Covariance of kinetic parameter estimators based on time activity curve reconstructions: preliminary study on 1D dynamic imaging

We provide approximate expressions for the covariance matrix of kinetic parameter estimators based on time activity curve (TAC) reconstructions when TACs are modeled as a linear combination of temporal basis functions such as B-splines. The approximations are useful tools for assessing and optimizing the basis functions for TACs and the temporal bins for data in terms of computation and efficiency. In this paper we analyze a 1D temporal problem for simplicity, and we consider a scenario where TACs are reconstructed by penalized-likelihood (PL) estimation incorporating temporal regularization, and kinetic parameters are obtained by maximum likelihood (ML) estimation. We derive approximate formulas for the covariance of the kinetic parameter estimators using 1) the mean and variance approximations for PL estimators in (Fessler, 1996) and 2) Cramer-Rao bounds. The approximations apply to list-mode data as well as bin-mode data.