Research Article Multisite Kinetic Modeling of 13 C Metabolic MR Using [1- 13 C]Pyruvate Pedro A. Gómez Damián, 1,2,3 Jonathan I. Sperl, 1 Martin A. Janich, 1,4,5 Oleksandr Khegai, 1,5 Florian Wiesinger, 1 Steffen J. Glaser, 5 Axel Haase, 3 Markus Schwaiger, 4 Rolf F. Schulte, 1 and Marion I. Menzel 1 1 GE Global Research, 85748 Garching bei M¨ unchen, Germany 2 Medical Engineering, Tecnol´ ogico de Monterrey, 64849 Monterrey, NL, Mexico 3 Medical Engineering, Technische Universit¨ at M¨ unchen, 85748 Garching bei M¨ unchen, Germany 4 Nuclear Medicine, Technische Universit¨ at M¨ unchen, 81675 Munich, Germany 5 Chemistry, Technische Universit¨ at M¨ unchen, 85748 Garching bei M¨ unchen, Germany Correspondence should be addressed to Marion I. Menzel; menzel@ge.com Received 30 August 2014; Revised 6 November 2014; Accepted 13 November 2014; Published 8 December 2014 Academic Editor: David Maintz Copyright © 2014 Pedro A. G´ omez Dami´ an et al. his is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Hyperpolarized 13 C imaging allows real-time in vivo measurements of metabolite levels. Quantiication of metabolite conversion between [1- 13 C]pyruvate and downstream metabolites [1- 13 C]alanine, [1- 13 C]lactate, and [ 13 C]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 itting the multisite model to time-domain dynamic metabolite data. he results for diferent pyruvate doses were compared with those of diferent 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 diferences 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 diferent signal- to-noise ratio. Pyruvate dose efects observed previously were conirmed and quantiied through metabolic conversion rate values. Parameter interdependency allowed an accurate quantiication and can therefore be useful for monitoring metabolic activity in diferent tissues. 1. Introduction While 13 C 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 sensitiv- ity limit; as through hyperpolarization using DNP followed by rapid dissolution, the 13 C MR signal can be ampliied by more than 10,000-fold [2]. One of the most common and viable agents for in vivo use is [1- 13 C]pyruvate (PYR) [3]. Ater intravenous injection, it is transported to the observed tissue or organ under observation, where it is enzymatically metabolized to its downstream metabolites [1- 13 C]alanine (ALA) by alanine transaminase (ALT), [1- 13 C]lactate (LAC) by lactate dehy- drogenase (LDH), and [ 13 C]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- 13 C]pyruvate-hydrate (PYRH). As part of gluconeogenesis, PYR may also be car- boxylated to oxaloacetate [4]. In order to quantify the metabolic exchange between PYR and its downstream metabolites, MRS data acquired over a certain time period ater injection irst require assignment of Hindawi Publishing Corporation Radiology Research and Practice Volume 2014, Article ID 871619, 10 pages http://dx.doi.org/10.1155/2014/871619