In vivo measurement of apparent diffusion coefficients of hyperpolarized ¹³C-labeled metabolites

The combination of hyperpolarized MRS with diffusion weighting (dw) allows for determination of the apparent diffusion coefficient (ADC), which is indicative of the intra- or extracellular localization of the metabolite. Here, a slice-selective pulsed-gradient spin echo sequence was implemented to acquire a series of dw spectra from rat muscle in vivo to determine the ADCs of multiple metabolites after a single injection of hyperpolarized [1-¹³C]pyruvate. An optimal control optimized universal-rotation pulse was used for refocusing to minimize signal loss caused by B₁ imperfections. Non-dw spectra were acquired interleaved with the dw spectra and these were used to correct for signal decay during the acquisition as a result of T₁ decay, pulse imperfections, flow etc. The data showed that the ADC values for [1-¹³C]lactate (0.4-0.7μm²/ms) and [1-¹³C]alanine (0.4-0.9μm²/ms) were about a factor of two lower than the ADC of [1-¹³C]pyruvate (1.1-1.5μm²/ms). This indicates a more restricted diffusion space for the former two metabolites consistent with lactate and alanine being intracellular. The higher ADC for pyruvate (similar to the proton ADC) reflected that the injected substance was not confined inside the muscle cells but also present extracellular.