Moving the goal posts: enhancing the sensitivity of PARASHIFT proton magnetic resonance imaging and spectroscopy

Paramagnetic probes for chemical shift imaging are described, in which a reporting tert-butyl resonance is integrated and placed about 6 to 6.5 Aa from a lanthanide ion. At this distance, the resonance is shifted to a region of the super(1)H NMR spectral window far away from the usual 0-12 ppm range, permitting selective observation. Furthermore, judicious selection of the lanthanide ion, according to the applied magnetic field strength, leads to relaxation rate enhancements of the order of 100-200, permitting more rapid data acquisition per unit time in both spectroscopy and imaging experiments. The enhanced sensitivity allows the detection of these complexes in mice within a few minutes using shift imaging, following tail vein injection of doses of the order of 0.1 mmol kg super(-1).