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Biomedical subjects

D F Wong

Publications and source records attributed to D F Wong.

106 records · Page 6Linked to original sources

Right ventricular ejection fraction measured by first-pass intravenous krypton-81m: reproducibility and comparison with technetium-99m.

Study of the effects of various diseases and therapeutic manipulation of pulmonary vascular resistance on the right ventricle has been restricted by methodologic limitations. The radioactive gas in solution, krypton-81m was used to study the right ventricle and the technique was compared with a technetium-99m method. In 22 subjects, first-pass krypton-81m right ventricular ejection fraction, acquired both in list mode and electrocardiogram-gated frame mode, correlated well (r = 0.81 and 0.86, respectively, p less than 0.01) with that determined by technetium-99m first-pass studies over a broad range of ventricular function. The reproducibility of the technique was excellent (r = 0.84 and 0.95 for each acquisition mode, respectively). Krypton-81m first-pass studies provide accurate and reproducible estimates of right ventricular function. Use of krypton allows multiple measurements, with or without perturbations, over a short period of time.

Heart Ventricles↗

Absorbed fractions for dose calculations of neuroreceptor PET studies.

A simple Monte Carlo program was constructed for the purpose of calculating absorbed fractions of relevance to neurologic positron-emission-tomography studies. The caudate, putamen, and cerebellum regions of the brain were mathematically modeled to serve as source regions for the absorbed-fraction calculations for positron-annihilation photons. The target organs were the caudate, putamen, cerebellum, brain, spine portion in the head, skull, and head. Absorbed fractions were also calculated for a uniform ring source which encircled the head phantom.

Absorption↗

Design, preparation, and biodistribution of a technetium-99m triaminedithiol complex to assess regional cerebral blood flow.

A new ligand (N-piperidinylethyl-DADT, 5) has been prepared which forms two complexes with 99mTc when stannous chloride is used as a reducing agent for [99mTc] pertechnetate. Biodistribution studies of one of the complexes in mice showed that 2.2% of the injected dose of the tracer was in the brain at 5 min postintravenous injection with 0.53% of the dose remaining in the brain at 30 min postinjection. Brain-to-blood ratios at these times were 5.3 and 3.0, respectively. Biodistribution studies of the other complex showed similar behavior with a slightly lower initial uptake by and faster clearance from the brain. Imaging studies of the more promising of the two complexes were conducted in a monkey and a baboon. In both cases, rapid uptake of the tracer in the brain was observed and clear brain images were obtained. Time-activity curves showed peak uptake in the brain at approximately 5 to 7 min postintravenous injection followed by a plateau of about 11 min. The half-lives for clearance of the tracer from the brains of the monkey and baboon were found to be 63 and 58 min, respectively. These results suggest that this tracer may be useful for brain imaging in humans.

Animals↗

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↗

Assessment of dopamine receptor densities in the human brain with carbon-11-labeled N-methylspiperone.

We describe the use of carbon-11-labeled 3-N-methylspiperone, a ligand that preferentially binds to dopamine receptors in vivo, to image the receptors by positron emission tomography scanning in baboons and, for the first time, in a human. The method has now been used in 58 humans for noninvasive assessment of the state of brain dopamine receptors under normal and pathological conditions.

Animals↗

(3-N-[11C]methyl)spiperone, a ligand binding to dopamine receptors: radiochemical synthesis and biodistribution studies in mice.

Carbon-11-labeled 3-N-methylspiperone, a positron-emitting dopamine-receptor antagonist with potential for use in positron emission tomography studies of human neurotransmitter receptors, was synthesized from 11CO2 in 40 min, with a radiochemical yield of approximately 20-40%. The specific activity of the (3-N-[11C]methyl)-spiperone was determined by ultraviolet spectroscopy to be approximately 270 mCi/mumol at the end of synthesis. In in vitro binding experiments, the Ki for 3-N-methylspiperone was found to be approximately 250 pM (against H-3 spiperone). The brain-to-blood ratios in normal ICR mice were 2.8 or greater at the times studied, and the striatum-to-cerebellum ratio at 60 min after injection was 20:1.

Animals↗

Imaging dopamine receptors in the human brain by positron tomography.

Neurotransmitter receptors may be involved in a number of neuropsychiatric disease states. The ligand 3-N-[11C]methylspiperone, which preferentially binds to dopamine receptors in vivo, was used to image the receptors by positron emission tomography scanning in baboons and in humans. This technique holds promise for noninvasive clinical studies of dopamine receptors in humans.

Animals↗

Utility of three-phase skeletal scintigraphy in suspected osteomyelitis: concise communication.

Three-phase skeletal scintigraphy, consisting of a radionuclide angiogram, an immediate postinjection "blood-pool" image, and 2--3 hr delayed images, was performed on 98 patients with suspected osteomyelitis. This procedure was evaluated by first interpreting only the delayed images, next the combination of "blood-pool" and delayed images, and finally the three-phase study. There was no change in the sensitivity (12/13 = 0.92) for detecting osteomyelitis, but the false-positive rate for osteomyelitis decreased from 0.25 (21/85) to 0.06 (5/85). In 21 of 64 patients (33%) with abnormal studies, the "blood-pool" image and/or the radionuclide angiogram led to a more accurate scintigraphic diagnosis. In 12 patients (19%) the "blood pool" alone was enough to achieve the correct final diagnosis and was used most often to identify noninfectious skeletal disease. In 9 patients (14%) the radionuclide angiogram was required for an accurate interpretation and was considered essential most often in cases of soft-tissue infection. Both radionuclide angiography and "blood-pool" imaging appear to augment the specificity of skeletal scintigraphy in patients with suspected osteomyelitis.

Adolescent↗

Imaging opiate receptors in the human brain by positron tomography.

Carfentanil is a potent, synthetic opiate that binds to mu opiate receptors with very high affinity (KI = 0.051 nM, 37 degrees C). In rat brain, carfentanil is 90 and 250 times more selective for mu opiate receptors compared with delta and kappa opiate receptors, respectively. Carbon-11-carfentanil was synthesized by reacting [11C]methyliodide with the carboxylic acid precursor of carfentanil. Carbon-11-carfentanil was injected intravenously in man and a baboon and the distribution of the radioactivity in the brain was monitored using positron emission tomography. High concentrations of radioactivity were observed in the basal ganglia and thalamus, intermediate concentrations in the frontal and parietal cerebral cortex, and low concentrations in the cerebellum and occipital cortex; this distribution corresponds to the known regional density of opiate receptors measured using in vitro techniques. This heterogeneous distribution could be abolished by pretreatment with naloxone (1 mg/kg), an opiate antagonist. The percent inhibition of binding by naloxone is approximately 90% in the caudate nucleus and medial thalamus for the period 30-60 min after injection; therefore, this method is associated with a high level of specific binding to opiate receptors compared with nonspecific binding sites. The ability to measure opiate receptors in vivo in man makes it possible to study a variety of neurologic and psychiatric disorders in which opiate receptors are thought to be abnormal and to study physiologic role of opiate receptors in the central nervous system.

Animals↗

Irreversible regional cerebral ischemia: serial MR imaging and proton MR spectroscopy in a nonhuman primate model.

PURPOSE: To delineate the changes in proton MR spectroscopy and imaging that occur with acute, irreversible ischemia of the basal ganglia of a baboon. MATERIALS AND METHODS: The M1 segments of the middle cerebral arteries of six adult male baboons were occluded by endovascular means with microcatheters and N-butyl cyanoacrylate adhesive. Cerebral blood flow measurements were taken with positron emission tomography or radioactive microsphere techniques. Serial spatially localized proton MR spectroscopy of the basal ganglia and MR imaging of the brain were performed. The distribution of ischemic and infarcted tissue was demonstrated by histopathologic techniques or triphenyltetrazolium chloride staining. RESULTS: Radioactive microsphere or positron emission tomography measurements demonstrated no significant cerebral blood flow within the basal ganglia after occlusion of the middle cerebral artery. Proton MR spectroscopy of the basal ganglia demonstrated increasing cerebral lactate and decreasing N-acetyl aspartate within 30 minutes of middle cerebral artery occlusion. Changes in the MR imaging signal intensity of the basal ganglia were observed as early as 3.1 hours on T2-weighted, 3.3 hours on T1-weighted, and 6.1 hours on spin density-weighted images. The distribution of these changes correlated well with the histopathologic features of ischemia and infarction that were seen throughout the basal ganglia. CONCLUSION: Changes in MR imaging signal intensity corresponded to ischemia and infarction in our baboon model of acute irreversible ischemia of the basal ganglia. Increasing cerebral lactate and decreasing N-acetyl aspartate preceded changes in MR imaging signal intensity.

Animals↗

Comparison of functional MR and H2 15O positron emission tomography in stimulation of the primary visual cortex.

PURPOSE: To locate spoiled gradient-echo functional MR signal changes in relation to brain parenchyma. METHODS: The region of the primary visual cortex was evaluated using functional MR and H2 15O positron emission tomography in each of six male subjects who were being visually stimulated by means of red light-emitting diode flash goggles. RESULTS: The positron emission tomography technique demonstrated substantially greater relative signal change with visual stimulation than did the functional MR technique. Furthermore, the functional MR signal changes were concentrated in loci around the periphery of brain parenchyma exhibiting increased radiotracer activity, as opposed to being collocated. CONCLUSIONS: Signal changes found using functional MR based on gradient-echo techniques reflect primarily phenomena occurring within small veins and underrepresent activity intrinsic to brain parenchyma, thus introducing potential inaccuracies in locating regions of activated brain tissue. Positron emission tomography, however, directly measures changes in metabolically related activity within the parenchyma.

Adult↗