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Karmen K Yoder

Publications and source records attributed to Karmen K Yoder.

7 recordsLinked to original sources
PubMed2006

Positron emission tomography displacement sensitivity: predicting binding potential change for positron emission tomography tracers based on their kinetic characteristics.

There is great interest in positron emission tomography (PET) as a noninvasive assay of fluctuations in synaptic neurotransmitter levels, but questions remain regarding the optimal choice of tracer for such a task. A mathematical method is proposed for predicting the utility of any PET tracer as a detector of changes in the concentration of an endogenous competitor via displacement of the tracer (a.k.a., its 'vulnerability' to competition). The method is based on earlier theoretical work by Endres and Carson and by the authors. A tracer-specific predictor, the PET Displacement Sensitivity (PDS), is calculated from compartmental model simulations of the uptake and retention of dopaminergic radiotracers in the presence of transient elevations of dopamine (DA). The PDS predicts the change in binding potential (DeltaBP) for a given change in receptor occupancy because of binding by the endogenous competitor. Simulations were performed using estimates of tracer kinetic parameters derived from the literature. For D(2)/D(3) tracers, the calculated PDS indices suggest a rank order for sensitivity to displacement by DA as follows: raclopride (highest sensitivity), followed by fallypride, FESP, FLB, NMSP, and epidepride (lowest). Although the PDS takes into account the affinity constant for the tracer at the binding site, its predictive value cannot be matched by either a single equilibrium constant, or by any one rate constant of the model. Values for DeltaBP have been derived from published studies that employed comparable displacement paradigms with amphetamine and a D(2)/D(3) tracer. The values are in good agreement with the PDS-predicted rank order of sensitivity to displacement.

Binding, Competitive↗
PubMed2005

A supervised method for calculating perfusion/diffusion mismatch volume in acute ischemic stroke.

Diffusion and perfusion (MR) imaging modalities identify overlapping but not identical areas of tissue as lesion following a stroke. It is thought that the 'mismatch' between modalities may represent tissue that could be recovered with proper (thrombolytic) treatment. We have designed a tool for semi-automated segmentation of the images and calculation of the mismatch volume. We present results from software phantoms and clinical data. Phantom results show our mismatch volume calculations are unbiased at realistic noise levels. Clinical data show that raters using our tool are consistent, fast (15min per subject) and indistinguishable from an expert using manual segmentation.

Adult↗
PubMed2005

Dopamine D(2) receptor availability is associated with subjective responses to alcohol.

BACKGROUND: The mesolimbic dopaminergic system is thought to mediate alcohol abuse and dependence. Determining the relationship between in vivo dopamine and the subjective response to alcohol could improve understanding of the mechanisms that lead to alcohol abuse and dependence. Here, we examined the relationship between dopamine D2 receptors in the nucleus accumbens and scores of perceived "high" and "intoxication" during an intravenous (IV) alcohol infusion. METHODS: Nine healthy control subjects received [C]raclopride PET scanning at baseline. Eight subjects received a second [C]raclopride scan during a pharmacodynamically modeled and controlled rise of IV alcohol, followed by steady state (60 mg% +/- 5 mg%) alcohol infusion. Numerical ratings of "high" and "intoxication" were tested for correlations with measures of dopaminergic function. RESULTS: Baseline D2 receptor availability in the left nucleus accumbens was significantly correlated with peak perceived "intoxication" (p = 0.02) and marginally correlated with peak perceived "high" (p = 0.07). CONCLUSIONS: Resting D2 receptor availability may predict healthy subject responses to alcohol exposure.

Adult↗
PubMed2004

Dopamine transporter density in schizophrenic subjects with and without tardive dyskinesia.

Striatal dopamine transporter (DAT) binding potential (BP) was compared between schizophrenic subjects with and without tardive dyskinesia and controls. Although the groups were not statistically different in striatal BP, tardive subjects had apparently lower DAT density than non-tardive schizophrenic subjects. Significant and trend-level inverse correlations were found between DAT BP in the striatum, and especially the severity of negative symptom scores, but also cognitive, and depression/anxiety scores on the PANSS.

Adult↗
PubMed2004

Change in binding potential as a quantitative index of neurotransmitter release is highly sensitive to relative timing and kinetics of the tracer and the endogenous ligand.

UNLABELLED: Change in binding potential (deltaBP) is often used to indicate alterations in neurotransmitter concentration in response to stimuli. Increasingly, it is being used in bolus studies as a quantitative index of dopamine (DA) release. In bolus studies, however, BP is an average quantity over time that is influenced by the dynamics of both the tracer and the neurotransmitter. We sought to characterize the sensitivity of deltaBP to changes in endogenous DA concentration and to elucidate possible biases in deltaBP with respect to timing of task-induced or drug-induced increases in DA. METHODS: Noiseless simulations of (11)C-raclopride PET curves were performed in a specific binding region with concomitant increases in endogenous DA. DA changes were modeled as delta-functions, gamma-variates, or as realistic drug-induced increases in DA over time, based on published results. Graphical estimation of BP with a reference region as the input function was used, with a multilinear formulation of the operational equation. RESULTS: Simulations demonstrated that deltaBP (a). is linear over a narrow range of integrated DA release, (b). has an inherent sensitivity to timing of DA perturbations, and (c). could incorrectly infer the relative amounts of DA released between subject populations or experimental conditions. These results are explained by what we term the effective weighted availability, which describes the interaction of a DA function and free raclopride concentration over time and follows directly from earlier work. CONCLUSION: We illustrate how, under quite plausible circumstances, deltaBP may lead to erroneous conclusions about relative amounts of DA released after dopaminergic perturbations. Our findings caution against using deltaBP as a quantitative or rank index of DA release when comparing different dopaminergic stimuli.

Binding Sites↗
PubMedDate not supplied

ntPET: a new application of PET imaging for characterizing the kinetics of endogenous neurotransmitter release.

We present a new application of positron emission tomography ("ntPET" or "neurotransmitter PET") designed to recover temporal patterns of neurotransmitter release from dynamic data. Our approach employs an enhanced tracer kinetic model that describes uptake of a labeled dopamine D2/D3 receptor ligand in the presence of a time-varying rise and fall in endogenous dopamine. Data must be acquired during both baseline and stimulus (transient dopamine release) conditions. Data from a reference region in both conditions are used as an input function, which alleviates the need for any arterial blood sampling. We use simulation studies to demonstrate the ability of the method to recover the temporal characteristics of an increase in dopamine concentration that might be expected following a drug treatment. The accuracy and precision of the method-as well as its potential for false-positive responses due to noise or changes in blood flow-were examined. Finally, we applied the ntPET method to small-animal imaging data in order to produce the first noninvasive assay of the time-varying release of dopamine in the rat striatum following alcohol.

Animals↗