In vivo 1H MRS detection of cystathionine in human brain tumors

Francesca Branzoli; Dinesh K Deelchand; Marc Sanson; Stéphane Lehéricy; Malgorzata Marjanska

doi:10.1002/mrm.27810

In vivo ¹H MRS detection of cystathionine in human brain tumors

Francesca Branzoli, Dinesh K Deelchand, Marc Sanson, Stéphane Lehéricy, Malgorzata Marjanska

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

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 (T_R = 2 s, T_E = 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.

Original language	English (US)
Pages (from-to)	1259-1265
Number of pages	7
Journal	Magnetic resonance in medicine
Volume	82
Issue number	4
DOIs	https://doi.org/10.1002/mrm.27810
State	Published - Oct 2019

Bibliographical note

Funding 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.

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.).

Publisher Copyright:
© 2019 International Society for Magnetic Resonance in Medicine

Keywords

2-hydroxyglutarate
MEGA-PRESS
brain glioma
cystathionine
editing

Center for Magnetic Resonance Research (CMRR) tags

SMCT
CTR

Publisher link

10.1002/mrm.27810

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@article{b3baaf346b8a4c95b7c0bbc330a5a757,

title = "In vivo 1H MRS detection of cystathionine in human brain tumors",

abstract = "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.",

keywords = "2-hydroxyglutarate, MEGA-PRESS, brain glioma, cystathionine, editing",

author = "Francesca Branzoli and Deelchand, {Dinesh K} and Marc Sanson and St{\'e}phane Leh{\'e}ricy and Malgorzata Marjanska",

note = "Funding 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. Funding Information: Investissements d{\textquoteright}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.). Publisher Copyright: {\textcopyright} 2019 International Society for Magnetic Resonance in Medicine",

year = "2019",

month = oct,

doi = "10.1002/mrm.27810",

language = "English (US)",

volume = "82",

pages = "1259--1265",

journal = "Magnetic resonance in medicine",

issn = "0740-3194",

publisher = "John Wiley and Sons Inc.",

number = "4",

}

TY - JOUR

T1 - In vivo 1H MRS detection of cystathionine in human brain tumors

AU - Branzoli, Francesca

AU - Deelchand, Dinesh K

AU - Sanson, Marc

AU - Lehéricy, Stéphane

AU - Marjanska, Malgorzata

N1 - Funding 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. 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.). Publisher Copyright: © 2019 International Society for Magnetic Resonance in Medicine

PY - 2019/10

Y1 - 2019/10

N2 - 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.

AB - 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.

KW - 2-hydroxyglutarate

KW - MEGA-PRESS

KW - brain glioma

KW - cystathionine

KW - editing

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U2 - 10.1002/mrm.27810

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