Evaluation of two graphical approaches for regional analysis and parametric mapping of dynamic [<sup>18</sup>F]FDDNP PET studies

Abstract

Positron emission tomography (PET) with 2-(1-{6-[(2-[ <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">18</sup> F]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malo-nonitrile ([ <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">18</sup> F]FDDNP) has been used for in vivo imaging of ?-amyloid plaques and neurofibrillary tangles, the neuropathological hallmarks of Alzheimer's disease (AD). Due to its simplicity as compared to other reference tissue modeling methods, Logan graphical analysis with cerebellum as reference region has been primarily used to estimate the distribution volume ratio (DVR) of [ <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">18</sup> F]FDDNP as a measure of amyloid burden and tau deposition in human brain. However, it sometimes produces spurious parametric DVR images when the noise level is high and the total scan duration is shortened. The purpose of this study was to characterize a new graphical analysis method against the Logan analysis for the estimation of the DVR estimates at regional and voxel-wise levels, using the cerebellum as the reference region. Effects on regional (frontal and medial temporal) DVR estimates and parametric DVR images obtained by the Logan and the new approaches using data in different time intervals and total scan durations (35-125 min, 65-125 min, 85-125 min, and 45-65 min) were investigated and compared to the reference values derived by the Logan analysis for the time interval 35-125 min. For regional analyses, with the exception of DVR estimates of medial temporal in ADs obtained by the Logan analysis for the interval 85-125 min, no significant difference was observed for all paired comparisons with the reference values. Logan DVR images generated using shortened time intervals (85-125 min and 45-65 min) were extremely noisy. In contrast, the new method produced DVR images comparable to the reference images even when shortened time intervals were used. The new method provides more reliable regional DVR estimates and less noisy parametric images, indicating that it is an improvement over the Logan graphical analysis for analyzing [ <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">18</sup> F]FDDNP PET data.