CC BY
9B-I-5
Optical micromechanics using laser speckle approaches
S. Nadkarni1
1Harvard Medical School, Wellman Center for Photomedicine, Boston, USA
It is well recognized that disease progression in most pathological conditions such as atherosclerosis, blood disorders, cancer, and orthopedic diseases is accompanied with alterations in the mechanical properties of affected tissues. For instance, the leading cause of death, myocardial infarction (MI) is caused by rupture of mechanically compromised atherosclerotic plaques. In a variety of clotting disorders that result in hyper- and hypo-coagulable states, coagulations defects are associated with changes in blood clot stiffness. In cancer diagnosis, mechanical cues have long been used to detect tumors by sensing tissue stiffness via palpation of the affected site. At the cellular level, altered mechanical properties of the tumor microenvironment have been shown to regulate malignant transformation and cancer cell proliferation independent of biochemical cues. Therefore, the significant evidence on the role of mechanical factors on disease initiation and progression calls for development of novel technologies for biomechanical evaluation of tissue in situ.
To meet the need for the mechanical analysis of tissue in its native state, we have developed an optical approach termed, Laser Speckle Rheology (LSR). In LSR, the sample is illuminated with coherent light and time-varying laser speckle patterns are acquired using a high speed CMOS camera. Laser speckle that occurs by the interference of coherent light scattered from the sample, is exquisitely sensitive to the passive Brownian motion of light scattering particles, in turn influenced by the viscoelastic susceptibility of the surrounding medium. We have previously shown, using LSR techniques, that the time scale of speckle intensity fluctuations is highly related with the viscoelastic properties of tissue. In this work, we discuss three opportunities for the application of the LSR technology platform for biomedical research and clinical use. In the first study, we discuss the feasibility of conducting LSR to evaluate the mechanical properties of human coronary plaques via a custom-developed, omni-directional viewing catheter suitable for intracoronary use. A second study demonstrates the utility of the LSR approach in detecting blood coagulation defects in patients by evaluating laser speckle patterns of clotting blood and measuring multiple coagulation parameters using a hand-held, smartphone compatible device. In the third case, we will describe an LSR instrument with improved spatial resolution that measures the mechanical properties of the tumor extracellular matrix and the heterogeneity of the invasive front in human breast carcinoma samples.
