Delivering Robust Proton-Only Sensing of Hyperpolarized [1,2-¹³C₂]-Pyruvate Using Broad-Spectral-Range Nuclear Magnetic Resonance Pulse Sequences

Abstract

Hyperpolarized [1-13C]­pyruvate is the leading hyperpolarized injectable contrast agent and is currently under evaluation in clinical trials for molecular imaging of metabolic diseases, including cardiovascular disease and cancer. One aspect limiting broad scalability of the technique is that hyperpolarized 13C MRI requires specialized 13C hardware and software that are not generally available on clinical MRI scanners, which employ proton-only detection. Here, we present an approach that uses pulse sequences to transfer 13C hyperpolarization to methyl protons for detection of the 13C–13C pyruvate singlet, employing proton-only excitation and detection only. The new pulse sequences are robust to the B1 and B0 magnetic field inhomogeneities. The work focuses on singlet-to-magnetization (S2M) and rotor-synchronized (R) pulses, both relying on trains of hard pulses with broad spectral width coverage designed to effectively transform hyperpolarized 13C2-singlet hyperpolarization to 1H polarization on the CH3 group of [1,2-13C2]­pyruvate. This approach may enable a broader adoption of hyperpolarized MRI as a molecular imaging technique.

Toward Next-Generation Molecular Imaging with a Clinical Low-Field (0.064 T) Point-of-Care MRI Scanner

“…A number of 1 H-detection schemes of HP [1- 13 C]­pyruvate and [1- 13 C]­lactate have been demonstrated in vivo, indicating that molecular imaging of pyruvate is well within reach of the sensitivity of this LF MRI scanner. Indeed, more recent development of 1 H-only approaches for sensing of pyruvate and its metabolic product lactate , raises an intriguing possibility of efficient molecular imaging of HP pyruvate metabolism in this scanner. We envision the near-future utility of such approaches for imaging of brain function and applications related to brain cancer and neurodegeneration.…”

“…The present work, along with recent efforts toward the preparation of biocompatible solutions with SABRE-hyperpolarized agents − and the first demonstrations of in vivo SABRE imaging, , bode well for future preclinical and clinical SABRE-enhanced MRI with LF point-of-care scanners for envisioned biomedical applications. Indeed, although the present scanner can only detect protons, the recent realization of proton-only detection of HP heteronuclei ,, opens the possibility of point-of-care molecular imaging of HP 13 C-based metabolic agents like HP pyruvate, the subject of 30-plus clinical trials to date.…”