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Methodology in Dynamic Nuclear Polarization

Applicant Comment Arnaud
Number 124901
Funding scheme Project funding (Div. I-III)
Research institution Institut de Physique des Nanostructures EPFL - FSB - IPN
Institution of higher education EPF Lausanne - EPFL
Main discipline Condensed Matter Physics
Start/End 01.10.2009 - 30.09.2012
Approved amount 333'478.00
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Keywords (13)

Dynamic Nuclear Polarization; Nuclear Magnetic Resonance; Hyperpolarization; Polarized targets; Polarizing agents; Radicals; DNP; MRI; MRS; NMR; paramagnetic centers; contrast agents; photo-excited triplet state

Lay Summary (English)

Lead
Lay summary
A consortium of Swiss researchers recently teamed up to develop techniques in the field of Dynamic Nuclear Polarization (DNP) for various applications ranging from particle physics to biomedical applications (http://sdnpi.epfl.ch). The present project concerns the development of methods for in vivo and in vitro biological Magnetic Resonance (MR), chemical MR, and polarized targets for particle physics.MR provides very accurate anatomical and physiological information in biomedicine. The spatial resolution of MR Imaging is high but its sensitivity is poor. Hyperpolarization by means of DNP leads to dramatic improvements in MR sensitivity, increasing the signal intensity by several orders of magnitude. DNP was developed for applications in particle physics and continued improvements are pursued to investigate the role of spin in nuclear and particle interactions. For MR applications, a frozen solution containing polarizing agents and molecules of biological interest is prepared. The nuclear spin polarization of the molecules is enhanced via DNP. The last step consists in dissolving the frozen solution in hot water.The crucial step for MR applications is an efficient dissolution of the frozen solution and a rapid transfer to the MR machine, 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 is shortened by the presence of residual polarizing agents. This effect must be minimized. The toxicity issue due the polarizing agents also has to be addressed. In the field of polarized targets, a new development is the use of photo-excited triplet states as polarizing agents, which requires neither high magnetic fields nor low temperatures. The simplified instrumentation opens applications in neutron science and particle physics that cannot be envisaged with present methods.Metabolic processes can be studied in real time in vivo following the infusion of hyperpolarized molecules. The clinical potential of hyperpolarization to probe the response to tumor treatment was recently demonstrated. Hyperpolarization also opened new perspectives for molecular imaging, which aims at determining the spatial distribution of biomolecules. Polarization analysis is a main concern at existing neutron scattering facilities and ways of polarizing neutrons over a broad velocity range has to be found. The investigation of magnetic materials with e.g. Small Angle Neutron Scattering would greatly benefit from the implementation of a spin filter based on photo-excited triplet states.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
In vivo detection of brain Krebs cycle intermediate by hyperpolarized magnetic resonance.
Mishkovsky Mor, Comment Arnaud, Gruetter Rolf (2012), In vivo detection of brain Krebs cycle intermediate by hyperpolarized magnetic resonance., in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cer, 32, 2108-2113.
Localized in vivo hyperpolarization transfer sequences
Mishkovsky M, Cheng T, Comment A, Gruetter R (2012), Localized in vivo hyperpolarization transfer sequences, in MAGNETIC RESONANCE IN MEDICINE, 68(2), 349-352.
Spin filtering neutrons with a proton target dynamically polarized using photo-excited triplet states
Haag M, van den Brandt B, Eichhorn TR, Hautle P, Wenckebach WT (2012), Spin filtering neutrons with a proton target dynamically polarized using photo-excited triplet states, in NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND, 678, 91-97.
BDPA: An Efficient Polarizing Agent for Fast Dissolution Dynamic Nuclear Polarization NMR Spectroscopy
Lumata L, Ratnakar SJ, Jindal A, Merritt M, Comment A, Malloy C, Sherry AD, Kovacs Z (2011), BDPA: An Efficient Polarizing Agent for Fast Dissolution Dynamic Nuclear Polarization NMR Spectroscopy, in CHEMISTRY-A EUROPEAN JOURNAL, 17(39), 10825-10827.
Feasibility of in vivo 15N MRS detection of hyperpolarized 15N labeled choline in rats.
Cudalbu Cristina, Comment Arnaud, Kurdzesau Fiodar, van Heeswijk Ruud B, Uffmann Kai, Jannin Sami, Denisov Vladimir, Kirik Deniz, Gruetter Rolf (2010), Feasibility of in vivo 15N MRS detection of hyperpolarized 15N labeled choline in rats., in Physical chemistry chemical physics : PCCP, 12(22), 5818-23.
Hyperpolarizing gases via dynamic nuclear polarization and sublimation.
Comment A, Jannin S, Hyacinthe J-N, Miéville P, Sarkar R, Ahuja P, Vasos P R, Montet X, Lazeyras F, Vallée J-P, Hautle P, Konter J A, van den Brandt B, Ansermet J-Ph, Gruetter R, Bodenhausen G (2010), Hyperpolarizing gases via dynamic nuclear polarization and sublimation., in Physical review letters, 105(1), 018104-018104.
Scavenging free radicals to preserve enhancement and extend relaxation times in NMR using dynamic nuclear polarization.
Miéville Pascal, Ahuja Puneet, Sarkar Riddhiman, Jannin Sami, Vasos Paul R, Gerber-Lemaire Sandrine, Mishkovsky Mor, Comment Arnaud, Gruetter Rolf, Ouari Olivier, Tordo Paul, Bodenhausen Geoffrey (2010), Scavenging free radicals to preserve enhancement and extend relaxation times in NMR using dynamic nuclear polarization., in Angewandte Chemie (International ed. in English), 49(35), 6182-5.
Long-lived states to sustain hyperpolarized magnetization.
Vasos P R, Comment A, Sarkar R, Ahuja P, Jannin S, Ansermet J-P, Konter J A, Hautle P, van den Brandt B, Bodenhausen G (2009), Long-lived states to sustain hyperpolarized magnetization., in Proceedings of the National Academy of Sciences of the United States of America, 106(44), 18469-73.
Proton NMR of (15)N-choline metabolites enhanced by dynamic nuclear polarization.
Sarkar Riddhiman, Comment Arnaud, Vasos Paul R, Jannin Sami, Gruetter Rolf, Bodenhausen Geoffrey, Hall Hélène, Kirik Deniz, Denisov Vladimir P (2009), Proton NMR of (15)N-choline metabolites enhanced by dynamic nuclear polarization., in Journal of the American Chemical Society, 131(44), 16014-5.

Associated projects

Number Title Start Funding scheme
133562 Hyperpolarization techniques for biomedical applications 01.04.2011 SNSF Professorships
143297 Development of a novel neutron spin filter 01.08.2013 Project funding (Div. I-III)
109479 New methods of dynamic nuclear polarisation for metabolic imgaging and particle scattering experiments 01.01.2006 Project funding (Div. I-III)
144424 Novel Developments in Dynamic Nuclear Polarization Methodology 01.10.2012 Project funding (Div. I-III)
109479 New methods of dynamic nuclear polarisation for metabolic imgaging and particle scattering experiments 01.01.2006 Project funding (Div. I-III)
131087 Metabolic and functional imaging of neural activation 01.12.2010 Project funding (Div. I-III)

Abstract

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 [1]. The clinical potential of the technique to probe the response to tumor treatment was recently discussed [2], and its clinical application in pH imaging was proposed [3].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 [4] 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 [5]. Neither high fields nor low temperatures are required to achieve high proton polarizations, but the knowledge and understanding of these methods [6] 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.
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