Measurement of Reaction Rates In Vivo Using Magnetization Transfer Techniques

Abstract

The knowledge of reaction rates, in addition to the absolute concentrations of metabolites, provides important information for a deeper understanding of physiological and pathological processes. In vivo NMR offers the unique possibility to determine, by magnetization transfer, reaction rates and fluxes noninvasively and without disturbing the chemical equilibrium. Several magnetization transfer methods, such as saturation transfer, inversion transfer, inversion recovery and two-dimensional exchange spectroscopy, have been developed to date and are dealt with, both from a theoretical as well as practical point of view. A general mathematical solution for a first-order reaction system with multiple exchanging sites is formulated. The hardware requirements, problems associated with inhomogeneous radiofrequency excitations, localization techniques and extraction of kinetic parameters from experimental data sets are discussed. The different magnetization transfer methods are compared in terms of measuring time, quality of information obtained, applicability, etc. Finally, the potential, limits, and problems in interpreting the experimental data are disclosed on the basis of selected examples, such as phosphocreatine kinase, F₁F₀ ATP synthase, adenylate kinase, membrane transport, etc. It is concluded that important information concerning the metabolism and function of an organ may be obtained by magnetization transfer methods in a most direct way.