Acoustic and photoacoustic imaging of spheroids

Abstract

Acoustic and photoacoustic high frequency imaging (50–100 MHz) can be used to generate images of cell constructs and spheroids with good spatial resolution and contrast. Here we demonstrate how co-registered acoustic and photoacoustic imaging can be used for imaging spheroids. Spheroids are widely used in cancer research and biology since they emulate a three-dimensional environment such as that experienced in tumors. Spheroids were made by the hanging-drop method using the MCF-7 cancer cell line. To generate photoacoustic contrast, MCF-7 cells were incubated with optical absorbing nanoparticles (e.g., gold nanorods, 780 nm absorption) for 24 h and mixed with native MCF-7 cells prior to spheroid formation. The spheroids were between 0.5 mm and 1mm in diameter. Imaging was performed with the VisualSonics VEVO 770 (25–55 MHz) and a high-resolution SASAM acoustic/photoacoustic microscope for frequencies over 80 MHz (Kibero GmbH, Germany). The spheroid was imaged first using pulse echo ultrasound, then with photoacoustics immediately after. The necrotic core of the spheroid had a 20 dB increase in ultrasound backscatter compared the viable cells surrounding the core, and the ultrasound/photoacoustic images of the spheroid were co-registered showing the distribution of the optical absorbing agents.