Optimization of PET activation studies based on the SNR measured in the 3-D Hoffman brain phantom

Li, H.J.; Votaw, John R.

doi:10.1109/42.730404

Cited by 15 publications

(6 citation statements)

References 18 publications

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“…A best-fit (least-squares sense) set of parameters was determined, and the fraction of transporters occu-pied by the competing ligand was then estimated as 1 Ϫ ([k 3 b/k 4 ]/[k 3 a/k 4 ]). Error in regional uptake has been determined from repeated 2-min measurements of [O-15]water and is reported to be approximately 5% (Li & Votaw, 1998). Using this as a conservative guide, the error was assumed to be 8% of the measured value for frames 2 min in duration and inversely proportional to the scan duration for other durations.…”

Section: Pet Neuroimaging Of Da Transporter Occupancy By Mdma Enantio...mentioning

confidence: 99%

In vivo pharmacology of MDMA and its enantiomers in rhesus monkeys.

Fantegrossi

2008

Experimental and Clinical Psychopharmacology

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The chiral nature of the MDMA molecule gives rise to two enantiomers, each of which is biologically active. This review attempts to cover the author's research into the in vivo effects of MDMA and its enantiomers, as well as other relevant publications which pertain to this topic. No particular differences between the capacities of racemic MDMA and its enantiomers to maintain behavior were noted, but antagonism of the 5-HT2A receptor produces a parallel rightward shift in the dose-effect function for the S(+)-enantiomer, but insurmountably reduces the reinforcing effects of R(-)-MDMA. Long-term self-administration of MDMA may lead to the development of chronic tolerance to the reinforcing effects of MDMA, but S(+)-MDMA is somewhat less susceptible to this effect than the racemate or the R(-)-enantiomer. Using PET neuroimaging, negligible occupancy at the dopamine transporter (DAT) was observed following administration of R(-)-MDMA, but reasonable DAT interaction was quantified following injection of S(+)-MDMA. The non-human primate studies reviewed herein caution that any results obtained in vivo with the MDMA enantiomers may not be particularly informative with regards to the racemate and vice versa.

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Section: Pet Neuroimaging Of Da Transporter Occupancy By Mdma Enantio...mentioning

confidence: 99%

In vivo pharmacology of MDMA and its enantiomers in rhesus monkeys.

Fantegrossi

2008

Experimental and Clinical Psychopharmacology

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“…The chi-squared function (Press et al, 1988) was used to determine the goodness of fit while adjusting the model parameters of the generalized reference tissue model . The error in regional uptake as determined from repeated 2-min measurements of [O-15]water has been reported to be approximately 5% (Li and Votaw, 1998). Using this as a conservative guide, the error was assumed to be 8% of the measured value…”

Section: Pet Neuroimaging Methodsmentioning

confidence: 99%

Effects of Dopamine Transporter Inhibitors on Cocaine Self-Administration in Rhesus Monkeys: Relationship to Transporter Occupancy Determined by Positron Emission Tomography Neuroimaging

Lindsey¹,

Wilcox²,

Votaw³

et al. 2004

J Pharmacol Exp Ther

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The dopamine transporter (DAT) is a critical recognition site for cocaine and contributes to its significant abuse liability. Accordingly, the development of compounds that target the DAT represents a logical approach in the pharmacological treatment of cocaine abuse. The present study characterized the effects of DAT inhibitors as pretreatments in rhesus monkeys trained to self-administer cocaine under a second-order schedule of i.v. drug delivery. The drugs also were substituted for cocaine to characterize their effectiveness in maintaining drug selfadministration. Positron emission tomography neuroimaging with [ All drugs produced dose-related reductions in cocaine self-administration. Doses of GBR 12909 and RTI-177 that reduced responding by 50% (ED 50 ) resulted in DAT occupancies of 67 Ϯ 5 and 73 Ϯ 5%, respectively. In contrast, DAT occupancy was below the limit of detection for the ED 50 dose of RTI-112. Both GBR 12909 and RTI-177 reliably maintained drug selfadministration, and DAT occupancies at doses that maintained peak rates of responding were 57 Ϯ 1 and 92 Ϯ 7%, respectively. In contrast, RTI-112 failed to maintain robust drug selfadministration in any subject. The results indicate that selective DAT inhibitors may require high DAT occupancy to reduce cocaine self-administration and maintain drug self-administration. Moreover, the behavioral profile of DAT inhibitors may be influenced by actions at other monoamine transporters.Despite extensive efforts directed toward the development of medications to treat cocaine abuse, no effective pharmacotherapy is currently in clinical use. The therapeutic approach of substitute agonist or replacement medication has been successful in the context of methadone maintenance for heroin dependence and nicotine replacement for tobacco use. These positive outcomes, combined with recent advances in the understanding of the neuropharmacology of cocaine, support efforts to develop a similar type of medication for cocaine abuse. Of the various types of medications being pursued, dopamine transporter (DAT) inhibitors represent a promising approach in drug development (Mello and Negus, 1996;Carroll et al., 1999;Howell and Wilcox, 2001). The DAT is an important recognition site for cocaine and likely mediates its reinforcing effects that contribute to significant abuse liability (Ritz et al., 1987;Kuhar et al., 1991;Woolverton and

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“…The measurements of a PET system can be well modeled as independent Poisson random variables y E JRM)<l with mean related to the emission intensity image x E JRNX 1 through an affine transform =Px+r (1) where P E EM x N the detection probability matrix and r E EM X 1 accounts for the presence of scatter and randoms in the data. Here we assume that the data are not precorrected for randoms and that an estimate of r is available.…”

Section: Theory 21 Map Reconstructionmentioning

confidence: 99%

<title>Fast computation of the covariance of MAP reconstructions of PET images</title>

Leahy

1999

SPIE Proceedings

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We develop an approximate theoretical formula for fast computation of the covariance of PET images reconstructed using maximum a posteviori (MAP) estimation. The results assume a Poisson likelihood for the data and a quadratic prior on the image. The covariance for each voxel is computed using 2D FFTs and is a function of a single data dependent parameter. This parameter is computed using a modified backprojection. For a small region of interest ( ROT) , the correlation can be assumed to be locally stationary so that computation of the variance of an ROT can be performed very rapidly. Previous approximate formulae for the variance of MAP estimators have performed poorly in areas of low activity since they do not account for the non-negativity constraints that are routinely used in MAP algorithms. Here a "truncated Gaussian" model is used to compensate for the effect of the non-negativity constraints. Accuracy of the theoretical expressions is evaluated using both Monte Carlo simulations and a multiple-frame 15O water brain study. The Monte Carlo studies show that the truncated Gaussian model is effective in compensating for the effect of the non-negativity constraint. These results also show good agreement between Monte Carlo covariances and the theoretical approximations. The 150-water brain study further confirms the accuracy of the theoretical approximations.

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Optimization of PET activation studies based on the SNR measured in the 3-D Hoffman brain phantom

Cited by 15 publications

References 18 publications

In vivo pharmacology of MDMA and its enantiomers in rhesus monkeys.

In vivo pharmacology of MDMA and its enantiomers in rhesus monkeys.

Effects of Dopamine Transporter Inhibitors on Cocaine Self-Administration in Rhesus Monkeys: Relationship to Transporter Occupancy Determined by Positron Emission Tomography Neuroimaging

<title>Fast computation of the covariance of MAP reconstructions of PET images</title>

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