Date of Graduation

12-2024

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Engineering (PhD)

Degree Level

Graduate

Department

Biomedical Engineering

Advisor/Mentor

Rajaram, Narasimhan

Committee Member

Muldoon, Timothy J.

Second Committee Member

Griffin, Robert J.

Third Committee Member

Barman, Ishan

Keywords

Cancer; Diffuse reflectance spectroscopy; Raman spectroscopy

Abstract

Every year there are millions of new cancer diagnoses and deaths worldwide. While great strides have been made in technologies and drugs for cancer treatment, there is still a need to understand tumor response to therapy as many patients still endure treatment failure after completing their treatment regimen. Current clinical imaging techniques for detecting response to therapy are utilized weeks to months after the course of treatment, and present limitations to measuring response during treatment. Optical spectroscopy techniques can help meet this need to determine the response of tumors to treatment as it allows for near real-time in vivo characterization of tissue and is minimally invasive.
This dissertation presents the use of two optical spectroscopy methods, diffuse reflectance spectroscopy (DRS) and Raman spectroscopy (RS), to monitor tumor microenvironmental changes in vivo. In Chapter 2, the sensitivity of diffuse reflectance spectroscopy to different doses of radiation therapy was investigated in a mouse model of breast cancer. Since radiation therapy is used as part of the treatment plan for many cancer patients, real-time monitoring of the radiation-induced changes on the tumor microenvironment will aid in understanding treatment response. From this study, it was concluded that DRS is sensitive to microenvironmental changes in tumors treated with doses as low as 1 Gy/fraction of radiation.
In Chapter 3, work to achieve the combination of diffuse reflectance spectroscopy and spatially offset Raman spectroscopy into a multimodal system with a fiber optic handheld probe and optical switch is presented. The probe was designed with spatially offset source-detector configuration to collect subsurface measurements for each modality, as well as ball lens-coupled fibers for surface measurements. The results of validation studies using the system with measurements on chicken breast tissue phantom consisting of fat and muscle tissue, as well as measurements acquired from the skin of a human volunteer are shown. This study demonstrated that both DRS and RS can acquire spectra from similar depths within tissue. Additionally, Raman peaks related to different biomolecules with both the conventional backscattering and spatially offset fibers were identified.
Finally in Chapter 4 the use of the multimodal spectroscopy system to observe changes in vivo in a murine model of melanoma is described. Mice were injected into one flank with either B16.F0 cells or B16.BL6 cells to form tumors, and spectroscopy measurements were acquired periodically as the tumors grew to 400 mm3. The collected spectra were assessed at different tumor volumes for both tumor types, and differences were seen in the intensity of hemoglobin concentration from DRS as well as melanin and collagen from RS.
Overall, the work in this dissertation presents efforts using optical spectroscopy to noninvasively study the tumor microenvironment to monitor tumor response to therapy. Multiple modalities were successfully integrated into a single, clinically relevant instrumentation platform which paves the way for further testing and validation of the importance of these measurements to personalized, multidisciplinary cancer care.

Download

Share

COinS