Parahydrogen-Polarized Fumarate for Preclinical in Vivo Metabolic Magnetic Resonance Imaging.

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.

Hyperpolarized Solution-State NMR Spectroscopy with Optically Polarized Crystals.

Nuclear spin hyperpolarization provides a promising route to overcome the challenges imposed by the limited sensitivity of nuclear magnetic resonance. Here we demonstrate that dissolution of spin-polarized pentacene-doped naphthalene crystals enables transfer of polarization to target molecules via intermolecular cross-relaxation at room temperature and moderate magnetic fields (1.45 T). This makes it possible to exploit the high spin polarization of optically polarized crystals, while mitigating the challenges of its transfer to external nuclei. With this method, we inject the highly polarized mixture into a benchtop NMR spectrometer and observe the polarization dynamics for target 1H nuclei. Although the spectra are radiation damped due to the high naphthalene magnetization, we describe a procedure to process the data to obtain more conventional NMR spectra and extract the target nuclei polarization. With the entire process occurring on a time scale of 1 min, we observe NMR signals enhanced by factors between -200 and -1730 at 1.45 T for a range of small molecules.

Radio-Frequency Sweeps at Microtesla Fields for Parahydrogen-Induced Polarization of Biomolecules.

Magnetic resonance imaging of 13C-labeled metabolites enhanced by parahydrogen-induced polarization (PHIP) enables real-time monitoring of processes within the body. We introduce a robust, easily implementable technique for transferring parahydrogen-derived singlet order into 13C magnetization using adiabatic radio frequency sweeps at microtesla fields. We experimentally demonstrate the applicability of this technique to several molecules, including some molecules relevant for metabolic imaging, where we show significant improvements in the achievable polarization, in some cases reaching above 60% nuclear spin polarization. Furthermore, we introduce a site-selective deuteration scheme, where deuterium is included in the coupling network of a pyruvate ester to enhance the efficiency of the polarization transfer. These improvements are enabled by the fact that the transfer protocol avoids relaxation induced by strongly coupled quadrupolar nuclei.

Scalable and Tunable Diamond Nanostructuring Process for Nanoscale NMR Applications.

Nanostructuring of a bulk material is used to change its mechanical, optical, and electronic properties and to enable many new applications. We present a scalable fabrication technique that enables the creation of densely packed diamond nanopillars for quantum technology applications. The process yields tunable feature sizes without the employment of lithographic techniques. High-aspect-ratio pillars are created through oxygen-plasma etching of diamond with a dewetted palladium film as an etch mask. We demonstrate an iterative renewal of the palladium etch mask, by which the initial mask thickness is not the limiting factor for the etch depth. Following the process, 300-400 million densely packed 100 nm wide and 1 µm tall diamond pillars were created on a 3 × 3 mm2 diamond sample. The fabrication technique is tailored specifically to enable applications and research involving quantum coherent defect center spins in diamond, such as nitrogen-vacancy (NV) centers, which are widely used in quantum science and engineering. To demonstrate the compatibility of our technique with quantum sensing, NV centers are created in the nanopillar sidewalls and are used to sense 1H nuclei in liquid wetting the nanostructured surface. This nanostructuring process is an important element for enabling the wide-scale implementation of NV-driven magnetic resonance imaging or NV-driven NMR.