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Title: Robust experiment design for estimating myocardial {beta} adrenergic receptor concentration using PET

Abstract

Myocardial {beta} adrenergic receptor ({beta}-AR) concentration can substantially decrease in congestive heart failure and significantly increase in chronic volume overload, such as in severe aortic valve regurgitation. Positron emission tomography (PET) with an appropriate ligand-receptor model can be used for noninvasive estimation of myocardial {beta}-AR concentration in vivo. An optimal design of the experiment protocol, however, is needed for sufficiently precise estimates of {beta}-AR concentration in a heterogeneous population. Standard methods of optimal design do not account for a heterogeneous population with a wide range of {beta}-AR concentrations and other physiological parameters and consequently are inadequate. To address this, we have developed a methodology to design a robust two-injection protocol that provides reliable estimates of myocardial {beta}-AR concentration in normal and pathologic states. A two-injection protocol of the high affinity {beta}-AR antagonist [{sup 18}F]-(S)-fluorocarazolol was designed based on a computer-generated (or synthetic) population incorporating a wide range of {beta}-AR concentrations. Timing and dosage of the ligand injections were optimally designed with minimax criterion to provide the least bad {beta}-AR estimates for the worst case in the synthetic population. This robust experiment design for PET was applied to experiments with pigs before and after {beta}-AR upregulation by chemical sympathectomy. Estimates ofmore » {beta}-AR concentration were found by minimizing the difference between the model-predicted and experimental PET data. With this robust protocol, estimates of {beta}-AR concentration showed high precision in both normal and pathologic states. The increase in {beta}-AR concentration after sympathectomy predicted noninvasively with PET is consistent with the increase shown by in vitro assays in pig myocardium. A robust experiment protocol was designed for PET that yields reliable estimates of {beta}-AR concentration in a population with normal and pathologic states. This methodology is applicable in general to optimal estimation of parameters in heterogeneous populations.« less

Authors:
; ; ;  [1];  [2];  [2];  [2]
  1. Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106 (United States)
  2. (United States)
Publication Date:
OSTI Identifier:
20853905
Resource Type:
Journal Article
Resource Relation:
Journal Name: Medical Physics; Journal Volume: 34; Journal Issue: 1; Other Information: DOI: 10.1118/1.2402585; (c) 2007 American Association of Physicists in Medicine; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ACCURACY; AUTONOMIC NERVOUS SYSTEM; BIOCHEMISTRY; BIOPHYSICS; DESIGN; FLUORINE 18; FLUORODEOXYGLUCOSE; HEART FAILURE; IN VITRO; IN VIVO; LIGANDS; MYOCARDIUM; POSITRON COMPUTED TOMOGRAPHY; RECEPTORS; SURGERY; SWINE

Citation Formats

Salinas, Cristian, Muzic, Raymond F. Jr., Ernsberger, Paul, Saidel, Gerald M., Radiology, Oncology, Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, Nutrition, Pharmacology, and Neuroscience, Case Western Reserve University, Cleveland, Ohio 44106, and Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106. Robust experiment design for estimating myocardial {beta} adrenergic receptor concentration using PET. United States: N. p., 2007. Web. doi:10.1118/1.2402585.
Salinas, Cristian, Muzic, Raymond F. Jr., Ernsberger, Paul, Saidel, Gerald M., Radiology, Oncology, Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, Nutrition, Pharmacology, and Neuroscience, Case Western Reserve University, Cleveland, Ohio 44106, & Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106. Robust experiment design for estimating myocardial {beta} adrenergic receptor concentration using PET. United States. doi:10.1118/1.2402585.
Salinas, Cristian, Muzic, Raymond F. Jr., Ernsberger, Paul, Saidel, Gerald M., Radiology, Oncology, Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, Nutrition, Pharmacology, and Neuroscience, Case Western Reserve University, Cleveland, Ohio 44106, and Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106. Mon . "Robust experiment design for estimating myocardial {beta} adrenergic receptor concentration using PET". United States. doi:10.1118/1.2402585.
@article{osti_20853905,
title = {Robust experiment design for estimating myocardial {beta} adrenergic receptor concentration using PET},
author = {Salinas, Cristian and Muzic, Raymond F. Jr. and Ernsberger, Paul and Saidel, Gerald M. and Radiology, Oncology, Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106 and Nutrition, Pharmacology, and Neuroscience, Case Western Reserve University, Cleveland, Ohio 44106 and Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106},
abstractNote = {Myocardial {beta} adrenergic receptor ({beta}-AR) concentration can substantially decrease in congestive heart failure and significantly increase in chronic volume overload, such as in severe aortic valve regurgitation. Positron emission tomography (PET) with an appropriate ligand-receptor model can be used for noninvasive estimation of myocardial {beta}-AR concentration in vivo. An optimal design of the experiment protocol, however, is needed for sufficiently precise estimates of {beta}-AR concentration in a heterogeneous population. Standard methods of optimal design do not account for a heterogeneous population with a wide range of {beta}-AR concentrations and other physiological parameters and consequently are inadequate. To address this, we have developed a methodology to design a robust two-injection protocol that provides reliable estimates of myocardial {beta}-AR concentration in normal and pathologic states. A two-injection protocol of the high affinity {beta}-AR antagonist [{sup 18}F]-(S)-fluorocarazolol was designed based on a computer-generated (or synthetic) population incorporating a wide range of {beta}-AR concentrations. Timing and dosage of the ligand injections were optimally designed with minimax criterion to provide the least bad {beta}-AR estimates for the worst case in the synthetic population. This robust experiment design for PET was applied to experiments with pigs before and after {beta}-AR upregulation by chemical sympathectomy. Estimates of {beta}-AR concentration were found by minimizing the difference between the model-predicted and experimental PET data. With this robust protocol, estimates of {beta}-AR concentration showed high precision in both normal and pathologic states. The increase in {beta}-AR concentration after sympathectomy predicted noninvasively with PET is consistent with the increase shown by in vitro assays in pig myocardium. A robust experiment protocol was designed for PET that yields reliable estimates of {beta}-AR concentration in a population with normal and pathologic states. This methodology is applicable in general to optimal estimation of parameters in heterogeneous populations.},
doi = {10.1118/1.2402585},
journal = {Medical Physics},
number = 1,
volume = 34,
place = {United States},
year = {Mon Jan 15 00:00:00 EST 2007},
month = {Mon Jan 15 00:00:00 EST 2007}
}