombinant profiles of alleles present in diploids, suggested polytopic origins of tetraploids and hexaploids. Our data indicate independent origins of polyploids in or near the southern Blue Ridge, Interior Highlands and Plains, and Atlantic Coastal Plain regions from progenitors most similar to C. glabra and C. lyonii. Extant tetraploids were not implicated in evolution of hexaploids, and plants similar to C. cuthbertii appeared unlikely as diploid progenitors for polyploids. We propose multiple differentiation and hybridization/polyploidization cycles in different geographic regions to explain the pattern of allopatry and inferred polytopic origins among polyploids.
Journal Article↗
Simultaneous recovery of size and radioactivity concentration of small spheroids with PET data.
UNLABELLED: Quantification of tumor activity is used to predict prognosis and discriminate benign from malignant lesions identified by PET. Accurate quantitation of small lesions requires correction for the partial volume effects. Such a correction is often based on the recovery coefficient (RC), which depends on the lesion size, the object-to-background ratio (OBR) and physical properties of the media. The purpose of this investigation was to determine whether a model-based optimization method to simultaneously recover the size and the activity concentration of small spheroids could improve estimates of lesion radioactivity when object size is unknown. For reference, we compared our method with a widely used approach, RC correction, that requires the object size to be known. METHODS: A three-dimensional, spatially varying, object size- and contrast-dependent Gaussian model of the point spread function (PSF) of an ECAT EXACT was developed. The observed dependence of the PSF on random coincidences and measured-peak/background activity were included in the PSF using three adjusting factors. Size and radioactivity concentration of a spheroid were estimated by adjusting size and concentration until model output best matched the image data. Elliptic and circular phantoms both containing seven hot spheroids, with OBRs ranging from 5.6 to 0 background, were evaluated. RESULTS: The proposed quantification method reduced the activity error by 11%-63% of the error obtained without correction. The greatest error reduction occurred for small spheroids. The average error in radius estimation ranged from 2% to 48%, wherein the smallest spheroid produced the largest errors. For spheroids with diameters from 8 to 22 mm, Student t test (paired, one-tail) showed the proposed method significantly improved accuracy (P < 0.05) in comparison with the RC method and also in comparison with optimization without the three adjusting factors. CONCLUSION: The model-based optimization method improved estimation of radioactivity concentration over that corrected by the RC method and that made without any correction. It also provided accurate estimation of size for spheroids larger than 6 mm in diameter.
Models, Theoretical↗
A method to correct for scatter, spillover, and partial volume effects in region of interest analysis in PET.
Scatter and spatial resolution effects degrade the accuracy of radioactivity concentration estimates obtained from positron emission tomography (PET) data. We present and evaluate a methodology for region quantification which accounts for these degradations. The method is based on analysis of sinogram data and does not require dynamic data sequences to be reconstructed. Moreover, estimates of region variance are also produced which may be used to define weights for model analyses that use weighted least squares minimization in order to obtain unbiased parameter estimates. We evaluate the method using both simulation and measured data and find that, with an appropriate model of scatter and spatial resolution effects, it is unbiased and capable of quantifying myocardial concentration with no more than a 5% error in accuracy for myocardium as thin as 10 mm.
Adrenergic beta-Antagonists↗
A nonlinear spatially variant object-dependent system model for prediction of partial volume effects and scatter in PET.
Accurate quantitation of small lesions with positron emission tomography (PET) requires correction for the partial volume effect. Traditional methods that use Gaussian models of the PET system were found to be insufficient. A new approach that models the non-Gaussian object-dependent scatter was developed. The model consists of eight simple functions with a total of 24 parameters. Images of line and disk sources in circular and elliptical cylinders, and an anthropomorphic chest phantom were used to determine the parameter values. Empirical rules to determine these parameter values for various objects based on those for a reference object, a 21.5-cm circular cylinder, were also proposed. For seven spheroids and a 3.4-cm cylinder, pixel values predicted by the model were compared with the measured values. The model-to-measurement-ratio was 1.03+/-0.07 near the center of the spheroids and 0.99+/-0.03 near the center of the 3.4-cm cylinder. In comparison, the standard single Gaussian model had corresponding ratios of 1.27+/-0.09 and 1.24+/-0.03, respectively, and the corresponding ratios for a double Gaussian model were 1.13+/-0.09 and 1.05+/-0.01. Scatter fraction (28.5%) for a line source in the 21.5-cm cylinder was correctly estimated by our model. Because of scatter, we found that errors in the measurement of activity in spheroids with diameters from 0.6 to 3.4 cm were more significant than previously appreciated.
Algorithms↗
Global cerebral blood flow, blood volume, and oxygen metabolism in patients with migraine headache.
OBJECTIVE: Migraine headaches with and without aura are representative of vascular headache states traditionally thought to be mediated by alterations in vascular tone. Validation of this theory has been hampered in part by technical difficulties inherent in the measurement of cerebral blood flow (CBF). The purpose of this study was to compare CBF measured during migraine and migraine-free states using PET. METHODS: Patients with a minimum of one migraine headache without aura per month (International Headache Society [IHS] criteria) underwent measurement of CBF, cerebral blood volume (CBV), oxygen extraction, and metabolism during an episode of spontaneous migraine headache. Imaging was repeated during a migraine-free period of at least 48 hours. PET radiotracers used were: CBF, H(2)15O; CBV, C15O; oxygen metabolism, 15O2. RESULTS: In nine patients (seven female and two male), global CBF (mL/min/100 g [SD]) was measured as 52.70 (6.9) during migraine and 59.65 (10.6) in the migraine-free state; p=0.028. CBV (mL/100 g [SD]) was 3.6 (0.43) during the symptomatic state and 3.8 (0.55) after the migraine; p=0.047. Oxygen metabolism (mL/min/100 g [SD]) was 3.68 (0.9) during migraine and 3.38 (1.02) without headache; p=0.211. The oxygen extraction ratio was 0.48 (0.15) and 0.41 (0.12) during migraine and migraine-free states, respectively; p=0.132. CONCLUSIONS: In patients experiencing migraine without aura, CBF and CBV are reduced during the headache phase. Cerebral oxygen metabolism and oxygen extraction are not significantly affected.
Adolescent↗
PET quantification of specific binding of carbon-11-nicotine in human brain.
UNLABELLED: Previous work on the PET measured uptake of (S)-[11C]nicotine presents conflicting findings as to whether it reflects specific binding. METHODS: We studied the uptake of (R)-[11C]nicotine and (S)-[11C]nicotine in normal volunteers at baseline conditions and after a challenge with unlabeled (S)-nicotine to decrease the concentration of free binding sites or with CO2 to increase perfusion. We analyzed the data using two- and three-compartment models. RESULTS: We found tissue pharmacokinetics of (R)- and (S)-[11C]nicotine are adequately described by the two-compartment model. (S)-nicotine challenge induced small but statistically significant reductions in distribution volume (DV) of both (R)- and (S)-[11C]nicotine. The changes in DV could not be attributed to perfusion changes because DV was not affected by CO2 challenge. Although the reduction in DV indicates sensitivity of [11C]nicotine to status of nicotinic binding sites, the small magnitude of the reduction suggests that most nicotine uptake is nonspecific. CONCLUSION: Although differences in DV attributable to specific binding were detected, (R)- and (S)-[11C]nicotine are relatively poor tracers for studying nicotinic binding sites using PET.
Blood-Brain Barrier↗
A robust edge detection method for gated radionuclide ventriculograms.
UNLABELLED: We present a myocardial edge detection technique that was developed for fast, reproducible measurements of left ventricular ejection fraction in the clinical setting. METHODS: This myocardial edge detection method compares three edge parameters--count amplitude and first and second count derivatives--in three consecutive locations along a radius to a predetermined template of these values. Each of the radii, defined at 10-degree intervals, has different template values that permit accurate edge detection even though adjacent structures, such as the left atrium and the right ventricle, alter edge parameters. The template for edge detection is based on either the average edge parameters determined from manually defined edges in 15 patients (automatic method) or an operator-defined edge in the first frame (semiautomatic method). RESULTS: The edge detection methods were tested in 100 patients, and intraobserver variabilities as well as comparison with clinically obtained ejection fractions were calculated. The standard error of the estimate was less than 3.1% for all observer comparisons. In 15 patients with both high-count (400,000 counts per image) and low count (50,000 counts per image) studies, the mean absolute difference in ejection fraction was 2.6% for intraobserver comparisons. CONCLUSION: A robust myocardial edge detection technique was developed that is applicable for routine clinical use.
Erythrocytes↗
Specific beta-adrenergic receptor binding of carazolol measured with PET.
UNLABELLED: Carazolol is a promising high-affinity beta-adrenergic receptor ligand for the noninvasive determination of beta receptor status using PET. Earlier investigations demonstrated specific receptor binding of carazolol in mice. These PET studies with S(-)-[2"-11C]carazolol in pigs were performed to explore the utility of the tracer for PET receptor studies. METHODS: Tracer uptake in the heart and lung was measured by PET as a function of time. Receptors were blocked with propranolol and different doses of ICI 118,551 to estimate specific binding. Fluorine-18-1"-Fluorocarazolol and the less active R-enantiomer of [11C]-carazolol were also studied. RESULTS: Specific receptor binding was 75% of the total uptake in the heart, preventable and displaceable by propranolol. Dose-dependent competition showed that carazolol binds in vivo to beta 1 and to beta 2 subtypes. Uptake of the labeled R(+) enantiomer of carazolol was not receptor-specific. CONCLUSIONS: Carazolol labeled with 11C or 18F is a strong candidate for use in receptor estimation with PET. The in vivo observations were consistent with its known high affinity and slow receptor dissociation rate. Its high specific receptor uptake and low metabolism allow existing kinetic models to be applied for receptor measurements. The 11C label is convenient for repeated administrations, though 18F allowed the long observation periods necessary for measurement of the receptor dissociation rate. If needed, nonspecific uptake can be estimated without pharmacologic intervention by using the labeled R enantiomer.
Adrenergic beta-Antagonists↗
Noninvasive arterial monitor for quantitative oxygen-15-water blood flow studies.
A noninvasive monitor has been developed for monitoring arterial radioactivity in quantitative PET studies of blood flow. The significance of this probe is that quantitative blood flow studies can be performed without the use of arterial catheterization. The method employed is based on the flux of photons emanating from the superior lobe of the right lung following an intravenous bolus of H2(15)O. Calibration of the monitor is obtained by measuring the relationship between lung monitor counts and arterial radioactivity after arterial and venous radioactivity levels have equilibrated following inhalation of C15O. To determine the accuracy of the lung probe as a measure of arterial radioactivity, 44 brain blood flow determinations were made in 11 volunteers using arterial radioactivity measures based both on the lung probe and continuous sampling from a radial artery. Repeated measures analysis of variance found no differences between invasive and noninvasive estimates of blood flow. These results suggest that the lung monitor enables quantitation of cerebral blood flow yet avoids the trauma of an arterial puncture.
Adult↗
Tn4556 and luciferase: synergistic tools for visualizing transcription in Streptomyces.
Progress in understanding genetic regulatory controls in the Actinomycetes has been rate limited by the properties of in vivo transcriptional probes. We have developed a set of plasmid- and transposon-based promoter-probe vectors that employ the Vibrio harveyi luciferase-encoding luxAB cassette as a reporter of transcription. The primary advantages of luciferase (Lux) over other reporter gene products are: (i) unsurpassed sensitivity; (ii) utility during stationary-phase gene expression; and (iii) the ability to localize promoter activity spatially within developing colonies. We have used these vectors to screen for Streptomyces coelicolor promoters that exhibit developmental phenotypes or that are induced by various environmental stimuli. The plasmid-based probes have proved invaluable for identifying cis- and trans-acting elements that are required for stationary-phase expression of the S. coelicolor sapA gene. A collection of novel bld and whi insertion mutants has been obtained by use of the Lux-encoding transposon, Tn5353.
DNA Transposable Elements↗
Comparative assessment of the effect of lomefloxacin, ciprofloxacin, and placebo on cerebral blood flow, and glucose and oxygen metabolism in healthy subjects by positron emission tomography.
The mechanism by which the fluorinated quinolones produce central nervous system (CNS) effects is currently unknown. We measured the effect of lomefloxacin on cerebral blood flow and metabolism using positron emission tomography. Eighteen healthy, nonsmoking volunteers were randomized to receive lomefloxacin 400 mg, ciprofloxacin 750 mg, or placebo given in a single-blind fashion every 12 hours for 72 hours, the time window for maximum lomefloxacin CNS effects. Subjects receiving lomefloxacin had a mean (+/- SEM) cerebral blood flow (CBF) of 46 (2.9) ml/min/100 g, glucose metabolism (FDG) 4.7 (0.4) mg/min/100 g, oxygen metabolism (OM) 3.3 (0.3) ml/min/100 g, and oxygen extraction (%OM) 0.4 (0.04). Posttreatment values were 43 (3.6) ml/min/100 g, 4.2 (0.4) mg/min/100 g, 2.6 (0.3) ml/min/100 g, and 0.4 (0.03), respectively. Values for subjects receiving ciprofloxacin were CBF 44.8 (1.6) ml/min/100 g, FDG 4.9 (0.7) mg/min/100 g, OM 4.1 (0.4) ml/min/100 g, and %OM 0.6 (0.03) at baseline, and 40.3 (3.5), 4.5 (0.6), 3.4 (0.4), and 0.5 (0.09), respectively, after treatment. For placebo-treated subjects, baseline values were CBF 41.4 (1.9) ml/min/100 g, FDG 4.9 (0.5) mg/min/100 g, OM 3.3 (0.4) ml/min/100 g, and %OM 0.5 (0.07), and respective posttreatment values were 42.1 (2.3), 5.0 (0.6), 3.5 (0.3), and 0.5 (0.02). No effect was observed on visual (qualitative), blinded reading of the scans. No significant effect on cerebral blood flow or metabolism was detected. We conclude that short-term administration of lomefloxacin or ciprofloxacin to healthy volunteers does not have a significant effect on cerebral blood flow, or on oxygen or glucose metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
A dual-radioisotope technique for the evaluation of penile blood flow during tumescence.
A technique is described for concomitant study of both arterial and venous penile blood flow during tumescence. Dual-isotope acquisition is started after labeling red cells in vivo with 99mTc. Xenon-133 in saline is then injected into the corpus cavernosum followed with vasoactive drugs to induce an erection. The resulting xenon and technetium time-activity curves are inputs for a one-compartment model. In 14 subjects, the average peak arterial flow rate (PAF) for normal males was calculated as 13.0 +/- 1.28 ml/min (avg +/- s.d.) compared to 16.1 +/- 5.14 and 5.02 +/- 1.78 ml/min for patients with venous leak (VL) or arterial insufficiency (AI), respectively. Peak venous flows (PVF) were 4.25 +/- 1.17, 12.1 +/- 3.75, and 3.78 +/- 1.00 ml/min for normal, VL and AL respectively. Al patients have significantly lower PAF than normal (p = 0.002) or VL patients (p = 0.018), and VL patients had significantly higher PVF than normal (p = 0.012) or Al (p = 0.018). The technique may be helpful in the study of impotence.
Adult↗
An assessment of cerebral blood flow and metabolism after fleroxacin therapy.
Cerebral blood flow (CBF), glucose (FDG), and oxygen metabolism (OM) were evaluated by positron emission tomography (PET) in 18 healthy volunteers who were randomized to a 72-hour course of either 600 mg/d of fleroxacin or placebo. Such studies attempted to assess potentially serious, yet unexplained, central nervous system adverse effects of the fluorinated quinolone class. Baseline and postplacebo values for CBF (mL/min/100 g) and FDG (mg/min/100 g) were: 53 +/- 6 and 5.7 +/- 1.8; and 49.6 +/- 4.4, and 5.2 +/- 1.2, respectively. Identical values for fleroxacin were: 53.9 +/- 4.8 and 6.3 +/- 1.1; and 54.4 +/- 2.2 and 6.8 +/- 1.5, respectively. The differences between fleroxacin and placebo were not significant. There was also no effect seen in OM between placebo and the active drug. The authors conclude that short-term administration of fleroxacin does not alter CBF, FDG, or OM in healthy volunteers.
Adult↗
Comparison of the effect of temafloxacin, ciprofloxacin, or placebo on cerebral blood flow, glucose, and oxygen metabolism in healthy subjects by means of positron emission tomography.
STUDY OBJECTIVE: To determine the cause of the central nervous system effect of the fluorinated quinolones temafloxacin and ciprofloxacin by measuring cerebral blood flow and metabolism by use of positron emission tomography. DESIGN: This was a prospective, randomized, double-blind, placebo-controlled study. PATIENTS: The patients were 13 healthy, nonsmoking volunteers whose ages ranged from 18 to 40 years. RESULTS: We measured brain blood flow and metabolism by use of positron emission tomography before and after a five-dose course of 750 mg ciprofloxacin, 600 mg temafloxacin, or placebo given every 12 hours. Quinolone administration produced no significant effect on visual (qualitative) reading of the positron emission tomography scans. CONCLUSIONS: We conclude that short-term administration of temafloxacin, ciprofloxacin, or placebo does not significantly alter cerebral glucose or oxygen metabolism. Subjects treated with ciprofloxacin demonstrated a significant decrease in brain blood flow compared with baseline and with temafloxacin- or placebo-treated subjects.
Adolescent↗
Measurement of human cerebral blood flow with [15O]butanol and positron emission tomography.
Although H2(15)O is widely used for CBF measurement by positron tomography, it underestimates CBF, especially at elevated flow rates. Several tracers, including butanol, overcome this problem, but the short half-life of 15O provides advantages that cause water to remain the tracer of choice. We report the first use and evaluation of 15O-labeled butanol for CBF measurement. Flow measurements made in a similar fashion with water and butanol at 10-min intervals were compared in normal volunteers under resting and hypercapnic conditions. Regional analysis showed good agreement between the tracers at low flows, and significant underestimation of flow by water relative to butanol in regions of elevated flow. The observed relationship between the tracers and the curve-fitted permeability-surface area product for water (133 ml.100 g-1.min-1) follow the known relationship between water and true flow. These observations indicate that [15O]-butanol provided accurate measurements of human regional CBF under conditions of elevated perfusion. We conclude that butanol is a convenient and accurate method for routine CBF determination by positron emission tomography.
Adult↗