Siamese neural networks for continuous disease severity evaluation and change detection in medical imaging

Using medical images to evaluate disease severity and change over time is a routine and important task in clinical decision making. Grading systems are often used, but are unreliable as domain experts disagree on disease severity category thresholds. These discrete categories also do not reflect the underlying continuous spectrum of disease severity. To address these issues, we developed a convolutional Siamese neural network approach to evaluate disease severity at single time points and change between longitudinal patient visits on a continuous spectrum. We demonstrate this in two medical imaging domains: retinopathy of prematurity (ROP) in retinal photographs and osteoarthritis in knee radiographs. Our patient cohorts consist of 4861 images from 870 patients in the Imaging and Informatics in Retinopathy of Prematurity (i-ROP) cohort study and 10,012 images from 3021 patients in the Multicenter Osteoarthritis Study (MOST), both of which feature longitudinal imaging data. Multiple expert clinician raters ranked 100 retinal images and 100 knee radiographs from excluded test sets for severity of ROP and osteoarthritis, respectively. The Siamese neural network output for each image in comparison to a pool of normal reference images correlates with disease severity rank ( ρ  = 0.87 for ROP and ρ  = 0.89 for osteoarthritis), both within and between the clinical grading categories. Thus, this output can represent the continuous spectrum of disease severity at any single time point. The difference in these outputs can be used to show change over time. Alternatively, paired images from the same patient at two time points can be directly compared using the Siamese neural network, resulting in an additional continuous measure of change between images. Importantly, our approach does not require manual localization of the pathology of interest and requires only a binary label for training (same versus different). The location of disease and site of change detected by the algorithm can be visualized using an occlusion sensitivity map-based approach. For a longitudinal binary change detection task, our Siamese neural networks achieve test set receiving operator characteristic area under the curves (AUCs) of up to 0.90 in evaluating ROP or knee osteoarthritis change, depending on the change detection strategy. The overall performance on this binary task is similar compared to a conventional convolutional deep-neural network trained for multi-class classification. Our results demonstrate that convolutional Siamese neural networks can be a powerful tool for evaluating the continuous spectrum of disease severity and change in medical imaging.

[1]  Yann LeCun,et al.  Signature Verification Using A "Siamese" Time Delay Neural Network , 1993, Int. J. Pattern Recognit. Artif. Intell..

[2]  W. Tasman,et al.  Revised indications for the treatment of retinopathy of prematurity: results of the early treatment for retinopathy of prematurity randomized trial. , 2004, Archives of ophthalmology.

[3]  Yann LeCun,et al.  Dimensionality Reduction by Learning an Invariant Mapping , 2006, 2006 IEEE Computer Society Conference on Computer Vision and Pattern Recognition (CVPR'06).

[4]  D. Wallace,et al.  Predictive value of pre-plus disease in retinopathy of prematurity. , 2011, Archives of ophthalmology.

[5]  Rob Fergus,et al.  Visualizing and Understanding Convolutional Networks , 2013, ECCV.

[6]  Michael F. Chiang,et al.  Development and Evaluation of Reference Standards for Image-based Telemedicine Diagnosis and Clinical Research Studies in Ophthalmology , 2014, AMIA.

[7]  Ursula Schmidt-Erfurth,et al.  Inter-expert and intra-expert agreement on the diagnosis and treatment of retinopathy of prematurity. , 2015, American journal of ophthalmology.

[8]  James Philbin,et al.  FaceNet: A unified embedding for face recognition and clustering , 2015, 2015 IEEE Conference on Computer Vision and Pattern Recognition (CVPR).

[9]  Jimmy Ba,et al.  Adam: A Method for Stochastic Optimization , 2014, ICLR.

[10]  Elena Losina,et al.  Reliability and Accuracy of Cross-sectional Radiographic Assessment of Severe Knee Osteoarthritis: Role of Training and Experience , 2016, The Journal of Rheumatology.

[11]  Deniz Erdogmus,et al.  Plus Disease in Retinopathy of Prematurity: A Continuous Spectrum of Vascular Abnormality as a Basis of Diagnostic Variability. , 2016, Ophthalmology.

[12]  Jian Sun,et al.  Deep Residual Learning for Image Recognition , 2015, 2016 IEEE Conference on Computer Vision and Pattern Recognition (CVPR).

[13]  Subhashini Venugopalan,et al.  Development and Validation of a Deep Learning Algorithm for Detection of Diabetic Retinopathy in Retinal Fundus Photographs. , 2016, JAMA.

[14]  Deniz Erdogmus,et al.  Plus Disease in Retinopathy of Prematurity: Improving Diagnosis by Ranking Disease Severity and Using Quantitative Image Analysis. , 2016, Ophthalmology.

[15]  M. D. Kohn,et al.  Classifications in Brief: Kellgren-Lawrence Classification of Osteoarthritis , 2016, Clinical orthopaedics and related research.

[16]  Joseph Antony,et al.  Quantifying radiographic knee osteoarthritis severity using deep convolutional neural networks , 2016, 2016 23rd International Conference on Pattern Recognition (ICPR).

[17]  Simo Saarakkala,et al.  A Novel Method for Automatic Localization of Joint Area on Knee Plain Radiographs , 2017, SCIA.

[18]  Sebastian Thrun,et al.  Dermatologist-level classification of skin cancer with deep neural networks , 2017, Nature.

[19]  Jianliang Xu,et al.  Similarity Measure for Patients via A Siamese CNN Network , 2018, ICA3PP.

[20]  J. Babb,et al.  Discrepancy Rates and Clinical Impact of Imaging Secondary Interpretations: A Systematic Review and Meta-Analysis. , 2018, Journal of the American College of Radiology : JACR.

[21]  M. Mallar Chakravarty,et al.  Modeling and prediction of clinical symptom trajectories in Alzheimer’s disease using longitudinal data , 2018, PLoS Comput. Biol..

[22]  S. García,et al.  A Tutorial on Distance Metric Learning: Mathematical Foundations, Algorithms and Software , 2018, ArXiv.

[23]  Jonathan Krause,et al.  Grader variability and the importance of reference standards for evaluating machine learning models for diabetic retinopathy , 2017, Ophthalmology.

[24]  Simo Saarakkala,et al.  Automatic Knee Osteoarthritis Diagnosis from Plain Radiographs: A Deep Learning-Based Approach , 2017, Scientific Reports.

[25]  James M. Brown,et al.  Automated Diagnosis of Plus Disease in Retinopathy of Prematurity Using Deep Convolutional Neural Networks , 2018, JAMA ophthalmology.

[26]  Stratis Ioannidis,et al.  A Quantitative Severity Scale for Retinopathy of Prematurity Using Deep Learning to Monitor Disease Regression After Treatment. , 2019, JAMA ophthalmology.

[27]  Kaiming He,et al.  Rethinking ImageNet Pre-Training , 2018, 2019 IEEE/CVF International Conference on Computer Vision (ICCV).

[28]  James M. Brown,et al.  Monitoring Disease Progression With a Quantitative Severity Scale for Retinopathy of Prematurity Using Deep Learning. , 2019, JAMA ophthalmology.

[29]  Stratis Ioannidis,et al.  Classification and comparison via neural networks , 2019, Neural Networks.