Complete characterization of 13C chemical shift tensor in magnetically oriented microcrystal suspension (MOMS) is demonstrated with an inhouse 1H-13C double resonance probe capable of rotating microcrystals and of tilting the sample temporarily during the period of NMR signal acquisition. The 13C chemical shift tensor in three-dimensional MOMS of l-alanine is determined from 13C rotation patterns around a tilted axis. The present results prove that even for micrometer-sized microcrystals the chemical shift tensor can be fully determined like in the case of a single piece of bulky crystal but without elaborate sample mounting. Two-dimensional experiments correlating chemical shifts for different sample orientations are also demonstrated.
{"title":"Full determination of chemical shift tensor in magnetically oriented microcrystals with modulated rotation and temporal tilt","authors":"Ryosuke Kusumi , Hayate Yasui , Hiroshi Kadoma , Masahisa Wada , Kazuyuki Takeda","doi":"10.1016/j.jmr.2025.107853","DOIUrl":"10.1016/j.jmr.2025.107853","url":null,"abstract":"<div><div>Complete characterization of <sup>13</sup>C chemical shift tensor in magnetically oriented microcrystal suspension (MOMS) is demonstrated with an inhouse <sup>1</sup>H-<sup>13</sup>C double resonance probe capable of rotating microcrystals and of tilting the sample temporarily during the period of NMR signal acquisition. The <sup>13</sup>C chemical shift tensor in three-dimensional MOMS of <span>l</span>-alanine is determined from <sup>13</sup>C rotation patterns around a tilted axis. The present results prove that even for micrometer-sized microcrystals the chemical shift tensor can be fully determined like in the case of a single piece of bulky crystal but without elaborate sample mounting. Two-dimensional experiments correlating chemical shifts for different sample orientations are also demonstrated.</div></div>","PeriodicalId":16267,"journal":{"name":"Journal of magnetic resonance","volume":"373 ","pages":"Article 107853"},"PeriodicalIF":2.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143519875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-18DOI: 10.1016/j.jmr.2025.107852
Samuel Perron , Claire S. Tully , Shivam Gupta , Matthew S. Fox , Dmitrij Zagidulin , James J. Noël , Alexei Ouriadov
Although the relaxation time constants of free water are relatively long, the relaxation of water in concrete and other sedimentary materials is significantly shorter. Dissolved ions and porous environments can cause increased magnetic susceptibility effects, leading to the apparent transverse relaxation time T2⁎ of this water to decrease drastically, from seconds to less than a millisecond. The longer T2⁎ of the low field regime (less than 0.5 T) should allow for 2D and even 3D imaging of water content in these types of materials; developing a suitable technique for imaging of short-T2⁎ samples would permit imaging of porous rocks and concrete.
A 12 mL wet bentonite clay sample was placed within a syringe and allowed to absorb increasing volumes of standing water. This progressing absorption was imaged on a 73.5 mT magnetic resonance imaging (MRI) system using the X-Centric pulse sequence. This pulse sequence is a modified version of the common gradient echo (GE) pulse sequence, in which each half of k-space is acquired separately, from the centre outwards in the readout direction, ensuring minimal T2⁎-weighting of the resulting image and allowing for 2D imaging within the short time frame of the shorter T2⁎ of water in the clay. Bulk relaxation measurements of T2⁎ and the longitudinal relaxation time T1 were performed for increasing water content, with a mean T1 of 12.0 ± 1.1 ms and mean T2⁎ of 4.5 ± 0.7 ms; 2D imaging of the clay sample was performed with both GE and X-Centric. In addition, a 2D T2⁎ map was generated from eight X-Centric images taken at different echo times.
The X-Centric pulse sequence was demonstrated to be an effective imaging method for short signal-lifetime samples, such as water trapped in bentonite clay. The ease of implementation, minimal diffusion-weighting and T2⁎ weighting of the k-space centre, and considerable gains in signal-to-noise ratio and imaging efficiency position this pulse sequence as a viable alternative or complement to conventional GE acquisitions. Additionally, the short echo-time of the X-Centric pulse sequence allows it to be used effectively with non-proton MRI, including 23Na and fluorinated gases (e.g., 19F) where the T2⁎-decay is a potentially significant source of signal decay.
{"title":"Implementation of the X-centric pulse sequence at low field for MRI of water penetration in clay","authors":"Samuel Perron , Claire S. Tully , Shivam Gupta , Matthew S. Fox , Dmitrij Zagidulin , James J. Noël , Alexei Ouriadov","doi":"10.1016/j.jmr.2025.107852","DOIUrl":"10.1016/j.jmr.2025.107852","url":null,"abstract":"<div><div>Although the relaxation time constants of free water are relatively long, the relaxation of water in concrete and other sedimentary materials is significantly shorter. Dissolved ions and porous environments can cause increased magnetic susceptibility effects, leading to the apparent transverse relaxation time <em>T</em><sub><em>2</em></sub><sup><em>⁎</em></sup> of this water to decrease drastically, from seconds to less than a millisecond. The longer <em>T</em><sub><em>2</em></sub><sup><em>⁎</em></sup> of the low field regime (less than 0.5 T) should allow for 2D and even 3D imaging of water content in these types of materials; developing a suitable technique for imaging of short-<em>T</em><sub><em>2</em></sub><sup><em>⁎</em></sup> samples would permit imaging of porous rocks and concrete.</div><div>A 12 mL wet bentonite clay sample was placed within a syringe and allowed to absorb increasing volumes of standing water. This progressing absorption was imaged on a 73.5 mT magnetic resonance imaging (MRI) system using the X-Centric pulse sequence. This pulse sequence is a modified version of the common gradient echo (GE) pulse sequence, in which each half of <em>k</em>-space is acquired separately, from the centre outwards in the readout direction, ensuring minimal <em>T</em><sub><em>2</em></sub><sup><em>⁎</em></sup>-weighting of the resulting image and allowing for 2D imaging within the short time frame of the shorter <em>T</em><sub><em>2</em></sub><sup><em>⁎</em></sup> of water in the clay. Bulk relaxation measurements of <em>T</em><sub><em>2</em></sub><sup><em>⁎</em></sup> and the longitudinal relaxation time <em>T</em><sub><em>1</em></sub> were performed for increasing water content, with a mean <em>T</em><sub><em>1</em></sub> of 12.0 ± 1.1 ms and mean <em>T</em><sub><em>2</em></sub><sup><em>⁎</em></sup> of 4.5 ± 0.7 ms; 2D imaging of the clay sample was performed with both GE and X-Centric. In addition, a 2D <em>T</em><sub><em>2</em></sub><sup><em>⁎</em></sup> map was generated from eight X-Centric images taken at different echo times.</div><div>The X-Centric pulse sequence was demonstrated to be an effective imaging method for short signal-lifetime samples, such as water trapped in bentonite clay. The ease of implementation, minimal diffusion-weighting and <em>T</em><sub><em>2</em></sub><sup><em>⁎</em></sup> weighting of the <em>k</em>-space centre, and considerable gains in signal-to-noise ratio and imaging efficiency position this pulse sequence as a viable alternative or complement to conventional GE acquisitions. Additionally, the short echo-time of the X-Centric pulse sequence allows it to be used effectively with non-proton MRI, including <sup>23</sup>Na and fluorinated gases (e.g., <sup>19</sup>F) where the <em>T</em><sub><em>2</em></sub><sup><em>⁎</em></sup>-decay is a potentially significant source of signal decay.</div></div>","PeriodicalId":16267,"journal":{"name":"Journal of magnetic resonance","volume":"373 ","pages":"Article 107852"},"PeriodicalIF":2.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","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.jmr.2025.107851
Giulia Fischetti , Nicolas Schmid , Simon Bruderer , Björn Heitmann , Andreas Henrici , Alessandro Scarso , Guido Caldarelli , Dirk Wilhelm
One-dimensional 1H Nuclear Magnetic Resonance (NMR) stands out as the quickest and simplest among various NMR experimental setups. Unfortunately, it suffers from lengthy annotation times and does not always have a clear and unique interpretation. From NMR discovery, efforts have been dedicated to introducing an automated approach to streamline the characterization of chemical compounds while ensuring consistency of the results across the scientific community. Nonetheless, this remains an ongoing challenge that has garnered renewed interest with the emergence of deep learning techniques. Here, we present MuSe Net, a novel supervised probabilistic deep learning framework that can emulate the tasks performed by an expert spectroscopist in annotating one-dimensional NMR spectra generated by small molecules. Considering only the spectrum, MuSe Net detects and classifies multiplets with up to four coupling constants for their splitting phenotype, providing a segmentation of the spectral range. We exploit uncertainty quantification to produce a confidence score to both assess classification reliability and to detect signals that do not fit into any other phenotype class. The results of the evaluation against 48 experimental 1H NMR spectra of small molecules annotated by experts demonstrate that MuSe Net can deal with anomalies and unclear signals while correctly classifying multiplets and detecting overlapping peaks.
{"title":"A deep learning framework for multiplet splitting classification in 1H NMR","authors":"Giulia Fischetti , Nicolas Schmid , Simon Bruderer , Björn Heitmann , Andreas Henrici , Alessandro Scarso , Guido Caldarelli , Dirk Wilhelm","doi":"10.1016/j.jmr.2025.107851","DOIUrl":"10.1016/j.jmr.2025.107851","url":null,"abstract":"<div><div>One-dimensional <sup>1</sup>H Nuclear Magnetic Resonance (NMR) stands out as the quickest and simplest among various NMR experimental setups. Unfortunately, it suffers from lengthy annotation times and does not always have a clear and unique interpretation. From NMR discovery, efforts have been dedicated to introducing an automated approach to streamline the characterization of chemical compounds while ensuring consistency of the results across the scientific community. Nonetheless, this remains an ongoing challenge that has garnered renewed interest with the emergence of deep learning techniques. Here, we present MuSe Net, a novel supervised probabilistic deep learning framework that can emulate the tasks performed by an expert spectroscopist in annotating one-dimensional NMR spectra generated by small molecules. Considering only the spectrum, MuSe Net detects and classifies multiplets with up to four coupling constants for their splitting phenotype, providing a segmentation of the spectral range. We exploit uncertainty quantification to produce a confidence score to both assess classification reliability and to detect signals that do not fit into any other phenotype class. The results of the evaluation against 48 experimental <sup>1</sup>H NMR spectra of small molecules annotated by experts demonstrate that MuSe Net can deal with anomalies and unclear signals while correctly classifying multiplets and detecting overlapping peaks.</div></div>","PeriodicalId":16267,"journal":{"name":"Journal of magnetic resonance","volume":"373 ","pages":"Article 107851"},"PeriodicalIF":2.0,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143444601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dynamic nuclear polarization (DNP) is widely used in a wide range of applications in solid-state NMR nowadays due to recent advancements of magic-angle spinning (MAS) DNP. Conventionally, an MAS-DNP system employs a gyrotron as a microwave source and operates at 100 K using nitrogen gas. As an alternative, we present a 400 MHz/263 GHz MAS-DNP system utilizing a compact solid-state microwave source and an ultra-low temperature (ULT) helium MAS probe equipped with a cryogenic preamplifier. Compared to gyrotrons, solid-state microwave sources are compact, cost-effective, and frequency agile. The ULT compensates for the decreased DNP efficiency resulting from the lower microwave power of the solid-state source. Additionally, the large Boltzmann polarization at ULT and the improved signal-to-noise ratio provided by the cryogenic preamplifier enhance the sensitivity of the MAS-DNP system. The system is tested using a DNP standard sample of proline in a mixture of deuterated glycerol and partially deuterated water doped with AMUPol, achieving a DNP enhancement of 85 using a 2 mm-diameter rotor at a sample temperature of 30 K and microwave power of 160 mW. Experimental data show that the Boltzmann polarization and the cryogenic preamplifier contribute an additional sensitivity gain of 11 at 30 K compared to 100 K. Overall, the ULT-DNP related sensitivity gain of this system is estimated to be roughly twice that of a 100 K gyrotron system, although the DNP enhancement factor alone is smaller using a solid-state microwave source.
{"title":"400 MHz/263 GHz ultra-low temperature MAS-DNP using a closed-cycle helium gas cooling system and a solid-state microwave source","authors":"Fumio Hobo , Yusuke Tanimoto , Yuki Endo , Yoh Matsuki , Hiroki Takahashi","doi":"10.1016/j.jmr.2025.107842","DOIUrl":"10.1016/j.jmr.2025.107842","url":null,"abstract":"<div><div>Dynamic nuclear polarization (DNP) is widely used in a wide range of applications in solid-state NMR nowadays due to recent advancements of magic-angle spinning (MAS) DNP. Conventionally, an MAS-DNP system employs a gyrotron as a microwave source and operates at <span><math><mo>∼</mo></math></span>100 K using nitrogen gas. As an alternative, we present a 400 MHz/263 GHz MAS-DNP system utilizing a compact solid-state microwave source and an ultra-low temperature (ULT) helium MAS probe equipped with a cryogenic preamplifier. Compared to gyrotrons, solid-state microwave sources are compact, cost-effective, and frequency agile. The ULT compensates for the decreased DNP efficiency resulting from the lower microwave power of the solid-state source. Additionally, the large Boltzmann polarization at ULT and the improved signal-to-noise ratio provided by the cryogenic preamplifier enhance the sensitivity of the MAS-DNP system. The system is tested using a DNP standard sample of proline in a mixture of deuterated glycerol and partially deuterated water doped with AMUPol, achieving a DNP enhancement of 85 using a 2 mm-diameter rotor at a sample temperature of 30 K and microwave power of 160 mW. Experimental data show that the Boltzmann polarization and the cryogenic preamplifier contribute an additional sensitivity gain of 11<span><math><mo>×</mo></math></span> at 30 K compared to 100 K. Overall, the ULT-DNP related sensitivity gain of this system is estimated to be roughly twice that of a 100 K gyrotron system, although the DNP enhancement factor alone is smaller using a solid-state microwave source.</div></div>","PeriodicalId":16267,"journal":{"name":"Journal of magnetic resonance","volume":"373 ","pages":"Article 107842"},"PeriodicalIF":2.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143387540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.jmr.2025.107830
Agide Gimenez Marassi , Arthur Gustavo de Araújo-Ferreira , Everton Lucas-Oliveira , Aparecido Donizeti Fernandes de Amorim , Edson Luiz Géa Vidoto , Willian Andrighetto Trevizan , Tito José Bonagamba
Among the numerous measurements carried out during a well-logging procedure, the Nuclear Magnetic Resonance (NMR) assessment is one of the fundamental analyses in determining the economic viability of a well for the oil industry. Nowadays, two reliable approaches, Wireline Logging (WL) and Logging While Drilling (LWD), stand out. WL comprises the acquisition of NMR data under static conditions. On the other hand, in LWD, the NMR measurements happen simultaneously with the drilling process, while the NMR tool experiences translation, rotation, and vibration motions relative to the rock formation. In order to comprehend better the NMR response acquired under LWD conditions, a setup emulating an LWD tool was developed, consisting of a single-sided magnet, rf probes, and a mechanical device that emulates a relative sinusoidal movement between the sample and the applied magnetic field. A bulk sample and three representative rocks, Fontainebleau Sandstone, Berea Sandstone, and Indiana Limestone, were investigated. Even though the diffusion coefficient measurements remain neglected for their intrinsic characteristics of data acquisition, the findings demonstrate that the diffusion coefficient parameter of a fluid in a bulk sample or confined in a porous rock can be precise and accurately predicted. In strong magnetic field gradients, the Hahn spin echo is predominantly weighted by the diffusion process, an effect used to measure diffusion coefficients. Under LWD conditions, the diffusion coefficient measurement is considerably affected by signal phase modulation due to sample movement in the presence of strong magnetic field gradients, making this measurement difficult. This article present solutions for correct diffusion coefficient measurements, synchronizing Hahn spin echo experiments with sample movement.
{"title":"Diffusion coefficient measurements for moving samples under strong magnetic field gradients","authors":"Agide Gimenez Marassi , Arthur Gustavo de Araújo-Ferreira , Everton Lucas-Oliveira , Aparecido Donizeti Fernandes de Amorim , Edson Luiz Géa Vidoto , Willian Andrighetto Trevizan , Tito José Bonagamba","doi":"10.1016/j.jmr.2025.107830","DOIUrl":"10.1016/j.jmr.2025.107830","url":null,"abstract":"<div><div>Among the numerous measurements carried out during a well-logging procedure, the Nuclear Magnetic Resonance (NMR) assessment is one of the fundamental analyses in determining the economic viability of a well for the oil industry. Nowadays, two reliable approaches, Wireline Logging (WL) and Logging While Drilling (LWD), stand out. WL comprises the acquisition of NMR data under static conditions. On the other hand, in LWD, the NMR measurements happen simultaneously with the drilling process, while the NMR tool experiences translation, rotation, and vibration motions relative to the rock formation. In order to comprehend better the NMR response acquired under LWD conditions, a setup emulating an LWD tool was developed, consisting of a single-sided magnet, rf probes, and a mechanical device that emulates a relative sinusoidal movement between the sample and the applied magnetic field. A bulk sample and three representative rocks, Fontainebleau Sandstone, Berea Sandstone, and Indiana Limestone, were investigated. Even though the diffusion coefficient measurements remain neglected for their intrinsic characteristics of data acquisition, the findings demonstrate that the diffusion coefficient parameter of a fluid in a bulk sample or confined in a porous rock can be precise and accurately predicted. In strong magnetic field gradients, the Hahn spin echo is predominantly weighted by the diffusion process, an effect used to measure diffusion coefficients. Under LWD conditions, the diffusion coefficient measurement is considerably affected by signal phase modulation due to sample movement in the presence of strong magnetic field gradients, making this measurement difficult. This article present solutions for correct diffusion coefficient measurements, synchronizing Hahn spin echo experiments with sample movement.</div></div>","PeriodicalId":16267,"journal":{"name":"Journal of magnetic resonance","volume":"371 ","pages":"Article 107830"},"PeriodicalIF":2.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.jmr.2024.107810
Stephen Wimperis , Galina E. Pavlovskaya
Double-quantum filtered 23Na NMR experiments with one or two “magic angle” (54.7°) pulses in the filter step are widely used for selective observation of sodium ions that are interacting with ordered biological structures (“ordered sodium”) and hence exhibit a distribution of quadrupolar splittings in their NMR spectrum. This approach has recently been extended to 23Na MRI where the conventional experiment has been modified, omitting the 180° pulse to reduce the absorption of radiofrequency energy during human studies. Here, the “magic angle” double-quantum filtered 23Na NMR experiment (without a 180° pulse) is analysed in terms of coherence pathways that lead to refocusing in an inhomogeneous B0 field (“echoes”) and those that do not (“antiechoes”). It is shown that the echo and antiecho pathways can be separated by phase cycling and that the antiecho pathway contributes very little to the overall signal in an inhomogeneous B0 field. Hence, a double-quantum filtered 23Na NMR experiment that utilises just the echo pathway and so achieves complete refocusing of the effects of B0 inhomogeneity without making use of a 180° pulse is proposed. The new method is demonstrated both in 23Na NMR spectroscopy in an inhomogeneous B0 field and in 23Na MRI of a three-component phantom.
{"title":"Double-quantum filtered 23Na NMR and MRI: Selective detection of ordered sodium in an inhomogeneous B0 field","authors":"Stephen Wimperis , Galina E. Pavlovskaya","doi":"10.1016/j.jmr.2024.107810","DOIUrl":"10.1016/j.jmr.2024.107810","url":null,"abstract":"<div><div>Double-quantum filtered <sup>23</sup>Na NMR experiments with one or two “magic angle” (54.7°) pulses in the filter step are widely used for selective observation of sodium ions that are interacting with ordered biological structures (“ordered sodium”) and hence exhibit a distribution of quadrupolar splittings in their NMR spectrum. This approach has recently been extended to <sup>23</sup>Na MRI where the conventional experiment has been modified, omitting the 180° pulse to reduce the absorption of radiofrequency energy during human studies. Here, the “magic angle” double-quantum filtered <sup>23</sup>Na NMR experiment (without a 180° pulse) is analysed in terms of coherence pathways that lead to refocusing in an inhomogeneous B<sub>0</sub> field (“echoes”) and those that do not (“antiechoes”). It is shown that the echo and antiecho pathways can be separated by phase cycling and that the antiecho pathway contributes very little to the overall signal in an inhomogeneous B<sub>0</sub> field. Hence, a double-quantum filtered <sup>23</sup>Na NMR experiment that utilises just the echo pathway and so achieves complete refocusing of the effects of B<sub>0</sub> inhomogeneity without making use of a 180° pulse is proposed. The new method is demonstrated both in <sup>23</sup>Na NMR spectroscopy in an inhomogeneous B<sub>0</sub> field and in <sup>23</sup>Na MRI of a three-component phantom.</div></div>","PeriodicalId":16267,"journal":{"name":"Journal of magnetic resonance","volume":"371 ","pages":"Article 107810"},"PeriodicalIF":2.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","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.jmr.2024.107827
Mária Šoltésová , Arthur C. Pinon , Fabien Aussenac , Judith Schlagnitweit , Christian Reiter , Armin Purea , Roberto Melzi , Frank Engelke , Dave Martin , Stefanie Krambeck , Annabelle Biscans , Emma Kay , Lyndon Emsley , Staffan Schantz
A new 3.2 mm 1H–19F–X magic angle spinning dynamic nuclear polarization NMR (MAS DNP-NMR) probe was developed with a unique coil design with separate radiofrequency channels for 1H excitation and 13C or 19F detection to enable acquisition of 1H–19F cross-polarization (CP) MAS experiments, direct-detected 19F spectra with proton decoupling, and acquisition on 13C with simultaneous double decoupling on the 1H and 19F channels as well as 1H–19F–13C double-CP experiments under low temperature MAS DNP conditions. We use these sequences to study AZD2811, which is an active pharmaceutical ingredient (API), in its pure dry state as well as in its corresponding drug delivery formulation consisting of drug-loaded polymeric nanoparticles (PNPs). Included in this study are also small interfering RNAs (siRNAs) for therapeutic targeting of peptidyl-prolyl cis–trans isomerase B (Ppib) mRNA. We demonstrate that 1H–19F CP MAS experiments performed on the new HFX probe represent a notable advantage over usually acquired direct-detected 19F experiments. The indirect 19F DNP enhancement εon/off(19F) = 26 was obtained via 1H–19F CP for the pure API impregnated with DNP solution, with an overall 30-fold sensitivity gain compared to the direct-detected 19F experiment under similar conditions. DNP enhancement value of εon/off(19F) = 42 was obtained via 1H–19F CP for the polymeric nanoparticle suspension and εon/off(19F) ≈ 150 were obtained for two different siRNAs in frozen DNP solution.
{"title":"1H–19F cross-polarization magic angle spinning dynamic nuclear polarization NMR investigation of advanced pharmaceutical formulations","authors":"Mária Šoltésová , Arthur C. Pinon , Fabien Aussenac , Judith Schlagnitweit , Christian Reiter , Armin Purea , Roberto Melzi , Frank Engelke , Dave Martin , Stefanie Krambeck , Annabelle Biscans , Emma Kay , Lyndon Emsley , Staffan Schantz","doi":"10.1016/j.jmr.2024.107827","DOIUrl":"10.1016/j.jmr.2024.107827","url":null,"abstract":"<div><div>A new 3.2 mm <sup>1</sup>H–<sup>19</sup>F–X magic angle spinning dynamic nuclear polarization NMR (MAS DNP-NMR) probe was developed with a unique coil design with separate radiofrequency channels for <sup>1</sup>H excitation and <sup>13</sup>C or <sup>19</sup>F detection to enable acquisition of <sup>1</sup>H–<sup>19</sup>F cross-polarization (CP) MAS experiments, direct-detected <sup>19</sup>F spectra with proton decoupling, and acquisition on <sup>13</sup>C with simultaneous double decoupling on the <sup>1</sup>H and 19F channels as well as <sup>1</sup>H–<sup>19</sup>F–<sup>13</sup>C double-CP experiments under low temperature MAS DNP conditions. We use these sequences to study AZD2811, which is an active pharmaceutical ingredient (API), in its pure dry state as well as in its corresponding drug delivery formulation consisting of drug-loaded polymeric nanoparticles (PNPs). Included in this study are also small interfering RNAs (siRNAs) for therapeutic targeting of peptidyl-prolyl <em>cis–trans</em> isomerase B (<em>Ppib</em>) mRNA. We demonstrate that <sup>1</sup>H–<sup>19</sup>F CP MAS experiments performed on the new HFX probe represent a notable advantage over usually acquired direct-detected <sup>19</sup>F experiments. The indirect <sup>19</sup>F DNP enhancement ε<sub>on/off</sub>(<sup>19</sup>F) = 26 was obtained via <sup>1</sup>H–<sup>19</sup>F CP for the pure API impregnated with DNP solution, with an overall 30-fold sensitivity gain compared to the direct-detected <sup>19</sup>F experiment under similar conditions. DNP enhancement value of ε<sub>on/off</sub>(<sup>19</sup>F) = 42 was obtained via <sup>1</sup>H–<sup>19</sup>F CP for the polymeric nanoparticle suspension and ε<sub>on/off</sub>(<sup>19</sup>F) ≈ 150 were obtained for two different siRNAs in frozen DNP solution.</div></div>","PeriodicalId":16267,"journal":{"name":"Journal of magnetic resonance","volume":"371 ","pages":"Article 107827"},"PeriodicalIF":2.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","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.jmr.2025.107829
Matthew M. Willmering , Brice J. Albert , Joseph W. Plummer , Josh Greer , Laura L. Walkup , Diana M. Lindquist , Zackary I. Cleveland
Harmonizing and validating 129Xe gas exchange imaging across multiple sites is hampered by a lack of a quantitative standard that 1) displays the unique spectral properties of 129Xe observed from human subjects in vivo and 2) has short enough times to enable practical imaging. This work describes and demonstrates the development of two dissolved-phase, thermally polarized phantoms that mimic the in-vivo, red blood cell and membrane resonances of 129Xe dissolved in human lungs. Following optimization, combinations of two common organic solvents, acetone and dimethyl sulfoxide, resulted in two in-vivo-like dissolved-phase 129Xe phantoms yielding chemical shifts of 212.4 ppm and 193.9 ppm. By doping the solutions with iron(iii) acetylacetonate, the longitudinal relaxation time was reduced = 1.2 s for both phantoms at 3 T and 7 T. There was minimal change in chemical shift (+1.58 ppm) and (+1.2 %) over 1 year. In a 2D Dixon-type acquisition with 3 mm2 in-plane resolution, 129Xe dissolved-phase images yielded signal-to-noise ratios 6 and 12 for the RBC and membrane phantoms, respectively. A simple scaling of these phantoms to clinically relevant volumes of several liters would result in an SNR of 7 for the RBC phantom acquired in less than one minute. These findings demonstrate the ability to fabricate robust, quantitative, thermally polarized dissolved-phase phantoms, which will be needed to validate and harmonize gas exchange imaging in multi-site clinical trials.
{"title":"A thermally polarized, dissolved-phase 129Xe phantom for quality-control and multisite comparisons of gas-exchange imaging","authors":"Matthew M. Willmering , Brice J. Albert , Joseph W. Plummer , Josh Greer , Laura L. Walkup , Diana M. Lindquist , Zackary I. Cleveland","doi":"10.1016/j.jmr.2025.107829","DOIUrl":"10.1016/j.jmr.2025.107829","url":null,"abstract":"<div><div>Harmonizing and validating <sup>129</sup>Xe gas exchange imaging across multiple sites is hampered by a lack of a quantitative standard that 1) displays the unique spectral properties of <sup>129</sup>Xe observed from human subjects <em>in vivo</em> and 2) has short enough <span><math><msub><mi>T</mi><mn>1</mn></msub></math></span> times to enable practical imaging. This work describes and demonstrates the development of two dissolved-phase, thermally polarized phantoms that mimic the <em>in-vivo</em>, red blood cell and membrane resonances of <sup>129</sup>Xe dissolved in human lungs. Following optimization, combinations of two common organic solvents, acetone and dimethyl sulfoxide, resulted in two <em>in-vivo</em>-like dissolved-phase <sup>129</sup>Xe phantoms yielding chemical shifts of 212.4 ppm and 193.9 ppm. By doping the solutions with iron(iii) acetylacetonate, the longitudinal relaxation time was reduced <span><math><msub><mi>T</mi><mn>1</mn></msub></math></span> = 1.2 s for both phantoms at 3 T and 7 T. There was minimal change in chemical shift (+1.58 ppm) and <span><math><msub><mi>T</mi><mn>1</mn></msub></math></span> (+1.2 %) over 1 year. In a 2D Dixon-type acquisition with 3 mm<sup>2</sup> in-plane resolution, <sup>129</sup>Xe dissolved-phase images yielded signal-to-noise ratios 6 and 12 for the RBC and membrane phantoms, respectively. A simple scaling of these phantoms to clinically relevant volumes of several liters would result in an SNR of 7 for the RBC phantom acquired in less than one minute. These findings demonstrate the ability to fabricate robust, quantitative, thermally polarized dissolved-phase phantoms, which will be needed to validate and harmonize gas exchange imaging in multi-site clinical trials.</div></div>","PeriodicalId":16267,"journal":{"name":"Journal of magnetic resonance","volume":"371 ","pages":"Article 107829"},"PeriodicalIF":2.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.jmr.2024.107825
Maarit H. Lahtinen , Tuomas Niemi-Aro , Danila Morais de Carvalho , Kirsi S. Mikkonen , Ilkka Kilpeläinen , Sami Heikkinen
Pseudo-3D HSQC0 provides an alternative and easy way to record and analyze quantitative HSQC0-data. In the original time-zero extrapolated 1H–13C HSQC (HSQC0), three separate 2D constant-time (CT) HSQC-experiments (HSQCi, i = 1–3) are acquired, where either 1,2 or 3 consecutive CT-HSQC-propagators are repeated in each pulse sequence, and the 2D integral data from the three 2D experiments is analyzed via linear regression. In the presented pseudo-3D HSQC0, HSQCi is one of the dimensions and all data is contained within one dataset, which is recorded in interleaved manner by acquiring the same t1-value for each HSQCi-point before t1-incrementation. The 3D-nature of the data allows the utilization of backward linear prediction to calculate an actual time-zero 2D HSQC0 spectrum, which can be analyzed using normal 2D integration procedures for quantitative results. In all, the pseudo-3D enables straightforward, intuitive and easy analysis of the quantitative 2D HSQC0 spectrum/plane. As the recorded pseudo 3D data contains the normal HSQCi planes, also the classic linear regression analysis can be applied.
伪3d HSQC0提供了一种记录和分析定量HSQC0数据的简便方法。在原始的时间零外推1H-13C HSQC （HSQC0）中，获得3个独立的二维恒定时间（CT） HSQC实验（HSQCi, i = 1-3），在每个脉冲序列中重复1、2或3个连续的CT-HSQC传播子，并对3个二维实验的二维积分数据进行线性回归分析。在本文提出的伪三维HSQC0中，HSQCi是其中一个维度，所有数据都包含在一个数据集中，通过在t1递增之前对每个HSQCi点获取相同的t1值，以交错方式记录。数据的3d性质允许利用反向线性预测来计算实际的时间零二维HSQC0光谱，可以使用正常的二维积分程序进行分析以获得定量结果。总之，伪3d可以直接，直观和轻松地分析定量二维HSQC0光谱/平面。由于记录的伪三维数据包含正常的HSQCi平面，因此也可以应用经典的线性回归分析。
{"title":"Pseudo-3D HSQC0, a method to create a true 2D HSQC0-plane. Application to softwood extract analysis","authors":"Maarit H. Lahtinen , Tuomas Niemi-Aro , Danila Morais de Carvalho , Kirsi S. Mikkonen , Ilkka Kilpeläinen , Sami Heikkinen","doi":"10.1016/j.jmr.2024.107825","DOIUrl":"10.1016/j.jmr.2024.107825","url":null,"abstract":"<div><div>Pseudo-3D HSQC<sub>0</sub> provides an alternative and easy way to record and analyze quantitative HSQC<sub>0</sub>-data. In the original time-zero extrapolated <sup>1</sup>H–<sup>13</sup>C HSQC (HSQC<sub>0</sub>), three separate 2D constant-time (CT) HSQC-experiments (HSQC<sub>i</sub>, <em>i</em> = 1–3) are acquired, where either 1,2 or 3 consecutive CT-HSQC-propagators are repeated in each pulse sequence, and the 2D integral data from the three 2D experiments is analyzed via linear regression. In the presented pseudo-3D HSQC<sub>0</sub>, HSQC<sub>i</sub> is one of the dimensions and all data is contained within one dataset, which is recorded in interleaved manner by acquiring the same t<sub>1</sub>-value for each HSQC<sub>i</sub>-point before t<sub>1</sub>-incrementation. The 3D-nature of the data allows the utilization of backward linear prediction to calculate an actual time-zero 2D HSQC<sub>0</sub> spectrum, which can be analyzed using normal 2D integration procedures for quantitative results. In all, the pseudo-3D enables straightforward, intuitive and easy analysis of the quantitative 2D HSQC<sub>0</sub> spectrum/plane. As the recorded pseudo 3D data contains the normal HSQC<sub>i</sub> planes, also the classic linear regression analysis can be applied.</div></div>","PeriodicalId":16267,"journal":{"name":"Journal of magnetic resonance","volume":"371 ","pages":"Article 107825"},"PeriodicalIF":2.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142904576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","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.jmr.2025.107832
Sule Sahin , Anna Bennett Haller , Jeremy Gordon , Yaewon Kim , Jasmine Hu , Tanner Nickles , Qing Dai , Andrew P. Leynes , Daniel B. Vigneron , Zhen Jane Wang , Peder E.Z. Larson
Fitting rate constants to Hyperpolarized [1-13C]Pyruvate (HP C13) MRI data is a promising approach for quantifying metabolism in vivo. Current methods typically fit each voxel of the dataset using a least-squares objective. With these methods, each voxel is considered independently, and the spatial relationships are not considered during fitting.
In this work, we use a convolutional neural network, a U-Net, with convolutions across the 2D spatial dimensions to estimate pyruvate-to-lactate conversion rate, kPL, maps from dynamic HP C13 datasets. We designed a framework for creating simulated anatomically accurate brain data that matches typical HP C13 characteristics to provide large amounts of data for training with ground truth results. The U-Net is initially trained with the digital phantom data and then further trained with in vivo datasets for regularization.
In simulation where ground-truth kPL maps are available, the U-Net outperforms voxel-wise fitting with and without spatiotemporal denoising, particularly for low SNR data. In vivo data was evaluated qualitatively, as no ground truth is available, and before regularization the U-Net predicted kPL maps appear oversmoothed. After further training with in vivo data, the resulting kPL maps appear more realistic.
This study demonstrates how to use a U-Net to estimate rate constant maps for HP C13 data, including a comprehensive framework for generating a large amount of anatomically realistic simulated data and an approach for regularization. This simulation and architecture provide a foundation that can be built upon in the future for improved performance.
{"title":"Spatially constrained hyperpolarized 13C MRI pharmacokinetic rate constant map estimation using a digital brain phantom and a U-Net","authors":"Sule Sahin , Anna Bennett Haller , Jeremy Gordon , Yaewon Kim , Jasmine Hu , Tanner Nickles , Qing Dai , Andrew P. Leynes , Daniel B. Vigneron , Zhen Jane Wang , Peder E.Z. Larson","doi":"10.1016/j.jmr.2025.107832","DOIUrl":"10.1016/j.jmr.2025.107832","url":null,"abstract":"<div><div>Fitting rate constants to Hyperpolarized [1-<sup>13</sup>C]Pyruvate (HP C13) MRI data is a promising approach for quantifying metabolism in vivo. Current methods typically fit each voxel of the dataset using a least-squares objective. With these methods, each voxel is considered independently, and the spatial relationships are not considered during fitting.</div><div>In this work, we use a convolutional neural network, a U-Net, with convolutions across the 2D spatial dimensions to estimate pyruvate-to-lactate conversion rate, k<sub>PL</sub>, maps from dynamic HP C13 datasets. We designed a framework for creating simulated anatomically accurate brain data that matches typical HP C13 characteristics to provide large amounts of data for training with ground truth results. The U-Net is initially trained with the digital phantom data and then further trained with in vivo datasets for regularization.</div><div>In simulation where ground-truth k<sub>PL</sub> maps are available, the U-Net outperforms voxel-wise fitting with and without spatiotemporal denoising, particularly for low SNR data. In vivo data was evaluated qualitatively, as no ground truth is available, and before regularization the U-Net predicted k<sub>PL</sub> maps appear oversmoothed. After further training with in vivo data, the resulting k<sub>PL</sub> maps appear more realistic.</div><div>This study demonstrates how to use a U-Net to estimate rate constant maps for HP C13 data, including a comprehensive framework for generating a large amount of anatomically realistic simulated data and an approach for regularization. This simulation and architecture provide a foundation that can be built upon in the future for improved performance.</div></div>","PeriodicalId":16267,"journal":{"name":"Journal of magnetic resonance","volume":"371 ","pages":"Article 107832"},"PeriodicalIF":2.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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