Graduation Semester and Year

2013

Language

English

Document Type

Thesis

Degree Name

Master of Science in Biomedical Engineering

Department

Bioengineering

First Advisor

Ralph Mason

Abstract

A variety of solid tumors reveal oxygen deficiency as a result of rapid growth and insufficient tumor angiogenesis. Hypoxia in solid tumors appears to speed up malignant progression and metastatic potential of primary tumors thus leading to resistance against anticancer drugs and decreased response to radiotherapy.Of various in vivo non-invasive techniques to assess tumor hypoxia, oxygen-sensitive MRI (BOLD and TOLD) is an attractive and reliable option. Blood Oxygen Level Dependent (BOLD) and Tissue Oxygen Level Dependent (TOLD) MRI offer potential insight into tumor hypoxia. BOLD (Blood Oxygen Level Dependant) contrast MRI which measures R2* (1/T2*) is sensitive to endogenous paramagnetic deoxyhemoglobin and TOLD (Tissue Oxygen Level Dependant) MRI which measures R1 (1/T1) is based on T1-weighted imaging, which is sensitive to actual tumor tissue oxygenation. In this study, I investigate the efficacy of BOLD and TOLD to evaluate tumor hypoxia in response to oxygen challenge in rats.All MRI experiments were performed on a 4.7T small animal Varian scanner. Variation in BOLD and TOLD signal response observed in syngeneic Dunning R3327-AT1 prostatevtumor, with respect to oxygen breathing were compared with [18F]-Fluoromisonidazole (18FMISO) PET in hypoxic regions. In addition, variation in BOLD and TOLD signal response in syngeneic Dunning R3327-H, -HI, -AT1, -MAT-Lu prostate tumor sublines with respect to oxygen breathing was examined. The dependence of BOLD and TOLD signal response on tumor size is investigated. Preliminary studies on orthotopic PC3 tumors were done to examine the efficacy of BOLD and TOLD contrast MRI to assess tumor hypoxia.Significant correlations were found between BOLD and TOLD MRI and [18F] FMISO PET measurements for oxygen breathing. Considerable correlations were found between oxygen sensitive MRI (BOLD and TOLD) and tumor size. Preliminary studies on orthotopic tumors yielded convincing results providing a potential approach to translate BOLD and TOLD contrast MRI for clinical translation.

Disciplines

Biomedical Engineering and Bioengineering | Engineering

Comments

Degree granted by The University of Texas at Arlington

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