Andrey Pravdivtsev - Academia.edu (original) (raw)
Papers by Andrey Pravdivtsev
arXiv (Cornell University), Dec 13, 2021
arXiv (Cornell University), Aug 29, 2023
![Research paper thumbnail of Sensitivity-enhanced magnetic resonance reveals hydrogen intermediates during active [Fe]-hydrogenase catalysis](https://attachments.academia-assets.com/117690660/thumbnails/1.jpg)
](bioRxiv (Cold Spring Harbor Laboratory), May 11, 2023
ChemPhysChem, Feb 1, 2021
Journal of Magnetic Resonance, Dec 1, 2018
ChemPhysChem, Feb 11, 2020
Chemistry: A European Journal, Apr 11, 2019
Analytical Chemistry, Oct 20, 2022
ChemPhysChem, Sep 12, 2019
Molecular hydrogen has unique nuclear spin properties. Its nuclear spin isomer, parahydrogen (pH2... more Molecular hydrogen has unique nuclear spin properties. Its nuclear spin isomer, parahydrogen (pH2), was instrumental in the early days of quantum mechanics and allows to boost the NMR signal by several orders of magnitude. pH2‐induced polarization (PHIP) is based on the survival of pH2 spin order in solution, yet its lifetime has not been investigated in aqueous or biological media required for in vivo applications. Herein, we report longitudinal relaxation times (T1) and lifetimes of pH2 ( ) in methanol and water, with or without O2, NaCl, rhodium‐catalyst or human blood. Furthermore, we present a relaxation model that uses T1 and for more precise theoretical predictions of the H2 spin state in PHIP experiments. All measured T1 values were in the range of 1.4–2 s and values were of the order of 10–300 minutes. These relatively long lifetimes hold great promise for emerging in vivo implementations and applications of PHIP.
Scientific Reports, Jul 8, 2022
The setup, operational procedures and performance of a cryogen-free device for producing hyperpol... more The setup, operational procedures and performance of a cryogen-free device for producing hyperpolarized contrast agents using dissolution dynamic nuclear polarization (dDNP) in a preclinical imaging center is described. The polarization was optimized using the solid-state, DNP-enhanced NMR signal to calibrate the sample position, microwave and NMR frequency and power and flip angle. The polarization of a standard formulation to yield ~ 4 mL, 60 mM 1-13 C-pyruvic acid in an aqueous solution was quantified in five experiments to P(13 C) = (38 ± 6) % (19 ± 1) s after dissolution. The monoexponential time constant of the build-up of the solid-state polarization was quantified to (1032 ± 22) s. We achieved a duty cycle of 1.5 h that includes sample loading, monitoring the polarization build-up, dissolution and preparation for the next run. After injection of the contrast agent in vivo, pyruvate, pyruvate hydrate, lactate, and alanine were observed, by measuring metabolite maps. Based on this work sequence, hyperpolarized 15 N urea was obtained (P(15 N) = (5.6 ± 0.8) % (30 ± 3) s after dissolution). Magnetic Resonance Imaging (MRI) has revolutionized modern diagnostics by providing high resolution anatomical and functional imaging in 3D without ionizing radiation 1,2. Many of the biochemical processes in vivo, however, still elapse our best efforts, and accessing these remains a prime objective of much research. Here, hyperpolarized contrast agents hold great promise as they provide a unique window into metabolism, non-invasively and in vivo. By boosting the signal of selected, often endogenous molecules, their fate can be followed-for a limited time-with high spatial and chemical resolution. These properties have allowed the identification of cancerous tissue before a tumor was apparent, and has helped monitoring treatment response. Dissolution dynamic nuclear polarization (dDNP) 3 is the most established technique for hyperpolarizing (HP) biomolecules for in vivo imaging, and it shares the applicability to humans 4,5 only with hyperpolarized Xenon 6. Other HP techniques include brute-force 7 , parahydrogen-induced polarization 8 , chemically induced dynamic nuclear polarization 9 and, for noble gases, spin-exchange optical pumping 10,11. dDNP has allowed to polarize biomolecules to more than 50% in about 1 h 12,13. The nuclear polarization of the target is achieved by polarizing electronic spin first, using low temperatures (≈ 1.4 K) and high magnetic fields (≈ 6.7 T). Then, the electron polarization is transferred to nuclear polarization using the interactions between the electronic and nuclear spin under the action of electromagnetic waves, transmitted at a frequency corresponding to the difference in Larmor frequency of the two electron spins involved 14. The unpaired electron spins are added in the form of stable radicals: TEMPO 15 , TEMPOL, or trityl radicals 16,17 or induced by UV radiation 18. In addition, there are other types of sample formulations, for instance HYPOP 19. When the desired level of nuclear spin polarization is achieved, the frozen sample is rapidly melted, dissolved and ejected from the polarizer by pressurized overheated water, such that an injectable contrast agent results. Overall, dDNP is a complex process combining nuclear magnetic resonance (NMR) electron spin resonance (ESR), radical chemistry, high magnetic fields, fast dissolution, and cryogenictemperatures. Making this process available for biomedical research routinely is not straight forward. Over the last decades, several experimental implementations of dDNP were presented such as a cryogen-consumption-free DNP 9.4 T polarizer 20 , a 129-GHz dynamic nuclear polarizer in an ultra-wide bore superconducting magnet 21 , a Dynamic Nuclear Polarization
Chemistry: A European Journal, Mar 28, 2019
Signal amplification by reversible exchange (SABRE) with parahydrogen is a unique method to boost... more Signal amplification by reversible exchange (SABRE) with parahydrogen is a unique method to boost the NMR signal by several orders of magnitude. Many effects that govern SABRE were described before, or at least mentioned in the literature. A comprehensive model bringing together the separate pieces, however, was missing so far. This is what we did here. What prompted you to investigate this topic/problem? So far, seeing (or simulating) "the full picture" of SABRE was difficult. SABRE is complex! Many effects are intertwined, depending on each other in a non-linear way. Picking up the pieces, we came up with a single, comprehensive model, combining the linear and non-linear "chemical and physical" (CAP) effects that control SABRE. The CAP(tain) master equation was our rescue! We are particularly happy that the CAPtain is flexible with respect to the interactions and size of the spin system-it can be tailored to the problem at hand with (relative) ease!
Analytical Chemistry, Apr 5, 2023
Angewandte Chemie, Aug 13, 2021
Die Kernspinresonanz (NMR) hat sich zu einer universellen Methode für biochemische und biomedizin... more Die Kernspinresonanz (NMR) hat sich zu einer universellen Methode für biochemische und biomedizinische Studien, einschließlich Metabolomik, Proteomik und Magnetresonanztomographie (MRT), entwickelt. Durch die Vervielfachung des NMR‐Signals ausgewählter Moleküle hat die Kernspin‐Hyperpolarisation das Anwendungsspektrum von NMR und MRT bedeutsam erweitert (z. B. hyperpolarisierte Festkörper‐NMR und metabolische Bildgebung in vivo). Parawasserstoff (pH2) erlaubt es, Moleküle schnell und kostengünstig zu hyperpolarisieren. In diesem Gebiet wurden in den letzten zehn Jahren umfangreiche Fortschritte erzielt, einschließlich der Synthese neuer Tracer, Katalysatoren und Methoden für die Polarisationsübertragung. Das Portfolio an hyperpolarisierten Molekülen umfasst nunmehr Aminosäuren, die für viele Anwendungen von großem Interesse sind. In diesem Beitrag beleuchten wir die aktuelle Literatur zur Hyperpolarisation von Aminosäuren und Peptiden.
Physical Chemistry Chemical Physics, 2020
Simulation of the interplay of coherent polarization transfer and chemical exchange described by ... more Simulation of the interplay of coherent polarization transfer and chemical exchange described by superoperators and Monte Carlo simulations alike.
Die Radiologie, May 20, 2022
arXiv (Cornell University), Dec 13, 2021
arXiv (Cornell University), Aug 29, 2023
bioRxiv (Cold Spring Harbor Laboratory), May 11, 2023
ChemPhysChem, Feb 1, 2021
Journal of Magnetic Resonance, Dec 1, 2018
ChemPhysChem, Feb 11, 2020
Chemistry: A European Journal, Apr 11, 2019
Analytical Chemistry, Oct 20, 2022
ChemPhysChem, Sep 12, 2019
Molecular hydrogen has unique nuclear spin properties. Its nuclear spin isomer, parahydrogen (pH2... more Molecular hydrogen has unique nuclear spin properties. Its nuclear spin isomer, parahydrogen (pH2), was instrumental in the early days of quantum mechanics and allows to boost the NMR signal by several orders of magnitude. pH2‐induced polarization (PHIP) is based on the survival of pH2 spin order in solution, yet its lifetime has not been investigated in aqueous or biological media required for in vivo applications. Herein, we report longitudinal relaxation times (T1) and lifetimes of pH2 ( ) in methanol and water, with or without O2, NaCl, rhodium‐catalyst or human blood. Furthermore, we present a relaxation model that uses T1 and for more precise theoretical predictions of the H2 spin state in PHIP experiments. All measured T1 values were in the range of 1.4–2 s and values were of the order of 10–300 minutes. These relatively long lifetimes hold great promise for emerging in vivo implementations and applications of PHIP.
Scientific Reports, Jul 8, 2022
The setup, operational procedures and performance of a cryogen-free device for producing hyperpol... more The setup, operational procedures and performance of a cryogen-free device for producing hyperpolarized contrast agents using dissolution dynamic nuclear polarization (dDNP) in a preclinical imaging center is described. The polarization was optimized using the solid-state, DNP-enhanced NMR signal to calibrate the sample position, microwave and NMR frequency and power and flip angle. The polarization of a standard formulation to yield ~ 4 mL, 60 mM 1-13 C-pyruvic acid in an aqueous solution was quantified in five experiments to P(13 C) = (38 ± 6) % (19 ± 1) s after dissolution. The monoexponential time constant of the build-up of the solid-state polarization was quantified to (1032 ± 22) s. We achieved a duty cycle of 1.5 h that includes sample loading, monitoring the polarization build-up, dissolution and preparation for the next run. After injection of the contrast agent in vivo, pyruvate, pyruvate hydrate, lactate, and alanine were observed, by measuring metabolite maps. Based on this work sequence, hyperpolarized 15 N urea was obtained (P(15 N) = (5.6 ± 0.8) % (30 ± 3) s after dissolution). Magnetic Resonance Imaging (MRI) has revolutionized modern diagnostics by providing high resolution anatomical and functional imaging in 3D without ionizing radiation 1,2. Many of the biochemical processes in vivo, however, still elapse our best efforts, and accessing these remains a prime objective of much research. Here, hyperpolarized contrast agents hold great promise as they provide a unique window into metabolism, non-invasively and in vivo. By boosting the signal of selected, often endogenous molecules, their fate can be followed-for a limited time-with high spatial and chemical resolution. These properties have allowed the identification of cancerous tissue before a tumor was apparent, and has helped monitoring treatment response. Dissolution dynamic nuclear polarization (dDNP) 3 is the most established technique for hyperpolarizing (HP) biomolecules for in vivo imaging, and it shares the applicability to humans 4,5 only with hyperpolarized Xenon 6. Other HP techniques include brute-force 7 , parahydrogen-induced polarization 8 , chemically induced dynamic nuclear polarization 9 and, for noble gases, spin-exchange optical pumping 10,11. dDNP has allowed to polarize biomolecules to more than 50% in about 1 h 12,13. The nuclear polarization of the target is achieved by polarizing electronic spin first, using low temperatures (≈ 1.4 K) and high magnetic fields (≈ 6.7 T). Then, the electron polarization is transferred to nuclear polarization using the interactions between the electronic and nuclear spin under the action of electromagnetic waves, transmitted at a frequency corresponding to the difference in Larmor frequency of the two electron spins involved 14. The unpaired electron spins are added in the form of stable radicals: TEMPO 15 , TEMPOL, or trityl radicals 16,17 or induced by UV radiation 18. In addition, there are other types of sample formulations, for instance HYPOP 19. When the desired level of nuclear spin polarization is achieved, the frozen sample is rapidly melted, dissolved and ejected from the polarizer by pressurized overheated water, such that an injectable contrast agent results. Overall, dDNP is a complex process combining nuclear magnetic resonance (NMR) electron spin resonance (ESR), radical chemistry, high magnetic fields, fast dissolution, and cryogenictemperatures. Making this process available for biomedical research routinely is not straight forward. Over the last decades, several experimental implementations of dDNP were presented such as a cryogen-consumption-free DNP 9.4 T polarizer 20 , a 129-GHz dynamic nuclear polarizer in an ultra-wide bore superconducting magnet 21 , a Dynamic Nuclear Polarization
Chemistry: A European Journal, Mar 28, 2019
Signal amplification by reversible exchange (SABRE) with parahydrogen is a unique method to boost... more Signal amplification by reversible exchange (SABRE) with parahydrogen is a unique method to boost the NMR signal by several orders of magnitude. Many effects that govern SABRE were described before, or at least mentioned in the literature. A comprehensive model bringing together the separate pieces, however, was missing so far. This is what we did here. What prompted you to investigate this topic/problem? So far, seeing (or simulating) "the full picture" of SABRE was difficult. SABRE is complex! Many effects are intertwined, depending on each other in a non-linear way. Picking up the pieces, we came up with a single, comprehensive model, combining the linear and non-linear "chemical and physical" (CAP) effects that control SABRE. The CAP(tain) master equation was our rescue! We are particularly happy that the CAPtain is flexible with respect to the interactions and size of the spin system-it can be tailored to the problem at hand with (relative) ease!
Analytical Chemistry, Apr 5, 2023
Angewandte Chemie, Aug 13, 2021
Die Kernspinresonanz (NMR) hat sich zu einer universellen Methode für biochemische und biomedizin... more Die Kernspinresonanz (NMR) hat sich zu einer universellen Methode für biochemische und biomedizinische Studien, einschließlich Metabolomik, Proteomik und Magnetresonanztomographie (MRT), entwickelt. Durch die Vervielfachung des NMR‐Signals ausgewählter Moleküle hat die Kernspin‐Hyperpolarisation das Anwendungsspektrum von NMR und MRT bedeutsam erweitert (z. B. hyperpolarisierte Festkörper‐NMR und metabolische Bildgebung in vivo). Parawasserstoff (pH2) erlaubt es, Moleküle schnell und kostengünstig zu hyperpolarisieren. In diesem Gebiet wurden in den letzten zehn Jahren umfangreiche Fortschritte erzielt, einschließlich der Synthese neuer Tracer, Katalysatoren und Methoden für die Polarisationsübertragung. Das Portfolio an hyperpolarisierten Molekülen umfasst nunmehr Aminosäuren, die für viele Anwendungen von großem Interesse sind. In diesem Beitrag beleuchten wir die aktuelle Literatur zur Hyperpolarisation von Aminosäuren und Peptiden.
Physical Chemistry Chemical Physics, 2020
Simulation of the interplay of coherent polarization transfer and chemical exchange described by ... more Simulation of the interplay of coherent polarization transfer and chemical exchange described by superoperators and Monte Carlo simulations alike.
Die Radiologie, May 20, 2022