Pub Date : 2025-03-01DOI: 10.1016/j.jmro.2025.100185
Lucio Frydman , Jeffrey A. Reimer
{"title":"Tribute to Alexander Pines (1945-2024)","authors":"Lucio Frydman , Jeffrey A. Reimer","doi":"10.1016/j.jmro.2025.100185","DOIUrl":"10.1016/j.jmro.2025.100185","url":null,"abstract":"","PeriodicalId":365,"journal":{"name":"Journal of Magnetic Resonance Open","volume":"22 ","pages":"Article 100185"},"PeriodicalIF":2.624,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-16DOI: 10.1016/j.jmro.2025.100191
Andreas Brinkmann
Where the first part of our tutorial Introduction to average Hamiltonian theory (Brinkmann, 2016) introduced in detail the basic concepts and demonstrated the application to two composite radio-frequency (rf) pulses in nuclear magnetic resonance (NMR) spectroscopy, this second part will present in a comprehensive but educational manner two, more advanced examples for the application of average Hamiltonian theory in solid-state NMR spectroscopy, both to analyse and design rf pulse sequences: (i) The Rotational-Echo Double Resonance (REDOR) sequence, which recouples the heteronuclear dipolar coupling during sample rotation around an axis at the magic-angle of with respect to the external static magnetic field. We will gradually increase the complexity of applying average Hamiltonian theory by first considering ideal, infinitesimally short rf pulses. Next, we will examine finite pulses with an rf phase of zero, and finally, we will explore finite pulses with arbitrary rf phases. In the latter case, if a first order average Hamiltonian proportional to heteronuclear longitudinal two-spin order () is desired, solutions for the choice of rf phases include the XY and MLEV type schemes. (ii) The Lee–Goldburg homonuclear dipolar decoupling sequence under static samples conditions and its improved successors, Flip-Flop Lee–Goldburg (FFLG) and Frequency-Switched Lee–Goldburg (FSLG).
{"title":"Introduction to average Hamiltonian theory. II. Advanced examples","authors":"Andreas Brinkmann","doi":"10.1016/j.jmro.2025.100191","DOIUrl":"10.1016/j.jmro.2025.100191","url":null,"abstract":"<div><div>Where the first part of our tutorial <em>Introduction to average Hamiltonian theory</em> (Brinkmann, 2016) introduced in detail the basic concepts and demonstrated the application to two composite radio-frequency (rf) pulses in nuclear magnetic resonance (NMR) spectroscopy, this second part will present in a comprehensive but educational manner two, more advanced examples for the application of average Hamiltonian theory in solid-state NMR spectroscopy, both to analyse and design rf pulse sequences: (i) The Rotational-Echo Double Resonance (REDOR) sequence, which recouples the heteronuclear dipolar coupling during sample rotation around an axis at the magic-angle of <span><math><mrow><mn>54</mn><mo>.</mo><mn>7</mn><msup><mrow><mn>4</mn></mrow><mrow><mo>∘</mo></mrow></msup></mrow></math></span> with respect to the external static magnetic field. We will gradually increase the complexity of applying average Hamiltonian theory by first considering ideal, infinitesimally short rf pulses. Next, we will examine finite pulses with an rf phase of zero, and finally, we will explore finite pulses with arbitrary rf phases. In the latter case, if a first order average Hamiltonian proportional to heteronuclear longitudinal two-spin order (<span><math><mrow><mn>2</mn><msub><mrow><mi>I</mi></mrow><mrow><mi>z</mi></mrow></msub><msub><mrow><mi>S</mi></mrow><mrow><mi>z</mi></mrow></msub></mrow></math></span>) is desired, solutions for the choice of rf phases include the XY and MLEV type schemes. (ii) The Lee–Goldburg homonuclear dipolar decoupling sequence under static samples conditions and its improved successors, Flip-Flop Lee–Goldburg (FFLG) and Frequency-Switched Lee–Goldburg (FSLG).</div></div>","PeriodicalId":365,"journal":{"name":"Journal of Magnetic Resonance Open","volume":"23 ","pages":"Article 100191"},"PeriodicalIF":2.624,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143474023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-10DOI: 10.1016/j.jmro.2025.100188
Dihong Fu , Xiaoyun Guo , Bo Duan , Bin Xia
Staphylococcus aureus infections have long been a significant challenge to public health, particularly due to the emergence of multiple drug-resistant strains. SarA is a critical global regulator in S. aureus which binds to AT-rich sequences in the promoter regions of various genes, but the DNA-binding mechanism of SarA remains unclear. Here, we determined the solution structures of a monomeric DNA binding domain of SarA (SarAΔN19) and its complex with an AT-rich double-stranded DNA. The winged helix domain of SarAΔN19 binds to DNA in a classic way, with the α4 helix binding to the major groove of DNA, while the L5 loop binding to the minor groove, covering 10 AT base pairs. Residues L53, P65, and V68 of the α4 helix have hydrophobic interactions with thymine bases and sugar rings. The side chains of Arg90 and Arg84 from the wing are inserted into the minor groove, forming hydrogen bonds with A/T bases. Multiple positively charged or hydrophilic residues, including Lys54, Lys63, Lys69, Lys72, Lys82, and Gln64, interact with the phosphate groups on the DNA backbones. This complex structure provides an in-depth understanding of the molecular mechanism for SarA to bind DNA, and a better structure basis for future anti-bacterial drug design targeting SarA.
{"title":"DNA Binding Mechanism of The Virulence Regulator SarA in Staphylococcus aureus","authors":"Dihong Fu , Xiaoyun Guo , Bo Duan , Bin Xia","doi":"10.1016/j.jmro.2025.100188","DOIUrl":"10.1016/j.jmro.2025.100188","url":null,"abstract":"<div><div><em>Staphylococcus aureus</em> infections have long been a significant challenge to public health, particularly due to the emergence of multiple drug-resistant strains. SarA is a critical global regulator in <em>S. aureus</em> which binds to AT-rich sequences in the promoter regions of various genes, but the DNA-binding mechanism of SarA remains unclear. Here, we determined the solution structures of a monomeric DNA binding domain of SarA (SarA<sup>ΔN19</sup>) and its complex with an AT-rich double-stranded DNA. The winged helix domain of SarA<sup>ΔN19</sup> binds to DNA in a classic way, with the α4 helix binding to the major groove of DNA, while the L5 loop binding to the minor groove, covering 10 AT base pairs. Residues L53, P65, and V68 of the α4 helix have hydrophobic interactions with thymine bases and sugar rings. The side chains of Arg90 and Arg84 from the wing are inserted into the minor groove, forming hydrogen bonds with A/T bases. Multiple positively charged or hydrophilic residues, including Lys54, Lys63, Lys69, Lys72, Lys82, and Gln64, interact with the phosphate groups on the DNA backbones. This complex structure provides an in-depth understanding of the molecular mechanism for SarA to bind DNA, and a better structure basis for future anti-bacterial drug design targeting SarA.</div></div>","PeriodicalId":365,"journal":{"name":"Journal of Magnetic Resonance Open","volume":"22 ","pages":"Article 100188"},"PeriodicalIF":2.624,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143422621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.jmro.2025.100189
Bowen Han , Jing He , Shaohua Huang
Chiral amino acids play an indispensable role in living organisms. Diffusion-ordered NMR spectroscopy is an effective NMR tool and a noninvasive analytical method for the analyses of mixture without the need for physical separation of the analytes. However, conventional diffusion-ordered NMR spectroscopy method usually fails to resolve the mixtures of chiral amino acids because of their same molecular masses, sizes, and shapes. Microcrystalline cellulose has been gradually gained more and more interest owing to its wide compatibility, surface area, excellent separation efficiency, non-toxicity, cost-effective, and mechanical stability in many fields. Herein we provide a fast, simple, specific and sensitive method to resolve some D and L-amino acids mixtures by using microcrystalline cellulose as a matrix. This work recognized some D and L- proteinogenic amino acid enantiomers with diffusion-ordered NMR for the first time.
{"title":"Chiral recognition of some D and L-amino acids by microcrystalline cellulose assisted diffusion-ordered NMR spectroscopy","authors":"Bowen Han , Jing He , Shaohua Huang","doi":"10.1016/j.jmro.2025.100189","DOIUrl":"10.1016/j.jmro.2025.100189","url":null,"abstract":"<div><div>Chiral amino acids play an indispensable role in living organisms. Diffusion-ordered NMR spectroscopy is an effective NMR tool and a noninvasive analytical method for the analyses of mixture without the need for physical separation of the analytes. However, conventional diffusion-ordered NMR spectroscopy method usually fails to resolve the mixtures of chiral amino acids because of their same molecular masses, sizes, and shapes. Microcrystalline cellulose has been gradually gained more and more interest owing to its wide compatibility, surface area, excellent separation efficiency, non-toxicity, cost-effective, and mechanical stability in many fields. Herein we provide a fast, simple, specific and sensitive method to resolve some D and L-amino acids mixtures by using microcrystalline cellulose as a matrix. This work recognized some D and L- proteinogenic amino acid enantiomers with diffusion-ordered NMR for the first time.</div></div>","PeriodicalId":365,"journal":{"name":"Journal of Magnetic Resonance Open","volume":"22 ","pages":"Article 100189"},"PeriodicalIF":2.624,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143164179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-28DOI: 10.1016/j.jmro.2025.100190
Ditte Bentsen Christensen , Ingeborg Sæten Skre , Jan Henrik Ardenkjær-Larsen , Mor Mishkovsky , Mathilde H Lerche
Metabolic magnetic resonance spectroscopic imaging using hyperpolarized contrast agents offers a non-invasive approach to monitoring real-time in vivo energy metabolism. The technique involves hyperpolarizing a contrast agent in a polarizer, administering it to a living system, and then imaging its distribution and metabolites using a magnetic resonance scanner. Over the past two decades, the method has transitioned from in vitro studies to clinical research, with an increasing focus on clinical applications.
Here, we present a hybrid system that adapts a clinical magnetic resonance scanner for pre-clinical rodent experiments. The hybrid system includes (1) a customizable, 3D-printable animal cradle setup and (2) optimized imaging strategies, including coil configurations, metabolic contrast agent administration, and proton imaging acquisition. The system enables 13C dynamic imaging, which we illustrate with detection of hyperpolarized [1–13C]pyruvate and its metabolites in the mouse brain. We detail the experimental procedure, provide practical guidance, and showcase the capabilities of the system with example data from mouse brain imaging.
This hybrid setup bridges the gap between clinical and pre-clinical research, enabling iterative testing of equipment, imaging sequences, and hypotheses across phantoms, in vivo rodent models and clinical settings. By facilitating a smoother translation, both forward and reverse, between pre-clinical and clinical applications, this approach enhances the potential for advancing metabolic imaging research.
{"title":"A hybrid setup for rodent hyperpolarized metabolic imaging using a clinical magnetic resonance scanner","authors":"Ditte Bentsen Christensen , Ingeborg Sæten Skre , Jan Henrik Ardenkjær-Larsen , Mor Mishkovsky , Mathilde H Lerche","doi":"10.1016/j.jmro.2025.100190","DOIUrl":"10.1016/j.jmro.2025.100190","url":null,"abstract":"<div><div>Metabolic magnetic resonance spectroscopic imaging using hyperpolarized contrast agents offers a non-invasive approach to monitoring real-time in vivo energy metabolism. The technique involves hyperpolarizing a contrast agent in a polarizer, administering it to a living system, and then imaging its distribution and metabolites using a magnetic resonance scanner. Over the past two decades, the method has transitioned from in vitro studies to clinical research, with an increasing focus on clinical applications.</div><div>Here, we present a hybrid system that adapts a clinical magnetic resonance scanner for pre-clinical rodent experiments. The hybrid system includes (1) a customizable, 3D-printable animal cradle setup and (2) optimized imaging strategies, including coil configurations, metabolic contrast agent administration, and proton imaging acquisition. The system enables <sup>13</sup>C dynamic imaging, which we illustrate with detection of hyperpolarized [1–<sup>13</sup>C]pyruvate and its metabolites in the mouse brain. We detail the experimental procedure, provide practical guidance, and showcase the capabilities of the system with example data from mouse brain imaging.</div><div>This hybrid setup bridges the gap between clinical and pre-clinical research, enabling iterative testing of equipment, imaging sequences, and hypotheses across phantoms, in vivo rodent models and clinical settings. By facilitating a smoother translation, both forward and reverse, between pre-clinical and clinical applications, this approach enhances the potential for advancing metabolic imaging research.</div></div>","PeriodicalId":365,"journal":{"name":"Journal of Magnetic Resonance Open","volume":"22 ","pages":"Article 100190"},"PeriodicalIF":2.624,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143353597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-27DOI: 10.1016/j.jmro.2025.100187
D. Levi Love, Michael R. Gryk, Adam D. Schuyler
In pursuit of an adaptive approach to nonuniform sampling (NUS), two critical determinants arise: (1) the ability to determine an endpoint by way of quantitatively assessing spectral quality and (2) the ability to systematically determine what additional FIDs to collect if the aforementioned stop criteria is not met. As previously established, in situ receiver operator characteristic (IROC, (Zambrello et al., 2017)) assesses the recovery of injected synthetic ground truth signals to define spectral quality. The Nonuniform Sampling Contest (NUScon, (Pustovalova et al., 2021)), defines a workflow for processing NUS experiments and quantitatively evaluating spectral quality. We augmented that workflow by including an IROC module, which we believe to be an effective component of defining stop criteria for adaptive FID collection. As for the decision of what additional FIDs, this study builds off the work of prior studies on the influence the seed used to generate a nonuniform sample schedule has on the quality of a NUS reconstruction (Hyberts et al., 2011), i.e., whether a sampling method yields “high-variance” or “low-variance” schedules (Zambrello et al., 2020). Namely, existing work has been focused on reducing seed-dependence (Eddy et al., 2012; Mobli, 2015; Worley, 2016) or “optimizing” the seed (Hyberts and Wagner, 2022) by evaluating sample schedules using a computationally inexpensive metric based on the characterization of the point-spread function, like sidelobe-to-peak ratio (Lustig et al., 2007) and peak-to-sidelobe ratio (PSR, (Eddy et al., 2012; Mobli, 2015; Worley, 2016; Craft et al., 2018)). This study assesses the ability of PSR, an a priori metric that is based solely on the nonuniform sample schedule, to predict spectral quality as assessed by IROC. This work uses IROC to show that seed optimization via PSR does not result in better quality spectra. In addition, the trends observed in the spectral quality reported by IROC informs our future designs for adaptive FID selection.
{"title":"Evaluating metrics of spectral quality in nonuniform sampling","authors":"D. Levi Love, Michael R. Gryk, Adam D. Schuyler","doi":"10.1016/j.jmro.2025.100187","DOIUrl":"10.1016/j.jmro.2025.100187","url":null,"abstract":"<div><div>In pursuit of an adaptive approach to nonuniform sampling (<strong>NUS</strong>), two critical determinants arise: (1) the ability to determine an endpoint by way of quantitatively assessing spectral quality and (2) the ability to systematically determine what additional FIDs to collect if the aforementioned stop criteria is not met. As previously established, <em>in situ</em> receiver operator characteristic (<strong>IROC</strong>, (Zambrello et al., 2017)) assesses the recovery of injected synthetic ground truth signals to define spectral quality. The Nonuniform Sampling Contest (<strong>NUScon</strong>, (Pustovalova et al., 2021)), defines a workflow for processing NUS experiments and quantitatively evaluating spectral quality. We augmented that workflow by including an IROC module, which we believe to be an effective component of defining stop criteria for adaptive FID collection. As for the decision of what additional FIDs, this study builds off the work of prior studies on the influence the seed used to generate a nonuniform sample schedule has on the quality of a NUS reconstruction (Hyberts et al., 2011), i.e., whether a sampling method yields “high-variance” or “low-variance” schedules (Zambrello et al., 2020). Namely, existing work has been focused on reducing seed-dependence (Eddy et al., 2012; Mobli, 2015; Worley, 2016) or “optimizing” the seed (Hyberts and Wagner, 2022) by evaluating sample schedules using a computationally inexpensive metric based on the characterization of the point-spread function, like sidelobe-to-peak ratio (Lustig et al., 2007) and peak-to-sidelobe ratio (<strong>PSR</strong>, (Eddy et al., 2012; Mobli, 2015; Worley, 2016; Craft et al., 2018)). This study assesses the ability of PSR, an <em>a priori</em> metric that is based solely on the nonuniform sample schedule, to predict spectral quality as assessed by IROC. This work uses IROC to show that seed optimization via PSR does not result in better quality spectra. In addition, the trends observed in the spectral quality reported by IROC informs our future designs for adaptive FID selection.</div></div>","PeriodicalId":365,"journal":{"name":"Journal of Magnetic Resonance Open","volume":"23 ","pages":"Article 100187"},"PeriodicalIF":2.624,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143464323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-20DOI: 10.1016/j.jmro.2025.100186
Haoyu Li , Yifan Song , Yu Yin , Juntao Xia , Yun Chen , Maria Grazia Concilio , Xueqian Kong
The phenomenon of intermolecular multiple-quantum coherences (iMQCs) has been known for decades, mainly for spin-1/2 nuclei. However, the iMQC of 23Na, a spin-3/2 quadrupolar nucleus, has not been studied previously. In this communication, we report the observation of 23Na iMQC signals arising from 23Na–23Na long-range dipolar interaction in the aqueous solutions of various sodium salts. We investigated the iMQC signal in response to different experimental parameters. We also formulated a theoretical model to explain the experimental results. Since sodium ions play important roles in biology and industry, 23Na iMQC experiments could bring new insights into ion dynamics and interactions in solutions.
{"title":"23Na intermolecular multiple-quantum coherences in salt solutions","authors":"Haoyu Li , Yifan Song , Yu Yin , Juntao Xia , Yun Chen , Maria Grazia Concilio , Xueqian Kong","doi":"10.1016/j.jmro.2025.100186","DOIUrl":"10.1016/j.jmro.2025.100186","url":null,"abstract":"<div><div>The phenomenon of intermolecular multiple-quantum coherences (iMQCs) has been known for decades, mainly for spin-1/2 nuclei. However, the iMQC of <sup>23</sup>Na, a spin-3/2 quadrupolar nucleus, has not been studied previously. In this communication, we report the observation of <sup>23</sup>Na iMQC signals arising from <sup>23</sup>Na–<sup>23</sup>Na long-range dipolar interaction in the aqueous solutions of various sodium salts. We investigated the iMQC signal in response to different experimental parameters. We also formulated a theoretical model to explain the experimental results. Since sodium ions play important roles in biology and industry, <sup>23</sup>Na iMQC experiments could bring new insights into ion dynamics and interactions in solutions.</div></div>","PeriodicalId":365,"journal":{"name":"Journal of Magnetic Resonance Open","volume":"22 ","pages":"Article 100186"},"PeriodicalIF":2.624,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143387344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-27DOI: 10.1016/j.jmro.2024.100184
Ditte B. Christensen , Ingeborg S. Skre , Jan Henrik Ardenkjær-Larsen, Magnus Karlsson, Mathilde H. Lerche
Dissolution Dynamic Nuclear Polarization (dDNP) polarizers have achieved high field strengths and large sample volumes. These advancements necessitate new formulations of hyperpolarized metabolic contrast agents (HMCAs) to enable large animal studies. While several metabolic substrates have been investigated at lower field dDNP and tested as HMCAs in rodents, 13C-labeled pyruvate remains the most studied HMCA and is currently the only one actively used in clinical trials due to its favorable biological and physical properties. Effective human and large animal dDNP formulations require high molar substrate concentrations, low DNP sample viscosity for efficient dissolution, and adequate dilution of the DNP sample to minimize signal decay and maximize HMCA concentration.
We present substrate formulations optimized for high-field polarization and large-volume dissolution. Specifically, we validate the upscaling of [1–13C]pyruvate under high-field conditions and demonstrate that [1–13C]2-keto-isocaproate and [1,4–13C2]fumarate, which have been proven successful in rodent studies, can be formulated to yield high polarization at suitable concentrations and volumes for large animal metabolic MR imaging.
{"title":"Developing hyperpolarized metabolic contrast agents at high field dDNP for large animal research","authors":"Ditte B. Christensen , Ingeborg S. Skre , Jan Henrik Ardenkjær-Larsen, Magnus Karlsson, Mathilde H. Lerche","doi":"10.1016/j.jmro.2024.100184","DOIUrl":"10.1016/j.jmro.2024.100184","url":null,"abstract":"<div><div>Dissolution Dynamic Nuclear Polarization (dDNP) polarizers have achieved high field strengths and large sample volumes. These advancements necessitate new formulations of hyperpolarized metabolic contrast agents (HMCAs) to enable large animal studies. While several metabolic substrates have been investigated at lower field dDNP and tested as HMCAs in rodents, <sup>13</sup>C-labeled pyruvate remains the most studied HMCA and is currently the only one actively used in clinical trials due to its favorable biological and physical properties. Effective human and large animal dDNP formulations require high molar substrate concentrations, low DNP sample viscosity for efficient dissolution, and adequate dilution of the DNP sample to minimize signal decay and maximize HMCA concentration.</div><div>We present substrate formulations optimized for high-field polarization and large-volume dissolution. Specifically, we validate the upscaling of [1–<sup>13</sup>C]pyruvate under high-field conditions and demonstrate that [1–<sup>13</sup>C]2-keto-isocaproate and [1,4–<sup>13</sup>C<sub>2</sub>]fumarate, which have been proven successful in rodent studies, can be formulated to yield high polarization at suitable concentrations and volumes for large animal metabolic MR imaging.</div></div>","PeriodicalId":365,"journal":{"name":"Journal of Magnetic Resonance Open","volume":"22 ","pages":"Article 100184"},"PeriodicalIF":2.624,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143164938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-20DOI: 10.1016/j.jmro.2024.100183
Lisa M. Fries , Denis Moll , Ruhuai Mei , Theresa L․ K․ Hune , Josef Elsaßer , Stefan Glöggler
Magnetic Resonance Imaging (MRI) is a valuable non-invasive technique widely used in clinical diagnostics; however, its sensitivity is limited, posing challenges in various medical conditions. Hyperpolarization techniques represent a promising approach to dramatically enhance signals in magnetic resonance imaging (MRI) and allow the use endogenous metabolites as contrast media. In this study, we synthesized N-acetyl-alanine ethyl ester as a novel imaging agent and assessed its in vivo imaging capabilities, potentially offering diagnostic and monitoring capabilities for cardiovascular diseases. It is derived from N-acetyl-alanine, an endogenous metabolic end product of protein degradation. The in vivo experiments resulted in high-resolution images of the circulatory system acquired within sub-seconds. Our findings not only highlight the potential preclinical utility of this new, generally available agent, but also advance the frontier of hyperpolarized contrast agents.
{"title":"Assessing a hyperpolarized [1-13C]-labeled alanine derivative enhanced via parahydrogen for in vivo studies","authors":"Lisa M. Fries , Denis Moll , Ruhuai Mei , Theresa L․ K․ Hune , Josef Elsaßer , Stefan Glöggler","doi":"10.1016/j.jmro.2024.100183","DOIUrl":"10.1016/j.jmro.2024.100183","url":null,"abstract":"<div><div>Magnetic Resonance Imaging (MRI) is a valuable non-invasive technique widely used in clinical diagnostics; however, its sensitivity is limited, posing challenges in various medical conditions. Hyperpolarization techniques represent a promising approach to dramatically enhance signals in magnetic resonance imaging (MRI) and allow the use endogenous metabolites as contrast media. In this study, we synthesized N-acetyl-alanine ethyl ester as a novel imaging agent and assessed its <em>in vivo</em> imaging capabilities, potentially offering diagnostic and monitoring capabilities for cardiovascular diseases. It is derived from N-acetyl-alanine, an endogenous metabolic end product of protein degradation. The <em>in vivo</em> experiments resulted in high-resolution images of the circulatory system acquired within sub-seconds. Our findings not only highlight the potential preclinical utility of this new, generally available agent, but also advance the frontier of hyperpolarized contrast agents.</div></div>","PeriodicalId":365,"journal":{"name":"Journal of Magnetic Resonance Open","volume":"22 ","pages":"Article 100183"},"PeriodicalIF":2.624,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143164181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-10DOI: 10.1016/j.jmro.2024.100182
Yi Ji , Kuizhi Chen , Aijing Hao , Guangjin Hou
Recent advances in the 17O-enrichment techiques and high-resolution nuclear magnetic resonance (NMR) methods have opened new opportunities to utilize 17O NMR to disentangle the zeolitic structure−property relationship that has not been well resolved through traditional 1H, 27Al, and 29Si NMR spectroscopy. Compared with one-dimensional 17O magic angle spinning (MAS) NMR experiments, 1H-17O correlation spectrocopy has become a crucial method for revealing the structures and dynamics of reactive hydroxyl species in zeolites with higher resolution and precision. However, the introduction of 17O can induce changes in 1H MAS NMR signals due to the second-order 1H-17O quadrupolar-dipolar (2nd-QD) cross interaction, which has recently been revealed by us on H-ZSM-5 (H-MFI) zeolites with 10-membered-ring (MR) channels. Herein, we performed various 1H-17O correlation experiments (1H{17O}-J-heteronuclear multiple quantum coherence (HMQC), 1H{17O}-D-HMQC, and 1H→17O-D-RINEPT) on two other types of 17O-enriched zeolites, i.e., H-Mordenite (H-MOR) with 8-/12-MR channels and H-ZSM-35 (H-FER) with 8-/10-MR channels. Notably, unusual 1H-17O correlation signals with tilted patterns and magnetic-field-dependent shifts were observed on both samples and all tested correlation experiments at high fields up to 18.8 T. These observations were further comprehensively explained by theoretical analysis of the 1H-17O quadrupolar-dipolar interaction, thus demonstrating that the 1H-17O 2nd-QD interaction generally affects the 1H and 1H-17O correlation MAS NMR spectra of the dehydrated 17O-enriched zeolites, irrespective of the framework types. Beyond zeolites, the non-ignorable 2nd-QD interaction on NMR spectroscopy can complicate NMR identification of 17O-labeled hydroxyls in many other inorganic materials and biomolecules. The analysis methods proposed in this study are expected to effectively address these challenges and provide clearer insights into such systems.
17O富集技术和高分辨率核磁共振（NMR）方法的最新进展为利用17O NMR来解开传统1H、27Al和29Si核磁共振光谱无法很好解决的沸石结构-性质关系开辟了新的机会。与一维17O魔角旋转（MAS）核磁共振实验相比，1H-17O相关光谱以更高的分辨率和精度成为揭示沸石中活性羟基结构和动力学的重要方法。然而，17O的引入会引起1H MAS NMR信号的变化，这是由于二阶1H-17O四极-偶极（2 - qd）交叉相互作用，最近我们在具有10元环（MR）通道的H-ZSM-5 （H-MFI）沸石上发现的。在此，我们对另外两种富含17O的沸石，即具有8-/12-MR通道的h -丝光沸石（H-MOR）和具有8-/10-MR通道的H-ZSM-35 （H-FER）进行了各种1H-17O相关实验（1H{17O}- j -异核多重量子相干性（HMQC）、1H{17O}- d -HMQC和1H→17O- d - rinept）。值得注意的是，在两个样品和所有测试的相关实验中，在高达18.8 t的高场下，都观察到异常的倾斜模式和磁场依赖位移的1H- 17o相关信号。这些观察结果进一步通过1H- 17o四极-偶极相互作用的理论分析得到了全面的解释，从而表明1H- 17o第2 - qd相互作用通常影响脱水富17o沸石的1H和1H- 17o相关MAS NMR谱。不管框架类型如何。除沸石外，核磁共振波谱上不可忽视的第二量子点相互作用使许多其他无机材料和生物分子中17o标记羟基的核磁共振鉴定复杂化。本研究提出的分析方法有望有效解决这些挑战，并为此类系统提供更清晰的见解。
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