Acoustic-property maps of the cornea for improved high-frequency ultrasound corneal biometric accuracy

Early diagnosis of keratoconus, a progressive disease characterized by corneal thinning and bulging, is important for avoiding corneal refractive surgery and for treatment planning. Current gold-standard procedures rely on surface topography and corneal-thickness measurements using high-frequency ultrasound (HFU) or optical coherence tomography (OCT). In a previous study of more than 200 normal corneas, OCT measurements of epithelial thickness were systematically thinner than those obtained from 40-MHz HFU measurements. In the present study, acoustic impedance (Z), attenuation (a) and speed of sound (c) of the corneal epithelium and stroma were independently measured using a scanning acoustic microscope (SAM) to investigate the discrepancy in thickness estimates. Corneas of two pigs were snap-frozen and 12-µm thick sections were scanned using a custom-built SAM with an F-1.16, 250-MHz transducer with a 160-MHz bandwidth. 2D maps of c, Z and a, with a spatial resolution of 7 µm were derived. These maps were used to model HFU propagation in silico and to provide more-accurate estimates of corneal and epithelial thicknesses. HFU significantly overestimated epithelial thickness by 1.2 to 2.2 µm because a single value of c (1636 m/s) was used to estimate thickness for all corneal layers. SAM showed that the value of c in the epithelium is substantially lower (i.e., 1539 ± 18 m/s) than the value of c in the stroma (i.e., 1591 ± 28 m/s). After using the SAM-based values in the simulations, no significant difference between HFU and OCT thickness determinations occurred, which showed that the assumption of a constant value of c for all corneal layers is incorrect. SAM permitted obtaining reliable thickness measurements because it provides accurate acoustic-property estimates at fine resolution.