Rapid Quantitative Pharmacodynamic Imaging with Bayesian Estimation.
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.
Department of Psychiatry, Washington University in St. Louis St. Louis, MO, USA.
Jonathan M
JM
Koller
College of Arts and Sciences, Washington University in St. Louis St. Louis, MO, USA.
M Jonathan
MJ
Vachon
Department of Radiology, Washington University in St. Louis St. Louis, MO, USA.
G Larry
GL
Bretthorst
Departments of Psychiatry, Neurology, Radiology, and Neuroscience, Washington University in St. Louis St. Louis, MO, USA.
Kevin J
KJ
Black
Bayesian parameter estimation; PK-PD modeling; pharmacodynamics; pharmacological imaging