In the post-genomics era movement disorders research is shifting toward more specialized clinical trials that subdivide patients into groups based on molecular characteristics. In other words, personalized medicine promises specialized therapies for each individual by delivering more effective drug treatments, while avoiding or reducing adverse drug reactions. Hereditary spinocerebellar ataxia type 1 (SCA1), a polyglutamine movement disorder, was the first SCA for which the genetic defect was uncovered (1). As potential treatments for SCA1 enter the pipeline, robust, noninvasive biomarkers of cerebral pathology are urgently needed for early diagnosis, monitoring of treatment and post-treatment evaluation. A prior MRS study demonstrated neurochemical alterations in SCA1 using a 4T research scanner (2). With wide availability of 3T and increasing availability of 7T scanners for clinical research and trials, a need arises to establish the added value of the ultra-high field (7T) relative to high field (3T). Therefore, here we compared the sensitivity of single-voxel, short-echo MRS using a FASTMAP+semi-LASER protocol at 3T vs. 7T to distinguish genetically confirmed subjects with SCA1 at early-moderate disease stage from age and gender frequency-matched controls. Specifically, we evaluated the ability of the protocol to make a diagnostic decision on a single subject basis.18 individuals with early-moderate SCA1 (age 50.9 ± 10.2 years, mean ± SD, 8M/10F, Scale for the Assessment and Rating of Ataxia (SARA) score, 9.0 ± 3.5) and 29 age range matched healthy volunteers (53.3 ± 15.1 years, 13M / 16F, SARA, 0.1 ± 0.2) were studied. Two patients were presymptomatic (SARA=0-1). Subjects were scanned at both 3T and 7T (Siemens) on consecutive days. Spectra were acquired from the vermis (10 x 25 x 25 mm³), cerebellar hemisphere (17 x 17 x17 mm³) and pons (16 x 16 x 16 mm³) using a semi-LASER sequence (TR=5s, TE= 26-28ms, NEX=64) with VAPOR water suppression and outer volume saturation (3). Metabolites were quantified with LCModel (4) using the unsuppressed water signal as reference. Only those measured reliably (Cramér Rao lower bounds < 50%, cross correlation coefficients r > -0.5) from more than half of the spectra at a given field strength and subject group were reported. Concentrations were corrected for the amount of CSF present in each VOI. Finally, the quantified metabolites from all brain regions were used as an input to distance-weighted discrimination (DWD) for classification (5). Leave-one-out Cross-Validation (LOOCV) was used to correct for overfitting when estimating the mis-classification rate. Spectra with good signal-to-noise ratio and spectral resolution were consistently obtained from both patients and controls at 3T and 7T (Fig. 1). The spectral quality enabled the quantification of a neurochemical profile consisting of 15 metabolites in the vermis and cerebellar hemisphere and 13 in the pons at 7T (Fig. 2). Concentrations of major metabolites (total NAA (tNAA), total choline (tCho), total creatine (tCr), myo-inositol, Glutamate+Glutamine) obtained at 3T and 7T were strongly correlated (r² = 0.86, p <0.001). Higher myo-inositol and tCr and lower tNAA were detected in patients at both magnetic fields, in agreement with previous findings (2). The projection space plot of the DWD classifier showed a distinct clustering with almost complete separation between SCA1 and controls at both fields, except for two patients who were misclassified at 3T, one of whom was again misclassified at 7T (Fig. 3). The subject who had the smallest SARA among symptomatic patients was incorrectly classified at 3T, but correctly classified at 7T. One presymptomatic patient, who did show neurochemical (high tCr and myo-Inositol and low tNAA) signs of disease was correctly classified with the SCA1 group at both fields, while the other presymptomatic individual who effectively had no signs of disease onset, both from the neurochemical and clinical perspective, was classified as control at both 3T and 7T. In addition, the improved sensitivity and resolution at 7T resulted in a higher significance level for group separation than 3T (7T: t = 9.2, p-value = 4.7e-09; 3T: t = 8.5, p-value = 1.8e-08). Finally, the DWD score significantly correlated with the SARA score for patients pooled with controls at both fields (Spearman r=0.8, p<0.0001). In conclusion, the increased sensitivity at 7T enabled group separation with higher significance and identification of subtle neurochemical alterations in early symptomatic disease stage more robustly than at 3T, while 3T showed great potential by enabling detection of abnormal metabolite levels in an individual in the presymptomatic disease stage. Furthermore, the demonstration of a high correlation between MRS and clinical scores supports a role for the methodology in clinical applications at both magnetic fields.