Delineating Corneal Elastic Anisotropy in a Porcine Model Using Noncontact OCT Elastography and Ex Vivo Mechanical Tests

Abstract

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.

Probing elastic anisotropy of human skin in vivo with light using non-contact acoustic micro-tapping OCE and polarization sensitive OCT

“…To generate elastic waves without any contact to the skin surface, we applied an excitation push with acoustic micro-tapping (AμT), a technique using a cylindrically focused, air-coupled ultrasound transducer to induce a localized radiation force at the tissue surface 18 – 21 , 64 , 65 . The AμT transducer effectively applied a line load to the surface over a wide region relative to the propagation distance of interest, resulting in approximately planar elastic waves (normal to the OCT imaging plane).…”

“…Recently, we developed a model of a nearly incompressible transversely isotropic (NITI) medium 20 , opening the way for quantitative evaluation of anisotropic elastic properties in biological tissues. We used the NITI model to quantify corneal elasticity and justified it by direct comparison with mechanical tests 21 .…”

Acoustic micro-tapping optical coherence elastography (AuT-OCE) to quantify biomechanical changes following corneal collagen crosslinking: Ex vivo study

“…Notably, AµT-OCE is the only reported method that can accurately measure both 𝜇 (and therefore 𝐸 = 3𝜇) and 𝐺 simultaneously in a non-invasive, non-contact manner. 41 This is critical for in vivo studies of human corneal physiology and pathophysiology.…”

“…Accounting for cornea collagen microstructure consisting of thin layers (lamellas) primarily oriented in-plane of the stroma, the macroscopic stress-strain relationship in the cornea for small deformations can be described by Hook's law in a NITI material and takes the form (in Voigt notation) 41 :…”

“…𝐺 and 𝜇 represent out-of-plane and in-plane shear moduli, respectively, whose magnitudes were shown to differ in the corneal tissue. Indeed, several studies (including OCE, 28,41 and mechanical testing 30,44,45 ) have reported modulus 𝐺 to be on the order of tens of kPa, whereas modulus 𝜇 -to be on the order of MPa in corneal tissue. 38,41 The in-plane Young's modulus…”