Semi-Automated Digital Image Analysis of Pick's Disease and TDP-43 Proteinopathy

J Histochem Cytochem. 2016 Jan;64(1):54-66. doi: 10.1369/0022155415614303. Epub 2015 Nov 4.


Digital image analysis of histology sections provides reliable, high-throughput methods for neuropathological studies but data is scant in frontotemporal lobar degeneration (FTLD), which has an added challenge of study due to morphologically diverse pathologies. Here, we describe a novel method of semi-automated digital image analysis in FTLD subtypes including: Pick's disease (PiD, n=11) with tau-positive intracellular inclusions and neuropil threads, and TDP-43 pathology type C (FTLD-TDPC, n=10), defined by TDP-43-positive aggregates predominantly in large dystrophic neurites. To do this, we examined three FTLD-associated cortical regions: mid-frontal gyrus (MFG), superior temporal gyrus (STG) and anterior cingulate gyrus (ACG) by immunohistochemistry. We used a color deconvolution process to isolate signal from the chromogen and applied both object detection and intensity thresholding algorithms to quantify pathological burden. We found object-detection algorithms had good agreement with gold-standard manual quantification of tau- and TDP-43-positive inclusions. Our sampling method was reliable across three separate investigators and we obtained similar results in a pilot analysis using open-source software. Regional comparisons using these algorithms finds differences in regional anatomic disease burden between PiD and FTLD-TDP not detected using traditional ordinal scale data, suggesting digital image analysis is a powerful tool for clinicopathological studies in morphologically diverse FTLD syndromes.

Keywords: FTLD; Pick’s disease; TDP-43; Tau; digital image analysis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Algorithms
  • Automation*
  • Female
  • Humans
  • Image Processing, Computer-Assisted / methods*
  • Immunohistochemistry / methods*
  • Male
  • Middle Aged
  • Pick Disease of the Brain / metabolism
  • Pick Disease of the Brain / pathology*
  • Software*
  • TDP-43 Proteinopathies / metabolism
  • TDP-43 Proteinopathies / pathology*