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Development of acoustic radiation force optical coherence elastography system for in vivo mapping of biological tissues

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Abstract

Mechanical elasticity often serves as a major indicator for pathological changes in ocular as well as intravascular diseases. For example, age-related macular degeneration is an ocular disease that occurs in the posterior eye, where central vision gets damaged due to drusen formation and neovascularization. The mechanical elasticity of the tissue is often altered during the onset of disease before structural changes are detectable with existing technologies. It is necessary to detect these changes early and provide timely treatment due to either the irreversible nature of the disease progression or the fatal consequences associated with late diagnosis. This thesis focuses on the development of an acoustic radiation force optical coherence elastography (ARF-OCE) system to map the mechanical elasticity of tissues, and the translation of this laboratory technology to in vivo animal studies. This technique uses ultrasonic excitation to apply a force onto the tissue and optical coherence elastography to detect the spatial and frequency responses of the tissue, which combines to quantify the elasticity and provide an elasticity map. The resonance frequency method is validated and used to measure the bulk modulus of the tissue while a Voigt spring model calculates the individual layer elasticity. We first test the feasibility of the system using tissue-mimicking phantoms. Then we perform tissue imaging on the ex vivo anterior and posterior eye, where we are able to provide quantified elasticity maps of the rabbit cornea and porcine retina The system is then translated to in vivo imaging, for which quantified elasticity mapping of the rabbit retinal layers can be obtained. In addition, we have also fabricated an ARF-OCE catheter with a diameter of 3.5 mm, which was validated using phantom studies, and intravascular imaging was performed on a human cadaver artery. This study is a major stepping stone to the translation of the ARF-OCE technology in measuring the mechanical properties of tissues in clinical settings. Future studies using this technology include monitoring the retinal elasticity during and after electrode stimulation treatment and also intravascular elasticity imaging to diagnose atherosclerosis.

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