Using bidirectional chemical exchange for improved hyperpolarized [13 C]bicarbonate pH imaging

Abstract

Purpose: Rapid chemical exchange can affect SNR and pH measurement accuracy for hyperpolarized pH imaging with [¹³ C]bicarbonate. The purpose of this work was to investigate chemical exchange effects on hyperpolarized imaging sequences to identify optimal sequence parameters for high SNR and pH accuracy.

Methods: Simulations were performed under varying rates of bicarbonate-CO₂ chemical exchange to analyze exchange effects on pH quantification accuracy and SNR under different sampling schemes. Four pulse sequences, including 1 new technique, a multiple-excitation 2D EPI (multi-EPI) sequence, were compared in phantoms using hyperpolarized [¹³ C]bicarbonate, varying parameters such as tip angles, repetition time, order of metabolite excitation, and refocusing pulse design. In vivo hyperpolarized bicarbonate-CO₂ exchange measurements were made in transgenic murine prostate tumors to select in vivo imaging parameters.

Results: Modeling of bicarbonate-CO₂ exchange identified a multiple-excitation scheme for increasing CO₂ SNR by up to a factor of 2.7. When implemented in phantom imaging experiments, these sampling schemes were confirmed to yield high pH accuracy and SNR gains. Based on measured bicarbonate-CO₂ exchange in vivo, a 47% CO₂ SNR gain is predicted.

Conclusion: The novel multi-EPI pulse sequence can boost CO₂ imaging signal in hyperpolarized ¹³ C bicarbonate imaging while introducing minimal pH bias, helping to surmount a major hurdle in hyperpolarized pH imaging.

Keywords: MRI; NMR spectroscopy pH imaging; bicarbonate; chemical exchange; hyperpolarized13C.