title: Contrast-enhanced ultrasonography parameters in neural network diagnosis of liver tumors.
abstract: OBJECTIVE
  To study the role of time-intensity curve (TIC) analysis parameters in a complex system of neural networks designed to classify liver tumors.
  
  
  METHODS
  We prospectively included 112 patients with hepatocellular carcinoma (HCC) (n = 41), hypervascular (n = 20) and hypovascular (n = 12) liver metastases, hepatic hemangiomas (n = 16) or focal fatty changes (n = 23) who underwent contrast-enhanced ultrasonography in the Research Center of Gastroenterology and Hepatology, Craiova, Romania. We recorded full length movies of all contrast uptake phases and post-processed them offline by selecting two areas of interest (one for the tumor and one for the healthy surrounding parenchyma) and consecutive TIC analysis. The difference in maximum intensities, the time to reaching them and the aspect of the late/portal phase, as quantified by the neural network and a ratio between median intensities of the central and peripheral areas were analyzed by a feed forward back propagation multi-layer neural network which was trained to classify data into five distinct classes, corresponding to each type of liver lesion.
  
  
  RESULTS
  The neural network had 94.45% training accuracy (95% CI: 89.31%-97.21%) and 87.12% testing accuracy (95% CI: 86.83%-93.17%). The automatic classification process registered 93.2% sensitivity, 89.7% specificity, 94.42% positive predictive value and 87.57% negative predictive value. The artificial neural networks (ANN) incorrectly classified as hemangyomas three HCC cases and two hypervascular metastases, while in turn misclassifying four liver hemangyomas as HCC (one case) and hypervascular metastases (three cases). Comparatively, human interpretation of TICs showed 94.1% sensitivity, 90.7% specificity, 95.11% positive predictive value and 88.89% negative predictive value. The accuracy and specificity of the ANN diagnosis system was similar to that of human interpretation of the TICs (P = 0.225 and P = 0.451, respectively). Hepatocellular carcinoma cases showed contrast uptake during the arterial phase followed by wash-out in the portal and first seconds of the late phases. For the hypovascular metastases did not show significant contrast uptake during the arterial phase, which resulted in negative differences between the maximum intensities. We registered wash-out in the late phase for most of the hypervascular metastases. Liver hemangiomas had contrast uptake in the arterial phase without agent wash-out in the portal-late phases. The focal fatty changes did not show any differences from surrounding liver parenchyma, resulting in similar TIC patterns and extracted parameters.
  
  
  CONCLUSIONS
  Neural network analysis of contrast-enhanced ultrasonography - obtained TICs seems a promising field of development for future techniques, providing fast and reliable diagnostic aid for the clinician.
authors.affiliation: Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania.
authors.forename: Costin Teodor
authors.initials: CT
authors.lastname: Streba
authors.forename: Mihaela
authors.initials: M
authors.lastname: Ionescu
authors.forename: Dan Ionut
authors.initials: DI
authors.lastname: Gheonea
authors.forename: Larisa
authors.initials: L
authors.lastname: Sandulescu
authors.forename: Tudorel
authors.initials: T
authors.lastname: Ciurea
authors.forename: Adrian
authors.initials: A
authors.lastname: Saftoiu
authors.forename: Cristin Constantin
authors.initials: CC
authors.lastname: Vere
authors.forename: Ion
authors.initials: I
authors.lastname: Rogoveanu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000000981:diagnostic imaging; D005260:Female; D006391:Hemangioma / Q000175:diagnosis / Q000000981:diagnostic imaging; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D008113:Liver Neoplasms / Q000145:classification* / Q000175:diagnosis / Q000000981:diagnostic imaging*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000175:diagnosis / Q000000981:diagnostic imaging; D016571:Neural Networks, Computer; D011446:Prospective Studies; D012383:Romania; D012680:Sensitivity and Specificity; D013997:Time Factors; D014463:Ultrasonography / Q000379:methods*