Clinical applications of ultra-high resolution and phase-sensitive optical coherence tomography

The transparency of the human cornea is vital in maintaining vision. The cells on the surface, corneal epithelium cells, are constantly replaced by differentiated limbal stem cells. Damage to the limbus can cause a deficiency in the limbal stem cell population which can cause cornea opacity and vascularisation consequently leading to blindness. Currently limbal stem cell deficiency can be detected clinically and treated surgically by transplanting stem cells onto the damaged cornea. However, the long term success rate is low 68\% and the results vary from patient to patient. There is an interest to understand the cause for this variability in results and the low long term success rates.

The aim of the project was to develop an Ultrahigh resolution OCT (UHROCT) to locate the transplanted corneal epithelium cells. Optical Coherence Tomography system (OCT) is a non-invasive micron resolution imaging technique that can image several millimetres in tissue. The cells to be transplanted are labelled with super paramagnetic iron oxide (SPIO) nanoparticles. After uptake these SPIO embedded cells are displaced with an external magnetic field at a known frequency whilst being imaged by the UHROCT. This technique known as phased resolved magnetomotive OCT, allowed us to locate the oscillating nanoparticle which is embedded in the cell by detecting the location of the modulation frequency. For the Ultrahigh resolution OCT a super luminescent diode (SLD) light with centre wavelength at \num{890e-9}m and a bandwidth of \num{150e-9}m. The system has an axial and lateral resolution of 2.5$\mu$m and 6.20 $\mu$m in air respectively. The system was able to detect as low as 1273 SPIO loaded cells/ $mm^2$ on rabbit cornea.

The spectral domain UHROCT constructed was also used to image 3D oral mucosa constructs. The system shows superior contrast in comparison to 1310 nm swept source systems. The UHROCT was able to identify key difference between the normal, dysplastic and malignant construct. For the malignant construct Cal27’s, hematoxylin and eosin staining was used to confirm the formation of a keratinized superficial layer. The keratinized layer was presented as a hyper-reflective thickened layer superficial to a darker region on both OCT platforms. This keratinized layer causes a sharp fall in the signal in the UHROCT making it difficult to visualise the underlying structures of the construct.