3D virtual biopsy of in vivo pH and metabolism using PRESS and semi-LASER MRS of hyperpolarized ¹³C nuclei

Purpose: To develop and evaluate sequences for multi-voxel magnetic resonance spectroscopy using hyperpolarized molecules. Methods: A standard single voxel PRESS sequence was extended to acquire multiple voxels consecutively. Its SNR was compared against a 2D FID-CSI with both ¹H and hyperpolarized ¹³C nuclei in phantoms and in a healthy mouse at 7T. This sequence was also used to determine tumor pH and metabolic activity in an endogenous murine pancreatic ductal adenocarcinoma model. Furthermore, a semi-LASER sequence, using adiabatic full passage RF pulses for refocusing, was implemented. Multi-voxel PRESS and semi-LASER were then compared in healthy mice for measuring metabolic activity and pH using hyperpolarized [1-¹³C]pyruvate and [1,5-¹³C₂]Z-OMPD, respectively. Results: Multi-voxel PRESS and semi-LASER detected ¹³C metabolites in mouse kidneys and endogenous pancreatic ductal adenocarcinoma (PDAC) tumors with SNR comparable to that of standard 2D FID-CSI. They enable fast MRS with a high spectral resolution that is highly customizable to recover spectra from regions not coverable by a single CSI slice. Conclusion: For the first time, we show hyperpolarized MRS using multi-voxel PRESS and semi-LASER sequences for hyperpolarized ¹³C-labeled molecules. By implementing a semi-LASER sequence using adiabatic full passage refocusing pulses, RF saturation was reduced. Semi-LASER allows flexible overlapping of voxel refocusing planes, while for PRESS, signal from these regions is attenuated.