Automatic Cone Photoreceptor Localisation in Healthy and Stargardt Afflicted Retinas Using Deep Learning

We present a robust deep learning framework for the automatic localisation of cone photoreceptor cells in Adaptive Optics Scanning Light Ophthalmoscope (AOSLO) split-detection images. Monitoring cone photoreceptors with AOSLO imaging grants an excellent view into retinal structure and health, provides new perspectives into well known pathologies, and allows clinicians to monitor the effectiveness of experimental treatments. The MultiDimensional Recurrent Neural Network (MDRNN) approach developed in this paper is the first method capable of reliably and automatically identifying cones in both healthy retinas and retinas afflicted with Stargardt disease. Therefore, it represents a leap forward in the computational image processing of AOSLO images, and can provide clinical support in on-going longitudinal studies of disease progression and therapy. We validate our method using images from healthy subjects and subjects with the inherited retinal pathology Stargardt disease, which significantly alters image quality and cone density. We conduct a thorough comparison of our method with current state-of-the-art methods, and demonstrate that the proposed approach is both more accurate and appreciably faster in localizing cones. As further validation to the method’s robustness, we demonstrate it can be successfully applied to images of retinas with pathologies not present in the training data: achromatopsia, and retinitis pigmentosa.

[1]  Xiaogang Wang,et al.  Pyramid Scene Parsing Network , 2016, 2017 IEEE Conference on Computer Vision and Pattern Recognition (CVPR).

[2]  Robert F Cooper,et al.  Fully Automated Estimation of Spacing and Density for Retinal Mosaics , 2019, Translational vision science & technology.

[3]  Sina Farsiu,et al.  RAC-CNN: multimodal deep learning based automatic detection and classification of rod and cone photoreceptors in adaptive optics scanning light ophthalmoscope images. , 2019, Biomedical optics express.

[4]  Bolei Zhou,et al.  Object Detectors Emerge in Deep Scene CNNs , 2014, ICLR.

[5]  Sébastien Ourselin,et al.  Generalised Dice overlap as a deep learning loss function for highly unbalanced segmentations , 2017, DLMIA/ML-CDS@MICCAI.

[6]  Austin Roorda,et al.  Automated identification of cone photoreceptors in adaptive optics retinal images. , 2007, Journal of the Optical Society of America. A, Optics, image science, and vision.

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

[8]  Jürgen Schmidhuber,et al.  Long Short-Term Memory , 1997, Neural Computation.

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

[10]  Hermann Ney,et al.  Handwriting Recognition with Large Multidimensional Long Short-Term Memory Recurrent Neural Networks , 2016, 2016 15th International Conference on Frontiers in Handwriting Recognition (ICFHR).

[11]  Jürgen Schmidhuber,et al.  Multi-dimensional Recurrent Neural Networks , 2007, ICANN.

[12]  Robert F. Cooper,et al.  Photoreceptor-Based Biomarkers in AOSLO Retinal Imaging , 2017, Investigative ophthalmology & visual science.

[13]  Christopher S. Langlo,et al.  In vivo imaging of human cone photoreceptor inner segments. , 2014, Investigative ophthalmology & visual science.

[14]  Zhen Li,et al.  RGB-D Scene Labeling with Long Short-Term Memorized Fusion Model , 2016, ArXiv.

[15]  Christopher S. Langlo,et al.  Repeatability of In Vivo Parafoveal Cone Density and Spacing Measurements , 2012, Optometry and vision science : official publication of the American Academy of Optometry.

[16]  Sina Farsiu,et al.  Automatic detection of cone photoreceptors in split detector adaptive optics scanning light ophthalmoscope images , 2016, Biomedical optics express.

[17]  Jianfei Liu,et al.  Automated Photoreceptor Cell Identification on Nonconfocal Adaptive Optics Images Using Multiscale Circular Voting , 2017, Investigative ophthalmology & visual science.

[18]  Fei Huang,et al.  Brief Introduction of Back Propagation (BP) Neural Network Algorithm and Its Improvement , 2012 .

[19]  David Alonso-Caneiro,et al.  Automatic Detection of Cone Photoreceptors With Fully Convolutional Networks , 2019, Translational vision science & technology.

[20]  Christopher Joseph Pal,et al.  Brain tumor segmentation with Deep Neural Networks , 2015, Medical Image Anal..

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

[22]  Y. Yao,et al.  On Early Stopping in Gradient Descent Learning , 2007 .

[23]  Jürgen Schmidhuber,et al.  Parallel Multi-Dimensional LSTM, With Application to Fast Biomedical Volumetric Image Segmentation , 2015, NIPS.

[24]  Austin Roorda,et al.  Adaptive optics retinal imaging: emerging clinical applications. , 2010, Optometry and vision science : official publication of the American Academy of Optometry.

[25]  A. Dubra,et al.  Reliability and Repeatability of Cone Density Measurements in Patients With Stargardt Disease and RPGR-Associated Retinopathy , 2017, Investigative ophthalmology & visual science.

[26]  Sina Farsiu,et al.  Open source software for automatic detection of cone photoreceptors in adaptive optics ophthalmoscopy using convolutional neural networks , 2017, Scientific Reports.

[27]  Anupam K. Garg,et al.  The reliability of parafoveal cone density measurements , 2014, British Journal of Ophthalmology.

[28]  Razvan Pascanu,et al.  On the difficulty of training recurrent neural networks , 2012, ICML.

[29]  L. R. Dice Measures of the Amount of Ecologic Association Between Species , 1945 .

[30]  Emily J Patterson,et al.  Adaptive optics imaging of inherited retinal diseases , 2017, British Journal of Ophthalmology.

[31]  Trevor Darrell,et al.  Fully Convolutional Networks for Semantic Segmentation , 2017, IEEE Transactions on Pattern Analysis and Machine Intelligence.

[32]  Xiaolin Hu,et al.  Convolutional Neural Networks with Intra-Layer Recurrent Connections for Scene Labeling , 2015, NIPS.

[33]  Rachel E Linderman,et al.  Interocular symmetry, intraobserver repeatability, and interobserver reliability of cone density measurements in the 13-lined ground squirrel , 2019, PloS one.

[34]  Gang Wang,et al.  DAG-Recurrent Neural Networks for Scene Labeling , 2015, 2016 IEEE Conference on Computer Vision and Pattern Recognition (CVPR).

[35]  Tobias Grüning,et al.  Cells in Multidimensional Recurrent Neural Networks , 2016, J. Mach. Learn. Res..

[36]  S. Ourselin,et al.  Unsupervised identification of cone photoreceptors in non-confocal adaptive optics scanning light ophthalmoscope images. , 2017, Biomedical optics express.

[37]  Joseph A. Izatt,et al.  Automatic cone photoreceptor segmentation using graph theory and dynamic programming , 2013, Biomedical optics express.