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 H-1 resonances of tissue CCMs exhibit small chemical shift differences and overlap significantly in 19 H-1 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 H-1-N-14 HSQC technique is targeted on the two methylene H-1 in the CH2O group ((3)J(1H14N) = 2.7 Hz) and applied to ex vivo mouse and human liver samples at physiological temperature (37 degrees C). Specifically, the H-1-N-14 HSQC technique is modified into a 2D H-1-N-14 three-bond correlation (HN3BC) experiment, which selectively detects the H-1 of CH2O coupled to N-14 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 14.1 T. (C) 2011 Elsevier Inc. All rights reserved.