Establishing sample-preparation protocols for X-ray phase-contrast CT of rodent spinal cords: Aldehyde fixations and osmium impregnation.

Micro-CT Multiscale neuroimaging Soft-tissue fixation Spinal cord imaging Synchrotron radiation X-ray phase-contrast

Journal

Journal of neuroscience methods
ISSN: 1872-678X
Titre abrégé: J Neurosci Methods
Pays: Netherlands
ID NLM: 7905558

Informations de publication

Date de publication:
01 06 2020
Historique:
received: 10 03 2020
revised: 14 04 2020
accepted: 15 04 2020
pubmed: 1 5 2020
medline: 22 6 2021
entrez: 1 5 2020
Statut: ppublish

Résumé

Dense and unbiased cellular-resolution representations of extended volumetric central nervous system soft-tissue anatomy are difficult to obtain, even in experimental post-mortem settings. Interestingly, X-ray phase-contrast computed tomography (X-PCI-CT), an emerging soft-tissue-sensitive volumetric imaging technique, can provide multiscale organ- to cellular-level morphological visualizations of neuroanatomical structure. Here, we tested different nervous-tissue fixation procedures, conventionally used for transmission electron microscopy, to better establish X-PCI-CT-specific sample-preparation protocols. Extracted rat spinal medullas were alternatively fixed with a standard paraformaldehyde-only aldehyde-based protocol, or in combination with glutaraldehyde. Some specimens were additionally post-fixed with osmium tetroxide. Multiscale X-PCI-CT datasets were collected at several synchrotron radiation facilities, using state-of-the-art setups with effective image voxel sizes of 3.0 Multiscale X-PCI-CT of aldehyde-fixed spinal cord specimens resulted in dense histology-like volumetric representations and quantifications of extended deep spinal micro-vascular networks and of intra-medullary cell populations. Osmium post-fixation increased intra-medullary contrast between white and gray-matter tissues, and enhanced delineation of intra-medullary cellular structure, e.g. axon fibers and motor neuron perikarya. Volumetric X-PCI-CT provides complementary contrast and higher spatial resolution compared to 9.4 T MRI. X-PCI-CT's advantage over planar histology is the volumetric nature of the cellular-level data obtained, using samples much larger than those fit for volumetric vascular fluorescence microscopy. Deliberately choosing (post-)fixation protocols tailored for optimal nervous-tissue structural preservation is of paramount importance in achieving effective and targeted neuroimaging via the X-PCI-CT technique.

Sections du résumé

BACKGROUND
Dense and unbiased cellular-resolution representations of extended volumetric central nervous system soft-tissue anatomy are difficult to obtain, even in experimental post-mortem settings. Interestingly, X-ray phase-contrast computed tomography (X-PCI-CT), an emerging soft-tissue-sensitive volumetric imaging technique, can provide multiscale organ- to cellular-level morphological visualizations of neuroanatomical structure.
NEW METHOD
Here, we tested different nervous-tissue fixation procedures, conventionally used for transmission electron microscopy, to better establish X-PCI-CT-specific sample-preparation protocols. Extracted rat spinal medullas were alternatively fixed with a standard paraformaldehyde-only aldehyde-based protocol, or in combination with glutaraldehyde. Some specimens were additionally post-fixed with osmium tetroxide. Multiscale X-PCI-CT datasets were collected at several synchrotron radiation facilities, using state-of-the-art setups with effective image voxel sizes of 3.0
RESULTS
Multiscale X-PCI-CT of aldehyde-fixed spinal cord specimens resulted in dense histology-like volumetric representations and quantifications of extended deep spinal micro-vascular networks and of intra-medullary cell populations. Osmium post-fixation increased intra-medullary contrast between white and gray-matter tissues, and enhanced delineation of intra-medullary cellular structure, e.g. axon fibers and motor neuron perikarya.
COMPARISON WITH EXISTING METHODS
Volumetric X-PCI-CT provides complementary contrast and higher spatial resolution compared to 9.4 T MRI. X-PCI-CT's advantage over planar histology is the volumetric nature of the cellular-level data obtained, using samples much larger than those fit for volumetric vascular fluorescence microscopy.
CONCLUSIONS
Deliberately choosing (post-)fixation protocols tailored for optimal nervous-tissue structural preservation is of paramount importance in achieving effective and targeted neuroimaging via the X-PCI-CT technique.

Identifiants

pubmed: 32353471
pii: S0165-0270(20)30167-9
doi: 10.1016/j.jneumeth.2020.108744
pii:
doi:

Substances chimiques

Aldehydes 0
Osmium 2E7M255OPY

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

108744

Informations de copyright

Copyright © 2020 Elsevier B.V. All rights reserved.

Auteurs

Giacomo E Barbone (GE)

Department of Medical Physics, Faculty of Physics, Ludwig-Maximilians-Universität München, Garching, Germany. Electronic address: giacomo.e.barbone@gmail.com.

Alberto Bravin (A)

European Synchrotron Radiation Facility, Grenoble, France. Electronic address: bravin@esrf.fr.

Alberto Mittone (A)

European Synchrotron Radiation Facility, Grenoble, France. Electronic address: amittone@cells.es.

Markus J Kraiger (MJ)

Institute of Experimental Genetics and German Mouse Clinic, German Research Center for Environmental Health, Neuherberg, Germany. Electronic address: markus.kraiger@helmholtz-muenchen.de.

Martin Hrabě de Angelis (M)

Institute of Experimental Genetics and German Mouse Clinic, German Research Center for Environmental Health, Neuherberg, Germany; Department of Experimental Genetics, School of Life Science Weihenstephan, Technical University of Munich, Freising, Germany; German Center for Diabetes Research, Neuherberg, Germany. Electronic address: hrabe@helmholtz-muenchen.de.

Mario Bossi (M)

Experimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; Milan Center for Neuroscience, University of Milano-Bicocca, Milan, Italy. Electronic address: mario.bossi@unimib.it.

Elisa Ballarini (E)

Experimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; Milan Center for Neuroscience, University of Milano-Bicocca, Milan, Italy. Electronic address: elisa.ballarini@unimib.it.

Virginia Rodriguez-Menendez (V)

Experimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; Milan Center for Neuroscience, University of Milano-Bicocca, Milan, Italy. Electronic address: virginia.rodriguez1@unimib.it.

Cecilia Ceresa (C)

Experimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; Milan Center for Neuroscience, University of Milano-Bicocca, Milan, Italy. Electronic address: cecilia.ceresa@gmail.com.

Guido Cavaletti (G)

Experimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; Milan Center for Neuroscience, University of Milano-Bicocca, Milan, Italy. Electronic address: guido.cavaletti@unimib.it.

Paola Coan (P)

Department of Medical Physics, Faculty of Physics, Ludwig-Maximilians-Universität München, Garching, Germany; Department of Clinical Radiology, Faculty of Medicine, Ludwig-Maximilians-Universität München, Munich, Germany. Electronic address: paola.coan@physik.uni-muenchen.de.

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Classifications MeSH