Mapping pH using stimulated echoes formed via chemical exchange

RACETE (refocused acquisition of chemical exchange transferred excitations) is a recently developed approach to imaging solute exchange with water. However, it lacks biophysical specificity, as it is sensitive to exchange rates, relaxation rates, solute concentration, and macromolecular content. We modified this sequence and developed a protocol and corresponding metric with specific sensitivity to the solute exchange rate and hence a means for mapping pH.

RACETE splits the two gradients traditionally used in a stimulated-echo sequence into one applied after exciting solutes and one applied after exciting water, hence requiring exchange for echo formation. In this work, we leverage the dependence of the stimulated-echo signal on the exchange process. By preserving the total irradiation power and using a ratio metric, the other signal dependencies cancel, leaving a specific measure of exchange rate. Additionally, artifacts due to off-resonance excitation of water are addressed using a phase cancelling approach; and a gradient-echo imaging sequence with a variable flip angle excitation is tailored for a fast read-out of RECETE prepared signals. This method is validated using numerical simulations and salicylic acid phantom experiments at 9.4 T.

Numerical simulations and phantom experiments demonstrate that the ratio-metric is a single-variable function of exchange rate with extremely low dependence on confounding factors. Additionally, artifacts due to direct water excitation are removed and robustness to B0 and B1 inhomogeneities is demonstrated.

The proposed method can be used for fast pH mapping with robustness against the confounding effects that widely exist in other methods.