Visualizing histopathologic deep learning classification and anomaly detection using nonlinear feature space dimensionality reduction

BackgroundThere is growing interest in utilizing artificial intelligence, and particularly deep learning, for computer vision in histopathology. While accumulating studies highlight expert-level performance of convolutional neural networks (CNNs) on focused classification tasks, most studies rely on probability distribution scores with empirically defined cutoff values based on post-hoc analysis. More generalizable tools that allow humans to visualize histology-based deep learning inferences and decision making are scarce.ResultsHere, we leverage t-distributed Stochastic Neighbor Embedding (t-SNE) to reduce dimensionality and depict how CNNs organize histomorphologic information. Unique to our workflow, we develop a quantitative and transparent approach to visualizing classification decisions prior to softmax compression. By discretizing the relationships between classes on the t-SNE plot, we show we can super-impose randomly sampled regions of test images and use their distribution to render statistically-driven classifications. Therefore, in addition to providing intuitive outputs for human review, this visual approach can carry out automated and objective multi-class classifications similar to more traditional and less-transparent categorical probability distribution scores. Importantly, this novel classification approach is driven by a priori statistically defined cutoffs. It therefore serves as a generalizable classification and anomaly detection tool less reliant on post-hoc tuning.ConclusionRoutine incorporation of this convenient approach for quantitative visualization and error reduction in histopathology aims to accelerate early adoption of CNNs into generalized real-world applications where unanticipated and previously untrained classes are often encountered.

[1]  Elizabeth Gibney,et al.  Google AI algorithm masters ancient game of Go , 2016, Nature.

[2]  R. Nakhleh Role of Informatics in Patient Safety and Quality Assurance. , 2015, Surgical pathology clinics.

[3]  Adrien Depeursinge,et al.  Automated classification of brain tumor type in whole-slide digital pathology images using local representative tiles , 2016, Medical Image Anal..

[4]  Robert P. W. Duin,et al.  Approximating the multiclass ROC by pairwise analysis , 2007, Pattern Recognit. Lett..

[5]  Andrew R. Jamieson,et al.  Exploring nonlinear feature space dimension reduction and data representation in breast Cadx with Laplacian eigenmaps and t-SNE. , 2009, Medical physics.

[6]  Demis Hassabis,et al.  Mastering the game of Go with deep neural networks and tree search , 2016, Nature.

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

[8]  Mehrdad Nourani,et al.  Nonlinear dimension reduction for EEG-based epileptic seizure detection , 2016, 2016 IEEE-EMBS International Conference on Biomedical and Health Informatics (BHI).

[9]  Raouf E Nakhleh,et al.  Patient safety and error reduction in surgical pathology. , 2008, Archives of pathology & laboratory medicine.

[10]  K. Aldape,et al.  Precision histology: how deep learning is poised to revitalize histomorphology for personalized cancer care , 2017, npj Precision Oncology.

[11]  Andrew Zisserman,et al.  Very Deep Convolutional Networks for Large-Scale Image Recognition , 2014, ICLR.

[12]  B. van Ginneken,et al.  Deep learning as a tool for increased accuracy and efficiency of histopathological diagnosis , 2016, Scientific Reports.

[13]  Geoffrey E. Hinton,et al.  Visualizing Data using t-SNE , 2008 .

[14]  J. Barnholtz-Sloan,et al.  CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007-2011. , 2012, Neuro-oncology.

[15]  G. Reifenberger,et al.  The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary , 2016, Acta Neuropathologica.

[16]  Paulo E. Rauber,et al.  Visualizing the Hidden Activity of Artificial Neural Networks , 2017, IEEE Transactions on Visualization and Computer Graphics.

[17]  Aleksey Boyko,et al.  Detecting Cancer Metastases on Gigapixel Pathology Images , 2017, ArXiv.

[18]  Izhar Wallach,et al.  The protein-small-molecule database, a non-redundant structural resource for the analysis of protein-ligand binding , 2009, Bioinform..

[19]  Zhipeng Jia,et al.  Large scale tissue histopathology image classification, segmentation, and visualization via deep convolutional activation features , 2017, BMC Bioinformatics.

[20]  B. Scheithauer,et al.  The 2007 WHO classification of tumours of the central nervous system , 2007, Acta Neuropathologica.

[21]  Angel Cruz-Roa,et al.  Mitosis detection in breast cancer pathology images by combining handcrafted and convolutional neural network features , 2014, Journal of medical imaging.

[22]  Ce Zhang,et al.  Predicting non-small cell lung cancer prognosis by fully automated microscopic pathology image features , 2016, Nature Communications.