title: Cumulative input function method for linear compartmental models and spectral analysis in PET.
abstract: Compartmental modeling and spectral analysis are often used for tracer kinetic modeling in positron emission tomography (PET). The concentrations in kinetic equations are usually considered to be instantaneous, whereas PET data are inherently integrated over time, which leads to uncertainties in the results. A new formalism for kinetic analysis that uses cumulative tracer concentrations and avoids approximating the image-derived input function and PET measurements with midframe instantanous values was developed. We assessed the improvements of the new formalism over the midframe approximation methods for three commonly used radiopharmaceuticals: [(11)C]raclopride, 2'-deoxy-2'-[(18)F]fluoro-D-glucose (FDG), and 3'-deoxy-3'-[(18)F]fluoro-thymidine (FLT). We found that improvements are case dependent and often not negligible. Improvements for determination of binding potential for [(11)C]raclopride ranged from 5% to 25%. Improvements in estimation accuracy of FDG and FLT microparameters ranged up to 25%. On the other hand, estimation of macroparameter K(i)=K(1)k(3)/(k(2)+k(3)) for FDG or FLT did not show significant benefit with the new method; only modest improvement up to 2% was observed. Assessment of the benefits of using new method is far from being exhaustive, but possibly significant improvement was demonstrated. Therefore, we consider the proposed algorithm a necessary component of any kinetic analysis software.
authors.affiliation: Jozef Stefan Institute, Ljubljana, Slovenia. urban.simoncic@ijs.si
authors.forename: Urban
authors.initials: U
authors.lastname: Simoncic
authors.forename: Robert
authors.initials: R
authors.lastname: Jeraj
mesh_terms: D000465:Algorithms; D003342:Corpus Striatum / Q000000981:diagnostic imaging; D015224:Dideoxynucleosides / Q000493:pharmacokinetics; D018491:Dopamine Agonists / Q000493:pharmacokinetics; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006801:Humans; D007700:Kinetics; D016014:Linear Models; D008953:Models, Anatomic; D049268:Positron-Emission Tomography / Q000379:methods*; D020891:Raclopride / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013268:Stimulation, Chemical
chemical_list: D015224:Dideoxynucleosides; D018491:Dopamine Agonists; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D020891:Raclopride; C002854:alovudine
references.citation: J Nucl Med. 2001 Apr;42(4):636-45
references.pmid: 11337554
references.citation: Pharmacol Rev. 1951 Mar;3(1):1-41
references.pmid: 14833874
references.citation: J Neurochem. 1977 May;28(5):897-916
references.pmid: 864466
references.citation: J Nucl Med. 2006 Oct;47(10):1612-21
references.pmid: 17015896
references.citation: Am J Physiol. 1980 Jan;238(1):E69-82
references.pmid: 6965568
references.citation: Ann Neurol. 1979 Nov;6(5):371-88
references.pmid: 117743
references.citation: Mol Imaging Biol. 2002 Jan;4(1):83-9
references.pmid: 14538051
references.citation: Ann Nucl Med. 2003 Sep;17(6):427-34
references.pmid: 14575374
references.citation: J Cereb Blood Flow Metab. 1993 Jan;13(1):15-23
references.pmid: 8417003
references.citation: J Nucl Med. 2005 Feb;46(2):274-82
references.pmid: 15695787
references.citation: Ann Neurol. 1984 Mar;15(3):217-27
references.pmid: 6609679
references.citation: J Nucl Med. 2007 Nov;48(11):1889-96
references.pmid: 17942803
references.citation: J Nucl Med. 2005 Feb;46(2):371-80
references.pmid: 15695799
references.citation: Metabolism. 1998 Apr;47(4):484-92
references.pmid: 9550550
references.citation: Metabolism. 2004 Apr;53(4):483-7
references.pmid: 15045696
references.citation: J Cereb Blood Flow Metab. 1996 Jan;16(1):42-52
references.pmid: 8530554
references.citation: J Comput Assist Tomogr. 2003 Jul-Aug;27(4):597-605
references.pmid: 12886150
references.citation: J Cereb Blood Flow Metab. 1999 May;19(5):560-9
references.pmid: 10326723
references.citation: J Cereb Blood Flow Metab. 2001 Jun;21(6):635-52
references.pmid: 11488533
references.citation: J Nucl Med. 1997 Nov;38(11):1818-23
references.pmid: 9374364