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Title:Photoacoustic imaging: development of near infrared platforms for non-invasive deep-tissue imaging
Author(s):Zhang, Pamela Yuhua
Department / Program:Chemistry
Degree Granting Institution:University of Illinois at Urbana-Champaign
Subject(s):ratiometric photoacoustic imaging
Copper(II) sensing
deep-tissue imaging
Abstract:Fluorescence imaging has been employed as the gold-standard in molecular imaging. However, despite its ubiquitous usage, this technique is only viable for studying molecular interactions within a cellular system. Fluorescence imaging is limited by optical diffusion, at depths greater than 1 mm, sensitivity of this technique dramatically decreases. As light passes through biological tissues, it is scattered and absorbed, resulting in an exponential loss in light intensity as a function of sample thickness. This physical limitation in fluorescence-based imaging has prevented high resolution analyte-specific molecular interaction studies to be performed on multi-cellular organisms. Despite optimization of quantum yield and near-infrared absorbance (NIR), the resolution achievable to optical imaging is insufficient. To image deeper through tissue, new techniques need to be developed. Of interest is the application of the photoacoustic (PA) effect toward imaging. The PA effect occurs when optical excitation generates non-radiative relaxation through thermoelastic expansion, which produces sound waves that can be detected as ultrasound emissions. The PA signal is subject to minimal scattering in comparison to traditional fluorescence imaging, as sound scatters considerably less than light through biological matter. Coupled with excitation in the NIR window, PA imaging has the potential image in the cm range with micron resolution, Given the depth penetration PA imaging is capable of, the field lacks analyte-specific probe development. The most commonly used analyte specific probes consist of a chromophore and reactive handle, which is commonly referred to as a "trigger," will recognize a specific analyte and upon coordination will induce a reaction or a shift in electronics within the system, outputting a colorimetric or fluorescent response. Due to the prolific usage of optical imaging, fluorescence-based probes have been designed to recognize a multitude of biomolecules and enzymatic activities. Within biologically relevant ions, of special interest to the Chan lab is copper. Copper is a vital transition metal that acts as an important cofactor for many enzymes in biological systems. Misregulation of copper has been linked to multiple neurological disorders, such as Alzheimer’s disease. Given its essential function, in vivo imaging of copper has the potential to provide insight into its role in disease models. Current PA exogenous contrast agents generate enhanced signal as a result of increased concentration in the area of interest. Synthesis of analyte specific PA probes provides an important chemical tool required for non-invasive deep-tissue imaging. Similar to fluorescent probes, PA probes benefit from absorbance in the NIR window. Due to the lack of viable probes in the current field, this work focuses on the design and synthesis of a PA probe platform that can be coupled with a variety of triggers and capable of deep-tissue imaging of biologically relevant analytes.
Issue Date:2016-01-22
Rights Information:Copyright 2016 Pamela Zhang
Date Available in IDEALS:2016-07-07
Date Deposited:2016-05

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