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@ARTICLE{Kislinger:271081,
      author       = {Kislinger, Georg and Fabig, Gunar and Wehn, Antonia and
                      Rodriguez, Lucia and Jiang, Hanyi and Niemann, Cornelia and
                      Klymchenko, Andrey S and Plesnila, Nikolaus and Misgeld,
                      Thomas and Müller-Reichert, Thomas and Khalin, Igor and
                      Schifferer, Martina},
      title        = {{C}ombining array tomography with electron tomography
                      provides insights into leakiness of the blood-brain barrier
                      in mouse cortex.},
      journal      = {eLife},
      volume       = {12},
      issn         = {2050-084X},
      address      = {Cambridge},
      publisher    = {eLife Sciences Publications},
      reportid     = {DZNE-2024-00953},
      pages        = {RP90565},
      year         = {2024},
      abstract     = {Like other volume electron microscopy approaches, automated
                      tape-collecting ultramicrotomy (ATUM) enables imaging of
                      serial sections deposited on thick plastic tapes by scanning
                      electron microscopy (SEM). ATUM is unique in enabling
                      hierarchical imaging and thus efficient screening for target
                      structures, as needed for correlative light and electron
                      microscopy. However, SEM of sections on tape can only access
                      the section surface, thereby limiting the axial resolution
                      to the typical size of cellular vesicles with an order of
                      magnitude lower than the acquired xy resolution. In
                      contrast, serial-section electron tomography (ET), a
                      transmission electron microscopy-based approach, yields
                      isotropic voxels at full EM resolution, but requires
                      deposition of sections on electron-stable thin and fragile
                      films, thus making screening of large section libraries
                      difficult and prone to section loss. To combine the strength
                      of both approaches, we developed 'ATUM-Tomo, a hybrid
                      method, where sections are first reversibly attached to
                      plastic tape via a dissolvable coating, and after screening
                      detached and transferred to the ET-compatible thin films. As
                      a proof-of-principle, we applied correlative ATUM-Tomo to
                      study ultrastructural features of blood-brain barrier (BBB)
                      leakiness around microthrombi in a mouse model of traumatic
                      brain injury. Microthrombi and associated sites of BBB
                      leakiness were identified by confocal imaging of injected
                      fluorescent and electron-dense nanoparticles, then
                      relocalized by ATUM-SEM, and finally interrogated by
                      correlative ATUM-Tomo. Overall, our new ATUM-Tomo approach
                      will substantially advance ultrastructural analysis of
                      biological phenomena that require cell- and tissue-level
                      contextualization of the finest subcellular textures.},
      keywords     = {Animals / Mice / Electron Microscope Tomography: methods /
                      Blood-Brain Barrier: ultrastructure / Cerebral Cortex:
                      diagnostic imaging / Cerebral Cortex: ultrastructure / Mice,
                      Inbred C57BL / Male / Microscopy, Electron, Scanning:
                      methods / Microtomy / CLEM (Other) / array tomography
                      (Other) / blood brain barrier (Other) / cell biology (Other)
                      / correlation (Other) / imaging (Other) / mouse (Other) /
                      neuroscience (Other) / volume electron microscopy (Other)},
      cin          = {AG Misgeld / AG Simons},
      ddc          = {600},
      cid          = {I:(DE-2719)1110000-4 / I:(DE-2719)1110008},
      pnm          = {351 - Brain Function (POF4-351)},
      pid          = {G:(DE-HGF)POF4-351},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39102289},
      pmc          = {pmc:PMC11299977},
      doi          = {10.7554/eLife.90565},
      url          = {https://pub.dzne.de/record/271081},
}