PROJECT SUMMARY/ABSTRACT Proton magnetic resonance spectroscopy (1H MRS) and spectroscopic imaging (MRSI) allow noninvasive study of brain chemistry. However, subject motion remains a major obstacle in MRS, especially in motion-prone populations such as children, the elderly, and patients with movement disorders. Motion results in inaccurate localization and degrades MRS spectral quality. Most of these effects cannot be corrected retroactively, and must be corrected prospectively (i.e. in real-time). In the brain, existing prospective motion-corrected MRS sequences are currently limited to a handful of research centers and are not widely used. In the spinal cord, prospective motion and shim correction has not been reported. The main objective of this application is to develop fully automated, high performance, motion-corrected MRS sequences for the brain and spinal cord, that are also easy to share (no additional external hardware needed) with other institutions and easy to use. Our specific aims are as follows. In Aim 1A, we will develop improved brain navigators that are faster and less sensitivity to B0 inhomogeneities, and will allow adjustment of 2nd order shims in the MRS voxel at 3T and 7T. In Aim 1B, we will develop prospective motion correction in the spinal cord at 3T and 7T. In Aim 2, we will fully automate the sequence workflow to allow “push-button” acquisition of reproducible, high quality MRS data, even by non-MRS experts. In Aim 3, we will assess the performance of techniques developed in Aims 1 and 2 in real- life conditions in healthy volunteers (children, young and elderly adults) and in children with mucopolysaccharidosis type I, adrenoleukodystrophy and Friedreich ataxia. We will initially develop these new techniques on Siemens scanners, with the goal of translating them to other manufacturers in the next funding period. We expect that “push-button” data acquisition together with prospective motion correction will remove remaining obstacles for acquisition of MRS data with consistently high quality. Both improving spectral quality as a whole and decreasing the variability in spectral quality are key for reliable MRS measurements. With improved reliability and ease of use, the full potential of brain and spinal cord MRS will be widely available for upcoming clinical studies and gene therapy trials.