Optical Chopper for Longitudinal-Detected Electron Paramagnetic Resonance at 188 GHz/6.7 T.

Dynamic nuclear polarization (DNP) is a nuclear magnetic resonance (NMR) hyperpolarization technique that mediates polarization transfer from unpaired electrons to nuclear spins. DNP performance can vary significantly depending on the types of polarizing agents employed, and the criteria for optimum DNP efficiency are not fully understood. Thus, a better understanding of the structure, electron paramagnetic resonance (EPR) line widths, and relaxation properties would aid in designing more efficient DNP polarizing agents.

Long-lived enhanced magnetization-A practical metabolic MRI contrast material.

Noninvasive tracking of biochemical processes in the body is paramount in diagnostic medicine. Among the leading techniques is spectroscopic magnetic resonance imaging (MRI), which tracks metabolites with an amplified (hyperpolarized) magnetization signal injected into the subject just before scanning. Traditionally, the brief enhanced magnetization period of these agents limited clinical imaging.

Xe Dynamic Nuclear Polarization Demystified: The Influence of the Glassing Matrix on the Radical Properties.

Xe dissolution dynamic nuclear polarization (DNP) is a controversial topic. The gold standard technique for hyperpolarized xenon magnetic resonance imaging (MRI) is spin exchange optical pumping, which received FDA approval in 2022. Nevertheless, the versatility of DNP for enhancing the signal of any NMR active nucleus might provide new perspectives for hyperpolarized Xe NMR/MRI.

Multi-sample/multi-nucleus parallel polarization and monitoring enabled by a fluid path technology compatible cryogenic probe for dissolution dynamic nuclear polarization.

Low throughput is one of dissolution Dynamic Nuclear Polarization (dDNP) main shortcomings. Especially for clinical and preclinical applications, where direct C nuclei polarization is usually pursued, it takes hours to generate one single hyperpolarized (HP) sample. Being able to hyperpolarize more samples at once represents a clear advantage and can expand the range and complexity of the applications.

Design and performance of a small bath cryostat with NMR capability for transport of hyperpolarized samples.

As of today, dissolution Dynamic Nuclear Polarization (dDNP) is the only clinically available hyperpolarization technique for C-MRI. Despite the clear path towards personalized medicine that dDNP is paving as an alternative and/or complement to Positron Emission Tomography (PET), the technique struggles to enter everyday clinical practice. Because of the minute-long hyperpolarization lifetime after dissolution, one of the reasons lies in the need and consequent complexities of having the machine that generates the hyperpolarization (i.

How to improve the efficiency of a traditional dissolution dynamic nuclear polarization (dDNP) apparatus: Design and performance of a fluid path compatible dDNP/LOD-ESR probe.

Dissolution Dynamic Nuclear Polarization (dDNP) was invented almost twenty years ago. Ever since, hardware advancement has observed 2 trends: the quest for DNP at higher field and, more recently, the development of cryogen free polarizers. Despite the DNP community is slowly migrating towards "dry" systems, many "wet" polarizers are still in use.

Radical-free hyperpolarized MRI using endogenously occurring pyruvate analogues and UV-induced nonpersistent radicals.

It was recently demonstrated that nonpersistent radicals can be generated in frozen solutions of metabolites such as pyruvate by irradiation with UV light, enabling radical-free dissolution dynamic nuclear polarization. Although pyruvate is endogenous, the presence of pyruvate may interfere with metabolic processes or the detection of pyruvate as a metabolic product, making it potentially unsuitable as a polarizing agent. Therefore, the aim of the current study was to characterize solutions containing endogenously occurring alternatives to pyruvate as UV-induced nonpersistent radical precursors for in vivo hyperpolarized MRI.

Measuring Glycolytic Activity with Hyperpolarized [H, U-C] D-Glucose in the Naive Mouse Brain under Different Anesthetic Conditions.

Glucose is the primary fuel for the brain; its metabolism is linked with cerebral function. Different magnetic resonance spectroscopy (MRS) techniques are available to assess glucose metabolism, providing complementary information. Our first aim was to investigate the difference between hyperpolarized C-glucose MRS and non-hyperpolarized H-glucose MRS to interrogate cerebral glycolysis.

Metabolic contrast agents produced from transported solid C-glucose hyperpolarized via dynamic nuclear polarization.

Magnetic Resonance Imaging combined with hyperpolarized C-labelled metabolic contrast agents produced via dissolution Dynamic Nuclear Polarization can, non-invasively and in real-time, report on tissue specific aberrant metabolism. However, hyperpolarization equipment is expensive, technically demanding and needs to be installed on-site for the end-user. In this work, we provide a robust methodology that allows remote production of the hyperpolarized C-labelled metabolic contrast agents.

Hyperpolarization via dissolution dynamic nuclear polarization: new technological and methodological advances.

Dissolution-DNP is a method to boost liquid-state NMR sensitivity by several orders of magnitude. The technique consists in hyperpolarizing samples by solid-state dynamic nuclear polarization at low temperature and moderate magnetic field, followed by an instantaneous melting and dilution of the sample happening inside the polarizer. Although the technique is well established and the outstanding signal enhancement paved the way towards many applications precluded to conventional NMR, the race to develop new methods allowing higher throughput, faster and higher polarization, and longer exploitation of the signal is still vivid.

C Dynamic Nuclear Polarization using SA-BDPA at 6.7 T and 1.1 K: Coexistence of Pure Thermal Mixing and Well-Resolved Solid Effect.

SA-BDPA is a water-soluble, narrow-line width radical previously used for dynamic nuclear polarization (DNP) signal enhancement in solid-state magic angle spinning NMR spectroscopy. Here, we report the first study using SA-BDPA under dissolution DNP conditions (6.7 T and 1.

Hyperpolarized water through dissolution dynamic nuclear polarization with UV-generated radicals.

In recent years, hyperpolarization of water protons via dissolution Dynamic Nuclear Polarization (dDNP) has attracted increasing interest in the magnetic resonance community. Hyperpolarized water may provide an alternative to Gd-based contrast agents for angiographic and perfusion Magnetic Resonance Imaging (MRI) examinations, and it may report on chemical and biochemical reactions and proton exchange while perfoming Nuclear Magnetic Resonance (NMR) investigations. However, hyperpolarizing water protons is challenging.

Optimized microwave delivery in dDNP.

Dissolution dynamic nuclear polarization (dDNP) has permitted the production of highly polarized liquid-state samples, enabling real-time imaging of metabolic processes non-invasively in vivo. The desire for higher magnetic resonance sensitivity has led to the development of multiple home-built and commercial dDNP polarizers employing solid-state microwave sources. Providing efficient microwave delivery that avoids unwanted heating of the sample is a crucial step to achieve high nuclear polarization.

Gadolinium Effect at High-Magnetic-Field DNP: 70% C Polarization of [U-C] Glucose Using Trityl.

We show that the trityl electron spin resonance (ESR) features, crucial for an efficient dynamic nuclear polarization (DNP) process, are sample-composition-dependent. Working at 6.7 T and 1.

Efficient Hyperpolarization of U- C-Glucose Using Narrow-Line UV-Generated Labile Free Radicals.

Free radicals generated by UV-light irradiation of a frozen solution containing a fraction of pyruvic acid (PA) have demonstrated their dissolution dynamic nuclear polarization (dDNP) potential, providing up to 30 % [1- C]PA liquid-state polarization. Moreover, their labile nature has proven to pave a way to nuclear polarization storage and transport. Herein, differently from the case of PA, the issue of providing dDNP UV-radical precursors (trimethylpyruvic acid and its methyl-deuterated form) not involved in any metabolic pathway was investigated.

Photogenerated Radical in Phenylglyoxylic Acid for in Vivo Hyperpolarized C MR with Photosensitive Metabolic Substrates.

Whether for C magnetic resonance studies in chemistry, biochemistry, or biomedicine, hyperpolarization methods based on dynamic nuclear polarization (DNP) have become ubiquitous. DNP requires a source of unpaired electrons, which are commonly added to the sample to be hyperpolarized in the form of stable free radicals. Once polarized, the presence of these radicals is unwanted.

Probing cardiac metabolism by hyperpolarized 13C MR using an exclusively endogenous substrate mixture and photo-induced nonpersistent radicals.

Purpose: To probe the cardiac metabolism of carbohydrates and short chain fatty acids simultaneously in vivo following the injection of a hyperpolarized C-labeled substrate mixture prepared using photo-induced nonpersistent radicals.

Methods: Droplets of mixed [1- C]pyruvic and [1- C]butyric acids were frozen into glassy beads in liquid nitrogen. Ethanol addition was investigated as a means to increase the polarization level.

Thermal annihilation of photo-induced radicals following dynamic nuclear polarization to produce transportable frozen hyperpolarized C-substrates.

Hyperpolarization via dynamic nuclear polarization (DNP) is pivotal for boosting magnetic resonance imaging (MRI) sensitivity and dissolution DNP can be used to perform in vivo real-time C MRI. The type of applications is however limited by the relatively fast decay time of the hyperpolarized spin state together with the constraint of having to polarize the C spins in a dedicated apparatus nearby but separated from the MRI magnet. We herein demonstrate that by polarizing C with photo-induced radicals, which can be subsequently annihilated using a thermalization process that maintains the sample temperature below its melting point, hyperpolarized C-substrates can be extracted from the DNP apparatus in the solid form, while maintaining the enhanced C polarization.

Direct dynamic measurement of intracellular and extracellular lactate in small-volume cell suspensions with (13)C hyperpolarised NMR.

Hyperpolarised (HP) (13)C NMR allows enzymatic activity to be probed in real time in live biological systems. The use of in vitro models gives excellent control of the cellular environment, crucial in the understanding of enzyme kinetics. The increased conversion of pyruvate to lactate in cancer cells has been well studied with HP (13)C NMR.

Over 35% liquid-state 13C polarization obtained via dissolution dynamic nuclear polarization at 7 T and 1 K using ubiquitous nitroxyl radicals.

The most versatile method to increase liquid-state (13)C NMR sensitivity is dissolution dynamic nuclear polarization. The use of trityl radicals is usually required to obtain very large (13)C polarization via this technique. We herein demonstrate that up to 35% liquid-state (13)C polarization can be obtained in about 1.

Hyperpolarization without persistent radicals for in vivo real-time metabolic imaging.

Hyperpolarized substrates prepared via dissolution dynamic nuclear polarization have been proposed as magnetic resonance imaging (MRI) agents for cancer or cardiac failure diagnosis and therapy monitoring through the detection of metabolic impairments in vivo. The use of potentially toxic persistent radicals to hyperpolarize substrates was hitherto required. We demonstrate that by shining UV light for an hour on a frozen pure endogenous substance, namely the glucose metabolic product pyruvic acid, it is possible to generate a concentration of photo-induced radicals that is large enough to highly enhance the (13)C polarization of the substance via dynamic nuclear polarization.