High‐resolution <sup>1</sup>H NMR spectroscopy in organs and tissues using slow magic angle spinning

Wind, Robert A.; Hu, Jianzhi; Rommereim, D. N.

doi:10.1002/mrm.1181

“…Figure 7.5 c) shows more closely the region between 0-4ppm in which distinct resonances can be assigned based on previous studies, given in the caption. [54,62] The projected spectrum, Figure 7.5 d), shows the same resonances which are in the MAS spectrum.…”

Section: Resultssupporting

confidence: 54%

New Methodology For Use in Rotating Field Nuclear MagneticResonance

Jachmann

¹

2007

0

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High-resolution NMR spectra of samples with anisotropic broadening are simplified to their isotropic spectra by fast rotation of the sample at the magic angle 54.7 • . This dissertation concerns the development of novel Nuclear Magnetic Resonance(NMR) methodologies which would rotate the magnetic field instead of the sample, i.e. rotating field NMR. It also provides an overview of the NMR concepts, procedures, and experiments needed to understand the methodologies that will be used for rotating field NMR.A simple two-dimensional shimming method based on harmonic corrector rings provides arbitrary multiple order shimming corrections that are necessary for rotating field systems, but can be used in shimming other systems as well. Those results demonstrate, for example, that quadrupolar order shimming improves the linewidth by up to a factor of ten. An additional order of magnitude reduction is in principle achievable by utilizing this shimming method for z-gradient correction and higher order xy gradients.Additionally, initial investigations into a specialized pulse sequence for the rotating field NMR experiment, which allows for spinning at angles other than the magic angle and spinning slower than the anisotropic broadening is discussed. This will be useful for rotating field NMR because there are limits on how fast a field can be spun and difficulties of reaching the magic angle. This pulse sequence is a combination of the previously established projected magic angle spinning (p-MAS) and magic angle turning (MAT) pulse sequences. One of the goals of this project is for rotating field NMR to be used on biological systems. The p-MAS pulse sequence was successfully tested on bovine tissue samples, which suggests that it will be a viable methodology to use in rotating field NMR.A side experiment on steering magnetic particles by MRI gradients was also carried out.Initial investigations indicate some movement, but for total steering control, further experiments are needed.1

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“…High-resolution 1 H nuclear magnetic resonance (NMR) metabolomics using the technique of slow magic angle spinning (i.e., 1 H-PASS) (29), was used to determine the concentrations of lactic acid in fibroblast cell lysates and in whole lung homogenates from patients with IPF and from healthy control subjects using previously reported procedures (11).…”

Section: Nuclear Magnetic Resonance Spectroscopymentioning

confidence: 99%

Lactic Acid Is Elevated in Idiopathic Pulmonary Fibrosis and Induces Myofibroblast Differentiation via pH-Dependent Activation of Transforming Growth Factor-β

Kottmann¹,

Kulkarni²,

Smolnycki³

et al. 2012

Am J Respir Crit Care Med

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Rationale: Idiopathic pulmonary fibrosis (IPF) is a complex disease for which the pathogenesis is poorly understood. In this study, we identified lactic acid as a metabolite that is elevated in the lung tissue of patients with IPF. Objectives: This study examines the effect of lactic acid on myofibroblast differentiation and pulmonary fibrosis. Methods: We used metabolomic analysis to examine cellular metabolism in lung tissue from patients with IPF and determined the effects of lactic acid and lactate dehydrogenase-5 (LDH5) overexpression on myofibroblast differentiation and transforming growth factor (TGF)-b activation in vitro. Measurements and Main Results: Lactic acid concentrations from healthy and IPF lung tissue were determined by nuclear magnetic resonance spectroscopy; a-smooth muscle actin, calponin, and LDH5 expression were assessed by Western blot of cell culture lysates. Lactic acid and LDH5 were significantly elevated in IPF lung tissue compared with controls. Physiologic concentrations of lactic acid induced myofibroblast differentiation via activation of TGF-b. TGF-b induced expression of LDH5 via hypoxia-inducible factor 1a (HIF1a). Importantly, overexpression of both HIF1a and LDH5 in human lung fibroblasts induced myofibroblast differentiation and synergized with low-dose TGF-b to induce differentiation. Furthermore, inhibition of both HIF1a and LDH5 inhibited TGF-b-induced myofibroblast differentiation. Conclusions: We have identified the metabolite lactic acid as an important mediator of myofibroblast differentiation via a pHdependent activation of TGF-b. We propose that the metabolic milieu of the lung, and potentially other tissues, is an important driving force behind myofibroblast differentiation and potentially the initiation and progression of fibrotic disorders.

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“…The MAS spectra in Figure 7.3 b) shows several more resonances. The assignments known from previously published work [54,61] are presented in the figure caption. Figure 7.3 c) shows the appropriately projected p-MAS spectrum after a shearing transformation and re-scaling to the isotropic spectrum, using λ .…”

Section: Resultsmentioning

confidence: 99%

“…Other sequences like Magic Angle Hopping (MAH) [50],which uses three distinct stationary positions, and Magic Angle Turning (MAT) [51] [52] [53] have been used to take spectra of metabolites in tissue and organs for both excised tissues [54] and a living mouse. [46] Slow spinning speed is an arbitrary term, but generally implies that the sample rotates significantly more slowly than the time scale of the anisotropy.…”

Section: Introductionmentioning

confidence: 99%

New Methodology For Use in Rotating Field Nuclear MagneticResonance

Jachmann

¹

2007

0

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High-resolution NMR spectra of samples with anisotropic broadening are simplified to their isotropic spectra by fast rotation of the sample at the magic angle 54.7 • . This dissertation concerns the development of novel Nuclear Magnetic Resonance(NMR) methodologies which would rotate the magnetic field instead of the sample, i.e. rotating field NMR. It also provides an overview of the NMR concepts, procedures, and experiments needed to understand the methodologies that will be used for rotating field NMR.A simple two-dimensional shimming method based on harmonic corrector rings provides arbitrary multiple order shimming corrections that are necessary for rotating field systems, but can be used in shimming other systems as well. Those results demonstrate, for example, that quadrupolar order shimming improves the linewidth by up to a factor of ten. An additional order of magnitude reduction is in principle achievable by utilizing this shimming method for z-gradient correction and higher order xy gradients.Additionally, initial investigations into a specialized pulse sequence for the rotating field NMR experiment, which allows for spinning at angles other than the magic angle and spinning slower than the anisotropic broadening is discussed. This will be useful for rotating field NMR because there are limits on how fast a field can be spun and difficulties of reaching the magic angle. This pulse sequence is a combination of the previously established projected magic angle spinning (p-MAS) and magic angle turning (MAT) pulse sequences. One of the goals of this project is for rotating field NMR to be used on biological systems. The p-MAS pulse sequence was successfully tested on bovine tissue samples, which suggests that it will be a viable methodology to use in rotating field NMR.A side experiment on steering magnetic particles by MRI gradients was also carried out.Initial investigations indicate some movement, but for total steering control, further experiments are needed.1

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High‐resolution ¹H NMR spectroscopy in organs and tissues using slow magic angle spinning

Cited by 61 publications

References 27 publications

New Methodology For Use in Rotating Field Nuclear MagneticResonance

New Methodology For Use in Rotating Field Nuclear MagneticResonance

Lactic Acid Is Elevated in Idiopathic Pulmonary Fibrosis and Induces Myofibroblast Differentiation via pH-Dependent Activation of Transforming Growth Factor-β

New Methodology For Use in Rotating Field Nuclear MagneticResonance

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High‐resolution 1H NMR spectroscopy in organs and tissues using slow magic angle spinning

Cited by 61 publications

References 27 publications

New Methodology For Use in Rotating Field Nuclear MagneticResonance

New Methodology For Use in Rotating Field Nuclear MagneticResonance

Lactic Acid Is Elevated in Idiopathic Pulmonary Fibrosis and Induces Myofibroblast Differentiation via pH-Dependent Activation of Transforming Growth Factor-β

New Methodology For Use in Rotating Field Nuclear MagneticResonance

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Product

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High‐resolution ¹H NMR spectroscopy in organs and tissues using slow magic angle spinning