T1 values of water, glucose, Glx, and lactate were estimated on the basis of a three-parameter fit of the signal amplitude acquired using a nonlocalized inversion-recovery method with 12 logarithmatically spaced inversion times between 10 and 2560 ms and a TR of 2560 ms (42). The inversion-recovery experiments were performed using an adiabatic inversion pulse to assure homogeneous excitation.

Global T2 measurements were performed with a nonlocalized spin-echo sequence with 12 different echo times between 6 and 400 ms. The decaying signal amplitudes were fit with a monoexponential function in case of labeled glucose, Glx, and lactate and a biexponential function for 2H-labeled water. Note that 2H-2H scalar couplings are on the order of 0.1 to 0.2 Hz and therefore do not significantly influence the T2 estimates of the metabolites, which are in the range of 50 to 100 ms (43).

T1 and T2 relaxation measurements were performed after the metabolite 2H label incorporation reached a steady state, typically between 90 and 150 min following the onset of 2H-labeled substrate administration. T2* relaxation times of water were obtained from the 3D DMI data by measuring the frequency width at half maximum (FWHM) amplitude of the phased absorption resonance line. Under the assumption of a Lorentzian line shape, T2* is calculated as 1/(πFWHM).

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