Dynamic Nuclear Polarization; Nuclear Magnetic Resonance; Hyperpolarization; Polarized targets; Polarizing agents; Radicals; DNP; MRI; MRS; NMR; paramagnetic centers; contrast agents; photo-excited triplet state
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Dynamic Nuclear Polarization (DNP) methods were developed during the past decades for applications in nuclear and particle physics research. Continued improvements in DNP are pursued not only for the development of increasingly sophisticated polarized targets (used to investigate the role of spin in nuclear and particle interactions), but in particular to open up new fields in neutron science (exploiting the strong spin dependence of the neutron scattering).Recently, a unique enthusiasm for the DNP technique has developed in the magnetic resonance (MR) community, most prominently in its biomedical part, following an idea of researchers at Amersham (now part of GE Healthcare) who created very large nuclear spin polarizations in a liquid sample starting from DNP-enhanced frozen beads, such as used in polarized targets. This is now widely considered as one of the most promising techniques to increase the sensitivity of liquid-state NMR and in vivo MR, in particular for heteronuclei such as 13C . The clinical potential of the technique to probe the response to tumor treatment was recently discussed , and its clinical application in pH imaging was proposed .A consortium of Swiss researchers, now well-known as the Swiss DNP Initiative (SdnpI), was set up very soon after this “dissolution-DNP” method became available. It bundles together the unique know-how of the polarized-targets group at the Paul Scherrer Institute with the advanced spectroscopic and imaging methods available at two leading MR institutes sited at the EPFL: the Center for Biomedical Imaging (CIBM) and the Laboratory for Biological MR (LRMB). The SdnpI operates at the moment DNP machines at both these sites, and access to them is searched by highly-reputed scientists, also from outside Switzerland. It is the goal of the present proposal not only to consolidate this existing effort, but in particular to explore new avenues, several untested so far, that have a good chance to lead to new possibilities in neutron research and/or in dissolution-DNP. Although very different in their science, the two fields share a large underlying base of experimental methods, that will yield important synergies when developed simultaneously. The crucial step for Magnetic Resonance Spectroscopy (MRS) and Magnetic Resonance Imaging (MRI) applications is an efficient dissolution of the solid-state sample to obtain the “hyperpolarized” solution  and a rapid transfer to the MR equipment, because an intrinsic limitation of the technique is the finite life time of the hyperpolarized state. The signal is very intense, but only available for a limited amount of time. Furthermore its characteristic decay time T1 is shortened by the presence of the residual radicals necessary to perform the DNP. This effect must be minimized. In addition, the toxicity issue due the few mM of radical in the hyperpolarized solution has to be addressed and so far this problem has been largely overlooked.In the field of polarized targets a rather new DNP development is the use of photo-excited triplet states as source of electron polarization . Neither high fields nor low temperatures are required to achieve high proton polarizations, but the knowledge and understanding of these methods  remains fragmentary and dispersed. In principle, their simplified instrumentation (both in cryogenics and in magnetic fields) opens applications in neutron science and particle physics that cannot be envisaged with present methods. Obviously photo-excited triplet states are also attractive for dissolution DNP, since they disappear after the light is turned off. No attempts have been made so far to adapt this method to MRS/MRI, and more generally no molecule of biological interest has been investigated. Other paramagnetic centers that have not been considered so far for in vivo applications: biradicals, irradiated organic compounds or short-lived radicals that are quenched at room temperature.To evaluate the efficiency of a paramagnetic agent in dissolution-DNP as well as to monitor the polarization of a target at low temperature, it is essential to develop new NMR techniques. Indeed, probing polarization levels with high precision without destroying part of the enhanced polarization is not trivial.The present project concerns the development of DNP methods for three categories of applications: in vivo biological MR, in vitro biological and chemical MR, polarized targets. Although each of them has its specificities and requirements, many overlapping issues exist and will be addressed.