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Automatic, computer-aided determination of endoscopic and histological inflammation in patients with mild to moderate ulcerative colitis based on red density
  1. Peter Bossuyt1,2,
  2. Hiroshi Nakase3,
  3. Séverine Vermeire1,
  4. Gert de Hertogh4,
  5. Tom Eelbode5,
  6. Marc Ferrante1,
  7. Tadashi Hasegawa6,
  8. Hilde Willekens1,
  9. Yousuke Ikemoto7,
  10. Takao Makino7,
  11. Raf Bisschops1
  1. 1 Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium
  2. 2 Department of Gastroenterology, Imelda GI Clinical Research Centre, Imelda General Hospital, Bonheiden, Belgium
  3. 3 Department of Gastroenterology, Sapporo Medical University, Sapporo, Japan
  4. 4 Department of Pathology, University Hospitals Leuven, KU Leuven, Leuven, Belgium
  5. 5 Medical Imaging Research Center, University Hospitals Leuven, KU Leuven, Leuven, Belgium
  6. 6 Department of Surgical Pathology, Sapporo Medical University, Sapporo, Japan
  7. 7 Product Development Department, Pentax Medical, Tokyo, Japan
  1. Correspondence to Dr Peter Bossuyt, Department of Gastroenterology, KU Leuven University Hospitals Leuven Gasthuisberg Campus, Leuven B-3000, Belgium; peter.bossuyt{at}


Background The objective evaluation of endoscopic disease activity is key in ulcerative colitis (UC). A composite of endoscopic and histological factors is the goal in UC treatment. We aimed to develop an operator-independent computer-based tool to determine UC activity based on endoscopic images.

Methods First, we built a computer algorithm using data from 29 consecutive patients with UC and 6 healthy controls (construction cohort). The algorithm (red density: RD) was based on the red channel of the red-green-blue pixel values and pattern recognition from endoscopic images. The algorithm was refined in sequential steps to optimise correlation with endoscopic and histological disease activity. In a second phase, the operating properties were tested in patients with UC flares requiring treatment escalation. To validate the algorithm, we tested the correlation between RD score and clinical, endoscopic and histological features in a validation cohort.

Results We constructed the algorithm based on the integration of pixel colour data from the redness colour map along with vascular pattern detection. These data were linked with Robarts histological index (RHI) in a multiple regression analysis. In the construction cohort, RD correlated with RHI (r=0.74, p<0.0001), Mayo endoscopic subscores (r=0.76, p<0.0001) and UC Endoscopic Index of Severity scores (r=0.74, p<0.0001). The RD sensitivity to change had a standardised effect size of 1.16. In the validation set, RD correlated with RHI (r=0.65, p=0.00002).

Conclusions RD provides an objective computer-based score that accurately assesses disease activity in UC. In a validation study, RD correlated with endoscopic and histological disease activity.

  • artificial intelligence
  • evaluation
  • response to treatment
  • remission

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  • Contributors HN developed the concept of red density (RD) based on the Magic score system. HN, PB and RB contributed equally to the concept of the study and the further development of the RD system in this study. PB, HN, GdH, MF, TH, SV and RB: acquisition of data; PB, YI, TM, RD: analysis and interpretation of data; PB: drafting of the manuscript; all: critical revision of the manuscript for important intellectual content; PB, TM: statistical analysis; RB: obtained funding; HW, YI and TM administrative, technical or material support; RB: study supervision.

  • Funding This project was supported by an unrestricted grant from Pentax. The authors codeveloped the system where the clinical input came from the authors' side and Pentax provided the technical input to fine-tune the algorithm. As clinical researchers, the authors are not involved with the potential commercialisation of this technique.

  • Competing interests PB has received financial support for research from AbbVie, Mundipharma, Pfizer, Janssen and Mylan; lecture fees from AbbVie, Takeda, Pfizer and Janssen; advisory board fees from Abbvie, Takeda, Hospira, Janssen, MSD, Mundipharma, Roche, Pfizer, Sandoz and Pentax. HN has received advisory board fees from Kyorin Pharmaceutical, Mochida Pharmaceutical, Janssen Pharmaceutical K.K., Pfizer; lecture fee from: Janssen Pharmaceutical K.K., Pfizer, Takeda Pharmaceutical, Mitsubishi Tanabe Pharma (MTP), Abbvie GK(AGK), Eisai Corporation (EC), Kyorin Pharmaceutical, Zeria Pharmaceutical, Mochida Pharmaceutical, Janssen Pharmaceutical K.K., Nippon Kayaku; commissioned/joint research grant: Hoya Group Pentax Medical, Boehringer Ingelheim GmbH. SV has received financial support for research: MSD, AbbVie, Takeda, Pfizer, J&J; Lecture fee(s): MSD, AbbVie, Takeda, Ferring, Centocor, Hospira, Pfizer, J&J, Genentech/Roche; Consultancy: MSD, AbbVie, Takeda, Ferring, Centocor, Hospira, Pfizer, J&J, Genentech/Roche, Celgene, Mundipharma, Celltrion, SecondGenome, Prometheus, Shire, Prodigest, Gilead, Galapagos, MRM Health. GdH’s institution KULeuven received fees for his activities as central pathology reviewer in clinical trials of Centocor and Takeda. TE reports no conflict of interest. MF has received research grants: Janssen, Pfizer, Takeda; consultancy fees: Abbvie, Boehringer-Ingelheim, Celltrion, Ferring, Janssen, Lilly, Mitsubishi Tanabe, MSD, Pfizer, Takeda; speakers fees: Abbvie, Amgen, Biogen, Boehringer-Ingelheim, Chiesi, Falk, Ferring, Janssen, Lamepro, Mitsubishi Tanabe, MSD, Pfizer, Takeda, Tramedico, Tillotts and Zeria. HW reports no conflict of interest. YI is an employee of Pentax Medical. TM is an employee of Pentax Medical. RB has received research grant consultancy and speaker’s fees: Pentax Medical and Fujifilm.

  • Patient consent for publication Not required.

  • Ethics approval The study was conducted in accordance with the ethical principles stated in the Declaration of Helsinki 2008 and in compliance with the principles of Good Clinical Practice (GCP), according to the International Conference on Harmonisation Harmonised Tripartite Guideline. Prior to initiation of the study at any site, the study, including the protocol, informed consent, and other study documents, was approved by an appropriate Independent Ethics Committee of the participating centres (s59405 EC approval number Leuven, 282-185 EC approval number Sapporo).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request. Data may be obtained from a third party and are not publicly available. All data relevant to the study are included in the article or uploaded as supplementary information. All data are deidentified clinical data from participant. Mathematic details on the algorithm are not included but are available on reasonable request. Technical details on the endoscope system need to be obtained by a third party (Pentax Medical) and are not publicly available.