Date of Graduation

5-2017

Document Type

Thesis

Degree Name

Master of Science in Biomedical Engineering (MSBME)

Degree Level

Graduate

Department

Biomedical Engineering

Advisor/Mentor

Narasimhan Rajaram

Committee Member

Kartik Balachandran

Second Committee Member

Timothy J. Muldoon

Keywords

Applied sciences, Cancer, Diffuse reflectance spectroscopy, Lookup table model, Radioresistance, Radiotherapy

Abstract

Along with chemotherapy, immunotherapy, and surgery, radiotherapy is one of the most common treatments used against cancer. Around 50% of all cancer patients undergo radiation therapy. While for some patients radiotherapy works efficiently and lead to a complete cancer disappearance, for others treatment outcome may be less favorable due to radioresistance processes happening within a tumor on the molecular level. Radioresistance remains a big challenge for modern oncology. The ability to identify radioresistance at the early stage of radiotherapy would help physicians to improve therapy efficiency. At the current moment, despite the rapid progress in cancer understanding and diagnostic modalities, there is no established technique that would enable early identification of tumor radioresistance.

Tumor oxygenation plays a crucial role for radiotherapy efficiency. We hypothesize that diffuse reflectance spectroscopy (DRS) enabling repeated non-invasive measurements of tumor vascular oxygen saturation can provide surrogate measures of tumor oxygenation to predict tumor response to therapy. The goal of this study is to determine the sensitivity of diffuse reflectance spectroscopy to changes in tumor oxygenation after single-dose radiation therapy in a preclinical tumor xenograft model. We established three specific aims addressing the ability of DRS to provide accurate measures of tumor properties. The first aim is to determine the effect skin thickness on the extraction of optical parameters using one-layer Lookup Table (LUT) model. The second aim is to determine depth- and dose-dependent changes in DRS-measured vascular oxygenation during radiotherapy. The third aim is to determine the association between DRS-measured vascular oxygenation and immunohistochemically assessed intracellular hypoxia.

Our results demonstrate a significant impact of skin thickness on the extraction of optical parameters for short source-detector separations caused by the one-layer assumption of the LUT model. We also detected LUT model failure to identify the absence of melanin when skin is mechanically removed. These findings suggest that existing LUT model needs to be modified to account for the effect of the skin layer. Measurements with different source-detector separations revealed higher concentration of hemoglobin in superficial layer of tumors and blood supply disruption after exposure to 8 Gy of radiation.

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