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Biomedical subjects

D F Wong

Publications and source records attributed to D F Wong.

At least 55 records · Page 3Linked to original sources
PubMed1995

Magnetic resonance imaging reveals no ventriculomegaly in polydrug abusers.

Previous studies of cerebral structure in substance abusers yielded controversial results, largely due to issues of subject selection and/or limitations of experimental techniques. The purpose of the present study was to assess whether the ventricle-to-brain ratio (VBR), determined volumetrically by magnetic resonance imaging (MRI), differed in polysubstance abusers (n = 10), as compared with age-matched controls (n = 10). Subjects were male volunteers 21-39 years of age. The values of VBR in the polydrug abuse group were not larger than those in control group, nor was there any tendency toward relative ventriculomegaly in the substance abusers. Therefore, the present findings provide no evidence that polysubstance abuse produces abnormalities of gross brain structure in relatively young and physically healthy men.

Adult↗
PubMed1995

An improved method to calculate cerebral metabolic rates of glucose using PET.

UNLABELLED: PET methods for single-scan measurement of the cerebral metabolic rate of glucose (CMRglc) generally involve sampling of radioactivity in arterial plasma over the course of the experiment. The purpose of this study was to develop an analytic procedure that would require substantially fewer plasma samples to measure CMRglc using the single-scan method. METHODS: This technique uses a model for the curve describing the time course of radioactivity in plasma. RESULTS: This model obviates the need to draw arterial samples at short time intervals or at all during the first 30 min after radiotracer injection. The new technique uses six samples to provide the same accuracy and precision as the conventional method provides with 30 or more samples. CONCLUSION: The proposed method greatly simplifies quantitative PET studies of glucose metabolism.

Adult↗
PubMed1994

Elevated dopa decarboxylase activity in living brain of patients with psychosis.

The hypofrontality theory of the pathogenesis of schizophrenia predicts that cortical lesions cause psychosis. During a search for abnormalities of catecholaminergic neurotransmission in patients with complex partial seizures of the mesial temporal lobe, we discovered an increase of the rate of metabolism of an exogenous dopa tracer (6-[18F]fluoro-L-dopa) in the neostriatum of a subgroup of patients with a history of psychosis. When specifically assayed for this abnormality, patients with schizophrenia revealed the same significant increase of the rate of metabolism in the striatum. The finding is consistent with the theory that a state of psychosis arises when episodic dopamine excess is superimposed on a trait of basic dopamine deficiency in the striatum. The finding is explained by the hypothesis that cortical insufficiency, a proposed pathogenetic mechanism of both disorders, causes an up-regulation of the enzymes responsible for dopa turnover in the neostriatum as well as the receptors mediating dopaminergic neurotransmission.

Adult↗
PubMed1994

High performance liquid chromatography of carbon-11 labeled thymidine and its major catabolites for clinical PET studies.

The identity and pharmacology of the rapidly formed radiolabeled metabolites formed following i.v. injection of C-11 thymidine (TdR) labeled in the 5-methyl-position are being studied in animal models and patients with cancer. A high performance liquid chromatographic (HPLC) procedure has been developed for the separation of these metabolites including thymine, dihydrothymine, beta-ureidoisobutyric acid, and beta-aminoisobutyric acid from plasma and tissue extracts. Information obtained regarding the pharmacokinetics of the metabolites are being used to generate mathematical models for C-11 TdR incorporation rates into DNA.

Animals↗
PubMed1994

Multimodality correlative study of canine brain tumors. Proton magnetic resonance spectroscopy, positron emission tomography, and histology.

RATIONALE AND OBJECTIVES: Structural/functional relationships in an induced canine brain tumor were studied using proton-magnetic resonance spectroscopy (1H-MRS), positron emission tomography (PET), and histology. METHODS: Proton-MRS and PET data of implanted canine brain tumors were correlated with quantitative analysis of the tissue composition within the MRS and PET regions of interest (ROIs). Linear regression analysis was employed to correlate the 1H-MRS and PET data with the percent tumor and the percent total lesion (comprising tumor plus associated pathology ie, edema, cysts, hemorrhage, inflammation) within the ROI. RESULTS: Using 1H-MRS, N-acetyl aspartate concentrations were indirectly correlated with the amount of tumor (P = .058), as well as the amount of tumor plus associated pathology (P = .032) within the ROI. Total creatine concentrations were indirectly correlated with the amount of tumor and the amount of tumor plus associated pathology within the ROI (P < .05). Lactate concentrations were directly correlated with the amount of tumor (P = .053) and the amount of tumor plus associated pathology (P = .058) within the ROI. Using PET, Oxygen metabolic rates were indirectly correlated with the amount of tumor and with the amount of tumor plus associated pathology within the ROI (P < .05). Glucose metabolic rates were directly correlated with both the amount of tumor and with the amount of tumor plus associated pathology at P < .05. Proton-MRS measured concentrations of choline and PET measured values for blood flow, and oxygen extraction showed correlations with the amount of tumor and with the amount of tumor plus associated pathology at P > or = .08. CONCLUSIONS: The PET and MRS data were complementary with respect to suggesting anaerobic glucose metabolism for the tumor. Unlike other tumors, no increase in choline was noted in the canine tumor.

Animals↗
PubMed1993

In vivo imaging of baboon and human dopamine transporters by positron emission tomography using [11C]WIN 35,428.

[11C]WIN 35,428 was evaluated as a specific in vivo radioligand for the dopamine transporter site by PET scanning in nonhuman primates and humans. In studies with a baboon (Papio anubis), [11C]WIN 35,428 accumulated in brain regions containing dopamine transporters, i.e., the striata. This accumulation was partially blocked by prior administration of (-)cocaine (4 mg/kg, i.v.). Placement of a unilateral lesion of dopamine-containing nerve terminals with MPTP resulted in a unilateral reduction in [11C]WIN 35,428 accumulation in the striatum on the side of the lesion. Imaging of D2 dopamine receptors with [11C]NMSP in the same MPTP-treated animals showed much less reduction in the postsynaptic D2 dopamine receptors as compared to the much larger reduction in the dopamine transporters labeled with [11C]WIN 35,428. A total of ten normal human volunteers (five males and five females) with ages ranging from 19 to 81 years were studied. The caudate/cerebellar and putamen/cerebellar ratios ranged from 4.4 to 5.7 90 min after injection of the tracer. Preliminary kinetic modeling with arterial plasma sampling resulted in an average binding potential (k3/k4) of 4.98 in the caudate nucleus and 5.13 in putamen. To demonstrate in vivo blockade with dopamine reuptake inhibitors, two subjects received prior oral doses of 6 mg mazindol. Subject 5 had significant reductions of 29% in the caudate/cerebellar ratio at 90 min, 35% in the putamen/cerebellar ratio at 90 min, 45% in the caudate k3/k4 ratio from 6.7 to 3.7, and 46% in the putamen k3/k4 from 4.7 to 2.5. Subject 8 had significant reductions of 20% in both the caudate/cerebellar ratio and the putamen/cerebellar ratio at 90 min. During the human PET studies, a number of neuropsychological tests and physiological measurements were performed. No significant changes were found after administration of the [11C]WIN 35,428 alone. Taken together, these data indicate that [11C]WIN 35,428 is a promising radioligand for future studies of neuropsychiatric disorders that involve the dopamine transporter site.

Adult↗
PubMed1993

Dopamine D2 receptor density estimates in schizophrenia: a positron emission tomography study with 11C-N-methylspiperone.

Positron emission tomography (PET) with 11C-N-methylspiperone as the radioligand was carried out in 25 chronic schizophrenic patients to determine dopamine D2 receptor density estimates in the corpus striatum. The sample included 18 neuroleptic-naive and 7 neuroleptic-free patients. Dopamine D2 receptor density estimates (Bmax) were obtained using a two-scan/four-compartment model. The Bmax estimates for the entire group (33.39 +/- 3.43 pmole/g) were significantly elevated when compared with estimates for the control group (Bmax = 15.63 +/- 2.38). The Bmax values for the entire group of schizophrenic patients showed a significant decline as a function of age. The Bmax values were significantly related to duration of illness (y = 13.2 + 10.3795x - 0.7931x2; r = 0.48). Thirteen patients and seven control subjects were added to our original publication sample (Wong et al., 1986c). The patients' Bmax values, when adjusted for age and sex effects, were significantly different compared with those of control subjects. Clinical data from the entire group were compared with published data from other research groups that have estimated dopamine D2 receptor density using different radioligands and different methods of data analysis. Comparisons of the clinical characteristics of the published studies show significant differences in patient populations, suggesting that discrepancies among published studies may reflect, in part, heterogeneity among groups of schizophrenic patients. The D2 receptor abnormality described in this study may be a late manifestation of disease, and the implications of this observation are discussed.

Adult↗
PubMed1993

Quantitative D2 dopamine receptor PET and structural MRI changes in late-onset schizophrenia.

Late-onset schizophrenia (LOS) is likely a syndrome of diverse etiology. In a series of related studies, we compared LOS patients with normal controls, elderly patients with early-onset schizophrenia (EOS), and Alzheimer's disease patients, using magnetic resonance imaging (MRI) and neuroreceptor positron emission tomography measures, which had previously been reported to be abnormal in EOS. EOS and LOS patients showed similar MRI changes. LOS drug-naive patients had elevated Bmax (receptor density) values for dopamine D2 receptors compared with age and gender norms, a phenomenon previously reported by our group in young schizophrenia patients.

Aged↗
PubMed1993

Sensitivity to subjective effects of cocaine in drug abusers: relationship to cerebral ventricle size.

OBJECTIVE: The purpose of this study was to assess the functional significance of ventricle-brain ratio (VBR) in terms of how it might affect sensitivity to cocaine, an indirect dopamine agonist. METHOD: Relationships between VBR and subjective responses to acute intravenous cocaine hydrochloride were examined in 20 male polydrug abusers. Tests were performed in conjunction with positron emission tomography scans to measure cerebral glucose metabolism. RESULTS: Subjective measures of effects of cocaine, including self-report ratings of intensity of the drug effect, scores on the morphine-benzedrine scale of the Addiction Research Center Inventory, and several items on visual analogue scales, correlated negatively with VBR. VBR also differed significantly among subjects who were grouped according to scores on items ("rush" and "crash") of the Cocaine-Sensitive Scale (larger VBR in subjects with weaker responses). VBR was not correlated with cocaine-induced changes in cerebral metabolic rates for glucose. CONCLUSIONS: Relative insensitivity to the subjective effects of cocaine in polydrug abusers with ventricle enlargement suggests that ventriculomegaly may reflect changes in periventricular brain regions that mediate these effects of cocaine.

Adult↗
PubMed1993

A preliminary study of cortical S2 serotonin receptors and cognitive performance following stroke.

Cortical serotonin receptor binding was measured with positron-emission tomography (PET) in uninjured regions of cortex in 26 stroke patients. Cognitive function was assessed with the Mini-Mental State Exam (MMSE) and a neuropsychological test battery. Left frontal cortex serotonin binding was correlated positively with MMSE total score (r = 0.50, P = 0.01) and with the MMSE concentration, writing, and copying tasks (r = 0.42, 0.56, 0.53, respectively; P < 0.05). Tests of orientation and repetition of difficult phrases were significantly correlated with serotonin binding (r = 0.53 and 0.52, respectively; P < 0.05). These findings suggest that cognitive performance after stroke may be influenced by alterations in the serotonergic system.

Adult↗
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

Dopamine transporter imaging with novel, selective cocaine analogs.

RTI-121 and RTI-122 are 3 beta-substituted phenyltropane analogs of cocaine that have high, selective binding affinity for dopamine transporters. [123I]RTI-121 and [123I]RTI-122 bind to dopamine transporters in vivo after intravenous administration and permit imaging of the transporters.

Animals↗
PubMed1992

Positron emission tomography in the Rett syndrome: clinical, biochemical and pathological correlates.

A consistent constellation of clinical signs and symptoms define the Rett syndrome, the most prominent of which are disorders of movement and tone. Preliminary pathologic and neurochemical data indicate predominant involvement of the nigrostriatal dopaminergic pathways and the cholinergic system of the basal forebrain region. The age of onset differentiates the Rett syndrome from Alzheimer and Parkinson disease with similar lesions. PET scanning makes it possible to relate the chemistry of the brain to function by measuring the number and affinity of neuroreceptors, metabolism in specific brain regions, and provide important determinants of the underlying mechanisms in disease states.

Adolescent↗