Abstract
Elastography, the imaging of elastic properties of soft tissues, is well developed for macroscopic clinical imaging of soft tissues and can provide useful information about various pathological processes which is complementary to that provided by the original modality. Scaling down of this technique should ply the field of cellular biology with valuable information with regard to elastic properties of cells and their environment. This paper evaluates the potential to develop such a tool by modifying a commercial optical coherence tomography (OCT) device to measure the speed of shear waves propagating in a three-dimensional (3D) medium. A needle, embedded in the gel, was excited to vibrate along its long axis and the displacement as a function of time and distance from the needle associated with the resulting shear waves was detected using four M-mode images acquired simultaneously using a commercial four-channel swept-source OCT system. Shear-wave time of arrival (TOA) was detected by tracking the axial OCT-speckle motion using cross-correlation methods. Shear-wave speed was then calculated from inter-channel differences of TOA for a single burst (the relative TOA method) and compared with the shear-wave speed determined from positional differences of TOA for a single channel over multiple bursts (the absolute TOA method). For homogeneous gels the relative method provided shear-wave speed with acceptable precision and accuracy when judged against the expected linear dependence of shear modulus on gelatine concentration (R2 = 0.95) and ultimate resolution capabilities limited by 184μm inter-channel distance. This overall approach shows promise for its eventual provision as a research tool in cancer cell biology. Further work is required to optimize parameters such as vibration frequency, burst length and amplitude, and to assess the lateral and axial resolutions of this type of device as well as to create 3D elastograms.
Highlights
The cellular microenvironment plays a critical role in cancer initiation, progression, and the ability to invade and metastasise [1,2]
Elastography, the imaging of elastic properties of soft tissues, employs an existing imaging modality to derive elasticity information by detecting displacement, strain or shear-wave speed in response to an applied stress and can provide useful information about various pathological processes which is complementary to that provided by the original modality
We report a novel 4-channel technique that was developed to take advantage of the multi-channel feature of the VivoSightTM to measure the difference in time of arrival (TOA) of a single shearwave burst between multiple spatial locations along the direction of propagation, which obviates the need for synchronisation between optical coherence tomography (OCT) data acquisition and shear wave generation
Summary
The cellular microenvironment plays a critical role in cancer initiation, progression, and the ability to invade and metastasise [1,2]. Most of the research and development in the field of elastography has been directed at clinical applications, where the requirement is for non-invasive imaging of the mechanical properties of tissues on a macroscopic scale [8]. Scaling down of elastography methods could provide invaluable information on soft tissue mechanobiology, by facilitating hitherto impossible experiments in living three dimensional (3D) cell cultures or in vivo, to study the relationship between local spatial and temporal variations in ECM stiffness and cellular behaviour. Experiments could be conducted to gain an improved understanding of the manner in which the mechanical properties of tumours and nearby host tissues may be associated with the invasive phenotype of cancer cells, or with cellular response to treatment
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