X-Ray and Optical Techniques for Classification & Characterization of Tissue for Applications in Cancer

Abstract

In this work, x-ray and optical techniques were utilized to analyze tissue for two main applications in cancer: intraoperative breast cancer margin assessment and contrast agent development for prostate cancer magnetic resonance imaging (MRI). A clinically compatible combined time-resolved fluorescence and diffuse reflectance (TRF-DR) spectroscopy system was used to measure breast tissue from 80 patients with invasive ductal carcinoma (IDC). A procedure was developed to compare extracted optical parameters with histological analysis. Trends in optical parameters between breast tumor, adipose, and fibroglandular tissue were investigated. Optical parameters that showed statistically significant differences between tissue groups were used in multivariate analysis and tissue modelling. Tissue classification using the combined system resulted in tumor detection sensitivity and specificity of 83.9% and 96.2%, respectively. Further work studying more fibroglandular tissue and tissue of mixed composition would develop this system for intraoperative use for tumor margin detection. In addition, micro-synchrotron radiation x-ray fluorescence (μ-SRXRF) was used to determine the efficacy of a novel gadolinium-based contrast agent for zinc-targeting in prostate cancer imaging. Trends in elements of interest such as Gd, Zn, Fe, Cu, and S between mice with prostate cancer, castrate-resistant prostate cancer, and normal mice were observed. Raster scans were collected of large regions of the prostate as well as within the lateral lobe specifically. Significant Zn and Gd co-localization was observed in both healthy and malignant tissues. Also, a marked decrease in Zn was found in the lateral lobe of the prostate obtained from mice with prostate cancer. The sample preparation and processing procedure outlined in this work provide a feasible and effective method of assessing the efficacy of MRI contrast agents in vivo. With the ability to use a beam as small as 5μm × 5μm, this optimized technique also lends itself to the investigation of other elements and contrast agents in biological tissue.