Measuring extracellular pH in 3D using an iterative least squares frequency decomposition and hyperpolarized 13C-labelled Z-OMPD

Motivation: Hyperpolarized [1,5-13C2]Z-OMPD exhibits a pH-dependent chemical shift and serves as a pH-sensitive probe. However, multiple pH compartments in vivo lead to multiple closely located resonances, which currently limits acquisition to slow 2D spectroscopic sequences. Goal(s): To develop a method to decompose an unknown number of frequencies from multiple echo images, thereby enabling faster 3D multi-compartment pH mapping. Approach: An IDEAL-like iterative least squares method was developed for a voxel-wise signal approximation and frequency decomposition. Results: 3D pH maps acquired in vitro and in vivo showed good agreement with pH-electrode measurements and results of other studies. Impact: The proposed iterative least squares frequency decomposition method enables fast 3D pH measurement using hyperpolarized [1,5-13C2]Z-OMPD, providing an alternative to the previously used 2D spectroscopic sequences. The acquisition of 3D pH maps enhances the ability to investigate tumor acidification.