Optical elastography techniques are rapidly emerging as preferred methods of measuring tissue mechanical properties due to a variety of benefits, such as resolution, speed, and noninvasive imaging. However, there remains a lack of research on the inter-operability of these methods, which makes inter-study and inter-method mechanical comparisons difficult. Therefore, this work aims to compare measurements obtained by various optical coherence elastography (OCE) techniques, Brillouin spectroscopy, and ultrasound-based shear wave elastography (USE) to the gold standard of uniaxial mechanical testing. This study utilized three sets of tissue-mimicking silicone phantoms with varying elasticities. We compared measurements of common optical elastography methods, including air-pulse OCE, aircoupled ultrasound OCE, reverberant OCE, and compression OCE, along with ultrasound elastography and Brillouin spectroscopy. The measurements from these methods were compared to the gold standard of uniaxial mechanical testing. The results of the quasistatic methods, i.e., mechanical testing and compression OCE, showed very good agreement for all three samples. The dynamic wave-based OCE and USE methods also had good inter-agreement, showing the inter-operability of air-pulse, air-coupled, and reverberant OCE and USE. Additionally, Brillouin spectroscopy measurements yielded the Brillouin frequency shift, which was able to discriminate all three sample sets. These results are the first step of a more robust framework for studying the relationship between mechanical measurements performed by various excitation methods.
The purpose of this study is to evaluate the changes in elasticity of the corneo-scleral limbus when the eye-globe is subjected to different intraocular pressures. Continuous elastic waves were mechanically induced in the sclera and imaged using a phase-sensitive optical coherence tomography system. Experimental results showed a marked heterogeneity of wave speed across the corneal-limbal-scleral region, which increased as a function of IOP. The conclusion of this study reveals that the corneo-scleral limbus tissue is more mechanically nonlinear compared to the cornea and sclera. This suggests that limbus acts as a supporting and accommodating mechanical structure for the cornea.
We have designed and developed an air-coupled ultrasonic radiation force probe co-focused with a phase-sensitive optical coherence tomography system (ACUS-OCT). Our custom-made 1 MHz spherically focused piezo-electric transducer with a concentric circular opening of 10 mm diameter allows for the confocal micro-excitation of waves and the spatial (2D, 3D) motion measurement of tissues. Phantom studies demonstrated the capabilities of this probe to produce quasi-harmonic excitation up to 4 kHz for the generation of highly localized elastic waves. Experimental results in ocular tissues showed the highly localized 2D/3D elasticity mapping capabilities of this approach with great potential for clinical translation.
In this study, we propose to measure the spatial deformation spreading (SDS) produced by an air-pulse on the surface of tissues during the near-field regime of propagation as a metric to characterize degree of anisotropy. Experiments in isotropic tissue-mimicking phantoms and anisotropic chicken tibialis muscle were conducted using an optical coherence tomography system synchronized with a confocal air-pulse stimulation. SDS ratio measured along versus across the direction of fibers in chicken muscle agreed with the wave speed ratio taken at the same directions, demonstrating the capabilities of the air-pulse SDS technique in measuring the elastic anisotropy of transverse isotropic tissues.
Optical elastography emerged in the late 1990s as a way to non-invasively assess tissue biomechanical properties (i.e. optical palpation to sense tissue stiffness). Advances in optical engineering, such as optical coherence tomography, were essential to the growth of this field and provided the high-speed, high-resolution imaging required to quantify microscopic tissue deformation dynamics, which can be the basis for distinguishing normal and diseased tissue. This review will cover the development and evolution of optical elastography applications for ocular tissues and discuss the challenges to deploying this technology for clinical use.
Several methods have been proposed to assess changes in corneal biomechanical properties due to various factors, such as degenerative diseases, intraocular pressure, and therapeutic interventions (e.g. corneal collagen crosslinking). However, the effect of the corneal tissue hydration state on corneal stiffness is not well understood. In this work, we induce low amplitude (< 10 μm) elastic waves with a focused micro air-pulse in fresh in situ rabbit corneas (n = 10) in the whole eye-globe configuration at an artificially controlled intraocular pressure. The waves were then detected with a phase-stabilized swept source optical coherence elastography system. Baseline measurements were taken every 20 minutes for an hour while the corneas were hydrated with 1X PBS. After the measurement at 60 minutes, a 20% dextran solution was topically instilled to dehydrate the corneas. The measurements were repeated every 20 minutes again for an hour. The results showed that the elastic wave velocity decreased as the corneal thickness decreased. Finite element modeling (FEM) was performed using the corneal geometry and elastic wave propagation speed to assess the stiffness of the samples. The results show that the stiffness increased from ~430 kPa during hydration with PBS to ~500 kPa after dehydration with dextran, demonstrating that corneal hydration state, apart from geometry and intraocular pressure, can change the stiffness of the cornea.
Screening for ocular diseases, such as glaucoma and keratoconus, includes measuring the eye-globe intraocular pressure (IOP) and corneal biomechanical properties. However, currently available clinical tools cannot quantify corneal tissue material parameters, which can provide critical information for detecting diseases and evaluating therapeutic outcomes. Here, we demonstrate measurement of eye-globe IOP, corneal elasticity, and corneal geometry of in situ porcine corneas with a technique termed applanation optical coherence elastography (Appl-OCE) with single instrument. We utilize an ultrafast phase-sensitive optical coherence tomography system comprised of a 4X buffered Fourier domain mode-locked swept source laser with an Ascan rate of ~1.5 MHz and a 7.3 kHz resonant scanner. The IOP was measured by imaging the response of in situ porcine corneas to a large force air-puff. As with other noncontact tonometers, the time when the cornea was applanated during the inwards and outwards motion was correlated to a measure air-pressure temporal profile. The IOP was also measured with a commercially available rebound tonometer for comparison. The stiffness of the corneas was assessed by directly imaging and analyzing the propagation of a focused micro air-pulse induced elastic wave, and the corneal geometry was obtained from the OCT structural image. Our results show that corneal thickness decreased as IOP increased, and that corneal stiffness increased with IOP. Moreover, the IOP measurements made by Appl-OCE were more closely correlated with the artificially set IOP than the rebound tonometer, demonstrating the capabilities of Appl-OCE to measure corneal stiffness, eye-globe IOP, and corneal geometry with a single instrument.
The collagen fibril orientation of the cornea can provide critical information about cornea tissue health because diseases such as keratoconus and therapeutic interventions such as UV-A/riboflavin corneal collagen crosslinking (CXL) can alter the ultrastructural arrangement of collagen fibrils. Here, we quantify the elastic anisotropy and hysteresis of in situ porcine corneas as a function of intraocular pressure (IOP) with noncontact optical coherence elastography. Moreover, the effects of UV-A riboflavin corneal collagen crosslinking on the elastic anisotropy and hysteresis were evaluated. The propagation of an air-pulse induced elastic wave was imaged at stepped meridional angles by a home built phasestabilized swept source OCE system. The stiffness of the cornea was translated from the velocity of the wave, and the elastic anisotropy was quantified by modifying the planar anisotropy coefficient. As the IOP increased, the stiffness of the corneas increased from ~18 kPa at 15 mmHg IOP to ~ 120 kPa at 30 mmHg IOP. While there was a measureable hysteresis, it was not significant. After CXL, the Young’s modulus of the corneas significantly increased from ~18 kPa to ~44 kPa at 15 mmHg IOP. The mechanical anisotropy also increased significantly from ~10 a.u. in the untreated corneas to ~23 a.u. in the CXL treated corneas, 15 mmHg IOP. However, CXL did not change the elastic anisotropic orientation, and the mechanical anisotropic hysteresis was not significant after CXL.
Current clinical tools provide critical information about ocular health such as intraocular pressure (IOP). However, they lack the ability to quantify tissue material properties, which are potent markers for ocular tissue health and integrity. We describe a single instrument to measure the eye-globe IOP, quantify corneal biomechanical properties, and measure corneal geometry with a technique termed applanation optical coherence elastography (Appl-OCE). An ultrafast OCT system enabled visualization of corneal dynamics during noncontact applanation tonometry and direct measurement of micro air-pulse induced elastic wave propagation. Our preliminary results show that the proposed Appl-OCE system can be used to quantify IOP, corneal biomechanical properties, and corneal geometry, which builds a solid foundation for a unique device that can provide a more complete picture of ocular health.
Diseases such as keratoconus can alter the orientation of collagen fibrils in the cornea. Moreover, therapeutic
interventions such as UV-A/riboflavin corneal collagen crosslinking (CXL) can alter the collagen fibril arrangement.
Therefore, the anisotropic characteristics of the cornea can provide vital information about tissue integrity. In this work,
we utilize noncontact elastic wave imaging optical coherence elastography (EWI-OCE) to assess the elastic anisotropy
and hysteresis of in situ porcine corneas as various intraocular pressures (IOP). In addition, we evaluated the effects of
CXL on the mechanical anisotropy and hysteresis. OCE measurements were made at stepped meridional angles, and a
sliding window algorithm spatially mapped the elasticity. A modified planar anisotropy coefficient was utilized to
quantify the elastic anisotropy of the corneas. The results show that the stiffness and elastic anisotropy of the corneas
were significantly affected by CXL and IOP (P<0.001), but the hysteresis was not significant (P<0.05). Moreover, the
changes in elasticity due to CXL were angle-dependent (P<0.005). However, the changes in mechanical anisotropy from
CXL were not angle-dependent (P>0.05).
UV-A/riboflavin collagen cross-linking (UV-CXL) is a clinical treatment for keratoconus that stiffens mechanically
degraded corneal tissue. On the other hand, the intraocular pressure (IOP) can also affect the measured cornea elasticity.
However, the combined effects of CXL at different IOPs on the corneal biomechanical properties are not well
understood. In this work, the feasibility of assessing the viscoelasticity of the porcine cornea before and after CXL at
various IOPs was investigated by using a noncontact method of optical coherence elastography (OCE) and a modified
Lamb wave model. The modified wave model was first verified by comparison with finite element modeling, and then
utilized to quantify the viscoelasticity of porcine corneas in the whole eye-globe configuration before and after CXL
treatment at various IOPs. The results show that the elasticity of the cornea increased after CXL and that corneal stiffness
was linear as a function of IOP. At IOPs of 15, 20, 25, and 30 mmHg, the relative increase in Young’s modulus after
CXL was ~109%, ~86%, ~64%, and ~79%, respectively, while the shear viscosity decreased by ~86%, ~84%, ~83%,
and ~81%. The modified Lamb wave model and OCE show promise for quantifying corneal viscoelasticity, which could
provide a basis for customized CXL therapies and accurate disease detection.
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 (≤1 ms) focused air-pulse induced low amplitude (≤10 μm) 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.
Wave models, which have been utilized in the past to reconstruct corneal biomechanical properties based on the propagation of an elastic wave, were often developed assuming a thin-plate geometry. However, the curvature and thickness of the cornea are not considered when utilizing these models. In this work, optical coherence elastography (OCE) experiments were conducted on tissue-mimicking agar phantoms and contact lenses along with finite element (FE) modeling of four kinds of cornea-like structures to understand the effects of curvature and thickness on the group velocity of an elastic wave. As the radius of curvature increased from 19.1 to 47.7 mm, the group velocity of the elastic wave obtained by both FE and OCE from a spherical shell section model decreased from ~2.8 m/s to ~2.2 m/s. When the thickness of the agar phantom increased from 1.9 mm to 5.6 mm, the elastic wave velocity increased from ~3.0 m/s to ~4.1 m/s. Both the FE and OCE results show that the group velocity of the elastic wave decreased with radius of curvature but increased with thickness. Therefore, the curvature and thickness must be considered when developing accurate wave models for quantifying biomechanical properties of the cornea.
In this study we have evaluated the elastic anisotropy of porcine corneas with increasing intraocular pressures (IOPs) using a noncontact optical coherence elastography (OCE) technique. A focused air-pulse induced low amplitude (≤10 μm) elastic waves in fresh porcine corneas (n=9) in situ in the whole eye-globe configuration. A phase-stabilized swept source optical coherence elastography (PhS-SSOCE) system imaged the propagation of the elastic wave in different stepped radial directions. A closed-loop feedback system was utilized to artificially manipulate the IOP, and OCE measurements were repeated while the IOP was increased in 5 mmHg increments from 15 to 30 mmHg. The OCE measurements demonstrated that the elastic anisotropy of the cornea became more pronounced at higher IOPs, and that there were distinct radial angles of higher and lower stiffness. The presented noncontact OCE method was capable of detecting and assessing the corneal elastic anisotropy as a function of IOP. Due to the noninvasive nature and small amplitude of the elastic wave, this method may be able to provide additional information about corneal health and integrity in vivo.
The mechanical anisotropic properties of the cornea can be an important indicator for determining the onset and severity
of different diseases and can be used to assess the efficacy of various therapeutic interventions, such as cross-linking and
LASIK surgery. In this work, we introduce a noncontact method of assessing corneal mechanical anisotropy as a
function of intraocular pressure (IOP) using optical coherence elastography (OCE). A focused air-pulse induced low
amplitude (<10 μm) elastic waves in fresh porcine corneas in the whole eye-globe configuration in situ. A phase-stabilized
swept source optical coherence elastography (PhS-SSOCE) system imaged the elastic wave propagation at
stepped radial angles, and the OCE measurements were repeated as the IOP was cycled. The elastic wave velocity was
then quantified to determine the mechanical anisotropy and hysteresis of the cornea. The results show that the elastic
anisotropy at the corneal of the apex of the cornea becomes more pronounced at higher IOPs, and that there are distinct
radial angles of higher and lower stiffness. Due to the noncontact nature and small amplitude of the elastic wave, this
method may be useful for characterizing the elastic anisotropy of ocular and other tissues in vivo completely
noninvasively.
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.
The biomechanical properties of the cornea are critical factors which determine its health and subsequent visual acuity.
Keratoconus is a structural degeneration of the cornea which can diminish vision quality. Riboflavin/UV-A corneal
collagen cross-linking (UV-CXL) is an emerging treatment that increases the stiffness of the cornea and improves its
ability to resist further degeneration. While UV-CXL has shown great promise for effective therapy of the keratoconus,
there are concerns associated with the UV irradiation, such as keratocyte cytotoxicity. Rose-bengal/green light corneal
collagen cross-linking (RGX) has been proposed as an alternative to UV-CXL. Because of the high absorbance of the
rose-bengal dye at green wavelengths, the treatment time is significantly shorter than with UV-CXL. Moreover, because
green light is used in lieu of UV irradiation, there are no cytotoxic side-effects. In this study, noncontact optical
coherence elastography (OCE) was used to compare the outcomes of UV-CXL and RGX treatment in rabbit cornea.
Low-amplitude (micrometer scale) elastic waves were induced by a focused air-pulse loading system. The elastic wave
propagation was then imaged by a phase-stabilized swept source OCE (PhS-SSOCE) system. The changes in the
viscoelasticity of the corneas were quantified by a previously developed modified Rayleigh Lamb frequency model. The
depth-resolved micro-scale phase-velocity distribution in the cornea was used to reveal the depth-wise heterogeneity
before and after both cross-linking techniques. Our results show that UV-CXL and RGX increased the stiffness of the
corneas by ~54% and ~5% while reducing the viscosity by ~42% and ~17%, respectively. The depth-wise phase
velocities showed that UV-CXL affected the anterior ~1/3 of the corneas, while RGX only affected the anterior ~1/7 of
the corneas.
The biomechanical properties of the cornea have a profound influence on its health and function. Rose bengal/green light
corneal collagen cross-linking (RGX) has been proposed as an alternative to UV-A Riboflavin collagen cross-linking
(UV-CXL) for treatment of keratoconus. However, the effects of RGX on the biomechanical properties of the cornea are
not as well understood as UV-CXL. In this work, we demonstrate the feasibility of quantifying the viscoelasticity of the
rabbit cornea before and after RGX using a noncontact method of phase-stabilized swept source optical coherence
elastography (PhS-SSOCE) and finite element modeling (FEM). Viscoelastic FE models of the corneas were constructed
to simulate the elastic wave propagation based on the OCE measurements. In addition, the effect of the fluid-structure
interface (FSI) between the corneal posterior surface and aqueous humor on the elastic wave group velocity was also
investigated. The effect of the FSI was first validated by OCE measurements and FEM simulations on contact lenses, and
the OCE and FEM results were in good agreement. The Young’s modulus of the rabbit cornea before RGX was assessed
as E=80 kPa, and the shear viscosity was η=0.40 Pa•s at an intraocular pressure (IOP) of 15 mmHg. After RGX, the
Young’s modulus increased to E=112 kPa and shear viscosity decreased to η=0.37 Pa•s. Both the corneal OCE
experiments and the FE simulations also demonstrated that the FSI significantly reduced the group velocity of the elastic
wave, and thus, the FSI should be considered when determining the biomechanical properties of the cornea.
This study reports the application of a modified Rayleigh-Lamb frequency equation (RLFE) to a noncontact
optical coherence elastography (OCE) method for quantitative assessment of the biomechanical properties of a
porcine cornea. A focused air-pulse induced an elastic wave in the cornea, which was imaged by a phasestabilized
optical coherence tomography (OCT) system. From the displacement data acquired by the OCT
system, phase velocities of the mechanical wave were extracted by spectral analysis using a fast Fourier
transform. Experiments were conducted on 2% agar phantom samples, and the Young’s moduli were assessed
by the Rayleigh-Lamb frequency equation, which was validated using uniaxial mechanical compression testing.
The Rayleigh-Lamb frequency equation was then applied to OCE data from a normal porcine cornea, in which
the fluid-solid effect was considered. The Young’s modulus of the porcine cornea was measured to be ~60 kPa
and the shear viscosity was ~0.33 Pa·s. The combination of OCE and RLFE is a promising noninvasive method
for the estimation of the biomechanical properties of the cornea in vivo.
We demonstrate a novel method for noninvasive quantification of tissue biomechanical properties in 3D using
phase-stabilized swept source optical coherence elastography (PhS-SSOCE). A focused air-pulse delivery system
induces an elastic wave, which is then recorded by the PhS-SSOCE system. By calculating the velocity in all radial
directions and imaging depths from the origin of the stimulation, a volumetric elasticity map was generated.
Utilizing the high spatial sensitivity of PhS-SSOCE, the force applied on the surface of the cornea and subsequent
induced deformation amplitude was minimal, thus preserving the structure and function of delicate ocular tissues
such as the cornea and sclera. The results show that this noninvasive method for elasticity assessment can provide a
volumetric mapping of elasticity and can differentiate untreated and UV-induced collagen cross-linked (CXL)
corneas. As expected, the elastic wave velocity and subsequent Young’s modulus was significantly higher in the
CXL cornea as compared to the untreated cornea, indicating a substantial increase in corneal stiffness after the CXL
treatment.
We demonstrate a novel method for noninvasive elasticity mapping in three dimensions using phase stabilized swept source optical coherence elastography (PhS-SSOCE). By calculating the velocity in all radial directions from the origin of the induced shear wave, a volumetric elasticity map of the sample was generated. Due to the submicrometer spatial sensitivity of PhS-SSOCE, the loading force and the induced deformation amplitude can be minimal, thus preserving the structure and function of delicate tissues such as the cornea and sclera of the eye. Tissue mimicking agar phantoms were utilized for proof of concept testing and the results show that this method can noninvasively provide a three dimensional estimation of sample elasticity.
In this study we demonstrate the use of phase-stabilized swept-source optical coherence elastography (PhS-SSOCE) to assess the biomechanical properties of porcine corneas before and after collagen cross-linking (CXL) at different intraocular pressures by measuring the velocity of an air-pulse induced elastic wave and recovery process rate of an air-pulse induced deformation. Young’s moduli were estimated by two different methods: the shear wave equation and a newly developed elasticity reconstruction model. The results show that the corneas became stiffer after the CXL treatment, as evidenced by the increased elastic wave velocity and recovery process rate and greater Young’s modulus. This non-contact and noninvasive measurement technique utilizes minimal force for excitation (deformation less than 10 μm in amplitude) of the tissue. Thus, it can be potentially used to study the biomechanical properties of ocular and other delicate tissues.
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.
A systematic investigation was conducted on the accuracies of four analytical methods for obtaining the elasticity of soft samples by using optical coherence elastography (OCE). The results were compared to the elasticity measured by uniaxial mechanical testing. OCE has emerged as a noninvasive method for quantifying tissue biomechanical properties with spatial resolution of a few micrometers. A proper mechanical model is required for extracting the biomechanical parameters accurately from OCE measurements. In this work, tissuemimicking agar phantoms were utilized to analyze the accuracy and feasibility of four methods for reconstructing the Young’s modulus from OCE-measured elastic wave which were induced by a focused airpulse. These reconstruction methods are: the shear wave equation (SWE), the surface wave equation (SuWE), the Rayleigh-Lamb frequency equation (RLFE), and the finite element method (FEM). The reconstructed elasticity values were also compared with uniaxial mechanical testing results. It was shown that the RLFE and the FEM are more robust in quantifying elasticity than the other simplified models. This work may provide a reference for reconstructing the biomechanical properties of tissues based on OCE measurements. Accurate reconstruction of biomechanical properties is an important issue for further developing noninvasive elastography methods.
We report the first study on using optical coherence elastography (OCE) to quantitatively monitor the elasticity change of the hyaline cartilage during the optical clearing administrated by glucose solution. The measurement of the elasticity is verified using uniaxial compression test, demonstrating the feasibility of using OCE to quantify the Young’s modulus of the cartilage tissue. As the results, we found that the stiffness of the hyaline cartilage increases during the optical clearing of the tissue. This study might be potentially useful for the early detection of osteoarthritis disease.
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=3) and then applied to porcine corneas (n=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.
Structurally degenerative diseases, such as keratoconus, can significantly alter the stiffness of the cornea, directly affecting the quality of vision. Ultraviolet-induced collagen cross-linking (CXL) effectively increases corneal stiffness and is applied clinically to treat keratoconus. However, measured corneal stiffness is also influenced by intraocular pressure (IOP). Therefore, experimentally measured changes in corneal stiffness may be attributable to the effects of CXL, changes in IOP, or both. We present a noninvasive measurement method using phase-stabilized swept-source optical coherence elastography to distinguish between CXL and IOP effects on measured corneal stiffness. This method compared the displacement amplitude attenuation of a focused air-pulse-induced elastic wave. The damping speed of the displacement amplitudes at each measurement position along the wave propagation were compared for different materials. This method was initially tested on gelatin and agar phantoms of the same stiffness for validation. Consequently, untreated and CXL-treated porcine corneas of the same measured stiffness, but at different IOPs, were also evaluated. The results suggest that this noninvasive method may have the potential to detect the early stages of ocular diseases such as keratoconus or may be applied during CLX procedures by factoring in the effects of IOP on the measured corneal stiffness.
We characterize the relaxation rates of deformations created by focused air puffs with the use of phasestabilized
swept source optical coherence elastography (PhS-SSOCE) in tissue-mimicking gelatin phantoms of
various concentrations and mouse corneas of different ages in vivo. The results indicate that gelatin of varying
concentrations and corneas from different aged mice have different relaxation rates. In addition, the results show
that phantoms with higher concentration gelatin and corneas of older mice have higher relaxation rates, which can
be attributed to stiffer material. Because this method is non-contact, noninvasive, and utilizes a minimal force which
induces a deformation on the scale of μm, this method can be used to study the biomechanical properties of sensitive
tissues, such as the cornea.
We demonstrate the use of phase-stabilized swept-source optical coherence tomography to assess the propagation of low-amplitude (micron-level) waves induced by a focused air-pulse system in tissue-mimicking phantoms, a contact lens, a silicone eye model, and the mouse cornea in vivo. The results show that the wave velocity can be quantified from the analysis of wave propagation, thereby enabling the estimation of the sample elasticity using the model of surface wave propagation for the tissue-mimicking phantoms. This noninvasive, noncontact measurement technique involves low-force methods of tissue excitation that can be potentially used to assess the biomechanical properties of ocular and other delicate tissues in vivo.
Structural properties of the cornea determine the shape and optical quality of the eye. Keratoconus, a structural
degeneration of the cornea, is often treated with UV-induced collagen cross-linking to increase tissue resistance to
further deformation and degeneration. Optimal treatments would be customized to the individual and consider preexisting structural properties as well as the effects induced by treatment and this requires the capability to noninvasively measure tissue properties. The purpose of this study is to use novel methods of optical elastography to study the effects of UV-induced corneal collagen cross-linking in the rabbit eye. Low-amplitude (<1μm) elastic flexural waves were generated using focused air-pulse stimulation. Elastic wave propagation was measured over a 10x10mm area using Phase Stabilized Swept Source Optical Coherence Elastography (PhS-SSOCE) with a sensitivity of ~ 10 nm. Wave amplitude and velocity were computed and compared in tissues before and after UV cross-linking. Wave amplitude was decreased by the cross-linking treatment, while wave velocity was greater in cross-linked tissue than it was in the untreated cornea. Decreased wave amplitude and increased wave velocity after cross-linking is consistent with increased tissue stiffness. This was confirmed by conventional mechanical tension testing. These results demonstrate that the combination of the PhS-SSOCE and focused air pulse stimulation is capable of measuring low amplitude tissue motion and quantifying corneal stiffness.
We combine a focused air-puff system with phase-sensitive optical coherence tomography (PhS-OCT) to measure the elasticity of soft tissues. Surface waves (SWs) on soft tissues are induced by a low-pressure, short-duration air stream from an air-puff system and measured using a high-sensitivity PhS-OCT imaging system. Young’s modulus of soft tissues can be quantified based on the group velocity of SWs. To precisely control the excitation pressure, the air-puff system was characterized with a high-resolution analog pressure transducer. We studied the feasibility of this method for the non-contact detection of soft-tissue tumors. Ex vivo human fat and myxoma were used for these pilot experiments. Results demonstrate that this optical non-contact technique can be used to differentiate soft-tissue tumors from normal tissues based on measurements of their elasticity.
Here we demonstrate our use of phase stabilized swept-source optical coherence elastography (PhS-SSOCE) to assess elastic wave propagation in gelatin phantoms. From these measurements, Young’s moduli of the samples were determined. Low-amplitude (<10μm) mechanical waves were introduced using a focused air pulse on gelatin of different concentrations. Elastic wave amplitude and velocity were measured at multiple points on the phantom surface using a phase-resolved method. The results demonstrate that this method is capable of resolving very small changes in wave amplitude (~ 10 nm) as well as differences in wave velocity due to material stiffness. We further demonstrate use of this method for measurements with a contact lens, a silicone eye model and with the eye of an 18-month-old mouse in vivo. This non-destructive, non-invasive measurement system produces minimal tissue excitation and has high measurement sensitivity. These traits make this make this method useful for in vivo study of the biomechanical properties of ocular and other tissues.
In this paper, we report the use of phase stabilized swept source optical coherence tomography (PhSSSOCT)
for the measurement of surface mechanical wave propagation in ocular tissue in-situ. Mechanical wave
propagation was measured in the mouse cornea for both young and older mice to assess tissue properties as a
function of age. The measurements were performed by inducing low amplitude (< 100 μm) waves and measuring
the wave attenuation at spatially distributed points using a phase-sensitive analysis of OCT signals. Obtained results
indicate that the attenuation of the wave amplitude was 0.27 μm/mm in the one month-old mouse cornea and 0.37
μm/mm for 9 month old mice (and presumably of different stiffness for 1 month and 9 months old). Results also
suggest that PhS-SSOCT is capable of measuring the changes in the wave amplitude as small as 0.03 μm (limited by
the phase stability of the system) that allowed the measurements with a very low amplitude excitation wave, thus
making the method minimally invasive. Therefore, this method could potentially be used to assess tissue
biomechanical properties and to reconstruct stiffness maps of the cornea.
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