ABSTRACTPURPOSEWe quantitatively compared sagittal and transverse echo planar spectroscopic imaging (EPSI) on the quantification of metabolite concentrations with consideration of tissue variation. A quantification strategy is proposed to collect the necessary information for quantification of concentrations in a minimized acquisition time.METHODSSix transverse and six sagittal EPSI data were collected on healthy volunteers. Metabolite concentrations of N‐acetyl‐aspartate (NAA), total creatine (tCr), total choline (tCho), myo‐inositol (mI), and glutamate and glutamine complex (Glx) were quantified using water scaling with partial volume and relaxation correction. Linear regression analysis was performed to extract concentrations in gray matter (GM) and white matter (WM). The inter‐ and intrasubject coefficients of variance (CV) were estimated.RESULTSConcentrations and fitting errors of sagittal and transverse EPSI were at same level. GM to WM contrast of concentrations was found in NAA, tCr, and tCho. The intersubject CVs revealed greater variability in the sagittal EPSI than in the transverse EPSI. The intrasubject CVs of the transverse EPSI were below 5% for NAA, tCr, and tCho.CONCLUSIONWe showed that quantified concentrations of sagittal and transverse EPSI after partial volume correction are comparable and reproducible. The proposed quantification strategy can be conveniently adapted into various MRI protocols.