Mutual-Information Based Optimal Experimental Design for Hyperpolarized $^{13}$C-Pyruvate MRI

Hyperpolarized (HP) $^{13}$C-Pyruvate MR imaging provides unique information about metabolic alterations indicative of the aggressiveness of certain cancer types. The information content of the HP-MRI data is fundamentally limited by the physics and chemistry of specific processes that take place at an atomic scale during a well-defined chemical reaction. The HP signal (magnetization of pyruvate and lactate) is a fixed resource that is established at the polarizer and naturally decays over time, and cannot be renewed after injection. The signal is further reduced with every radio-frequency excitation by the MR pulse sequence. Therefore, optimal experimental design (OED) for data acquisition is fundamentally important. A key parameter of interest recovered from HP-MRI measurements is the apparent pyruvate-to-lactate exchange rate, $k_{PL}$, for measuring tumor metabolism. This manuscript presents an information-theory-based OED approach that minimizes the uncertainty in the rate parameter, $k_{PL}$, recovered from the HP-MRI measurements. Results suggest that the mutual information-based optimal data acquisition strategy is likely to improve the precision of the measurements. For the particular MRI data examined here, pyruvate and lactate flip angles of 35 and 28 degrees, respectively, were the best choice in terms of accuracy and precision of the parameter recovery. Moreover, the recovery of rate parameter $k_{PL}$ from the data generated from the high-fidelity model highlights the influence of diffusion and strength of vascular source on the recovered rate parameter. Since the existing pharmacokinetic models for HP-MRI do not account for spatial variation, the optimized design parameters may not be fully optimal in a more general 3D setting.