Automated Diagnosis of Lymphoma with Digital Pathology Images Using Deep Learning

Recent studies have shown promising results in using Deep Learning to detect malignancy in whole slide imaging, however, they were limited to just predicting a positive or negative finding for a specific neoplasm. We attempted to use Deep Learning with a convolutional neural network (CNN) algorithm to build a lymphoma diagnostic model for four diagnostic categories: (1) benign lymph node, (2) diffuse large B-cell lymphoma, (3) Burkitt lymphoma, and (4) small lymphocytic lymphoma. Our software was written in Python language. We obtained digital whole-slide images of Hematoxylin and Eosin stained slides of 128 cases including 32 cases for each diagnostic category. Four sets of 5 representative images, 40x40 pixels in dimension, were taken for each case. A total of 2,560 images were obtained from which 1,856 were used for training, 464 for validation, and 240 for testing. For each test set of 5 images, the predicted diagnosis was combined from the prediction of five images. The test results showed excellent diagnostic accuracy at 95% for image-by-image prediction and at 100% for set-by-set prediction. This preliminary study provided a proof of concept for incorporating automated lymphoma diagnostic screen into future pathology work-flow to augment the pathologists' productivity.

[1]  Lisa Tang,et al.  Deep 3D Convolutional Encoder Networks With Shortcuts for Multiscale Feature Integration Applied to Multiple Sclerosis Lesion Segmentation , 2016, IEEE Transactions on Medical Imaging.

[2]  Christopher Ré,et al.  Learning to Compose Domain-Specific Transformations for Data Augmentation , 2017, NIPS.

[3]  Lukás Burget,et al.  Empirical Evaluation and Combination of Advanced Language Modeling Techniques , 2011, INTERSPEECH.

[4]  Anil K. Jain Fundamentals of Digital Image Processing , 2018, Control of Color Imaging Systems.

[5]  Jason Weston,et al.  Joint Learning of Words and Meaning Representations for Open-Text Semantic Parsing , 2012, AISTATS.

[6]  Andrew Janowczyk,et al.  Deep learning for digital pathology image analysis: A comprehensive tutorial with selected use cases , 2016, Journal of pathology informatics.

[7]  T. Hermanns,et al.  Automated Gleason grading of prostate cancer tissue microarrays via deep learning , 2018, Scientific Reports.

[8]  Berkman Sahiner,et al.  Classification of follicular lymphoma: the effect of computer aid on pathologists grading , 2015, BMC Medical Informatics and Decision Making.

[9]  Yee Whye Teh,et al.  A Fast Learning Algorithm for Deep Belief Nets , 2006, Neural Computation.

[10]  Dong Yu,et al.  Context-Dependent Pre-Trained Deep Neural Networks for Large-Vocabulary Speech Recognition , 2012, IEEE Transactions on Audio, Speech, and Language Processing.

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

[12]  Tara N. Sainath,et al.  Deep Neural Networks for Acoustic Modeling in Speech Recognition: The Shared Views of Four Research Groups , 2012, IEEE Signal Processing Magazine.

[13]  Ronald M. Summers,et al.  Deep Learning in Medical Imaging: Overview and Future Promise of an Exciting New Technique , 2016 .

[14]  Geoffrey E. Hinton,et al.  Phone Recognition with the Mean-Covariance Restricted Boltzmann Machine , 2010, NIPS.

[15]  Lior Shamir,et al.  Automatic Classification of Lymphoma Images With Transform-Based Global Features , 2010, IEEE Transactions on Information Technology in Biomedicine.

[16]  Uri Shaham,et al.  A Deep Learning Approach to Unsupervised Ensemble Learning , 2016, ICML.

[17]  Geoffrey E. Hinton,et al.  ImageNet classification with deep convolutional neural networks , 2012, Commun. ACM.

[18]  Guigang Zhang,et al.  Deep Learning , 2016, Int. J. Semantic Comput..

[19]  John R. Gilbertson,et al.  Whole slide imaging for human epidermal growth factor receptor 2 immunohistochemistry interpretation: Accuracy, Precision, and reproducibility studies for digital manual and paired glass slide manual interpretation , 2015, Journal of pathology informatics.

[20]  François Chollet,et al.  Keras: The Python Deep Learning library , 2018 .

[21]  W Feiden,et al.  Automated nuclear segmentation in the determination of the Ki-67 labeling index in meningiomas. , 2006, Clinical neuropathology.

[22]  Muhammad Imran Razzak,et al.  Deep Learning for Medical Image Processing: Overview, Challenges and Future , 2017, ArXiv.

[23]  A. Madabhushi,et al.  Histopathological Image Analysis: A Review , 2009, IEEE Reviews in Biomedical Engineering.

[24]  Geoffrey E. Hinton,et al.  Acoustic Modeling Using Deep Belief Networks , 2012, IEEE Transactions on Audio, Speech, and Language Processing.

[25]  Ronald M. Summers,et al.  Deep Convolutional Neural Networks for Computer-Aided Detection: CNN Architectures, Dataset Characteristics and Transfer Learning , 2016, IEEE Transactions on Medical Imaging.

[26]  M. Henry,et al.  Automated cellular imaging system III for assessing HER2 status in breast cancer specimens: development of a standardized scoring method that correlates with FISH. , 2009, American journal of clinical pathology.

[27]  Dumitru Erhan,et al.  Going deeper with convolutions , 2014, 2015 IEEE Conference on Computer Vision and Pattern Recognition (CVPR).

[28]  Jeffrey Pennington,et al.  Dynamic Pooling and Unfolding Recursive Autoencoders for Paraphrase Detection , 2011, NIPS.

[29]  S. Swerdlow WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues , 2017 .

[30]  Yoshua Bengio,et al.  Greedy Layer-Wise Training of Deep Networks , 2006, NIPS.

[31]  Dong Yu,et al.  Conversational Speech Transcription Using Context-Dependent Deep Neural Networks , 2012, ICML.

[32]  C. Bellan,et al.  Burkitt lymphoma versus diffuse large B‐cell lymphoma: a practical approach , 2009, Hematological oncology.