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H N Wagner

Publications and source records attributed to H N Wagner.

At least 145 records · Page 8Linked to original sources
PubMed1988

Automatic drawing of the left epicardial region of interest on thallium 201 scintigraphic images.

An algorithm has been written which automatically selects a left epicardial region of interest on 201Tl myocardial images. It accomplishes a radial search from the geometric center of the myocardium. On each of the 30 profiles, the local maximum of the 1st derivative is selected as the epicardial edge. The algorithm has been tested in 40 patients at stress and redistribution. In ten patients, conventional planar images were obtained in three views. In 30 patients conventional short axis tomographic images were obtained after reconstruction of 32 projections acquired over 180 degrees. The rate of success is 97% for both imaging modalities. This procedure is another step towards fully automated assessment of myocardial defects and redistribution.

Algorithms↗
PubMed1988

The putative endogenous convulsant 3-hydroxykynurenine decreases benzodiazepine receptor binding affinity: implications to seizures associated with neonatal vitamin B-6 deficiency.

The kynurenines, endogenous tryptophan metabolites with convulsant properties, have been postulated to play a role in the genesis of seizure disorders. We have previously reported that concentrations of 3-hydroxykynurenine (3-HK) higher than 0.2 mM are present in the brains of neonatal rats perinatally deprived of vitamin B-6. At a 1 mM concentration 3-HK significantly decreased the affinity of 3H-flunitrazepam for benzodiazepine receptor sites in rat brain membrane preparations. Furthermore, lower concentrations (Ki = 250 microM) of 3-HK antagonized the enhancing effect of GABA on 3H-flunitrazepam binding. These results suggest that 3-HK may have a modulatory effect on the GABA/benzodiazepine/barbiturate receptor complex.

Animals↗
PubMed1988

Synthesis of radiotracers for studying muscarinic cholinergic receptors in the living human brain using positron emission tomography: [11C]dexetimide and [11C]levetimide.

Dexetimide (Fig. 1a), a potent muscarinic cholinergic receptor antagonist, and levetimide (Fig. 1b), its pharmacologically inactive enantiomer, were labeled with 11C for non-invasive in vivo studies of muscarinic cholinergic receptors in the human brain using positron emission tomography. The syntheses were completed in approximately 32 min using [alpha-11C]benzyl iodide as the precursor. The synthesis, purification, characterization and determination of specific activity are presented and discussed.

Brain↗
PubMed1988

(N-methyl-[11C])pyrilamine, a radiotracer for histamine H-1 receptors: radiochemical synthesis and biodistribution study in mice.

The histamine H-1 receptor antagonist, pyrilamine (N-((4-methoxyphenyl)methyl)-N',N'-dimethyl-N-2-pyridinyl-1,2-ethaned i ami ne) was labeled with carbon-11 by N-alkylation of desmethylpyrilamine with [11C]iodomethane, and purified by preparative high performance liquid chromatography. The chemically and radiochemically pure labeled pyrilamine was obtained with specific activity of approximately 2500 mCi/mumol (EOS). In vivo distribution studies in mice suggest that the distribution of this compound parallels the known histamine H-1 receptor density in the brain.

Aminopyridines↗
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↗
PubMed1988

Non-invasive measurement of pulmonary arterial pressure: I. A haemodynamic modelling approach.

In order to monitor pulmonary arterial pressure (P) by any non-invasive imaging technique, a haemodynamic model of blood flow kinetics and wall mechanics has been developed. It is a one-dimensional model of pulsatile flow in an elastic pulmonary arterial trunk, assuming that blood is an incompressible fluid and viscous effects are negligible. The equations are P(t)-Pd = rho c2lnS(t)/Sd-1/2pw-2(t) Pd = (Sd/Ss)1/2Pp where, at any time of the ejection phase of systole, P(t), S(t) and w(t) are the pulmonary arterial pressure, cross-sectional area of the pulmonary artery and blood velocity averaged on the cross section S, respectively, PP is the pulse pressure, the difference between the peak systolic pressure and the diastolic pressure Pd; rho is blood density, c pulse wave velocity, and Ss and Sd are maximum (systolic) and minimum (diastolic) values of the cross-sectional area S. Using these equations, P(t) can be calculated if the three parameters, i.e. c, S(t) and w(t) are measured. So far, it has been impossible to measure the pulse wave velocity c non-invasively. We have investigated the calculation of c from S(t) and w(t) using the equation of continuity in the absence and presence of reflected pressure waves. The hypotheses of the haemodynamic model are discussed.

Blood Flow Velocity↗
PubMed1988

Non-invasive measurement of pulmonary arterial pressure: II. A radionuclide method.

Pulmonary artery pulse pressure (PP) and diastolic pressure (Pd) may be obtained by applying a haemodynamic model of blood flow kinetics and wall mechanics to the pulmonary artery: Pp = rho(ws/(Ss/Sd-1))2log(Ss/Sd)-1/2 rho w2s Pd = (Sd/Ss)1/2Pp where rho is blood density, ws is peak ejection velocity, and Ss and Sd are peak maximal and end diastolic cross-sectional areas of the main pulmonary artery. The different parameters of the equations were measured from radionuclide first pass and equilibrium studies. Radionuclide first pass studies were performed in 24 patients with intravenous injection of 20 mCi of 99Tcm red blood cells with a gamma camera in a 20 degrees right anterior oblique position: data were collected in list mode, i.e. a continuous sequence of spatial and temporal coordinates of each photon. Pulmonary arterial pressure was recorded simultaneously with a microtip catheter during the first pass study. Gated first pass images of the right side of the heart were reconstructed, regions of interest drawn over the right ventricle and the main pulmonary artery (MPA) and time-activity curves generated. Peak systolic (Cs) and end diastolic (Cd) counts obtained from the MPA curve were proportional to the cross sections Ss and Sd of the MPA and Ss/Sd = Cs/Cd. The diameter (D) of the pulmonary artery was calculated as the distance between the two zeros of the second derivative of a cross-sectional profile. The averaged cross-sectional area was S = pi D2/4. ECG gated blood pool studies were performed in a LAO 40 degrees position when the tracer was at equilibrium; they were processed automatically and the right ventricular end diastolic counts (EDC) converted into volume (EDV) using an aortic volume/count ratio. Right ventricular peak ejection rate (PER) was obtained from the RV time-activity curve and the instantaneous peak ejection velocity was calculated, ws = PER X EDV/S X EDC. PP and Pd were calculated in mmHg and the radionuclide method yielded pressure values that correlated reasonably with catheterisation values: PP(rad) = 0.99 PP(cath)-0.55, r = 0.84 and Pd(rad) = 0.67 Pd(cath) + 4.91, r = 0.74. We conclude that radionuclide techniques can provide a non-invasive method based on a haemodynamic model for measuring pulmonary arterial pressure.

Adult↗
PubMed1988

Accuracy of gated equilibrium radioventriculography in measuring left ventricular function in dogs.

To assess the precision of gated equilibrium radioventriculography in measuring changes in left ventricular stroke volume (LVSV), we studied five dogs each with a chronically implanted electromagnetic flowmeter on the ascending aorta. Per cent changes in left ventricular stroke counts (LVSC) were compared to those in LVSV following acute changes induced by positive end respiratory pressure. We have compared LVSCs calculated in five different ways: (1) Manual outlining of LV region of interest (LVROI), either single fixed enddiastolic (ED) ROI or ED and endsystolic (ES) ROIs with the aid of functional images (first harmonic of Fourier analysis); (2-5) automatic outlining of LV ROI (the algorithm generated 30 profiles on which the maximum of second derivative delineated the LV edges) was performed either on ED image or both ED and ES images. For these four methods a crescent-shaped ROI for background correction was manually drawn at the border of the LV ROI. The fifth method used an automatically drawn single fixed LVED ROI with interpolative background substraction (IBS) between LV and RV edges. LVSC changes, calculated with the IBS method correlated better with LVSV changes than the other four methods. Thus assessment of small LVSC changes is highly processing-dependent.

Animals↗
PubMed1988

Short-axis circumferential profiles of the heart in healthy subjects: comparison of T1-201 SPECT and two-dimensional echocardiography.

To correlate the findings at thallium-201 single photon emission computed tomography (SPECT) with left ventricular anatomy, circumferential wall thickness was measured in 12 healthy subjects with two-dimensional echocardiography. At the midpapillary level, eight anatomic structures were identified with echocardiography, as were four maxima (papillary muscles and junctions of the left ventricular myocardium with the right ventricle, both anteriorly and posteriorly) and the intervening minima (including the septum). Tl-201 SPECT was performed in the same subjects. The normalized circumferential count profiles of the short-axis sections that included the papillary muscles showed the same basic pattern as that on echocardiograms. In most cases, the posterior papillary muscle and the posterior junction with the right ventricle were not distinguishable from each other, which produced three circumferential profile maxima instead of four. When values from all subjects were averaged, left ventricular anatomy was less evident in the circumferential profile. Left ventricular anatomic structures were reflected to a similar degree with either 180 degrees or 360 degrees data sampling.

Adult↗
PubMed1988

Duration of occupancy of opiate receptors by naltrexone.

To determine the duration of blockade of mu-opiate receptors by naltrexone, we measured the binding of [11C]carfentanil in the brain of five normal volunteers with a positron radiation detection system before and 1, 48, 72, 120, and 168 hr after naltrexone administration. The half-time of blockade by naltrexone in the brain ranged from 72 to 108 hr which is greater than the fast plasma clearance components (4-12 hr) of naltrexone or its metabolite, beta-naltrexol, but corresponds well to the half-time of the terminal phase of plasma naltrexone clearance (96 hr). These results are consistent with the duration of the pharmacologic effects of naltrexone in response to heroin administration and indicate that 50 mg/day of oral naltrexone results in plasma levels in excess of that needed to saturate opiate receptors. This is the first example of the use of a simple dual-detector system with positron-emitting radioactive drugs to provide information regarding the duration of action of the drug on its specific receptor site. The plasma clearance half-time of a drug may not give an accurate reflection of the duration of action of the drug on a specific neuroreceptor site. Direct measurement of drug effects on recognition sites greatly extend current studies of pharmacokinetics.

Administration, Oral↗
PubMed1988

Technetium-99m methoxyisobutyl isonitrile (RP30) for quantification of myocardial ischemia and reperfusion in dogs.

This study was done to determine whether [99mTc]methoxyisobutyl isonitrile (RP30), a nonredistributing myocardial perfusion agent, could be used to quantify regional myocardial blood flow distribution during ischemia and reperfusion, employing sequential injections of tracer, tomographic imaging, and appropriate image subtraction. Dogs underwent transient (6 min) coronary artery occlusion, followed by two paired injections of RP30 and radioactive microspheres combined with tomographic imaging, the first during coronary occlusion and the second after 60 min of reperfusion. To obtain a true image representative of reperfusion, the first set of images was corrected for 99mTc decay and subtracted from the second. During occlusion, tissue microsphere content and scintigraphic RP30 activity in the center of the ischemic region (both expressed as a fraction of the nonischemic region) were closely correlated, although RP30 consistently exceeded microsphere content (0.43 +/- 0.03 vs. 0.24 +/- 0.04, p less than 0.01). Direct tissue counting of RP30 confirmed its relative excess in ischemic myocardium. Reperfusion was successful in 7/8 dogs, with an increase in RP30 activity to 0.98 +/- 0.04 compared to 0.89 +/- 0.03 for microspheres (p = N.S.). In one dog with microsphere-documented persistent ischemia, the RP30 defect was still present after reflow. Our results indicate that because of the lack of myocardial clearance and redistribution, repeat injections of RP30 can be used to quantify serial changes in regional myocardial blood flow.

Animals↗
PubMed1988

Iodine-123 SPECT of the thyroid in multinodular goiter.

Iodine-123 single photon emission computed tomography (SPECT) imaging of the thyroid was performed in two patients with multinodular goiter and swallowing difficulty to provide the functional and anatomic orientation of the goiter in relation to the airway. Transaxial slices showed the retrolaryngeal extension of the enlarged thyroid and the tracheal compression by the goiter in both patients. Sagittal and coronal sections confirmed the posterior extension of the goiter. Tracheal displacement was confirmed by roentgenography of the neck in both patients. Vocal cord paralysis demonstrated by fiberoptic laryngoscope and esophageal compression shown by esophagography were found in a patient with toxic multinodular goiter with coexisting papillary carcinoma of the thyroid. In this patient, both the tracheal compression noted in SPECT imaging and the tracheomalacia suggested by the flow volume loop pattern in pulmonary function test were confirmed at the time of thyroidectomy. Our observation suggests that SPECT imaging of large multinodular goiter may be useful in preoperative delineation of the functional anatomy and the extension of goiter in relation to the airway.

Adult↗
PubMed1988

Comparison of technetium-99m aminoalkyl diaminodithiol (DADT) analogs as potential brain blood flow imaging agents.

N-ethyl piperidinyl diaminodithiol (NEP-DADT), complexed with 99mTc has been developed as an agent for the measurement of brain blood flow using SPECT. Studies in patients have shown that 99mTc NEP-DADT enters rapidly into the brain, but also clears rapidly (t1/2 = 17 min). In this study nine new aminoalkyl DADT derivatives were synthesized, labeled with 99mTc and tested in mice with the aim of developing an agent with increased retention in the brain. In addition, relationships between chemical properties of the derivatives and their in vivo localization were investigated. The results were as follows: (a) the R-group and its isomeric configuration has a profound influence on the biodistribution; (b) 99mTc aminoalkyl DADT derivatives with apparent pKa values of greater than 6.9 show poor brain uptake (less than 0.40% dose at 5 min); (c) lengthening of the chain between the DADT moiety and the amino-R group from ethyl to hexyl generally increases the apparent pKa and consequently lowers brain uptake; (d) a correlation (r = 0.71) exists between initial brain uptake and the octanol-buffer partition coefficient; (e) 99mTc-4'-methyl NEP-DADT has the highest partition coefficient, relatively high uptake, and longest retention in the mouse brain. This complex has characteristics suited for brain blood flow measurements.

Animals↗
PubMed1988

Simplified assessment of fine aerosol distribution in human airways.

We characterized homogeneity of bronchopulmonary distribution of a 0.9% saline aerosol with a mass median aerodynamic diameter (MMAD) of 1.12 micron (sigma g = 2.04) labeled with [99mTc]sulfur colloid in nine normal subjects and nine patients with asthma. Aerosol distribution was quantified from frequency distribution histograms generated from Anger camera scans. Skew (a measure of histogram asymmetry) and kurtosis (a measure of histogram range) were significantly elevated (p less than 0.05) in the asthma patients with 0.68 +/- 0.30 and 2.62 +/- 0.81, respectively, compared with 0.39 +/- 0.12 and 1.89 +/- 0.18, respectively, in the normal subjects. Skew and kurtosis were significantly correlated with baseline forced expiratory volume in 1 sec (FEV1, an index of airway obstruction) with rs = -0.4799 (p less than 0.05) and -0.5929 (p less than 0.01), respectively. Skew and kurtosis were also significantly correlated with mucociliary clearance after approximately 90 min (an index of large, central airway deposition) with rs = 0.6801 and 0.6373, respectively (p less than 0.01). This simplified method of analysis does not require additional study days or procedures and facilitates the detection of airflow obstruction in asthma.

Adult↗