Magnetic resonance fingerprinting has been proposed as a method for undersampling k-space while simultaneously yielding multiparametric tissue maps. In the context of single voxel spectroscopy, fingerprinting can provide a unified framework for parameter estimation. We demonstrate the utility of such a magnetic resonance spectroscopic fingerprinting (MRSF) framework for simultaneously quantifying metabolite concentrations, T and T relaxation times and transmit inhomogeneity for major singlets of N-acetylaspartate, creatine and choline. This is achieved by varying T , T and the flip angle of the first pulse in a PRESS sequence between successive excitations (i.e. successive T values). The need for multiparametric schemes such as MRSF for accurate medical diagnostics is demonstrated with the aid of realistic in vivo simulations; these show that certain schemes lead to substantial increases to the area under receiver operating characteristics of metabolite concentrations, when viewed as classifiers of pathologies. Numerical simulations and phantom and in vivo experiments using several different schedules of variable length demonstrate superior precision and accuracy for metabolite concentrations and longitudinal relaxation, and similar performance for the quantification of transverse relaxation.

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Clinical magnetic resonance spectroscopy (MRS) mainly concerns itself with the quantification of metabolite concentrations. Metabolite relaxation values, which reflect the microscopic state of specific cellular and sub-cellular environments, could potentially hold additional valuable information, but are rarely acquired within clinical scan times. By varying the flip angle, repetition time and echo time in a preset way (termed a schedule), and matching the resulting signals to a pre-generated dictionary an approach dubbed magnetic resonance fingerprintingit is possible to encode the spins' relaxation times into the acquired signal, simultaneously quantifying multiple tissue parameters for each metabolite. Herein, we optimized the schedule to minimize the averaged root mean square error (RMSE) across all estimated parameters: concentrations, longitudinal and transverse relaxation time, and transmitter inhomogeneity. The optimal schedules were validated in phantoms and, subsequently, in a cohort of healthy volunteers, in a 4.5 mL parietal white matter single voxel and an acquisition time under 5 minutes. The average intra-subject, inter-scan coefficients of variation (CVs) for metabolite concentrations, T 1 and T 2 relaxation times were found to be 3.4%, 4.6% and 4.7% in-vivo, respectively, averaged over all major singlets. Coupled metabolites were quantified using the short echo time schedule entries and spectral fitting, and reliable estimates of glutamate+glutamine, glutathione and myo-inositol were obtained.

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