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@ARTICLE{Kim:872613,
      author       = {Kim, Chang-Beom and Park, Sang-Jin and Jeong, Jae-Chan and
                      Choi, Seung-Min and Krause, Hans-Joachim and Song, Dae-Yong
                      and Hong, Hyobong},
      title        = {{C}onstruction of 3{D}-rendering imaging of an ischemic rat
                      brain model using the planar {FMMD} technique},
      journal      = {Scientific reports},
      volume       = {9},
      number       = {1},
      issn         = {2045-2322},
      address      = {[London]},
      publisher    = {Macmillan Publishers Limited, part of Springer Nature},
      reportid     = {FZJ-2020-00106},
      pages        = {19050},
      year         = {2019},
      abstract     = {Occlusion of the major cerebral artery usually results in
                      brain hypoxic-ischemic injury, which evokes
                      neuroinflammation and microglial activation. Activated
                      microglia are considered a source of multiple neurotoxic
                      factors, such as reactive oxygen species (ROS), in the
                      central nervous system (CNS). We herein present a
                      3D-rendering brain imaging technique in an experimental
                      rodent model of cerebral ischemia based on 2D magnetic
                      images of superparamagnetic iron oxide nanoparticles
                      (SPIONs) using the planar frequency mixing magnetic
                      detection (p-FMMD) technique. A rat model of cerebral
                      ischemia was established by unilateral middle cerebral
                      artery occlusion with reperfusion (MCAO/R) injury.
                      2,3,5-Triphenyltetrazolium chloride (TTC) staining was
                      performed to demonstrate the irreversibly damaged ischemic
                      brain tissues, and double immunofluorescent labeling of OX6
                      (activated microglial marker) and ethidium (ROS marker) was
                      conducted to confirm ROS generation in the activated
                      microglia in the infarcted brain region. The ischemic brain
                      sections treated with OX6-conjugated SPIONs were scanned
                      using our p-FMMD system, yielding 2D images on the basis of
                      the nonlinear magnetic characteristics inherent in SPIONs.
                      The p-FMMD signal images representing microglia activation
                      show an infarct ratio of $44.6 ± 7.1\%$ compared to the
                      contralateral counterpart, which is smaller than observed by
                      TTC $(60.9 ± 4.9\%)$ or magnetic resonance imaging
                      (MRI, $65.7 ± 2.7\%).$ Furthermore, we developed a
                      3D-rendering brain imaging process based on the 2D p-FMMD
                      signal images. The 3D reconstructed model showed a decreased
                      ratio of coincidence of the ischemic regions compared with
                      MRI models. In this study, we successfully conducted a
                      feasibility test on whether our p-FMMD technology, a
                      technique for signaling and imaging based on the
                      nonlinearity of SPIONs, can be used to visualize the
                      ischemic brain region in real time by detecting activated
                      microglia in an MCAO/R animal model. Therefore, our method
                      might allow for a different approach to analyze the
                      pathophysiology of ischemic stroke through molecular
                      imaging. Furthermore, we propose that this magnetic particle
                      imaging (MPI) technique that detects the nonlinear
                      magnetization properties of SPIONs could be applied not only
                      to a stroke model but also to various types of
                      pathophysiological studies as a new bioimaging tool.},
      cin          = {ICS-8},
      ddc          = {600},
      cid          = {I:(DE-Juel1)ICS-8-20110106},
      pnm          = {523 - Controlling Configuration-Based Phenomena (POF3-523)},
      pid          = {G:(DE-HGF)POF3-523},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:31836804},
      UT           = {WOS:000503162100001},
      doi          = {10.1038/s41598-019-55585-x},
      url          = {https://juser.fz-juelich.de/record/872613},
}