Clifford Bowers

Efficiently Generates Hyperpolarized Metabolites Used as Biomarkers in Disease Detection and Monitoring in Magnetic Resonance Imaging

This system uses an ultrasonic spray injection hydrogenation reactor to rapidly prepare hyperpolarized metabolites for sensitivity-enhanced nuclear magnetic resonance spectroscopy and magnetic resonance imaging. Using hyperpolarized metabolites in diagnostic imaging can enable the study of metabolic processes by enhancing magnetic resonance imaging signals by over five orders of magnitude. The global diagnostic imaging market should reach $35 billion by 2026. Previous methods to produce hyperpolarized metabolites with less efficient mixing processes resulted in comparatively lower hyperpolarization levels and polarization yields.

Researchers at the University of Florida have developed a system that rapidly generates hyperpolarized metabolites in bulk using an ultrasonic spray injection nozzle. Ultrasonic spray injection into parahydrogen gas generates higher rates of hyperpolarization and higher polarization yields than conventional production methods. The ultrasonic spray injection process is essentially isobaric, eliminating the expansion cooling accompanied by large pressure drops that occurs using standard spray injection.

Application

This system achieves efficient and continuous generation of hyperpolarized metabolites for use in sensitivity-enhanced nuclear magnetic resonance spectroscopy and magnetic resonance imaging

Advantages

• Optimizes hydrogenation of unsaturated precursors with parahydrogen, delivering higher performance than conventional spray-injection systems
• Efficiently mixes liquid reactants and para-enriched hydrogen gas, generating high polarization yields of hyperpolarized metabolites
• Ultrasonic spray injection produces smaller and uniformly sized microdroplets, increasing the reaction rate and reducing spin-lattice relaxation losses in hyperpolarized metabolite production
• Enables utilization of acetate, pyruvate, pyruvate, and other biomolecules, allowing for the detection and treatment monitoring of cancers and other diseases

Technology

This system rapidly generates hyperpolarized metabolites for use in biomedical magnetic resonance imaging. Precursors are injected into a reaction chamber pressurized with para-enriched hydrogen gas through the ultrasonically vibrated nozzle. The nozzle optimizes the formation of small uniform microdroplets, promoting the rate of hydrogenation reactions with para-hydrogenation in the formation of hyperpolarized metabolites.

Related publication: Ferrer, M.-J., Kuker, E., Semenova, E., Gangano, A., Lapak, M., Grenning, A., Dong, V., & Bowers, C. (n.d.). Adiabatic Passage through Level Anticrossings in Systems of Chemically Inequivalent Protons Incorporating Parahydrogen: Theory, Experiment, and Prospective Applications. Journal of the American Chemical Society, 144(45), 20847–20853. https://doi.org/10.1021/jacs.2c09000 

Polarizes Water Molecules from Parahydrogen to Intensify Their Nuclear Magnetic Resonance Signals for Detection in Low Magnetic Fields

The use of hyperpolarized water as a contrast agent in magnetic resonance imaging (MRI) could dramatically shorten scanning times for patients, provide new imaging modalities, and avoid the risks associated with conventional contrast agents (e.g. gadolinium). However, the only existing method for making hyperpolarized water, i.e. dynamic nuclear polarization (DNP), requires complex instrumentation incorporating cryogenics, high frequency microwaves, and a powerful superconducting magnet system. In a new process developed at the University of Florida, hyperpolarized liquid water is produced from parahydrogen* by heterogeneous spin conversion catalysis (SCC) at low magnetic field. The key advantages of this parahydrogen-based SCC method include its far greater simplicity, reliability, and scalability. Most importantly, the SCC process can be performed at low magnetic field and does not require a superconducting magnet. In principle, hyperpolarized water can be continuously produced by flowing it over the specially formulated insoluble SCC nanoparticles, rending pure hyperpolarized water that is suitable for in vivo biomedical use. Production of hyperpolarized water by the SCC process has far-reaching implications. Since it is relatively inexpensive and does not require a superconducting magnet, it can be deployed for low-field medical MRI in remote or impoverished regions. *Parahydrogen is a metastable quantum state of molecular hydrogen that can be quickly and inexpensively prepared, stored and transported

Application

A catalytic process that hyperpolarizes a fluid, such as water, ethanol, or methanol, to enhance the molecular nuclear magnetic resonance signals for use in sensitivity-enhanced NMR spectroscopy and MRI at low magnetic fields

Advantages

• Increases the proton spin polarization in water molecules, thereby decreasing the amount of time required for an MRI scan
• Produces hyperpolarized water that yields intense NMR signals, improving the performance of ultra-low field MRI and low-field NMR spectroscopy
• Establishes a continuous, scalable catalysis system that utilizes parahydrogen, providing a fast, flexible, and inexpensive source of hyperpolarized water with improved throughput
• Uses a non-toxic catalyst that is insoluble and easily separates from the water, enabling the production of highly-pure hyperpolarized water suitable for in vivo use as an MRI contrast agent

Technology

This heterogeneous spin conversion catalytic process yields hyperpolarized water from parahydrogen without the use of high magnetic fields or microwave irradiation. The hyperpolarized water is produced by dissolution of parahydrogen gas in a suspension of the specially formulated catalyst, composed of synthesized metallic nanoparticles, which is insoluble in liquid water. The water molecules in hyperpolarized water exhibit strong nuclear magnetic resonance signals, enabling it to function as an intrinsic MRI contrast agent. In addition to water, this same catalytic process can also hyperpolarize other fluids, including ethanol and methanol, for other applications.