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Development and Translation of Multimodal Microscopic and Endoscopic Biomedical Imaging Technologies

Creative Commons 'BY' version 4.0 license
Abstract

Each endoscopic imaging technique, including optical coherence tomography, fluorescence, ultrasound, or photoacoustic, has unique features as well as limitations. Presently, since no single technique can provide a complete assessment of biological tissue, such as plaque and colorectal wall, several imaging methods are often performed in sequence to achieve a comprehensive evaluation. While the sequential imaging approach can compensate for limitations of each individual technique, the increased X-ray exposure, procedure length, and associated risks cannot be overlooked. As multiple imaging probes are required, repeated probe insertions to the arteries are required, and the associated costs (e.g., guide wires, sterilization, etc.) also increase significantly. In addition, since data acquisition is performed individually, image co-registration is necessary, which is often performed off-line manually or semi-automatically. Not only is image co-registration a tedious and time-consuming task, it also has limited accuracy due to human error and interobserver variances. Therefore, a technique that can simultaneously perform multiple imaging technologies through a single imaging probe would greatly improve clinical outcomes in clinical applications. Here, we present different kinds of multimodal imaging modalities for cardiology and gastrointestinal tract. In vivo and ex vivo studies using rabbit and rat were performed for system validation. The results show that multimodal technology is able to overcomes the limitations of individual intravascular imaging modality, providing more comprehensive information on morphology and/or composition for better characterization.

Since the first demonstration of Doppler OCT in 1997, several functional extensions of Doppler OCT have been developed, including velocimetry, angiogram, and optical coherence elastography (OCE). OCT Angiogram (OCTA) is able to reconstruct the microvasculature by detecting fluctuations in the amplitude and phase of the interference signal induced by moving blood cells and plasma. Here, we developed a 1.7-micron OCT/OCTA system for characterization of skin cancer. The use of the longer wavelength allows for a ~25% improvement in penetration depth as well as better identification of microvasculature in the deeper layers of the skin tissue. The feasibility and performance of our system were tested and validated in vivo in human subjects. The developed 1.7-micron OCT/OCTA system has the capability of providing more structural and vascular information at greater skin depths than previous OCT systems, and it has great potential to bring new insights in diagnosis as well as management of skin cancer.

OCE possesses micron-level resolution and an axial displacement sensitivity on the order of a few nanometers and, therefore has become an attractive research tool for ophthalmology, dermatology, cardiology, and oncology. Here, we developed an OCE system, which is able to perform a simultaneous evaluation of elasticity in both cornea and crystalline lens. In vivo rabbit experiments were performed to verify the performance as well as investigate the relationship between elasticity of ocular tissue and intraocular pressure and between elasticity and age. In addition, we developed an ultrahigh sensitivity OCE system using a common-path configuration to further improve the system performance. The system has a phase stability of 4.2 mrad without external stabilization or extensive post-processing, such as averaging. We validated the SS-OCECP performance in a tissue-mimicking phantom and an in vivo rabbit model, and the results demonstrated significantly improved phase stability compared to conventional SS-OCE. The significant improved capability suggests that the developed OCE system has great potential to advance ophthalmic research in disorders affecting the lens and the cornea.

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