A deep convolutional neural network approach for astrocyte detection

Astrocytes are involved in various brain pathologies including trauma, stroke, neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases, or chronic pain. Determining cell density in a complex tissue environment in microscopy images and elucidating the temporal characteristics of morphological and biochemical changes is essential to understand the role of astrocytes in physiological and pathological conditions. Nowadays, manual stereological cell counting or semi-automatic segmentation techniques are widely used for the quantitative analysis of microscopy images. Detecting astrocytes automatically is a highly challenging computational task, for which we currently lack efficient image analysis tools. We have developed a fast and fully automated software that assesses the number of astrocytes using Deep Convolutional Neural Networks (DCNN). The method highly outperforms state-of-the-art image analysis and machine learning methods and provides precision comparable to those of human experts. Additionally, the runtime of cell detection is significantly less than that of other three computational methods analysed, and it is faster than human observers by orders of magnitude. We applied our DCNN-based method to examine the number of astrocytes in different brain regions of rats with opioid-induced hyperalgesia/tolerance (OIH/OIT), as morphine tolerance is believed to activate glia. We have demonstrated a strong positive correlation between manual and DCNN-based quantification of astrocytes in rat brain.

[1]  R. Peyron,et al.  Functional imaging of brain responses to pain. A review and meta-analysis (2000) , 2000, Neurophysiologie Clinique/Clinical Neurophysiology.

[2]  Steven A Sloan,et al.  Mechanisms of astrocyte development and their contributions to neurodevelopmental disorders , 2014, Current Opinion in Neurobiology.

[3]  Lawrence D. Jackel,et al.  Handwritten Digit Recognition with a Back-Propagation Network , 1989, NIPS.

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

[5]  Ting Chen,et al.  Deep Learning Based Automatic Immune Cell Detection for Immunohistochemistry Images , 2014, MLMI.

[6]  Andriezen Wl,et al.  The Neuroglia Elements in the Human Brain , 1893 .

[7]  J. Hedreen,et al.  Unbiased stereology? , 1999, Trends in Neurosciences.

[8]  Geoffrey E. Hinton,et al.  Reducing the Dimensionality of Data with Neural Networks , 2006, Science.

[9]  Mikko Airavaara,et al.  Differential Spinal and Supraspinal Activation of Glia in a Rat Model of Morphine Tolerance , 2018, Neuroscience.

[10]  Mi-Ryoung Song,et al.  The complex morphology of reactive astrocytes controlled by fibroblast growth factor signaling , 2014, Glia.

[11]  S. Herculano‐Houzel,et al.  The search for true numbers of neurons and glial cells in the human brain: A review of 150 years of cell counting , 2016, The Journal of comparative neurology.

[12]  Irene Tracey,et al.  The Cerebral Signature for Pain Perception and Its Modulation , 2007, Neuron.

[13]  E. Ullian,et al.  New roles for astrocytes in developing synaptic circuits , 2008, Communicative & integrative biology.

[14]  Nilanjan Ray,et al.  Cell Detection in Microscopy Images with Deep Convolutional Neural Network and Compressed Sensing , 2017 .

[15]  M. Zimmermann,et al.  Ethical guidelines for investigations of experimental pain in conscious animals , 1983, Pain.

[16]  Dong Yu,et al.  Deep Learning: Methods and Applications , 2014, Found. Trends Signal Process..

[17]  Lei Wang,et al.  HEp-2 Cell Image Classification With Deep Convolutional Neural Networks , 2015, IEEE Journal of Biomedical and Health Informatics.

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

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

[20]  Anna-Maija Penttinen,et al.  Characterization of a new low‐dose 6‐hydroxydopamine model of Parkinson's disease in rat , 2016, Journal of neuroscience research.

[21]  K. Zahs,et al.  Confocal microscopic study of glial‐vascular relationships in the retinas of pigmented rats , 2001, The Journal of comparative neurology.

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

[23]  Martin S. Angst,et al.  Opioid-induced Hyperalgesia: A Qualitative Systematic Review , 2006, Anesthesiology.

[24]  Luca Maria Gambardella,et al.  Mitosis Detection in Breast Cancer Histology Images with Deep Neural Networks , 2013, MICCAI.

[25]  B. Weidow,et al.  Enumeration of leukocyte infiltration in solid tumors by confocal laser scanning microscopy , 2006, BMC Immunology.

[26]  Lakhmi C. Jain,et al.  Recurrent Neural Networks: Design and Applications , 1999 .

[27]  Hanchuan Peng,et al.  Bioimage informatics: a new area of engineering biology , 2008, Bioinform..

[28]  Mark R Hutchinson,et al.  The "toll" of opioid-induced glial activation: improving the clinical efficacy of opioids by targeting glia. , 2009, Trends in pharmacological sciences.

[29]  Kevin W Eliceiri,et al.  NIH Image to ImageJ: 25 years of image analysis , 2012, Nature Methods.

[30]  G. Zhang,et al.  Resveratrol reduces morphine tolerance by inhibiting microglial activation via AMPK signalling , 2014, European journal of pain.

[31]  Ullrich Köthe,et al.  Ilastik: Interactive learning and segmentation toolkit , 2011, 2011 IEEE International Symposium on Biomedical Imaging: From Nano to Macro.

[32]  M. Cecchini,et al.  Ultrastructural Characterization of the Lower Motor System in a Mouse Model of Krabbe Disease , 2016, Scientific Reports.

[33]  Zoltan Kato,et al.  Accurate Morphology Preserving Segmentation of Overlapping Cells based on Active Contours , 2016, Scientific Reports.

[34]  Ling Shao,et al.  Deep learning for automatic cell detection in wide-field microscopy zebrafish images , 2015, 2015 IEEE 12th International Symposium on Biomedical Imaging (ISBI).

[35]  Trevor Darrell,et al.  Caffe: Convolutional Architecture for Fast Feature Embedding , 2014, ACM Multimedia.

[36]  Alexei Verkhratsky,et al.  Neuroglia: Definition, Classification, Evolution, Numbers, Development , 2013 .

[37]  W L Andriezen,et al.  The Neuroglia Elements in the Human Brain , 1893, British medical journal.

[38]  Nasir M. Rajpoot,et al.  Locality Sensitive Deep Learning for Detection and Classification of Nuclei in Routine Colon Cancer Histology Images , 2016, IEEE Trans. Medical Imaging.