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Microscopy

“I stumbled upon the idea of formalin fixed tissue much later and realized with satisfaction, that formalin fixation does not impair the birefringence of myelinated nerve fibers. Therefore, we can study nerve fibers hardened and conserved in formalin … with polarization microscopy and observe possible pathological alterations”

(K. Brodmann, J Psych Neurol, 1903).

We have brought this observation into the 21st century, developing and adapting polarimetric technologies to the requirements of high-throughput large-scale polarization microscopy of hair-thin, unstained brain sections. We have named the approach 3D Polarized Light Imaging (3D-PLI), since we are aiming for contrasting distinct fibers and tracts and investigating their three-dimensional courses across serial brain sections.

Polarimetry + FOVImage acquisition in a polarimetric setup. The optical filters (two linear polarizers and one quarter-wave retarder) are synchronously rotated relative to the brain section placed in-between. The birefringent fiber structures induce characteristic sinusoidal changes in the transmitted light intensity (left). Section- and pixel-wise analysis of the measured sinusoidal signals result in a color-coded description of fiber orientations referred to as fiber orientation map (right).
Copyright: INM-1, Forschungszentrum Jülich

High quality polarimetric measurements require specific preparation and handling of the studied brain tissue in order to preserve the integrity of the myelin sheaths which are responsible for the optical effect referred to as birefringence. Cryo-sectioning of formalin conserved and glycerol soaked tissue was demonstrated to comply with this condition. During sectioning, en face images of the remaining brain block are acquired (blockface imaging) serving as reference images for later reconstruction of the initial brain shape. The generated unstained histological brain sections are scanned with different types of polarimetric setups, which are generally speaking composed of two rotating linear polarizers, one quarter-wave retarder and a green-wavelength light source (see above figure, left). High-performance computing-based signal and image analysis as well as simulation approaches finally enable reliable interpretation and visualization of the targeted fiber architecture (see above figure, right).

Selected Publications

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Teaching NeuroImages: In vivo visualization of Edinger comb and Wilson pencils
Neurology 92(14), e1663 () [10.1212/WNL.0000000000007252]  Download fulltext Files BibTeX | EndNote: XML, Text | RIS

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Ex vivo visualization of the trigeminal pathways in the human brainstem using 11.7T diffusion MRI combined with microscopy polarized light imaging
Brain structure & function 224(1), 159-170 () [10.1007/s00429-018-1767-1]  Download fulltext Files BibTeX | EndNote: XML, Text | RIS

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The hippocampus of birds in a view of evolutionary connectomics
Cortex 118, 165 () [10.1016/j.cortex.2018.09.025] OpenAccess  Download fulltext Files  Download fulltextFulltext by OpenAccess repository BibTeX | EndNote: XML, Text | RIS

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Decoding the microstructural correlate of diffusion MRI
NMR in biomedicine 32(4), e3779 () [10.1002/nbm.3779]  Download fulltext Files BibTeX | EndNote: XML, Text | RIS

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Derivation of Fiber Orientations From Oblique Views Through Human Brain Sections in 3D-Polarized Light Imaging
Frontiers in neuroanatomy 12, 75 () [10.3389/fnana.2018.00075] OpenAccess  Download fulltext Files  Download fulltextFulltext by OpenAccess repository BibTeX | EndNote: XML, Text | RIS

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Post-mortem inference of the human hippocampal connectivity and microstructure using ultra-high field diffusion MRI at 11.7 T
Brain structure & function 223(5), 2157–2179 () [10.1007/s00429-018-1617-1] OpenAccess  Download fulltext Files  Download fulltextFulltext by OpenAccess repository BibTeX | EndNote: XML, Text | RIS

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Diattenuation of Brain Tissue and its Impact on 3D Polarized Light Imaging
Biomedical optics express 8(7), 3163-3197 () [10.1364/BOE.8.003163] OpenAccess  Download fulltext Files  Download fulltextFulltext by OpenAccess repository BibTeX | EndNote: XML, Text | RIS

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Direct Visualization and Mapping of the Spatial Course of Fiber Tracts at Microscopic Resolution in the Human Hippocampus
Cerebral cortex 27(3), 1779-1794 () [10.1093/cercor/bhw010]  Download fulltext Files BibTeX | EndNote: XML, Text | RIS

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3D Reconstructed cyto- muscarinic M2 receptor, and fiber archtiecture of the rat brain registered to the Waxholm Space Atlas
Frontiers in neuroanatomy 10, 51 () [10.3389/fnana.2016.00051] OpenAccess  Download fulltext Files  Download fulltextFulltext by OpenAccess repository BibTeX | EndNote: XML, Text | RIS

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Estimating Fiber Orientation Distribution Functions in 3D-Polarized Light Imaging
Frontiers in neuroanatomy 10, 40 () [10.3389/fnana.2016.00040] OpenAccess  Download fulltext Files  Download fulltextFulltext by OpenAccess repository BibTeX | EndNote: XML, Text | RIS

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A multiscale approach for the reconstruction of the fiber architecture of the human brain based on 3D-PLI
Frontiers in neuroanatomy 9, 118 () [10.3389/fnana.2015.00118] OpenAccess  Download fulltext Files  Download fulltextFulltext by OpenAccess repository BibTeX | EndNote: XML, Text | RIS

Additional Information

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Groupleader

Dr. rer. nat. Markus Axer

Building: 15.9, Room: 3029

Institute of Neuroscience and Medicine (INM-1)
Forschungszentrum Jülich
52425 Jülich

Tel.: +49 2461 61-6314
Fax: +49 2461 61-2820
E-Mail: m.axer@fz-juelich.de

Management

Stefanie Hennen

Building: 15.9, Room: 3021

+49 2461 61-2481
 +49-2461 61-3483
s.hennen@fz-juelich.de

Janine Hucko

Building: 15.9, Room: 3020

+49 2461 61-6443
+49 2461 61-3483
j.hucko@fz-juelich.de

Address

Institut für Neurowissenschaften und Medizin (INM-1)
Forschungszentrum Jülich
52425 Jülich

Building: 15.9


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