Iterative optimal design of PET experiments for estimating beta-adrenergic receptor concentration

Medical & Biological Engineering & Computing
R F MuzicM S Berridge

Abstract

To estimate in vivo myocardial beta-adrenergic receptor concentration with sufficient precision and to reduce the experimental complexities in positron emission tomography (PET), an iterative optimal design method is applied. An initial three-injection protocol, utilising [F-18]-labelled (R)- and (S)-fluorocarazolol and unlabelled (S)-fluorocarazolol, is optimised for ligand dosages and administration times to maximise the precision of all model parameters using the D-optimal criterion. Using this experimental protocol, PET data are collected in porcine studies, and model parameters are estimated. All model parameters are identified with satisfactory precision. The in vivo myocardial beta-receptor concentration is 7.5+/-0.6 pmol x ml(-1), which corresponds to the in vitro result of 10.1+/-1.3 pmol x ml(-1). With more accurate parameter values, a simplified two-injection protocol is optimally designed, utilising only radiolabelled and unlabelled (S)-fluorocarazolol, based on a new criterion to maximise the precision of the beta-receptor concentration. This revised optimum design predicts that the in vivo beta-receptor concentration can be estimated with good precision but reduced experiment complexity.

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Citations

Dec 13, 2005·Annals of Biomedical Engineering·Kwangdeok LeeMarc S Penn
Jun 9, 2007·Medical Physics·Cristian A SalinasGerald M Saidel
Apr 5, 2012·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Dustin W WootenBradley T Christian
Apr 22, 2003·IEEE Transactions on Medical Imaging·Raymond F Muzic, Gerald M Saidel
May 24, 2007·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Jean-Dominique GallezotMarie-Claude Grégoire
Apr 20, 2004·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Bradley T ChristianJogeshwar Mukherjee
Jul 27, 2005·Journal of Cardiovascular Pharmacology·Cristian SalinasPaul Ernsberger
Aug 3, 2013·Cold Spring Harbor Protocols·Scott K LyonsKevin M Brindle

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