Feasibility of Dual Optical/Ultrasound Imaging and Contrast Media for the Detection and Characterization of Prostate Cancer

This research project focuses on prostate cancer, a devestating socioeconomic disease, whose detection is plagued with inadequate sensitivity and specificity. Hypoxia is the hallmark of malignancy because aggressive cancers outgrow their blood supply. We ultimately aim to build an instrument that combines OPtics and UltraSound (OPUS) to quantify hypoxia via optical imaging but with the improved spatial resolution of US imaging. Specifically, the acoustooptic effect will be used to nly modulate light (at the ultrasound frequency) which propagates through a small ultrasound focal zone. This DOD Idea Development Award is concerned with the development of a novel acousto-optic detection method and using microbubble-based contrast agents to significantly increase the light modulation and, moreover, the use of fluorescent microbubbles to provide additional enhancement. During the first year of the research project we demonstrated the detection of ultrasound-modulated incoherent photons followed by novel quadrature detection of ultrasound-modulated photons and fluorescence photons with a gain-modulated image intensified CCD camera approach. During the second year of the research project we demonstrated significant signal enhancement with ultrasound microbubbles and generation of higher harmonic modulation. We also demonstrated acoustooptic detection with a novel SPAD detector. During the third year of this research project we developed a novel acousto-optic light scattering system to robustly characterize ultrasound-induced oscillation of individual microbubbles and also observed microbubble collapse and implosion at higher ultrasound pressures. In the fourth and final year of this project we manufactured quenchable fluorescent microbubbles and modified the system to detect their ultrasound-modulated fluorescence. As such, this project was an overall success with all tasks completed.
The original document contains color images.