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000874246 1001_ $$0P:(DE-Juel1)161196$$aMenzel, Miriam$$b0$$eCorresponding author
000874246 245__ $$aToward a High-Resolution Reconstruction of 3D Nerve Fiber Architectures and Crossings in the Brain Using Light Scattering Measurements and Finite-Difference Time-Domain Simulations
000874246 260__ $$aCollege Park, Md.$$bAPS$$c2020
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000874246 520__ $$aUnraveling the structure and function of the brain requires a detailed knowledge about the neuronal connections, i.e., the spatial architecture of the nerve fibers. One of the most powerful histological methods to reconstruct the three-dimensional nerve fiber pathways is 3D-polarized light imaging (3D-PLI). The technique measures the birefringence of histological brain sections and derives the spatial fiber orientations of whole human brain sections with micrometer resolution. However, the technique yields only a single fiber orientation for each measured tissue voxel even if it is composed of fibers with different orientations, so that in-plane crossing fibers are misinterpreted as out-of-plane fibers. When generating a detailed model of the three-dimensional nerve fiber architecture in the brain, a correct detection and interpretation of nerve fiber crossings is crucial. Here, we show how light scattering in transmission microscopy measurements can be leveraged to identify nerve fiber crossings in 3D-PLI data and demonstrate that measurements of the scattering pattern can resolve the substructure of brain tissue like the crossing angles of the nerve fibers. For this purpose, we develop a simulation framework that permits the study of transmission microscopy measurements—in particular, light scattering—on large-scale complex fiber structures like brain tissue, using finite-difference time-domain (FDTD) simulations and high-performance computing. The simulations are used not only to model and explain experimental observations, but also to develop new analysis methods and measurement techniques. We demonstrate in various experimental studies on brain sections from different species (rodent, monkey, and human) and in FDTD simulations that the polarization-independent transmitted light intensity (transmittance) decreases significantly (by more than 50%) with an increasing out-of-plane angle of the nerve fibers and that it is mostly independent of the in-plane crossing angle. Hence, the transmittance can be used to distinguish regions with low fiber density and in-plane crossing fibers from regions with out-of-plane fibers, solving a major problem in 3D-PLI and allowing for a much better reconstruction of the complex nerve fiber architecture in the brain. Finally, we show that light scattering (oblique illumination) in the visible spectrum reveals the underlying structure of brain tissue like the crossing angle of the nerve fibers with micrometer resolution, enabling an even more detailed reconstruction of nerve fiber crossings in the brain and opening up new fields of research.
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000874246 536__ $$0G:(EU-Grant)720270$$aHBP SGA1 - Human Brain Project Specific Grant Agreement 1 (720270)$$c720270$$fH2020-Adhoc-2014-20$$x4
000874246 536__ $$0G:(EU-Grant)785907$$aHBP SGA2 - Human Brain Project Specific Grant Agreement 2 (785907)$$c785907$$fH2020-SGA-FETFLAG-HBP-2017$$x5
000874246 536__ $$0G:(DE-Juel1)NIH-R01MH092311$$aNIH-R01MH092311 - Postnatal Development of Cortical Receptors and White Matter Tracts in the Vervet (NIH-R01MH092311)$$cNIH-R01MH092311$$fPostnatal Development of Cortical Receptors and White Matter Tracts in the Vervet$$x6
000874246 536__ $$0G:(DE-Juel1)jinm11_20181101$$a3D Reconstruction of Nerve Fibers in the Human, the Monkey, the Rodent, and the Pigeon Brain (jinm11_20181101)$$cjinm11_20181101$$f3D Reconstruction of Nerve Fibers in the Human, the Monkey, the Rodent, and the Pigeon Brain$$x7
000874246 536__ $$0G:(DE-Juel1)jjsc24_20150501$$aSIMULATIONS FOR THE RECONSTRUCTION OF NERVE FIBERS BY 3D POLARIZED LIGHT IMAGING (jjsc24_20150501)$$cjjsc24_20150501$$fSIMULATIONS FOR THE RECONSTRUCTION OF NERVE FIBERS BY 3D POLARIZED LIGHT IMAGING$$x8
000874246 536__ $$0G:(DE-Juel1)jjsc43_20181101$$aSimulations for a better Understanding of the Impact of Different Brain Tissue Components on 3D Polarized Light Imaging (jjsc43_20181101)$$cjjsc43_20181101$$fSimulations for a better Understanding of the Impact of Different Brain Tissue Components on 3D Polarized Light Imaging$$x9
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000874246 7001_ $$0P:(DE-Juel1)131632$$aAxer, Markus$$b1
000874246 7001_ $$0P:(DE-HGF)0$$aDe Raedt, Hans$$b2
000874246 7001_ $$00000-0002-8464-7324$$aCostantini, Irene$$b3
000874246 7001_ $$0P:(DE-HGF)0$$aSilvestri, Ludovico$$b4
000874246 7001_ $$0P:(DE-HGF)0$$aPavone, Francesco S.$$b5
000874246 7001_ $$0P:(DE-Juel1)131631$$aAmunts, Katrin$$b6
000874246 7001_ $$0P:(DE-Juel1)138295$$aMichielsen, Kristel$$b7
000874246 773__ $$0PERI:(DE-600)2622565-7$$a10.1103/PhysRevX.10.021002$$gVol. 10, no. 2, p. 021002$$n2$$p021002$$tPhysical review / X$$v10$$x2160-3308$$y2020
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