Corneal Tissue Water Content Research Articles

Ballistic delivery of compounds to inner layers of the cornea is limited by tough mechanical properties of stromal tissue

The barrier characteristics of the cornea are interrogated using the impact of micro-particles into ex vivo porcine cornea. Using a commercial gene gun (BioRad; PDS1000), microparticles were accelerated and made to embed in target materials: either ballistic gelatin as a reference or corneal tissue. Statistical analysis of penetration of polydisperse spherical microparticles (5–22 μm dia.) with density of 2.5 g/cc, 4.2 g/cc, and 7.8 g/cc (soda-lime glass, barium-titanate glass and stainless steel; more limited examination of 1.1 g/cc polyethylene and 19.2 g/cc tungsten) spanned almost two decades in kinetic energy. Penetration profiles in ballistic gelatin show that the particle embedding depth is sensitive to particle size and density. In the cornea, penetration is a weak function of size and density, and the corneal stroma is an effective stopping medium for high velocity microparticles. Despite the high water content of corneal tissue (76% w/w) compared to the stratum corneum of skin (40% w/w), the resistance to penetration of the cornea is comparable to what is seen in previous research of penetration in skin tissue. Using low density polymer particles with a therapeutic agent payload, it is demonstrated that bulk material can be ballistically delivered to the central 1 cm2 of the corneal epithelium in an even layer with high bioavailability of therapeutic compound.

THz imaging system for in vivo human cornea.

Terahertz (THz) imaging of corneal tissue water content (CTWC) is a proposed method for early, accurate detection and study of corneal diseases. Despite promising results from ex vivo and in vivo cornea studies, interpretation of the reflectivity data is confounded by the contact between corneal tissue and rigid dielectric window used to flatten the imaging field. This work develops a novel imaging system and image reconstruction methods specifically for nearly spherical targets such as human cornea. A prototype system was constructed using a 650 GHz multiplier source and Schottky diode detector. Resolution and imaging field strength measurement from characterization targets correlate well with those predicted by the quasioptical theory and physical optics analysis. Imaging experiments with corneal phantoms and ex vivo corneas demonstrate the hydration sensitivity of the imaging system and reliable measurement of CTWC. We present successful acquisition of non-contact THz images of in vivo human cornea, and discuss strategies for optimizing the imaging system design for clinical use.

Optical System Design for Noncontact, Normal Incidence, THz Imaging of in vivo Human Cornea

Reflection mode Terahertz (THz) imaging of corneal tissue water content (CTWC) is a proposed method for early, accurate detection and study of corneal diseases. Despite promising results from ex vivo and in vivo cornea studies, interpretation of the reflectivity data is confounded by the contact between corneal tissue and dielectric windows used to flatten the imaging field. Herein, we present an optical design for non-contact THz imaging of cornea. A beam scanning methodology performs angular, normal incidence sweeps of a focused beam over the corneal surface while keeping the source, detector, and patient stationary. A quasioptical analysis method is developed to analyze the theoretical resolution and imaging field intensity profile. These results are compared to the electric field distribution computed with a physical optics analysis code. Imaging experiments validate the optical theories behind the design and suggest that quasioptical methods are sufficient for designing of THz corneal imaging systems. Successful imaging operations support the feasibility of non-contact in vivo imaging. We believe that this optical system design will enable the first, clinically relevant, in vivo exploration of CTWC using THz technology.

THz and mm-Wave Sensing of Corneal Tissue Water Content: In Vivo Sensing and Imaging Results.

A pulsed terahertz (THz) imaging system and millimeter-wave reflectometer were used to acquire images and point measurements, respectively, of five rabbit cornea in vivo. These imaging results are the first ever produced of in vivo cornea. A modified version of a standard protocol using a gentle stream of air and a Mylar window was employed to slightly dehydrate healthy cornea. The sensor data and companion central corneal thickness (CCT) measurements were acquired every 10-15 min over the course of two hours using ultrasound pachymmetry.. Statistically significant positive correlations were established between CCT measurements and millimeter wave reflectivity. Local shifts in reflectivity contrast were observed in the THz imagery; however, the THz reflectivity did not display a significant correlation with thickness in the region probed by the 100 GHz and CCT measurements. This is explained in part by a thickness sensitivity at least 10× higher in the mm-wave than the THz systems. Stratified media and effective media modeling suggest that the protocol perturbed the thickness and not the corneal tissue water content (CTWC). To further explore possible etalon effects, an additional rabbit was euthanized and millimeter wave measurements were obtained during death induced edema. These observations represent the first time that the uncoupled sensing of CTWC and CCT have been achieved in vivo.

THz and mm-Wave Sensing of Corneal Tissue Water Content: Electromagnetic Modeling and Analysis.

Terahertz (THz) spectral properties of human cornea are explored as a function of central corneal thickness (CCT) and corneal water content, and the clinical utility of THz-based corneal water content sensing is discussed. Three candidate corneal tissue water content (CTWC) perturbations, based on corneal physiology, are investigated that affect the axial water distribution and total thickness. The THz frequency reflectivity properties of the three CTWC perturbations were simulated and explored with varying system center frequency and bandwidths (Q-factors). The modeling showed that at effective optical path lengths on the order of a wavelength the cornea presents a lossy etalon bordered by air at the anterior and the aqueous humor at the posterior. The simulated standing wave peak-to-valley ratio is pronounced at lower frequencies and its effect on acquired data can be modulated by adjusting the bandwidth of the sensing system. These observations are supported with experimental spectroscopic data. The results suggest that a priori knowledge of corneal thickness can be utilized for accurate assessments of corneal tissue water content. The physiologic variation of corneal thickness with respect to the wavelengths spanned by the THz band is extremely limited compared to all other structures in the body making CTWC sensing unique amongst all proposed applications of THz medical imaging.