Advanced Multimodal Imaging Technology Of The Eye

Retinal diseases are one of the major causes of blindness in both developed and developing countries. Ophthalmic imaging technology has played a crucial role in the diagnosis and management of retinal diseases. Optical coherence tomography (OCT) and photoacoustic imaging (PA) are two recently developed non-invasive high resolution imaging technologies. With the capability of strauctural and functional imaging these imaging technologies have potentially significant impact on the research and diagnosis of retinal diseases.OCT is based on low coherence optical interferometry which uses the coherence properties of broadband light to achieve depth resolving capability. The state-of-the-art OCT can provide in vivo real-time high-resolution three-dimensional imaging of the retina, which can help doctors in the early diagnosis, understanding the pathological development and making treatment planning. PA imaging has been becoming a hot research topic in recent years due to its advantages of scalability and novel contrast mechanisms. PA imaging is based on the optical absorption properties of biological tissues. My doctoral research was focused on the development of multimodal ophthalmic imaging technology to provide comprehensive diagnostic information for retinal diseases. By combining OCT with PA imaging we were able to image the scattering and absorption contrasts simultaneously. By further combining OCT and PA imaging with adaptive optics we were able to significantly improve the spatial resolution. Although we only tested the technology on imaing ex-vivo ocular samples, it laid the foundation for future in vivo applications.The research work can be summarized as following:First, a high-resolution spectral-domain OCT system was built to image the retina of human eye and the eye of small animals. We were able to use SD-OCT to calculate the dimensional parameters of the whole mouse eye with single-shot imaging. This experimentdemonstrated the capability of SD-OCT for single-shot biometric measurement of the eye, which is important for myopia research.Second, the technology of adaptive optics was applied in SD-OCT to improve its lateral resolution. We first systematically analyzed and compared the aberration generation capabilities of the membrane deformable mirror (MMDM) and piezoelectric deformable mirror (PDM). We then combined adaptive optics system into OCT and conducted experiments on rat eye for aberration measurement and correction. We evaluated the influence of AO system by comparing the OCT images acquired before and after the aberration correction.Third, we did research on the technology of multimodal photoacoustic microscopy . For the first time AO technology was applied in PAM to improve the lateral resolution. The aberrations of the optical system delivering the illuminating light to the sample in PAM were corrected with a close-loop AO system. The photoacoustic signal induced by the illuminating laser beam was detected by a custom-built needle ultrasonic transducer. When the wavefront errors were corrected by the AO system, the lateral resolution of PAM was measured to be better than 2.5μm using a low NA objective lens. We tested the system on imaging ex vivo ocular samples, e.g., the ciliary body and retinal pigment epithelium (RPE) of a pig eye. The AO-PAM images showed significant quality improvement. For the first time we were able to resolve single RPE cells with PAM. As a model of multimodal ophthalmic imaging, we developt an OCT-guided photoacoustic ophthalmoscopy (PAOM). This system demonstrated the advantages of OCT and PA technologies, realizing the structural and functional imaging of the retina.The research demonstrated the potential of providing clinicians a more advanced multimodal ophthalmic imaging technology, not only maintaining the advantages of the original two imaging techniques, but also improving their imaging resolution. The multimodal imaging technology extended the capability of each individual imaging technique in tructural imaging and functional imaging and opened a new window for the early diagnosis of eye diseases.