BME Colloquium Series: Stanislav Emelianov, Ph.D.

Light, Sound, nanoAction: Ultrasound-guided Photoacoustics in Cancer Imaging and Therapy

Ultrasound, Imaging, and Therapeutics Research Laboratory, Department of Biomedical Engineering

University of Texas at Austin

Abstract

An in-vivo imaging technique that can monitor molecular events during various stages of tumor progression and cancer treatment is desired for many biomedical, preclinical and clinical applications. For example, small animal models are recognized as powerful discovery tools in cancer research. However, the potential of animal models has not yet fully been realized since they are often sacrificed to perform tissue analysis and to determine the effects of therapy. This prevents in vivo observation of the natural or perturbed processes. Therefore, there is a need for a functional, molecular, and morphologic quantitative imaging technique capable of visualizing biochemical, pharmacological and other processes in vivo and repetitively in the same animal.

Recently, we introduced high-resolution, high-sensitivity, depth-resolved ultrasound-guided photoacoustic (USPA) imaging where ultrasound (US) is used to visualize anatomical structures and photoacoustics (PA) is used to provide functional information about the tissue. Furthermore, targeted contrast agents were developed to enable the cellular and molecular sensitivity of USPA imaging. We will first demonstrate the ability of ultrasound and nanoparticle-mediated photoacoustic imaging to simultaneously obtain the anatomical and molecular map of tumor in-vivo. Here, spherical gold nanoparticles (NPs) were functionalized to target cancer biomarkers such as epidermal growth factor receptor (EGFR). Once injected intravenously, the gold nanospheres undergo molecular specific aggregation at the site of active cancerous cells. This receptor mediated clustering of NPs leads to an optical red-shift of the plasmon resonance frequency. Capitalizing on this effect we obtained three-dimensional ultrasound (US) and molecular specific photoacoustic (PA) images of mouse tumor in-vivo.

Furthermore, we will demonstrate the role of ultrasound and photoacoustic (USPA) imaging in cancer therapy. Specifically, we developed an image-guided, molecularly specific, temperature-controlled photothermal therapy of cancer using targeted metal nanoparticles. In our approach, before the therapeutic procedure, using ultrasound (anatomical and blood flow imaging) and elastography (biomechanical functional imaging), the tumor is non-invasively imaged to develop an appropriate treatment plan. Furthermore, the delivery and interaction of molecular specific photoabsorbers with cancerous tissue is imaged using photoacoustics – a technique capable of in-vivo imaging of plasmonic nanoparticles at sufficient depth. During the therapy, the USPA imaging system is used to guide photothermal therapy by tracking the temperature rise and, therefore, monitoring cancer treatment. Finally, after the therapy, the combined imaging is used to accurately assess the short-term and the long-term treatment outcome.