Computer Aided Diagnosis for Confocal Laser Endomicroscopy in Advanced Colorectal Adenocarcinoma

PLoS One. 2016 May 4;11(5):e0154863. doi: 10.1371/journal.pone.0154863. eCollection 2016.


Introduction: Confocal laser endomicroscopy (CLE) is becoming a popular method for optical biopsy of digestive mucosa for both diagnostic and therapeutic procedures. Computer aided diagnosis of CLE images, using image processing and fractal analysis can be used to quantify the histological structures in the CLE generated images. The aim of this study is to develop an automatic diagnosis algorithm of colorectal cancer (CRC), based on fractal analysis and neural network modeling of the CLE-generated colon mucosa images.

Materials and methods: We retrospectively analyzed a series of 1035 artifact-free endomicroscopy images, obtained during CLE examinations from normal mucosa (356 images) and tumor regions (679 images). The images were processed using a computer aided diagnosis (CAD) medical imaging system in order to obtain an automatic diagnosis. The CAD application includes image reading and processing functions, a module for fractal analysis, grey-level co-occurrence matrix (GLCM) computation module, and a feature identification module based on the Marching Squares and linear interpolation methods. A two-layer neural network was trained to automatically interpret the imaging data and diagnose the pathological samples based on the fractal dimension and the characteristic features of the biological tissues.

Results: Normal colon mucosa is characterized by regular polyhedral crypt structures whereas malignant colon mucosa is characterized by irregular and interrupted crypts, which can be diagnosed by CAD. For this purpose, seven geometric parameters were defined for each image: fractal dimension, lacunarity, contrast correlation, energy, homogeneity, and feature number. Of the seven parameters only contrast, homogeneity and feature number were significantly different between normal and cancer samples. Next, a two-layer feed forward neural network was used to train and automatically diagnose the malignant samples, based on the seven parameters tested. The neural network operations were cross-entropy with the results: training: 0.53, validation: 1.17, testing: 1.17, and percent error, resulting: training: 16.14, validation: 17.42, testing: 15.48. The diagnosis accuracy error was 15.5%.

Conclusions: Computed aided diagnosis via fractal analysis of glandular structures can complement the traditional histological and minimally invasive imaging methods. A larger dataset from colorectal and other pathologies should be used to further validate the diagnostic power of the method.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnosis*
  • Adenocarcinoma / pathology*
  • Colon / pathology
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / pathology*
  • Diagnosis, Computer-Assisted / methods
  • Entropy
  • Fractals
  • Humans
  • Image Processing, Computer-Assisted / methods
  • Intestinal Mucosa / pathology
  • Microscopy, Confocal / methods
  • Retrospective Studies

Grants and funding

This work was supported by the European Social Fund, Human Resources Development Operational Programme 2007-2013, project no. POSDRU/159/1.5/S/136893 to DS. This work was also supported by the EEA Financial Mechanism 2009 - 2014 under the project EEA-JRP-RO-NO-2013-1-0123 - Navigation System For Confocal Laser Endomicroscopy To Improve Optical Biopsy Of Peripheral Lesions In The Lungs (NAVICAD), contract no. 3SEE/30.06.2014. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.