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@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},
}