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ROBUST EXPERIMENTAL DESIGN FOR ESTIMATING MYOCARDIAL BETA ADRENERGIC RECEPTOR CONCENTRATION USING POSITRON EMISSION TOMOGRAPHY

Salinas, Cristian Andres
http://rave.ohiolink.edu/etdc/view?acc_num=case1144088920

Abstract Details

2006, Doctor of Philosophy, Case Western Reserve University, Biomedical Engineering.
Receptor concentration quantification using positron emission tomography (PET) is an effective tool for evaluating brain and heart physiology and pathophysiology because it allows probing the molecular interactions in vivo. A difficulty in this task is the determination of an experimental protocol that leads to precise estimates of the receptor concentration. The problem is even more challenging in heterogeneous populations with varied physiological states. The standard approach for optimizing experimental protocols achieves precise estimates for only a subpopulation of individual with similar physiological states. We present a methodology to design a robust two-injection protocol that provides precise estimates of myocardial Β-adrenergic receptor (Β-AR) concentration in normal and pathologic states. Methods A two-injection protocol of the high affinity Β-AR antagonist [18F]-(S)-fluorocarazolol was designed based on a synthetic population of individuals representing a wide range of Β-AR concentrations. The design figure of merit was calculated for each individual and timing and dosage of ligand injection were optimized to make the worst-case precision least bad. The resultant protocol was applied to pigs before and after chemical sympathectomy which induces Β-AR upregulation. Results In vitro assays on hearts harvested from euthanized pigs demonstrate sympathectomy increases the receptor concentration. Consistent with this, the PET-estimated Β-AR concentrations revealed the increases. Importantly, the precision of the PET estimates of receptor concentration demonstrated high precision in normal and pathologic states. The methodology presented here could be applied to other applications such as dopamine receptor concentration estimation in the brain which can differ from one region to another.
Raymond Muzic (Advisor)
PET experiment design; quantification; beta adrenergic receptors

Recommended Citations

Citations

  • Salinas, C. A. (2006). ROBUST EXPERIMENTAL DESIGN FOR ESTIMATING MYOCARDIAL BETA ADRENERGIC RECEPTOR CONCENTRATION USING POSITRON EMISSION TOMOGRAPHY [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1144088920

    APA Style (7th edition)

  • Salinas, Cristian. ROBUST EXPERIMENTAL DESIGN FOR ESTIMATING MYOCARDIAL BETA ADRENERGIC RECEPTOR CONCENTRATION USING POSITRON EMISSION TOMOGRAPHY. 2006. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1144088920.

    MLA Style (8th edition)

  • Salinas, Cristian. "ROBUST EXPERIMENTAL DESIGN FOR ESTIMATING MYOCARDIAL BETA ADRENERGIC RECEPTOR CONCENTRATION USING POSITRON EMISSION TOMOGRAPHY." Doctoral dissertation, Case Western Reserve University, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=case1144088920

    Chicago Manual of Style (17th edition)

case1144088920
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© 2006, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.