Monitoring of tissue coagulation during thermotherapy using optoacoustic technique

Optical contrast agents have been widely applied to enhance the sensitivity and specificity of optical imaging with near-infrared (NIR) light. However, because of the overwhelming scattering of light in biological tissues, the spatial resolution of traditional optical imaging degrades drastically as the imaging depth increases. Here, for the first time to our knowledge, we present noninvasive photoacoustic angiography of animal brains in vivo with NIR light and an optical contrast agent. When indocyanine green polyethylene glycol, a novel absorption dye with prolonged clearance, is injected into the circulatory system of a rat, it obviously enhances the absorption contrast between the blood vessels and the background tissues. Because NIR light can penetrate deep into the brain tissues through the skin and skull, we are able to successfully reconstruct the vascular distribution in the rat brain from the photoacoustic signals. On the basis of differential optical absorption with and without contrast enhancement, a photoacoustic angiograph of a rat brain is acquired that matches the anatomical photograph well and exhibits high spatial resolution and a much-reduced background. This new technology demonstrates the potential for dynamic and molecular biomedical imaging.

Optoacoustic tomography (OAT) is a novel medical imaging method that uses optical illumination and ultrasonic detection to produce deep tissue images based on their light absorption. Abnormal angiogenesis in advanced tumors, that increases the blood content of the tumor, is an endogenous contrast agent for OAT. In early stages, however, angiogenesis is not sufficient to differentiate a tumor from normal tissue; justifying the application of an exogenous contrast agent. We have developed a molecular based contrast agent composed of gold nanoparticles conjugated to a monoclonal antibody that improves OAT imaging to potentiate its use in imaging deep tumors in early stages of cancer or metastatic lesions. Due to their strong optoacoustic signal, we used gold nanoparticles (NPs) as a contrast agent. To target NPs to breast cancer cells, we conjugated NPs to a monoclonal antibody that specifically binds cell surface receptors known to be overexpressed in human breast tumors. In a series of in vitro experiments, Herceptin (monoclonal antibody that binds HER2/neu) conjugated to 40 nm NPs (Mab/NPs) selectively targeted human SK-BR-3 breast cancer cells. The breast cancer cells were detected and imaged by OAT in a gelatin phantom that optically resembled breast tissue. Sensitivity experiments showed that a concentration as low as 10(9) NPs per ml were detectable at a depth of 6 cm. Experimental data together with theoretical analysis demonstrate the feasibility of detection of deeply seeded small tumors that express tumor associated antigens using targeted gold NPs and OAT.

This article reviews two types of ultrasound-mediated biophotonic imaging–acousto-optical tomography (AOT, also called ultrasound-modulated optical tomography) and photo-acoustic tomography (PAT, also called opto-acoustic or thermo-acoustic tomography)–both of which are based on non-ionizing optical and ultrasonic waves. The goal of these technologies is to combine the contrast advantage of the optical properties and the resolution advantage of ultrasound. In these two technologies, the imaging contrast is based primarily on the optical properties of biological tissues, and the imaging resolution is based primarily on the ultrasonic waves that either are provided externally or produced internally, within the biological tissues. In fact, ultrasonic mediation overcomes both the resolution disadvantage of pure optical imaging in thick tissues and the contrast and speckle disadvantages of pure ultrasonic imaging. In our discussion of AOT, the relationship between modulation depth and acoustic amplitude is clarified. Potential clinical applications of ultrasound-mediated biophotonic imaging include early cancer detection, functional imaging, and molecular imaging.