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.
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.