Isocitrate dehydrogenase IDH mutations in gliomas have ability to produce R-2-hydroxyglutarate (2HG). Directly measuring 2HG using non-invasive MR spectroscopy is an attractive strategy to accurately predict IDH mutation status and provide useful diagnostic and prognostic information. Quantification of 2HG metabolite may have potential advatages to evaluate treatment response in IDH1/2 targeted inhibitor trails . Here we report the optimization of subecho times on GE 3T scanners using phantoms to detect 2HG with the maximum sensitivity. We also evaluated the effect of different refocusing pulses on 2HG sensitivity with and without outer volume suppression (OVS) pulses. Part of these results were demonstrated with in-vivo data. The detection and quantification of hydroxyglutarate (2HG) in IDH1/2 mutated tumors is of clinical interest due to the elevation of 2HG, onco-metabolite, levels. In-vivo MR Spectroscopy can be used to noninvasively measure 2HG as a biomarker for diagnosis of IDH mutations in gliomas as well as to monitor treatment response in patients undergoing IDH1/2 inhibitor trials. The point-resolved spectroscopy (PRESS) technique is a commonly used on clinical systems and it has been shown that optimizations of subecho times (TE1/TE2) [1] increase the sensitivity of 2HG detection on Philips 3T and long TE is the method of choice for 2HG detection [2]. The goal of present work was to optimize subecho times, on 3.0T GE MR 750 scanners, using asymmetric PRESS for optimal 2HG sensitivity and compare these results using different refocusing pulses [3]. The effect of OVS pulses [4] on selection of MRS volume selection was also studied.Experiments were performed both in a MRS phantom (13 mM 2HG, 20mM Glycine, pH 7.2 ) and in-vivo in a 3.0T clinical scanner (GE MR750). 2HG has five protons and the major proton resonance appears at ~2.25ppm [1]. Currently at TE=97ms, the default for Probe-P on GE scanner was 26ms for the first echo time. Due to the default settings on GE scanners, we used (26ms, 71ms) to detect 2HG in patients. Subecho times TE1 and TE2 are varied to find optimal pair using standard reduced flip angle refocusing pulses (5.2ms, 137°, 1.4kHz bandwidth) [3] of PROton Brain Exam using PRESS (PROBE-P). TE1 was increased from 20ms up to 44ms in steps of 6ms and TE2 was increased from 65ms to 89ms in steps of 6ms. Refocusing 167 RF pulse (6.5 ms, 167o, 1.1 kHz bandwidth) [3] were also implemented to replace 137° pulse to test the 2HG sensitivity. Center frequency was set to 2.7ppm (default). The effect of OVS pulses [4] on 2HG multiplet resonances was studied. Data analysis was performed by home build matlab code. 2HG quantification was done using LCmodel fitting software. 2HG basis spectrum was simulated using the GAMMA library with ideal pulses (Simplified Hamiltonian Approach). For (26,71ms) pair used for collecting in-vivo data, 2HG basis set was calculated using with non-ideal pulses and volume localization gradients (Full Hamiltonian Approach).Experimental demonstration of 2HG signal as a function of TE1 and TE2 yielded the largest 2HG signal at the optimal pair of (20,77ms) with 137 pulse (Figure 1A). We also observed that 2HG signal intensity at 2.25ppm for the (26ms, 71ms) pair is similar to the optimal (TE1,TE2) pair (Figure 1B). By replacing 137^o pulse with 167^o RF pulse, the 2HG sensitivity was improved (Figure 2). Effect of OVS pulses has negligible effect on the 2HG signal pattern (Figure 3). Example of mutant IDH glioma was shown in Figure 4. The presence of elevated 2HG peak at 2.25ppm is correlated with the positive IDH mutation. The normal MR voxel spectra do not show any reliable 2HG peak.We found that 2HG can be detected and quantified in-vivo using conventional PRESS sequence. Due to the default settings on GE, currently we used (26, 71)ms subecho times to detect 2HG in patients . Use of reduced flip angle 137^o refocusing pulses lead to slightly different optimal TE1/TE2 pair (20,77)ms compared to previous reports from Choi et al. However slight changes in TE1/TE2 doesn’t change much in the pattern of 2HG major resonance. As we are using the exact Hamiltonian approach, this may not be an issue for 2HG quantification. As expected, we have shown that the use of 167 flip angle refocusing pulses in a PRESS sequence increases the sensitivity for 2HG detection. We expect an increase in SNR as 167° is close to ideal 180° while 137° loses approximately 25% SNR. The slightly lower bandwidth of 167^o doesn’t seem to change pattern. The effect of outer volume suppression pulses does not appear to change the 2HG multiplet pattern as well.