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Title: Tissue scale agent-based simulation of premalignant progressions in Barrett’s esophagus

Abstract

Barrett’s esophagus (BE) is a benign condition of the distal esophagus that initiates a multistage pathway to esophageal adenocarcinoma (EAC). Short of frequent intrusive (and costly) surveillance, effective screening for neoplasia in BE populations is yet to be established since progressors are rare and virtually undetectable without routine biopsies, which often sample only a small portion of the BE tissue. As a result, reliable estimation of the true prevalence of dysplasia in a BE population and evidence-based optimization of screening for at-risk individuals is challenging. Data-driven microsimulations, i.e., model-generated instances of disease history in a predefined virtual population, have found utility in the EAC screening literature as low-overhead alternatives to real-world hypothesis testing of optimal interventions for dysplasia. Despite the successes, computational limitations, paucity of knowledge and data on Barrett’s dysplasia, and the complexities of disease progression as a multiscale multiphysics process have hindered the treatment of disease progression in BE as a spatial process. Agent-based modeling of nucleation and proliferation processes in dysplasia warrants exploration in this context as an approximation that operates at a trade-off between computational tractability and precise representation of the composition and physics of the substrate (tissue). In this study, we describe spatially resolved simulationsmore » of premalignant progression toward EAC in a coarse-grained model of Barrett’s tissue that resolves the metaplastic tissue at a length scale of 0.42 mm (~3300 crypts/mm2). Finally, the model is calibrated to reproduce historical high-grade dysplasia prevalence when model-generated patients are screened using the Seattle protocol.« less

Authors:
ORCiD logo [1]; ORCiD logo [1];  [2];  [2];  [3]
  1. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
  2. Columbia Univ., New York, NY (United States)
  3. Icahn School of Medicine at Mount Sinai, New York, NY (United States); Massachusetts General Hospital, Boston, MA (United States)
Publication Date:
Research Org.:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Sponsoring Org.:
USDOE; National Institutes of Health (NIH)
OSTI Identifier:
1817610
Grant/Contract Number:  
AC05-00OR22725
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Simulation
Additional Journal Information:
Journal Volume: 98; Journal Issue: 4; Journal ID: ISSN 0037-5497
Publisher:
SAGE
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; agent-based simulation; discrete-event simulation; simulation optimization; sensitivity analysis; Barrett's esophagus

Citation Formats

Ozmen, Ozgur, Nutaro, James J., Ostvar, Sassan, Hur, Chin, and Kong, Chung Yin. Tissue scale agent-based simulation of premalignant progressions in Barrett’s esophagus. United States: N. p., 2021. Web. doi:10.1177/00375497211040074.
Ozmen, Ozgur, Nutaro, James J., Ostvar, Sassan, Hur, Chin, & Kong, Chung Yin. Tissue scale agent-based simulation of premalignant progressions in Barrett’s esophagus. United States. https://doi.org/10.1177/00375497211040074
Ozmen, Ozgur, Nutaro, James J., Ostvar, Sassan, Hur, Chin, and Kong, Chung Yin. 2021. "Tissue scale agent-based simulation of premalignant progressions in Barrett’s esophagus". United States. https://doi.org/10.1177/00375497211040074. https://www.osti.gov/servlets/purl/1817610.
@article{osti_1817610,
title = {Tissue scale agent-based simulation of premalignant progressions in Barrett’s esophagus},
author = {Ozmen, Ozgur and Nutaro, James J. and Ostvar, Sassan and Hur, Chin and Kong, Chung Yin},
abstractNote = {Barrett’s esophagus (BE) is a benign condition of the distal esophagus that initiates a multistage pathway to esophageal adenocarcinoma (EAC). Short of frequent intrusive (and costly) surveillance, effective screening for neoplasia in BE populations is yet to be established since progressors are rare and virtually undetectable without routine biopsies, which often sample only a small portion of the BE tissue. As a result, reliable estimation of the true prevalence of dysplasia in a BE population and evidence-based optimization of screening for at-risk individuals is challenging. Data-driven microsimulations, i.e., model-generated instances of disease history in a predefined virtual population, have found utility in the EAC screening literature as low-overhead alternatives to real-world hypothesis testing of optimal interventions for dysplasia. Despite the successes, computational limitations, paucity of knowledge and data on Barrett’s dysplasia, and the complexities of disease progression as a multiscale multiphysics process have hindered the treatment of disease progression in BE as a spatial process. Agent-based modeling of nucleation and proliferation processes in dysplasia warrants exploration in this context as an approximation that operates at a trade-off between computational tractability and precise representation of the composition and physics of the substrate (tissue). In this study, we describe spatially resolved simulations of premalignant progression toward EAC in a coarse-grained model of Barrett’s tissue that resolves the metaplastic tissue at a length scale of 0.42 mm (~3300 crypts/mm2). Finally, the model is calibrated to reproduce historical high-grade dysplasia prevalence when model-generated patients are screened using the Seattle protocol.},
doi = {10.1177/00375497211040074},
url = {https://www.osti.gov/biblio/1817610}, journal = {Simulation},
issn = {0037-5497},
number = 4,
volume = 98,
place = {United States},
year = {Sat Aug 21 00:00:00 EDT 2021},
month = {Sat Aug 21 00:00:00 EDT 2021}
}

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