Faculty Bibliography

For the quantitative analysis of ligand-receptor dynamic positron emission tomography (PET) studies, it is often desirable to apply reference tissue methods that eliminate the need for arterial blood sampling. A common technique is to apply a simplified reference tissue model (SRTM). Applications of this method are generally based on an analytical solution of the SRTM equation with parameters estimated by nonlinear regression. In this study, we derive, based on the same assumptions used to derive the SRTM, a new set of operational equations of integral form with parameters directly estimated by conventional weighted linear regression (WLR). In addition, a linear regression with spatial constraint (LRSC) algorithm is developed for parametric imaging to reduce the effects of high noise levels in pixel time activity curves that are typical of PET dynamic data. For comparison, conventional weighted nonlinear regression with the Marquardt algorithm (WNLRM) and nonlinear ridge regression with spatial constraint (NLRRSC) were also implemented using the nonlinear analytical solution of the SRTM equation. In contrast to the other three methods, LRSC reduces the percent root mean square error of the estimated parameters, especially at higher noise levels. For estimation of binding potential (BP), WLR and LRSC show similar variance even at high noise levels, but LRSC yields a smaller bias. Results from human studies demonstrate that LRSC produces high-quality parametric images. The variance of R(1) and k(2) images generated by WLR, WNLRM, and NLRRSC can be decreased 30%-60% by using LRSC. The quality of the BP images generated by WLR and LRSC is visually comparable, and the variance of BP images generated by WNLRM can be reduced 10%-40% by WLR or LRSC. The BP estimates obtained using WLR are 3%-5% lower than those estimated by LRSC. We conclude that the new linear equations yield a reliable, computationally efficient, and robust LRSC algorithm to generate parametric images of ligand-receptor dynamic PET studies.

Accurate identification of the demographic characteristics of subjects is crucial for clinical, research, teaching, and administrative purposes in psychology. The Demographic Coding Form is a simple, self-report tool to identify essential demographic data. Secondary categorization as "Hispanic" is obtained to facilitate comparison with the general population data. The form requests information about ethnic mixtures in subjects. Psychometric properties are being elucidated.

A mentor is the key person to assist a student who wishes to become an independent investigator. The federal government provides long-term funding for decades of research by an investigator, and short-term funding for years of transition from student to investigator is available from both governmental and private agencies. Grants designed for men and women and various ethnic groups are valuable resources. Courteous acknowledgment of sponsorship by the grantee facilitates continued grants from the funding source.

To study alcohol's effects on the structure and function of the brain in living human beings, researchers can use various imaging techniques. Positron emission tomography (PET) is a functional imaging approach used to study the metabolism and physiology of the brain. PET studies have found that both acute and chronic alcohol ingestion alter blood flow and metabolism in various brain regions, including the frontal lobes and cerebellum. Other analyses focusing on alcohol's effects on brain chemical (i.e., neurotransmitter) systems have found that both acute and chronic alcohol consumption alter the activities of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and the excitatory neurotransmitters glutamate, dopamine, and serotonin. These alterations may contribute to the reinforcing and rewarding effects of alcohol as well as to symptoms of alcohol withdrawal. Imaging studies also have demonstrated that some of alcohol's adverse effects on brain function can be reversed by abstinence or alcoholism treatment interventions. In addition, imaging studies may help in the development of new medications for alcoholism treatment.

Although the United States Food and Drug Administration banned its use for nocturnal leg cramps due to lack of safety and efficacy, quinine is widely available in beverages including tonic water and bitter lemon. Numerous anecdotal reports suggest that products containing quinine may produce neurological complications, including confusion, altered mental status, seizures, and coma, particularly in older women. Psychologists need to inquire about consumption of quinine-containing beverages as part of an evaluation process.

We have tested the hypothesis that striatal dopamine (DA) release accompanies cocaine craving. We studied cocaine users (n=24) and comparison subjects (n=21), all of whom viewed neutral and craving stimuli complex (video & audiotape) played for 95 minutes. Each subject received a minimum of two 11C-raclopride PET scans. All received 2 PET scans as a bolus (BL), but some also as a continuous infusion (CI). BL or CI were performed on separate days. Each PET scan was preceded by the presentation of the relevant stimulus complex. Frame by frame head movement corrections were applied to PET images and MRI-based volumes of interest (VOI) were used. BL data were analyzed using Logan plot to determine the DA release. Baseline binding potential (BP) in cocaine users was significantly lower than controls (mean

[I-123]5-I-A-85380 ([I-123]5-IA) is a ligand specific for the alpha4beta2 nicotinic acetylcholine receptor (nAChR) subtype. It was reported that distribution volume (DV) is an appropriate measurement for alpha4beta2 nAChR density in baboon [I-123]5-IA dynamic SPECT studies. To evaluate the kinetics obtained from human [I-123]5-IA dynamic SPECT, three different methods were applied to region of interest (ROI) kinetics analysis as folows: A: a 2-compartment 3-parameters model, B: 3-compartment 5-parameter model, and C: same model as in B but fitting with a constraint of ratio of K-1/k(2)e stimated by fitting occipital kinetics to model in A. The DV was estimated as DV = K-1/k(2) for A, and DV=(K-1/k(2))(1+k(3)/k(4)) for B and C. Nonlinear least squares fitting using Marquardt algorithm was performed for A-C. Akaike information criterion (AIC) and R-2 were used for evaluation of fitting results. A linear parametric imaging algorithm derived from model in method A was used for generating images of K, and DV. Four normal human [I-123]5-IA dynamic studies were evaluated by A-C. In each study, after a bolus of [I-123]5-IA (5similar to10 mCi, specific activity>10 Ci/umol) was injected intravenously, a dynamic scanning with 20 acquistions over 6 hour was started immediately on a Trionix TriadXLT scanner. 30-40 arterial plasma samples were taken during the study and HPLC was performed to determine the metabolite-corrected arterial plasma radioactivity as input function. The ROI regions (cerebellum, frontal cortex, occipital cortex, pones, and thalamus) were drawn on co-registered MRI images. Results show that A fits to all ROI kinetics very well (R-2>0.99), and paired T-test for AIC showed there is no statistical significantly improvement of model fitting from B, C methods The K-1 and DV images are of good image quality. Conclusion: A is best for ROI kinetic analysis and parametric imaging for DV and K-1.