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Medical Physics / Volume 38 / Issue 5 / RADIATION IMAGING PHYSICS

Med. Phys. 38, 2558 (2011); http://dx.doi.org/10.1118/1.3578606 (5 pages)

Restricted maximum likelihood estimation of PET neuroreceptor occupancy in the absence of a reference region

Joaquim Radua

CRC-Centre d’Imatge Molecular (CIM), Parc de Recerca Biomèdica de Barcelona, Barcelona 08003, Spain; Institute of Psychiatry, King’s College London, London SE5 8AF, United Kingdom; and FIDMAG, CIBERSAM, Sant Boi de Llobregat 08830, Spain

Santiago Bullich

CRC-Centre d’Imatge Molecular (CIM), Parc de Recerca Biomèdica de Barcelona, Barcelona 08003, Spain

Natalia Lopez

CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Grupo de Imagen Biomédica de la Universidad de Barcelona (GIB-UB), Barcelona 08036, Spain

Ana M. Catafau

Discovery Medicine, Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline, Barcelona 08019, Spain and Barcelona Imaging Group SL, Barcelona 08193, Spain

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(Received 1 December 2010; accepted 25 March 2011; revised 25 March 2011; published online 5 May 2011)

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Purpose: Brain positron emission tomography (PET) is a useful technique for estimating the neuroreceptor occupancy of a drug in vivo. In the absence of a reference region, occupancy can be obtained from an “occupancy plot” with ordinary least squares (OLS) regression. However, OLS has been found to return inefficient occupancy estimations. The aim of this study was to improve the accuracy and precision of occupancy estimations.
Methods: Within a simulation framework, the efficiency of several model II regression approaches (accounting for error in the independent variable) and restricted maximum likelihood estimator (REML, specifically modeling the drug occupancy) was compared to the efficiency of OLS.
Results: Efficiency of REML was 171%–210% the efficiency of OLS, while model II regressions were found to be substantially less efficient.
Conclusions: In the absence of a reference region, it is recommended to use occupancy REML instead of OLS in order to increase the validity of occupancy estimations and thus decrease the costs of PET research.

© 2011 American Association of Physicists in Medicine

ACKNOWLEDGMENT

The authors have no competing interests to declare.

Article Outline

  1. INTRODUCTION
  2. MATERIALS AND METHODS
    1. Theory
    2. Simulations
    3. Efficiency assessment
  3. RESULTS
  4. DISCUSSION
Digital Object Identifier
http://dx.doi.org/10.1118/1.3578606

KEYWORDS and PACS

Keywords

brain, drugs, least squares approximations, maximum likelihood estimation, neurophysiology, positron emission tomography, restricted maximum likelihood estimation, neuroreceptor occupancy, occupancy plot, positron emission tomography, reference region

PACS

PUBLICATION DATA

ISSN

0094-2405 (print)  

Publisher

$abstract.society.value is a Member of CrossRef American Association of Physicists in Medicine

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Medical Physics is an official science journal of the AAPM and of the COMP/CCPM/IOMP
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