Purpose: To report the technical aspects of noninvasive detection of cystathionine in human brain glioma with edited MRS, and to investigate possible further acquisition improvements for robust quantification of this metabolite. Methods: In vivo 1H MR spectra were acquired at 3 T in 15 participants with an isocitrate dehydrogenase-mutated glioma using a MEGA-PRESS (MEscher GArwood point resolved spectroscopy) sequence previously employed for 2-hydroxyglutarate detection (TR = 2 s, TE = 68 ms). The editing pulse was applied at 1.9 ppm for the edit-on condition and at 7.5 ppm for the edit-off condition. To evaluate the editing efficiency, spectra were acquired in 1 participant by placing the editing pulse for the edit-on condition at 1.9, 2.03, and 2.16 ppm. Cystathionine concentration was quantified using LCModel and a simulated basis set. To confirm chemical shifts and J-coupling values of cystathionine, the 1H NMR cystathionine spectrum was measured using a high-resolution 500 MHz spectrometer. Results: In 12 gliomas, cystathionine was observed in the in vivo edited MR spectra at 2.72 and 3.85 ppm and quantified. The signal intensity of the cystathionine resonance at 2.72 ppm increased 1.7 and 2.13 times when the editing pulse was moved to 2.03 and 2.16 ppm, respectively. Cystathionine was not detectable in normal brain tissue. Conclusion: Cystathionine can be detected in vivo by edited MRS using the same protocol as for 2-hydroxyglutarate detection. This finding may enable a more accurate, noninvasive investigation of cellular metabolism in glioma.
Bibliographical noteFunding Information:
Funding information Investissements d'avenir: ANR-10-IAIHU-06 and ANR-11-INBS-0006 (f.b. s.l.); the National Institutes of Health (NIH): BTRC P41 EB015894 and P30 NS076408 (d.d., m.m.); and INCa-DGOS-Inserm_12560 (SiRIC CURAMUS) (m.s.). The authors would like to thank Neil Taylor from Chenomx Inc. (Edmonton, Alberta, Canada) for providing the chemical shifts and J-couplings of cystathionine; Sylvie Pailloux, PhD, for acquiring NMR spectrum; and Edward J. Auerbach, PhD, for implementing MRS sequences on the Siemens platform and for careful reading of the manuscript. f.b. and s.l. acknowledge support from Investissements d'avenir. d.d. and m.m. acknowledge support from National Institutes of Health. m.s. acknowledges support from INCa-DGOS-Inserm_12560.
Investissements d’avenir: ANR‐10‐ IAIHU‐06 and ANR‐11‐INBS‐0006 (f.b. s.l.); the National Institutes of Health (NIH): BTRC P41 EB015894 and P30 NS076408 (d.d., m.m.); and INCa‐DGOS‐ Inserm_12560 (SiRIC CURAMUS) (m.s.).
© 2019 International Society for Magnetic Resonance in Medicine
- brain glioma