Singlet-Contrast Magnetic Resonance Imaging: Unlocking Hyperpolarization with Metabolism*.

Hyperpolarization-enhanced magnetic resonance imaging can be used to study biomolecular processes in the body, but typically requires nuclei such as 13 C, 15 N, or 129 Xe due to their long spin-polarization lifetimes and the absence of a proton-background signal from water and fat in the images. Here we present a novel type of 1 H imaging, in which hyperpolarized spin order is locked in a nonmagnetic long-lived correlated (singlet) state, and is only liberated for imaging by a specific biochemical reaction. In this work we produce hyperpolarized fumarate via chemical reaction of a precursor molecule with para-enriched hydrogen gas, and the proton singlet order in fumarate is released as antiphase NMR signals by enzymatic conversion to malate in D2 O. Using this model system we show two pulse sequences to rephase the NMR signals for imaging and suppress the background signals from water. The hyperpolarization-enhanced 1 H-imaging modality presented here can allow for hyperpolarized imaging without the need for low-abundance, low-sensitivity heteronuclei.

A tailored multi-frequency EPR approach to accurately determine the magnetic resonance parameters of dynamic nuclear polarization agents: application to AMUPol.

To understand the dynamic nuclear polarization (DNP) enhancements of biradical polarizing agents, the magnetic resonance parameters need to be known. We describe a tailored EPR approach to accurately determine electron spin-spin coupling parameters using a combination of standard (9 GHz), high (95 GHz) and ultra-high (275 GHz) frequency EPR. Comparing liquid- and frozen-solution continuous-wave EPR spectra provides accurate anisotropic dipolar interaction D and isotropic exchange interaction J parameters of the DNP biradical AMUPol. We found that D was larger by as much as 30% compared to earlier estimates, and that J is 43 MHz, whereas before it was considered to be negligible. With the refined data, quantum mechanical calculations confirm that an increase in dipolar electron-electron couplings leads to higher cross-effect DNP efficiencies. Moreover, the DNP calculations qualitatively reproduce the difference of TOTAPOL and AMUPol DNP efficiencies found experimentally and suggest that AMUPol is particularly effective in improving the DNP efficiency at magnetic fields higher than 500 MHz. The multi-frequency EPR approach will aid in predicting the optimal structures for future DNP agents.

Para-hydrogen induced polarization in multi-spin systems studied at variable magnetic field.

A theoretical description of para-hydrogen-induced polarization (PHIP) is developed, applicable to coupled multi-spin systems that are polarized at an arbitrary magnetic field. Scalar spin-spin interaction is considered to be the leading factor governing PHIP formation and transfer. At low magnetic fields, these interactions make the spins strongly coupled and cause efficient, coherent re-distribution of spin polarization. We describe the effects of strong coupling and field cycling for a three-spin system and compare calculated spectra with the experimental examples available. By using a fast field-cycling device, which shuttles the whole NMR probe, and thereby makes high-resolution NMR detection at high field possible, we studied PHIP patterns for a set of different fields between 0.1 mT and 7 T. PHIP spectra were measured for ethylbenzene as the product of a catalytic reaction between para-hydrogen and styrene. Additionally, the polarizations of ethylbenzene bound to the catalyst, and of the starting styrene molecule were analyzed. This is the first time that the full field dependence of PHIP has been determined experimentally. The spectra obtained are in perfect agreement with the simulations for the CH(2) and CH(3) protons of ethylbenzene and even for its weakly-polarized aromatic protons. Analysis of styrene polarization shows that the time profile of the field variation has pronounced effects on the PHIP pattern. Our study gives evidence that scalar spin-spin interactions determine the PHIP patterns. Possible applications of the theory are discussed.

A method for simulating level anti-crossing spectra of diamond crystals containing NV- color centers.

We propose an efficient method for calculating level anti-crossing spectra (LAC spectra) of interacting paramagnetic defect centers in crystals. By LAC spectra we mean the magnetic field dependence of the photoluminescence intensity of paramagnetic color centers: such field dependences often exhibit sharp features, such as peaks or dips, originating from LACs in the spin system. Our approach takes into account the electronic Zeeman interaction with the external magnetic field, dipole-dipole interaction of paramagnetic centers, hyperfine coupling of paramagnetic defects to magnetic nuclei and zero-field splitting. By using this method, not only can we obtain the positions of lines in LAC spectra, but also reproduce their shapes as well as the relative amplitudes of different lines. As a striking example, we present a calculation of LAC spectra in diamond crystals containing negatively charged NV centers.

Net and multiplet CIDEP of the observer spin in recombination of radical-biradical pair.

Net and multiplet chemically induced dynamic electron polarization (CIDEP) of the observer/catalyst spin formed in recombination of the radical-biradical pair is studied theoretically. We obtained analytical expressions for the observer spin CIDEP in the high magnetic field and for the multiplet polarization in zero magnetic field. Polarization in the vicinity of the so-called J resonance and its magnetic field dependence are investigated numerically. The observer spin methodology can be useful for probing magnetic interactions in the short-lived spin triads.

Spin evolution of radical pair with radical containing two groups of equivalent magnetic nuclei.

Analytical solution is obtained for time-resolved magnetic field effects (TR-MFE) on recombination fluorescence of radical-ion pair (RIP) containing radical ion with two groups of magnetically equivalent nuclei. The present theoretical approach is applied to three experimental systems: RIPs containing radical cations of 2,3-dimethylbutane, 2,2,6,6-tetramethylpiperidine, or diisopropylamine and radical anion of p-terphenyl-d14 in nonpolar alkane solutions. Good agreement between theory and experiment is found for all the three systems, hyperfine coupling constants of radical cations are obtained by fitting the experimental TR-MFE traces. The potential of the TR-MFE technique for studying radical ions with nonequivalent nuclei is discussed in detail. The wide applicability of the theoretical model and the experimental technique make them useful for studying short-lived radical species that are often beyond the reach of the conventional electron paramagnetic resonance spectroscopy.