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  Developing 3D microscopy with CLARITY on human brain tissue: Towards a tool for informing and validating MRI-based histology

Morawski, M., Kirilina, E., Scherf, N., Jäger, C., Reimann, K., Trampel, R., et al. (2018). Developing 3D microscopy with CLARITY on human brain tissue: Towards a tool for informing and validating MRI-based histology. NeuroImage, 182, 417-428. doi:10.1016/j.neuroimage.2017.11.060.

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Item Permalink: https://hdl.handle.net/11858/00-001M-0000-002E-7529-8 Version Permalink: https://hdl.handle.net/21.11116/0000-0003-8B13-B
Genre: Journal Article

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Morawski, Markus1, Author
Kirilina, Evgeniya2, 3, Author           
Scherf, Nico2, Author           
Jäger, Carsten2, Author           
Reimann, Katja1, Author
Trampel, Robert2, Author           
Gavriilidis, Filippos2, Author           
Geyer, Stefan2, Author           
Biedermann, Bernd1, Author
Arendt, Thomas1, Author
Weiskopf, Nikolaus2, Author           
Affiliations:
1Paul Flechsig Institute for Brain Research, University of Leipzig, Germany, ou_persistent22              
2Department Neurophysics (Weiskopf), MPI for Human Cognitive and Brain Sciences, Max Planck Society, Leipzig, DE, ou_2205649              
3Center for Cognitive Neuroscience Berlin (CCNB), FU Berlin, Germany, ou_persistent22              

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 Abstract: Recent breakthroughs in magnetic resonance imaging (MRI) enabled quantitative relaxometry and diffusion-weighted imaging with sub-millimeter resolution. Combined with biophysical models of MR contrast the emerging methods promise in vivo mapping of cyto- and myelo-architectonics, i.e., in vivo histology using MRI (hMRI) in humans. The hMRI methods require histological reference data for model building and validation. This is currently provided by MRI on post mortem human brain tissue in combination with classical histology on sections. However, this well established approach is limited to qualitative 2D information, while a systematic validation of hMRI requires quantitative 3D information on macroscopic voxels.

We present a promising histological method based on optical 3D imaging combined with a tissue clearing method, Clear Lipid-exchanged Acrylamide-hybridized Rigid Imaging compatible Tissue hYdrogel (CLARITY), adapted for hMRI validation. Adapting CLARITY to the needs of hMRI, is challenging due to poor antibody penetration into large sample volumes and high opacity of aged post mortem human brain tissue. In a pilot experiment we achieved transparency of up to 8 mm-thick and immunohistochemical staining of up to 5 mm-thick post mortem brain tissue by combination of active and passive clearing, prolonged clearing and staining times. We combined 3D optical imaging of the cleared samples with tailored image processing methods. We demonstrated feasibility for quantification of neuron density, fiber orientation distribution and cell type classification within a volume with size similar to typical MRI voxel. The presented combination of MRI, 3D optical microscopy and image processing is a promising tool for validation of MRI-based microstructure estimates.

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Language(s): eng - English
 Dates: 2017-05-302017-11-262017-11-282018-11-15
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.neuroimage.2017.11.060
BibTex Citekey: Morawski2017
PMID: 29196268
PMC: PMC6189522
Other: Epub 2017
 Degree: -

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Project name : Mikrostrukturelle Konnektivität des menschlichen Gehirns: Computergestützte Modellierung und Validierung mit Histologie und CLARITY
Grant ID : GE 2967/1-1
Funding program : Schwerpunktprogramm: Computational Connectomics (SPP2041)
Funding organization : Deutsche Forschungsgemeinschaft (DFG)
Project name : Non-invasive in vivo histology in health and disease using Magnetic Resonance Imaging (MRI) / HMRI
Grant ID : 616905
Funding program : Funding Programme 7 (FP7)
Funding organization : European Commission (EC)
Project name : -
Grant ID : MO 2 249/3–1
Funding program : Schwerpunktprogramm: Computational Connectomics
Funding organization : Deutsche Forschungsgemeinschaft (DFG)

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Title: NeuroImage
Source Genre: Journal
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Publ. Info: Orlando, FL : Academic Press
Pages: - Volume / Issue: 182 Sequence Number: - Start / End Page: 417 - 428 Identifier: ISSN: 1053-8119
CoNE: https://pure.mpg.de/cone/journals/resource/954922650166