Objectives:

1. lp-ntPET finds significant fast dopamine responses to cigarette smoking in sub-regions of the striatum Su Jin Kim1, Jenna M. Sullivan1, Kelly P. Cosgrove1,2, Evan D. Morris1,2 1Yale PET Center, Yale University, New Haven, CT, USA 2Department of Psychiatry, Yale University, New Haven, CT, USA Objectives: To use PET imaging to detect and characterize transient dopamine elevations in the brains of smokers smoking cigarettes. Methods: Three male smokers received a bolus plus constant infusion of [11C]raclopride in two conditions: a baseline and a scan that included smoking two consecutive cigarettes inside the PET scanner. Subjects began smoking 45 minutes after the initial tracer bolus. Event-by-event motion correction was incorporated into reconstruction using data from the Polaris tracking system. Dynamic data were filtered with HYPR (Christian, 2010) to increase the SNR of PET TACs while preserving spatial resolution and relevant temporal behavior. Constrained estimation of dopamine responses by voxel was accomplished with our previously published and validated linearized ntPET (‘lp-ntPET’) model (Normandin, 2012). Ninety minutes of dynamic data were fitted everywhere within an anatomically-based dorsal striatal mask. The operational equation was implemented with basis functions that encode a wide range of dopamine responses. The possible responses were constrained to take-off no earlier than 5 minutes prior to the start of smoking and no later than a latest-allowable time (e.g., 70 min). Only significant responses were retained. Significance was determined by F-test comparing the fit of each voxel-wise TAC with lp-ntPET to its corresponding fit with standard reference model, MRTM (no time-variation in dopamine). [11C]raclopride B a s e l i n e s c a n 2 hours Transmission 2 Cigarette (45min) [11C]raclopride Constraint response starting time 40-60min MRTM lp-ntPET flowchart = Basis function Bi(t) Conclusions: tD=40min tD=50min