Constrained Multiple Instance Learning for Ulcerative Colitis prediction using Histological Images

Journal article


del Amor, R., Meseguera, P., Parigi, T.L., Villanacci, V., Colomer, A., Launet, L., Bazarova, A., Tontini, G.E., Bisschops, R., de Hertogh, G., Ferraz, J.G., Götz, M., Gui, Xi., Hayeem, B., Lazarev, M., Panaccione, R., Parra-Blanco, A., Bhandari, P., Pastorelli, L., Rath, T., Synnøve Røyset, E., Vieth, M., Zardo, D., Grisan, E., Ghosh, S., Iacucci, M. and Naranjo, V. (2022). Constrained Multiple Instance Learning for Ulcerative Colitis prediction using Histological Images. Computer methods and programs in biomedicine. 224, p. 107012. https://doi.org/10.1016/j.cmpb.2022.107012
Authorsdel Amor, R., Meseguera, P., Parigi, T.L., Villanacci, V., Colomer, A., Launet, L., Bazarova, A., Tontini, G.E., Bisschops, R., de Hertogh, G., Ferraz, J.G., Götz, M., Gui, Xi., Hayeem, B., Lazarev, M., Panaccione, R., Parra-Blanco, A., Bhandari, P., Pastorelli, L., Rath, T., Synnøve Røyset, E., Vieth, M., Zardo, D., Grisan, E., Ghosh, S., Iacucci, M. and Naranjo, V.
Abstract

Background and Objective: Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) affecting the colon and the rectum characterized by a remitting-relapsing course. To detect mucosal inflammation associated with UC, histology is considered the most stringent criteria. In turn, histologic
remission (HR) correlates with improved clinical outcomes and has been recently recognized as a desirable treatment target. The leading biomarker for assessing histologic remission is the presence or absence of neutrophils. Therefore, the finding of this cell in specific colon structures indicates that the patient has UC activity. However, no previous studies based on deep learning have been developed
to identify UC based on neutrophils detection using whole-slide images (WSI).
Methods: The methodological core of this work is a novel multiple instance learning (MIL) framework with location constraints able to determine the presence of UC activity using WSI.
In particular, we put forward an effective way to introduce constraints about positive instances to effectively explore additional weakly supervised information that is easy to obtain and enjoy a significant boost to the learning process. In addition, we propose a new weighted embedding to enlarge
the relevance of the positive instances.
Results: Extensive experiments on a multi-center dataset of colon and rectum WSIs, PICASSO-MIL, demonstrate that using the location information we can improve considerably the results at WSI-level.
In comparison with prior MIL settings, our method allows for 10% improvements in bag-level accuracy.
Conclusion: Our model, which introduces a new form of constraints, surpass the results achieved from current state-of-the-art methods that focus on the MIL paradigm. Our method can be applied to other histological concerns where the morphological features determining a positiveWSI are tiny and
similar to others in the image.

KeywordsHistologic remission; Location Constraints; Neutrophils ; Attention-embedding weights; Ulcerative Colitis
Year2022
JournalComputer methods and programs in biomedicine
Journal citation224, p. 107012
PublisherElsevier
ISSN0169-2607
Digital Object Identifier (DOI)https://doi.org/10.1016/j.cmpb.2022.107012
Web address (URL)https://www.sciencedirect.com/science/article/abs/pii/S0169260722003947
Publication dates
Print09 Jul 2022
Publication process dates
Accepted06 Jul 2022
Deposited06 Sep 2022
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Grisan, E., Zandon`a, A. and Di Camillo, B. (2019). Deep Convolutional Neural Network for Survival Estimation of Amyotrophic Lateral Sclerosis patients. European Symposium on Artificial Neural Networks, Computational Intelligence and Machine Learning. Bruges, Belgium 24 - 26 Apr 2019 i6doc.
Prediction of Adverse Glycemic Events from Continuous Glucose Monitoring Signal
Gadaleta, M., Facchinetti, A., Grisan, E. and Rossi, M. (2019). Prediction of Adverse Glycemic Events from Continuous Glucose Monitoring Signal. IEEE Journal of Biomedical and Health Informatics. 23 (2). https://doi.org/10.1109/JBHI.2018.2823763
Sparse Image Reconstruction for Contrast Enhanced Cardiac Ultrasound using Diverging Waves
Stanziola, A., Toulemonde, M., Papadopoulou, V., Corbett, R., Duncan, N., Grisan, E. and Tang, M-X. (2019). Sparse Image Reconstruction for Contrast Enhanced Cardiac Ultrasound using Diverging Waves. IEEE International Ultrasonics Symposium 2019. Glasgow 09 2009 - 06 Oct 2019 Institute of Electrical and Electronics Engineers (IEEE).
Super resolution ultrasound image filtering with machine learning to reduce the localization error
Harput, S., Fong, L.H., Stanziola, A., Zhang, G., Toulemonde, M., Zhou, J., Christensen-Jeffries, K., Brown, J., Eckersley, R., Grisan, E., Dunsby, C. and Tang, M. (2019). Super resolution ultrasound image filtering with machine learning to reduce the localization error. IEEE International Ultrasonics Symposium 2019. Glasgow 09 2009 - 06 Oct 2019 Institute of Electrical and Electronics Engineers (IEEE).
Temporal Convolution Networks for Real-Time Abdominal Fetal Aorta Analysis with Ultrasound
Savioli, N., Visentin, S., Cosmi, E., Grisan, E., Lamata, P. and Montana, G. (2018). Temporal Convolution Networks for Real-Time Abdominal Fetal Aorta Analysis with Ultrasound. Artificial Neural Networks and Machine Learning – ICANN 2018. Rhodes, Greece 04 - 07 Oct 2018 Springer. https://doi.org/10.1007/978-3-030-01421-6_15
Quantitative imaging by pixel-based contrast-enhanced ultrasound reveals a linear relationship between synovial vascular perfusion and the recruitment of pathogenic IL-17A-F+IL-23+ CD161+ CD4+ T helper cells in psoriatic arthritis joints
Fiocco, U, Stramare, R, Martini, V, Coran, A, Caso, F, Costa, L, Felicetti, M, Rizzo, G, Tonietto, M, Scanu, A, Oliviero, F, Raffeiner, B, Vezzù, M, Lunardi, F, Scarpa, R, Sacerdoti, D, Rubaltelli, L, Punzi, L, Doria, A and Grisan, E (2017). Quantitative imaging by pixel-based contrast-enhanced ultrasound reveals a linear relationship between synovial vascular perfusion and the recruitment of pathogenic IL-17A-F+IL-23+ CD161+ CD4+ T helper cells in psoriatic arthritis joints. Clinical Rheumatology. 36 (2), pp. 391-399. https://doi.org/10.1007/s10067-016-3500-x
Boosting the Battery Life of Wearables for Health Monitoring Through the Compression of Biosignals
Hooshmand, M, Zordan, D, Del Testa, D, Grisan, E and Rossi, M (2017). Boosting the Battery Life of Wearables for Health Monitoring Through the Compression of Biosignals. IEEE Internet of Things Journal. 4, pp. 1647-1662. https://doi.org/10.1109/JIOT.2017.2689164
Detection of a slow-flow component in contrast-enhanced ultrasound of the synovia for the differential diagnosis of arthritis
Rizzo, G, Tonietto, M, Castellaro, M, Raffeiner, B, Coran, A, Fiocco, U, Stramare, R and Grisan, E (2017). Detection of a slow-flow component in contrast-enhanced ultrasound of the synovia for the differential diagnosis of arthritis. SPIE Medical Imaging. Orlando, FL, USA 11 - 16 Feb 2017 SPIE. https://doi.org/10.1117/12.2250818
Improving the quantification of contrast enhanced ultrasound using a Bayesian approach
Rizzo, G, Tonietto, M, Castellaro, M, Raffeiner, B, Coran, A, Fiocco, U, Stramare, R and Grisan, E (2017). Improving the quantification of contrast enhanced ultrasound using a Bayesian approach. SPIE Medical Imaging. Orlando, FL , USA 16 2016 - 11 Feb 2017 SPIE. https://doi.org/10.1117/12.2250195
Superpixel-based classification of gastric chromoendoscopy images
Boschetto, D and Grisan, E (2017). Superpixel-based classification of gastric chromoendoscopy images. SPIE Medical Imaging. Orlando, FL, USA 11 - 16 Feb 2017 SPIE. https://doi.org/10.1117/12.2254187
Boosted learned kernels for data-driven vesselness measure
Grisan, E (2017). Boosted learned kernels for data-driven vesselness measure. Proceedings Volume 10137, Medical Imaging 2017: Biomedical Applications in Molecular, Structural, and Functional Imaging; 101370Z (2017). Orlando, FL, USA 11 - 16 Feb 2017 SPIE. https://doi.org/10.1117/12.2250370
Cortical Thickness variability in Multiple Sclerosis: The role of lesion segmentation and filling
Palombit, A, Castellaro, M, Calabrese, M, Romualdi, C, Pizzini, FB, Montemezzi, S, Grisan, E and Bertoldo, A (2017). Cortical Thickness variability in Multiple Sclerosis: The role of lesion segmentation and filling. 2017 IEEE 14th International Symposium on Biomedical Imaging (ISBI 2017). Melbourne, VIC, Australia 18 - 21 Apr 2017 pp. 792-795 https://doi.org/10.1109/ISBI.2017.7950637
From macro to nano: Linking quantitative CEUS perfusion parameters to CD4+ T cells subtypes in spondyloarthtitis
Grisan, E, Rizzo, G, Tonietto, M, Coran, A, Raffeiner, B, Scanu, A, Martini, V, Stramare, R and Fiocco, U (2017). From macro to nano: Linking quantitative CEUS perfusion parameters to CD4+ T cells subtypes in spondyloarthtitis. 2017 IEEE 14th International Symposium on Biomedical Imaging (ISBI 2017). Melbourne, VIC, Australia 17 - 21 Apr 2017 Institute of Electrical and Electronics Engineers (IEEE). pp. 899-902 https://doi.org/10.1109/ISBI.2017.7950661
Grade and location of power doppler are predictive of damage progression in rheumatoid arthritis patients in clinical remission by anti-tumour necrosis factor α
Raffeiner, B, Grisan, E, Botsios, C, Stramare, R, Rizzo, G, Bernardi, L, Punzi, L, Ometto, F and Doria, A (2017). Grade and location of power doppler are predictive of damage progression in rheumatoid arthritis patients in clinical remission by anti-tumour necrosis factor α. Rheumatology (United Kingdom). 56, pp. 1320-1325. https://doi.org/10.1093/rheumatology/kex084
Bayesian Quantification of Contrast-Enhanced Ultrasound Images with Adaptive Inclusion of an Irreversible Component
Rizzo, G, Tonietto, M, Castellaro, M, Raffeiner, B, Coran, A, Fiocco, U, Stramare, R and Grisan, E (2017). Bayesian Quantification of Contrast-Enhanced Ultrasound Images with Adaptive Inclusion of an Irreversible Component. IEEE Transactions on Medical Imaging. 36, pp. 1027-1036. https://doi.org/10.1109/TMI.2016.2637698
Tcf7l2 plays pleiotropic roles in the control of glucose homeostasis, pancreas morphology, vascularization and regeneration
Facchinello, N, Tarifeño-Saldivia, E, Grisan, E, Schiavone, M, Peron, M, Mongera, A, Ek, O, Schmitner, N, Meyer, D, Peers, B, Tiso, N and Argenton, F (2017). Tcf7l2 plays pleiotropic roles in the control of glucose homeostasis, pancreas morphology, vascularization and regeneration. Scientific Reports. 7. https://doi.org/10.1038/s41598-017-09867-x
Growth abnormalities of fetuses and infants
Cosmi, E, Grisan, E, Fanos, V, Rizzo, G, Sivanandam, S and Visentin, S (2017). Growth abnormalities of fetuses and infants. BioMed Research International. 2017. https://doi.org/https://www.doi.org/10.1155/2017/3191308
A possible new approach in the prediction of late gestational hypertension: The role of the fetal aortic intima-media thickness
Visentin, S, Londero, AP, Camerin, M, Grisan, E and Cosmi, E (2017). A possible new approach in the prediction of late gestational hypertension: The role of the fetal aortic intima-media thickness. Medicine (United States). 96. https://doi.org/https://www.doi.org/10.1097/MD.0000000000005515
Automatic classification of small bowel mucosa alterations in celiac disease for confocal laser endomicroscopy
Boschetto, D, Di Claudio, G, Mirzaei, H, Leong, R and Grisan, E (2016). Automatic classification of small bowel mucosa alterations in celiac disease for confocal laser endomicroscopy. Medical Imaging 2016: Biomedical Applications in Molecular, Structural, and Functional Imaging. San Diego, United States 27 Feb - 03 Mar 2016 SPIE. https://doi.org/10.1117/12.2217183
Automatic classification of endoscopic images for premalignant conditions of the esophagus
Boschetto, D, Gambaretto, G and Grisan, E (2016). Automatic classification of endoscopic images for premalignant conditions of the esophagus. Medical Imaging 2016: Biomedical Applications in Molecular, Structural, and Functional Imaging. San Diego, United States 27 Feb - 03 Mar 2016 https://doi.org/10.1117/12.2216826
Superpixel-based automatic segmentation of villi in confocal endomicroscopy
Boschetto, D, Mirzaei, H, Leong, RWL and Grisan, E (2016). Superpixel-based automatic segmentation of villi in confocal endomicroscopy. 2016 IEEE-EMBS International Conference on Biomedical and Health Informatics (BHI). Las Vegas, NV, USA 24 - 27 Feb 2016 pp. 168-171 https://doi.org/10.1109/BHI.2016.7455861
Quantification of kidneys from 3D ultrasound in pediatric hydronephrosis
Cerrolaza, J.J., Grisan, E., Safdar, N., Myers, E., Jago, J., Peters, C.A. and Linguraru, M.G. (2015). Quantification of kidneys from 3D ultrasound in pediatric hydronephrosis. Institute of Electrical and Electronics Engineers (IEEE). https://doi.org/10.1109/embc.2015.7318324