The stiffness of the extra cellular matrix (ECM) is recognized as a key regulator of cancer cell proliferation, migration and invasion. Therefore technologies that quantify ECM stiffness with micro-scale scale resolution will likely provide important insights into neoplastic progression. Laser Speckle Micro-Rheology (LSM) is a novel optical tool for measuring tissue viscoelastic properties with micro-scale resolution. In LSM, speckle images are collected through an objective lens by a high-speed camera. Spatio-temporal correlation analysis of speckle frames yields the intensity autocorrelation function, g2(t), for each pixel, and subsequently a 2D map of viscoelastic modulus, G*(ω) is reconstructed. Here, we investigate the utility of LSM for micro-mechanical evaluation of the ECM in human breast lesions. Specimens collected 18 women undergoing lumpectomy or mastectomy were evaluated with LSM. Because collagen is the key protein associated with ECM stiffness, G*(ω) maps obtained from LSM were compared with collagen content measured by second harmonic generation (SHG) microscopy. Regions of low G*(ω), identified by LSM, corresponded to low-intensity SHG signal and adipose tissue. Likewise, regions with high G*(ω) in LSM images matched high intensity SHG signal caused by desmoplastic collagen accumulation. Quantitative regression analysis demonstrated a strong, statistically significant correlation between G*(ω) and SHG signal intensity (R=0.66 p< 0.01). These findings highlight the capability of LSM for quantifying the ECM micro-mechanics, potentially providing important insights into the biomechanical regulators of breast cancer progression.
Zeinab Hajjarian Kashany and Seemantini K. Nadkarni, "Laser speckle micro-rheology for biomechanical evaluation of breast tumors
(Conference Presentation)," Proc. SPIE 9710, Optical Elastography and Tissue Biomechanics III, 971008 (Presented at SPIE BiOS: February 13, 2016; Published: 27 April 2016); https://doi.org/10.1117/12.2213804.4848767196001.
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