Nearly all benchtop studies of corneal biomechanics have relied on protocols which stiffen the cornea, such as riboflavin-UV crosslinking, as a way of providing contrast and validation of biomechanical measurements. However, there are strong clinical motivations to detect softening of the cornea. In this work, we present the evidence that phase-decorrelation OCT (PhD-OCT) is able to detect a small degree of corneal softening due to enzymatic digestion. This benchtop study supports the idea that PhD-OCT may detect keratoconus and early ectasia clinically.
Purpose: To measure the spatially resolved compressive stiffness properties under in vivo conditions to evaluate the effects of clinical corneal crosslinking (CXL) on patients with keratoconus.
Methods: Patients with keratoconus who were scheduled to undergo CXL were imaged before (<1 week) and after (3 to 6 months) treatment. The study was approved under the Cleveland Clinic Institutional Review Board (IRB #13-213). The imaging procedure consists of a continuous compression with a flat glass plate while imaging with swept-source OCT. The frame-to-frame displacements were measured using speckle tracking. Maps of the first order fit of applied force vs cumulative axial displacement were created. Spatially averaged central anterior and posterior regions were defined to generate a relative stiffness value (k) expressing anterior properties relative to posterior stromal properties. Data previously collected from normal patients were also used for group comparison purposes.
Results: Qualitative comparison of the color map representation showed significant differences in the distribution of compressive mechanical properties between all three patient types. Mean k-value were 1.129 ± 0.067 in normal eyes (n=12), 0.988 ± 0.089 in keratoconus eyes (n=8), and 1.27 ± 0.16 in keratoconus eyes after CXL (n=6, p<0.05 for all groups using Mann-Whitney U test).
Conclusions: The spatial biomechanical effects of CXL are measurable with in vivo compressive OCE. The normal anterior to posterior stromal force/displacement ratio appears to be reduced in keratoconus and is increased to or even beyond normal levels after CXL due to selective stiffening of the anterior stroma.
Introduction: Optical coherence tomography (OCT) is a high-resolution imaging modality which can be used to acquire detailed elastograms of biological tissue. In this investigation, we demonstrate the use of OCT to generate µm-scale strain maps of articular cartilage (AC) under compressive and shear deformations. AC is a dense connective tissue which provides a low-friction surface in synovial joints. The specific alignment of collagen fibrils and proteoglycans (which contribute primarily to shear and compressive stiffness, respectively) give rise to depth-dependent mechanical properties.
Methods: Six 6mm diameter samples of articular cartilage were harvested from a calf femur. A custom-designed biaxial loading apparatus applied compressive and shear displacements. Three-dimensional images of the tissue were obtained using a spectral-domain OCT system as the sample was loaded at constant rate of displacement. Both speckle-tracking and phase-shift methods were used to generate strain maps from these images.
Results: Under both shear and compressive loading, clear differences in local strain distribution were observed between the superficial, transitional, and radial zones of the cartilage. In shear, the superficial/transitional zones are stiffest while in compression these regions are more compliant than the radial zone. These distributions correspond with existing literature and the known orientation of collagen in the AC.
Conclusion: It is feasible to rapidly acquire strain maps in AC using OCT. This technique may be extended to high-throughput screening to nondestructively determine the functionality and failure modes of engineered AC as compared to native tissue.
Corneal collagen crosslinking (CXL) is a treatment used for corneal ectasia, a major cause of impaired vision in the United States and a leading indication for corneal transplantation. Existing methods of measuring the mechanical properties of normal and ectatic corneas still face a number of hurdles, including low spatial resolution, patient motion, measurement speed, patient comfort, and intraocular-pressure dependence. We have recently developed a phase-decorrelation OCT (PhD-OCT) method which avoids these drawbacks. PhD-OCT is sensitive to the endogenous random motion within the cornea. This nanometer-level motion can be detected with 5ms (M-scan) measurements using spectral-domain OCT. The random motion is reduced in crosslinked regions of the cornea, which provides contrast to enable mapping of corneal properties during CXL. These maps agree well with the current understanding of the CXL process, showing a distinct region of increased stiffness in the anterior portion of the cornea which corresponds to the demarcation line sometimes visible in conventional OCT. The PhD-OCT method uses conventional OCT and does not involve perturbing the cornea. This method may be useful clinically for pre-surgical screening, ectasia diagnosis, and treatment monitoring and customization.
KEYWORDS: Cornea, Optical coherence tomography, Elastography, Tissues, Signal to noise ratio, Tissue optics, Coherence (optics), Surgery, Detection and tracking algorithms, In vivo imaging
The material properties of the cornea are important determinants of corneal shape and refractive power. Corneal ectatic diseases, such as keratoconus, are characterized by material property abnormalities, are associated with progressive thinning and distortion of the cornea, and represent a leading indication for corneal transplantation. We describe a corneal elastography technique based on optical coherence tomography (OCT) imaging, in which displacement of intracorneal optical features is tracked with a 2-D cross-correlation algorithm as a step toward nondestructive estimation of local and directional corneal material properties. Phantom experiments are performed to measure the effects of image noise and out-of-plane displacement on effectiveness of displacement tracking and demonstrated accuracy within the tolerance of a micromechanical translation stage. Tissue experiments demonstrate the ability to produce 2-D maps of heterogeneous intracorneal displacement with OCT. The ability of a nondestructive optical method to assess tissue under in situ mechanical conditions with physiologic-range stress levels provides a framework for in vivo quantification of 3-D corneal elastic and viscoelastic resistance, including analogs of shear deformation and Poisson's ratio that may be relevant in the early diagnosis of corneal ectatic disease.
The viscoelastic properties of the cornea are important determinants of the corneal response to surgery and disease. The purpose of this work is to develop an OCT-based technique for non-contact, high-resolution pan-corneal strain mapping using clinically-achievable pressure changes as a stressor. Porcine corneas were excised and mounted on an artificial anterior chamber that facilitated maintenance of a simulated intraocular pressure (IOP). Pressure was controlled and monitored continuously by saline infusion with an in-line transducer and digital monitor. Mounted specimens were positioned under a laboratory-based high-speed OCT system and imaged in three dimensions at various IOP levels. Matlab and C++ routines were written to perform 2-D bitmap cross-correlation analyses on corresponding images at different pressure levels. Resulting correlations produced a likelihood estimate of the 2-D vector displacement of corneal optical features. Strain maps from cross-correlation analyses revealed local areas of highly consistent displacements interspersed with inter-regional variability. Displacements occurred predominantly along axial vectors. Our analysis produces results consistent with expected and observed displacement of the cornea with varying IOP. Cross-correlation analysis of optical feature flow in the corneal stroma can provide high-resolution strain maps capable of distinguishing spatial heterogeneity in the corneal response to pressure change. A non-destructive, non-contact technique for corneal strain mapping offers numerous potential advantages over tensile testing of excised tissue strips for inferring viscoelastic behavior, and the membrane inflation model employed here could potentially be extended to clinical biomechanical characterizations.
High intensity focused ultrasound (HIFU) is a promising method for ablation therapy in the heart. Little is understood about early lesion development with HIFU because the lesions cannot be imaged reliably with sufficient resolution, and no other real time monitoring techniques are available to date. We investigated Optical coherence tomography (OCT) for monitoring early lesion formation. We created a series of lesions in fresh canine cardiac tissue using 5W (frequency=4.23Mhz, F#=1.2) of acoustic power with 10sec., 7sec., and 5sec. exposures. The lesions were then imaged using an OCT imaging system with an axial resolution of 12μm and a lateral resolution of 15μm. The maximum width of the lesions were measured using custom software. In separate experiments, lesion formation was investigated under varying acoustic power levels ranging from 5W to 20W at 0.1sec. and 0.2 sec. exposures. The average maximum widths of the lesions were 1.06mm for 10sec. lesions, .65mm for 7sec. lesions, and .59mm for 5sec. lesions. We observed both subsurface lesions and superficial blister-like formations, which may be a precursor of cavitation inception or tissue vaporization. The subsurface lesion forms over time as expected from thermal energy deposition. The surface blister forms prior to the subsurface lesion at high power, and after subsurface lesion formation at lower powers. OCT provides a method for monitoring HIFU lesion formation at high resolution, and can potentially be used to optimize HIFU dose for clinical applications.
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