Metabolic monitoring and reaction rate estimation using hyperpolarized NMR technology requires accurate quantitative analysis of multidimensional data scenarios. Currently, this analysis is often performed in a two-stage procedure, which is prone to errors in uncertainty propagation and estimation. We propose an approach derived from a Bayesian hierarchical model that intrinsically propagates uncertainties and operates on the full data to maximize the precision at minimal uncertainty. In an analytic treatment, we reduce the estimation procedure to a least-squares optimization problem which can be understood as an extension of the Variable Projection (VarPro) approach for data scenarios with two predictors. We investigate the method's efficacy in two experiments with hyperpolarized metabolites recorded with conventional high-field NMR devices and a micronscale NMR setup using Nitrogen-Vacancy centers in diamond for detection, respectively. In both examples, the new approach improves estimates compared to Fourier methods and proves operational advantages over a two-stage procedure employing VarPro. While the approach presented is motivated by NMR analysis, it is straightforwardly applicable to further estimation scenarios with similar data structure, such as time-resolved photospectroscopy.

Hyperpolarized 13C Magnetic Resonance Imaging (HP-MRI) enables real-time, non-invasive assessment of metabolism in diseases including cancer and neurodegeneration. Broader adoption has been limited by the complexity, duration, and lack of standardization of current hyperpolarization methods. This study evaluated POLARIS Preclinical, a parahydrogen-induced polarization (PHIP) hyperpolarizer designed to streamline production of hyperpolarized 13C agents. Four POLARIS systems were deployed across eight international research centers to produce hyperpolarized [1-13C]pyruvate doses within 90 seconds. In vitro and in vivo imaging was conducted in multiple animal models using MRI systems operating at 1.4, 3, 7, and 9.4 Tesla. Metabolic conversion of pyruvate to lactate and bicarbonate was successfully measured across all sites. POLARIS enabled rapid, reproducible production of hyperpolarized [1-13C]pyruvate and demonstrated consistent performance across instruments, institutions, and field strengths. These results support standardized, high-throughput metabolic MRI for multicenter studies and translational research in oncology, neurology, and cardiovascular disease.

Nuclear spin hyperpolarization techniques, such as dynamic nuclear polarization (DNP) and parahydrogen-induced polarization (PHIP), have revolutionized nuclear magnetic resonance and magnetic resonance imaging. In these methods, a readily available source of high spin order, either electron spins in DNP or singlet states in hydrogen for PHIP, is brought into close proximity with nuclear spin targets, enabling efficient transfer of spin order under external quantum control. Despite vast disparities in energy scales and interaction mechanisms between electron spins in DNP and nuclear singlet states in PHIP, a pseudo-spin formalism allows us to establish an intriguing equivalence. As a result, the important low-field polarization transfer regime of PHIP can be mapped onto an analogous system equivalent to pulsed-DNP. This establishes a correspondence between key polarization transfer sequences in PHIP and DNP, facilitating the transfer of sequence development concepts. This promises fresh insights and significant cross-pollination between DNP and PHIP polarization sequence developers.

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.

Metabolic Magnetic Resonance Imaging Hyperpolarization techniques increase nuclear spin polarization by more than four orders of magnitude, enabling metabolic MRI. In article number 2303441, Stephan Knecht, Michael Keim, Franz Schilling, Ilai Schwartz, and co-workers demonstrate a polarization procedure of [1-13C]pyruvate based on parahydrogen-induced polarization by side-arm hydrogenation (PHIP-SAH). It is benchmarked in preclinical in vivo experiments against a commercial dissolution dynamic nuclear polarization (DNP) device. The safety profile, image quality, as well as the quantitative perfusion and lactate-topyruvate ratios, are equivalent for PHIP and DNP, rendering PHIP a viable alternative to established hyperpolarization techniques.

There is a fundamental issue with the use of dynamic nuclear polarization (DNP) to enhance nuclear spin polarization: the same polarizing agent (PA) needed for DNP is also responsible for shortening the lifetime of the hyperpolarization. As a result, long-term storage and transport of hyperpolarized samples is severely restricted and the apparatus for DNP is necessarily located near or integrated with the apparatus using the hyperpolarized spins. In this paper, we demonstrate that naphthalene single crystals can serve as a long-lived reservoir of proton polarization that can be exploited to enhance signals in benchtop and high-field NMR of target molecules in solution at a site 300 km away by a factor of several thousand. The naphthalene protons are polarized using short-lived optically excited triplet states of pentacene instead of stable radicals. In the absence of optical excitation, the electron spins remain in a singlet ground state, eliminating the major pathway of nuclear spin-lattice relaxation. The polarization decays with a time constant of about 50 h at 80 K and 0.5 T or above 800 h at 5 K and 20 mT. A module based on a Halbach array yielding a field of 0.75 T and a conventional cryogenic dry shipper, operating at liquid nitrogen temperature, allows storage and long distance transport of the polarization to a remote laboratory, where the polarization of the crystal is transferred after dissolution to a target molecule of choice by intermolecular cross-relaxation. The procedure has been executed repeatedly and has proven to be reliable and robust.

The HYPNOESYS method (Hyperpolarized NOE System), which relies on the dissolution of optically polarized crystals, has recently emerged as a promising approach to enhance the sensitivity of NMR spectroscopy in the solution state. However, HYPNOESYS is a single-shot method that is not generally compatible with multidimensional NMR. Here we show that 2D NMR spectra can be obtained from HYPNOESYS-polarized samples, using single-scan acquisition methods. The approach is illustrated with a mixture of terpene molecules and a benchtop NMR spectrometer, paving the way to a sensitive, information-rich and affordable analytical method.

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

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.

Hyperpolarization of nuclear spins enhances nuclear magnetic resonance signals, which play a key role for imaging and spectroscopy in the natural and life sciences. This signal amplification unlocks previously inaccessible techniques, such as metabolic imaging of cancer cells. In this work, electron spins from the photoexcited triplet state of pentacene-doped naphthalene crystals are used to polarize surrounding protons. As existing strategies are rendered less effective by experimental constraints, they are replaced with optimal control pulses designed with RedCRAB. In contrast to previous optimal control approaches, which consider an average single nucleus, this closed-loop optimization is macroscopic. A 28% improvement in signal and 15% faster polarization rate is observed. Additionally, a strategy called Autonomously-optimized Repeated Linear Sweep (ARISE) is introduced to efficiently tailor existing hyperpolarization sequences in the presence of experimental uncertainty to enhance their performance. ARISE is expected to be broadly applicable in many experimental settings.

Diffusion noise is a major source of spectral line broadening in liquid state nano-scale nuclear magnetic resonance with shallow nitrogen-vacancy centres, whose main consequence is a limited spectral resolution. This limitation arises by virtue of the widely accepted assumption that nuclear spin signal correlations decay exponentially in nano-NMR. However, a more accurate analysis of diffusion shows that correlations survive for a longer time due to a power-law scaling, yielding the possibility for improved resolution and altering our understanding of diffusion at the nano-scale. Nevertheless, such behaviour remains to be demonstrated in experiments. Using three different experimental setups and disparate measurement techniques, we present overwhelming evidence of power-law decay of correlations. These result in sharp-peaked spectral lines, for which diffusion broadening need not be a limitation to resolution.

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.

Here we report the synthesis of 13C-enriched diamond powder with sub-micron particle sizes via High Pressure High Temperature (HPHT) growth. Diamond powder with a tailored isotopic enrichment is particularly interesting for implementation of Dynamic Nuclear spin Polarization (DNP) and 13C enrichment plays an important role for increasing the signal to noise ratio in Nuclear Magnetic Resonance (NMR) and Magnetic Resonance Imaging. We applied Electron Paramagnetic Resonance (EPR) and NMR spectroscopy to the sub-micron diamond material as well as Optically Detected Magnetic Resonance (ODMR) and atomic force microscopy to investigate preselected nano-sized particles. The 13C spin concentrations were evaluated with NMR for the initial particle ensemble and with ODMR for the nanodiamond fraction, showing the homogeneous distribution of 13C density in particles with different sizes. The 13C nuclear spin-lattice relaxation decay (T1) shows a multiexponential behavior, where the fast relaxing component is attributed to relaxation from surface defects. Additionally, an optical method for estimating the NV− concentration in nanodiamonds is presented. The obtained powder is promising as a base material for the production of 13C-enriched nanodiamonds for DNP applications.

Fluorescent nanodiamonds containing negatively-charged nitrogen-vacancy (NV-) centers are promising for a wide range of applications, such as for sensing, as fluorescence biomarkers, or to hyperpolarize nuclear spins. NV- centers are formed from substitutional nitrogen (P1 centers) defects and vacancies in the diamond lattice. Maximizing the concentration of NVs is most beneficial, which justifies the search for methods with a high yield of conversion from P1 to NV-. We report here the characterization of surface cleaned fluorescent micro- and nanodiamonds, obtained by irradiation of commercial diamond powder with high-energy (10 MeV) electrons and simultaneous annealing at 800 degrees C. Using this technique and increasing the irradiation dose, we demonstrate the creation of NV- with up to 25% conversion yield. Finally, we monitor the creation of irradiation-induced spin-1 defects in microdiamond particles, which we associate with W16 and W33 centers, and investigate the effects of irradiation dose and particle size on the coherence time of NV-. (C) 2020 Elsevier Ltd. All rights reserved.

In this Letter, we demonstrate initialization and readout of nuclear spins via a negatively charged silicon-vacancy (SiV) electron spin qubit. Under Hartmann-Hahn conditions the electron spin polarization is coherently transferred to the nuclear spin. The readout of the nuclear polarization is observed via the fluorescence of the SiV. We also show that the coherence time of the nuclear spin (6 ms) is limited by the electron spin-lattice relaxation due to the hyperfine coupling to the electron spin. This Letter paves the way toward realization of building blocks of quantum hardware with an efficient spin-photon interface based on the SiV color center coupled to a long lasting nuclear memory.

Efficient polarization of organic molecules is of extraordinary relevance when performing nuclear magnetic resonance (NMR) and imaging. Commercially available routes to dynamical nuclear polarization (DNP) work at extremely low temperatures, relying on the solidification of organic samples and thus bringing the molecules out of their ambient thermal conditions. In this work, we investigate polarization transfer from optically pumped nitrogen vacancy centers in diamond to external molecules at room temperature. This polarization transfer is described by both an extensive analytical analysis and numerical simulations based on spin bath bosonization and is supported by experimental data in excellent agreement. These results set the route to hyperpolarization of diffusive molecules in different scenarios and consequently, due to an increased signal, to high-resolution NMR.