% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @ARTICLE{Menzel:874246, author = {Menzel, Miriam and Axer, Markus and De Raedt, Hans and Costantini, Irene and Silvestri, Ludovico and Pavone, Francesco S. and Amunts, Katrin and Michielsen, Kristel}, title = {{T}oward a {H}igh-{R}esolution {R}econstruction of 3{D} {N}erve {F}iber {A}rchitectures and {C}rossings in the {B}rain {U}sing {L}ight {S}cattering {M}easurements and {F}inite-{D}ifference {T}ime-{D}omain {S}imulations}, journal = {Physical review / X}, volume = {10}, number = {2}, issn = {2160-3308}, address = {College Park, Md.}, publisher = {APS}, reportid = {FZJ-2020-01337}, pages = {021002}, year = {2020}, abstract = {Unraveling 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.}, cin = {INM-1 / JSC / JARA-HPC}, ddc = {530}, cid = {I:(DE-Juel1)INM-1-20090406 / I:(DE-Juel1)JSC-20090406 / $I:(DE-82)080012_20140620$}, pnm = {574 - Theory, modelling and simulation (POF3-574) / 571 - Connectivity and Activity (POF3-571) / 511 - Computational Science and Mathematical Methods (POF3-511) / SMHB - Supercomputing and Modelling for the Human Brain (HGF-SMHB-2013-2017) / HBP SGA1 - Human Brain Project Specific Grant Agreement 1 (720270) / HBP SGA2 - Human Brain Project Specific Grant Agreement 2 (785907) / NIH-R01MH092311 - Postnatal Development of Cortical Receptors and White Matter Tracts in the Vervet (NIH-R01MH092311) / 3D Reconstruction of Nerve Fibers in the Human, the Monkey, the Rodent, and the Pigeon Brain $(jinm11_20181101)$ / SIMULATIONS FOR THE RECONSTRUCTION OF NERVE FIBERS BY 3D POLARIZED LIGHT IMAGING $(jjsc24_20150501)$ / Simulations for a better Understanding of the Impact of Different Brain Tissue Components on 3D Polarized Light Imaging $(jjsc43_20181101)$}, pid = {G:(DE-HGF)POF3-574 / G:(DE-HGF)POF3-571 / G:(DE-HGF)POF3-511 / G:(DE-Juel1)HGF-SMHB-2013-2017 / G:(EU-Grant)720270 / G:(EU-Grant)785907 / G:(DE-Juel1)NIH-R01MH092311 / $G:(DE-Juel1)jinm11_20181101$ / $G:(DE-Juel1)jjsc24_20150501$ / $G:(DE-Juel1)jjsc43_20181101$}, typ = {PUB:(DE-HGF)16}, UT = {WOS:000523402300001}, doi = {10.1103/PhysRevX.10.021002}, url = {https://juser.fz-juelich.de/record/874246}, }