Artificial intelligence in neuropathology: deep learning-based assessment of tauopathy.

Journal: Laboratory investigation; a journal of technical methods and pathology
PMID:

Abstract

Accumulation of abnormal tau in neurofibrillary tangles (NFT) occurs in Alzheimer disease (AD) and a spectrum of tauopathies. These tauopathies have diverse and overlapping morphological phenotypes that obscure classification and quantitative assessments. Recently, powerful machine learning-based approaches have emerged, allowing the recognition and quantification of pathological changes from digital images. Here, we applied deep learning to the neuropathological assessment of NFT in postmortem human brain tissue to develop a classifier capable of recognizing and quantifying tau burden. The histopathological material was derived from 22 autopsy brains from patients with tauopathies. We used a custom web-based informatics platform integrated with an in-house information management system to manage whole slide images (WSI) and human expert annotations as ground truth. We utilized fully annotated regions to train a deep learning fully convolutional neural network (FCN) implemented in PyTorch against the human expert annotations. We found that the deep learning framework is capable of identifying and quantifying NFT with a range of staining intensities and diverse morphologies. With our FCN model, we achieved high precision and recall in naive WSI semantic segmentation, correctly identifying tangle objects using a SegNet model trained for 200 epochs. Our FCN is efficient and well suited for the practical application of WSIs with average processing times of 45 min per WSI per GPU, enabling reliable and reproducible large-scale detection of tangles. We measured performance on test data of 50 pre-annotated regions on eight naive WSI across various tauopathies, resulting in the recall, precision, and an F1 score of 0.92, 0.72, and 0.81, respectively. Machine learning is a useful tool for complex pathological assessment of AD and other tauopathies. Using deep learning classifiers, we have the potential to integrate cell- and region-specific annotations with clinical, genetic, and molecular data, providing unbiased data for clinicopathological correlations that will enhance our knowledge of the neurodegeneration.

Authors

  • Maxim Signaevsky
    Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Marcel Prastawa
    Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Kurt Farrell
    Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Nabil Tabish
    Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Elena Baldwin
    Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Natalia Han
    Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Megan A Iida
    Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • John Koll
    Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Clare Bryce
    Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Dushyant Purohit
    Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Vahram Haroutunian
    Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Ann C McKee
    Department of Neurology, Boston University School of Medicine, Boston, MA, 02118, USA.
  • Thor D Stein
    Department of Pathology, Boston University School of Medicine, Boston, MA, 02118, USA.
  • Charles L White
    Neuropathology Laboratory, Department of Pathology, UT Southwestern Medical Center, Dallas, TX, 75390, USA.
  • Jamie Walker
    Neuropathology Laboratory, Department of Pathology, UT Southwestern Medical Center, Dallas, TX, 75390, USA.
  • Timothy E Richardson
    Neuropathology Laboratory, Department of Pathology, UT Southwestern Medical Center, Dallas, TX, 75390, USA.
  • Russell Hanson
    Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Michael J Donovan
    Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Carlos Cordon-Cardo
    Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Jack Zeineh
    Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Gerardo Fernandez
    Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • John F Crary
    Department of Pathology, Nash Family Department of Neuroscience, Department of Artificial Intelligence & Human Health, Neuropathology Brain Bank & Research CoRE, Ronald M. Loeb Center for Alzheimer's Disease, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.