Understanding Ductal Carcinoma in Situ Invasion using a Multiscale Agent-Based Model

D. Joseph Butner, Vittorio Cristini, Zhihui Wang

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Ductal carcinoma in situ (DCIS) is commonly treated clinically through surgical resection. Although surgical options exist for resection, it is unclear which is optimal to reduce the likelihood of future invasive disease. This is further complicated by challenges in determining correct surgical margins from disease diagnostics, with mammographic imaging misidentifying surgical margins by as much as 2 cm vs. histological examination. We have implemented a threedimensional, hybrid multiscale model of DCIS to study disease initiation and progression. In order to shed new light on current biological questions and clinical challenges surrounding the disease, we present here an improved version of this model, with more biologically relevant molecular signaling pathways, cell phenotype hierarchies, and duct architecture variation. In particular, a cell necrosis, lysis and calcification pathway has been incorporated into the model to help better understand the relationship between diagnostic imaging and the true extent of disease invasion. We observe that deficiencies in availability of molecular signaling molecules that upregulate cell proliferation may be overcome by dynamic shifts in phenotypic distributions within the disease mass. Hypoxia, necrosis, and calcification together functioned as a hypoxia relief mechanism, and were observed to maintain a consistent distance between the DCIS leading edge and the site of necrosis onset, providing insights for improving surgical margins.

Original languageEnglish (US)
Title of host publication40th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBC 2018
PublisherInstitute of Electrical and Electronics Engineers Inc.
Pages5846-5849
Number of pages4
ISBN (Electronic)9781538636466
DOIs
StatePublished - Oct 26 2018
Event40th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBC 2018 - Honolulu, United States
Duration: Jul 18 2018Jul 21 2018

Publication series

NameProceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS
Volume2018-July
ISSN (Print)1557-170X

Other

Other40th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBC 2018
CountryUnited States
CityHonolulu
Period7/18/187/21/18

ASJC Scopus subject areas

  • Signal Processing
  • Biomedical Engineering
  • Computer Vision and Pattern Recognition
  • Health Informatics

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