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Nuclear hyperpolarization comes of age
Journal of Magnetic Resonance 264 (2016) 1–2
Contents lists available at ScienceDirect
Journal of Magnetic Resonance journal homepage: www.elsevier.com/locate/jmr
Editorial
Nuclear hyperpolarization comes of age
The last decade has seen transformative developments and previously unthinkable opportunities opening in the fields of solidstate, solution and imaging NMR, thanks to the advent of methods for hyperpolarizing the nuclear spins. Probably since the introduction of the Fourier Transform, and to some extent for similar reasons, few single concepts have had the potential to affect so many areas of magnetic resonance, as the dissemination of these sensitivity-enhancing methods. The generality of these methods, particularly those based on dynamic nuclear polarization (DNP), has triggered exciting new research over a wide range of applications ranging from material sciences and structural biology to metabolic analysis, biochemistry, biology and clinical diagnosis. This excitement has been accompanied by concurrent efforts to better understand the physical basis of nuclear hyperpolarization to optimize the instrumentation that will achieve higher levels of nuclear polarization over a wide range of conditions, and with new NMR and MRI sequences and experiments that will better fit the particular demands of these experiments. This concentrated attention has also brought in close synergy the electron and nuclear magnetic resonance communities, particularly as the former showed the latter that electrons could be exploited via DNP to originate nuclear hyperpolarization over a wide range of solution and solid state systems. Such ‘‘DNP revolution” also rekindled similar searches based on alternatives such as para-Hydrogen induced polarization and optical pumping. The kind of NMR enhancement that all these techniques could provide would have been unreachable by traditional approaches, for instance further optimizations of the NMR receiving hardware or increasing the NMR/MRI observation fields. Notably, the sensitivity enhancing potential of all these techniques – and particularly that of DNP – had been known for several decades. But it was only thanks to the recent realization that the gains of DNP could be achieved without giving up on the use of high magnetic fields or rescinding on ‘‘usual” operating temperatures, that interest in these techniques was revived. The expanding scope of hyperpolarized NMR has been intensively profiled in the pages of the Journal of Magnetic Resonance, with its proven track record in the exposition of new spin-physics insights, of new experiments combining electron and nuclear magnetic resonance, and on new NMR applications on solids, liquids and in vivo systems. With the first decade of the hyperpolarization MR renaissance behind us, JMR continues its tradition of synergizing EPR/ NMR/MRI research by presenting a series of ‘‘Perspectives” on the current state of the art in this rapidly changing field. To date, hyperpolarization of nuclear spins from electron spins by continuous microwave irradiation at pumped liquid helium http://dx.doi.org/10.1016/j.jmr.2016.01.020 1090-7807/Ó 2016 Elsevier Inc. All rights reserved.
temperature (1–1.5 K) and subsequent dissolution of the polarized sample, has found the largest range of applications among all hyperpolarization methods. One of the fathers of this ‘‘Dissolution DNP” approach, Jan Henrik Ardenkjær-Larsen, provides this Special Issue with a thought-provoking overview, including a short history, a critical assessment of current capabilities, and a short list of blind spots in the state of the technique. Aurélien Bornet and Sami Jannin follow this contribution by going into the details of Dissolution DNP NMR, and consider a variety of aspects including new agents with better efficiency for 1H-directed polarization, DNP at higher fields, microwave frequency modulation, DNP including 1 H–13C cross polarization, and a transfer regime for the dissolved sample that avoids passing through low magnetic fields where polarization is easily lost. An alternative view of optimization of dissolution DNP is provided by Fabian Jähnig et al., who discuss the different ways that have been used to date for boosting the polarization level achieved in the first step at low temperature, the efforts for reducing the time required to reach this polarization level, and several strategies for avoiding loss of polarization during dissolution and transfer of the sample. For narrow-line polarizing agents, which appear to be the optimal choice for polarizing heteronuclei via the solid-effect, Daniel Wis´niewski et al. use a model of a central electron spin surrounded by many nuclear spins to better study and understand this process. Five additional Perspectives follow these fundamental introduction to Dissolution DNP, and variations and applications of this methodology in the framework of different applications. The method’s most revolutionary application is arguably in in vivo MRI; the paper by Arnaud Comment presents current state-of-the-art and challenges arising in this kind of molecular and metabolic imaging, for in vivo pre-clinical settings. The contribution by Greg Olsen et al. discusses the potential use of 1H-enhancement in hyperpolarized water, as a source for enhancing the sensitivity of biomolecular NMR; peptides and proteins are thus shown to exhibit over 300fold sensitivity enhancements, in their 2D HMQC spectra. In a third type of application, the Perspective by Jan van Bentum et al. discusses a new general way of achieving hyperpolarization in solution NMR spectroscopy, by including rapid-melt DNP (a ‘‘cousin” of dissolution DNP) as well as in situ Overhauser DNP. Interestingly, these authors argue that supercritical solvents such as CO2, are attractive for Overhauser DNP due to faster dynamics and less background than can be achieved with ‘normal’ solvents. Overhauser DNP in solution at high fields is also discussed in depth in the contribution by Prisner et al., who show that two key problems in such experiments – strong microwave absorption of water at high frequencies and decreasing efficiency of the Overhauser
2
Editorial / Journal of Magnetic Resonance 264 (2016) 1–2
mechanism with increasing field – can actually be surmounted. Another account on the emerging field of high field Overhauser DNP comes from Enrico Ravera et al., who also discuss the recent assignment of solid-state hyperpolarization with unexpected dependence on magnetic field and microwave frequency at a temperature of 100 K to an Overhauser mechanism and 13C Overhauser DNP. One of the most active branches of hyperpolarization NMR is DNP at low temperatures in solid samples under magic angle sample spinning (MAS DNP NMR). To a large extent this is thanks to availability of commercial spectrometers for this purpose; to highlight this opportunity the Bruker team, represented by Melanie Rosay et al., discuss available options, considerations in developing such instrumentation, and the next steps to be expected. These spectrometers operate at 100 K with liquid nitrogen cooling and nitrogen as a driving gas for the spinner and a gyrotron as a microwave source. The required microwave power can be drastically reduced by operating at 25–30 K, as discussed in the Perspective by Kent Thurber and Robert Tycko, who combined helium cooling with nitrogen as spinning gas to show first results for calmodulin. An alternative way for operating down to 30 K without prohibitive helium costs is the use of closed-loop helium recycling; this is described in the contribution by Matsuki et al., a Perspective that also describes millimeter-wave gyrotron designs for operating at 395 and 460 GHz electron Larmor frequencies. Another closed-loop system is for MAS DNP NMR at about 30 K is presented by Daniel Lee et al., who point to the higher spinning speeds at given rotor diameter that are available with helium as a driving gas because of the lower velocity of sound compared to nitrogen close to its boiling point. A crucial point in all these unusual experiments involves clarifying the extent to which the microwave employed in the sample irradiation, reaches the electron spins in these MAS systems; using ingenious techniques melding imaging, solid state NMR and DNP, Marek Pruski and coworkers present unexpected insights on the nature of this process. The close relation between the polarization mechanisms driven by the microwave irradiation and the EPR parameters of the polarizing agents, also calls for ancillary measurements focused on the electron’s behav-
ior; the contribution of Ting Ann Siaw et al. addresses this matter, using a combined DNP/EPR instrument that operates at 200 GHz electron/300 MHz 1H frequencies. Last but not least insight on another kind of electron ? nuclear hyperpolarization process, this one including optically polarizable centers in diamonds by Jeffrey Reimer and coworkers, closes these expositions with a Perspective of what might be a completely new world in terms of NMR sensitization and even detection. We would like to use this opportunity to thank all our contributors for their timely and comprehensive views on a variety of important areas in hyperpolarized magnetic resonance. While the prospects opened up by these methodologies is unique, it is clear that continuous progress in this area – at levels of fundamental understanding, of experimental optimizations, and of achieving a wider range of applications – is still needed to fulfill hyperpolarization’s full potential. Such progress will have to be, first of foremost, of an advanced technical nature – a nature that we not only encourage but also celebrate and are proud of at JMR. We hope that you will find the articles included in this Special Issue stimulating, and we look forward to your feedback and to your contributions to JMR to serve in this key emerging area of research in our community. Gunnar Jeschke ETH Zurich, Laboratory of Physical Chemistry, Zurich CH-8093, Switzerland E-mail address: [email protected] Lucio Frydman Weizmann Institute, Chemical Physics Department, Rehovot 76100, Israel E-mail address: [email protected] Received 27 January 2016
Contents lists available at ScienceDirect
Journal of Magnetic Resonance journal homepage: www.elsevier.com/locate/jmr
Editorial
Nuclear hyperpolarization comes of age
The last decade has seen transformative developments and previously unthinkable opportunities opening in the fields of solidstate, solution and imaging NMR, thanks to the advent of methods for hyperpolarizing the nuclear spins. Probably since the introduction of the Fourier Transform, and to some extent for similar reasons, few single concepts have had the potential to affect so many areas of magnetic resonance, as the dissemination of these sensitivity-enhancing methods. The generality of these methods, particularly those based on dynamic nuclear polarization (DNP), has triggered exciting new research over a wide range of applications ranging from material sciences and structural biology to metabolic analysis, biochemistry, biology and clinical diagnosis. This excitement has been accompanied by concurrent efforts to better understand the physical basis of nuclear hyperpolarization to optimize the instrumentation that will achieve higher levels of nuclear polarization over a wide range of conditions, and with new NMR and MRI sequences and experiments that will better fit the particular demands of these experiments. This concentrated attention has also brought in close synergy the electron and nuclear magnetic resonance communities, particularly as the former showed the latter that electrons could be exploited via DNP to originate nuclear hyperpolarization over a wide range of solution and solid state systems. Such ‘‘DNP revolution” also rekindled similar searches based on alternatives such as para-Hydrogen induced polarization and optical pumping. The kind of NMR enhancement that all these techniques could provide would have been unreachable by traditional approaches, for instance further optimizations of the NMR receiving hardware or increasing the NMR/MRI observation fields. Notably, the sensitivity enhancing potential of all these techniques – and particularly that of DNP – had been known for several decades. But it was only thanks to the recent realization that the gains of DNP could be achieved without giving up on the use of high magnetic fields or rescinding on ‘‘usual” operating temperatures, that interest in these techniques was revived. The expanding scope of hyperpolarized NMR has been intensively profiled in the pages of the Journal of Magnetic Resonance, with its proven track record in the exposition of new spin-physics insights, of new experiments combining electron and nuclear magnetic resonance, and on new NMR applications on solids, liquids and in vivo systems. With the first decade of the hyperpolarization MR renaissance behind us, JMR continues its tradition of synergizing EPR/ NMR/MRI research by presenting a series of ‘‘Perspectives” on the current state of the art in this rapidly changing field. To date, hyperpolarization of nuclear spins from electron spins by continuous microwave irradiation at pumped liquid helium http://dx.doi.org/10.1016/j.jmr.2016.01.020 1090-7807/Ó 2016 Elsevier Inc. All rights reserved.
temperature (1–1.5 K) and subsequent dissolution of the polarized sample, has found the largest range of applications among all hyperpolarization methods. One of the fathers of this ‘‘Dissolution DNP” approach, Jan Henrik Ardenkjær-Larsen, provides this Special Issue with a thought-provoking overview, including a short history, a critical assessment of current capabilities, and a short list of blind spots in the state of the technique. Aurélien Bornet and Sami Jannin follow this contribution by going into the details of Dissolution DNP NMR, and consider a variety of aspects including new agents with better efficiency for 1H-directed polarization, DNP at higher fields, microwave frequency modulation, DNP including 1 H–13C cross polarization, and a transfer regime for the dissolved sample that avoids passing through low magnetic fields where polarization is easily lost. An alternative view of optimization of dissolution DNP is provided by Fabian Jähnig et al., who discuss the different ways that have been used to date for boosting the polarization level achieved in the first step at low temperature, the efforts for reducing the time required to reach this polarization level, and several strategies for avoiding loss of polarization during dissolution and transfer of the sample. For narrow-line polarizing agents, which appear to be the optimal choice for polarizing heteronuclei via the solid-effect, Daniel Wis´niewski et al. use a model of a central electron spin surrounded by many nuclear spins to better study and understand this process. Five additional Perspectives follow these fundamental introduction to Dissolution DNP, and variations and applications of this methodology in the framework of different applications. The method’s most revolutionary application is arguably in in vivo MRI; the paper by Arnaud Comment presents current state-of-the-art and challenges arising in this kind of molecular and metabolic imaging, for in vivo pre-clinical settings. The contribution by Greg Olsen et al. discusses the potential use of 1H-enhancement in hyperpolarized water, as a source for enhancing the sensitivity of biomolecular NMR; peptides and proteins are thus shown to exhibit over 300fold sensitivity enhancements, in their 2D HMQC spectra. In a third type of application, the Perspective by Jan van Bentum et al. discusses a new general way of achieving hyperpolarization in solution NMR spectroscopy, by including rapid-melt DNP (a ‘‘cousin” of dissolution DNP) as well as in situ Overhauser DNP. Interestingly, these authors argue that supercritical solvents such as CO2, are attractive for Overhauser DNP due to faster dynamics and less background than can be achieved with ‘normal’ solvents. Overhauser DNP in solution at high fields is also discussed in depth in the contribution by Prisner et al., who show that two key problems in such experiments – strong microwave absorption of water at high frequencies and decreasing efficiency of the Overhauser
2
Editorial / Journal of Magnetic Resonance 264 (2016) 1–2
mechanism with increasing field – can actually be surmounted. Another account on the emerging field of high field Overhauser DNP comes from Enrico Ravera et al., who also discuss the recent assignment of solid-state hyperpolarization with unexpected dependence on magnetic field and microwave frequency at a temperature of 100 K to an Overhauser mechanism and 13C Overhauser DNP. One of the most active branches of hyperpolarization NMR is DNP at low temperatures in solid samples under magic angle sample spinning (MAS DNP NMR). To a large extent this is thanks to availability of commercial spectrometers for this purpose; to highlight this opportunity the Bruker team, represented by Melanie Rosay et al., discuss available options, considerations in developing such instrumentation, and the next steps to be expected. These spectrometers operate at 100 K with liquid nitrogen cooling and nitrogen as a driving gas for the spinner and a gyrotron as a microwave source. The required microwave power can be drastically reduced by operating at 25–30 K, as discussed in the Perspective by Kent Thurber and Robert Tycko, who combined helium cooling with nitrogen as spinning gas to show first results for calmodulin. An alternative way for operating down to 30 K without prohibitive helium costs is the use of closed-loop helium recycling; this is described in the contribution by Matsuki et al., a Perspective that also describes millimeter-wave gyrotron designs for operating at 395 and 460 GHz electron Larmor frequencies. Another closed-loop system is for MAS DNP NMR at about 30 K is presented by Daniel Lee et al., who point to the higher spinning speeds at given rotor diameter that are available with helium as a driving gas because of the lower velocity of sound compared to nitrogen close to its boiling point. A crucial point in all these unusual experiments involves clarifying the extent to which the microwave employed in the sample irradiation, reaches the electron spins in these MAS systems; using ingenious techniques melding imaging, solid state NMR and DNP, Marek Pruski and coworkers present unexpected insights on the nature of this process. The close relation between the polarization mechanisms driven by the microwave irradiation and the EPR parameters of the polarizing agents, also calls for ancillary measurements focused on the electron’s behav-
ior; the contribution of Ting Ann Siaw et al. addresses this matter, using a combined DNP/EPR instrument that operates at 200 GHz electron/300 MHz 1H frequencies. Last but not least insight on another kind of electron ? nuclear hyperpolarization process, this one including optically polarizable centers in diamonds by Jeffrey Reimer and coworkers, closes these expositions with a Perspective of what might be a completely new world in terms of NMR sensitization and even detection. We would like to use this opportunity to thank all our contributors for their timely and comprehensive views on a variety of important areas in hyperpolarized magnetic resonance. While the prospects opened up by these methodologies is unique, it is clear that continuous progress in this area – at levels of fundamental understanding, of experimental optimizations, and of achieving a wider range of applications – is still needed to fulfill hyperpolarization’s full potential. Such progress will have to be, first of foremost, of an advanced technical nature – a nature that we not only encourage but also celebrate and are proud of at JMR. We hope that you will find the articles included in this Special Issue stimulating, and we look forward to your feedback and to your contributions to JMR to serve in this key emerging area of research in our community. Gunnar Jeschke ETH Zurich, Laboratory of Physical Chemistry, Zurich CH-8093, Switzerland E-mail address: [email protected] Lucio Frydman Weizmann Institute, Chemical Physics Department, Rehovot 76100, Israel E-mail address: [email protected] Received 27 January 2016