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Robust experiment design for estimating myocardial β adrenergic receptor concentration using PET
Author(s) -
Salinas Cristian,
Muzic Raymond F.,
Ernsberger Paul,
Saidel Gerald M.
Publication year - 2007
Publication title -
medical physics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.473
H-Index - 180
eISSN - 2473-4209
pISSN - 0094-2405
DOI - 10.1118/1.2402585
Subject(s) - population , positron emission tomography , in vivo , biomedical engineering , nuclear medicine , medicine , biology , environmental health , microbiology and biotechnology
Myocardial β adrenergic receptor ( β ‐ 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 β ‐ AR concentration in vivo . An optimal design of the experiment protocol, however, is needed for sufficiently precise estimates of β ‐ AR concentration in a heterogeneous population. Standard methods of optimal design do not account for a heterogeneous population with a wide range of β ‐ 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 β ‐ AR concentration in normal and pathologic states. A two‐injection protocol of the high affinity β ‐ AR antagonist[ F18 ] ‐ ( S ) ‐fluorocarazolol was designed based on a computer‐generated (or synthetic) population incorporating a wide range of β ‐ AR concentrations. Timing and dosage of the ligand injections were optimally designed with minimax criterion to provide the least bad β ‐ 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 β ‐ AR upregulation by chemical sympathectomy. Estimates of β ‐ AR concentration were found by minimizing the difference between the model‐predicted and experimental PET data. With this robust protocol, estimates of β ‐ AR concentration showed high precision in both normal and pathologic states. The increase in β ‐ 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 β ‐ AR concentration in a population with normal and pathologic states. This methodology is applicable in general to optimal estimation of parameters in heterogeneous populations.