A volume-localized, two-dimensional NMR method for lactate-edited diffusion coefficient measurements using zero-quantum coherence-transfer spectroscopy

Abstract

The noninvasive measurement of the self-diffusion coefficient of biological metabolites would be a powerful tool for evaluating the microenvironment of these compounds. The molecular displacement of in vivo metabolites is a complex function of, for example, cellular compartment size, active and passive transport across cell membranes, and immobilization due to adsorption processes (I), which are in turn associated with the biological activities of the cell and its immediate surroundings. Consequently, the study of metabolite diffusion would be important for understanding these processes and may prove useful in characterizing the disease state of a tissue or an organ. Diffusion-coefficient measurements of in vivo metabolites have recently been initiated using spin-echo NMR spectroscopy pulse sequences which contain diffusion-sensitive pulsed field gradients (1, 2). In addition to the classical Stejskal-Tanner spin-echo method (3), the stimulated-echo (STE) sequence (4), shown in Fig. 1, has been found to be particularly useful for applications to metabolites, which frequently have short T, but relatively long T, relaxation times. For the STE sequence in Fig. 1, molecular diffusion in the presence of the pulsed field gradients results in an attenuation of the echo signal amplitude given by