Interplay of Near-Zero-Field Dephasing, Rephasing, and Relaxation Dynamics and [1-13C]Pyruvate Polarization Transfer Efficiency in Pulsed SABRE-SHEATH

Hyperpolarized [1-C-13]pyruvate is a revolutionary molecular probe enabling ultrafast metabolic MRI scans in 1 min. This technology is now under evaluation in over 30 clinical trials, which employ dissolution Dynamic Nuclear Polarization (d-DNP) to prepare a batch of the contrast agent; however, d-DNP technology is slow and expensive. The emerging SABRE-SHEATH hyperpolarization technique enables fast (under 1 min) and robust production of hyperpolarized [1-C-13]pyruvate via simultaneous chemical exchange of parahydrogen and pyruvate on IrIMes hexacoordinate complexes. Here, we study the application of microtesla pulses to investigate their effect on C-13 polarization efficiency, compared to that of conventional SABRE-SHEATH employing a static field (similar to 0.4 mu T), to provide the matching conditions of polarization transfer from parahydrogen-derived hydrides to the C-13-1 nucleus. Our results demonstrate that using square-microtesla pulses with optimized parameters can produce C-13-1 polarization levels of up to 14.8% (when detected, averaging over all resonances), corresponding to signal enhancement by over 122,000-fold at the clinically relevant field of 1.4 T. We anticipate that our results can be directly translated to other structurally similar biomolecules such as [1-C-13]alpha-ketoglutarate and [1-C-1(3)]alpha-ketoisocaproate. Moreover, other more advanced pulse shapes can potentially further boost heteronuclear polarization attainable via pulsed SABRE-SHEATH.

Automated summary

This study investigates the effect of microtesla pulses on C-13 polarization efficiency and compares it with the conventional SABRE-SHEATH method employing a static field. The results demonstrate that square-microtesla pulses with optimized parameters can achieve high levels of C-13 polarization at clinically relevant fields.