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Optical micro-mechanical mapping for studying the mechanobiology of breast cancer progression (Conference Presentation)
Author(s): Zeinab Hajjarian Kashany; Elena F. Brachtel; Diane M. Tshikudi; Seemantini K. Nadkarni
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Paper Abstract

Cancerous breast lesions are often stiffer than normal tissue and the stiffening of the tumor extra-cellular matrix (ECM) likely triggers neoplastic progression. Nevertheless, the course of ECM micro-mechanical alteration during cancer progression and its role in tumor aggression remains poorly understood. This is largely due to absence of imaging tool for micro-mechanical mapping of tissue at cellular scales. We have developed a novel optical tool, termed laser speckle microrheology (LSM) for imaging the micro-mechanical properties of tumor ECM. In this approach, tissue is illuminated by a coherent beam and back-scattered speckle patterns are collected by a high-speed camera. Spatio-temporal analysis of speckle fluctuations yields the map of viscoelastic modulus, G. We investigated the relationship between tumor stiffness measured by LSM and known markers of tumor progression, including histopathological grade and lymph-node status. De-identified specimens from 100 patients were evaluated. Analysis of Variance revealed that grades 1 and 2 carcinoma were significantly stiffer than normal fibro-adipose tissue (ḠgradeI = 830 µmPa, ḠgradeII = 715 µmPa, Ḡfibro-adipose = 238 µmPa, pGrade I vs fibroadipose=0.004, pGrade II vs fibroadipose =0.0006). Nevertheless, grade 3 tumors were significantly softer that grade 1 and 2 lesions (ḠgradeIII = 327 µmPa, pGrade I vs III=0.02, p Grade II vs III=0.0057). Moreover, lymph node positive tumors were softer than node negative ones (Ḡln+ = 355 µmPa , Ḡln-= 753 µmPa, p<0.0001). These findings open new avenues for understanding the link between ECM micromechanical properties and tumor progression towards identifying the mechano-biological mediators of malignancy, as potential therapeutic targets.

Paper Details

Date Published: 13 March 2019
Proc. SPIE 10856, Diseases in the Breast and Reproductive System V, 1085608 (13 March 2019); doi: 10.1117/12.2510124
Show Author Affiliations
Zeinab Hajjarian Kashany, Harvard Medical School (United States)
Elena F. Brachtel, Harvard Medical School (United States)
Diane M. Tshikudi, Harvard Medical School (United States)
Seemantini K. Nadkarni, Harvard Medical School (United States)

Published in SPIE Proceedings Vol. 10856:
Diseases in the Breast and Reproductive System V
Melissa C. Skala; Paul J. Campagnola; Darren M. Roblyer, Editor(s)

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