Metabolic properties in stroked rats revealed by relaxation-enhanced magnetic resonance spectroscopy at ultrahigh fields

Shemesh, Noam; Rosenberg, Jens T.; Dumez, Jean‐Nicolas; Muniz, Jose A.; Grant, Samuel C.; Frydman, Lucio

doi:10.1038/ncomms5958

Cited by 62 publications

(102 citation statements)

References 48 publications

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“…It is difficult to draw conclusions on whether the orientation dispersion arises within intra-or extra-axonal spaces (or both), or, whether undulations [90] or passing collateral fibers [91] can contribute to these observations. Performing similar spectroscopic measurements utilizing cell-specific markers such as NAA or mI [52,53], or performing much more extensive time/frequency/b-valuedependent measurements on water [19,59,92], or on metabolites [93,94] may further assist in addressing this question in the future.…”

Section: Discussionmentioning

confidence: 99%

“…Numerous promising studies have also been performed on human scanners [37,38,[48][49][50][51], suggesting quite promising potential for disentangling µFA from the underlying orientation dispersion. Additional recent experiments have even extended the DDE methodology toward MR spectroscopy, aiming to impart specificity toward specific cell populations via cellularspecific metabolites [52,53].…”

Section: Introductionmentioning

confidence: 99%

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Axon Diameters and Myelin Content Modulate Microscopic Fractional Anisotropy at Short Diffusion Times in Fixed Rat Spinal Cord

Shemesh

2018

Front. Phys.

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Mapping tissue microstructure accurately and noninvasively is one of the frontiers of biomedical imaging. Diffusion Magnetic Resonance Imaging (MRI) is at the forefront of such efforts, as it is capable of reporting on microscopic structures orders of magnitude smaller than the voxel size by probing restricted diffusion. Double Diffusion Encoding (DDE) and Double Oscillating Diffusion Encoding (DODE) in particular, are highly promising for their ability to report on microscopic fractional anisotropy (µFA), a measure of the pore anisotropy in its own eigenframe, irrespective of orientation distribution. However, the underlying correlates of µFA have insofar not been studied. Here, we extract µFA from DDE and DODE measurements at ultrahigh magnetic field of 16.4T with the goal of probing fixed rat spinal cord microstructure. We further endeavor to correlate µFA with Myelin Water Fraction (MWF) derived from multiexponential T 2 relaxometry, as well as with literature-based spatially varying axon diameter. In addition, a simple new method is presented for extracting unbiased µFA from three measurements at different b-values. Our findings reveal strong anticorrelations between µFA (derived from DODE) and axon diameter in the distinct spinal cord tracts; a moderate correlation was also observed between µFA derived from DODE and MWF. These findings suggest that axonal membranes strongly modulate µFA, which-owing to its robustness toward orientation dispersion effects-reflects axon diameter much better than its typical FA counterpart. µFA varied when measured via oscillating or blocked gradients, suggesting selective probing of different parallel path lengths and providing insight into how those modulate µFA metrics. Our findings thus shed light into the underlying microstructural correlates of µFA and are promising for future interpretations of this metric in health and disease.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Axon Diameters and Myelin Content Modulate Microscopic Fractional Anisotropy at Short Diffusion Times in Fixed Rat Spinal Cord

Shemesh

2018

Front. Phys.

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“…A partial solution to this problem is provided by the double diffusion encoding (DDE) family of NMR methods [8], which can give estimates of the pore size and shape even in the presence of orientational disorder [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. Current in vivo versions of DDE permit detection of anisotropy in areas of the human brain that are macroscopically isotropic [24] and the assignment of metabolitespecific compartment shapes in animal models [25]. Despite these impressive feats, DDE yields ambiguous results if the investigated volume element comprises several types of water environments, the presence of which has been inferred by fitting multicomponent biophysical models [26][27][28][29] to in vivo data acquired with the StejskalTanner method [30,31].…”

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confidence: 99%

Two-Dimensional Correlation of Isotropic and Directional Diffusion Using NMR

Martins

Topgaard

2016

Phys. Rev. Lett.

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Diffusion nuclear magnetic resonance (NMR) is a powerful technique for studying porous media, but yields ambiguous results when the sample comprises multiple regions with different pore sizes, shapes, and orientations. Inspired by solid-state NMR techniques for correlating isotropic and anisotropic chemical shifts, we propose a diffusion NMR method to resolve said ambiguity. Numerical data inversion relies on sparse representation of the data in a basis of radial and axial diffusivities. Experiments are performed on a composite sample with a cell suspension and a liquid crystal. DOI: 10.1103/PhysRevLett.116.087601 Many porous materials of biological, geological, and synthetic origin contain water in a range of microscopic environments with different local pore geometries. Information about the structure of the pore space can be inferred from nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) measurements of the self-diffusion of the pore water [1,2]. The diffusion MRI approach has been especially powerful for noninvasive studies of the living human brain [3], allowing for quantification of axon diameter [4], mean orientation [5], and orientation distribution [6]. Although useful, classical diffusion MRI protocols relying on the Stejskal-Tanner experiment [7] suffer from the fact that the effects of distributions in pore size, anisotropy, and orientation are intrinsically entangled. A partial solution to this problem is provided by the double diffusion encoding (DDE) family of NMR methods [8], which can give estimates of the pore size and shape even in the presence of orientational disorder [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. Current in vivo versions of DDE permit detection of anisotropy in areas of the human brain that are macroscopically isotropic [24] and the assignment of metabolitespecific compartment shapes in animal models [25]. Despite these impressive feats, DDE yields ambiguous results if the investigated volume element comprises several types of water environments, the presence of which has been inferred by fitting multicomponent biophysical models [26][27][28][29] to in vivo data acquired with the StejskalTanner method [30,31]. Selection of a single model from all the ones that are able to reproduce the experimental data remains a challenge [29]. The key to future progress in diffusion NMR and MRI of heterogeneous anisotropic materials lies in designing a method to unambiguously resolve and quantify water compartments with respect to their size and anisotropy, irrespective of the details of their orientations. Once this goal has been achieved, the obtained information could be used as input for existing methods to estimate distributions of axon diameters [4] and orientations [32][33][34].In solid-state NMR spectroscopy [35], the eigenvalues and eigenvectors of the chemical shift tensors can be determined through the dependence of the nuclear spin Hamiltonian on the orientation of the tensors with respect to the static magnetic field. We have recently poin...

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“…This method has been combined with localized imaging of the brain, achieved by use of gradients, to allow a comparison between damaged and normal tissue in stroke. Numerous crucial resonances that constitute the spectral fingerprints for stroke are obtained for the first time due to the suppression of the nearby water peak [34].…”

Section: Magnetic Resonance Imagingmentioning

confidence: 99%

A Decade of Experience With the UltraWide-Bore 900-MHz NMR Magnet

Markiewicz

Brey

Cross

et al. 2015

IEEE Trans. Appl. Supercond.

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The ultrawide-bore (UWB) 900 MHz NMR magnet was commissioned in 2004. The magnet was conceived as part of the long range goal of NMR at fields in excess of 25 T that would require inner high temperature superconductor coils in the bore of a low temperature superconductor outer magnet of a sufficiently large bore. In order to address the combined interest in reaching 900 MHz while at the same time advancing the technology of large LTS NMR magnets, the decision was made to produce a 900 MHz magnet with an extended large bore to force the development of technology and for demonstration. Several advances in magnet technology were made in addition to the large bore in the areas of epoxy for impregnation and quench protection. During fabrication of the magnet, a joint between coil sections was possibly damaged, resulting in a large field drift in persistent mode. The cancelation of the field drift was initially a challenge but resulted in an excellent opportunity for the further development of drift compensation methods. Once the extended large bore was available, it was found to be increasingly of interest for unique NMR measurements. Since commissioning, the UWB magnet has played a central role in the NMR science program at the NHMFL. Major programs conducted in the magnet include biological solid state NMR both of uniformly oriented samples of membrane proteins that often represent drug targets for the pharmaceutical industry and magic angle sample spinning. The extended wide bore has allowed the magnet to be used for imaging at the high field of 21 T, including studies of high resolution 1 H images of adult rodents, 23 Na imaging in models ranging from single cells to in vivo rats to establish dynamic distributions of ionic sodium in pathological (stroke) and non-pathological (activation) conditions, and multi-modal nanoparticles used to track implanted cells as part of a cellular therapy for neurodegeneration. In addition 23 Na and 35 Cl images of in vivo tumors in animal models have suggested important potential roles for evaluating pharmaceutical efficacy and other medical applications.

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Metabolic properties in stroked rats revealed by relaxation-enhanced magnetic resonance spectroscopy at ultrahigh fields

Cited by 62 publications

References 48 publications

Axon Diameters and Myelin Content Modulate Microscopic Fractional Anisotropy at Short Diffusion Times in Fixed Rat Spinal Cord

Axon Diameters and Myelin Content Modulate Microscopic Fractional Anisotropy at Short Diffusion Times in Fixed Rat Spinal Cord

Two-Dimensional Correlation of Isotropic and Directional Diffusion Using NMR

A Decade of Experience With the UltraWide-Bore 900-MHz NMR Magnet

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