Non-dDNP HP approaches: PHIP-SAH and nano-diamonds

The main objective of this work package is to develop non dDNP hyperpolarisation technologies: PHIP-SAH and nano- diamonds, for generating other viable means for generating HP CAs as alternatives for GBCAs, that could, in the longer term, translate to the clinic.

Task 2.1: A set-up for PHIP-SAH polarisation and optimisation

We will build a dedicated set-up that will allow the whole sequence of events involved in PHIP-SAH (hydrogenation, spin order transfer from parahydrogen to 13C, hydrolysis, and phase separation) to be carried out in a continuous flow. The aim is to increase the concentration of the HP agents in aqueous solution (≥80mM) and the hyperpolarisation level (≥ 10% polarisation on 13C). To this end new hydrogenation complexes and supported catalysts will be developed and routes for efficient removal of the catalyst will be established. Polarisation transfer will be optimised using magnetic field cycling and dedicated RF pulse sequences.

Task 2.2: PHIP-SAH agents

We will develop PHIP-SAH driven HP 13C labelled agents that are non-metabolic and suitable for perfusion and tissue- retention imaging (e.g. urea, acetate-D3, and carbonate).

Task 2.3: Optically driven 13C hyperpolarisation in ensembles of nano-diamonds

Optically-driven polarisation of 13C in ensembles of nano-diamonds will be pursued through modulation of the orientation and strength of the applied magnetic field during optical pumping in combination with microwave pulse schemes.

Task 2.4: Polarisation transfer from nano-diamonds

We will explore the effects of nano-diamond size, NV concentration, 13C isotopic abundance, and surface treatments on the polarization build-up and transfer. Surface treatment consists of removal of other carbon (non diamond) impurities and oxidation of surface groups, which will be optimised. Standardised protocols will be established to guarantee reproducibility.

Task 2.5: Production of 13C enriched nano-diamonds and polarisation with dDNP

To test dDNP driven polarisation of the nano-diamonds, we will enrich nano-diamonds with 13C, optimise surface treatments, and apply coating with a biopolymer to prohibit aggregation. Polarisation in solution will be tested in a dDNP device.