Configuration and Performance of a Mobile 129Xe Polarizer

A stand-alone, self-contained and transportable system for the polarization of (129)Xe by spin exchange optical pumping with Rb is described. This mobile polarizer may be operated in batch or continuous flow modes with medium amounts of hyperpolarized (129)Xe for spectroscopic or small animal applications. A key element is an online nuclear magnetic resonance module which facilitates continuous monitoring of polarization generation in the pumping cell as well as the calculation of the absolute (129)Xe polarization. The performance of the polarizer with respect to the crucial parameters temperature, xenon and nitrogen partial pressures, and the total gas flow is discussed. In batch mode the highest (129)Xe polarization of P(Xe) = 40 % was achieved using 0.1 mbar xenon partial pressure. For a xenon flow of 6.5 and 26 mln/min, P(Xe) = 25 % and P(Xe) = 13 % were reached, respectively. The mobile polarizer may be a practical and efficient means to make the applicability of hyperpolarized (129)Xe more widespread

Production of highly concentrated and hyperpolarized metabolites within seconds in high and low magnetic fields

Hyperpolarized metabolites are very attractive contrast agents for in vivo magnetic resonance imaging studies enabling early diagnosis of cancer, for example. Real-time production of concentrated solutions of metabolites is a desired goal that will enable new applications such as the continuous investigation of metabolic changes. To this end, we are introducing two NMR experiments that allow us to deliver high levels of polarization at high concentrations (50 mM) of an acetate precursor (55% 13C polarization) and acetate (17% 13C polarization) utilizing 83% para-state enriched hydrogen within seconds at high magnetic field (7 T). Furthermore, we have translated these experiments to a portable low-field spectrometer with a permanent magnet operating at 1 T. The presented developments pave the way for a rapid and affordable production of hyperpolarized metabolites that can be implemented in e.g. metabolomics labs and for medical diagnosis

Influence of spin 1/2 hetero-nuclei on spin relaxation and polarization transfer among strongly coupled protons

Effects of spin-spin interactions on the nuclear magnetic relaxation dispersion (NMRD) of protons were studied in a situation where spin ½ hetero- nuclei are present in the molecule. As in earlier works [K. L. Ivanov, A. V. Yurkovskaya, and H.-M. Vieth, J. Chem. Phys.129, 234513 (2008)10.1063/1.3040272;S. E. Korchak, K. L. Ivanov, A. V. Yurkovskaya, and H.-M. Vieth, J. Chem. Phys.133, 194502 (2010)10.1063/1.3495988], spin-spin interactions have a pronounced effect on the relaxivity tending to equalize the longitudinal relaxation times once the spins become strongly coupled at a sufficiently low magnetic field. In addition, we have found influence of 19F nuclei on the proton NMRD, although in the whole field range, studied protons and fluorine spins were only weakly coupled. In particular, pronounced features in the proton NMRD were found; but each feature was predominantly observed only for particular spin states of the hetero-nuclei. The features are explained theoretically; it is shown that hetero-nuclei can affect the proton NMRD even in the limit of weak coupling when (i) protons are coupled strongly and (ii) have spin-spin interactions of different strengths with the hetero-nuclei. We also show that by choosing the proper magnetic field strength, one can selectively transfer proton spin magnetization between spectral components of choice

Оценка влияния динамики инвестиций на рост валового регионального продукта в регионах Севера и Арктической зоны Российской Федерации

This article presents results of a study conducted using mathematical and statistical modelling of regional economic specifics of the Russian Northern and Arctic regions in comparison to the national economic trend. The research continues a series of works on modelling the dynamics of GRP production aimed at improving the measurement quality of the interaction between the main production factors and assessing the specificity of their influence on the economic growth in the regions under review. The article considers the impact of investments on the GRP production in the Northern and Arctic regions is argued which is determined by a new approach to the management of these territories through the formation of support zones of development based on the implementation of interconnected different scale investment projects. Mathematical and statistical modelling of GRP production in the Northern and Arctic regions and the Russian Federation as a whole was carried out using the multiplicative production function and the CES production function. For the eight regions of the North [Karelia, Komi Republic, Arkhangelsk region, Nenets autonomous area, Yamal-Nenets autonomous area, Republic of Tuva, Republic of Sakha (Yakutia), Kamchatka territory, and Magadan region] and for the Russian Federation as a whole, were matched variants of a model, linking GRP with investments. For four constituent entities (Murmansk region, Sakhalin region, Khanty-Mansi autonomous area - Yugra, and Chukotka autonomous area), it was not possible to select such variants of the model. In this regard the authors point out that there is a need for further improvement of mathematical and statistical modelling of the dependence of economic development of the regions on the dynamics of investment activity.Данная публикация отражает результаты исследования с использованием математико-статистического моделирования региональных особенностей экономического развития Севера и Арктической зоны Российской Федерации в сравнении с общероссийским экономическим трендом. Исследование продолжает серию работ авторов по моделированию динамики производства на основе показателя валового регионального продукта (ВРП) с целью повышения качества измерения взаимодействия основных факторов производства, адекватной оценки специфики их влияния на экономический рост в рассматриваемых регионах страны. Аргументирована актуальность анализа влияния инвестиций на производство ВРП, определяемая новым подходом к управлению северными и арктическими территориями России посредством формирования опорных зон развития на основе реализации взаимосвязанных инвестиционных проектов разного масштаба. Проведено математико-статистическое моделирование факторов динамики производства ВРП в регионах Севера, Арктики и Российской Федерации в целом с использованием мультипликативной производственной функции и производственной функции CES. Для восьми регионов Севера [Республика Карелия, Республика Коми, Архангельская область, Ненецкий автономный округ, Ямало-Ненецкий автономный округ, Республика Тыва, Республика Саха (Якутия), Камчатский край, Магаданская область] и Российской Федерации в целом были подобраны варианты модели, отображающие взаимосвязь роста ВРП и динамики инвестиций. Для четырех субъектов Российской Федерации - Мурманской и Сахалинской областей, Ханты-Мансийского автономного округа - Югры, Чукотского автономного округа - адекватные варианты моделей подобрать не удалось. В этой связи авторами обоснована необходимость дальнейшего совершенствования математико-статистического моделирования зависимости экономического развития регионов от динамики инвестиционной деятельности

Hyperpolarisation in gekoppelten Vielspinsystemen

Introduction 1 1\. Hyperpolarization of nuclear spins 4 1.1 Chemically induced dynamic nuclear polarization 4 1.2 Dynamic nuclear polarization 11 1.3 Parahydrogen induced polarization 14 1.4 Hyperpolarization transfer among coupled spins 18 1.5 Nuclear magnetic relaxation dispersion in scalar coupled systems 25 2\. Experimental setup 28 2.1 Spectrometer control unit: DAMARIS 28 2.2 Field-cycling part 33 General description 35 Auxiliary magnetic system 36 Mechanical shuttling system 38 Light irradiation 39 Probehead 39 Influence of magnetic susceptibility 40 Reduction of eddy currents 43 Mathematical correction of FID 44 Summary 45 2.3 High field time-resolved CIDNP setup 46 2.4 DNP setup 48 3\. Polarization transfer in scalar coupled multi spin systems 51 3.1 Photo-CIDNP transfer in AMP, N-acetylhistidine and cycloundecanone 52 Experimental part 52 Photo-CIDNP transfer in AMP 53 Photo- CIDNP transfer in N-acetylhistidine 56 Long-range polarization transfer in cycloundecanone 58 Summary and conclusions 60 3.2 Relaxation experiments with scalar coupled spin systems 61 Experimental part 61 Coherent polarization transfer during relaxation in two-spin system 63 Relaxation dispersion of two- spin 1/2 system 66 Relaxation dispersion of three-spin 1/2 system 68 Relaxation dispersion of two-proton and two-fluorine system 71 Relaxation dispersion of N-acetylhistidine (five coupled spins 1/2) 74 Summary and conclusions 80 4\. Parahydrogen induced polarization in the hydrogenation reaction of styrene 81 Experimental part 82 Results and discussion 85 Summary and conclusions 90 5\. Dynamic nuclear polarization 93 Experimental part 94 Theoretical description of the pulsed DNP experiment 97 DNP spectra 102 DNP effect as resonance phenomenon 106 Exploiting coherent spin motion for optimizing DNP efficiency 107 Summary and conclusions 112 6\. Application of CIDNP to biomolecules (amino acids and peptides) 115 Experimental part 116 6.1 Methionine, N-acetylmethionine and 3-(methylthio)propylamine 117 CIDNP spectra 119 CIDNP field dependence 123 CIDNP kinetics 129 6.2 Met-Gly, Gly-Met dipeptides 141 Transient radicals in the photo-oxidation of Gly-Met 141 Transient radicals in the photo-oxidation of Met-Gly 145 Summary and conclusions 154 7\. Conclusions and outlook 157 Curriculum Vitae 161 Publications 162 Acknowledgements 166 Bibliography 167Nuclear magnetic resonance experiments on multi-spin systems using variation of the external magnetic field were performed with high spectral resolution. The main focus was investigating the behaviour of hyperpolarized nuclear spin states in the coupled spin systems in its dependence on the strength of the magnetic field in order to discriminate field dependent effects from others and to optimize the hyperpolarization (HP) yield. The experimental method of the field dependent measurements employs fast transfer of the spins between two field positions: the desired field at which the system is studied and the constant detection field. Extensive improvements of the field-cycling setup were introduced making the field variation faster and enhancing the spectral resolution. For this task, a novel material with compensated magnetic susceptibility was developed and a probehead with reduced metallic parts was constructed in order to suppress eddy currents and their magnetic field and, thus, preserve the detection field from disturbances. A new control unit of the experimental setup was devised allowing a better timing control of the experiments. Thus, for the first time variable field measurements were obtained with high spectral resolution that allow distinguishing signals of individual nuclei in the molecules at a controllable time profile of field variation in a range between 100 T and 7 T. All experiments were done on liquid state solutions, thus, the main interaction between the spins was scalar spin-spin coupling, which is not averaged in low viscosity liquids in contrast to dipolar spin-spin interaction. It was demonstrated that scalar coupling despite its small value has a high impact on the hyperpolarization experiments. At sufficiently low magnetic field the spins reach the regime of strong coupling where all hyperpolarization measurements as well as relaxation experiments are affected by the scalar interaction In the nuclear magnetic relaxation dispersion (NMRD), i.e. in the dependence of the relaxation rate on the field strength, strong coupling in multi-spin systems was shown to lead to several distinct features that have to be taken into account in a quantitative analysis. For instance, strongly coupled spins tend to relax with a common rate even when at high field their relaxation is distinctly different. Also, pronounced peaks and dips were observed in the NMRD curves of systems with more than two nuclear spins 1/2 that were attributed to spin level anti- crossings. In addition, a site specific influence of paramagnetic additives in the solution on the NMRD of the solute was analysed. It was possible to separate this paramagnetic effect from the strong coupling effect. Several methods of hyperpolarization were explored: Chemically Induced Dynamic Nuclear Polarization (CIDNP), Parahydrogen Induced Polarization (PHIP), and Dynamic Nuclear Polarization (DNP). Experiments were performed with the aim to manipulate hyperpolarization by control of spin coherences and to exploit the encoded information for analytical purposes. In all cases it was found that hyperpolarization is distributed among coupled spins when they are in the strong coupling regime. It was proven that the transfer has a coherent nature that manifests itself as quantum beats in the NMR signal amplitude upon changing the spin evolution time at the polarization field and subsequent non- adiabatic field variation to the high detection field. Such oscillations were observed both in CIDNP experiments and in relaxation measurements. Criteria for the polarization manipulation at variable field were derived and experimentally checked. The DNP experiments were conducted with driving the electronic spins off equilibrium by applying a train of radio-frequency pulses in comparison with cw irradiation. The electron pumping was done at low field where the coupling factor is close to its theoretical maximum. Length, amplitude and repetition time of the pulses were optimized to achieve maximal DNP while keeping the average pumping power constant. For analyzing the data an adequate theoretical approach to pulsed DNP was developed. Optimal conditions for getting maximum signal enhancement at minimal microwave power and thus avoiding sample heating were studied on solute and solvent molecules. Strong hyperpolarization was obtained in the hydrogenation reaction of styrene with the singlet spin isomer of hydrogen gas (parahydrogen) and studied at variable field. While for the protons originating from parahydrogen the high polarization was observed at all field amplitudes, in low field also polarization of the phenyl ring protons of the product was detected as a result of polarization transfer among strongly coupled spins. The highest transfer efficiency was seen at the field of spin level anti-crossing. The theoretical simulations reproduce the shape of the PHIP spectra in excellent agreement with the experimental data. CIDNP techniques were applied to amino acids, nucleotides and cycloketones. The most extensive investigation was performed on radical intermediates of the essential amino acid methionine and of methionine containing peptides. Their reactions with photo-exited dye molecules were investigated by combining field dependent and time-resolved CIDNP that allowed revealing the radical structure and the reaction kinetics. It was found that in aqueous solution the pH influences the branching of the radical formation not only through the protonation state of the precursor but also through the reaction intermediates. Exploiting these results formation of four methionine radicals was observed. Simple methionine containing dipeptides chosen to model the behaviour of methionine residues in proteins showed a behaviour similar to that of the free amino acid although they have several additional peculiarities. It was shown that the effects of neighbouring groups, of position at N vs C terminus, and of degenerate electron transfer have to be taken into account when studying proteins by CIDNP. The kinetic constants of the radical reaction as well as the nuclear relaxation times at the radical stage were determined from the CIDNP kinetics. In summary, it was shown that field variation can be used for optimizing the generation of hyperpolarization, for preserving it from relaxation and for transferring it to target nuclei of interest. In addition, the hyperpolarization methods in combination with high spectral resolution were demonstrated to be versatile tools that allow extracting structural and dynamic information on diamagnetic molecules and on short-lived radical intermediates.Kernspinresonanz-Experimente an skalar gekoppelten Vielspinsystemen wurden erstmals bei Variation des äußeren Magnetfelds in Kombination mit hoher spektraler Auflösung durchgeführt. Schwerpunkt dabei war die Untersuchung von hyperpolarisierten Kernspin-zuständen in den gekoppelten Systemen als Funktion der Feldstärke, um feldabhängige Effekte von feldunabhängigen zu unterscheiden und den Polarisationsgrad zu optimieren. Die experimentelle Realisierung der Feldvariation basiert auf schnellem mechanischen Transfer der Spins zwischen Positionen unterschiedlicher Feldstärke: für die gewünschte Spinevolution im variablem Feld bzw. den optimierten Nachweis im konstanten Hochfeld. Umfangreiche apparative Verbesserungen der Feldzyklisierung werden beschrieben, die insbesondere zu einer erheblichen Verbesserung der Auflösung und zur Erhöhung der Transfer-Geschwindigkeit bei genauerer Kontrolle des zeitlichen Ablaufs geführt haben. Zu diesem Zweck wurde unter anderem ein neuartiges Kompositmaterial mit verschwindender magnetischer Suszeptibilität entwickelt und für einen NMR-Probenkopf verwendet, dessen Metallteile zudem reduziert waren, um Wirbelstrom-Effekte beim Feldschalten zu unterdrücken. Außerdem wurde die Rechnersteuerung des Spektrometers komplett erneuert. Dadurch gelang es die Signale der unterschiedlichen Spinpositionen im Molekül bei zeitlich genau gesteuerter Feldvariation im Bereich zwischen 100 T und 7T mit einer Auflösung von 10-9 nachzuweisen. Alle Untersuchungen fanden an flüssigen Proben statt, wo die Wechselwirkungung unter den Spins durch skalare Kopplung gegeben ist, die in niederviskosen Flüssigkeiten im Gegensatz zu dipolarer Kopplung nicht ausgemittelt ist. Die Messungen zeigen, dass die skalare Kopplung trotz ihrer geringen Stärke große Auswirkungen auf die Evolution von Spinpolarisation hat, insbesondere wenn die Spinzustände Populationsverteilungen fernab vom thermischen Gleichgewicht aufweisen. Bei ausreichend kleiner externer Feldstärke wird der sogenannte Fall starker Kopplung erreicht, bei dem die Spin-Spin-Kopplung dominant wird und alle Hyperpolarisations- und Relaxationsexperimente beeinflusst. So führt bei der Magnetfeldabhängigkeit der Spin-Gitter-Relaxation, der sogenannten Relaxationsdispersion (NMRD) die skalare Kopplung dazu, dass in Vielspinsystemen bei starker Kopplung sich die Relaxationsraten einander annähern, selbst wenn im Fall schwacher Kopplung die Raten der einzelnen Spins deutlich verschieden sind. Darüber hinaus wurden scharfe Strukturen in den Dispersionskurven nachgewiesen, die bei Feldern in der Nähe von Niveaukreuzungen (level anti-crossings) auftreten. Der Effekt der starken Spinkopplung konnte von dem feldabhängigen Einfluss paramagnetischer Metallionen auf die Relaxationsdispersion diskriminiert werden. In einer weiteren Gruppe von Experimenten wurden verschiedene Methoden zur Erzeugung von Hyperpolarisation untersucht: Chemisch induzierte dynamische Kernspinpolarisation (CIDNP), Parawasserstoff-induzierte Polarisation (PHIP) und dynamische Kernspinpolarisation vom Overhauser-Typ (DNP). Diese Experimente hatten das Ziel die Hyperpolarisation durch Steuerung von Spinkohärenzen zu manipulieren sowie die im Polarisationsprozess verschlüsselte Information für analytische Zwecke zu nutzen. In diesem Zusammenhang ließ sich nachweisen, dass sich die Hyperpolarisation auf alle gekoppelten Spins verteilt, wenn der Fall starker Kopplung gegeben ist. Die Untersuchungen ergaben, dass dieser Verteilungsprozess von kohärenter Natur ist und sich in Oszillationen der NMR-Signalamplitude niederschlägt, wenn die Dauer der Spinevolution im Niederfeld systematisch verändert wird, wobei der Transfer ins Nachweisfeld nicht-adiabatisch durchgeführt muss. Derartige Oszillationen konnten sowohl in CIDNP Experimenten als auch bei Relaxationsmessungen aufgezeigt werden. Bei den DNP-Untersuchungen ging es hauptsächlich um die Überprüfung, inwieweit das elektronische Spinsystem durch gepulste Anregung und damit durch Ausnutzung kohärenter Spinbewegung effizienter aus dem thermischen Gleichgewicht getrieben werden kann als durch konstantes Pumpen. Ziel war unter es anderem, bei gleichem Polarisationsgrad die Erwärmung der Probe zu vermindern. Im Niederfeld sind die Bedingungen für solche Messungen wesentlich günstiger als im Hochfeld. Eine besonders hohe Polarisation (PHIP) wurde mit Hilfe von Parawasserstoff erzielt, dem Singulett-Spinisomer von Wasserstoffgas, das sich bei tiefen Temperaturen anreichern lässt und zur Hydrierung von Styrol zu Ethylbenzol verwendet wurde. Der Einbau der beiden singulett-korrelierten H-Atome führt zu spektralen Polarisationsmustern, deren Änderung als Funktion des Magnetfeldes untersucht wurde. Insbesondere der Polarisationtransfer auf benachbarte Kerne ist von großem Interesse im Hinblick auf Kontrastmittel in der Kernspintomographie. Hier konnte gezeigt werden, dass solch ein Transfer besonders effektiv im Bereich von Level-Crossings ist. Numerische Simulationen konnten das gemessene Polarisationsmuster und seine Feldabhängigkeit mit hoher Genauigkeit reproduzieren. Die Einsatzmöglichkeiten von Hyperpolarisation zur Analyse von chemischen Reaktionen wurden vor allem durch Kombination mehrer CIDNP- Techniken aufgezeigt. Untersuchungsobjekte waren Aminosäuren, Nukleotide und zyklische Ketone. Die umfangreichsten Studien betreffen kurzlebige Radikale der essentiellen Aminosäure Methionin und verschiedener Peptide mit Methionin- Residuen, die bei Photoreaktionen mit Triplett-angeregten Farbstoffmolekülen entstehen. Dabei wurden sowohl Feldabhängigkeit als auch Zeitverlauf der dabei erzeugten Hyperpolarisation gemessen, um daraus Struktur der Radikale einerseits und Reaktionswege und -kinetik andererseits zu bestimmen. Die Ergebnisse zeigen unter anderem, dass in wässriger Lösung der pH-Wert das Verzweigungsverhältnis verschiedener Reaktionswege nicht nur über den Protonierungszustand der Ausgangssubstanz, sondern auch über die Reaktionsintermediate beeinflusst. Aufgrund dieser Kenntnis war es möglich vier verschiedene Methionin-Radikale nachzuweisen und mithilfe ihrer magnetischen Parameter (Hyperfeinkopplung, g-Faktor) zu charakterisieren. Bei den Peptiden konnten außerdem Effekte von Nachbargruppen oder der Einfluss von C und N Terminus gezeigt werden. Insgesamt gesehen erwies sich die Variation der Magnetfeldstärke in Kombination mit hochauflösendem NMR-Nachweis als sehr vielseitige und aussagekräftige Methode, die sowohl für die optimale Generierung von Hyperpolarisation, für der Verlängerung ihrer Lebensdauer und beim Transfer auf gewünschte Spins eingesetzt werden, die aber auch bei der Analyse komplexer Reaktionen und der dabei auftretenden Zwischenprodukte wertvolle Informationen bringen kann

Dynamic Real-Time Magnetic Resonance at Very Low Magnetic Fields

The phenomenon of nuclear magnetic resonance (NMR) is widely applied in biomedical and biological science to study structures and dynamics of proteins and their reactions. Despite its impact, NMR is an inherently insensitive phenomenon and has driven the field to construct spectrometers with increasingly higher magnetic fields leading to more detection sensitivity. Here, we are demonstrating that enzymatic reactions can be followed in real-time at millitesla fields, 1000-fold lower than state-of-the-art spectrometers. This requires signal-enhancing samples via hyperpolarization. Within seconds, we have enhanced the signals of 2- 13Cpyruvate, an important metabolite to probe cancer metabolism, in 22 mM concentrations (up to 10.1%±0.1% polarization) and show that such a large signal allows for the real-time detection of enzymatic conversion of pyruvate to lactate. This development paves the pathways for biological studies in portable and affordable NMR systems with a potential for medical diagnostics. <br /

Nuclear hyperpolarization of (1-¹³C)-pyruvate in aqueous solution by proton-relayed side-Arm hydrogenation

We employ Parahydrogen Induced Polarization with Side-Arm Hydrogenation (PHIP-SAH) to polarize (1-13C)-pyruvate. We introduce a new method called proton-relayed side-Arm hydrogenation (PR-SAH) in which an intermediate proton is used to transfer polarization from the side-Arm to the 13C-labelled site of the pyruvate before hydrolysis. This significantly reduces the cost and effort needed to prepare the precursor for radio-frequency transfer experiments while still maintaining acceptable polarization transfer efficiency. Experimentally we have attained on average 4.33% 13C polarization in an aqueous solution of (1-13C)-pyruvate after about 10 seconds of cleavage and extraction. PR-SAH is a promising pulsed NMR method for hyperpolarizing 13C-labelled metabolites in solution, conducted entirely in high magnetic field.</p

High resolution NMR study of T1magnetic relaxation dispersion. III. Influence of spin 1/2 hetero-nuclei on spin relaxation and polarization transfer among strongly coupled protons

Effects of spin-spin interactions on the nuclear magnetic relaxation dispersion (NMRD) of protons were studied in a situation where spin ½ hetero-nuclei are present in the molecule. As in earlier works [K. L. Ivanov, A. V. Yurkovskaya, and H.-M. Vieth, J. Chem. Phys. 129, 234513 (2008)10.1063/1.3040272; S. E. Korchak, K. L. Ivanov, A. V. Yurkovskaya, and H.-M. Vieth, J. Chem. Phys. 133, 194502 (2010)10.1063/1.3495988], spin-spin interactions have a pronounced effect on the relaxivity tending to equalize the longitudinal relaxation times once the spins become strongly coupled at a sufficiently low magnetic field. In addition, we have found influence of 19F nuclei on the proton NMRD, although in the whole field range, studied protons and fluorine spins were only weakly coupled. In particular, pronounced features in the proton NMRD were found; but each feature was predominantly observed only for particular spin states of the hetero-nuclei. The features are explained theoretically; it is shown that hetero-nuclei can affect the proton NMRD even in the limit of weak coupling when (i) protons are coupled strongly and (ii) have spin-spin interactions of different strengths with the hetero-nuclei. We also show that by choosing the proper magnetic field strength, one can selectively transfer proton spin magnetization between spectral components of choic