Abstract
Background: Video capsule endoscopy (VCE) is an attractive method for diagnosing and objectively monitoring disease activity in celiac disease (CeD). Its use, facilitated by artificial intelligence- based tools, may allow computer-assisted interpretation of VCE studies, transforming a subjective test into a quantitative and reproducible measurement tool.
Objective: To evaluate and compare objective CeD severity assessment as determined with VCE by expert human readers and a machine learning algorithm (MLA).
Methods: Patients ≥ 18 years with histologically proven CeD underwent VCE. Examination frames were scored by three readers from one center and the MLA, using a 4-point ordinal scale for assessing the severity of CeD enteropathy. After scoring, curves representing CeD severity across the entire small intestine (SI) and individual tertiles (proximal, mid, and distal) were fitted for each reader and the MLA. All comparisons used Krippendorff’s alpha; values > 0.8 represent excellent to ‘almost perfect’ inter-reader agreement.
Results: VCEs from 63 patients were scored. Readers demonstrated strong inter-reader agreement on celiac villous damage (alpha=0.924), and mean value reader curves showed similarly excellent agreement with MLA curves (alpha=0.935). Average reader and MLA curves were comparable for mean and maximum values for the first SI tertile (alphas=0.932 and 0.867, respectively) and the mean value over the entire SI (alpha=0.945).
Conclusion: A novel MLA demonstrated excellent agreement on whole SI imaging with three expert gastroenterologists. An ordinal scale permitted high inter-reader agreement, accurately and reliably replicated by the MLA. Interpreting VCEs using MLAs may allow automated diagnosis and disease burden assessment in CeD.
Graphical Abstract
[1]
Kelly CP, Bai JC, Liu E, Leffler DA. Advances in diagnosis and management of celiac disease. Gastroenterology 2015; 148(6): 1175-86.
[http://dx.doi.org/10.1053/j.gastro.2015.01.044] [PMID: 25662623]
[http://dx.doi.org/10.1053/j.gastro.2015.01.044] [PMID: 25662623]
[2]
Rostom A, Murray JA, Kagnoff MF. American Gastroenterological Association (AGA) Institute technical review on the diagnosis and management of celiac disease. Gastroenterology 2006; 131(6): 1981-2002.
[http://dx.doi.org/10.1053/j.gastro.2006.10.004] [PMID: 17087937]
[http://dx.doi.org/10.1053/j.gastro.2006.10.004] [PMID: 17087937]
[3]
Ludvigsson JF, Leffler DA, Bai JC, et al. The Oslo definitions for coeliac disease and related terms. Gut 2013; 62(1): 43-52.
[http://dx.doi.org/10.1136/gutjnl-2011-301346] [PMID: 22345659]
[http://dx.doi.org/10.1136/gutjnl-2011-301346] [PMID: 22345659]
[4]
Lidums I, Teo E, Field J, Cummins AG. Capsule endoscopy: a valuable tool in the follow-up of people with celiac disease on a gluten-free diet. Clin Transl Gastroenterol 2011; 2(8): e4.
[http://dx.doi.org/10.1038/ctg.2011.3] [PMID: 23237971]
[http://dx.doi.org/10.1038/ctg.2011.3] [PMID: 23237971]
[5]
Murray JA, Rubio-tapia A, Van Dyke CT, et al. Mucosal atrophy in celiac disease: extent of involvement, correlation with clinical presentation, and response to treatment. Clin Gastroenterol Hepatol 2008; 6(2): 186-93.
[http://dx.doi.org/10.1016/j.cgh.2007.10.012] [PMID: 18096440]
[http://dx.doi.org/10.1016/j.cgh.2007.10.012] [PMID: 18096440]
[6]
Mearns ES, Taylor A, Boulanger T, et al. Systematic literature review of the economic burden of celiac disease. PharmacoEconomics 2019; 37(1): 45-61.
[http://dx.doi.org/10.1007/s40273-018-0707-5] [PMID: 30221333]
[http://dx.doi.org/10.1007/s40273-018-0707-5] [PMID: 30221333]
[7]
Ludvigsson JF, Bai JC, Biagi F, et al. Diagnosis and management of adult coeliac disease: Guidelines from the British Society of Gastroenterology. Gut 2014; 63(8): 1210-28.
[http://dx.doi.org/10.1136/gutjnl-2013-306578] [PMID: 24917550]
[http://dx.doi.org/10.1136/gutjnl-2013-306578] [PMID: 24917550]
[8]
Silvester JA, Kurada S, Szwajcer A, Kelly CP, Leffler DA, Duerksen DR. Tests for serum transglutaminase and endomysial antibodies do not detect most patients with celiac disease and persistent villous atrophy on gluten-free diets: A meta-analysis. Gastroenterology 2017; 153(3): 689-701.
[http://dx.doi.org/10.1053/j.gastro.2017.05.015]
[http://dx.doi.org/10.1053/j.gastro.2017.05.015]
[9]
Chetcuti Zammit S, Sanders DS, Sidhu R. Bone mineral density in patients with celiac disease: A further association with extent of disease on capsule endoscopy. J Clin Gastroenterol 2020; 54(3): 294-5.
[http://dx.doi.org/10.1097/MCG.0000000000001294] [PMID: 31851101]
[http://dx.doi.org/10.1097/MCG.0000000000001294] [PMID: 31851101]
[10]
Chetcuti Zammit S, Sanders DS, Sidhu R. A comprehensive review on the utility of capsule endoscopy in coeliac disease: From computational analysis to the bedside. Comput Biol Med 2018; 102: 300-14.
[http://dx.doi.org/10.1016/j.compbiomed.2018.06.025] [PMID: 29980284]
[http://dx.doi.org/10.1016/j.compbiomed.2018.06.025] [PMID: 29980284]
[11]
Al-Toma A, Volta U, Auricchio R, et al. European Society for the Study of Coeliac Disease (ESsCD) guideline for coeliac disease and other gluten-related disorders. United Europ Gastroenterol J 2019; 7(5): 583-613.
[http://dx.doi.org/10.1177/2050640619844125] [PMID: 31210940]
[http://dx.doi.org/10.1177/2050640619844125] [PMID: 31210940]
[12]
Molder A, Balaban DV, Jinga M, Molder CC. Current evidence on computer-aided diagnosis of celiac disease: Systematic review. Front Pharmacol 2020; 11: 341.
[http://dx.doi.org/10.3389/fphar.2020.00341] [PMID: 32372947]
[http://dx.doi.org/10.3389/fphar.2020.00341] [PMID: 32372947]
[13]
Leighton JA, Triester SL, Sharma VK. Capsule endoscopy: a meta-analysis for use with obscure gastrointestinal bleeding and Crohn’s disease. Gastrointest Endosc Clin N Am 2006; 16(2): 229-50.
[http://dx.doi.org/10.1016/j.giec.2006.03.004] [PMID: 16644453]
[http://dx.doi.org/10.1016/j.giec.2006.03.004] [PMID: 16644453]
[14]
Enns RA, Hookey L, Armstrong D, et al. Clinical practice guidelines for the use of video capsule endoscopy. Gastroenterology 2017; 152(3): 497-514.
[http://dx.doi.org/10.1053/j.gastro.2016.12.032] [PMID: 28063287]
[http://dx.doi.org/10.1053/j.gastro.2016.12.032] [PMID: 28063287]
[15]
Delvaux M, Gay G. Capsule endoscopy: Technique and indications. Best Pract Res Clin Gastroenterol 2008; 22(5): 813-37.
[http://dx.doi.org/10.1016/j.bpg.2008.06.003] [PMID: 18790434]
[http://dx.doi.org/10.1016/j.bpg.2008.06.003] [PMID: 18790434]
[16]
Petroniene R, Dubcenco E, Baker JP, et al. Given capsule endoscopy in celiac disease: Evaluation of diagnostic accuracy and interobserver agreement. Am J Gastroenterol 2005; 100(3): 685-94.
[http://dx.doi.org/10.1111/j.1572-0241.2005.41069.x] [PMID: 15743369]
[http://dx.doi.org/10.1111/j.1572-0241.2005.41069.x] [PMID: 15743369]
[17]
Biagi F, Rondonotti E, Campanella J, et al. Video capsule endoscopy and histology for small-bowel mucosa evaluation: A comparison performed by blinded observers. Clin Gastroenterol Hepatol 2006; 4(8): 998-1003.
[http://dx.doi.org/10.1016/j.cgh.2006.04.004] [PMID: 16814612]
[http://dx.doi.org/10.1016/j.cgh.2006.04.004] [PMID: 16814612]
[18]
Rondonotti E, Spada C, Cave D, et al. Video capsule enteroscopy in the diagnosis of celiac disease: A multicenter study. Am J Gastroenterol 2007; 102(8): 1624-31.
[http://dx.doi.org/10.1111/j.1572-0241.2007.01238.x] [PMID: 17459022]
[http://dx.doi.org/10.1111/j.1572-0241.2007.01238.x] [PMID: 17459022]
[19]
Rey J-F, Gay G, Kruse A, Lambert R. European Society of Gastrointestinal Endoscopy guideline for video capsule endoscopy. Endoscopy 2004; 36(7): 656-8.
[http://dx.doi.org/10.1055/s-2004-814557] [PMID: 15243892]
[http://dx.doi.org/10.1055/s-2004-814557] [PMID: 15243892]
[20]
Panescu D. An imaging pill for gastrointestinal endoscopy. IEEE Eng Med Biol Mag 2005; 24(4): 12-4.
[http://dx.doi.org/10.1109/MEMB.2005.1463383] [PMID: 16119206]
[http://dx.doi.org/10.1109/MEMB.2005.1463383] [PMID: 16119206]
[21]
Leonard MM, Silvester JA, Leffler D, et al. Evaluating responses to gluten challenge: A randomized, double-blind, 2-dose gluten challenge trial. Gastroenterology 2021; 160(3): 720-33.e8.
[http://dx.doi.org/10.1053/j.gastro.2020.10.040] [PMID: 33130104]
[http://dx.doi.org/10.1053/j.gastro.2020.10.040] [PMID: 33130104]
[22]
Leffler D, Kupfer SS, Lebwohl B, et al. Development of celiac disease therapeutics: report of the third gastroenterology regulatory endpoints and advancement of therapeutics workshop. Gastroenterology 2016; 151(3): 407-11.
[http://dx.doi.org/10.1053/j.gastro.2016.07.025] [PMID: 27456385]
[http://dx.doi.org/10.1053/j.gastro.2016.07.025] [PMID: 27456385]
[23]
Ding Z, Shi H, Zhang H, et al. Gastroenterologist-level identification of small-bowel diseases and normal variants by capsule endoscopy using a deep-learning model. Gastroenterology 2019; 157(4): 1044-54.
[http://dx.doi.org/10.1053/j.gastro.2019.06.025]
[http://dx.doi.org/10.1053/j.gastro.2019.06.025]
[24]
Byrne MF, Chapados N, Soudan F, et al. Real-time differentiation of adenomatous and hyperplastic diminutive colorectal polyps during analysis of unaltered videos of standard colonoscopy using a deep learning model. Gut 2019; 68(1): 94-100.
[http://dx.doi.org/10.1136/gutjnl-2017-314547] [PMID: 29066576]
[http://dx.doi.org/10.1136/gutjnl-2017-314547] [PMID: 29066576]
[25]
Kudo S, Misawa M, Mori Y, et al. Artificial intelligence-assisted system improves endoscopic identification of colorectal neoplasms. Clin Gastroenterol Hepatol 2020; 18(8): 1874-81.e2.
[http://dx.doi.org/10.1016/j.cgh.2019.09.009] [PMID: 31525512]
[http://dx.doi.org/10.1016/j.cgh.2019.09.009] [PMID: 31525512]
[26]
Kominami Y, Yoshida S, Tanaka S, et al. Computer-aided diagnosis of colorectal polyp histology by using a real-time image recognition system and narrow-band imaging magnifying colonoscopy. Gastrointest Endosc 2016; 83(3): 643-9.
[http://dx.doi.org/10.1016/j.gie.2015.08.004] [PMID: 26264431]
[http://dx.doi.org/10.1016/j.gie.2015.08.004] [PMID: 26264431]
[27]
Zhou T, Han G, Li BN, et al. Quantitative analysis of patients with celiac disease by video capsule endoscopy: A deep learning method. Comput Biol Med 2017; 85: 1-6.
[http://dx.doi.org/10.1016/j.compbiomed.2017.03.031] [PMID: 28412572]
[http://dx.doi.org/10.1016/j.compbiomed.2017.03.031] [PMID: 28412572]
[28]
Siegelman J, Greenblatt E, Galinsky K, et al. A novel ordinal severity scale allows for reproducible assessment of severity of celiac enteropathy by video capsule endoscopy Presented at Digestive Disease Week 2020 (virtual congress) 2020.
[29]
Siegelman J, Lewis S, Feuerstein J, et al. Assessment of celiac disease severity by video capsule endoscopy with the celiac enteropathy-villous atrophy scale (CE-VASt). Presented at the International Celiac Disease Symposium 2019; (P1-19).
[31]
He K, Zhang X, Ren S, Sun J. In Deep residual learning for image recognition, Proceedings of the IEEE conference on computer vision and pattern recognition, 2016; pp 770-78.
[http://dx.doi.org/10.1109/CVPR.2016.90]
[http://dx.doi.org/10.1109/CVPR.2016.90]
[32]
Cullen NC, Avants BB. Convolutional neural networks for rapid and simultaneous brain extraction and tissue segmentation Brain Morphometry. Springer 2018; pp. 13-34.
[http://dx.doi.org/10.1007/978-1-4939-7647-8_2]
[http://dx.doi.org/10.1007/978-1-4939-7647-8_2]
[34]
Krippendorff K. Recent developments in reliability analysis. Departmental Papers. ASC 1992; p. 44.
[35]
Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics 1977; 33(1): 159-74.
[http://dx.doi.org/10.2307/2529310] [PMID: 843571]
[http://dx.doi.org/10.2307/2529310] [PMID: 843571]
[36]
Krippendorff K. Content analysis: An introduction to its methodology; SAGE Publications: NY, USA 2018.
[37]
Koh JEW, Hagiwara Y, Oh SL, et al. Automated diagnosis of celiac disease using DWT and nonlinear features with video capsule endoscopy images. Future Gener Comput Syst 2019; 90: 86-93.
[http://dx.doi.org/10.1016/j.future.2018.07.044]
[http://dx.doi.org/10.1016/j.future.2018.07.044]
[38]
Hamza R, Muhammad K, Lv Z, Titouna F. Secure video summarization framework for personalized wireless capsule endoscopy. Pervasive Mobile Comput 2017; 41: 436-50.
[http://dx.doi.org/10.1016/j.pmcj.2017.03.011]
[http://dx.doi.org/10.1016/j.pmcj.2017.03.011]
[39]
Maiden L, Elliott T, McLaughlin SD, Ciclitira P. A blinded pilot comparison of capsule endoscopy and small bowel histology in unresponsive celiac disease. Dig Dis Sci 2009; 54(6): 1280-3.
[http://dx.doi.org/10.1007/s10620-008-0486-5] [PMID: 18975089]
[http://dx.doi.org/10.1007/s10620-008-0486-5] [PMID: 18975089]
[40]
Spada C, Riccioni ME, Urgesi R, Costamagna G. Capsule endoscopy in celiac disease. World J Gastroenterol 2008; 14(26): 4146-51.
[http://dx.doi.org/10.3748/wjg.14.4146] [PMID: 18636659]
[http://dx.doi.org/10.3748/wjg.14.4146] [PMID: 18636659]
