Periodic Reporting for period 4 - FunMagResBeacons (Functionalized Magnetic Resonance Beacons for Enhanced Spectroscopy and Imaging)
Reporting period: 2023-04-01 to 2024-09-30
This project aimed to design and test methodology for addressing the general problem of imaging metabolism, deep inside opaque objects, such as the human body. Although magnetic resonance imaging (MRI) is a powerful method for imaging anatomic structure, its signal strength is generally too weak to detect compounds in low concentration such as common metabolites. The project exploited a phenomenon called nuclear hyperpolarization to greatly enhance the MRI signals, and to exploit a property of certain molecules called long-lived states to store and transport such hyperpolarised spin order. The agents under development provide a new set of versatile spectroscopic tools for the spatially resolved study of chemistry, biochemistry, diffusion, flow and percolation inside opaque objects. The fMRB agents support hyperpolarised long-lived spin order, and are functionalised, so that they “light up" in an NMR or magnetic resonance imaging (MRI) experiment, upon triggering by specific chemical signals. Potential applications of this methodology including the imaging and staging of cancer, so that the progress of cancerous tissue may be judged by its metabolic activity, rather than a crude measure of its size.
The first stage of the project concerned the design and study of “core” modules which support the long-lived hyperpolarised states under ambient conditions, the development of methodology for hyperpolarising these modules, and the technology for understanding the decay of the hyperpolarised spin order and for optimising its lifetime. During the project several candidate chemical systems were synthesized and studied, including the very novel chemical systems known as endofullerenes, in which single atoms or molecules are encapsulated in closed carbon cages. In particular the novel 3He@C60 endofullerene was synthesized and studied. In this material a single atom of the helium isotope He-3 was encapsulated in a C60 cage, and a novel interaction was detected between the trapped 3He atoms and the 13C nuclei of the surrounding cage. In addition, during the project, we discovered some important deficiencies in the theory of magnetic resonance under highly non-equilibrium conditions, and developed a new theory to cover this novel but increasingly important regime. We also developed new methodology for generating long-lived nuclear spin order, and performed, in collaboration with other groups, some indicative proof-of-concept hyperpolarised MRI experiments showing that the release of strong NMR signals from long-lived nuclear spin states may be triggered by metabolism, and used for imaging. These results were disseminated in academic journals, and also received publicity through the award of research prizes for this work, including the 2021 Erwin Schrödinger award of the Helmholtz association.
We progressed beyond the state-of-the-art on many different fronts: (1) new chemical compounds including highly novel atomic and molecular endofullerenes, and new synthetic routes to novel isotopically labelled “core modules” for the storage of hyperpolarised nuclear spin order; (2) new methodology for interconverting long-lived nuclear spin order and ordinary nuclear magnetization; (3) new theories of nuclear spin relaxation, far from equilibrium, and for the physical boundaries of such non-equilibrium states; (3) new methods for generating hyperpolarised nuclear spin order starting from hydrogen gas enriched in the para nuclear spin isomer; (4) new methods for generating hyperpolarised nuclear spin order through a sequence of applied radiofrequency fields; (5) proof-of-concept demonstrations of hyperpolarised magnetic resonance imaging, using the release of hyperpolarised spin order from a long-lived state, triggered by a metabolic process; (6) proof-of-concept demonstration of the hyperpolarization, purification and storage of a hyperpolarised metabolite fumarate.