Thermoacoustic Imaging and Spectroscopy for Enhanced Cancer Diagnostics

Abstract

Early detection of cancer is paramount for improved patient survival. This dissertation presents work developing imaging techniques to improve cancer diagnostics and detection utilizing light and microwave induced thermoacoustic imaging. In the second chapter, the well-established pre-clinical mouse window chamber model is interfaced with simultaneously acquired high-resolution pulse echo (PE) ultrasound and photoacoustic (PA) imaging. Co-registered PE and PA imaging, coupled with developed image segmentation algorithms, are used to quantitatively track and monitor the size, shape, heterogeneity, and neovasculature of the tumor microenvironment during a month long study. Average volumetric growth was 5.35 mm³/day, which correlated well with two dimensional results from fluorescent imaging (R = 0.97, p < 0.01). Spectroscopic PA imaging is also employed to probe the assumed oxygenation status of the tumor vasculature. The window chamber model combined with high-resolution PE and PA imaging could form a powerful testbed for characterizing cancers and evaluating new contrast and therapeutic agents. The third chapter utilizes a clinical ultrasound array to facilitate fast volumetric spectroscopic PA imaging to detect and discriminate endogenous absorbers (i.e. oxy/deoxygenated hemoglobin) as well as exogenous PA contrast agents (i.e. gold nanorods, fluorophores). In vivo spatiotemporal tracking of administered gold nanorods is presented, with the contrast agent augmenting the PA signal 18 dB. Furthermore, through the use of spectral unmixing algorithms, the relative concentrations of multiple endogenous and exogenous co-localized absorbers were reconstructed in tumor bearing mice. The concentration of Alexaflour647 was calculated to increase nearly 20 dB in the center of a prostate tumor after a tail-vein injection of the contrast agent. Additionally, after direct subcutaneous injections of two different gold nanorods into a breast tumor, the concentration of each nanoparticle was discriminated in vivo with a signal-to-noise ratio of greater than 25 dB. This technique has great potential for improved early cancer detection and individualized cancer treatment through advanced pharmacokinetic monitoring of therapeutic agents. Finally, the fourth chapter presents significant improvements made to enhance breast cancer detection with thermoacoustic (TA) imaging. In a breast cancer simulating phantom, the initial demonstration of TA spectroscopy (TAS) is used to detect and discriminate relative water / fat composition based solely on the sample's intrinsic spectral absorption. The slope of the TA signal was highly correlated with that of the absorption coefficient (R² = 0.98, p < 0.01), indicating TAS can distinguish materials based on their dielectric properties. Furthermore, the use of carbon nanotubes as a potential TA contrast agent is explored. These nanoparticles significantly enhance the magnitude of the TA signal (8 dB larger than water), and also demonstrate unique absorption spectra. Finally, short microwave pulses (Δt ≥ 10 ns) are achieved through novel microwave hardware, and used to generate high-frequency TA signals. In conclusion, this section presents advancements made to the sensitivity, contrast, and resolution of TA imaging. Overall, this dissertation presents enhancements made to the diagnostic capabilities of PA and TA imaging for improved detection and characterization of cancer.