Yan XuFollow

Date of Completion

11-5-2013

Embargo Period

11-5-2013

Keywords

Diffuse optical tomography; Breast cancer imaging; Ultrasound guided reconstruction; Tumor oxygen saturation; Tumor hypoxia; Fluorescence tomography; Indocyanine green; 2-nitroimidazole; Layered structure imaging

Major Advisor

Quing Zhu

Associate Advisor

Rajeev Bansal

Associate Advisor

Michael Smith

Field of Study

Electrical Engineering

Degree

Doctor of Philosophy

Open Access

Open Access

Abstract

Breast cancer is the most common cancer and the second major cause of cancer death among women. Screening tries to detect the disease in the early stage, and can save more lives. Diffuse optical tomography (DOT) in the near-infrared (NIR) spectrum is a promising noninvasive approach for functional diagnostic breast imaging. Our group has explored the use of ultrasound (US)-guided DOT to improve lesion localization and light quantification accuracy. In this dissertation, several special cases of breast cancer imaging were studied with theUSguided DOT technique.

Firstly, the heterogeneous absorption distributions of advanced cancers were characterized. A series of simulations and phantom experiments were then performed to systematically evaluate the effects of target parameters, target locations, and target optical properties on imaging the periphery enhancement absorption distribution using a reflection geometry. A clinical example is given to demonstrate the complexity of tumor vasculature. Secondly, to improve the light quantification of clustered lesions, a new multi-zone reconstruction algorithm guided by co-registered US image is investigated using simulations and phantoms experiments. The performance of the algorithm is demonstrated with clinical examples. Thirdly, the DOT mapping of tumor deoxy-hemoglobin (deoxyHb) and oxy-hemoglobin (oxyHb) concentrations in blood phantoms and in in-vivo patients is presented. Targets of different sizes located at different depths were used to validate the accuracy of oxygen saturation estimation. Clinical examples are given to demonstrate the mapping of heterogeneous deoxyHb and oxyHb distributions in breast cancers. Fourthly, in vivo mouse tumor imaging using fluorescence DOT were conducted; this demonstrated an improved imaging capability of a new synthesized 2-nitroimidazole-indocyanine green conjugate using a piperazine linker (piperazine-2-nitroimidazole-ICG) relative to an earlier version with an ethanolamine linker (ethanolamine-2-nitroimidazole-ICG). All the findings have been supported with the fluorescence images of histological sections of tumor samples and an immunohistochemistry technique for identifying tumor hypoxia. Lastly, a two-step imaging model was set up for the two-layer tissue structure of breast imaging. Absorption and scattering distributions of the lesions in the layered structure could be reconstructed simultaneously. Simulation and phantom experiments show promising accuracy and clinical examples were applied to demonstrate the utility of this imaging method.

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