title: Assessment of tumour viability in human lung cancer xenografts with texture-based image analysis.
abstract: OBJECTIVE
  To build and evaluate an automated method for assessing tumour viability in histological tissue samples using texture features and supervised learning.
  
  
  METHODS
  H&E-stained sections (n=56) of human non-small cell lung adenocarcinoma xenografts were digitised with a whole-slide scanner. A novel image analysis method based on local binary patterns and a support vector machine classifier was trained with a set of sample regions (n=177) extracted from the whole-slide images and tested with another set of images (n=494). The extracted regions, or single-tissue entity images, were chosen to represent as pure as possible examples of three morphological tissue entities: viable tumour tissue, non-viable tumour tissue and mouse host tissue.
  
  
  RESULTS
  An agreement of 94.5% (area under the curve=0.995, kappa=0.90) was achieved to classify the single-tissue entity images in the test set (n=494) into the viable tumour and non-viable tumour tissue categories. The algorithm assigned 250 of the 252 non-viable and 219 of the 242 of viable sample regions to the correct categories, respectively. This corresponds to a sensitivity of 90.5% and specificity of 99.2%.
  
  
  CONCLUSIONS
  The proposed image analysis-based tumour viability assessment resulted in a high agreement with expert annotations. By providing extraction of detailed information of the tumour microenvironment, the automated method can be used in preclinical research settings. The method could also have implications in cancer diagnostics, cancer outcome prognostics and prediction.
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
authors.forename: Riku
authors.initials: R
authors.lastname: Turkki
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
authors.forename: Nina
authors.initials: N
authors.lastname: Linder
authors.affiliation: Translational Cancer Biology Laboratory, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
authors.forename: Tanja
authors.initials: T
authors.lastname: Holopainen
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
authors.forename: Yinhai
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
authors.forename: Anne
authors.initials: A
authors.lastname: Grote
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
authors.forename: Mikael
authors.initials: M
authors.lastname: Lundin
authors.affiliation: Translational Cancer Biology Laboratory, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland Wihuri Research Institute, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
authors.forename: Kari
authors.initials: K
authors.lastname: Alitalo
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland Department of Public Health Sciences, Global Health/IHCAR, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Lundin
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000465:Algorithms; D000818:Animals; D019540:Area Under Curve; D001185:Artificial Intelligence; D057205:Automation, Laboratory; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival; D064593:Heterografts; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008175:Lung Neoplasms / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011237:Predictive Value of Tests; D012372:ROC Curve; D015203:Reproducibility of Results; D013194:Staining and Labeling / Q000379:methods*; D059016:Tumor Microenvironment
keywords: AUTOMATED SCREENING; DIGITAL PATHOLOGY; IMAGE ANALYSIS; LUNG CANCER; tumour necrosis