Can We Improve Vaginal Tissue Healing Using Customized Devices: 3D Printing and Biomechanical Changes in Vaginal Tissue.

BACKGROUND: Determining biomechanical changes in vaginal tissue with tissue stretch is critical for understanding the role of mechanotransduction on vaginal tissue healing. Noncontact dynamic optical coherence elastography (OCE) can quantify biomechanical changes in vaginal tissues noninvasively. Improved vaginal tissue healing will reduce postoperative complications from vaginal surgery. AIMS: (1) To complete dimensional assessments (DAs) of the vaginal tract. (2) To elucidate biomechanical properties (BMP) of porcine vaginal tissues (PVT). (3) Compare BMPs of piglet and adult PVTs after placement of customized vaginal dilators (VD) by OCE and uniaxial mechanical testing (MT). METHODS: Pilot study using adult nulliparous pig and piglet PVTs (n = 20 each). DA of PVTs was performed using silicone molding. 3D-printed VDs were used to achieve different Relative Diameter Change (RDC) of the PVTs (no dilatation, and -50%, 0%, 50% RDC). Elastographic testing using OCE and MT. RESULTS: Using OCE, no significant differences (SD) were noted between adult and piglet PVT (p = 0.74) or by stretch direction (p = 0.300). SD was noted with increasing RDC (p = 0.023). Using MT, there were SD in tissue stiffness between adult and piglet PVT (p = 0.048), but no SD as a function of RDC (p = 0.750) or stretch direction (p = 0.592). CONCLUSIONS: This study quantified biomechanical changes in PVT with customized stretching by 3D printed VD using both OCE and MT. This work has implications for the mechanotransduction of vaginal wound healing and noninvasive assessment of vaginal diseases.

Nanobomb optical coherence elastography.

Wave-based optical elastography is rapidly emerging as a powerful technique for quantifying tissue biomechanical properties due to its noninvasive nature and high displacement sensitivity. However, current approaches are limited in their ability to produce high-frequency waves and highly localized mechanical stress. In this Letter, we demonstrate that the rapid liquid-to-gas phase transition of dye-loaded perfluorocarbon nanodroplets ("nanobombs") initiated by a pulsed laser can produce highly localized, high-frequency, and broadband elastic waves. The waves were detected by an ultra-fast line-field low-coherence holography system. For comparison, we also excited waves using a focused micro-air-pulse. Results from tissue-mimicking phantoms showed that the nanobombs produced elastic waves with frequencies up to ∼9 kHz, which was much greater than the ∼2 kHz waves excited by the air-pulse. Consequently, the nanobombs enabled more accurate quantification of sample viscoelasticity. Combined with their potential for functionalization, the nanobombs show promise for accurate and highly specific noncontact all-optical elastography.

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 work we present a noncontact method of optical coherence elastography to evaluate the changes in the mechanical properties of the cornea after UV-induced collagen cross-linking. A focused air-pulse induced a low amplitude (µm scale) elastic wave, which then propagated radially and was imaged in three dimensions by a phase-stabilized swept source optical coherence tomography (PhS-SSOCT) system. The elastic wave velocity was translated to Young's 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 cross-linking (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.

Air puff induced corneal vibrations: theoretical simulations and clinical observations.

PURPOSE: To investigate air puff induced corneal vibrations and their relationship to the intraocular pressure (IOP), viscoelasticity, mass, and elasticity of the cornea based on theoretical simulations and preliminary clinical observations. METHODS: To simulate the corneal movement during air puff deformation, a kinematic viscoelastic corneal model was developed involving the factors of corneal mass, damping coefficient, elasticity, and IOP. Different parameter values were taken to investigate how factors would affect the corneal movements. Two clinical ocular instruments, CorVis ST (Oculus Optikgeräte GmbH, Wetzlar, Germany) and the Ocular Response Analyzer (ORA; Reichert, Inc., Buffalo, NY), were employed to observe the corneal dynamical behaviors. RESULTS: Numerical results showed that during the air puff deformation, there would be vibrations along with the corneal deformation, and the damping viscoelastic response of the cornea had the potential to reduce the vibration amplitude. With consistent IOP, the overall vibration amplitude and inward motion depths were smaller with a stiffer cornea. CONCLUSIONS: A kinematic viscoelastic model of the cornea is presented to illustrate how the vibrations are associated with factors such as corneal mass, viscoelasticity, and IOP. Also, the predicted corneal vibrations during air puff deformation were confirmed by clinical observation.

Biomechanical and refractive behaviors of keratoconic cornea based on three-dimensional anisotropic hyperelastic models.

PURPOSE: To investigate the biomechanical and refractive behaviors of normal and keratoconic corneas based on three-dimensional anisotropic hyperelastic corneal models with two layers. METHODS: Based on an anisotropic hyperelastic formula, the finite element method was employed to develop normal and keratoconic corneal models in which the fiber orientations and the biomechanical differences between corneal layers were taken into account. The displacements for normal and keratoconic corneal models were studied, as well as changes in corneal refractive power with intraocular pressure (IOP). RESULTS: There were different displacements for keratoconic and normal corneas. Positive correlations were found in the keratoconic cornea between IOP and apical displacement, as well as between IOP and corneal refractive power. Under normal IOP, both the corneal shape and refractive power map were affected by the stiffness distributions of the corneal layers. CONCLUSIONS: Finite element analysis can be used to demonstrate the biomechanical and refractive behavior of a cornea with keratoconus. From a biomechanical viewpoint, the displacement changes seen under normal IOP were due to the decreased stiffness in the keratoconic corneal tissue and local thinning disorders. Thus, the curvature and corneal refractive power map will be abnormal in keratoconus.

Corneal hysteresis with intraocular pressure of a wide range: a test on porcine eyes.

PURPOSE: To investigate the relationship between corneal hysteresis (CH) and intraocular pressure (IOP) using porcine eyes in the low to high IOP ranges. METHODS: In vitro porcine eyes were used to investigate the relationship of CH and IOP. IOP was altered by changing the height of a drip stand within the dynamic range of 60 mm Hg. CH and IOP were measured with the Ocular Response Analyzer (ORA; Reichert Ophthalmic Instruments, Depew, NY) at different heights. Second-order polynomial regression method was employed to assess the nonlinear correlation of CH and IOP. RESULTS: CH demonstrated an initial plateau stage with low IOP, which then decreased as IOP increased to higher values up to 60 mm Hg. The maximum CH value of approximately 6 to 8 mm Hg was achieved when IOP ranged from 11 to 25 mm Hg. The nonlinear regression lines of Goldmann correlated IOP (IOPg) and CH can be described as CH = − 0.0029 × IOPg2 + 0.1005 × IOPg + 5.2824, R2 = 0.3676, P < .05. CONCLUSIONS: CH was relatively constant for lower values of IOP and showed a decreasing relationship at higher values of IOP. This nonlinear relationship provides insight into understanding the viscoelastic nature of CH over a wider range of IOP values. The experimental data on porcine eyes may indicate that IOP should be taken into account when analyzing the deformation response of the cornea to an applied air puff.

Aluminum surface defect detection method based on a lightweight YOLOv4 network.

Deep learning is currently being used to automate surface defect detection in aluminum. The common target detection models based on neural networks often have a large number of parameters and a slow detection speed, which is not conducive to real-time detection. Therefore, this paper proposes a lightweight aluminum surface defect detection model, M2-BL-YOLOv4, based on the YOLOv4 algorithm. First, in the YOLOv4 model, the complex CSPDarkNet53 backbone network was modified into an inverted residual structure, which greatly reduced the number of parameters in the model and increased the detection speed. Second, a new feature fusion network, BiFPN-Lite, is designed to improve the fusion ability of the network and further improve its detection accuracy. The final results show that the mean average precision of the improved lightweight YOLOv4 algorithm in the aluminum surface defect test set reaches 93.5%, the number of model parameters is reduced to 60% of the original, and the number of frames per second (FPS) detected is 52.99, which increases the detection speed by 30%. The efficient detection of aluminum surface defects is realized.

Quantifying the effects of hydration on corneal stiffness with noncontact optical coherence elastography.

PURPOSE: To quantify the effects of the hydration state on the Young's modulus of the cornea. SETTING: Biomedical Optics Laboratory, University of Houston, Houston, Texas, USA. DESIGN: Experimental study. METHODS: Noncontact, dynamic optical coherence elastography (OCE) measurements were taken of in situ rabbit corneas in the whole eye-globe configuration (n = 10) and at an artificially controlled intraocular pressure of 15 mm Hg. Baseline OCE measurements were taken by topically hydrating the corneas with saline for 1 hour. The corneas were then dehydrated topically with a 20% dextran solution for another hour, and the OCE measurements were repeated. A finite element method was used to quantify the Young's modulus of the corneas based on the OCE measurements. RESULTS: The thickness of the corneas shrank considerably after topical addition of the 20% dextran solution (∼680 µm to ∼370 µm), and the OCE-measured elastic-wave speed correspondingly decreased (∼3.2 m/s to ∼2.6 m/s). The finite element method results showed an increase in Young's modulus (500 kPa to 800 kPa) resulting from dehydration and subsequent thinning. CONCLUSION: Young's modulus increased significantly as the corneas dehydrated and thinned, showing that corneal geometry and hydration state are critical factors for accurately quantifying corneal biomechanical properties.

Quantitative Assessment of Thin-Layer Tissue Viscoelastic Properties Using Ultrasonic Micro-Elastography With Lamb Wave Model.

Characterizing the viscoelastic properties of thin-layer tissues with micro-level thickness has long remained challenging. Recently, several micro-elastography techniques have been developed to improve the spatial resolution. However, most of these techniques have not considered the medium boundary conditions when evaluating the viscoelastic properties of thin-layer tissues such as arteries and corneas; this might lead to estimation bias or errors. This paper aims to integrate the Lamb wave model with our previously developed ultrasonic micro-elastography imaging system for obtaining accurate viscoelastic properties in thin-layer tissues. A 4.5-MHz ring transducer was used to generate an acoustic radiation force for inducing tissue displacements to produce guided wave, and the wave propagation was detected using a confocally aligned 40-MHz needle transducer. The phase velocity and attenuation were obtained from k-space by both the impulse and the harmonic methods. The measured phase velocity was fit using the Lamb wave model with the Kelvin-Voigt model. Phantom experiments were conducted using 7% and 12% gelatin and 1.5% agar phantoms with different thicknesses (2, 3, and 4 mm). Biological experiments were performed on porcine cornea and rabbit carotid artery ex vivo. Thin-layer phantoms with different thicknesses were confirmed to have the same elasticity; this was consistent with the estimates of bulk phantoms from mechanical tests and the shear wave rheological model. The trend of the measured attenuations was also confirmed with the viscosity results obtained using the Lamb wave model. Through the impulse and harmonic methods, the shear viscoelasticity values were estimated to be 8.2 kPa for $0.9~\text {Pa}{\cdot} \text {s}$ and 9.6 kPa for $0.8~\text {Pa}{\cdot} \text {s}$ in the cornea and 27.9 kPa for $0.1~\text {Pa}\cdot \text {s}$ and 26.5 kPa for $0.1~\text {Pa}\cdot \text {s}$ in the artery.

Assessing the biomechanical properties of the porcine crystalline lens as a function of intraocular pressure with optical coherence elastography.

In this study, we investigated the relationship between the biomechanical properties of the crystalline lens and intraocular pressure (IOP) using a confocal acoustic radiation force (ARF) and phase-sensitive optical coherence elastography (OCE) system. ARF induced a small displacement at the apex of porcine lenses in situ at various artificially controlled IOPs. Maximum displacement, relaxation rate, and Young's modulus were utilized to assess the stiffness of the crystalline lens. The results showed that the stiffness of the crystalline increased as IOP increased, but the lens stiffening was not as significant as the stiffening of other ocular tissues such as the cornea and the sclera. A mechanical hysteresis in the lens was also observed while cycling IOP, indicating that the viscoelastic response of the lens is crucial to fully understanding its biomechanical properties.

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

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 ?? ? m ) 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.

Applanation optical coherence elastography: noncontact measurement of intraocular pressure, corneal biomechanical properties, and corneal geometry with a single instrument.

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.

Ultra-fast line-field low coherence holographic elastography using spatial phase shifting.

Optical coherence elastography (OCE) is an emerging technique for quantifying tissue biomechanical properties. Generally, OCE relies on point-by-point scanning. However, long acquisition times make point-by-point scanning unfeasible for clinical use. Here we demonstrate a noncontact single shot line-field low coherence holography system utilizing an automatic Hilbert transform analysis based on a spatial phase shifting technique. Spatio-temporal maps of elastic wave propagation were acquired with only one air-pulse excitation and used to quantify wave velocity and sample mechanical properties at a line rate of 200 kHz. Results obtained on phantoms were correlated with data from mechanical testing. Finally, the stiffness of porcine cornea at different intraocular pressures was also quantified in situ.

Assessing the effects of riboflavin/UV-A crosslinking on porcine corneal mechanical anisotropy with optical coherence elastography.

In this work we utilize optical coherence elastography (OCE) to assess the effects of UV-A/riboflavin corneal collagen crosslinking (CXL) on the mechanical anisotropy of in situ porcine corneas at various intraocular pressures (IOP). There was a distinct meridian of increased Young's modulus in all samples, and the mechanical anisotropy increased as a function of IOP and also after CXL. The presented noncontact OCE technique was able to quantify the Young's modulus and elastic anisotropy of the cornea and their changes as a function of IOP and CXL, opening new avenues of research for evaluating the effects of CXL on corneal biomechanical properties.

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.

Investigating Elastic Anisotropy of the Porcine Cornea as a Function of Intraocular Pressure With Optical Coherence Elastography.

PURPOSE: To evaluate the elastic anisotropy of porcine corneas at different intraocular pressures (IOPs) using a noncontact optical coherence elastography (OCE) technique. METHODS: A focused air-pulse induced low amplitude (≤ 10 µm) elastic waves in fresh porcine corneas (n = 7) in situ in the whole eye globe configuration. A home-built phase-stabilized swept source optical coherence elastography (PhS-SSOCE) system imaged the elastic wave propagation at different stepped radial directions. A closed-loop feedback system was used to artificially control the IOP and the OCE measurements were repeated as the IOP was incrementally increased from 15 to 30 mm Hg in 5-mm Hg increments. RESULTS: The OCE measurements demonstrated that the stiffness of the cornea increased as a function of IOP and elastic anisotropy of the cornea became more pronounced at higher IOPs. The standard deviation of the modified planar anisotropy coefficient increased from 0.72 ± 0.42 at an IOP of 15 mm Hg to 1.58 ± 0.40 at 30 mm Hg. CONCLUSIONS: 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 further information about corneal health and integrity in vivo. [J Refract Surg. 2016;32(8):562-567.].

Quantifying tissue viscoelasticity using optical coherence elastography and the Rayleigh wave model.

This study demonstrates the feasibility of using the Rayleigh wave model (RWM) in combination with optical coherence elastography (OCE) technique to assess the viscoelasticity of soft tissues. Dispersion curves calculated from the spectral decomposition of OCE-measured air-pulse induced elastic waves were used to quantify the viscoelasticity of samples using the RWM. Validation studies were first conducted on 10% gelatin phantoms with different concentrations of oil. The results showed that the oil increased the viscosity of the gelatin phantom samples. This method was then used to quantify the viscoelasticity of chicken liver. The Young's modulus of the chicken liver tissues was estimated as E=2.04±0.88??kPa with a shear viscosity ?=1.20±0.13??Pa?s. The analytical solution of the RWM correlated very well with the OCE-measured phased velocities (R2=0.96±0.04). The results show that the combination of the RWM and OCE is a promising method for noninvasively quantifying the biomechanical properties of soft tissues and may be a useful tool for detecting disease.

Lorentz force optical coherence elastography.

Quantifying tissue biomechanical properties can assist in detection of abnormalities and monitoring disease progression and/or response to a therapy. Optical coherence elastography (OCE) has emerged as a promising technique for noninvasively characterizing tissue biomechanical properties. Several mechanical loading techniques have been proposed to induce static or transient deformations in tissues, but each has its own areas of applications and limitations. This study demonstrates the combination of Lorentz force excitation and phase-sensitive OCE at ?1.5??million A-lines per second to quantify the elasticity of tissue by directly imaging Lorentz force-induced elastic waves. This method of tissue excitation opens the possibility of a wide range of investigations using tissue biocurrents and conductivity for biomechanical analysis.

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.

Classifying murine glomerulonephritis using optical coherence tomography and optical coherence elastography.

Acute glomerulonephritis caused by antiglomerular basement membrane marked by high mortality. The primary reason for this is delayed diagnosis via blood examination, urine analysis, tissue biopsy, or ultrasound and X-ray computed tomography imaging. Blood, urine, and tissue-based diagnoses can be time consuming, while ultrasound and CT imaging have relatively low spatial resolution, with reduced sensitivity. Optical coherence tomography is a noninvasive and high-resolution imaging technique that provides superior spatial resolution (micrometer scale) as compared to ultrasound and CT. Changes in tissue properties can be detected based on the optical metrics analyzed from the OCT signals, such as optical attenuation and speckle variance. Furthermore, OCT does not rely on ionizing radiation as with CT imaging. In addition to structural changes, the elasticity of the kidney can significantly change due to nephritis. In this work, OCT has been utilized to quantify the difference in tissue properties between healthy and nephritic murine kidneys. Although OCT imaging could identify the diseased tissue, its classification accuracy is clinically inadequate. By combining optical metrics with elasticity, the classification accuracy improves from 76% to 95%. These results show that OCT combined with OCE can be a powerful tool for identifying and classifying nephritis. Therefore, the OCT/OCE method could potentially be used as a minimally invasive tool for longitudinal studies during the progression and therapy of glomerulonephritis as well as complement and, perhaps, substitute highly invasive tissue biopsies. Elastic-wave propagation in mouse healthy and nephritic kidneys.