Chemical Exchange Saturation Transfer (CEST) Signal at −1.6 ppm and Its Application for Imaging a C6 Glioma Model

The chemical exchange saturation transfer (CEST) signal at −1.6 ppm is attributed to the choline methyl on phosphatidylcholines and results from the relayed nuclear Overhauser effect (rNOE), that is, rNOE(−1.6). The formation of rNOE(−1.6) involving the cholesterol hydroxyl is shown in liposome mode...

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Main Authors: Qi-Xuan Wu, Hong-Qing Liu, Yi-Jiun Wang, Tsai-Chen Chen, Zi-Ying Wei, Jung-Hsuan Chang, Ting-Hao Chen, Jaya Seema, Eugene C. Lin
Format: Article
Language:English
Published: MDPI AG 2022-05-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/10/6/1220
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author Qi-Xuan Wu
Hong-Qing Liu
Yi-Jiun Wang
Tsai-Chen Chen
Zi-Ying Wei
Jung-Hsuan Chang
Ting-Hao Chen
Jaya Seema
Eugene C. Lin
author_facet Qi-Xuan Wu
Hong-Qing Liu
Yi-Jiun Wang
Tsai-Chen Chen
Zi-Ying Wei
Jung-Hsuan Chang
Ting-Hao Chen
Jaya Seema
Eugene C. Lin
author_sort Qi-Xuan Wu
collection DOAJ
description The chemical exchange saturation transfer (CEST) signal at −1.6 ppm is attributed to the choline methyl on phosphatidylcholines and results from the relayed nuclear Overhauser effect (rNOE), that is, rNOE(−1.6). The formation of rNOE(−1.6) involving the cholesterol hydroxyl is shown in liposome models. We aimed to confirm the correlation between cholesterol content and rNOE(−1.6) in cell cultures, tissues, and animals. C57BL/6 mice (N = 9) bearing the C6 glioma tumor were imaged in a 7 T MRI scanner, and their rNOE(−1.6) images were cross-validated through cholesterol staining with filipin. Cholesterol quantification was obtained using an 18.8-T NMR spectrometer from the lipid extracts of the brain tissues from another group of mice (N = 3). The cholesterol content in the cultured cells was manipulated using methyl-β-cyclodextrin and a complex of cholesterol and methyl-β-cyclodextrin. The rNOE(−1.6) of the cell homogenates and their cholesterol levels were measured using a 9.4-T NMR spectrometer. The rNOE(−1.6) signal is hypointense in the C6 tumors of mice, which matches the filipin staining results, suggesting that their tumor region is cholesterol deficient. The tissue extracts also indicate less cholesterol and phosphatidylcholine contents in tumors than in normal brain tissues. The amplitude of rNOE(−1.6) is positively correlated with the cholesterol concentration in the cholesterol-manipulated cell cultures. Our results indicate that the cholesterol dependence of rNOE(−1.6) occurs in cell cultures and solid tumors of C6 glioma. Furthermore, when the concentration of phosphatidylcholine is carefully considered, rNOE(−1.6) can be developed as a cholesterol-weighted imaging technique.
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spelling doaj.art-4bf94b4ee31b4035a4d8f52b8642c4802023-11-23T15:41:00ZengMDPI AGBiomedicines2227-90592022-05-01106122010.3390/biomedicines10061220Chemical Exchange Saturation Transfer (CEST) Signal at −1.6 ppm and Its Application for Imaging a C6 Glioma ModelQi-Xuan Wu0Hong-Qing Liu1Yi-Jiun Wang2Tsai-Chen Chen3Zi-Ying Wei4Jung-Hsuan Chang5Ting-Hao Chen6Jaya Seema7Eugene C. Lin8Department of Chemistry and Biochemistry, National Chung Cheng University, Chiayi 62102, TaiwanDepartment of Chemistry and Biochemistry, National Chung Cheng University, Chiayi 62102, TaiwanDepartment of Chemistry and Biochemistry, National Chung Cheng University, Chiayi 62102, TaiwanInstitute of Biomedical Sciences, Academia Sinica, Taipei 11529, TaiwanDepartment of Chemistry and Biochemistry, National Chung Cheng University, Chiayi 62102, TaiwanDepartment of Chemistry and Biochemistry, National Chung Cheng University, Chiayi 62102, TaiwanDepartment of Chemistry and Biochemistry, National Chung Cheng University, Chiayi 62102, TaiwanInstitute of Biomedical Sciences, Academia Sinica, Taipei 11529, TaiwanDepartment of Chemistry and Biochemistry, National Chung Cheng University, Chiayi 62102, TaiwanThe chemical exchange saturation transfer (CEST) signal at −1.6 ppm is attributed to the choline methyl on phosphatidylcholines and results from the relayed nuclear Overhauser effect (rNOE), that is, rNOE(−1.6). The formation of rNOE(−1.6) involving the cholesterol hydroxyl is shown in liposome models. We aimed to confirm the correlation between cholesterol content and rNOE(−1.6) in cell cultures, tissues, and animals. C57BL/6 mice (N = 9) bearing the C6 glioma tumor were imaged in a 7 T MRI scanner, and their rNOE(−1.6) images were cross-validated through cholesterol staining with filipin. Cholesterol quantification was obtained using an 18.8-T NMR spectrometer from the lipid extracts of the brain tissues from another group of mice (N = 3). The cholesterol content in the cultured cells was manipulated using methyl-β-cyclodextrin and a complex of cholesterol and methyl-β-cyclodextrin. The rNOE(−1.6) of the cell homogenates and their cholesterol levels were measured using a 9.4-T NMR spectrometer. The rNOE(−1.6) signal is hypointense in the C6 tumors of mice, which matches the filipin staining results, suggesting that their tumor region is cholesterol deficient. The tissue extracts also indicate less cholesterol and phosphatidylcholine contents in tumors than in normal brain tissues. The amplitude of rNOE(−1.6) is positively correlated with the cholesterol concentration in the cholesterol-manipulated cell cultures. Our results indicate that the cholesterol dependence of rNOE(−1.6) occurs in cell cultures and solid tumors of C6 glioma. Furthermore, when the concentration of phosphatidylcholine is carefully considered, rNOE(−1.6) can be developed as a cholesterol-weighted imaging technique.https://www.mdpi.com/2227-9059/10/6/1220magnetic resonance imaging (MRI)chemical exchange saturation transfer (CEST)relayed nuclear Overhauser effect (rNOE)cholesterolglioma
spellingShingle Qi-Xuan Wu
Hong-Qing Liu
Yi-Jiun Wang
Tsai-Chen Chen
Zi-Ying Wei
Jung-Hsuan Chang
Ting-Hao Chen
Jaya Seema
Eugene C. Lin
Chemical Exchange Saturation Transfer (CEST) Signal at −1.6 ppm and Its Application for Imaging a C6 Glioma Model
Biomedicines
magnetic resonance imaging (MRI)
chemical exchange saturation transfer (CEST)
relayed nuclear Overhauser effect (rNOE)
cholesterol
glioma
title Chemical Exchange Saturation Transfer (CEST) Signal at −1.6 ppm and Its Application for Imaging a C6 Glioma Model
title_full Chemical Exchange Saturation Transfer (CEST) Signal at −1.6 ppm and Its Application for Imaging a C6 Glioma Model
title_fullStr Chemical Exchange Saturation Transfer (CEST) Signal at −1.6 ppm and Its Application for Imaging a C6 Glioma Model
title_full_unstemmed Chemical Exchange Saturation Transfer (CEST) Signal at −1.6 ppm and Its Application for Imaging a C6 Glioma Model
title_short Chemical Exchange Saturation Transfer (CEST) Signal at −1.6 ppm and Its Application for Imaging a C6 Glioma Model
title_sort chemical exchange saturation transfer cest signal at 1 6 ppm and its application for imaging a c6 glioma model
topic magnetic resonance imaging (MRI)
chemical exchange saturation transfer (CEST)
relayed nuclear Overhauser effect (rNOE)
cholesterol
glioma
url https://www.mdpi.com/2227-9059/10/6/1220
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