Article
Chemistry, Multidisciplinary
Victor Ribay, Arnab Dey, Benoit Charrier, Clement Praud, Joris Mandral, Jean-Nicolas Dumez, Marine P. M. Letertre, Patrick Giraudeau
Summary: Hyperpolarized nuclear magnetic resonance (NMR) methods, particularly Dissolution Dynamic Nuclear Polarization (d-DNP), greatly enhance the sensitivity of detecting C-13 NMR signals. This study demonstrates the first application of d-DNP-enhanced C-13 NMR analysis of biofluid (urine) at natural abundance, providing unprecedented resolution and sensitivity. Accurate quantitative information on multiple targeted metabolites can be obtained through a standard addition procedure.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Review
Chemistry, Multidisciplinary
Yohei Kondo, Hiroshi Nonaka, Yoichi Takakusagi, Shinsuke Sando
Summary: Nuclear hyperpolarization is a method to enhance the sensitivity of NMR spectroscopy, allowing for highly sensitive biomedical molecular imaging. Recent development of molecular probes for hyperpolarized in vivo analysis has shown the unique metabolic and physiological information that this technique can provide.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Tim R. Eichhorn, Anna J. Parker, Felix Josten, Christoph Mueller, Jochen Scheuer, Jakob M. Steiner, Martin Gierse, Jonas Handwerker, Michael Keim, Sebastian Lucas, Mohammad Usman Qureshi, Alastair Marshall, Alon Salhov, Yifan Quan, Jan Binder, Kay D. Jahnke, Philipp Neumann, Stephan Knecht, John W. Blanchard, Martin B. Plenio, Fedor Jelezko, Lyndon Emsley, Christophoros C. Vassiliou, Patrick Hautle, Ilai Schwartz
Summary: Nuclear spin hyperpolarization can be transferred to target molecules through dissolution of spin-polarized pentacene-doped naphthalene crystals at room temperature and moderate magnetic fields. This method allows for enhanced NMR signals for small molecules within a time scale of 1 minute.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Review
Biochemistry & Molecular Biology
Victor Ribay, Clement Praud, Marine P. M. Letertre, Jean-Nicolas Dumez, Patrick Giraudeau
Summary: Hyperpolarized NMR is a promising method to overcome the limited sensitivity of conventional NMR metabolomics in detecting minute metabolite concentrations in biological samples. This review discusses the utilization of dissolution dynamic nuclear polarization and parahydrogen-based techniques for molecular omics sciences, as well as recent advancements in combining hyperpolarization with fast multi-dimensional NMR and quantitative workflows. The review also proposes a comprehensive comparison of existing hyperpolarization techniques and addresses challenges in high throughput, sensitivity, and resolution for the general application of hyperpolarized NMR in metabolomics.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Theo El Darai, Samuel F. Cousin, Quentin Stern, Morgan Ceillier, James Kempf, Dmitry Eshchenko, Roberto Melzi, Marc Schnell, Laurent Gremillard, Aurelien Bornet, Jonas Milani, Basile Vuichoud, Olivier Cala, Damien Montarnal, Sami Jannin
Summary: The study introduces a new method for preparing hyperpolarized samples, utilizing hyperpolarizing polymers to generate radical- and contaminant-free samples within minutes with long-term stability. This approach could potentially facilitate widespread application of dissolution dynamic nuclear polarization.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Physical
Zefan Zhang, Christian Hilty
Summary: The reversible adsorption of CO2-derived species to graphene quantum dots in CO2 electroreduction reaction was characterized using nuclear spin hyperpolarized NMR. The study found a significant difference in the relaxation rates of bound and free species, indicating reversible binding. pH-dependent adsorption and desorption rate constants were measured, along with the average binding distance.
Article
Chemistry, Multidisciplinary
Ludovica Martina Epasto, Philipp Honegger, Kateryna Che, Fanny Kozak, Florian Joerg, Christian Schroeder, Dennis Kurzbach
Summary: Dissolution dynamic nuclear polarization (dDNP) is a versatile hyperpolarization technique to enhance signal intensities in nuclear magnetic resonance (NMR) spectroscopy. By dissolving biomolecules in hyperpolarized aqueous buffer under mild conditions, the scope of NMR has been expanded. However, the water-to-target hyperpolarization transfer mechanisms are still unclear, and the limited structural information is obtained due to the restricted data acquisition.
CHEMICAL COMMUNICATIONS
(2022)
Article
Biochemical Research Methods
Jose Yeste, Marc Azagra, Maria A. Ortega, Alejandro Portela, Gergo Matajsz, Alba Herrero-Gomez, Yaewon Kim, Renuka Sriram, John Kurhanewicz, Daniel B. Vigneron, Irene Marco-Rius
Summary: We developed a microfluidic device compatible with hyperpolarization-enhanced MR spectroscopic imaging. It measures up to 8 chemical reactions simultaneously with a single hyperpolarized sample. This technology allows for real-time, in situ analysis of chemical reactions and provides a new high-throughput method for chemical research and biological metabolic analysis.
Article
Chemistry, Multidisciplinary
Chang Qi, Yunyi Wang, Christian Hilty
Summary: Nuclear spin relaxation dispersion parameters can serve as indicators of the binding mode of a ligand to a protein. Hyperpolarization techniques, such as dissolution dynamic nuclear polarization, can provide signal enhancement without the need for isotope enrichment, offering an alternative method for determining ligand binding modes.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Physics, Multidisciplinary
Yu Wang, Kazuyuki Takeda
Summary: The study proposes a correction to the nuclear spin diffusion coefficient by extending the Lowe-Gade theory, indicating that nuclear magnetization transportation accelerates when hyperpolarized and approaches unity for low polarization, coinciding with the conventional diffusion coefficient at high temperatures. This proposed scaling of the nuclear spin diffusion coefficient could have observable effects on the buildup of nuclear polarization by dynamic nuclear polarization.
NEW JOURNAL OF PHYSICS
(2021)
Article
Chemistry, Multidisciplinary
Victoria Aladin, Arun K. Sreemantula, Thomas Biedenbaender, Alexander Marchanka, Bjoern Corzilius
Summary: An approach is presented to enhance NMR spectroscopic signals by site-specific enhancement of the protein-RNA binding site within a ribonucleoprotein (RNP) using dynamic nuclear polarization (DNP). This approach utilizes biochemical techniques for sparse isotope labeling and exploits the molecular dynamics of C-13-labeled methyl groups exclusively present in the protein, resulting in improved sensitivity and specificity for solid-state NMR structure determination of large biomolecules.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Biochemical Research Methods
Jihyun Kim, Ratnamala Mandal, Christian Hilty
Summary: The study utilized polarization transfer from hyperpolarized water through proton exchange to enhance NMR signals of Ribonuclease Sa protein's amide protons. Spectra of the protein in different folding states were observed, with varying polarization transfer efficiency depending on the folding rate. This ability to acquire 2D NMR spectra under different refolding conditions could provide a new avenue for residue specific characterization of the folding process.
JOURNAL OF MAGNETIC RESONANCE
(2021)
Article
Chemistry, Physical
Robert Staeglich, Tobias W. Kemnitzer, Marie C. Harder, Adrian Schmutzler, Marcel Meinhart, Caroline D. Keenan, Ernst A. Roessler, Juergen Senker
Summary: This article presents a new polarizer that can generate a continuous stream of hyperpolarized Xe-129 and maintain stable polarization levels for several hours. The polarizer features excellent magnetization production rates and polarization values, and is adaptable for use in various sample environments.
JOURNAL OF PHYSICAL CHEMISTRY A
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Cornelius von Morze, John A. Engelbach, Tyler Blazey, James D. Quirk, Galen D. Reed, Joseph E. Ippolito, Joel R. Garbow
Summary: This study directly compared two isotopic metabolic imaging approaches, HP C-13 MRI and DMI, for imaging different segments of cerebral glucose metabolism at 4.7 T. The results showed that while HP-C-13 MRI had better SNR and spatial resolution compared to DMI, the latter provided maps of lactate and Glx production, albeit with poorer spectral discrimination.
MAGNETIC RESONANCE IN MEDICINE
(2021)
Article
Chemistry, Analytical
Quy Son Luu, Quynh Thi Nguyen, Jiwon Kim, Jeunghwan Kim, Uyen Thi Do, Nicholas Whiting, Jeong Hyun Shim, Sun-Joon Min, Youngbok Lee
Summary: Embedding radicals at different locations within core@shell silica nanoparticles enhances polarization capability and enables self-polarization. Homogeneously grafting the radical source inside the nanoparticles leads to a significant Si-29 hyperpolarization signal enhancement of 49.4.
Article
Biochemistry & Molecular Biology
Mukundan Ragavan, Mengchen Li, Anthony G. Giacalone, Charles E. Wood, Maureen Keller-Wood, Matthew E. Merritt
Summary: Ovine models have been widely used for studying maternal-fetal interactions and congenital heart diseases. This study demonstrates a comprehensive assessment of heart function and metabolism in a perinatal model, with the use of [U-C-13]glucose as a tracer to study central energy metabolism. The methodology presented can be applied to investigate acute and chronic effects of hormonal signaling in future studies.
Article
Radiology, Nuclear Medicine & Medical Imaging
Rohit Mahar, Huadong Zeng, Anthony Giacalone, Mukundan Ragavan, Thomas H. Mareci, Matthew E. Merritt
Summary: This study demonstrates for the first time the metabolic imaging of HDO as a marker of glucose, lactate, and glutamate/glutamine metabolism. The generation of HDO in the brain is linearly related to the appearance of lactate and glutamate/glutamine in the appropriate pseudo-steady state window. Selective imaging of HDO and glucose can be easily achieved using a gradient-echo method.
MAGNETIC RESONANCE IN MEDICINE
(2021)
Article
Endocrinology & Metabolism
Chris E. Shannon, Mukundan Ragavan, Juan Pablo Palavicini, Marcel Fourcaudot, Terry M. Bakewell, Ivan A. Valdez, Iriscilla Ayala, Eunsook S. Jin, Muniswamy Madesh, Xianlin Han, Matthew E. Merritt, Luke Norton
Summary: Insulin resistance and altered hepatic mitochondrial function are key features of type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD). This study found that insulin sensitization with pioglitazone can mitigate mitochondrial dysfunction in the liver, which is independent of changes in hepatic lipid accumulation. The research highlights potential therapeutic targets for T2D and NAFLD, emphasizing the benefits of insulin sensitization in managing obesity-related diseases.
MOLECULAR METABOLISM
(2021)
Article
Biotechnology & Applied Microbiology
Mohsin Rahim, Mukundan Ragavan, Stanislaw Deja, Matthew E. Merritt, Shawn C. Burgess, Jamey D. Young
Summary: Metabolic flux analysis is a method that combines experimental measurements and computational modeling to determine reaction rates in biological systems. This study introduces a software tool called INCA 2.0, which can integrate isotopomer measurements from both MS and NMR platforms and estimate metabolic fluxes with flexibility. The results demonstrate that INCA 2.0 accurately simulates and analyzes NMR datasets, outperforming other established tools. Additionally, combining NMR and MS datasets improves the precision of estimated fluxes.
METABOLIC ENGINEERING
(2022)
Article
Multidisciplinary Sciences
Michael J. Jaroszewicz, Mengxiao Liu, Jihyun Kim, Guannan Zhang, Yaewon Kim, Christian Hilty, Lucio Frydman
Summary: Nuclear magnetic resonance (NMR) spectroscopy provides detailed information about dynamic processes through line-shape changes under equilibrium conditions. However, studying chemical reactions under off-equilibrium conditions and monitoring the reactants and products in real time can provide additional valuable information. In this study, the authors propose and demonstrate a time-resolved kinetic NMR experiment that combines rapid mixing techniques, continuous flow, and single-scan spectroscopic imaging methods, leading to a 2D spectrotemporal NMR correlation that provides high-quality kinetic information of off-equilibrium chemical reactions.
NATURE COMMUNICATIONS
(2022)
Article
Physiology
Mukundan Ragavan, Marc A. McLeod, Anna Rushin, Matthew E. Merritt
Summary: The role of ketones in metabolic health has evolved over time, from being considered a simple byproduct to playing a central role in various diseases. This study found that ketones can be produced from carbohydrates, but only when the activity of pyruvate dehydrogenase is upregulated.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Chemistry, Physical
Jiandu Hu, Jihyun Kim, Christian Hilty
Summary: The transfer of nuclear spin hyperpolarization from water to ligand F-19 spins can be used to detect protein-ligand interaction without background noise. The calculated cross-relaxation rates indicate that these rates are sensitive to binding to medium- and large-sized proteins. The heteronuclear observation of hyperpolarization transfer from water can be applied in screening protein-ligand interactions in drug discovery and other applications.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Biochemical Research Methods
Christian Hilty, Dennis Kurzbach, Lucio Frydman
Summary: NMR spectroscopy is the only method to access the structural dynamics of biomolecules in their native solution state. To overcome its low sensitivity, researchers have developed a technique using "hyperpolarized water" to boost signal intensities in NMR of proteins and nucleic acids.
Article
Multidisciplinary Sciences
Anthony G. Giacalone, Matthew E. Merritt, Mukundan Ragavan
Summary: Metabolic diseases are on the rise, and understanding liver metabolism is crucial. Ex vivo liver perfusion combined with NMR allows for comprehensive analysis and reproducible results.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2022)
Article
Chemistry, Analytical
Ratnamala Mandal, Pierce Pham, Christian Hilty
Summary: SABRE technique enhances NMR signals of small molecules by using a purpose-designed reporter ligand to measure biomolecular interactions, screen ligands, and determine dissociation constants.
ANALYTICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Rohit Mahar, Mukundan Ragavan, Mario C. Chang, Savannah Hardiman, Nissin Moussatche, Adam Behar, Rolf Renne, Matthew E. Merritt
Summary: This study analyzed the early-stage metabolic changes in cancer cells associated with oncolytic myxoma virus infection and identified several potential metabolites that can serve as biomarkers for monitoring oncolytic viral action. The metabolic effects of viral infection varied across different cell lines.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Akash K. Kaushik, Amy Tarangelo, Lindsey K. Boroughs, Mukundan Ragavan, Yuanyuan Zhang, Cheng-Yang Wu, Xiangyi Li, Kristen Ahumada, Jui-Chung Chiang, Vanina T. Tcheuyap, Faeze Saatchi, Quyen N. Do, Cissy Yong, Tracy Rosales, Christina Stevens, Aparna D. Rao, Brandon Faubert, Panayotis Pachnis, Lauren G. Zacharias, Hieu Vu, Feng Cai, Thomas P. Mathews, Giannicola Genovese, Barbara S. Slusher, Payal Kapur, Xiankai Sun, Matthew Merritt, James Brugarolas, Ralph J. DeBerardinis
Summary: This study analyzed the metabolism of patient-derived xenografts from different subtypes of renal cell carcinoma. The findings showed that tumorgrafts from VHL-mutant clear cell RCC catabolize glutamine through multiple pathways, which may explain the challenges in achieving therapeutic responses by inhibiting glutaminase.
Article
Chemistry, Multidisciplinary
Anna Rushin, Marc A. McLeod, Mukundan Ragavan, Matthew E. Merritt
Summary: In clinical settings, ex vivo perfusions are commonly used to maintain and evaluate the viability of organs before transplants. By utilizing hyperpolarized (HP) C-13 NMR, exocrine pancreas perfusion technique via the common bile duct can assess acinar cell metabolism. The technique successfully detected various metabolites, indicating flux through pyruvate dehydrogenase and pyruvate carboxylase. The method has the potential to uncover mechanisms underlying pancreatic diseases.
MAGNETIC RESONANCE IN CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Ratnamala Mandal, Pierce Pham, Christian Hilty
Summary: The SABRE technique enhances the sensitivity of detecting biomacromolecular interactions through nuclear spin hyperpolarization. Ligand binding can be identified effectively using flow-NMR and CPMG experiments, providing a cost-effective means for identifying protein-ligand interactions.
Article
Chemistry, Multidisciplinary
Yaewon Kim, Hamidreza Samouei, Christian Hilty
Summary: In this study, polymerization reactions of propene, 1-butene, and isobutene catalyzed by a specific catalyst were characterized using in situ NMR. The dissolved gases were hyperpolarized using the DNP technique, allowing for the observation of reaction kinetics and product formation. The study also revealed the impact of catalyst concentration and reaction time on the monomer signals, indicating a rapid binding and unbinding process during the reactions.