Date of Graduation
5-2019
Document Type
Dissertation
Degree Name
Doctor of Philosophy in Engineering (PhD)
Degree Level
Graduate
Department
Biomedical Engineering
Advisor/Mentor
Muldoon, Timothy J.
Committee Member
Rajaram, Narasimhan
Second Committee Member
Quinn, Kyle P.
Third Committee Member
Wang, Yong
Keywords
Colorectal; Mouse; Oxyhemoglobin; Reflectance; Spectoscopy; Tumor
Abstract
Colorectal cancer is the 4th most common and 2nd deadliest cancer. Problems exist with predicting which patients will respond best to certain therapy regimens. Diffuse reflectance spectroscopy has been suggested as a candidate to optically monitor a patient’s early response to therapy and has been received favorably in experimentally managing other cancers such as breast and skin. In this dissertation, two diffuse reflectance spectroscopy probes were designed: one with a combined high-resolution microendoscopy modality, and one that was optimized for acquiring data from subcutaneous murine tumors. For both probes, percent errors for estimating tissue optical properties (reduced scattering coefficient and absorption coefficient) were less than 5% and 10%, respectively. Then, studies on tissue-simulating phantoms were performed to test probe sensitivity and to serve as testing platforms for investigators in biomedical optics. Next, the diffuse reflectance spectroscopy probe was applied to subcutaneous murine colon tumors (n=61) undergoing either antibody immunotherapy or standard 5-fluorouracil chemotherapy. Mice treated with a combination of these therapies showed reduced tumor growth compared to saline control, isotype control, immunotherapy, and chemotherapy groups (p<0.001, <0.001, <0.001, and 0.046, respectively) 7 days post-treatment. Additionally, at 7 days post-treatment, oxyhemoglobin, a marker currently being explored as a functional prognostic cancer marker, trended to increase in immunotherapy, chemotherapy, and combination therapy groups compared to controls (p=0.315, 0.149, and 0.190). Also of interest, an oxyhemoglobin flare (averageincrease of 1.44x from baseline, p=0.03 compared to controls) was shown in tumors treated with chemotherapy, indicating that diffuse reflectance spectroscopy may be useful as a complimentary tool to monitor early tumor therapeutic response in colon cancer. However, subject-to-subject variability was high and studies correlating survival to early oxyhemoglobin flares are suggested.
Citation
Greening, G. J. (2019). Diffuse Reflectance Spectroscopy to Quantify In Vivo Tissue Optical Properties: Applications in Human Epithelium and Subcutaneous Murine Colon Cancer. Graduate Theses and Dissertations Retrieved from https://scholarworks.uark.edu/etd/3251
Included in
Bioimaging and Biomedical Optics Commons, Biomedical Devices and Instrumentation Commons, Cancer Biology Commons, Molecular, Cellular, and Tissue Engineering Commons