Development of specialized magnetic resonance acquisition techniques for human hyperpolarized [13 C,15 N2 ]urea + [1-13 C]pyruvate simultaneous perfusion and metabolic imaging

Abstract

Purpose: This study aimed to develop and demonstrate the in vivo feasibility of a 3D stack-of-spiral balanced steady-state free precession(3D-bSSFP) urea sequence, interleaved with a metabolite-specific gradient echo (GRE) sequence for pyruvate and metabolic products, for improving the SNR and spatial resolution of the first hyperpolarized ¹³ C-MRI human study with injection of co-hyperpolarized [1-¹³ C]pyruvate and [¹³ C,¹⁵ N₂ ]urea.

Methods: A metabolite-specific bSSFP urea imaging sequence was designed using a urea-specific excitation pulse, optimized TR, and 3D stack-of-spiral readouts. Simulations and phantom studies were performed to validate the spectral response of the sequence. The image quality of urea data acquired by the 3D-bSSFP sequence and the 2D-GRE sequence was evaluated with 2 identical injections of co-hyperpolarized [1-¹³ C]pyruvate and [¹³ C,¹⁵ N₂ ]urea formula in a rat. Subsequently, the feasibility of the acquisition strategy was validated in a prostate cancer patient.

Results: Simulations and phantom studies demonstrated that 3D-bSSFP sequence achieved urea-only excitation, while minimally perturbing other metabolites (<1%). An animal study demonstrated that compared to GRE, bSSFP sequence provided an ∼2.5-fold improvement in SNR without perturbing urea or pyruvate kinetics, and bSSFP approach with a shorter spiral readout reduced blurring artifacts caused by J-coupling of [¹³ C,¹⁵ N₂ ]urea. The human study demonstrated the in vivo feasibility and data quality of the acquisition strategy.

Conclusion: The 3D-bSSFP urea sequence with a stack-of-spiral acquisition demonstrated significantly increased SNR and image quality for [¹³ C,¹⁵ N₂ ]urea in co-hyperpolarized [1-¹³ C]pyruvate and [¹³ C,¹⁵ N₂ ]urea imaging studies. This work lays the foundation for future human studies to achieve high-quality and high-SNR metabolism and perfusion images.

Keywords: 13C hyperpolarization; bSSFP; human clinical study; metabolism imaging; perfusion imaging; urea.