Corneal Lamb wave imaging for quantitative assessment of collagen cross-linking treatment based on comb-push ultrasound shear elastography.

Keratoconus, a serious corneal disorder, often causes highly irregular astigmatism and different degrees of visual impairment. Riboflavin/UVA corneal collagen cross-linking(CXL) is currently approved for effective treatment of keratoconus by enhancing the mechanical strength of collagen fibers in the cornea. However, few methods are capable of quantitatively and non-destructively assessing the mechanical properties of the cornea before and after CXL treatments. This study developed a corneal viscoelasticity imaging method based on comb-push ultrasound shear elastography (CUSE) and implemented this method on a Verasonics™ Vantage 256 ultrasound open system with a high-frequency linear array ultrasound transducer. Push beams were generated by three teeth each consisting of 10 elements (working frequency = 10.41 MHz) for inducing Lamb wave propagation in the cornea, and then the system immediately switched to the plane wave imaging mode using 60 elements in the middle (working frequency = 18 MHz). This method can provide a high-resolution 2D Lamb wave velocity image overlapping with a B-mode image as well as quantitative viscoelasticity estimation according to experimentally obtained phase velocity dispersion of Lamb waves. The validation experiments were performed on ex vivo porcine corneas, and the accuracy of elasticity estimation was verified by a tensile test. The results showed that the shear elasticity increased and the viscosity decreased after CXL treatment. The shear elasticity results (reported as mean ± standard deviation) of one control group with no CXL treatment and three CXL-treated groups named as 10 min, 30 min, and 60 min groups according to UV irradiation time were 14.62 ± 3.38 kPa, 49.47 ± 3.63 kPa, 116.54 ± 23.99 kPa, and 197.89 ± 39.64 kPa, respectively, which was in agreement with the results of tensile tests. The ultrasound safety measurement indicated that this method could have acceptable safety, but further to ocular tissue and vision function. The study demonstrated the possibility of using a commercial ultrasound system to obtain high-resolution images of corneal mechanical properties as well as the ability to quantify changes induced by CXL treatment. Therefore, the proposed method could serve as a helpful tool in the studies related in corneal biomechanics.