Srilatha Vantipalli

A focused air-pulse system for optical-coherence-tomography-based measurements of tissue elasticity

Accurate non-invasive assessment of tissue elasticity in vivo is required for early diagnostics of many tissue abnormalities. We have developed a focused air-pulse system that produces a low-pressure and short-duration air stream, which can be used to excite transient surface waves (SWs) in soft tissues. System characteristics were studied using a high-resolution analog pressure transducer to describe the excitation pressure. Results indicate that the excitation pressure provided by the air-pulse system can be easily controlled by the air source pressure, the angle of delivery, and the distance between the tissue surface and the port of the air-pulse system. Furthermore, we integrated this focused air-pulse system with phase-sensitive optical coherence tomography (PhS-OCT) to make non-contact measurements of tissue elasticity. The PhS-OCT system is used to assess the group velocity of SW propagation, which can be used to determine Youngs modulus. Pilot experiments were performed on gelatin phantoms with different concentrations (10%, 12% and 14% w/w). The results demonstrate the feasibility of using this focused air-pulse system combined with PhS-OCT to estimate tissue elasticity. This easily controlled non-contact technique is potentially useful to study the biomechanical properties of ocular and other tissues in vivo.

Spatial characterization of corneal biomechanical properties with optical coherence elastography after UV cross-linking

Corneal collagen cross-linking (CXL) is a clinical treatment for keratoconus that structurally reinforces degenerating ocular tissue, thereby limiting disease progression. Clinical outcomes would benefit from noninvasive methods to assess tissue material properties in affected individuals. Regional variations in tissue properties were quantified before and after CXL in rabbit eyes using optical coherence elastography (OCE) imaging. Low-amplitude (<1µm) elastic waves were generated using micro air-pulse stimulation and the resulting wave amplitude and speed were measured using phase-stabilized swept-source OCE. OCE imaging following CXL treatment demonstrates increased corneal stiffness through faster elastic wave propagation speeds and lower wave amplitudes.

Quantitative assessment of corneal viscoelasticity using optical coherence elastography and a modified Rayleigh–Lamb equation

We demonstrate the use of a modified Rayleigh–Lamb frequency equation in conjunction with noncontact optical coherence elastography to quantify the viscoelastic properties of the cornea. Phase velocities of air-pulse-induced elastic waves were extracted by spectral analysis and used for calculating the Young’s moduli of the samples using the Rayleigh–Lamb frequency equation (RLFE). Validation experiments were performed on 2% agar phantoms (n ¼ 3) and then applied to porcine corneas (n ¼ 3) in situ. The Young’s moduli of the porcine corneas were estimated to be ∼60 kPa with a shear viscosity ∼0.33 Pa · s. The results demonstrate that the RLFE is a promising method for noninvasive quantification of the corneal biomechanical properties and may potentially be useful for clinical ophthalmological applications.

Optical coherence elastography assessment of corneal viscoelasticity with a modified Rayleigh-Lamb wave model

The biomechanical properties of the cornea play a critical role in forming vision. Diseases such as keratoconus can structurally degenerate the cornea causing a pathological loss in visual acuity. UV-A/riboflavin corneal collagen crosslinking (CXL) is a clinically available treatment to stiffen the cornea and restore its healthy shape and function. However, current CXL techniques do not account for pre-existing biomechanical properties of the cornea nor the effects of the CXL treatment itself. In addition to the inherent corneal structure, the intraocular pressure (IOP) can also dramatically affect the measured biomechanical properties of the cornea. In this work, we present the details and development of a modified Rayleigh-Lamb frequency equation model for quantifying corneal biomechanical properties. After comparison with finite element modeling, the model was utilized to quantify the viscoelasticity of in situ porcine corneas in the whole eye-globe configuration before and after CXL based on noncontact optical coherence elastography measurements. Moreover, the viscoelasticity of the untreated and CXL-treated eyes was quantified at various IOPs. The results showed that the stiffness of the cornea increased after CXL and that corneal stiffness is close to linear as a function of IOP. These results show that the modified Rayleigh-Lamb wave model can provide an accurate assessment of corneal viscoelasticity, which could be used for customized CXL therapies.

Evaluating the Effects of Riboflavin/UV-A and Rose-Bengal/Green Light Cross-Linking of the Rabbit Cornea by Noncontact Optical Coherence Elastography.

Purpose The purpose of this study was to use noncontact optical coherence elastography (OCE) to evaluate and compare changes in biomechanical properties that occurred in rabbit cornea in situ after corneal collagen cross-linking by either of two techniques: ultraviolet-A (UV-A)/riboflavin or rose-Bengal/green light. Methods Low-amplitude (≤10 μm) elastic waves were induced in mature rabbit corneas by a focused air pulse. Elastic wave propagation was imaged by a phase-stabilized swept source OCE (PhS-SSOCE) system. Corneas were then cross-linked by either of two methods: UV-A/riboflavin (UV-CXL) or rose-Bengal/green light (RGX). Phase velocities of the elastic waves were fitted to a previously developed modified Rayleigh-Lamb frequency equation to obtain the viscoelasticity of the corneas before and after the cross-linking treatments. Micro-scale depth-resolved phase velocity distribution revealed the depth-wise heterogeneity of both cross-linking techniques. Results Under standard treatment settings, UV-CXL significantly increased the stiffness of the corneas by ∼47% (P < 0.05), but RGX did not produce statistically significant increases. The shear viscosities were unaffected by either cross-linking technique. The depth-wise phase velocities showed that UV-CXL affected the anterior ∼34% of the corneas, whereas RGX affected only the anterior ∼16% of the corneas. Conclusions UV-CXL significantly strengthens the cornea, whereas RGX does not, and the effects of cross-linking by UV-CXL reach deeper into the cornea than cross-linking effects of RGX under similar conditions.

Optical coherence elastography for evaluating customized riboflavin/UV-A corneal collagen crosslinking

Abstract. UV-induced collagen cross-linking is a promising treatment for keratoconus that stiffens corneal tissue and prevents further degeneration. Since keratoconus is generally localized, the efficacy of collagen cross-linking (CXL) treatments could be improved by stiffening only the weakened parts of the cornea. Here, we demonstrate that optical coherence elastography (OCE) can spatially resolve transverse variations in corneal stiffness. A short duration (≤1u2009u2009ms) focused air-pulse induced low amplitude (≤10u2009u2009μm) deformations in the samples that were detected using a phase-stabilized optical coherence tomography system. A two-dimensional map of material stiffness was generated by measuring the damped natural frequency (DNF) of the air-pulse induced response at various transverse locations of a heterogeneous phantom mimicking a customized CXL treatment. After validation on the phantoms, similar OCE measurements were made on spatially selective CXL-treated in situ rabbit corneas. The results showed that this technique was able to clearly distinguish the untreated and CXL-treated regions of the cornea, where CXL increased the DNF of the cornea by ∼51%. Due to the noncontact nature and minimal excitation force, this technique may be valuable for in vivo assessments of corneal biomechanical properties.

Analysis of the effect of the fluid-structure interface on elastic wave velocity in cornea-like structures by OCE and FEM

Air-pulse optical coherence elastography (OCE) is a promising technique for quantifying biomechanical properties of the cornea. This technique typically involves imaging and analysis of the propagation of the air-pulse induced elastic waves to reconstruct corneal biomechanical properties using an analytical model. However, the effect of the fluid-structure interface (FSI) at the corneal posterior surface on the elastic wave velocity is not accounted for in many models. In this study, we examined the effect of the FSI with OCE experiments on contact lenses with and without fluid in the posterior gap. Finite element models (FEM), also with and without the FSI, were constructed to simulate the elastic wave propagation based on the OCE measurements. The FEM and OCE results were in good agreement demonstrating the feasibility of the method. To further investigate the effect of the FSI, OCE experiments and subsequent FEM simulations were conducted on in situ rabbit corneas before and after rose bengal/green light corneal collagen cross-linking (RGX). Both the OCE experiments and the FE simulations demonstrated that the FSI significantly reduced the group velocity of the elastic wave, and thus, should be considered when determining corneal biomechanical properties from an appropriate mechanical model. By matching the FEM-calculated velocity to the OCE-measured velocity, the corneal elasticity was quantified. The Youngs modulus of the rabbit cornea before RGX was E??=??65?????10 kPa at a controlled intraocular pressure (IOP) of 15 mmHg. After RGX, the Youngs modulus increased to E??=??102?????7 kPa at the same IOP.

Noncontact Elastic Wave Imaging Optical Coherence Elastography for Evaluating Changes in Corneal Elasticity Due to Crosslinking

The mechanical properties of tissues can provide valuable information about tissue integrity and health and can assist in detecting and monitoring the progression of diseases such as keratoconus. Optical coherence elastography (OCE) is a rapidly emerging technique, which can assess localized mechanical contrast in tissues with micrometer spatial resolution. In this paper, we present a noncontact method of OCE to evaluate the changes in the mechanical properties of the cornea after UV-induced collagen crosslinking. A focused air-pulse induced a low-amplitude (micrometer scale) elastic wave, which then propagated radially and was imaged in three dimensions by a phase-stabilized swept-source optical coherence tomography system. The elastic wave velocity was translated to Youngs modulus in agar phantoms of various concentrations. Additionally, the speed of the elastic wave significantly changed in porcine cornea before and after UV-induced corneal collagen crosslinking (CXL). Moreover, different layers of the cornea, such as the anterior stroma, posterior stroma, and inner region, could be discerned from the phase velocities of the elastic wave. Therefore, because of noncontact excitation and imaging, this method may be useful for in vivo detection of ocular diseases such as keratoconus and evaluation of therapeutic interventions such as CXL.

Influence of corneal hydration on optical coherence elastography

Corneal biomechanical properties are influenced by several factors, including intraocular pressure, corneal thickness, and viscoelastic responses. Corneal thickness is directly proportional to tissue hydration and can influence corneal stiffness, but there is no consensus on the magnitude or direction of this effect. We evaluated the influence of corneal hydration on dynamic surface deformation responses using optical coherence elastography (OCE). Fresh rabbit eyes (n=10) were prepared by removing the corneal epithelium and dropping with 0.9% saline every 5 minutes for 1 hour, followed by 20% dextran solution every 5 minutes for one hour. Corneal thickness was determined from structural OCT imaging and OCE measurements were performed at baseline and every 20 minutes thereafter. Micron-scale deformations were induced at the apex of the corneal tissue using a spatially-focused (150μm) short-duration (<1ms) air-pulse delivery system. These dynamic tissue responses were measured non-invasively with a phase-stabilized swept source OCT system. The tissue surface deformation response (Relaxation Rate: RR) was quantified as the time constant, over which stimulated tissue recovered from the maximum deformation amplitude. Elastic wave group velocity (GV) was also quantified and correlated with change in corneal thickness due to hydration process. Corneal thickness rapidly increased and remained constant following epithelium removal and changed little thereafter. Likewise, corneal stiffness changed little over the first hour and then decreased sharply after Dextran application (thickness: -46% [-315/682 μm]; RR: - 24% [-0.7/2.88 ms-1]; GV: -19% [-0.6/3.2 m/s]). Corneal thickness and corneal stiffness (RR) were well correlated (R2 = .66). Corneal biomechanical properties are highly correlated with tissue hydration over a wide range of corneal thickness and these changes in corneal stiffness are quantifiable using OCE.

Spatial mapping of the biomechanical properties of rabbit cornea after cross-linking using optical coherence elastography

Keratoconus, a structural degeneration of the cornea, is often treated with UV-induced collagen cross-linking (CXL) to increase tissue resistance to further deformation and degeneration. Optimal treatment would be customized to the individual and consider pre-existing biomechanical properties as well as the effects induced by CXL. This requires the capability to noninvasively measure corneal mechanical properties. In this study, we demonstrate the use of phase-stabilized swept source optical coherence elastography (PhS-SSOCE) to assess the relaxation rate of a deformation which was induced by a focused air-pulse in tissue-mimicking gelatin phantoms of various concentration and partially cross-linked rabbit corneas. The temporal relaxation process was utilized to estimate the Young’s modulus from a newly developed model based elasticity reconstruction method. Due to the high spatial sensitivity of PhS-SSOCE, the deformation was only a few microns. The results show that the relaxation process was successfully used to differentiate the untreated (UT) and CXL region of the cornea. The results also indicate that the CXL regions had faster relaxation rates and greater Young’s moduli than the UT regions. Therefore, this method can be used to spatially assess the stiffness of the cornea. This non-contact and noninvasive measurement technique utilizes minimal force for excitation and can be potentially used to study the biomechanical properties of ocular and other sensitive tissues.