TRD 2: Metabolic Markers Lead Principal investigator: Richard Edden, Professor of Radiology Co-investigators: Peter van Zijl, Peter Barker, Georg Oeltzschner, Jiadi Xu, Hye-Young Heo, Nirbhay Yadav. This TRD will develop biomarkers of brain metabolism, using magnetic resonance spectroscopy (MRS) and chemical exchange-saturation transfer imaging (CEST-MRI). We will develop new editing schedules for multiplexed editing MRS, allowing the simultaneous resolution of several low-concentration metabolites of interest to collaborative projects, including neurotransmitters such as GABA, antioxidants such as glutathione, and neuromodulators such as N- acetylaspartylglutamate. We will combine these methods with spectroscopic imaging readouts and develop multi-spectrum linear combination modeling approached for quantification. Edited CEST approaches, tuning acquisition parameters to improve specificity of detection, CEST fingerprinting, and single-shot z-spectrum approaches will be developed. Deep learning tools for the analysis of these data will also be developed, with a particular focus on the integration of methods, and spectral resolution enhancement and metabolic editing by MRSI-based training of CEST analyses. Acquisition and analysis tools developed under this TRD will be disseminated to collaborative projects and service projects, to establish reproducibility in a new setting, and to the broader community.