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Raymond F Muzic

Publications and source records attributed to Raymond F Muzic.

7 recordsLinked to original sources
PubMed2006

Evaluation of objective functions for estimation of kinetic parameters.

There is growing interest in quantitatively analyzing in vivo image data, as this facilitates objective comparisons and measurement of effect. In this regard, people increasingly turn to pharmacokinetic models and estimation of parameters of such models. In this work several parameter estimation methodologies were compared within the context of the most common pharmacokinetic model used in positron emission tomography imaging to describe glucose metabolism and receptor-ligand interactions at tracer concentrations. Simulated data were generated with 1000 realizations at each of 5 different noise levels. Estimates of the kinetic parameters were made for each realization using seven iterative, nonlinear estimation methodologies: ordinary least squares (OLS), weighted least squares (WLS), penalized weighted least squares (PWLS), iteratively reweighted least squares (IRLS), and variations of extended least squares (ELS0, ELS1, ELS3). Additionally, generalized linear least squares (GLLS) was also used. With relatively noise-free data, the iterative nonlinear estimation methods generally produced low-bias, high-precision parameter estimates, whereas with GLLS the bias was more prominent. Greater distinction between the estimation methods was seen at the higher, more realistic noise levels, with ELS and IRLS methods generally achieving better precision than the other methods. At the high noise levels WLS, GLLS, and PWLS yielded parameter estimates with large bias (>200%) for some kinetic parameters. In general, there are more favorable estimator methodologies than the frequently employed WLS. Methods that determine values of weights based on model output--IRLS, ELS0, ELS1 and ELS3--generally perform better than methods that determine values of weights based directly on the experimental data.

Analysis of Variance↗
PubMed2006

Deformable and rigid registration of MRI and microPET images for photodynamic therapy of cancer in mice.

We are investigating imaging techniques to study the tumor response to photodynamic therapy (PDT). Positron emission tomography (PET) can provide physiological and functional information. High-resolution magnetic resonance imaging (MRI) can provide anatomical and morphological changes. Image registration can combine MRI and PET images for improved tumor monitoring. In this study, we acquired high-resolution MRI and microPET 18F-fluorodeoxyglucose (FDG) images from C3H mice with RIF-1 tumors that were treated with Pc 4-based PDT. We developed two registration methods for this application. For registration of the whole mouse body, we used an automatic three-dimensional, normalized mutual information algorithm. For tumor registration, we developed a finite element model (FEM)-based deformable registration scheme. To assess the quality of whole body registration, we performed slice-by-slice review of both image volumes; manually segmented feature organs, such as the left and right kidneys and the bladder, in each slice; and computed the distance between corresponding centroids. Over 40 volume registration experiments were performed with MRI and microPET images. The distance between corresponding centroids of organs was 1.5 +/- 0.4 mm which is about 2 pixels of microPET images. The mean volume overlap ratios for tumors were 94.7% and 86.3% for the deformable and rigid registration methods, respectively. Registration of high-resolution MRI and microPET images combines anatomical and functional information of the tumors and provides a useful tool for evaluating photodynamic therapy.

Animals↗
PubMed2005

PET imaging of myocardial beta-adrenergic receptors with fluorocarazolol: lack of interference by endogenous catecholamines.

beta-Adrenergic receptor (beta-AR) concentration can be measured in vivo using positron emission tomography (PET) and the high-affinity antagonist [18F]-(S)-fluorocarazolol {[18F]-(S)-FCZ}. However, the influence of endogenous catecholamines on the in vivo binding properties of [18F]-(S)-FCZ should be measured to aid in selection of the model used to estimate receptor concentration based on PET data. Herein we addressed the questions "What is the influence of endogenous catecholamines on the [18F]-(S)-FCZ binding in the heart?" and "In what range are the in vivo concentrations of endogenous beta-AR ligands?" In PET studies, 3 drug regimens were used to manipulate the levels of endogenous catecholamines. The time courses of myocardial concentration of [18F]-(S)-FCZ were compared before and after drug administration. In vitro binding assays and computer simulations were performed to complement the in vivo studies. Despite the large changes of endogenous catecholamines, no significant changes were observed in the [18F]-(S)-FCZ myocardial concentration. In vitro assays showed that (S)-FCZ has an affinity for beta-receptors that is 3900 and 9500 times higher than those of norepinephrine (NE) and epinephrine (EPI), respectively. Computer simulations support the hypothesis that the binding affinities relative to ligand concentrations in vivo are sufficient to explain the apparent lack of effect of endogenous catecholamines on [18F]-(S)-FCZ myocardial concentration. Increased levels of catecholamines in the physiological range do not affect the myocardial concentration of [18F]-(S)-FCZ as measured by PET. This lack of effect suggests that the myocardial concentration of NE at the synaptic sites cannot be higher than 300 nM.

Animals↗
PubMed2004

Porous phantoms for PET and SPECT performance evaluation and quality assurance.

UNLABELLED: Characterization of PET and SPECT imaging performance often requires phantoms with complex radionuclide distributions. For example, lesion detection studies use multiple spherical regions of specific target-to-background ratios to simulate cancerous lesions. Such complex distributions are typically created using phantoms with multiple fillable chambers. However, such phantoms are typically difficult and time-consuming to prepare accurately and reproducibly. A new approach using a single-chamber phantom with a porous core can overcome these difficulties. METHODS: Prototypes of two designs of porous core phantoms were produced and evaluated. The "hot spheres" phantom contained a multitude of simulated spherical lesions with diameters ranging from 6.35 to 25.4 mm ("multi-resolution" slice) and with lesion-to-background ratios ranging from 1.6 to 4.4 ("multi-contrast" slice). The "multi-attenuation" phantom consisted of two halves. One half contained a porous core to produce regions of different attenuation but uniform activity. The other half mimicked the NEMA-94 design with cold inserts of different attenuation. RESULTS: Both phantoms produced the expected radionuclide distributions while requiring the preparation of only a single radionuclide solution and with much reduced preparation time. In images taken on clinical PET and SPECT scanners, the porous core structures were found to contribute negligible background noise or artifact. The measured lesion-to-background ratios from the hot spheres phantom differed slightly from calculated values, with the differences attributed mainly to uncertainty in pore diameter. The measured attenuation coefficients from the multi-attenuation phantom agreed well with expected values. However, it was found that trapped air bubbles due to manufacturing defects in the porous core could potentially cause quantitative errors. CONCLUSION: The hot spheres and multi-attenuation porous phantoms exhibited a wide range of imaging features providing thorough tests of lesion detection and of attenuation and scatter correction accuracy. Because the local activity concentration is set by the relative volume of radionuclide solution in the porous core, the quantitative accuracy is limited mainly by mechanical tolerance, and strict quality control during manufacturing is essential. Nonetheless, the single-chamber design of the porous core phantoms is inherently more reproducible and more practical for routine use compared to conventional multi-chamber phantoms.

Equipment Design↗
PubMed2003

Distributed versus compartment models for PET receptor studies.

Although distributed models are generally accepted as being more realistic than compartment models, use of simpler compartment models is pervasive in nuclear medicine applications, particularly in positron emission tomography (PET). Here, we report on comparisons made between distributed and compartment model outputs to address the question of whether differences between them are sufficient to justify distributed models for analysis of PET receptor experiments. For both two- and three-injection experiments, "data" sets were obtained by simulation using a distributed model and a wide range of parameter values. Optimal fits of the compartment model output to these "data" were achieved with three strategies in which values of different groups of parameter were estimated. Compartment model outputs yielded good fits to all the distributed model outputs and the values of the corresponding parameters were in close agreement. Given the temporal resolution typically available with PET, the use of a distributed model has no advantage over a compartment model for PET receptor quantification.

Computer Simulation↗
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↗