Abstract
It is widely accepted that accurate mechanical properties of three-dimensional soft tissues and cellular samples are not available on the microscale. Current methods based on optical coherence elastography can measure displacements at the necessary resolution, and over the volumes required for this task. However, in converting this data to maps of elastic properties, they often impose assumptions regarding homogeneity in stress or elastic properties that are violated in most realistic scenarios. Here, we introduce novel, rigorous, and computationally efficient inverse problem techniques that do not make these assumptions, to realize quantitative volumetric elasticity imaging on the microscale. Specifically, we iteratively solve the three-dimensional elasticity inverse problem using displacement maps obtained from compression optical coherence elastography. This is made computationally feasible with adaptive mesh refinement and domain decomposition methods. By employing a transparent, compliant surface layer with known shear modulus as a reference for the measurement, absolute shear modulus values are produced within a millimeter-scale sample volume. We demonstrate the method on phantoms, on a breast cancer sample ex vivo, and on human skin in vivo. Quantitative elastography on this length scale will find wide application in cell biology, tissue engineering and medicine.
Highlights
Measuring the mechanical properties of a biological sample, from the sub-cellular [1] to the whole-organ scale [2], has proven useful in a variety of ways
We demonstrate our method in the context of compression optical coherence elastography (OCE) [16,17,18], in which the whole field of view being imaged undergoes quasi-static compression, and phasesensitive optical coherence tomography (OCT) is used to determine the resulting displacement field along the optical axis
The primary purpose of this figure is to assess the performance of the reconstruction method on a sample whose mechanical properties have been measured through a standard compression test performed on a custom-built rig
Summary
Measuring the mechanical properties of a biological sample, from the sub-cellular [1] to the whole-organ scale [2], has proven useful in a variety of ways. Some of this data has previously been published based on the algebraic method [18]. In this case, depicted, the pixels corresponding to regions of negative modulus are masked in yellow in the elastogram [18] This problem is not present in the iterative method, where the shear modulus parameter is constrained to remain positive throughout the domain leading to a more accurate representation of the elasticity This problem is not present in the iterative method, where the shear modulus parameter is constrained to remain positive throughout the domain leading to a more accurate representation of the elasticity (Figs. 3(d))
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