![]() Unsuppressed water scans were acquired from the same VOI for metabolite quantification and eddy current corrections using the same parameters as water suppressed spectra. Water suppression was performed using variable power with optimized relaxation delays (VAPOR) and outer volume suppression techniques ( 19). For 8 subjects, the MEGA-PRESS acquisition was also performed in the contralateral region outside the visible lesions. The final spectra were calculated by subtracting the spectra acquired at the edit-on and edit-off conditions. To evaluate the editing efficiency, two additional sets of spectra were acquired with editing pulse for the edit-on condition applied at 2.03 ppm and 2.16 ppm in one subject. PRESS spatial localization utilized a 90° Hamming-filtered sinc pulse (duration = 2.32 ms, bandwidth = 3.83 kHz) and two 180° mao pulses (duration = 5.80 ms, bandwidth = 1 kHz). The editing pulse (single-banded 180-degree Shinnar-Le-Roux duration = 19.2 ms bandwidth = 62 Hz) was applied at 1.9 ppm for the edit-on condition and at 7.5 ppm for the edit-off condition, in an interleaved fashion (128 pairs of scans, scan time = 8.5 minutes). MR spectra were acquired with a single-voxel spectral editing MEGA-PRESS sequence ( 18) using previously described procedures and parameters ( T R = 2 s, T E = 68 ms, T E1 = 13.08 ms, T E2 = 54.92 ms, VOI > 6 cm 3) ( 16). 3D FLAIR images (field-of-view = 255 × 255 × 144 mm 3, resolution: 1.0 × 1.0 × 1.1 mm 3, T R/ T E = 5000/399 ms, scan time = 5.02 minutes) were acquired to position the spectroscopic VOI in the glioma (hyper-intense region in the images). In vivo experiments, as well as simulations, allowed us to reliably assess the presence of cystathionine in the MR spectra of participants with glioma, and to investigate possible improvements in the acquisition strategy for an optimal detection and quantification of this metabolite.Īcquisitions were performed using a 3 T whole-body system (MAGNETOM Verio, Siemens, Erlangen, Germany) equipped with a 32-channel receive-only head coil. ![]() In this work, we report further technical details regarding the measurement of cystathionine in human brain glioma in vivo with edited 1H MRS at 3 T. Recently, we reported the detection of cystathionine using edited MRS, and explored the clinical utility of noninvasive cystathionine quantification in tumors, showing evidence of an association between cystathionine accumulation and 1p/19q codeletion in gliomas with IDH mutations ( 17). Edited MRS has been used in a number of studies to measure 2-hydroxyglutarate (2HG), a noninvasive marker of mutations in isocitrate dehydrogenase 1 and 2 genes ( IDH½) in gliomas ( 15, 16). Abnormal accumulation of cystathionine in breast cancer was also reported ( 14), and cystathionine was suggested to be a novel oncometabolite possibly contributing to drug resistance in cancer cells.Ībnormal cancer cell metabolism drives the accumulation of certain metabolites that may not be detected reliably using conventional MRS, due to the low concentration and the overlap with other metabolites. In general, the average cystathionine level in higher grade gliomas (II/III, III/IV, IV) was higher relative to low grade gliomas (II), with no genetic information provided ( 13). In particular, tumors of glial origin showed the highest cystathionine concentrations, suggesting that cystathionine is preferentially synthesized in glial cells ( 6). Higher cystathionine levels in brain tumors compared to normal tissue were reported previously from ex vivo tissue analysis ( 6, 13). The significance of variable cystathionine concentration in the brain is not known, and pharmacological studies have suggested a potential role as a neuromodulator ( 5, 12). Significant regional differences were observed within the brain ( 8– 10), with the lowest concentration found in the cerebellum and cortex, and with the highest concentration found in the thalamus, ranging from 4.71 to 55.34 nmol/mg protein ( 11). The presence of cystathionine at low concentration was reported in normal human brain tissue ex vivo ( 6), and its concentration was found to be higher in the brain than in other organs ( 7). In contrast, while the importance of cystathionine for the normal functioning of the brain was recognized several decades ago ( 5), the precise role of this amino acid in either healthy or diseased brain is still not clear. Decrease of glutathione levels in the brain induced by oxidative stress and elevated homocysteine levels in plasma and cerebrospinal fluid were suggested to play key roles in the pathogenesis of neurodegenerative diseases ( 1– 4). ![]() ![]() Cystathionine is synthesized from homocysteine by the transsulfuration pathway, and is an immediate precursor of cysteine and glutathione, a major antioxidant ( 1).
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