RT Journal Article
SR Electronic
T1 Rapid quantitative pharmacodynamic imaging with Bayesian estimation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 017921
DO 10.1101/017921
A1 Jonathan M. Koller
A1 M. Jonathan Vachon
A1 G. Larry Bretthorst
A1 Kevin J. Black
YR 2016
UL http://biorxiv.org/content/early/2016/02/17/017921.abstract
AB We recently described rapid quantitative pharmacodynamic imaging, a novel method for estimating sensitivity of a biological system to a drug. We tested its accuracy in simulated biological signals with varying receptor sensitivity and varying levels of random noise, and presented initial proof-of-concept data from functional MRI (fMRI) studies in primate brain. However, the initial simulation testing used a simple iterative approach to estimate pharmacokinetic-pharmacodynamic (PKPD) parameters, an approach that was computationally efficient but returned parameters only from a small, discrete set of values chosen a priori.Here we revisit the simulation testing using a Bayesian method to estimate the PKPD parameters. This improved accuracy compared to our previous method, and noise without intentional signal was never interpreted as signal. We also reanalyze the fMRI proof-of-concept data. The success with the simulated data, and with the limited fMRI data, is a necessary first step toward further testing of rapid quantitative pharmacodynamic imaging.