Magnetic resonance (MR) is an indispensable tool for diverse science, ranging from the most fundamental spin physics and chemistry, probed by NMR spectroscopy, to everyday clinical imaging performed by MRI. However, nuclear spin polarization remains weak even in magnetic fields of superconducting magnets, and only about 1 in 100,000 spins is detectable. Accordingly, NMR and MRI are cherished for their molecular specific spectra and contrast rich images, but suffer from very low sensitivity. We develop hyperpolarization chemistry that aligns much larger fractions of spins, enhancing NMR and MRI signals by up to 6 orders of magnitude, and breaking current sensitivity limitations in a wide range of applications.
Advancing Hyperpolarization Chemistry and Hyperpolarization Spin Physics
We use parahydrogen as the source of hyperpolarization. Para-hydrogen is the nuclear singlet state (up down – down up)/root(2) of dihydrogen, and represents a pure quantum reagent that is easy to produce. All that is required is cooling of hydrogen gas to ~30 K in the presence of iron oxide. With our latest techniques, the resulting para spin order can be converted to enhanced magnetization on a wide range of substrates, including vitamins, metabolites and drugs. Para-hydrogen is simply bubbled into room temperature solutions containing an inorganic Polarization Transfer Catalyst (PTC). and to-be-hyperpolarized substrates. We develop highly efficient PTCs, as well as ideal quantum mechanical strategies for maximum polarization transfer to substrates. This enables unprecedented applications for chemical analysis, metabolic screening, spectroscopy and imaging.
Portable and Nanoscale Hyperpolarized NMR using Optical Detection Schemes
With the simple and versatile parahydrogen hyperpolarization scheme on hand, it is now possible to detect the enhanced NMR signals with magnetic sensors that are sensitive at low-fields and low frequencies. This circumvents the need for expensive and bulky cryogenically cooled magnets, and opens unprecedented opportunities, ranging from handheld NMR devices to NMR of pL sized sample volumes . We integrate parahydrogen techniques with miniaturizable NMR sensors that do not require superconducting high-field magnets. As result, we progress towards miniaturized NMR devices to screen for drugs and specific metabolites in samples of bodily fluids, as well as NMR technology for the study of biochemistry on the nanoscale.
Hyperpolarized Elucidation of Biomolecular Structure and Dynamics
NMR is one of the most powerful tools for structural elucidation of biopolymers, such as proteins, DNA or RNA, and the study of their dynamics. However, many important structures remain elusive because of sensitivity limitations and associated difficulties in expressing and purifying sufficient material for successful characterization. Our hyperpolarization technologies have the potential to overcome these sensitivity limitations by creating hyperpolarization on small molecular substrates that interact with the macromolecules or even on the biopolymers themselves. The most attractive feature of our parahydrogen based technologies in this context is that they work directly in room temperature solutions and directly in the magnet where detection takes place permitting averaging over many scans and multidimensional NMR.
Affordable Molecular Imaging by Hyperpolarized Low-Field MRI
In general, our ability to track metabolism directly in vivo pales compared to its central relevance to life. It is my goal to establish hyperpolarization technology with the power to map metabolites and their journeys through metabolic pathways directly in animals and humans. We aim to combine parahydrogen based techniques with low-cost, high performance MRI to enable cost-efficient molecular imaging free of adverse effects, essentially using a vitamin shot for 3D molecular imaging. Hyperpolarized molecules are injected into rodents (and eventually patients) and the MRI signals reveal all information about chemical transformations and distribution, which leads to unprecedented insight into kinetic and mechanistic details in vivo.