title: Detection of lobular structures in normal breast tissue.
abstract: Ongoing research into inflammatory conditions raises an increasing need to evaluate immune cells in histological sections in biologically relevant regions of interest (ROIs). Herein, we compare different approaches to automatically detect lobular structures in human normal breast tissue in digitized whole slide images (WSIs). This automation is required to perform objective and consistent quantitative studies on large data sets.
  
  
  
  In normal breast tissue from nine healthy patients immunohistochemically stained for different markers, we evaluated and compared three different image analysis methods to automatically detect lobular structures in WSIs: (1) a bottom-up approach using the cell-based data for subsequent tissue level classification, (2) a top-down method starting with texture classification at tissue level analysis of cell densities in specific ROIs, and (3) a direct texture classification using deep learning technology.
  
  
  
  All three methods result in comparable overall quality allowing automated detection of lobular structures with minor advantage in sensitivity (approach 3), specificity (approach 2), or processing time (approach 1). Combining the outputs of the approaches further improved the precision.
  
  
  
  Different approaches of automated ROI detection are feasible and should be selected according to the individual needs of biomarker research. Additionally, detected ROIs could be used as a basis for quantification of immune infiltration in lobular structures.
authors.affiliation: ICube, University of Strasbourg, 300 bvd Sébastien Brant, 67412 Illkirch, France. Electronic address: gapou@unistra.fr.
authors.forename: Grégory
authors.initials: G
authors.lastname: Apou
authors.affiliation: Institute for Pathology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany.
authors.forename: Nadine S
authors.initials: NS
authors.lastname: Schaadt
authors.affiliation: ICube, University of Strasbourg, 300 bvd Sébastien Brant, 67412 Illkirch, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Naegel
authors.affiliation: MIPS, University of Haute Alsace, 12 rue des Frères Lumière, 68093 Mulhouse, France.
authors.forename: Germain
authors.initials: G
authors.lastname: Forestier
authors.affiliation: Definiens AG, Bernhard-Wicki-Strasse 5, 80636 Munich, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Schönmeyer
authors.affiliation: Institute for Pathology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Feuerhake
authors.affiliation: ICube, University of Strasbourg, 300 bvd Sébastien Brant, 67412 Illkirch, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Wemmert
authors.affiliation: Institute for Pathology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Grote
mesh_terms: D001940:Breast / Q000166:cytology* / Q000378:metabolism; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D007150:Immunohistochemistry / Q000379:methods
keywords: Convolutional neural network; Digital histopathology; Image analysis; Normal breast lobule; Whole slide image