Solid-state magnetic resonance is a unique technique that can reveal the dynamics of complex biological systems with atomic resolution. Longitudinal relaxation is a mechanism that returns ...longitudinal nuclear magnetization to its thermal equilibrium by incoherent processes. The measured longitudinal relaxation rate constant however represents the combination of both incoherent and coherent contributions to the change of nuclear magnetization. This work demonstrates the effect of magic angle spinning rate on the longitudinal relaxation rate constant in two model compounds: L-histidine hydrochloride monohydrate and glycine serving as proxies for isotopically-enriched biological materials. Most notably, it is demonstrated that the longitudinal N15 relaxation of the two nitrogen nuclei in the imidazole ring in histidine is reduced by almost three orders of magnitude at the condition of rotational resonance with the amine, while the amine relaxation rate constant is increased at these conditions. The observed phenomenon may have radical implications for the solid-state magnetic resonance in biophysics and materials, especially in the proper measurement of dynamics and as a selective serial transfer step in dynamic nuclear polarization.
We investigate the potential of 31P NMR with simple, maintenance-free benchtop spectrometers to probe phospholipids in complex mixtures. 31P NMR-based lipidomics has become an important topic in a ...wide range of applications in food- and health-sciences, and the continuous improvements of compact, maintenance- and cryogen-free instruments opens new opportunities for NMR routine analyses. A prior milestone is the evaluation of the analytical performance provided by 31P NMR at low magnetic field. To address this, we assess the ability of state-of-the-art benchtop NMR spectrometers to detect, identify, and quantify several types of phospholipids in mixtures. Relying on heteronuclear cross-polarization experiments, phospholipids can be detected in 2 h with a limit of detection of 0.5 mM at 1 T and 0.2 mM at 2 T, while the headgroups of phosphatidylcholine (PC), phosphatidyl-ethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS), and phosphatidyl-glycerol (PG) can be unambiguously assigned based on 2D 1H–31P total correlated spectroscopy (TOCSY) spectra. Furthermore, two quantitative methods to obtain absolute concentrations are proposed and discussed, and the performance is evaluated regarding precision and accuracy.
We investigate the potential of
P NMR with simple, maintenance-free benchtop spectrometers to probe phospholipids in complex mixtures.
P NMR-based lipidomics has become an important topic in a wide ...range of applications in food- and health-sciences, and the continuous improvements of compact, maintenance- and cryogen-free instruments opens new opportunities for NMR routine analyses. A prior milestone is the evaluation of the analytical performance provided by
P NMR at low magnetic field. To address this, we assess the ability of state-of-the-art benchtop NMR spectrometers to detect, identify, and quantify several types of phospholipids in mixtures. Relying on heteronuclear cross-polarization experiments, phospholipids can be detected in 2 h with a limit of detection of 0.5 mM at 1 T and 0.2 mM at 2 T, while the headgroups of phosphatidylcholine (PC), phosphatidyl-ethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS), and phosphatidyl-glycerol (PG) can be unambiguously assigned based on 2D
H-
P total correlated spectroscopy (TOCSY) spectra. Furthermore, two quantitative methods to obtain absolute concentrations are proposed and discussed, and the performance is evaluated regarding precision and accuracy.
X-nuclei (also called non-proton MRI) MRI and spectroscopy are limited by the intrinsic low SNR as compared to conventional proton imaging. Clinical translation of x-nuclei examination warrants the ...need of a robust and versatile tool improving image quality for diagnostic use. In this work, we compare a novel denoising method with fewer inputs to the current state-of-the-art denoising method.
Denoising approaches were compared on human acquisitions of sodium (
Na) brain, deuterium (
H) brain, carbon (
C) heart and brain, and simulated dynamic hyperpolarized
C brain scans, with and without additional noise. The current state-of-the-art denoising method Global-local higher order singular value decomposition (GL-HOSVD) was compared to the few-input method tensor Marchenko-Pastur principal component analysis (tMPPCA). Noise-removal was quantified by residual distributions, and statistical analyses evaluated the differences in mean-square-error and Bland-Altman analysis to quantify agreement between original and denoised results of noise-added data.
GL-HOSVD and tMPPCA showed similar performance for the variety of x-nuclei data analyzed in this work, with tMPPCA removing ˜5% more noise on average over GL-HOSVD. The mean ratio between noise-added and denoising reproducibility coefficients of the Bland-Altman analysis when compared to the original are also similar for the two methods with 3.09 ± 1.03 and 2.83 ± 0.79 for GL-HOSVD and tMPPCA, respectively.
The strength of tMPPCA lies in the few-input approach, which generalizes well to different data sources. This makes the use of tMPPCA denoising a robust and versatile tool in x-nuclei imaging improvements and the preferred denoising method.
Hyperpolarized carbon-13 labeled compounds are increasingly being used in medical MR imaging (MRI) and MR imaging (MRI) and spectroscopy (MRS) research, due to its ability to monitor tissue and cell ...metabolism in real-time. Although radiological biomarkers are increasingly being considered as clinical indicators, biopsies are still considered the gold standard for a large variety of indications. Bioreactor systems can play an important role in biopsy examinations because of their ability to provide a physiochemical environment that is conducive for therapeutic response monitoring ex vivo. We demonstrate here a proof-of-concept bioreactor and microcoil receive array setup that allows for ex vivo preservation and metabolic NMR spectroscopy on up to three biopsy samples simultaneously, creating an easy-to-use and robust way to simultaneously run multisample carbon-13 hyperpolarization experiments. Experiments using hyperpolarized 1-
Cpyruvate on ML-1 leukemic cells in the bioreactor setup were performed and the kinetic pyruvate-to-lactate rate constants (
) extracted. The coefficient of variation of the experimentally found
s for five repeated experiments was
. With this statistical power, treatment effects of 30%-40% change in lactate production could be easily differentiable with only a few hyperpolarization dissolutions on this setup. Furthermore, longitudinal experiments showed preservation of ML-1 cells in the bioreactor setup for at least 6 h. Rat brain tissue slices were also seen to be preserved within the bioreactor for at least 1 h. This validation serves as the basis for further optimization and upscaling of the setup, which undoubtedly has huge potential in high-throughput studies with various biomarkers and tissue types.
Solid-state magnetic resonance is a unique technique that can reveal the dynamics of complex biological systems with atomic resolution. Longitudinal relaxation is a mechanism that returns ...longitudinal nuclear magnetization to its thermal equilibrium by incoherent processes. The measured longitudinal relaxation rate constant however represents the combination of both incoherent and coherent contributions to the change of nuclear magnetization. This work demonstrates the effect of magic angle spinning rate on the longitudinal relaxation rate constant in two model compounds: L-histidine hydrochloride monohydrate and glycine serving as proxies for isotopically-enriched biological materials. Most notably, it is demonstrated that the longitudinal 15N relaxation of the two nitrogen nuclei in the imidazole ring in histidine is reduced by almost three orders of magnitude at the condition of rotational resonance with the amine, while the amine relaxation rate constant is increased at these conditions. The observed phenomenon may have radical implications for the solid-state magnetic resonance in biophysics and materials, especially in the proper measurement of dynamics and as a selective serial transfer step in dynamic nuclear polarization.
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