Positron emission tomography kinetic modeling algorithms for small animal dopaminergic system imaging

Small animal positron emission tomography (PET) imaging allows in vivo quantification of lesion- or treatment-induced neurochemical changes in animal models of disease. Important for quantification are the kinetic modeling methods used to determine biologically-relevant parameters of tracer-tissue interaction. In this work, we evaluate modeling algorithms for the dopaminergic tracers (11)C-dihydrotetrabenazine (DTBZ), (11)C-methylphenidate (MP), and (11)C-raclopride (RAC), used to image the dopaminergic system in the unilateral 6-hydroxydopamine lesioned rat model of Parkinson's disease. For the presynaptic tracers, PET measures are compared with autoradiographic binding measurements using DTBZ and [(3)H]WIN 35,428 (WIN). We independently developed a new variant of the tissue-input Logan graphical modeling method, and compared its performance with the simplified Logan graphical method and the simplified reference tissue with basis functions method (SRTM), for region of interest (ROI) averaged time activity curves (TACs) and parametric imaging. The modified graphical method was found to be effectively unbiased by target tissue noise and has advantages for parametric imaging, while all tested methods were equivalent for ROI-averaged data.