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Parahydrogen-induced polarization (PHIP) is an inexpensive way to produce hyperpolarized molecules with polarization levels of >10 % in the solution-state, but is strongly limited in generality since it requires chemical reactions/ interactions with H 2 . Here we report a new method to widen the scope of PHIP hyperpolarization: a source molecule is produced via PHIP with high 13 C polarization, and precipitated out of solution together with a target species. Spin diffusion within the solid carries the polarization onto 13 C spins of the target, which can then be dissolved for solution-state applications. We name this method PHIP-SSD (PHIP with solid-state spin diffusion) and demonstrate it using PHIP-polarized [1- 13 C]-fumarate as the source molecule, to polarize different 13 C-labelled target molecules. 13 C polarizations of between 0.01 and 3 % were measured on [1- 13 C]-benzoic acid, depending on the molar ratio of fumarate:benzoate in the solid state. We also show that PHIP-SSD does not require specific co-crystallization conditions by grinding dry powders of target molecules together with solid fumarate crystals, and obtain 13 C signal enhancements of between 100 and 200 on [ 13 C, 15 N 2 ]-urea, [1- 13 C]-pyruvate, and [1- 13 C]-benzoic acid. This approach appears to be a promising new strategy for facile hyperpolarization based on PHIP., (© 2024 Wiley-VCH GmbH.)

Hyperpolarization techniques increase nuclear spin polarization by more than four orders of magnitude, enabling metabolic MRI. Even though hyperpolarization has shown clear value in clinical studies, the complexity, cost and slowness of current equipment limits its widespread use. Here, a polarization procedure of [1- 13 C]pyruvate based on parahydrogen-induced polarization by side-arm hydrogenation (PHIP-SAH) in an automated polarizer is demonstrated. It is benchmarked in a study with 48 animals against a commercial dissolution dynamic nuclear polarization (d-DNP) device. Purified, concentrated (≈70-160 mM) and highly hyperpolarized (≈18%) solutions of pyruvate are obtained at physiological pH for volumes up to 2 mL within 85 s in an automated process. The safety profile, image quality, as well as the quantitative perfusion and lactate-to-pyruvate ratios, are equivalent for PHIP and d-DNP, rendering PHIP a viable alternative to established hyperpolarization techniques., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Carbon-13 hyperpolarized pyruvate is about to become the next-generation contrast agent for molecular magnetic resonance imaging of cancer and other diseases. Here, efficient and rapid pyruvate hyperpolarization is achieved via signal amplification by reversible exchange (SABRE) with parahydrogen through synergistic use of substrate deuteration, alternating, and static microtesla magnetic fields. Up to 22 and 6% long-lasting 13 C polarization ( T 1 = 3.7 ± 0.25 and 1.7 ± 0.1 min) is demonstrated for the C1 and C2 nuclear sites, respectively. The remarkable polarization levels become possible as a result of favorable relaxation dynamics at the microtesla fields. The ultralong polarization lifetimes will be conducive to yielding high polarization after purification, quality assurance, and injection of the hyperpolarized molecular imaging probes. These results pave the way to future in vivo translation of carbon-13 hyperpolarized molecular imaging probes prepared by this approach.

We present a versatile method for the preparation of hyperpolarized [1- 13 C]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- 13 C]-fumarate solution of volumes up to 3 mL with 13-20% 13 C-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 13 C-labeled precursor for the hydrogenation reaction with high yield, starting from 13 CO 2 as a cost-effective source for 13 C-labeled compounds.

Magnetic resonance imaging of 13 C-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 13 C 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.

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 mm 2 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 1 H 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., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

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 1 H 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.

In a cross-sectional survey we obtained figures on the current state of periodontal health of 14 to 16-year-old pupils who attend different types of schools in Lippstadt, a town with a balanced social structure. A rate of 82% of gingivitis morbidity was found, including an average CPITN of 0.49. Nevertheless, only 43.8% of the examined periodontia showed signs of gingivitis. Analysis of the individual values showed marked differences related with age, sex and type of school.

In a cross-sectional examination we received a current state of the prevalence of caries of 14-16 year old pupils, who attend different types of schools in Lippstadt, a town with a balanced social structure. An average DMF-S-Index of 14.6 (DMF-T: 7.8) was found. The particular results show a clear influence of age, sex and type of school. Comparing our results with former examinations a tendency of reduced caries-prevalence can be derived from the low annual caries-increment.