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Abstract: 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 1H resonances of tissue CCMs exhibit small chemical shift differences and overlap significantly in 1D 1H 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 1H–14N HSQC technique is targeted on the two methylene 1H in the CH2O group (3 J 1H14N =2.7Hz) and applied to ex vivo mouse and human liver samples at physiological temperature (37°C). Specifically, the 1H–14N HSQC technique is modified into a 2D 1H–14N three-bond correlation (HN3BC) experiment, which selectively detects the 1H of CH2O coupled to 14N 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 1.5min and from human carcinoma liver tissue in less than 3min with effective sample volume of 0.2ml at 14.1T. [Copyright &y& Elsevier]

Abstract: Choline nitrogen (14N) has a long relaxation time (seconds) which is due to the highly symmetric chemical environments. 14N in choline also has coupling constants with protons (0.6Hz to methyl protons, 2.7Hz to CH2O protons and 0.2Hz to NCH2 protons). Based on these properties, we introduce a two-dimensional NMR method to detect choline and its derivatives in solutions. This method is the 1H–14N hetero-nuclear single-quantum correlation (HSQC) experiment which has been developed in solid-state NMR in recent years. Experiments have demonstrated that the 1H–14N HSQC technique is a sensitive method for detection of choline-containing compounds in solutions. From 1mM choline solution in 16min on a 500MHz NMR spectrometer, a 1H–14N HSQC spectrum has been recorded with a signal-to-noise ratio of 1700. Free choline, phosphocholine and glycerophosphocholine in milk can be well separated in 1H–14N HSQC spectra. This technique would become a promising analytical approach to mixture analyses where choline-containing compounds are of interest, such as tissue extracts, body fluids and food solutions. [ABSTRACT FROM AUTHOR]