Periodic Reporting for period 4 - HP4all (Persistent and Transportable Hyperpolarization for Magnetic Resonance)
Periodo di rendicontazione: 2021-07-01 al 2022-12-31
Magnetic resonance imaging (MRI) and nuclear magnetic resonance (NMR) and are two well-established powerful and versatile tools that are extensively used in many fields of research, in clinics and in industry. Despite considerable efforts involving highly sophisticated instrumentation, these techniques suffer from low sensitivity, which keeps many of today’s most interesting problems in modern analytical sciences below the limits of MR detection. Hyperpolarization (HP) in principle provides a solution to this limitation by preparing molecules in a 'hyperpolarized' state which improves the detection sensitivity by more than 10'000 folds. However the lifetime of these hyperpolarized states usually are on the order of seconds. The HP4all project enabled generating molecules in a hyperpolarized state that persists for hours, and can therefore in principle be transported to any point of use (hospital, NMR centers, etc.).
During the HP4all project, we have developed strategies and methods to generate, store, and deliver hyperpolarized molecules. In order to reach this objective, we have:
1) designed and built a dDNP polarizer and successfully achieved state-of-the-art performances. We have equipped this polarizer with a new generation of 3D-printed NMR coil for cross-polarization experiments.
S. J. Elliott, M. Ceillier, O. Cala, Q. Stern, S. F. Cousin, and S. Jannin, Simple and Cost-Effective Cross-Polarization Experiments under Dissolution-Dynamic Nuclear Polarization Conditions with a 3D-Printed 1H-13C Background-Free Radiofrequency Coil, J. Magn. Reson. Open, 10, 100033 (IF=2.2)
M. Baudin, B. Vuichoud, A. Bornet, G. Bodenhausen, S. Jannin, A cryogen-consumption-free system for dynamic nuclear polarization at 9.4 T, J. Magn. Reson. 294, 115, (2018).
2) worked on methods for improving polarization transfers and studying spin relaxation and diffusion. This work was published in various journals, from NMR specialized to general audiences such as Science Advances.
S. J. Elliott, Q. Stern, O. Cala, S. Jannin, Protonation-tuned dipolar order mediated 1H→13C cross-polarization for dissolution-dynamic nuclear polarization experiments, Solid-State Nucl. Magn. Reson., vol 116, 101762, 2021
S. J. Elliott, O. Cala, Q. Stern, S. F. Cousin, D. Eshchenko, R. Melzi, J. G. Kempf, and S. Jannin, Pulse sequence and sample formulation optimization for dipolar order mediated1H→13C cross-polarization, Phys. Chem. Chem. Phys., vol. 23, no. 15, pp. 9457–9465, 2021,
S. J. Elliott, O. Cala, Q. Stern, S. F. Cousin, M. Ceillier, V. Decker, and S. Jannin Boosting Dissolution-Dynamic Nuclear Polarization by Multiple-Step Dipolar Order Mediated 1H→13C Cross-Polarization, J. Magn. Reson. Open, p. 100018, Apr. 2021, (IF=2.2)
Q. Stern, S. F. Cousin, F. Mentink-Vigier, A. C. Pinon, S. J. Elliott, O. Cala, and S. Jannin. Direct observation of hyperpolarization breaking through the spin diffusion barrier. Sci. Adv., vol. 7, no. 18, pp. 1–14, 2021 (IF=14.1)
S. J. Elliott, S. F. Cousin, Q Chappuis, O Cala, M Ceillier, A Bornet, and S Jannin, Dipolar order mediated 1H → 13C cross-polarization for dissolution-dynamic nuclear polarization, Magn. Reson. 1, 89, (2020).
3) synthesized micro-architectured hyperpolarizing matrices that enabled the preparation of long-lived hyperpolarization with lifetimes exceeding hours. This finding was published in Nature Communications.
T. El Daraï, S. F. Cousin, Q. Stern, M. Ceillier, J. Kempf, D. Eshchenko, R. Melzi, M. Schnell, L. Gremillard, A. Bornet, J. Milani, B. Vuichoud, O. Cala, D. Montarnal, and S. Jannin, Porous functionalized polymers enable generating and transporting hyperpolarized mixtures of metabolites, Nat. Commun., vol. 12, no. 1, pp. 1–9, (2021)
4) developed hardware for the final injection of the hyperpolarized compounds which was published in an NMR-specialized journal:
M. Ceillier, O. Cala, T. El Daraï, S. F. Cousin, Q. Stern, S. Guibert, S. J. Elliott, A. Bornet, B. Vuichoud, J. Milani, C. Pages, D. Eshchenko, J. G. Kempf, C. Jose, S. A. Lambert, and S. Jannin, An automated system for fast transfer and injection of hyperpolarized solutions, J. Magn. Reson. Open, vol. 8–9, p. 100017, 2021,
1) designed and built a dDNP polarizer and successfully achieved state-of-the-art performances. We have equipped this polarizer with a new generation of 3D-printed NMR coil for cross-polarization experiments.
S. J. Elliott, M. Ceillier, O. Cala, Q. Stern, S. F. Cousin, and S. Jannin, Simple and Cost-Effective Cross-Polarization Experiments under Dissolution-Dynamic Nuclear Polarization Conditions with a 3D-Printed 1H-13C Background-Free Radiofrequency Coil, J. Magn. Reson. Open, 10, 100033 (IF=2.2)
M. Baudin, B. Vuichoud, A. Bornet, G. Bodenhausen, S. Jannin, A cryogen-consumption-free system for dynamic nuclear polarization at 9.4 T, J. Magn. Reson. 294, 115, (2018).
2) worked on methods for improving polarization transfers and studying spin relaxation and diffusion. This work was published in various journals, from NMR specialized to general audiences such as Science Advances.
S. J. Elliott, Q. Stern, O. Cala, S. Jannin, Protonation-tuned dipolar order mediated 1H→13C cross-polarization for dissolution-dynamic nuclear polarization experiments, Solid-State Nucl. Magn. Reson., vol 116, 101762, 2021
S. J. Elliott, O. Cala, Q. Stern, S. F. Cousin, D. Eshchenko, R. Melzi, J. G. Kempf, and S. Jannin, Pulse sequence and sample formulation optimization for dipolar order mediated1H→13C cross-polarization, Phys. Chem. Chem. Phys., vol. 23, no. 15, pp. 9457–9465, 2021,
S. J. Elliott, O. Cala, Q. Stern, S. F. Cousin, M. Ceillier, V. Decker, and S. Jannin Boosting Dissolution-Dynamic Nuclear Polarization by Multiple-Step Dipolar Order Mediated 1H→13C Cross-Polarization, J. Magn. Reson. Open, p. 100018, Apr. 2021, (IF=2.2)
Q. Stern, S. F. Cousin, F. Mentink-Vigier, A. C. Pinon, S. J. Elliott, O. Cala, and S. Jannin. Direct observation of hyperpolarization breaking through the spin diffusion barrier. Sci. Adv., vol. 7, no. 18, pp. 1–14, 2021 (IF=14.1)
S. J. Elliott, S. F. Cousin, Q Chappuis, O Cala, M Ceillier, A Bornet, and S Jannin, Dipolar order mediated 1H → 13C cross-polarization for dissolution-dynamic nuclear polarization, Magn. Reson. 1, 89, (2020).
3) synthesized micro-architectured hyperpolarizing matrices that enabled the preparation of long-lived hyperpolarization with lifetimes exceeding hours. This finding was published in Nature Communications.
T. El Daraï, S. F. Cousin, Q. Stern, M. Ceillier, J. Kempf, D. Eshchenko, R. Melzi, M. Schnell, L. Gremillard, A. Bornet, J. Milani, B. Vuichoud, O. Cala, D. Montarnal, and S. Jannin, Porous functionalized polymers enable generating and transporting hyperpolarized mixtures of metabolites, Nat. Commun., vol. 12, no. 1, pp. 1–9, (2021)
4) developed hardware for the final injection of the hyperpolarized compounds which was published in an NMR-specialized journal:
M. Ceillier, O. Cala, T. El Daraï, S. F. Cousin, Q. Stern, S. Guibert, S. J. Elliott, A. Bornet, B. Vuichoud, J. Milani, C. Pages, D. Eshchenko, J. G. Kempf, C. Jose, S. A. Lambert, and S. Jannin, An automated system for fast transfer and injection of hyperpolarized solutions, J. Magn. Reson. Open, vol. 8–9, p. 100017, 2021,
The HP4all project has demonstrated generating high and persistent hyperpolarization in a broad range of molecules, in a way that should enable transport and delivery over long distances for molecular imaging in MRI centers or hospitals. The main advances beyond state-of-the-art are related to the invention and optimization of new generations of polarizing matrices and the development of a method to generate hyperpolarization in these matrices and then transport this hyperpolarization remotely. We anticipate that this will enable applications of hyperpolarization transport in various fields (drug discovery, metabolomics and preclinical imaging).