tissue microstructure

Internal gradient distributions: A susceptibility-derived tensor delivering morphologies by magnetic resonance | Scientific Reports

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Gonzalo A. Álvarez, Noam Shemesh & Lucio Frydman

Scientific Reports 7, 3311 (2017)


Nuclear magnetic resonance is a powerful tool for probing the structures of chemical and biological systems. Combined with field gradients it leads to NMR imaging (MRI), a widespread tool in non-invasive examinations. Sensitivity usually limits MRI’s spatial resolution to tens of micrometers, but other sources of information like those delivered by constrained diffusion processes, enable one extract morphological information down to micron and sub-micron scales. We report here on a new method that also exploits diffusion – isotropic or anisotropic– to sense morphological parameters in the nm-mm range, based on distributions of susceptibility-induced magnetic field gradients. A theoretical framework is developed to define this source of information, leading to the proposition of internal gradient-distribution tensors. Gradient-based spin-echo sequences are designed to measure these new observables. These methods can be used to map orientations even when dealing with unconstrained diffusion, as is here demonstrated with studies of structured systems, including tissues.

Source: Internal gradient distributions: A susceptibility-derived tensor delivering morphologies by magnetic resonance | Scientific Reports


Mapping Internal Gradient Distribution Tensors (IGDT) in biological tissues
Mapping IGDT in biological tissues. (a) IGDT eigenvalues observed for a spinal cord specimen, examined in a 10 mm NMR tube filled with Fluorinert® (cartoon in center exemplifies this model phantom). (b) Color-coded orientation maps generated from the directions of the first eigenvector (the one with lowest eigenvalue) with respect to the main magnetic field [red: z-axis (up-down), blue: x-axis (in-out), green: y-axis (left-right)]. The vector magnitude was weighted with a fractional anisotropy to highlight its orientation. Parameters for the NOGSE MRI measurements were: TR/TE = 4000/50 ms, resolution = 156 × 156 × 1000 μm3, six pairs of opposing-gradient NOGSE encodings according to the orientations given in Fig. 3, NA = 4, G = 35 G/cm, total number of NOGSE oscillations of ten, total NOGSE gradient modulation time =20 ms. A T 2~50–60 ms was measured in these white matter experiments, and the shortest delay x was 140 μs. (c) Microscopic DTI tensor determined from the sNOGSE amplitude modulation Δβ S is shown for comparison to demonstrate the consistency of the orientations. EPI sequences were used for collecting all images, the typical SNR was >35 at its lowest. A full set of measurements took 13 minutes to complete.

PLoS ONE: Size Distribution Imaging by Non-Uniform Oscillating-Gradient Spin Echo (NOGSE) MRI

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Noam Shemesh, Gonzalo A. Álvarez, Lucio Frydman

Published: July 21, 2015

DOI: 10.1371/journal.pone.0133201


Objects making up complex porous systems in Nature usually span a range of sizes. These size distributions play fundamental roles in defining the physicochemical, biophysical and physiological properties of a wide variety of systems – ranging from advanced catalytic materials to Central Nervous System diseases. Accurate and noninvasive measurements of size distributions in opaque, three-dimensional objects, have thus remained long-standing and important challenges. Herein we describe how a recently introduced diffusion-based magnetic resonance methodology, Non-Uniform-Oscillating-Gradient-Spin-Ec​ho(NOGSE), can determine such distributions noninvasively. The method relies on its ability to probe confining lengths with a (length)^6 parametric sensitivity, in a constant-time, constant-number-of-gradients fashion; combined, these attributes provide sufficient sensitivity for characterizing the underlying distributions in μm-scaled cellular systems. Theoretical derivations and simulations are presented to verify NOGSE’s ability to faithfully reconstruct size distributions through suitable modeling of their distribution parameters. Experiments in yeast cell suspensions – where the ground truth can be determined from ancillary microscopy – corroborate these trends experimentally. Finally, by appending to the NOGSE protocol an imaging acquisition, novel MRI maps of cellular size distributions were collected from a mouse brain. The ensuing micro-architectural contrasts successfully delineated distinctive hallmark anatomical sub-structures, in both white matter and gray matter tissues, in a non-invasive manner. Such findings highlight NOGSE’s potential for characterizing aberrations in cellular size distributions upon disease, or during normal processes such as development.

Citation: Shemesh N, Álvarez GA, Frydman L (2015) Size Distribution Imaging by Non-Uniform Oscillating-Gradient Spin Echo (NOGSE) MRI. PLoS ONE 10(7): e0133201. doi:10.1371/journal.pone.0133201

Editor: Ichio Aoki, National Institute of Radiological Sciences, JAPAN

Received: November 25, 2014; Accepted: June 24, 2015; Published: July 21, 2015

Copyright: © 2015 Shemesh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited


via PLOS ONE: Size Distribution Imaging by Non-Uniform Oscillating-Gradient Spin Echo (NOGSE) MRI.


Magnetic resonance virtual histology
Magnetic resonance virtual histology based on probing molecular diffusion in tissues. Non-uniform oscillating gradient spin-echo (NOGSE) sequences are applied to generate the magnetic resonance imaging (MRI) contrast. The compartment size distributions in a mouse corpus callosum are extracted highlighting the different anatomical regions.