title: Semi-Automated Digital Image Analysis of Pick's Disease and TDP-43 Proteinopathy.
abstract: 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.
authors.affiliation: Penn Frontotemporal Degeneration Center, Department of Neurology (DJI, MDB, CTM, FC, MG)
authors.forename: David J
authors.initials: DJ
authors.lastname: Irwin
authors.affiliation: Penn Frontotemporal Degeneration Center, Department of Neurology (DJI, MDB, CTM, FC, MG)
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Byrne
authors.affiliation: Penn Frontotemporal Degeneration Center, Department of Neurology (DJI, MDB, CTM, FC, MG)
authors.forename: Corey T
authors.initials: CT
authors.lastname: McMillan
authors.affiliation: Penn Frontotemporal Degeneration Center, Department of Neurology (DJI, MDB, CTM, FC, MG)
authors.forename: Felicia
authors.initials: F
authors.lastname: Cooper
authors.affiliation: Center for Neurodegenerative Disease Research,Department of Pathology & Laboratory Medicine(DJI, MDB, FC, SEA, EBL, VMVD, VML, JQT)
authors.forename: Steven E
authors.initials: SE
authors.lastname: Arnold
authors.affiliation: Center for Neurodegenerative Disease Research,Department of Pathology & Laboratory Medicine(DJI, MDB, FC, SEA, EBL, VMVD, VML, JQT)
authors.forename: Edward B
authors.initials: EB
authors.lastname: Lee
authors.affiliation: Center for Neurodegenerative Disease Research,Department of Pathology & Laboratory Medicine(DJI, MDB, FC, SEA, EBL, VMVD, VML, JQT)
authors.forename: Vivianna M
authors.initials: VM
authors.lastname: Van Deerlin
authors.affiliation: Department of Biostatistics and Epidemiology ,University of Pennsylvania Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (SXX)
authors.forename: Sharon X
authors.initials: SX
authors.lastname: Xie
authors.affiliation: Center for Neurodegenerative Disease Research,Department of Pathology & Laboratory Medicine(DJI, MDB, FC, SEA, EBL, VMVD, VML, JQT)
authors.forename: Virginia M-Y
authors.initials: VM
authors.lastname: Lee
authors.affiliation: Penn Frontotemporal Degeneration Center, Department of Neurology (DJI, MDB, CTM, FC, MG)
authors.forename: Murray
authors.initials: M
authors.lastname: Grossman
authors.affiliation: Center for Neurodegenerative Disease Research,Department of Pathology & Laboratory Medicine(DJI, MDB, FC, SEA, EBL, VMVD, VML, JQT)
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
mesh_terms: D000368:Aged; D000465:Algorithms; D001331:Automation; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D007150:Immunohistochemistry / Q000379:methods*; D008297:Male; D008875:Middle Aged; D020774:Pick Disease of the Brain / Q000378:metabolism / Q000473:pathology*; D012984:Software; D057177:TDP-43 Proteinopathies / Q000378:metabolism / Q000473:pathology*
keywords: FTLD; Pick’s disease; TDP-43; Tau; digital image analysis