Subsecond Terahertz Spectroscopic Mapping of Corneal Hydration Gradients

Terahertz time-domain spectroscopy (THz-TDS) is sensitive to tissue water content, but slow acquisition and stringent alignment requirements have hindered its in vivo applications, particularly in corneal imaging. We present a compact spherical-scanning THz imaging system that acquires 100-ps time-domain waveforms at a rate of 2 kHz and generates a 10 × 10-pixel image over a 40° × 40° field of view in 0.8 s. Time-of-arrival measurements across the image are used to estimate and automatically correct lateral and axial misalignments. The system was evaluated using a drying contact-lens corneal phantom and seven ex vivo porcine eye globes while sample mass was recorded continuously. In both models, the reflected THz signal exhibited strong correlations with gravimetrically measured hydration changes. Sparse deconvolution of the THz pulses reflected from the contact lens separated echoes from the anterior and posterior interfaces, enabling simultaneous mapping of interfacial reflectivity and optical thickness. The longitudinal sample hydration and optical thickness maps also revealed complementary spatially heterogeneous drying patterns, potentially indicating a limitation of using thickness as a surrogate for hydration evaluation in clinical practice. Finally, we evaluated the sensitivity of THz spectroscopy to hydration change in ex vivo eye globes and found a median 0.7% decrease in THz reflectivity per 1% hydration loss. These results demonstrate rapid, motion-tolerant THz spectral imaging of corneal-scale spherical surfaces and support its further development for noncontact in vivo assessment of corneal hydration.