A procedure to prevent the formation of image and spectral Nyquist ghosts in echo-planar spectroscopic imaging is introduced. It is based on a novel Cartesian center-out echo-planar spectroscopic imaging trajectory, referred to as EPSICO, and combined with a correction of the gradient-echo phase and time shifts. Processing of homogenous sets of forward and reflected echoes is no longer necessary, resulting in an optimized spectral width. The proposed center-out trajectory passively prevents the formation of Nyquist ghosts by privileging the acquisition of the center k-space line with forward echoes at the beginning of an echo-planar spectroscopic imaging dwell time and by ensuring that all k-space lines and their respective complex conjugates are acquired at equal time intervals. With the proposed procedure, concentrations of N-acetyl aspartate, creatine, choline, glutamate, and myo-inositol were reliably determined in human white matter at 3 T. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.