Model Free Approach to Kinetic Analysis of Real-Time Hyperpolarized 13C Magnetic Resonance Spectroscopy Data

• DOI: 10.1371/journal.pone.0071996
• Publication Date: 2013-09-04T21:12:33Z
• Authors: Deborah K. Hill; Matthew R. Orton; Erika Mariotti; Jessica K. R. Boult; Rafal Panek; Maysam Jafar; Harold G. Parkes; Yann Jamin; Maria Falck Miniotis; Nada M. S. Al-Saffar; Mounia Beloueche-...; Simon P. Robinson; Martin O. Leach; Yuen-Li Chung; Thomas R. Eykyn
• Keywords: Hyperpolarization

Real-time detection of the rates metabolic flux, or exchange endogenous enzymatic reactions, is now feasible in biological systems using Dynamic Nuclear Polarization Magnetic Resonance. Derivation reaction rate kinetics from this technique typically requires multi-compartmental modeling dynamic data, and results are therefore model-dependent prone to misinterpretation. We present a model-free formulism based on ratio total areas under curve (AUC) injected product metabolite, for example pyruvate lactate. A theoretical framework support novel analysis approach described, demonstrates that AUC proportional forward constant k. show strongly correlates with k whole cell vitro experiments across range cancer lines, detects response cells treated pan-class I PI3K inhibitor GDC-0941 comparable greater sensitivity. The same result seen vivo tumor xenograft-bearing mice, control tumors following drug treatment dichloroacetate. An important finding area independent both input function any other pathways arising metabolite. This provides robust clinically relevant alternative kinetic model-based measurements clinical translation hyperpolarized 13C imaging humans, where measurement can be problematic.