Carr-Purcell-Meiboom-Gill Research Articles

MQMAS spectra of half-integer quadrupolar nuclei enhanced by indirect DNP

The observation of half-integer quadrupolar nuclei, which represent 66 % of the NMR-active isotopes, is essential to understand the atomic-level structure of inorganic materials near the surfaces with applications in the field of catalysis, biomaterials and optoelectronics. For that purpose, we have recently introduced an efficient technique, which combines the sensitivity gain provided by indirect DNP (dynamic nuclear polarization) under MAS (magic-angle spinning) and the high resolution obtained by refocusing the second-order quadrupolar interaction (H. Nagashima et al., J. Phys. Chem. Lett. 15 (2024) 4858). This technique combines (i) a D-RINEPT (dipolar-mediated refocused INEPT) transfer, (ii) an MQMAS (multiple-quantum MAS) filter, and (iii) a QCPMG (quadrupolar Carr-Purcell Meiboom-Gill) detection. We explain the design of several variants of this pulse sequence and notably the selection of the coherence transfer pathways. In particular, the amplitudes of the coherence transfer pathways through the ±3Q coherence orders of the quadrupolar isotope can be equalized using a train of π-pulses selective of the central transition, instead of a z-filter. This equalization method has the advantage to limit the length of the phase cycles and to enhance slightly the signal intensity. Moreover, for spin-3/2 nuclei subject to moderate or large quadrupolar interactions, more efficient excitation and conversion of 3Q coherences are achieved using cosine-modulated long-pulses (cos-lp), instead of fast-amplitude-modulated (FAM) pulses. The performances of the different D-RINEPT-MQMAS-QCPMG variants are compared through the observation of 35Cl and 27Al isotopes without DNP in l-histidine hydrochloride and isopropylamine-templated microporous aluminophosphate (ipa-AlPO4–14), respectively, as well as the acquisition of DNP-enhanced high-resolution spectra of 11B and 17O nuclei near the surface of partially oxidized boron nitride supported on dendritic and fibrous nanosilica and γ-alumina enriched in 17O isotope using a slurrying approach. The spectra recorded for γ-alumina show that the slurrying method produces less disorder than grinding assisted by 17O-enriched water.

Preliminary Exploration of T1ρ and T2 Mapping in Porcine Articular Cartilage Using Very-Low-Field Magnetic Resonance Imaging.

The high prevalence of osteoarthritis emphasizes the need for a cost-effective and accessible method for its early diagnosis. Recently, the portability and affordability of very-low-field (VLF) magnetic resonance imaging (MRI, 10-100 mT) have caused it to gain popularity. Nevertheless, there is insufficient evidence to quantify early degenerative changes in cartilage using VLF MRI. This study assessed the potential of T1ρ and T2 mapping for detecting degenerative changes in porcine cartilage specimens using a 50 mT MRI scanner. T2- and T1ρ-weighted images were acquired using a 50 mT MRI scanner with 2D spin-echo and triple-refocused T1ρ preparation sequences. MRI scans of porcine cartilage were also acquired using a 3 T MRI scanner for comparison. A mono-exponential algorithm was applied to fit a series of T2- and T1ρ-weighted images. T2 values for CuSO4·5H2O solutions measured via Carr-Purcell-Meiboom-Gill (CPMG) and spin-echo sequences were compared to verify the algorithm's reliability. The nonparametric Kruskal-Wallis statistical test was used to compare T2 and T1ρ values. Experimental repeatability was assessed using the root-mean-square of the coefficient of variation (rmsCV). T2 values of the CuSO4·5H2O solutions obtained using the spin-echo sequence showed differences within 2.3% of those obtained using the CPMG sequence, indicating the algorithm's reliability. The T1ρ values for varying concentrations of agarose gel solutions were higher than the T2 values. Furthermore, 50 mT and 3 T MRI results showed that both the T1ρ and T2 values were significantly higher for porcine cartilage degraded for 6 h vs intact cartilage, with p-values of 0.006 and 0.01, respectively. Our experimental results showed good reproducibility (rmsCV < 8%). We demonstrated the feasibility of quantitative cartilage imaging via T2 and T1ρ mapping at 50 mT MRI for the first time.

An improved method to accelerate the acquisition efficiency of the T1-T2 spectrum based on the IR-BSSFP-CPMG pulse sequence

The correlation map of the longitudinal relaxation time (T1) and the transverse relaxation time (T2) offers valuable information of different proton contributions and is served as a significant data for identifying, quantifying and characterizing complex relaxation components in unconventional reservoirs. However, the acquisition speed and spectral resolution for existing pulse sequences cannot be guaranteed simultaneously. We designed an improved pulse sequence which integrates the inversion recovery-balanced steady-state free precession (IR-BSSFP) sequence and the Carr-Purcell-Meiboom-Gill (CPMG) sequence, allowing for the measurement of two-dimensional T1-T2 spectrums. The IR-BSSFP sequence adopts a low refocusing angle and reduced flip angle pulse transmission power, eliminating the need for complete polarization. Moreover, the parameters of the improved pulse sequence such as the value and the number of the flip angle, the repetition time are discussed by numerical simulations. The result showed that the new pulse sequence achieves high-precision measurement performance, and the T1-T2 spectrum can be achieved within a few seconds.

Existence of Singularities in NMR Relaxation Dispersion Profiles: Implications for Hidden Dynamics.

It is common for NMR relaxation dispersion experiments to suggest an absence of dynamics despite anecdotal indications of conformational dynamics. We explore the potential explanations and approaches to this conundrum. Some inconsistencies have been observed between two relaxation dispersion experiments, Carr-Purcell-Meiboom-Gill (CPMG) and adiabatic relaxation dispersion experiments, in recent dynamic studies of different biomolecules. Theoretical analyses show that such seemingly paradoxical results might come from a complex exchange topology that is concealed by the application of the simple two-site exchange model for interpretation of the relaxation dispersion data. Scenarios are explored and revealed in which the presence of complex millisecond conformational exchange could suppress the amplitude of CPMG relaxation dispersion profiles, even when the exchange rates are within the detectable range of the experiments. With experimental errors, the suppressed relaxation dispersion profiles could lead to the conclusion of "no millisecond conformational exchange". However, such hidden dynamics can potentially be detected by adiabatic relaxation dispersion experiments. Finally, we demonstrate some advantages of adiabatic relaxation dispersion experiments over conventional relaxation dispersion experiments and a simplified computational approach to analyze the adiabatic relaxation dispersion profiles.

Slaughterhouse Wastewater Properties Assessment by Modern and Classic Methods

Advanced 1H Nuclear Magnetic Resonance (NMR) relaxometry and diffusometry methods and VIS-nearIR spectroscopy combined with pH, electrical conductivity (EC) and totally dissolved solids (TDSSs) measurements were used to assess the properties of wastewater collected from a chicken slaughterhouse in each step of the treatment process (wastewater before treatment, biologically treated wastewater, chemically treated wastewater and discharged wastewater) and from sludge. The 1H NMR Carr–Purcell–Meiboom–Gill (CPMG) and Pulsed-Gradient-Stimulated-Echo (PGSE) decay curves recorded for all samples of wastewater were analyzed by inverse Laplace transform (ILT) to obtain the distributions of transverse relaxation times T2 and diffusion coefficient D. The VIS-nearIR total absorbance, T2-values, D-values, pH, EC and TDSS parameters were used for statistical analysis in principal component (PCA). The 1H T2-distributions measured for the slaughterhouse wastewater lie in two main regions reflecting the number of dissolved solids or the distribution of undissolved solids. The PCA analysis successfully differentiates between polluted and less polluted wastewaters and sludge. The wastewater treatment applied by the slaughterhouse is efficient. The recommended methods for wastewater monitoring are the NMR T2- and D-distributions and EC, TDSSs and NMR-D diffusion coefficient. Finally, Machine Learning algorithms are used to provide prediction maps of wastewater treatment stage.

Forward modeling of single-sided magnetic resonance and evaluation of [formula omitted] fitting error based on geometric analytical method

Single-sided magnetic resonance (SSMR) offers advantages of portability and noninvasive measurement for water detection, with significant potential applications in groundwater exploration, petroleum well logging, and soil moisture monitoring. However, the inherent highly inhomogeneous static magnetic field and radiofrequency (RF) field in SSMR necessitate the utilization of the Carr–Purcell–Meiboom–Gill (CPMG) sequence measurement scheme. To accelerate forward modeling during pulse excitation, we introduce a Geometric Analysis Method (GAM) and assess T2 error using its primary parameters. The GAM involves applying spatial geometric rotations on the magnetization vector, leading to an analytical solution to the Bloch equation that disregards relaxation effects. Compared with the rotation matrix (RM) method, the GAM demonstrates high accuracy and reduces computational time by approximately 20.9%. By analyzing the primary parameters governing the magnetization vector in the analytical formula, we evaluated their impact on the transverse relaxation time (T2) obtained through fitting the SE signal. Ultimately, the forward modeling results of the CPMG sequence within the region of interest (ROI) of a single-sided Halbach magnet array are validated. The T2 fitting error increases as the primary parameters deviate from the ideal values, highlighting their significant role in the T2 fitting results. This study provides a theoretical foundation for optimizing the design of SSMR magnets and RF coils.

WITHDRAWN: Ultra wideline dipolar NMR spectroscopy: Combining SEDOR and WURST-CPMG

A method to obtain dipolar information for nuclei exhibiting ultra wideline NMR spectra in disordered solids is presented. This is achieved via a constant time version of SEDOR (spin echo double resonance) employing WURST (wideband uniform rate smooth truncation) pulses and CPMG (Carr Purcell Meiboom Gill) detection. The method – coined constant time WUDOR (WURST SEDOR) NMR spectroscopy – is tested on two crystalline model compounds (31P{19F}-CT-WUDOR NMR and 31P{19F}-CT-WUDOR CPMG NMR on Na2PO3F, 125Te{31P}-CT-WUDOR CPMG NMR on Ba2(PO4)2TeO) and applied to obtain structural information on TeO2 – NaPO3 – NaF glasses.

Ligand Effects on the Spin Relaxation Dynamics and Coherent Manipulation of Organometallic La(II) Potential Qudits.

We present pulsed electron paramagnetic resonance (EPR) studies on three La(II) complexes, [K(2.2.2-cryptand)][La(Cp')3] (1), [K(2.2.2-cryptand)][La(Cp″)3] (2), and [K(2.2.2-cryptand)][La(Cptt)3] (3), which feature cyclopentadienyl derivatives as ligands [Cp' = C5H4SiMe3; Cp″ = C5H3(SiMe3)2; Cptt = C5H3(CMe3)2] and display a C3 symmetry. Long spin-lattice relaxation (T1) and phase memory (Tm) times are observed for all three compounds, but with significant variation in T1 among 1-3, with 3 being the slowest relaxing due to higher s-character of the SOMO. The dephasing times can be extended by more than an order of magnitude via dynamical decoupling experiments using a Carr-Purcell-Meiboom-Gill (CPMG) sequence, reaching 161 μs (5 K) for 3. Coherent spin manipulation is performed by the observation of Rabi quantum oscillations up to 80 K in this nuclear spin-rich environment (1H, 13C, and 29Si). The high nuclear spin of 139La (I = 7/2), and the ability to coherently manipulate all eight hyperfine transitions, makes these molecules promising candidates for application as qudits (multilevel quantum systems featuring d quantum states; d >2) for performing quantum operations within a single molecule. Application of HYSCORE techniques allows us to quantify the electron spin density at ligand nuclei and interrogate the role of functional groups to the electron spin relaxation properties.

A Metabolomics Study by 1H HRMAS NMR: From Sheep Milk to a Pressed-Curd Cheese: A Proof of Concept

For the first time, High-Resolution Magic Angle Nuclear Magnetic Resonance spectroscopy (NMR-HRMAS) was applied to directly identify specific metabolites from a Spanish raw ewe’s milk and enzymatic coagulation pressed-curd cheese (Protected Geographical Indication: Castellano) manufactured by two procedures (traditional/artisanal vs. industrial) and including the ewe’s raw milk. The NMR parameters were optimized to study the complex matrixes of this type of cheese. In addition, conventional overcrowded 1H-NMR-HRMAS spectra were selectively simplified by a Carr–Purcell–Meiboom–Gill (CPMG) sequence or a stimulated echo pulse sequence by bipolar gradients (DIFF), thus modulating spin–spin relaxation times and diffusion of molecular components, respectively. 1H-NMR-HRMAS spectroscopy displayed important information about cheese metabolites, which can be associated with different manufacturing processes (industrial vs. traditional) and ripening times (from 2 to 90 days). These results support that this spectroscopy is a useful technique to monitor the ripening process, from raw milk to commercial ripened cheese, using a minimum intact sample, implying the absence of time-consuming sample pretreatments.

Unravelling temperature-dependent molecular changes in hydrated wheat and maize starches using 1H time-domain NMR

This study proved that time-domain NMR (TD-NMR) experiments can accurately demonstrate the interaction between starch (wheat and maize) and water and the distribution of water molecules in starch-water systems during heating. Molecular properties in starch-water systems at 50% moisture content were monitored by Rhim and Kessemeier – Radiofrequency Optimized Solid-Echo (RK-ROSE) and Carr-Purcell-Meiboom-Gill (CPMG) pulse sequences at frequent (2 °C intervals) measurements during heating (55–80 °C). Starch-like and water-like phases were obtained by RK-ROSE and CPMG pulse sequences, respectively. The second moment, M2, along with the relaxation times of the populations, associated with fast-decaying protons, provided information on the crystal structure state during heating and the extent of gelatinisation. The relaxation times of the most abundant population from the CPMG signal decreased during heating due to strong interactions between starch and water. Temperature of stabilisation of this population aligned with the associated findings from the differential scanning calorimetry and rheological measurements.

Synthesis of α,ω-bis-Mercaptoacyl Poly(alkyl oxide)s and Development of Thioether Cross-Linked Liposome Scaffolds for Sustained Release of Drugs.

With the aim to develop novel scaffolds for the sustained release of drugs, we initially developed an easy approach for the synthesis of α,ω-homobifunctional mercaptoacyl poly(alkyl oxide)s. This was based on the esterification of the terminal hydroxyl groups of poly(alkyl oxide)s with suitably S-4-methoxytrityl (Mmt)-protected mercapto acids, followed by the removal of the acid labile S-Mmt group. This method allowed for the efficient synthesis of the title compounds in high yield and purity, which were further used in the development of a thioether cross-linked liposome scaffold, by thia-Michael reaction of the terminal thiol groups with pre-formed nano-sized liposomes bearing maleimide groups on their surface. The reaction process was followed by 1H-NMR, using a Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion NMR experiment (1H-NMR CPMG), which allowed for real-time monitoring and optimization of the reaction process. The thioether cross-linked liposomal scaffold that was synthesized was proven to preserve the nano-sized characteristics of the initial liposomes and allowed for the sustained release of calcein (which was used as a hydrophilic dye and a hydrophilic drug model), providing evidence for the efficient synthesis of a novel drug release scaffold consisting of nanoliposome building blocks.

Investigation of the soybean infiltration process utilizing low-field nuclear magnetic resonance technology.

This paper employs low-field nuclear magnetic resonance (LF-NMR) technology to meticulously analyze and explore the intricate soybean infiltration process. The methodology involves immersing soybeans in distilled water, with periodic implementation of Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence experiments conducted at intervals of 20 to 30 minutes to determine the relaxation time T2. Currently, magnetic resonance imaging (MRI) is conducted every 30 minutes. The analysis uncovers the existence of three distinct water phases during the soybean infiltration process: bound water denoted as T21, sub-bound water represented by T22, and free water indicated as T23. The evolution of these phases unfolds as follows: bound water T21 displays a steady oscillation within the timeframe of 0 to 400 minutes; sub-bound water T22 and free water T23 exhibit a progressive pattern characterized by a rise-stable-rise trajectory. Upon scrutinizing the magnetic resonance images, it is discerned that the soybean infiltration commences at a gradual pace from the seed umbilicus. The employment of LF-NMR technology contributes significantly by affording an expeditious, non-destructive, and dynamic vantage point to observe the intricate motion of water migration during soybean infiltration. This dynamic insight into the movement of water elucidates the intricate mass transfer pathway within the soybean-water system, thus furnishing a robust scientific foundation for the optimization of processing techniques.

From Milliseconds to Minutes: Melittin Self-Assembly from Concerted Non-Equilibrium Pressure-Jump and Equilibrium Relaxation Nuclear Magnetic Resonance.

Non-equilibrium kinetics techniques like pressure-jump nuclear magnetic resonance (NMR) are powerful in tracking changes in oligomeric populations and are not limited by relaxation rates for the time scales of exchange that can be probed. However, these techniques are less sensitive to minor, transient populations than are Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion experiments. We integrated non-equilibrium pressure-jump and equilibrium CPMG relaxation dispersion data to fully map the kinetic landscape of melittin tetramerization. While monomeric peptides weakly form dimers (Kd,D/M ≈ 26 mM) whose population never exceeds 1.6% at 288 K, dimers associate tightly to form stable tetrameric species (Kd,T/D ≈ 740 nM). Exchange between the monomer and dimer, along with exchange between the dimer and tetramer, occurs on the millisecond time scale. The NMR approach developed herein can be readily applied to studying the folding and misfolding of a wide range of oligomeric assemblies.

Stationary wavelet denoising of solid-state NMR spectra using multiple similar measurements

Accumulating several scans of free induction decays is always needed to improve the signal-to-noise ratio of NMR spectra, especially for the low gyromagnetic ratio solid-state NMR. In this study, we present a new denoising approach based on the correlations between multiple similar NMR spectra. Contrary to the simple averaging of multiple scans or denoising the final averaged spectrum, we propose a Wavelet-based Denoising technique for Multiple Similar scans(WDMS). Firstly, the stationary wavelet transform is applied to decompose every spectrum into approximation coefficients and detail coefficients. Then, the detail coefficients are multiplied by weights calculated based on Pearson's correlation coefficient and structural similarity index between approximation coefficients of different spectra. Finally, the average of these detailed components is used to denoise the spectra. The proposed method is carried on the assumption that noise between multiple spectra is uncorrelated while peak signal information is similar between different spectra, thus preserving the possibility of applying further processing to the data. As a demonstration, the standard wavelet denoise is applied to the WDMS-processed spectra, achieving a further increase in the S/N ratio. We confirm the reliability of the denoising approach based on multiple scans on 1D/2D solid-state MAS/static NMR spectra. In addition, we also show that this method can be used to deal with a single Car-Purcell-Meiboom-Gill (CPMG) echo train.

SAMHD1 Inhibitor Combined with Immune Checkpoint Inhibitor Elicits an Anti-AML Immunity

Despite advances in targeted therapy and use of molecular/cytogenetic risk stratification to guide treatment, clinical outcomes for patients with acute myeloid leukemia (AML) remain unfavorable. Harnessing the immune system with CAR-T or immune checkpoint inhibitors (ICIs) has been proven successful in other hematological malignancies and solid tumors. The use of these immunotherapies for the AML treatment remains challenging due to lack of selective target antigens or low expression of immune checkpoint proteins. Recently, one strategy proposed to transform AML from immune-cold to immune-hot is to trigger a type-I interferon (IFN-I) response via a dsDNA related cGAS/STING signaling or dsDNA related RIG-I/MDA5 signaling. We recently reported that the dNTP and Ara-CTP (active form of cytarabine [AraC]) hydrolase SAMHD1, whose expression levels are elevated in AML patients relative to normal donors, limits IFN-I and T cell responses in murine AML model ( Blood, 2022, 140 [Supplement 1]: 679-680). We also found that innate immune activation seen following SAMHD1 knockdown is associated with its catalytic activity inhibition in cancer cells, providing a rationale for the development of SAMHD1 inhibitor. To identify SAMHD1 inhibitor, we conducted a virtual screen on 8,000,000 compounds based on SAMHD1 crystal structure (PBD 6TXC). The top 500 hits were then assessed in SAMHD1-WT- or H233A (SAMHD1 loss-of-function mutant) -expressing Molm13 cells using a phenotypic screen for AraC sensitization. Specifically, a SAMHD1 inhibitor should sensitize SAMHD1-WT (S-WT) but not H233A (S-H233A) cells to AraC treatment. Among the top 20 hits from phenotypic screen, our HPLC-based cell-free and cell-based SAMHD1 enzymatic assay revealed Samin27 as the most potent hit in blocking SAMHD1 hydrolysis and promoting AraCTP accumulation. Therefore, we assessed the efficacy of Samin27 combined with AraC in vivo. Samin27 administration (25mg/kg i.p. qd, starting on day 8 for 7 days) enhanced AraC efficacy (50mg/kg i.p. qd, starting 8th day for 5 days) in NSG mice implanted with Molm13 cells, as evidenced by extended survival relative to AraC alone. Moreover, the physical interaction between Samin27 and SAMHD1 protein were confirmed in a Carr-Purcell-Meiboom-Gill (CPMG) nuclear magnetic resonance (NMR) titration assay. RNA-seq results revealed Samin27 ex-vivo treatment remarkably upregulated IFN-I response genes in Molm13 cells, consistent with transcriptome results of SAMHD1-knockdown (S-KD) Molm13 cells. SAMHD1 activity is known to restrict replication of LINE-1 (L1), which is the only autonomously active transposable elements (TE) in mammals; elevated retrotransposition induces DNA damage and promotes cytoplasmic DNA accumulation, resulting in an IFN-I response via cGAS signaling. Next, to explore the mechanism underlying SAMHD1-inhibition induced immunity, we asked if SAMHD1 loss promoted retrotransposition and upregulated TE transcripts in leukemia cells. Through re-analysis of RNA-seq data in Molm13 cells, we found SAMHD1 inhibition upregulated most L1 elements and LTR-containing endogenous retrovirus (ERV) subfamilies. To determine if Samin27 induced immunity via L1 upregulation, we employed 3TC treatment (3TC, the nucleoside reverse transcriptase inhibitor) to block L1 upregulation. 3TC treatment blocked Samin27-mediated IFN-I response genes upregulation. Given that IFN-I response can stimulate innate immune cells (macrophage and T cell) cross-priming, potentially rendering AML cells more susceptible to anti-CD47 monoclonal antibody (aCD47) treatment, we then assessed whether combining a SAMHD1 inhibitor with an aCD47 act synergistically. We first implanted murine MLL-AF9 (MA9) leukemia cells into WT B6 mice. Then we treated leukemic mice with isotype control (Ctrl), anti-CD47 (BE0283 [BioXCell], 10mg/kg, i.p. qd, 3 weeks), Samin27 (25mg/kg i.p. qd, 3 weeks) or combination. Notably, pharmacological inhibition of SAMHD1 remarkably inhibited leukemia progression, decreasing leukemia burden (Fig. A.B). In another cohort, combination treatment extended mouse survival (Fig. C). Collectively, our results may provide a rationale for combining Samin27 with aCD47 against AML population, where single anti-CD47 treatment shows little effects.

Pushing the Detection Limit of Static Wideline NMR Spectroscopy Using Ultrafast Frequency-Swept Pulses.

We report a simple design strategy for wideband uniform-rate smooth truncation (WURST) pulses that enables ultrafast frequency sweeps to maximize the sensitivity of Carr-Purcell-Meiboom-Gill (CPMG) acquisition in static wideline nuclear magnetic resonance (NMR). Three compelling examples showcase the advantage of ultrafast frequency sweeps over currently employed WURST-CPMG protocols, demonstrating the potential of investigating materials that are typically inaccessible to static wideline NMR techniques, e.g., paramagnetic solids with short homogeneous transverse relaxation times.

Do the enantiomers of ketamine bind enantioselectively to human serum albumin?

The binding of drugs to plasma proteins is an important process in the human body and has a significant influence on pharmacokinetic parameter. Human serum albumin (HSA) has the most important function as a transporter protein. The binding of ketamine to HSA has already been described in literature, but only of the racemate. The enantiomerically pure S-ketamine is used as injection solution for induction of anesthesia and has been approved by the Food and Drug Administration for the therapy of severe depression as a nasal spray in 2019. The question arises if there is enantioselective binding to HSA. Hence, the aim of this study was to investigate whether there is enantioselective binding of S-and R-ketamine to HSA or not. Ultrafiltration (UF) followed by chiral capillary electrophoretic analysis was used to determine the extent of protein binding. Bound fraction to HSA was 71.2 % and 64.9 % for enantiomerically pure R- and S-ketamine, respectively, and 66.5 % for the racemate. Detailed binding properties were studied by Saturation Transfer Difference (STD)-, waterLOGSY- and Carr-Purcell-Meiboom-Gill (CPMG)-NMR spectroscopy. With all three methods, the aromatic ring and the N-methyl group could be identified as the structural moieties most strongly involved in binding of ketamine to HSA. pKaff values determined using UF and NMR indicate that ketamine is a weak affinity ligand to HSA and no significant differences in binding behavior were found between the individual enantiomers and the racemate.

Bone marrow plasma metabonomics of idiopathic acquired aplastic anemia patients using 1H nuclear magnetic resonance spectroscopy.

Idiopathic acquired aplastic anemia (AA) is a bone marrow failure disorder where aberrant T-cell functions lead to depletion of hematopoietic stem and progenitor cells in the bone marrow (BM) microenvironment. T-cells undergo metabolic rewiring, which regulates their proliferation and differentiation. Therefore, studying metabolic variation in AA patients may aid us with a better understanding of the T-cell regulatory pathways governed by metabolites and their pathological engagement in the disease. To identify the differential metabolites in BM plasma of AA patients, AA follow-up (AAF) in comparison to normal controls (NC) and to identify potential disease biomarker(s). The study used 1D 1H NMR Carr-Purcell-Meiboom-Gill (CPMG) spectra to identify the metabolites present in the BM plasma samples of AA (n = 40), AAF (n = 16), and NC (n = 20). Metabolic differences between the groups and predictive biomarkers were identified by using multivariate analysis and receiver operating characteristic (ROC) module of Metaboanalyst V5.0 tool, respectively. The AA and AAF samples were well discriminated from NC group as per Principal Component analysis (PCA). Further, we found significant alteration in the levels of 17 metabolites in AA involved in amino-acid (Leucine, serine, threonine, phenylalanine, lysine, histidine, valine, tyrosine, and proline), carbohydrate (Glucose, lactate and mannose), fatty acid (Acetate, glycerol myo-inositol and citrate), and purine metabolism (hypoxanthine) in comparison to NC. Additionally, biomarker analysis predicted Hypoxanthine and Acetate can be used as a potential biomarker. The study highlights the significant metabolic alterations in the BM plasma of AA patients which may have implication in the disease pathobiology.

Revealing petroleum-water-CO2 emulsion stability by NMR about oil recovery and carbon storage

CO2 injection can simultaneously enhance oil recovery and carbon storage, but the stability of petroleum-water-CO2 emulsion affcet the production process and carbon storage. Emulsion characteristics is typically assessed via Nuclear Magnetic Resonance (NMR). It is essential to develop a theory to unlock the mechanisms of experimentation for harnessing the full potential of NMR in assessing emulsion stability and comprehending complex multiphase systems. The theory integrates experiments and a “quasi-lattice wave” physical model to understand the microscale mechanisms in NMR measurements of crude oil emulsion properties, and uncover the “transfer-transition” mode of 1H quantum excited states, explaining T2 relaxation. This forms a theoretical basis for numerical simulation of CPMG (Carr-Purcell-Meiboom-Gill) experiments by random walk algorithms and the boundary annihilation hypothesis. A strong link between NMR T2 times and various character properties of Petroleum-Water-CO2 Emulsion samples is reflected, such as environmental scale, viscosity, CO2 adsorption, and molecular thermal motion. Additionally, parameter Θ was proposed to characterize emulsion stability, for penetrating the theory presented in this paper, and to provide a scientifically rigorous representation of crude oil emulsion stability. The experiments with CO2 treatment on crude oil emulsions were performed, demonstrating a highly effective theoretical correlation between interfacial tension in crude oil emulsions and CO2 pressure, with an exceptional fit to experimental data (R2 > 0.99). When the pressure of CO2 treatment exceeds a critical threshold (approximately 17 MPa in this study), there is a substantial reduction in viscosity. Furthermore, a comparative assessment of samples before and after CO2 treatment using the parameter Θ demonstrated its reliability as an indicator of emulsion stability. It revealed a significant reduction of over 50% in the linear fit residual variance of Θ before and after subjecting the sample to 10 MPa carbon dioxide treatment, highlighting improved fluctuation stability. The slope of the Θ linear regression function signifies temporal stability. In a sample with 20% water content, the time evolution of the water phase decreases by 3.04%, while the oil phase experiences a substantial 57.77% reduction. Simultaneously, the midpoint of the range of the Θ linear regression function represents the environmental scale. The water phase environment scale increases by 8.72%, while the oil phase environment scale decreases by 8.74%, highlighting spatial evolution patterns.

T1rho and T2rho based myocardial tissue characterisation in small animals at high-field MRI

Abstract Introduction Cardiac tissue characterisation using T2-based MRI promises non-invasive diagnosis or monitoring of inflammatory heart disease, toxic heart damage after chemotherapy and myocardial infarction or post-infarction patients. T2 relaxation is also an indicator for the detection of myocardial oedema or intramyocardial haemorrhage [1]. However, accurate T2 quantification is challenging due to motion, blood flow and field inhomogeneities, especially in high-field MRI [2]. In this work, we present an alternative to T2 imaging that uses spin-locking (SL) to provide a robust measurement of T2ρ relaxation. It is known from relaxation theory that T2ρ has a sensitivity almost identical to T2 [3]. In the small animal study presented here, cardiac T2ρ quantification is tested for the first time using a newly developed pulse sequence and compared with established methods. Methods All measurements were performed on a preclinical 7T MRI. T2 contrast was prepared using a CPMG (Carr-Purcell-Meiboom-Gill) sequence. T2ρ contrast was conventionally generated by a balanced-SL (BSL) preparation [4]. Furthermore, a new approach for T2ρ was developed based on a MLEV sequence (Malcolm-Levitt, [2]). In contrast to [2], all pulse delays were minimised here, producing pure T2ρ contrast (Fig. 1). The new method was first validated in phantom experiments and then tested in three mice with radial image acquisition accelerated for cardio-MRI. Results The results of the phantom study are shown in figure 2. No significant differences were found between BSL and MLEV for T2ρ quantification (mean deviation 0.74%). In vivo, significant artefacts were observed for T2 (Fig. 3), while both T2ρ methods showed improved image quality. For the evaluation of relaxation times in the left ventricle, the mean across all animals was: T2=22.9±2.6ms (R2=0.979), BSL-T2ρ=51.4±5.4ms (R2=0.983) and MLEV-T2ρ=60.0±3.4ms (R2&amp;gt;0.99). Thus, the MLEV-T2ρ method achieves the most robust quantification with a mean R2&amp;gt;0.99 and provides relaxation time maps with diagnostic image quality. Discussion: In the present study, myocardial T2ρ mapping was tested at 7T. While no significant differences between BSL and MLEV appeared in phantom experiments, significant difference was found in vivo. Here, only the MLEV technique could achieve robust quantification. One reason for the improved performance is the continuous refocusing and minimisation of free dephasing of the transverse magnetisation. The results also show that MLEV-T2ρ has improved image quality and more robust quantification compared to CPMG-T2. Conclusion Cardiac T2ρ quantification is a robust alternative to established T2 imaging and can be applied under high-field conditions. A combined measurement of T1ρ and T2ρ relaxation time could be used for native detection of myocardial fibrosis and oedema.Figure 1)Comparison of image qualityFigure 2)Results in a knockout model