%0 Journal Article
%T Multisite Kinetic Modeling of 13C Metabolic MR Using [1-13C]Pyruvate
%A Pedro A. G¨®mez Dami¨˘n
%A Jonathan I. Sperl
%A Martin A. Janich
%A Oleksandr Khegai
%A Florian Wiesinger
%A Steffen J. Glaser
%A Axel Haase
%A Markus Schwaiger
%A Rolf F. Schulte
%A Marion I. Menzel
%J Radiology Research and Practice
%D 2014
%I Hindawi Publishing Corporation
%R 10.1155/2014/871619
%X Hyperpolarized 13C imaging allows real-time in vivo measurements of metabolite levels. Quantification of metabolite conversion between [1-13C]pyruvate and downstream metabolites [1-13C]alanine, [1-13C]lactate, and [13C]bicarbonate can be achieved through kinetic modeling. Since pyruvate interacts dynamically and simultaneously with its downstream metabolites, the purpose of this work is the determination of parameter values through a multisite, dynamic model involving possible biochemical pathways present in MR spectroscopy. Kinetic modeling parameters were determined by fitting the multisite model to time-domain dynamic metabolite data. The results for different pyruvate doses were compared with those of different two-site models to evaluate the hypothesis that for identical data the uncertainty of a model and the signal-to-noise ratio determine the sensitivity in detecting small physiological differences in the target metabolism. In comparison to the two-site exchange models, the multisite model yielded metabolic conversion rates with smaller bias and smaller standard deviation, as demonstrated in simulations with different signal-to-noise ratio. Pyruvate dose effects observed previously were confirmed and quantified through metabolic conversion rate values. Parameter interdependency allowed an accurate quantification and can therefore be useful for monitoring metabolic activity in different tissues. 1. Introduction While 13C magnetic resonance spectroscopy (MRS) has been utilized for in vivo imaging and spectroscopy of metabolism [1] for a long time, only the development of dynamic nuclear polarization (DNP) helped to overcome the inherent sensitivity limit; as through hyperpolarization using DNP followed by rapid dissolution, the 13C MR signal can be amplified by more than 10,000-fold [2]. One of the most common and viable agents for in vivo use is 1-13C]pyruvate (PYR) [3]. After intravenous injection, it is transported to the observed tissue or organ under observation, where it is enzymatically metabolized to its downstream metabolites 1-13C]alanine (ALA) by alanine transaminase (ALT), 1-13C]lactate (LAC) by lactate dehydrogenase (LDH), and 13C]bicarbonate (BC) by pyruvate dehydrogenase (PDH) to varying extent, depending on tissue type and predominant metabolic activity. At the same time PYR is in chemical exchange with 1-13C]pyruvate-hydrate (PYRH). As part of gluconeogenesis, PYR may also be carboxylated to oxaloacetate [4]. In order to quantify the metabolic exchange between PYR and its downstream metabolites, MRS data acquired over a certain
%U http://www.hindawi.com/journals/rrp/2014/871619/