Fast detection of choline-containing metabolites in liver using 2D 1H– 14N three-bond correlation (HN3BC) spectroscopy

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 CH 2O group ( 3 J 1H14N = 2.7 Hz) 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 CH 2O 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 1.5 min and from human carcinoma liver tissue in less than 3 min with effective sample volume of 0.2 ml at 14.1 T.