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

Hyperpolarized [1-C]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 C MRI requires specialized C 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 C hyperpolarization to methyl protons for detection of the C-C pyruvate singlet, employing proton-only excitation and detection only.

Spin dynamics of [1,2-C]pyruvate hyperpolarization by parahydrogen in reversible exchange at micro Tesla fields.

Hyperpolarization of C-pyruvate Signal Amplificaton By Reversibble Exchange (SABRE) is an important recent discovery because of both the relative simplicity of hyperpolarization and the central biological relevance of pyruvate as a biomolecular probe for or studies. Here, we analyze the [1,2-C]pyruvate-SABRE spin system and its field dependence theoretically and experimentally. We provide first-principles analysis of the governing 4-spin dihydride-C Hamiltonian and numerical spin dynamics simulations of the 7-spin dihydride-C-CH system.

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

Hyperpolarized [1-C]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]pyruvate via simultaneous chemical exchange of parahydrogen and pyruvate on IrIMes hexacoordinate complexes.

Triplet Photosensitized -Hydrogen Induced Polarization.

Despite its enormous utility in structural characterization, nuclear magnetic resonance (NMR) spectroscopy is inherently limited by low spin polarization. One method to address the low polarization is -hydrogen (-H) induced polarization (PHIP) which uses the singlet spin isomer of H to generate disparate nuclear spin populations to amplify the associated NMR signals. PHIP often relies on thermal catalysis or, more infrequently, UV-activated catalytic hydrogenation.

Order-Unity C Nuclear Polarization of [1- C]Pyruvate in Seconds and the Interplay of Water and SABRE Enhancement.

Signal Amplification By Reversible Exchange in SHield Enabled Alignment Transfer (SABRE-SHEATH) is investigated to achieve rapid hyperpolarization of C spins of [1- C]pyruvate, using parahydrogen as the source of nuclear spin order. Pyruvate exchange with an iridium polarization transfer complex can be modulated via a sensitive interplay between temperature and co-ligation of DMSO and H O. Order-unity C (>50 %) polarization of catalyst-bound [1- C]pyruvate is achieved in less than 30 s by restricting the chemical exchange of [1- C]pyruvate at lower temperatures.