Publications

Hyperpolarized nuclear spins in molecules exhibit high magnetization that is unachievable by classical polarization techniques, making them widely used as sensors in physics, chemistry, and medicine. The state of a hyperpolarized material, however, is typically only studied indirectly and with partial destruction of magnetization, due to the nature of conventional detection by resonant-pickup NMR spectroscopy or imaging. Here, we establish atomic magnetometers with sub-pT sensitivity as an alternative modality to detect in real time the complex dynamics of hyperpolarized materials without disturbing or interrupting the magnetogenesis process. As an example of dynamics that are impossible to detect in real time by conventional means, we examine parahydrogen-induced H-1 and C-13 magnetization during adiabatic eigenbasis transformations at mu mu T-field avoided crossings. Continuous but nondestructive magnetometry reveals previously unseen spin dynamics, fidelity limits, and magnetization backaction effects. As a second example, we apply magnetometry to observe the chemical-exchange-driven C-13 hyperpolarization of [1-C-13]-pyruvate-the most important spin tracer for clinical metabolic imaging. The approach can be readily combined with other high-sensitivity magnetometers and is applicable to a broader range of general observation scenarios involving production, transport, and systems interaction of hyperpolarized compounds.

JTD Keywords: Adiabaticity, Dnp, Field, Hyperpolarization, Nmr, Nuclear spins, Optical magnetometry, Order, Para-hydrogen, Parahydrogen, Polarimetry, Polarization transfer

From complex -mixture analysis to in vivo molecular imaging, applications of liquid -state nuclear spin hyperpolarization have expanded widely over recent years. In most cases, hyperpolarized solutions are generated and transported from the polarization instrument to the measurement device. The sample hyperpolarization usually survives this transport, since the changes in magnetic fields that are external to the sample are typically adiabatic (slow) with respect to the internal nuclear spin dynamics. The passage of polarized samples through weakly magnetic components such as stainless steel syringe needles and ferrules is not always adiabatic, can lead to near -complete destruction of the magnetization. To avoid this effect becoming "folklore"in field of hyperpolarized NMR, we present a systematic investigation to highlight the problem and investigate possible solutions. Experiments were carried out on: (i) dissolution-DNP-polarized [1-13C]pyruvate with detection at 1.4 T, and (ii) 1.5 -T -polarized H2O with NMR detection at 2.5 mu T. We show that the degree adiabaticity of solutions passing through metal parts is intrinsically unpredictable, likely depending on factors such as solution flow rate, degree of remanent ferromagnetism in the metal, and nuclear spin However, the magnetization destruction effects can be suppressed by application of an external field order of 0.1-10 mT.

JTD Keywords: Benchtop nmr, Hyperpolarization, Low-field mri, Non-adiabatic, Para-hydrogen, Spin relaxation

We present a versatile method for the preparation of hyperpolarized [1-13C]fumarate as a contrast agent for preclinical in vivo MRI, using parahydrogen-induced polarization (PHIP). To benchmark this process, we compared a prototype PHIP polarizer to a state-of-the-art dissolution dynamic nuclear polarization (d-DNP) system. We found comparable polarization, volume, and concentration levels of the prepared solutions, while the preparation effort is significantly lower for the PHIP process, which can provide a preclinical dose every 10 min, opposed to around 90 min for d-DNP systems. With our approach, a 100 mM [1-13C]-fumarate solution of volumes up to 3 mL with 13-20% 13C-hyperpolarization after purification can be produced. The purified solution has a physiological pH, while the catalyst, the reaction side products, and the precursor material concentrations are reduced to nontoxic levels, as confirmed in a panel of cytotoxicity studies. The in vivo usage of the hyperpolarized fumarate as a perfusion agent in healthy mice and the metabolic conversion of fumarate to malate in tumor-bearing mice developing regions with necrotic cell death is demonstrated. Furthermore, we present a one-step synthesis to produce the 13C-labeled precursor for the hydrogenation reaction with high yield, starting from 13CO2 as a cost-effective source for 13C-labeled compounds.

JTD Keywords: Animals, Contrast media, Fumarates, Hydrogenation, Magnetic resonance imaging, Magnetic resonance spectroscopy, Mice, Para-hydrogen

Zero- to ultralow-field nuclear magnetic resonance (ZULF NMR) is a rapidly developing form of spectroscopy that provides rich spectroscopic information in the absence of large magnetic fields. However, signal acquisition still requires a mechanism for generating a bulk magnetic moment for detection, and the currently used methods only apply to a limited pool of chemicals or come at prohibitively high cost. We demonstrate that the parahydrogen-based SABRE (signal amplification by reversible exchange)-Relay method can be used as a more general means of generating hyperpolarized analytes for ZULF NMR by observing zero-field J-spectra of [C-13]-methanol, [1-C-13]-ethanol, and [2(-13) C]-ethanol in both C-13-isotopically enriched and natural abundance samples. We explore the magnetic field dependence of the SABRE-Relay efficiency and show the existence of a second maximum at 19.0 +/- 0.3 mT. Despite presence of water, SABRE-Relay is used to hyperpolarize ethanol extracted from a store-bought sample of vodka (%P-H similar to 0.1%).

JTD Keywords: Nmr, Para-hydrogen, Sabre, Spectroscopy