Optical coherence elastography (OCE) can provide clinically valuable information based on local measurements of tissue stiffness. Improved light sources and scanning methods in optical coherence tomography (OCT) have led to rapid growth in systems for high-resolution, quantitative elastography using imaged displacements and strains within soft tissue to infer local mechanical properties. We describe in some detail the physical processes underlying tissue mechanical response based on static and dynamic displacement methods. Namely, the assumptions commonly used to interpret displacement and strain measurements in terms of tissue elasticity for static OCE and propagating wave modes in dynamic OCE are discussed with the ultimate focus on OCT system design for ophthalmic applications. Practical OCT motion-tracking methods used to map tissue elasticity are also presented to fully describe technical developments in OCE, particularly noting those focused on the anterior segment of the eye. Clinical issues and future directions are discussed in the hope that OCE techniques will rapidly move forward to translational studies and clinical applications.

The cornea provides the largest refractive power for the human visual system. Its stiffness, along with intraocular pressure (IOP), are linked to several pathologies, including keratoconus and glaucoma. Although mechanical tests can quantify corneal elasticity ex vivo, they cannot be used clinically. Dynamic optical coherence elastography (OCE), which launches and tracks shear waves to estimate stiffness, provides an attractive non-contact probe of corneal elasticity. To date, however, OCE studies report corneal moduli around tens of kPa, orders-of-magnitude less than those (few MPa) obtained by tensile/inflation testing. This large discrepancy impedes OCE’s clinical adoption. Based on corneal microstructure, we introduce and fully characterize a nearly-incompressible transversely isotropic (NITI) model depicting corneal biomechanics. We show that the cornea must be described by at least two shear moduli, contrary to current single-modulus models, decoupling tensile and shear responses. We measure both as a function of IOP in ex vivo porcine cornea, obtaining values consistent with both tensile and shear tests. At pressures above 30 mmHg, the model begins to fail, consistent with non-linear changes in cornea at high IOP.

Dynamic optical coherence elastography (OCE) tracks elastic wave propagation speed within tissue, enabling quantitative three-dimensional imaging of the elastic modulus. We show that propagating mechanical waves are mode converted at interfaces, creating a finite region on the order of an acoustic wavelength where there is not a simple one-to-one correspondence between wave speed and elastic modulus. Depending on the details of a boundary's geometry and elasticity contrast, highly complex propagating fields produced near the boundary can substantially affect both the spatial resolution and contrast of the elasticity image. We demonstrate boundary effects on Rayleigh waves incident on a vertical boundary between media of different shear moduli. Lateral resolution is defined by the width of the transition zone between two media and is the limit at which a physical inclusion can be detected with full contrast. We experimentally demonstrate results using a spectraldomain OCT system on tissue-mimicking phantoms, which are replicated using numerical simulations. It is shown that the spatial resolution in dynamic OCE is determined by the temporal and spatial characteristics (i.e., bandwidth and spatial pulse width) of the propagating mechanical wave. Thus, mechanical resolution in dynamic OCE inherently differs from the optical resolution of the OCT imaging system.

Collagen organization plays an important role in maintaining structural integrity and determining tissue function. Polarization-sensitive optical coherence tomography (PSOCT) is a promising noninvasive three-dimensional imaging tool for mapping collagen organization in vivo. While PSOCT systems with multiple polarization inputs have demonstrated the ability to visualize depth-resolved collagen organization, systems, which use a single input polarization state have not yet demonstrated sufficient reconstruction quality. Herein we describe a PSOCT based polarization state transmission model that reveals the depth-dependent polarization state evolution of light backscattered within a birefringent sample. Based on this model, we propose a polarization state tracing method that relies on a discrete differential geometric analysis of the evolution of the polarization state in depth along the Poincare sphere for depth-resolved birefringent imaging using only one single input polarization state. We demonstrate the ability of this method to visualize depth-resolved myocardial architecture in both healthy and infarcted rodent hearts (ex vivo) and collagen structures responsible for skin tension lines at various anatomical locations on the face of a healthy human volunteer (in vivo).

Dynamic elastography is an attractive method to evaluate tissue biomechanical properties. Recently, it was extended from US-and MR-based modalities to optical ones, such as optical coherence tomography for three-dimensional (3-D) imaging of propagating mechanical waves in subsurface regions of soft tissues, such as the eye. The measured group velocity is often used to convert wave speed maps into 3-D images of the elastic modulus distribution based on the assumption of bulk shear waves. However, the specific geometry of OCE measurements in bounded materials such as the cornea and skin calls into question elasticity reconstruction assuming a simple relationship between group velocity and shear modulus. We show that in layered media the bulk shear wave assumption results in highly underestimated shear modulus reconstructions and significant structural artifacts in modulus images. We urge the OCE community to be careful in using the group velocity to evaluate tissue elasticity and to focus on developing robust reconstruction methods to accurately reconstruct images of the shear elastic modulus in bounded media.

We describe surface wave propagation in soft elastic media at speeds exceeding the bulk shear wave speed. By linking these waves to the elastodynamic Green's function, we derive a simple relationship to quantify the elasticity of a soft medium from the speed of this supershear evanescent wave (SEW). We experimentally probe SEW propagation in tissue-mimicking phantoms, human cornea ex vivo, and skin in vivo using a high-speed optical coherence elastography system. Measurements confirm the predicted relationship between SEW and bulk shear wave speeds, agreeing well with both theoretical and numerical models. These results suggest that SEW measurements may be a robust method to quantify elasticity in soft media, particularly in complex, bounded materials where dispersive Rayleigh-Lamb modes complicate measurements.

Purpose: To compare noncontact acoustic microtapping (AmT) OCT elastography (OCE) with destructive mechanical tests to confirm corneal elastic anisotropy.Design: Ex vivo laboratory study with noncontact AmT-OCE followed by mechanical rheometry and extensometry.Participants: Inflated cornea of whole-globe porcine eyes (n ¼ 9). Methods: A noncontact AmT transducer was used to launch propagating mechanical waves in the cornea that were imaged with phase-sensitive OCT at physiologically relevant controlled pressures. Reconstruction of both Young's modulus (E) and out-of-plane shear modulus (G) in the cornea from experimental data was performed using a nearly incompressible transversely isotropic (NITI) medium material model assuming spatial isotropy of corneal tensile properties. Corneal samples were excised and parallel plate rheometry was performed to measure shear modulus, G. Corneal samples were then subjected to strip extensometry to measure the Young's modulus, E.Main Outcome Measures: Strong corneal anisotropy was confirmed with both AmT-OCE and mechanical tests, with the Young's (E) and shear (G) moduli differing by more than an order of magnitude. These results show that AmT-OCE can quantify both moduli simultaneously with a noncontact, noninvasive, clinically translatable technique.Results: Mean of the OCE measured moduli were E ¼ 12 AE 5 MPa and G ¼ 31 AE 11 kPa at 5 mmHg and E ¼ 20 AE 9 MPa and G ¼ 61 AE 29 kPa at 20 mmHg. Tensile testing yielded a mean Young's modulus of 1 MPa e 20 MPa over a strain range of 1% to 7%. Shear storage and loss modulus (G 0 /G 00 ) measured with rheometry was approximately 82/13 AE 12/4 kPa at 0.2 Hz and 133/29 AE 16/3 kPa at 16 Hz (0.1% strain).Conclusions: The cornea is confirmed to be a strongly anisotropic elastic material that cannot be characterized with a single elastic modulus. The NITI model is the simplest one that accounts for the cornea's incompressibility and in-plane distribution of lamellae. AmT-OCE has been shown to be the only reported noncontact, noninvasive method to measure both elastic moduli. Submillimeter spatial resolution and near real-time operation can be achieved. Quantifying corneal elasticity in vivo will enable significant innovation in ophthalmology, helping to develop personalized biomechanical models of the eye that can predict response to ophthalmic interventions.

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