title: Extracting morphologies from third harmonic generation images of structurally normal human brain tissue.
abstract: BACKGROUND
  The morphologies contained in 3D third harmonic generation (THG) images of human brain tissue can report on the pathological state of the tissue. However, the complexity of THG brain images makes the usage of modern image processing tools, especially those of image filtering, segmentation and validation, to extract this information challenging.
  
  
  RESULTS
  We developed a salient edge-enhancing model of anisotropic diffusion for image filtering, based on higher order statistics. We split the intrinsic 3-phase segmentation problem into two 2-phase segmentation problems, each of which we solved with a dedicated model, active contour weighted by prior extreme. We applied the novel proposed algorithms to THG images of structurally normal ex-vivo human brain tissue, revealing key tissue components-brain cells, microvessels and neuropil, enabling statistical characterization of these components. Comprehensive comparison to manually delineated ground truth validated the proposed algorithms. Quantitative comparison to second harmonic generation/auto-fluorescence images, acquired simultaneously from the same tissue area, confirmed the correctness of the main THG features detected.
  
  
  METHODS
  The software and test datasets are available from the authors.
  
  
  BACKGROUND
  z.zhang@vu.nl.
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: LaserLab Amsterdam, Department of Physics, Faculty of Sciences, VU University, HV Amsterdam, The Netherlands.|Physics and Medical Technology Department, VU University Medical Center,  HZ Amsterdam, The Netherlands.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: LaserLab Amsterdam, Department of Physics, Faculty of Sciences, VU University, HV Amsterdam, The Netherlands.|Neuroscience Campus Amsterdam, VU University, HV Amsterdam, The Netherlands.
authors.forename: Nikolay V
authors.initials: NV
authors.lastname: Kuzmin
authors.affiliation: LaserLab Amsterdam, Department of Physics, Faculty of Sciences, VU University, HV Amsterdam, The Netherlands.|Neuroscience Campus Amsterdam, VU University, HV Amsterdam, The Netherlands.
authors.forename: Marie Louise
authors.initials: ML
authors.lastname: Groot
authors.affiliation: Physics and Medical Technology Department, VU University Medical Center, ?HZ Amsterdam, The Netherlands.
authors.forename: Jan C
authors.initials: JC
authors.lastname: de Munck
mesh_terms: D000465:Algorithms; D001921:Brain / Q000033:anatomy & histology* / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D021621:Imaging, Three-Dimensional / Q000379:methods*; D000073798:Second Harmonic Generation Microscopy / Q000379:methods*; D012984:Software