title: Diagnosis system for hepatocellular carcinoma based on fractal dimension of morphometric elements integrated in an artificial neural network.
abstract: OBJECTIVE
  Hepatocellular carcinoma (HCC) remains a leading cause of death by cancer worldwide. Computerized diagnosis systems relying on novel imaging markers gained significant importance in recent years. Our aim was to integrate a novel morphometric measurement--the fractal dimension (FD)--into an artificial neural network (ANN) designed to diagnose HCC.
  
  
  METHODS
  The study included 21 HCC and 28 liver metastases (LM) patients scheduled for surgery. We performed hematoxylin staining for cell nuclei and CD31/34 immunostaining for vascular elements. We captured digital images and used an in-house application to segment elements of interest; FDs were calculated and fed to an ANN which classified them as malignant or benign, further identifying HCC and LM cases.
  
  
  RESULTS
  User intervention corrected segmentation errors and fractal dimensions were calculated. ANNs correctly classified 947/1050 HCC images (90.2%), 1021/1050 normal tissue images (97.23%), 1215/1400 LM (86.78%), and 1372/1400 normal tissues (98%). We obtained excellent interobserver agreement between human operators and the system.
  
  
  CONCLUSIONS
  We successfully implemented FD as a morphometric marker in a decision system, an ensemble of ANNs designed to differentiate histological images of normal parenchyma from malignancy and classify HCCs and LMs.
authors.affiliation: Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy of Craiova, Petru Rares Street, No. 2, 200349 Craiova, Romania.
authors.forename: Dan Ionuț
authors.initials: DI
authors.lastname: Gheonea
authors.affiliation: Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy of Craiova, Petru Rares Street, No. 2, 200349 Craiova, Romania.
authors.forename: Costin Teodor
authors.initials: CT
authors.lastname: Streba
authors.affiliation: Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy of Craiova, Petru Rares Street, No. 2, 200349 Craiova, Romania.
authors.forename: Cristin Constantin
authors.initials: CC
authors.lastname: Vere
authors.affiliation: Department of Medical Informatics, University of Medicine and Pharmacy of Craiova, Petru Rares Street, No. 2, 200349 Craiova, Romania.
authors.forename: Mircea
authors.initials: M
authors.lastname: Şerbănescu
authors.affiliation: Department of Histology, University of Medicine and Pharmacy of Craiova, Petru Rares Street, No. 2, 200349 Craiova, Romania.
authors.forename: Daniel
authors.initials: D
authors.lastname: Pirici
authors.affiliation: Department of Pathology, University of Medicine and Pharmacy "Carol Davilla," Bucharest, Bulevardul Eroii Sanitari 8, 050474 București, Romania.
authors.forename: Maria
authors.initials: M
authors.lastname: Comănescu
authors.affiliation: 2nd Medical Department, University of Medicine and Pharmacy of Craiova, Petru Rares Street, No. 2, 200349 Craiova, Romania.
authors.forename: Letiția Adela Maria
authors.initials: LA
authors.lastname: Streba
authors.affiliation: Department of Surgery, University of Medicine and Pharmacy of Craiova, Petru Rares Street, No. 2, 200349 Craiova, Romania.
authors.forename: Marius Eugen
authors.initials: ME
authors.lastname: Ciurea
authors.affiliation: Department of Surgery, University of Medicine and Pharmacy of Craiova, Petru Rares Street, No. 2, 200349 Craiova, Romania.
authors.forename: Stelian
authors.initials: S
authors.lastname: Mogoantă
authors.affiliation: Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy of Craiova, Petru Rares Street, No. 2, 200349 Craiova, Romania.
authors.forename: Ion
authors.initials: I
authors.lastname: Rogoveanu
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D005260:Female; D017709:Fractals; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016571:Neural Networks, Computer