Stiffness of the extra cellular matrix (ECM) is recognized as a key regulator of cancer cell proliferation, migration, and invasion. Therefore, technologies that enable non-invasive evaluation of ECM stiffness at cellular scales provide important insights into neoplastic progression. Laser Speckle Microrheology (LSM) is a novel optical tool for measuring tissue stiffness. In LSM, a laser beam illuminates the specimen and fluctuating speckle patterns are captured by a CMOS sensor. Spatio-temporal analysis of speckle intensity yields a map of viscoelastic modulus, G. We validated the accuracy, sensitivity, and dynamic range of LSM by preparing homogeneous gels of assorted viscoelastic properties and comparing LSM measurements with mechanical rheology. To assess the LSM resolution, substrates with micro-scale stiffness patterns were fabricated and tested. Next, we investigated the utility of LSM for mechanical evaluation of the ECM in human breast lesions. Results of phantom studies demonstrated a statistically significant, strong correlation between LSM and rheology (|G|: 30 Pa – 30 kPa, R=0.94, p<5×10-6). Moreover, |G| maps of micro-fabricated phantom, illustrated the capability of LSM in resolving mechanical heterogeneities below 50 µm. Results of tumor tissue measurements, further demonstrated the utility of LSM for micromechanical evaluation of the tumor ECM. To improve the resolution, we developed a novel spatio-temporal analysis of speckle series to obtain multiple sub-pixel shifted maps of the G, and reconstruct a resolution-enhanced |G| map. Studies in micro-fabricated phantoms demonstrated a 5-10 fold resolution enhancement. These results demonstrate competency of the LSM for answering key mechano-biological questions pertinent to caner pathogenies and progression.
Zeinab Hajjarian Kashany and Seemantini K. Nadkarni, "Laser speckle micro-rheology for studying cancer mechanobiology with resolution enhancement (Conference Presentation)," Proc. SPIE 10880, Optical Elastography and Tissue Biomechanics VI, 108800T (Presented at SPIE BiOS: February 03, 2019; Published: 4 March 2019); https://doi.org/10.1117/12.2510355.6008546660001.
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