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Biomedical subjects

H N Wagner

Publications and source records attributed to H N Wagner.

At least 19 recordsLinked to original sources
PubMed1992

Detection of left anterior descending coronary artery disease in patients with left bundle branch block.

The detection of coronary artery disease is difficult if a patient has electrocardiographic evidence of left bundle branch block (BBB). Septal blood flow may be reduced in patients with left BBB, despite no angiographic evidence of left anterior descending (LAD) coronary artery disease. We have developed a new method of quantification of Thallium-201 single-photon emission computed tomographic (SPECT) images with the aim of better separating patients with left BBB and LAD disease from those with left BBB alone. The study cohort comprised 8 normal subjects (group I) and 20 patients with left BBB and chest pain who underwent thallium-201 SPECT imaging and coronary angiography. Eight patients (group II) had < or = 50% LAD stenosis, and 12 (group III) had > or = 70% LAD stenosis. Septal abnormality scores on the second short-axis slice from the base were computed, based on comparison of each subject's short-axis circumferential profile with a normal reference curve. This followed a procedure in which each profile was scaled to minimize differences in its absolute level in relation to the reference curve. Septal abnormality scores on stress images were 0.8 +/- 22 for group I, 27 +/- 43 for group II, and 165 +/- 67 for group III (p = 0.15 for group I vs II, and p < 0.0001 between groups I and III, and II and III).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

In vivo binding of N1'-([11C]methyl)naltrindole to delta-opioid receptors in mouse brain.

The regional distribution of N1'-([11C]methyl)naltrindole ([11C]MeNTI) in vivo in mouse brain correlates with established delta opioid receptor densities in vitro. [11C]MeNTI binding is blocked by naltrindole, a delta antagonist, but not by cyprodime, a mu antagonist, of by (+/-)-U50,488, a kappa agonist. Thus, [11C]MeNTI selectively labels central delta opioid receptors in vivo in mouse, and shows promise for positron emission tomography studies of delta sites in human brain.

Animals↗
PubMed1992

In vivo studies of [125I]iodobenzamide and [11C]iodobenzamide: a ligand suitable for positron emission tomography and single photon emission tomography imaging of cerebral D2 dopamine receptors.

Iodobenzamide (IMB) labeled with either [11C] or [125I] was studied in mice and baboons. Pharmacological studies demonstrated an in vivo binding profile compatible with D2 dopamine receptors. Mouse biodistribution studies with both [11C]IMB and [125I]IMB showed a similar brain distribution of radioactivity. Mouse [125I]IMB studies with amphetamine and reserpine pretreatment suggested that IMB may be less susceptible to endogenous dopamine competition for D2 receptor binding in vivo as compared to raclopride. Preliminary baboon studies showed haloperidol competition for IMB binding sites.

Animals↗
PubMed1992

Rest thallium-201 myocardial perfusion imaging in a patient with leukaemic infiltration of the heart.

Despite the high incidence of leukaemic infiltration of the heart, only 8 cases of atrioventricular block due to leukaemia have been reported in the literature. Improvement in the heart block associated with disappearance of the leukaemic infiltrate has not been reported. A rest thallium-201 study was used in a 65-year-old man to demonstrate leukaemic infiltration of the heart which was associated with complete heart block. After chemotherapy, when the tumour burden was reduced and the leukaemia in remission, his heart block resolved, and a follow-up thallium scan was normal.

Aged↗
PubMed1992

Improved positron emission tomography quantification by Fourier-based restoration filtering.

Positron emission tomography (PET) images are characterized by both poor spatial resolution and high statistical noise. Conventional methods to reduce noise, such as local weighted averaging, produce further deteriorations in spatial resolution, while the use of deconvolution to recover resolution typically amplifies noise to unacceptable levels. We studied the use of two-dimensional Fourier filtering to simultaneously increase quantitative recovery and reduce noise. The filter was based on inversion of the scanner's measured transfer function, coupled with high frequency roll-off. In phantom studies, we found improvements in both "hot" and "cold" sphere quantification. Compared with ramp-only filtering, improvements in hot spot recovery for the highest accuracy filter averaged 13.6% +/- 6.6% for spheres larger than 15 mm; improvements in cold spot recovery averaged 30.7% +/- 4.7%. At the same time, the noise was reduced by a factor of 3 compared with randomly filtering. Fourier-based image restoration filtering is thus capable of improving both accuracy and precision in PET.

Brain↗
PubMed1992

Factor analysis of regional cerebral glucose metabolic rates in healthy men.

Cerebral glucose utilization measured with fluorine-18-fluoro-2-deoxy-D-glucose is characterized by considerable variability both among different persons and for the same person examined on different occasions. The goal of this study was to explore whether some regions of the brain were more variable than others with respect to glucose utilization and whether there was a pattern in their covariance. The global and regional cerebral utilization of glucose was measured in 12 healthy young volunteers on 3 or 4 occasions. In all, 24 regions were examined. The interrelation of the glucose utilization rates of the brain regions was investigated by factor analysis of the metabolic rates. Some 70% of the total variance was attributable to only 1 factor, while 80% of the total variance could be attributed to 2 factors. Regions making up the first factor were the frontal and temporal cortex, cingulate gyrus, caudate nucleus, thalamus and putamen. These regions are functionally related to the limbic system. Regions of the second factor were the parietal cortex, occipital cortex and cerebellum, regions more clearly related to sensory and motor functions. The 2-factor pattern was highly reproducible, being found with different algorithms for factor extraction and rotation. Under resting conditions, the variance of cerebral metabolism seems to be primarily related to regions which are closely involved with the limbic system. Cortical regions involved primarily in motor and sensory functions have less influence on the variance.

Adult↗
PubMed1992

Synthesis and biodistribution of a new radiotracer for in vivo labeling of serotonin uptake sites by PET, cis-N,N-[11C]dimethyl-3-(2',4'-dichlorophenyl)-indanamine (cis-[11C]DDPI).

A new PET radiotracer for in vivo labeling of serotonin (5-HT) uptake sites, cis-N,N-[11C]dimethyl-3-(2',4'-dichlorophenyl)-indanamine, cis-[11C]DDPI, was synthesized and its biological behavior was studied. The radiosynthesis of cis-[11C]DDPI was performed by N-methylation of cis-N-methyl-3-(2',4'-dichlorophenyl)-indanamine with [11C]iodomethane. The average radiochemical yield was approx. 8%, with an average specific activity of 600 mCi/mumol. Following intravenous administration, cis-[11C]DDPI accumulated in mouse brain regions rich in 5-HT uptake sites, such as olfactory tubercles, hypothalamus and frontal cortex. Following pre-injection of 1 mg/kg of paroxetine, a high affinity 5-HT uptake blocker, the binding of cis-[11C]DDPI in the olfactory tubercles, hypothalamus and frontal cortex was decreased by 23, 25 and 16%; this corresponds to 73, 82 and 59% of the specific binding in these regions. These results suggest that the accumulation of cis-[11C]DDPI in the tissues rich in 5-HT sites is a result of specific binding of cis-[11C]DDPI to 5-HT uptake sites. Due to the relatively high non-specific uptake and slow clearance of this compound from non-specific binding sites, the ratio between specific and non-specific binding increased slowly with time, reaching 1.5:1 at 60 min after injection.

Animals↗
PubMed1992

Position emission tomography at the turn of the century: a perspective.

Nuclear medicine translates advances in molecular biology into the care of patients. In the future, diseases will be characterized at the molecular rather than the cellular level, often before detectable structural changes have occurred. Position emission tomography (PET) will play a major role in the study of intercellular communication by making it possible to characterize the actions of "molecules with messages." Diseases will be characterized by defects in intercellular communication. Treatment will be planned based on molecular abnormalities, and the response to treatment will be monitored with molecular probes. PET studies of the brain, heart, and cancer will be extended to all organs of the body. Pharmacology will be strongly influenced by PET because most drugs act by stimulating or blocking "recognition sites" on the surface of cells. In the next century, will single photon emission computed tomography (SPECT) makes PET unnecessary? The answer is no, because both PET and SPECT will have achieved a permanent role in medical practice; both make it possible to examine regional in vivo chemistry in human beings. Carbon-11 and fluorine-18 will continue to lead the way, but many drugs, and some body constituents such as proteins, can be radiolabeled with iodine-123 and technetium-99m. Today, PET is limited by the need to make one's own radiotracers. This is likely to change when regional radiopharmacies become widespread.(ABSTRACT TRUNCATED AT 250 WORDS)

Forecasting↗
PubMed1992

The influence of biological and technical factors on the variability of global and regional brain metabolism of 2-[18F]fluoro-2-deoxy-D-glucose.

This study investigated the influence of biological and technical factors on variations of global and regional cerebral metabolic rate of glucose (CMRglc) measured with 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG). Twelve male volunteers (22-40 years) were investigated on three or four occasions for a total of 42 studies. We calculated the variance/covariance of the following parameters: CMRglc, six parameters of the blood clearance of [18F]FDG, hour of injection, peak time of blood radioactivity, and six components of the operational equation (nonradioactive blood glucose concentration, brain radioactivity, two integrals, numerator, and denominator). There was correlation among these six components, except for nonradioactive blood glucose. However, the correlation between the CMRglc and the individual components of the operational equation was poor. The inter- and intrapersonal CMRglc coefficients of variations were 13.8 and 7.1%, respectively. In contrast, coefficients of variations of the numerator and denominator of the operational equation were 34.6 and 32.6%, respectively, and were always in the same direction. No correlation was found between CMRglc and the technical factors in the numerator and denominator of the operational equation. Factor analysis disclosed that a single factor was responsible for 70% of the variance. This factor included caudate, putamen, thalamus, frontal cortex, temporal cortex, and cingulate gyrus. These structures are involved with multiple complex functions, from autonomic motor control to behavior and emotions. The intrinsic metabolic variability of these structures, along with the basal metabolic processes that are continuously going on in the brain, may be the best explanation for the variance encountered in our investigation.

Adult↗
PubMed1992

Imaging muscarinic cholinergic receptors in human brain in vivo with Spect, [123I]4-iododexetimide, and [123I]4-iodolevetimide.

A method to image muscarinic acetylcholine receptors (muscarinic receptors) noninvasively in human brain in vivo was developed using [123I]4-iododexetimide ([123I]IDex), [123I]4-iodolevetimide ([123I]ILev), and single photon emission computed tomography (SPECT). [123I]IDex is a high-affinity muscarinic receptor antagonist. [123I]ILev is its pharmacologically inactive enantiomer and measures nonspecific binding of [123I]IDex in vitro. Regional brain activity after tracer injection was measured in four young normal volunteers for 24 h. Regional [123I]IDex and [123I]ILev activities were correlated early after injection, but not after 1.5 h. [123I]IDex activity increased over 7-12 h in neocortex, neostriatum, and thalamus, but decreased immediately after the injection peak in cerebellum. [123I]IDex activity was highest in neostriatum, followed in rank order by neocortex, thalamus, and cerebellum. [123I]IDex activity correlated with muscarinic receptor concentrations in matching brain regions. In contrast, [123I]ILev activity decreased immediately after the injection peak in all brain regions and did not correspond to muscarinic receptor concentrations. [123I]IDex activity in neocortex and neostriatum during equilibrium was six to seven times higher than [123I]ILev activity. The data demonstrate that [123I]IDex binds specifically to muscarinic receptors in vivo, whereas [123I]ILev represents the nonspecific part of [123I]IDex binding. Subtraction of [123I]ILev from [123I]IDex images on a pixel-by-pixel basis therefore reflects specific [123I]IDex binding to muscarinic receptors. Owing to its high specific binding, [123I]IDex has the potential to measure small changes in muscarinic receptor characteristics in vivo with SPECT. The use of stereoisomerism directly to measure nonspecific binding of [123I]IDex in vivo may reduce complexity in modeling approaches to muscarinic acetylcholine receptors in human brain.

Adult↗
PubMed1992

Effects of vasopressin on blood-brain transfer of methionine in dogs.

We used a simplified probe detection system for positron-emitting radionuclides in order to measure blood-brain barrier transport of amino acids in anesthetized dogs. Plasma and brain time-activity curves were recorded after intravenous bolus injection of L-[11C]methionine before and after administration of 1 microgram of vasopressin. Three-compartment models with three or four transfer coefficients were used to derive the kinetics of L-[11C]methionine uptake in brain. The blood-brain clearance of the tracer (K1) was 0.075 ml ml-1 min-1 before and 0.041 ml ml-1 min-1 after injection of vasopressin. The partition volume and the initial distribution (plasma) volume of methionine were unchanged and within the expected limits. The net accumulation rate of methionine (K), estimated by both the four-parameter (kinetic) and three-parameter (graphic) approaches, decreased after vasopressin injection in all six studies.

Animals↗
PubMed1992

A noninvasive test of sphincter of Oddi dysfunction in postcholecystectomy patients: the scintigraphic score.

The ideal noninvasive test of sphincter of Oddi dysfunction (SOD) does not exist and the diagnosis of patients with postcholecystectomy pain often relies on invasive procedures. In this paper we describe a scintigraphic test for SOD: the scintigraphic score. This score combines quantitative and visual criteria for interpretation of hepatobiliary scans. Twenty-six consecutive postcholecystectomy patients underwent hepatobiliary imaging, ERCP, and sphincter manometry. Twelve patients had SOD and 14 had normal sphincters determined by clinical findings, ERCP, and manometric studies. All patients with normal sphincter had scores of 0-4, while patients with SOD had values of 5-12 for a perfect sensitivity and specificity of 100%. Hepatobiliary scans scored in this fashion may become the noninvasive test of choice to screen postcholecystectomy patients with suspected SOD.

Adult↗
PubMed1991

Quantification of mu and non-mu opiate receptors in temporal lobe epilepsy using positron emission tomography.

Alterations in a variety of neurotransmitter systems have been identified in experimental models of epilepsy and in brain tissue from patients with intractable temporal lobe seizures. The availability of new high-affinity radioligands permits the study of some neuroreceptors in vivo with positron emission tomography (PET). We previously characterized the in vivo binding of 11C-carfentanil, a potent and selective mu opiate receptor agonist, and described increases in 11C-carfentanil binding in the temporal neocortex of patients with unilateral temporal lobe epilepsy. These studies have been extended to 11C-diprenorphine, which labels mu, kappa, and delta opiate receptor subtypes. Paired measurements of opiate receptor binding were performed with PET using 11C-carfentanil and 11C-diprenorphine in patients with unilateral temporal lobe seizures. Carfentanil binding, reflecting changes in mu opiate receptors, was increased in the temporal neocortex and decreased in the amygdala on the side of the epileptic focus. Diprenorphine binding, reflecting mu as well as non-mu opiate subtypes, was not significantly different among regions in the focus and nonfocus temporal lobes. Regional glucose metabolism, measured using 18F-2-fluoro-2-deoxyglucose, was decreased in the mesial and lateral aspects of the temporal lobe ipsilateral to the epileptogenic focus. The variation in pattern of carfentanil and diprenorphine binding supports a differential regulation of opiate subtypes in unilateral temporal lobe epilepsy.

Amygdala↗
PubMed1991

Radiosynthesis of sigma receptor ligands for positron emission tomography: 11C- and 18F-labeled guanidines.

A series of analogues of the potent and selective sigma receptor ligand 1,3-ditolylguanidine (DTG) were synthesized and demonstrated to have high affinity for the sigma receptor as measured by in vitro [3H]DTG displacement studies using guinea pig brain tissue. Three of these 1-aryl-3-(1-adamantyl)guanidines were radiolabeled--two with carbon-11 and one with fluorine-18. Radiochemical yields and specific activities were sufficient for these radiotracers to be used in positron emission tomography imaging of the haloperidol-sensitive sigma receptor.

Animals↗