Open AccessA reference tissue forward model for improved PET accuracy using within-scan displacement studies
Author(s) -
Joseph B. Mandeville,
Michael A Levine,
John Arsenault,
Wim Vanduffel,
Bruce R. Rosen,
Christin Y. Sander
Publication year - 2021
Publication title -
journal of cerebral blood flow and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.167
H-Index - 193
eISSN - 1559-7016
pISSN - 0271-678X
DOI - 10.1177/0271678x211065212
Subject(s) - binding potential , nonhuman primate , computer science , nuclear medicine , positron emission tomography , artificial intelligence , medicine , biology , evolutionary biology
We report a novel forward-model implementation of the full reference tissue model (fFTRM) that addresses the fast-exchange approximation employed by the simplified reference tissue model (SRTM) by incorporating a non-zero dissociation time constant from the specifically bound compartment. The forward computational approach avoided errors associated with noisy and nonorthogonal basis functions using an inverse linear model. Compared to analysis by a multilinear single-compartment reference tissue model (MRTM), fFTRM provided improved accuracy for estimation of binding potentials at early times in the scan, with no worse reproducibility across sessions. To test the model's ability to identify small focal changes in binding potential using a within-scan challenge, we employed a nonhuman primate model of focal dopamine release elicited by deep brain microstimulation remote to ventral striatum (VST) during imaging by simultaneous PET and fMRI. The new model reported an unambiguously lateralized response in VST consistent with fMRI, whereas the MRTM-derived response was not lateralized and was consistent with simulations of model bias. The proposed model enabled better accuracy in PET [ 11 C]raclopride displacement studies and may also facilitate challenges sooner after injection, thereby recovering some sensitivity lost to radioactive decay of the PET tracer.