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An End-to-end System for Automatic Characterization of Iba1 Immunopositive Microglia in Whole Slide Imaging

  • Alexander D. Kyriazis
  • Shahriar Noroozizadeh
  • Amir Refaee
  • Woongcheol Choi
  • Lap-Tak Chu
  • Asma Bashir
  • Wai Hang Cheng
  • Rachel Zhao
  • Dhananjay R. Namjoshi
  • Septimiu E. Salcudean
  • Cheryl L. Wellington
  • Guy Nir
Original Article

Abstract

Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide. Detailed studies of the microglial response after TBI require high throughput quantification of changes in microglial count and morphology in histological sections throughout the brain. In this paper, we present a fully automated end-to-end system that is capable of assessing microglial activation in white matter regions on whole slide images of Iba1 stained sections. Our approach involves the division of the full brain slides into smaller image patches that are subsequently automatically classified into white and grey matter sections. On the patches classified as white matter, we jointly apply functional minimization methods and deep learning classification to identify Iba1-immunopositive microglia. Detected cells are then automatically traced to preserve their complex branching structure after which fractal analysis is applied to determine the activation states of the cells. The resulting system detects white matter regions with 84% accuracy, detects microglia with a performance level of 0.70 (F1 score, the harmonic mean of precision and sensitivity) and performs binary microglia morphology classification with a 70% accuracy. This automated pipeline performs these analyses at a 20-fold increase in speed when compared to a human pathologist. Moreover, we have demonstrated robustness to variations in stain intensity common for Iba1 immunostaining. A preliminary analysis was conducted that indicated that this pipeline can identify differences in microglia response due to TBI. An automated solution to microglia cell analysis can greatly increase standardized analysis of brain slides, allowing pathologists and neuroscientists to focus on characterizing the associated underlying diseases and injuries.

Keywords

Computer-aided detection and diagnosis Whole slide imaging Digital pathology Image analysis Classification Traumatic brain injury 

Notes

Acknowledgements

This work was supported in part by funding from Natural Sciences and Engineering Research Council of Canada (NSERC), Canadian Institutes of Health Research (CIHR), the BC Innovation Council NRAS Program, and the Weston Brain Institute. Support from Professor Salcudean’s C. A. Laszlo Chair is gratefully acknowledged. Dr. Nir is a recipient of a Prostate Cancer Canada Post-Doctoral Research Fellowship Award #PDF2016-1338.

Compliance with Ethical Standards

Ethical Approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

Conflict of interests

The authors declare that they have no conflict of interest.

Information Sharing Statement

The data and source code utilized in this work are available at https://www.frdr.ca/repo/handle/doi:10.20383/101.0120/ and https://github.com/rcldigitalpathology/Brain-Analyzer/, respectively.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Alexander D. Kyriazis
    • 1
  • Shahriar Noroozizadeh
    • 1
  • Amir Refaee
    • 1
  • Woongcheol Choi
    • 1
  • Lap-Tak Chu
    • 1
  • Asma Bashir
    • 2
  • Wai Hang Cheng
    • 2
  • Rachel Zhao
    • 2
  • Dhananjay R. Namjoshi
    • 2
  • Septimiu E. Salcudean
    • 3
  • Cheryl L. Wellington
    • 2
  • Guy Nir
    • 4
  1. 1.Engineering PhysicsUniversity of British ColumbiaVancouverCanada
  2. 2.Department of Pathology and Laboratory MedicineUniversity of British ColumbiaVancouverCanada
  3. 3.Department of Electrical and Computer EngineeringUniversity of British ColumbiaVancouverCanada
  4. 4.Department of Urologic SciencesUniversity of British ColumbiaVancouverCanada

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