MR spectroscopic imaging (MRSI) can be used to quantify an extended brain metabolic profile but is confounded by changes in tissue water levels due to disease. To develop a fast absolute quantification method for metabolite concentrations combining whole-brain MRSI with echo-planar time-resolved imaging (EPTI) relaxometry in individuals with glioma and healthy individuals. In this prospective study performed from August 2022 to August 2023, using internal water as concentration reference, the MRSI-EPTI quantification method was compared with the conventional method using population-average literature relaxation values. Healthy participants and participants with mutant IDH1 gliomas underwent imaging at 3 T with a 32-channel coil. Real-time navigated adiabatic spiral three-dimensional MRSI scans were acquired in approximately 8 minutes and reconstructed with a super-resolution pipeline to obtain brain metabolic images at 2.4-mm isotropic resolution. High-spatial-resolution multiparametric EPTI was performed in 3 minutes, with 1-mm isotropic resolution, to correct the relaxation and proton density of the water reference signal. Bland-Altman analysis and the Wilcoxon signed rank test were used to compare absolute quantifications from the proposed and conventional methods. Six healthy participants (four male; mean age, 37 years ± 11 [SD]) and nine participants with glioma (six male; mean age, 41 years ± 15; one with wild-type IDH1 and eight with mutant IDH1) were included. In healthy participants, there was good agreement (+4% bias) between metabolic concentrations derived using the two methods, with a CI of plus or minus 26%. In participants with glioma, there was large disagreement between the two methods (+39% bias) and a CI of plus or minus 55%. The proposed quantification method improved tumor contrast-to-noise ratio (median values) for total N-acetyl-aspartate (EPTI: 0.541 [95% CI: 0.217, 0.910]; conventional: 0.484 [95% CI: 0.199, 0.823]), total choline (EPTI: 1.053 [95% CI: 0.681, 1.713]; conventional: 0.940 [95% CI: 0.617, 1.295]), and total creatine (EPTI: 0.745 [95% CI: 0.628, 0.909]; conventional: 0.553 [95% CI: 0.444, 0.828]) (P = .03 for all). The whole-brain MRSI-EPTI method provided fast absolute quantification of metabolic concentrations with individual-specific corrections at 2.4-mm isotropic resolution, yielding concentrations closer to the true value in disease than the conventional literature-based corrections. © RSNA, 2024 Supplemental material is available for this article.