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Biomedical subjects

K H Douglass

Publications and source records attributed to K H Douglass.

At least 19 recordsLinked to original sources
PubMed1991

Quantification of human opiate receptor concentration and affinity using high and low specific activity [11C]diprenorphine and positron emission tomography.

[11C]Diprenorphine, a weak partial opiate agonist, and positron emission tomography were used to obtain noninvasive regional estimates of opiate receptor concentration (Bmax) and affinity (Kd) in human brain. Different compartmental models and fitting strategies were compared statistically to establish the most reliable method of parameter estimation. Paired studies were performed in six normal subjects using high (769-5,920 Ci/mmol) and low (27-80 Ci/mmol) specific activity (SA) [11C]diprenorphine. Two subjects were studied a third time using high SA [11C]diprenorphine after a pretreatment with 1-1.5 mg/kg of the opiate antagonist naloxone. After the plasma radioactivity was corrected for metabolites, the brain data were analyzed using a three-compartment model and nonlinear least-squares curve fitting. Linear differential equations were used to describe the high SA (low receptor occupancy) kinetics. The k3/k4 ratio varied from 1.0 +/- 0.2 (occipital cortex) to 8.6 +/- 1.6 (thalamus). Nonlinear differential equations were used to describe the low SA (high receptor occupancy) kinetics and the curve fits provided the konf2 product. The measured free fraction of [11C]diprenorphine in plasma (f1) was 0.30 +/- 0.03, the average K1/k2 ratio from the two naloxone studies was 1.1 +/- 0.2, and the calculated free fraction of [11C]diprenorphine in the brain (f2) was 0.3. Using the paired SA studies, the estimated kinetic parameters, and f2, separate estimates of Bmax and Kd were obtained. Bmax varied from 2.3 +/- 0.5 (occipital cortex) to 20.6 +/- 7.3 (cingulate cortex) nM. The average Kd (eight brain regions) was 0.85 +/- 0.17 nM.

Adult↗
PubMed1989

Multicompartmental analysis of [11C]-carfentanil binding to opiate receptors in humans measured by positron emission tomography.

[11C]-Carfentanil is a high affinity opiate agonist that can be used to localize mu opiate receptors in humans by positron emission tomography (PET). A four-compartment model was used to obtain quantitative estimates of rate constants for receptor association and dissociation. PET studies were performed in five normal subjects in the absence and presence of 1 mg/kg naloxone. Arterial plasma concentration of [11C]-carfentanil and its labeled metabolites were determined during each PET study. The value of k3/k4 = Bmax/kD was determined for each subject in the presence and absence of naloxone. There was a significant reduction in the value of k3/k4 from 3.4 +/- 0.92 to 0.26 +/- 0.13 in the thalamus (p less than 0.01) and from 1.8 +/- 0.33 to 0.16 +/- 0.065 in the frontal cortex (p less than 0.001). Mean values of frontal cortex/occipital cortex and thalamus/occipital cortex ratios were determined for the interval 35-70 min after injection when receptor binding is high relative to nonspecific binding. The relationship between the measured region/occipital cortex values and the corresponding values of k3/k4 in the presence and absence of naloxone was: regions/occipital cortex = 0.95 + 0.74 (k3/k4) with r = 0.98 (n = 20). Simulation studies also demonstrated a linear relationship between the thalamus/occipital cortex or frontal cortex/occipital cortex ratio and k3/k4 for less than twofold increases or decreases in k3/k4. Simulation studies in which thalamic blood flow was varied demonstrated no significant effect on the region/occipital cortex ratio at 35-70 min for a twofold increase or fourfold decrease in blood flow. Therefore, the region/occipital cortex ratio can be used to quantitate changes in k3/k4 when tracer kinetic modeling is not feasible.

Adult↗
PubMed1988

Mu-opiate receptors measured by positron emission tomography are increased in temporal lobe epilepsy.

Neurochemical studies in animal models of epilepsy have demonstrated the importance of multiple neurotransmitters and their receptors in mediating seizures. The role of opiate receptors and endogenous opioid peptides in seizure mechanisms is well developed and is the basis for measuring opiate receptors in patients with epilepsy. Patients with complex partial seizures due to unilateral temporal seizure foci were studied by positron emission tomography using 11C-carfentanil to measure mu-opiate receptors and 18F-fluoro-deoxy-D-glucose to measure glucose utilization. Opiate receptor binding is greater in the temporal neocortex on the side of the electrical focus than on the opposite side. Modeling studies indicate that the increase in binding is due to an increase in affinity or the number of unoccupied receptors. No significant asymmetry of 11C-carfentanil binding was detected in the amygdala or hippocampus. Glucose utilization correlated inversely with 11C-carfentanil binding in the temporal neocortex. Increased opiate receptors in the temporal neocortex may represent a tonic anticonvulsant system that limits the spread of electrical activity from other temporal lobe structures.

Adolescent↗
PubMed1988

Assessment of [11C]-L-methionine transport into the human brain.

Neutral amino acid transport into human brain was measured using a dual-probe positron detection system or positron emission tomography (PET). Rate constants (ml/min/cc) for brain accumulation of [11C]L-methionine measured with the dual detector ranged from 0.012 to 0.078 (average 0.031) under baseline conditions and from 0.010 to 0.017 (average 0.014) after administration of nonradioactive L-phenylalanine (100 mg/kg). The net rate of brain accumulation of L-methionine ranged from 0.42 to 2.89 (average 1.28) nmol/min/cc, and decreased by 27.5-91.2% (average 53.9%) after L-phenylalanine. PET-estimated accumulation rates (ml/min/cc) of [11C]L-methionine ranged from 0.004 to 0.028 (average 0.016) baseline and from 0.010 to 0.021 (average 0.017) after L-phenylalanine. Initial volumes of distribution (ml/cc) of [11C]L-methionine (dual detector) were 0.044-0.070 (average 0.058) baseline and 0.032-0.074 (average 0.051) after phenylalanine and (PET) 0.026-0.098 (average 0.051) baseline and 0.021-0.061 (average 0.042) after phenylalanine. PET permits more accurate measurement of tracer accumulation by brain, excluding noncerebral regions included in dual-detector measurements. The dual-detector system permits better temporal resolution, facilitating kinetic analysis, and requires only one-fortieth the dose of tracer needed for PET. Multiple studies in the same patient are thus possible at low cost.

Biological Transport↗
PubMed1988

Scatter correction in SPECT using non-uniform attenuation data.

Quantitative assessment of activity levels with SPECT is difficult because of attenuation and scattering of gamma rays within the object. To study the effect of attenuation and scatter on SPECT quantitation, phantom studies were performed with non-uniform attenuation. Simulated transmission CT data provided information about the distribution of attenuation coefficients within the source. Attenuation correction was performed by an iterative reprojection technique. Scatter correction was done by convolution of the attenuation-corrected image and an appropriate filter. The filter characteristics depended on the attenuation and activity measurement at each pixel. The scatter correction could compensate completely for the 28% scatter component from a line source, and the 61% component from a thick, extended source. Accuracy of regional activity ratios and the linearity of the relationship between true radioactivity and the SPECT measurement were both significantly improved by these corrections. The present method is expected to be valuable for the quantitative assessment of regional activity.

Models, Structural↗
PubMed1987

Linear discriminant analysis of regional ejection fractions in the diagnosis of coronary artery disease.

We studied the application of linear discriminant analysis to the computer assisted interpretation of rest and exercise gated blood pool studies. Data were obtained in 45 patients in whom the presence or absence of coronary artery disease was determined by coronary angiography. Automated analysis of regional ejection fractions using a linear discriminant function (LDF) was compared to the fully automated calculation of global ejection fraction and to the subjective evaluation of wall motion. A LDF constructed from the data for the first 31 consecutive patients correctly classified 25/31 (81%). The change in global ejection fraction correctly classified 24/31 (77%) and wall motion analysis 25/31 (81%). In a distinct group of 14 patients the same LDF correctly classified 12/14 (86%), global ejection fraction 9/14 (64%) and wall motion analysis 10/14 (71%).

Coronary Disease↗
PubMed1986

Quantification of Neuroreceptors in the living human brain. II. Inhibition studies of receptor density and affinity.

A method for estimating receptor density (Bmax) in the living human brain by positron emission tomography was exemplified by a ligand, 3-N-[11C]methylspiperone ([11C]NMSP), that binds to D2 dopamine receptors with high affinity. The ligand binds essentially irreversibly (i.e., with very little dissociation) to the receptors during the 2-h scanning period. Transfer constants were estimated at steady state. In a previous article, we presented a method for the determination of k3, the rate of binding of the labeled ligand. In the present work, we varied k3 by reducing the number of available receptors with a previously administered receptor blocking agent, haloperidol. We calculated a receptor density of 9.2 pmol g-1 in the caudate nucleus of four normal volunteers, and an inhibitory constant of haloperidol of 1.4 nM by comparing tracer accumulation in the absence and the presence of the blocking agent. The values agreed with measurements of NMSP receptor density and haloperidol inhibitory potency in vitro in brain homogenates from human autopsy material.

Adolescent↗
PubMed1984

Effects of age on dopamine and serotonin receptors measured by positron tomography in the living human brain.

D2 dopamine and S2 serotonin receptors were imaged and measured in healthy human subjects by positron emission tomography after intravenous injection of 11C-labeled 3-N-methylspiperone. Levels of receptor in the caudate nucleus, putamen, and frontal cerebral cortex declined over the age span studied (19 to 73 years). The decline in D2 receptor in males was different from that in females.

Aging↗
PubMed1983

Abnormalities of the spleen and liver in patients with hemophilia.

Previous studies have demonstrated functional and histologic abnormalities of the liver, and, more recently, splenomegaly in patients with hemophilia. Since these observations usually were derived from hemophiliacs who had received intensive replacement therapy, the question was posed as to whether the frequency of splenic and hepatic abnormalities was secondary to the amount of therapy utilized. In this study, a variety of tests were employed to evaluate spleen and liver size and function to determine if abnormalities in these organs correlated with the intensity of the transfusion program. The study group was comprised of 25 hemophiliacs (mean factor replacement-18,361 U/year; median factor replacement-12,920 U/year). Over 70% of our patients had elevations of aspartate and alanine aminotransferase. Immunoglobulin and complement levels were normal in most subjects. Ninety-six percent had evidence of exposure to hepatitis B virus. Liver-spleen imaging suggested significant hepatic abnormalities in most of the patients as evidenced by inhomogeneity of tracer uptake in the liver in 33% and relatively increased colloid uptake in the spleen in 90%. Splenomegaly (palpable spleen or enlargement on liver-spleen imaging) was detected in 40% of our patients, and tended to occur in the more frequently transfused patients. These findings indicate that significant abnormalities of the spleen and liver can occur in hemophiliacs who have received moderate amounts of replacement therapy and that liver-spleen imaging may be a useful method for monitoring the development of hepatic and splenic abnormalities.

Adolescent↗
PubMed1982

Performance of a fully automated program for measurement of left ventricular ejection fraction.

A fully automated program developed by us for measurement of left ventricular ejection fraction from equilibrium gated blood pool studies was evaluated in 130 additional patients. Both 6-min (130 studies) and 2-min (142 studies in 31 patients) gated blood pool studies were acquired and processed. The program successfully generated ejection fractions in 86% of the studies. These automatically generated ejection fractions were compared with ejection fractions derived from manually drawn regions of interest. When studies were acquired for 6-min with the patient at rest, the correlation between automated and manual ejection fractions was 0.92. When studies were acquired for 2-min, both at rest and during bicycle exercise, the correlation was 0.81. In 25 studies from patients who also underwent contrast ventriculography, the program successfully generated regions of interest in 22 (88%). The correlation between the ejection fraction determined by contrast ventriculography and the automatically generated radionuclide ejection fraction was 0.79.

Cardiac Output↗
PubMed1981

Quantification of left to right cardiac shunts by multiple deconvolution analysis.

A new method for quantification of left to right cardiac shunts was studied in 17 patients scheduled for cardiac catheterization who had also undergone radionuclide angiocardiography. The observed pulmonary transit curve was deconvoluted in two different ways: (1) by the superior vena caval ("bolus") time-activity curve, to yield the deconvoluted pulmonary transit curve, which represented the theoretical pulmonary transit curve with a perfect bolus injection, and (2) by the right ventricular time-activity curve, to yield the pulmonary transfer function, which represented the theoretical pulmonary transit curve with a perfect bolus injection an with no intracardiac shunts. The pulmonary transfer function was superimposed on the deconvoluted pulmonary transit curve, and the area A under it obtained. The pulmonary transfer function was then subtracted from the deconvoluted pulmonary transit curve. The pulmonary transfer function was scaled to fit the resulting shunt recirculation peak in the difference curve, and the area B under this scaled pulmonary transfer function obtained. Shunt size was quantified as the pulmonary (QP) to systemic (QS) flow ration QP/QS = A/(A-B). The method correlated closely with oximetry (r = 0.93). Use of this multiple deconvolution analysis technique provides accurate shunt quantification and reduces subjective operator decisions.

Adolescent↗
PubMed1980

Patterns of ventricular emptying by Fourier analysis of gated blood-pool studies.

Temporal Fourier analysis was applied to the processing of ECG-gated cardiac blood-pool studies on a pixel-by-pixel basis, to yield information about the pattern of ventricular emptying in normal hearts and in others with conduction abnormalities. The transform data at the fundamental frequency (the heart rate) were used to construct two types of display: (a) a distribution histogram of the pixel phase values, and (b) a cinematic display of the wave of emptying as it spread over the cardiac chambers. Preliminary results indicate that temporal Fourier analysis permits visualization of the pattern of ventricular emptying, which may prove useful in the study of motion abnormalities and asynergies, including those resulting from myocardial hypertrophy or conduction abnormalities, and as an aid in the optimum placement of pacemakers.

Arrhythmias, Cardiac↗
PubMed1979

Monitoring ventricular function at rest and during exercise with a nonimaging nuclear detector.

A portable nonimaging device, the nuclear stethoscope, for measuring beat to beat ventricular time-activity curves in normal people and patients with heart disease, both at rest and during exercise, is being developed and evaluated. The latest device has several operating modes that facilitate left ventricular and background localization, measurement of transit times and automatic calculation and display of left ventricular ejection fraction. The correlation coefficient of left ventricular ejection fraction obtained with the device and with a camera-computer system was 0.92 in 35 subjects. During bicycle exercise the ejection fraction in 15 normal persons increased from 44 to 64 percent (P less than 0.001), whereas among 12 patients with heart disease it was unchanged in 5 and decreased in 7.

Adult↗
PubMed1979

Deconvolution analysis in radionuclide quantitation of left-to-right cardiac shunts.

A poor bolus injection results in an unsatisfactory quantitative radionuclide angiocardiogram in as many as 20% of children with possible, left-to-right (L-R) cardiac shunts. Deconvolution analysis was applied to similar studies in experimental animals to determine whether dependence on the input bolus could be minimized. Repeated good-bolus, prolonged (greater than 2.5 sec), or multiple-peak injections were made in four normal dogs and seven dogs with surgically created atrial septal defects (ASD). QP/QS was determined using the gamma function. The mean QP/QS from ten good-bolus studies in each animal was used as the standard for comparison. In five trials in normal animals, where a prolonged or double-peak bolus led to a shunt calculation (QP/QS greater than 1.2 : 1), deconvolution resulted in QP/QS = 1.0. Deconvolution improved shunt quantitation in eight of ten trials in animals that received a prolonged bolus. The correlation between the reference QP/QS and the QP/QS calculated from uncorrected bad bolus studies was only 0.39 (p greater than 0.20). After deconvolution using a low pass filter, the correlation improved significantly (r = 0.77, p less than 0.01). The technique gave inconsistent results with multiple-peak bolus injections. Deconvolution analysis in these studies is useful in preventing normals from being classified as shunts, and in improving shunt quantitation after a prolonged bolus. Clinical testing of this technique in children with suspected L-R shunts seems warranted.

Angiocardiography↗