Very Deep Convolutional Neural Networks for Morphologic Classification of Erythrocytes.

BACKGROUND Morphologic profiling of the erythrocyte population is a widely used and clinically valuable diagnostic modality, but one that relies on a slow manual process associated with significant labor cost and limited reproducibility. Automated profiling of erythrocytes from digital images by capable machine learning approaches would augment the throughput and value of morphologic analysis. To this end, we sought to evaluate the performance of leading implementation strategies for convolutional neural networks (CNNs) when applied to classification of erythrocytes based on morphology. METHODS Erythrocytes were manually classified into 1 of 10 classes using a custom-developed Web application. Using recent literature to guide architectural considerations for neural network design, we implemented a "very deep" CNN, consisting of >150 layers, with dense shortcut connections. RESULTS The final database comprised 3737 labeled cells. Ensemble model predictions on unseen data demonstrated a harmonic mean of recall and precision metrics of 92.70% and 89.39%, respectively. Of the 748 cells in the test set, 23 misclassification errors were made, with a correct classification frequency of 90.60%, represented as a harmonic mean across the 10 morphologic classes. CONCLUSIONS These findings indicate that erythrocyte morphology profiles could be measured with a high degree of accuracy with "very deep" CNNs. Further, these data support future efforts to expand classes and optimize practical performance in a clinical environment as a prelude to full implementation as a clinical tool.

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

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

[3]  H. Ceelie,et al.  Examination of peripheral blood films using automated microscopy; evaluation of Diffmaster Octavia and Cellavision DM96 , 2006, Journal of Clinical Pathology.

[4]  C Briggs,et al.  Can automated blood film analysis replace the manual differential? An evaluation of the CellaVision DM96 automated image analysis system , 2009, International journal of laboratory hematology.

[5]  P W Barnes,et al.  The international consensus group for hematology review: suggested criteria for action following automated CBC and WBC differential analysis. , 2005, Laboratory hematology : official publication of the International Society for Laboratory Hematology.

[6]  Kilian Q. Weinberger,et al.  Densely Connected Convolutional Networks , 2016, 2017 IEEE Conference on Computer Vision and Pattern Recognition (CVPR).

[7]  Michael S. Bernstein,et al.  ImageNet Large Scale Visual Recognition Challenge , 2014, International Journal of Computer Vision.

[8]  Kent B Lewandrowski,et al.  Performance evaluation of the CellaVision DM96 system: WBC differentials by automated digital image analysis supported by an artificial neural network. , 2005, American journal of clinical pathology.

[9]  H. Robbins A Stochastic Approximation Method , 1951 .

[10]  Forrest N. Iandola,et al.  DenseNet: Implementing Efficient ConvNet Descriptor Pyramids , 2014, ArXiv.

[11]  Quoc V. Le,et al.  On optimization methods for deep learning , 2011, ICML.

[12]  John Salvatier,et al.  Theano: A Python framework for fast computation of mathematical expressions , 2016, ArXiv.

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

[14]  Yoshua Bengio,et al.  Gradient-based learning applied to document recognition , 1998, Proc. IEEE.

[15]  Laura Teodori,et al.  Automated analysis of morphometric parameters for accurate definition of erythrocyte cell shape , 2003, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[16]  C L Rümke,et al.  Imprecision of ratio-derived differential leukocyte counts. , 1985, Blood cells.

[17]  Jürgen Schmidhuber,et al.  Training Very Deep Networks , 2015, NIPS.

[18]  Adrian Holovaty,et al.  The Definitive Guide to Django: Web Development Done Right, Second Edition , 2009 .

[19]  P. Gallagher Red cell membrane disorders. , 2005, Hematology. American Society of Hematology. Education Program.

[20]  Lik Hang Lee,et al.  Performance of the CellaVision® DM96 system for detecting red blood cell morphologic abnormalities , 2015, Journal of pathology informatics.

[21]  J W Bacus,et al.  Image processing for automated erythrocyte classification. , 1976, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[22]  B. Bain,et al.  Diagnosis from the blood smear. , 2005, The New England journal of medicine.

[23]  Yoshua Bengio,et al.  Understanding the difficulty of training deep feedforward neural networks , 2010, AISTATS.

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

[25]  K. Stouten,et al.  Classification of several morphological red blood cell abnormalities by DM96 digital imaging , 2016, International journal of laboratory hematology.

[26]  M L Mendelsohn,et al.  THE ANALYSIS OF CELL IMAGES * , 1966, Annals of the New York Academy of Sciences.

[27]  Yoshua Bengio,et al.  Learning long-term dependencies with gradient descent is difficult , 1994, IEEE Trans. Neural Networks.

[28]  Rümke Cl Statistical reflections on finding atypical cells. , 1985 .

[29]  J. Ford,et al.  Red blood cell morphology , 2013, International journal of laboratory hematology.

[30]  Koepke Ja,et al.  A critical evaluation of the manual/visual differential leukocyte counting method. , 1985 .

[31]  B. Cauwelier,et al.  Evaluation of the Red Blood Cell Advanced Software Application on the CellaVision DM96 , 2016, International journal of laboratory hematology.

[32]  Lik Hang Lee,et al.  Performance of CellaVision DM96 in leukocyte classification , 2013, Journal of pathology informatics.

[33]  Colin Raffel,et al.  Lasagne: First release. , 2015 .