title: Restricted maximum likelihood estimation of PET neuroreceptor occupancy in the absence of a reference region.
abstract: OBJECTIVE
  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.
authors.affiliation: CRC-Centre d'Imatge Molecular (CIM), Parc de Recerca Biomèdica de Barcelona, Barcelona 08003, Spain. Joaquim.Radua@iop.kcl.ac.uk
authors.forename: Joaquim
authors.initials: J
authors.lastname: Radua
authors.forename: Santiago
authors.initials: S
authors.lastname: Bullich
authors.forename: Natalia
authors.initials: N
authors.lastname: Lopez
authors.forename: Ana M
authors.initials: AM
authors.lastname: Catafau
mesh_terms: D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D003627:Data Interpretation, Statistical; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D016013:Likelihood Functions; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D012016:Reference Values; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D011984:Sensory Receptor Cells / Q000000981:diagnostic imaging* / Q000378:metabolism*
chemical_list: D019275:Radiopharmaceuticals