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Transient Anomalous Diffusion MRI in Excised Mouse Spinal Cord: Comparison Among Different Diffusion Metrics and Validation With Histology

Neural tissue is a hierarchical multiscale system with intracellular and extracellular diffusion compartments at different length scales. The normal diffusion of bulk water in tissues is not able to detect the specific features of a complex system, providing nonlocal, diffusion measurement averaged...

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Autores principales: Caporale, Alessandra, Bonomo, Giovanni Battista, Tani Raffaelli, Giulio, Tata, Ada Maria, Avallone, Bice, Wehrli, Felix Werner, Capuani, Silvia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8885723/
https://www.ncbi.nlm.nih.gov/pubmed/35242002
http://dx.doi.org/10.3389/fnins.2021.797642
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author Caporale, Alessandra
Bonomo, Giovanni Battista
Tani Raffaelli, Giulio
Tata, Ada Maria
Avallone, Bice
Wehrli, Felix Werner
Capuani, Silvia
author_facet Caporale, Alessandra
Bonomo, Giovanni Battista
Tani Raffaelli, Giulio
Tata, Ada Maria
Avallone, Bice
Wehrli, Felix Werner
Capuani, Silvia
author_sort Caporale, Alessandra
collection PubMed
description Neural tissue is a hierarchical multiscale system with intracellular and extracellular diffusion compartments at different length scales. The normal diffusion of bulk water in tissues is not able to detect the specific features of a complex system, providing nonlocal, diffusion measurement averaged on a 10-20 μm length scale. Being able to probe tissues with sub-micrometric diffusion length and quantify new local parameters, transient anomalous diffusion (tAD) would dramatically increase the diagnostic potential of diffusion MRI (DMRI) in detecting collective and sub-micro architectural changes of human tissues due to pathological damage. In DMRI, the use of tAD parameters quantified using specific DMRI acquisition protocols and their interpretation has often aroused skepticism. Although the derived formulas may accurately fit experimental diffusion-weighted data, the relationships between the postulated dynamical feature and the underlying geometrical structure remains elusive, or at most only suggestive. This work aimed to elucidate and validate the image contrast and information that can be obtained using the tAD model in white matter (WM) through a direct comparison between different diffusion metrics and histology. Towards this goal, we compared tAD metrics extracted from pure subdiffusion (α-imaging) and super-pseudodiffusion (γ-imaging) in excised mouse spinal cord WM, together with T2 and T2* relaxometry, conventional (normal diffusion-based) diffusion tensor imaging (DTI) and q-space imaging (QSI), with morphologic measures obtained by optical microscopy, to determine which structural and topological characteristics of myelinated axons influenced tAD contrast. Axon diameter (AxDiam), the standard deviation of diameters (SD(ax.diam)), axonal density (AxDens) and effective local density (ELD) were extracted from optical images in several WM tracts. Among all the diffusion parameters obtained at 9.4 T, γ-metrics confirmed a strong dependence on magnetic in-homogeneities quantified by R2* = 1/T2* and showed the strongest associations with AxDiam and ELD. On the other hand, α-metrics showed strong associations with SD(ax.diam) and was significantly related to AxDens, suggesting its ability to quantify local heterogeneity degree in neural tissue. These results elucidate the biophysical mechanism underpinning tAD parameters and show the clinical potential of tAD-imaging, considering that both physiologic and pathologic neurodegeneration translate into alterations of WM morphometry and topology.
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spelling pubmed-88857232022-03-02 Transient Anomalous Diffusion MRI in Excised Mouse Spinal Cord: Comparison Among Different Diffusion Metrics and Validation With Histology Caporale, Alessandra Bonomo, Giovanni Battista Tani Raffaelli, Giulio Tata, Ada Maria Avallone, Bice Wehrli, Felix Werner Capuani, Silvia Front Neurosci Neuroscience Neural tissue is a hierarchical multiscale system with intracellular and extracellular diffusion compartments at different length scales. The normal diffusion of bulk water in tissues is not able to detect the specific features of a complex system, providing nonlocal, diffusion measurement averaged on a 10-20 μm length scale. Being able to probe tissues with sub-micrometric diffusion length and quantify new local parameters, transient anomalous diffusion (tAD) would dramatically increase the diagnostic potential of diffusion MRI (DMRI) in detecting collective and sub-micro architectural changes of human tissues due to pathological damage. In DMRI, the use of tAD parameters quantified using specific DMRI acquisition protocols and their interpretation has often aroused skepticism. Although the derived formulas may accurately fit experimental diffusion-weighted data, the relationships between the postulated dynamical feature and the underlying geometrical structure remains elusive, or at most only suggestive. This work aimed to elucidate and validate the image contrast and information that can be obtained using the tAD model in white matter (WM) through a direct comparison between different diffusion metrics and histology. Towards this goal, we compared tAD metrics extracted from pure subdiffusion (α-imaging) and super-pseudodiffusion (γ-imaging) in excised mouse spinal cord WM, together with T2 and T2* relaxometry, conventional (normal diffusion-based) diffusion tensor imaging (DTI) and q-space imaging (QSI), with morphologic measures obtained by optical microscopy, to determine which structural and topological characteristics of myelinated axons influenced tAD contrast. Axon diameter (AxDiam), the standard deviation of diameters (SD(ax.diam)), axonal density (AxDens) and effective local density (ELD) were extracted from optical images in several WM tracts. Among all the diffusion parameters obtained at 9.4 T, γ-metrics confirmed a strong dependence on magnetic in-homogeneities quantified by R2* = 1/T2* and showed the strongest associations with AxDiam and ELD. On the other hand, α-metrics showed strong associations with SD(ax.diam) and was significantly related to AxDens, suggesting its ability to quantify local heterogeneity degree in neural tissue. These results elucidate the biophysical mechanism underpinning tAD parameters and show the clinical potential of tAD-imaging, considering that both physiologic and pathologic neurodegeneration translate into alterations of WM morphometry and topology. Frontiers Media S.A. 2022-02-15 /pmc/articles/PMC8885723/ /pubmed/35242002 http://dx.doi.org/10.3389/fnins.2021.797642 Text en Copyright © 2022 Caporale, Bonomo, Tani Raffaelli, Tata, Avallone, Wehrli and Capuani. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Caporale, Alessandra
Bonomo, Giovanni Battista
Tani Raffaelli, Giulio
Tata, Ada Maria
Avallone, Bice
Wehrli, Felix Werner
Capuani, Silvia
Transient Anomalous Diffusion MRI in Excised Mouse Spinal Cord: Comparison Among Different Diffusion Metrics and Validation With Histology
title Transient Anomalous Diffusion MRI in Excised Mouse Spinal Cord: Comparison Among Different Diffusion Metrics and Validation With Histology
title_full Transient Anomalous Diffusion MRI in Excised Mouse Spinal Cord: Comparison Among Different Diffusion Metrics and Validation With Histology
title_fullStr Transient Anomalous Diffusion MRI in Excised Mouse Spinal Cord: Comparison Among Different Diffusion Metrics and Validation With Histology
title_full_unstemmed Transient Anomalous Diffusion MRI in Excised Mouse Spinal Cord: Comparison Among Different Diffusion Metrics and Validation With Histology
title_short Transient Anomalous Diffusion MRI in Excised Mouse Spinal Cord: Comparison Among Different Diffusion Metrics and Validation With Histology
title_sort transient anomalous diffusion mri in excised mouse spinal cord: comparison among different diffusion metrics and validation with histology
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8885723/
https://www.ncbi.nlm.nih.gov/pubmed/35242002
http://dx.doi.org/10.3389/fnins.2021.797642
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