Periodic Reporting for period 3 - AlternativesToGd (Hyperpolarised MR technologies and molecular probes as alternatives for conventional metal-containing contrast agents for MRI examinations)
Okres sprawozdawczy: 2022-04-01 do 2023-09-30
We have focused on the following aspects:
WP1 - Unconventional agents for dDNP HP MRI:
The polarization level of [15N2]urea and water protons has been increased. Novel encapsulation protocols aimed at encapsulating D2O with the above agents were further developed.
WP2 - Non-dDNP HP approaches: PHIP-SAH and nano-diamonds:
The PHIP-SAH technology has been further optimized and automated to reach high 13C polarization values and hydrogenation yields. An automated system has been developed that is fully open to the knowledgeable user. Nanodiamond polarisation via light sources was comprehensively studied and multiple setups were investigated in attempt transfer polarisation to small molecules external to the nanodiamond (without success). This warrants further investigation of dDNP polarisation of nanodiamonds. The reproducible production of synthetic nanodiamonds in the lab was established and well characterised. Desirable coating of the nanodiamonds has been established and warrants utility in multiple applications.
WP3 - MRI tools for HP X-nuclei:
The project has completed an independent transmit/receive insert prototype for MRI scanners. The quality of imaging using this insert was beyond expectations and will be instrumental in further development of the AlternativesToGd approach. In vivo application of a B1-insensitive transfer of spin polarization between hyperpolarized 15N and coupled protons has shown utility. In vivo application of low-coherence gradient trajectories for hyperpolarized acquisitions has been tested in vivo in clinical scanners and showed superb imaging quality.
WP4 - Validation:
Imaging of hyperpolarized compounds in vivo has been performed with hyperpolarized water and hyperpolarized [15N2]urea. Models for imaging cardiovascular conditions were established. PHIP-SAH driven hyperpolarized 13C-labelled agents were optimized and imaged in vivo. Most importantly, cancer tumours were visualized in vivo using dDNP hyperpolarized [15N2]urea dissolved in D2O. With this result, the project has achieved its goal which was “to demonstrate the feasibility of replacing GBCA with a metal-free approach in at least one type of contrast-enhanced MRI examination.
The results of the project have been published in more than 32 papers in high quality journals and in multiple conference presentations. Dedicated project sessions have been held in major conferences. The project shared primary data for all of the work curried out during the project on freely available archives. About 8 additional papers are in preparation and several continuation applications for funding to further develop the project’s results have been submitted.
Society will gain by having access to medical imaging that does not leave potentially toxic deposits in the bodies of children and adults undergoing MRI examinations and does not contaminate the environment.
Our results have the potential to access new markets for medical imaging and contrast media companies, whether established or young start-ups. There is clearly a market for new contrast agents that are free of the undesirable properties of GBCAs.
European scientists in academia and industry have been at the forefront of the fields of molecular imaging and contrast media for many years. AlternativesToGd has established new contrast mechanisms for contrast enhanced MRI. The outcomes of AlternativesToGd have the potential to build a new medical application, thereby building new leadership capacity in the field of novel non Gd-based contrast agents through collaboration of the key actors in related fields, ambitious biotech industries, as well as through contributions from excellent young researchers.
Other substantial impacts include:
• Build nascent European industry focused on betterment of MRI diagnostics and efficient hyperpolarisation.
• Provide tailored diagnostic tools for coronary heart disease, ischemic stroke, and cancer.
• Introduce long lived hyperpolarized nitrogen-15 compounds for clinical use.
• Introduce hyperpolarized water to clinical use in MRI diagnostics.
• Revolutionise PHIP technologies for generating contrast agents on the spot, for clinical use.
• New encapsulation technologies for use in hyperpolarized MRI for enhanced performance of medical imaging.