000874246 001__ 874246 000874246 005__ 20220930130231.0 000874246 0247_ $$2doi$$a10.1103/PhysRevX.10.021002 000874246 0247_ $$2Handle$$a2128/24646 000874246 0247_ $$2altmetric$$aaltmetric:78836372 000874246 0247_ $$2WOS$$aWOS:000523402300001 000874246 037__ $$aFZJ-2020-01337 000874246 082__ $$a530 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 000874246 3367_ $$2DRIVER$$aarticle 000874246 3367_ $$2DataCite$$aOutput Types/Journal article 000874246 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1619162295_2073 000874246 3367_ $$2BibTeX$$aARTICLE 000874246 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000874246 3367_ $$00$$2EndNote$$aJournal Article 000874246 520__ $$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. 000874246 536__ $$0G:(DE-HGF)POF3-574$$a574 - Theory, modelling and simulation (POF3-574)$$cPOF3-574$$fPOF III$$x0 000874246 536__ $$0G:(DE-HGF)POF3-571$$a571 - Connectivity and Activity (POF3-571)$$cPOF3-571$$fPOF III$$x1 000874246 536__ $$0G:(DE-HGF)POF3-511$$a511 - Computational Science and Mathematical Methods (POF3-511)$$cPOF3-511$$fPOF III$$x2 000874246 536__ $$0G:(DE-Juel1)HGF-SMHB-2013-2017$$aSMHB - Supercomputing and Modelling for the Human Brain (HGF-SMHB-2013-2017)$$cHGF-SMHB-2013-2017$$fSMHB$$x3 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 000874246 588__ $$aDataset connected to CrossRef 000874246 7001_ $$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$$y2020 000874246 8564_ $$uhttps://juser.fz-juelich.de/record/874246/files/INV_20_MAR_003280.pdf 000874246 8564_ $$uhttps://juser.fz-juelich.de/record/874246/files/INV_20_MAR_003280.pdf?subformat=pdfa$$xpdfa 000874246 8564_ $$uhttps://juser.fz-juelich.de/record/874246/files/PhysRevX.10.021002.pdf$$yOpenAccess 000874246 8564_ $$uhttps://juser.fz-juelich.de/record/874246/files/PhysRevX.10.021002.pdf?subformat=pdfa$$xpdfa$$yOpenAccess 000874246 8767_ $$8INV/20/MAR/003280$$92020-03-02$$d2020-03-19$$eAPC$$jZahlung erfolgt$$pXG10563$$zBelegnr. 1200151448 000874246 909CO $$ooai:juser.fz-juelich.de:874246$$popenCost$$pec_fundedresources$$pVDB$$pdriver$$pOpenAPC$$popen_access$$popenaire$$pdnbdelivery 000874246 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)161196$$aForschungszentrum Jülich$$b0$$kFZJ 000874246 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)131632$$aForschungszentrum Jülich$$b1$$kFZJ 000874246 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)131631$$aForschungszentrum Jülich$$b6$$kFZJ 000874246 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)138295$$aForschungszentrum Jülich$$b7$$kFZJ 000874246 9131_ $$0G:(DE-HGF)POF3-574$$1G:(DE-HGF)POF3-570$$2G:(DE-HGF)POF3-500$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bKey Technologies$$lDecoding the Human Brain$$vTheory, modelling and simulation$$x0 000874246 9131_ $$0G:(DE-HGF)POF3-571$$1G:(DE-HGF)POF3-570$$2G:(DE-HGF)POF3-500$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bKey Technologies$$lDecoding the Human Brain$$vConnectivity and Activity$$x1 000874246 9131_ $$0G:(DE-HGF)POF3-511$$1G:(DE-HGF)POF3-510$$2G:(DE-HGF)POF3-500$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bKey Technologies$$lSupercomputing & Big Data$$vComputational Science and Mathematical Methods$$x2 000874246 9132_ $$0G:(DE-HGF)POF4-899$$1G:(DE-HGF)POF4-890$$2G:(DE-HGF)POF4-800$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bProgrammungebundene Forschung$$lohne Programm$$vohne Topic$$x0 000874246 9141_ $$y2020 000874246 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS 000874246 915__ $$0LIC:(DE-HGF)CCBY4$$2HGFVOC$$aCreative Commons Attribution CC BY 4.0 000874246 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bPHYS REV X : 2017 000874246 915__ $$0StatID:(DE-HGF)9910$$2StatID$$aIF >= 10$$bPHYS REV X : 2017 000874246 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal 000874246 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ 000874246 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index 000874246 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded 000874246 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection 000874246 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess 000874246 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bDOAJ : Peer review 000874246 915__ $$0StatID:(DE-HGF)1150$$2StatID$$aDBCoverage$$bCurrent Contents - 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