Fast detection of choline-containing metabolites in liver using 2D ¹H-¹⁴N three-bond correlation (HN3BC) spectroscopy.
Detection and quantification of total choline-containing metabolites (CCMs) in tissues by magnetic resonance spectroscopy (MRS) has received considerable attention as a biomarker of cancer. Tissue CCMs are mainly choline (Cho), phosphocholine (PCho), and glycerophosphocholine (GPCho). Because the methyl (1)H resonances of tissue CCMs exhibit small chemical shift differences and overlap significantly in 1D (1)H MRS, quantification of individual components is precluded. Development of a MRS method capably of resolving individual components of tissue CCMs would be a significant advance. Herein, a modification of the 2D (1)H-(14)N HSQC technique is targeted on the two methylene (1)H in the CH(2)O group ((3)J(1H14N)=2.7 Hz) and applied to ex vivo mouse and human liver samples at physiological temperature (37°C). Specifically, the (1)H-(14)N HSQC technique is modified into a 2D (1)H-(14)N three-bond correlation (HN3BC) experiment, which selectively detects the (1)H of CH(2)O coupled to (14)N in CCMs. Separate signals from Cho, PCho, and GPCho components are resolved with high detection sensitivity. A 2D HN3BC spectrum can be recorded from mouse liver in only 1.5 min and from human carcinoma liver tissue in less than 3 min with effective sample volume of 0.2 ml at 14.1T.
State Key Laboratory of Magnetic Resonance and Atomic Molecular Physics, Wuhan Institute of Physics and Mathematics, The Chinese Academy of Sciences, Wuhan, Hubei 430071, China. xian.mao@case.edu
Xi-An
XA
Mao
Ning
N
Li
Jiezhen
J
Mao
Qiurong
Q
Li
Nan
N
Xiao
Bin
B
Jiang
Ling
L
Jiang
Xu-Xia
XX
Wang
Maili
M
Liu
D000465:Algorithms; D014408:Biomarkers, Tumor / Q000032:analysis*; D002794:Choline / Q000032:analysis*; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009587:Nitrogen Isotopes / Q000032:analysis; D011522:Protons
D014408:Biomarkers, Tumor; D009587:Nitrogen Isotopes; D011522:Protons; D002794:Choline