title: Balancing bias, reliability, noise properties and the need for parametric maps in quantitative ligand PET: [(11)C]diprenorphine test-retest data.
abstract: [(11)C]diprenorphine (DPN) is a non-subtype selective opioid receptor PET ligand with slow kinetics and no region devoid of specific binding. Parametric maps are desirable but have to overcome high noise at the voxel level. We obtained parameter values, parametric map image quality, test-retest reproducibility and reliability (using intraclass correlation coefficients (ICCs)) for conventional spectral analysis and a derived method (rank shaping), compared them with values obtained through sampling of volumes of interest (VOIs) on the dynamic data sets and tested whether smaller amounts of radioactivity injected maintained reliability. Ten subjects were injected twice with either approximately 185 MBq or approximately 135 MBq of [(11)C]DPN, followed by dynamic PET for 90 min. Data were movement corrected with a frame-to-frame co-registration method. Arterial plasma input functions corrected for radiolabelled metabolites were created. There was no overall effect of movement correction except for one subject with substantial movement whose test-retest differences decreased by approximately 50%. Actual parametric values depended heavily on the cutoff for slow frequencies (between 0.0008 s(-1) and 0.00063 s(-1)). Image quality was satisfactory for restricted base ranges when using conventional spectral analysis. The rank shaping method allowed maximising of this range but had similar bias. VOI-based methods had the widest dynamic range between regions. Average percentage test-retest differences were smallest for the parametric maps with restricted base ranges; similarly ICCs were highest for these (up to 0.86) but unacceptably low for VOI-derived VD estimates at the low doses of injected radioactivity (0.24/0.04). Our data can inform the choice of methodology for a given biological problem.
authors.affiliation: MRC Clinical Sciences Centre and Division of Neuroscience, Faculty of Medicine, Imperial College, Hammersmith Hospital, DuCane Road, London, UK. alexander.hammers@csc.mrc.ac.uk
authors.forename: Alexander
authors.initials: A
authors.lastname: Hammers
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Asselin
authors.forename: Federico E
authors.initials: FE
authors.lastname: Turkheimer
authors.forename: Rainer
authors.initials: R
authors.lastname: Hinz
authors.forename: Safiye
authors.initials: S
authors.lastname: Osman
authors.forename: Gary
authors.initials: G
authors.lastname: Hotton
authors.forename: David J
authors.initials: DJ
authors.lastname: Brooks
authors.forename: John S
authors.initials: JS
authors.lastname: Duncan
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Koepp
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D016477:Artifacts; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D004174:Diprenorphine / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D011957:Receptors, Opioid / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D011957:Receptors, Opioid; D004174:Diprenorphine