Ratiometric NOE(-1.6) contrast in brain tumors

Recently, a new nuclear Overhauser enhancement (NOE)-mediated saturation transfer effect at around -1.6 ppm from water, termed NOE(-1.6), was reported to show hypointense signals in brain tumors. Similar to chemical exchange saturation transfer or magnetization transfer (MT) effects, which depend on the solute pool concentration, the exchange/coupling rate, the solute transverse relaxation rate, etc., the NOE(-1.6) effect should also depend on these factors. Since the exchange rate is relevant to tissue pH, and the coupling rate and the solute transverse relaxation rate are relevant to the motional property of the coupled molecules, further studies to quantify the contribution from only the exchange/coupling rate and the solute transverse relaxation rate are always interesting. The purpose of this paper is to apply a ratiometric approach to the NOE(-1.6) effect to obtain a metric that is more specific to the NOE coupling rate and the solute transverse relaxation rate than the NOE(-1.6) signal amplitude. Simulations indicate that the ratiometric approach allows us to rule out nearly all of the non-specific factors including the solute pool concentration, solute and water longitudinal relaxation rates, direct water saturation, and semi-solid MT effects, and provides a more specific NOE coupling rate- and solute transverse relaxation rate-weighted signal. Animal studies show that the ratiometric NOE(-1.6) decreases dramatically in brain tumors, which suggests that the change in the NOE(-1.6) coupling rate and/or the solute transverse relaxation rate are major contributors to the previously observed hypointense NOE(-1.6) signal in tumors.