? The overall goal of this research is to create and apply a unique dual-modality system for time-series imaging of colon cancer development in mice. Miniaturized optical coherence tomography (OCT), laser induced fluorescence (LIF), and novel contrast agents are combined into a sensitive structural and biochemical imaging system. The minimally invasive nature of this system means that the development (and response to treatment) of each individual tumor can be tracked in vivo. This study is divided into 4 specific aims: 1. Design, build and test miniature combined OCTILIF catheters. We propose to build a high-throughput probe with ability to measure the entire lower colon with one insertion. Subsequently, we propose to build a large bandwidth catheter that supports very high resolution imaging. 2. Develop novel contrast agents for improved visualization of tumors. Contrast agents may help identify the earliest stages of carcinogenesis. We will investigate three classes: a) gold-coated nanoshells, which we have shown to have an extremely bright OCT signature, b) liposomes, which incorporate fluorescent dyes, and c) dietary cholorphyll, These agents will be tested in phantoms, cell cultures, and mouse models. 3. Perform studies of DMH-treated and MIN mice with and without contrast agents and NSAID administration. Two mouse models, DMH-treated and genetically altered multiple intestinal neoplasia (MIN) will be utilized in this specific aim. In a series of studies, the lower colon of these mice will be imaged every 3-6 weeks to evaluate tumorigenesis. The effect of non-steroidal anti-inflammatory agent (NSAID) preventive and therapeutic treatment will be assessed, as will enhancement of image contrast with the contrast agents in specific aim 2. 4. Develop analysis tools for interpreting OCT images and LIF spectra. Storage and retrieval software will be developed. For analyzing OCT images, texture analysis and automated layer thickness measurements will be used, and for LIF spectra, component analysis and intrinsic fluorescence extraction methods will be employed. ? ?
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