High frequency photoacoustic microscopy for high resolution imaging

Photoacoustic imaging (also called optoacoustic imaging) is a new hybrid imaging modality which offers tremendous potential for research and clinical applications and features main advantages of optical and acoustical techniques. It combines ultrasonic resolution with high optical contrast since signal generation is due to light absorption depending on the physiology of the examined biological tissue. The acoustic signal reports tissue-specific information about the local optical absorption. To increase the intrinsic contrast in tissue, plasmon-resonant gold nanostructures are of great interest for optical imaging because of their remarkable capacity to absorb and scatter light at visible and near-infrared wavelengths. Together with optimized nanoscale contrast agents, optoacoustic techniques can be used for molecular imaging purposes in many application fields in biology and medicine. The aim of the work presented here is to establish a scalable photoacoustic technolog y for volume imaging of biological samples down to diffraction limited microscopy. For this purpose we developed a photoacoustic microscopy platform allowing generation and detection of laser-induced ultrasound signals in a frequency range up to 300 MHz. The system based on an inverted microscope, a pulsed laser and a focused transducer provides high resolution images on a cellular level. It allows characterizing different types of nanoparticles with respect to their suitability as optoacoustic contrast agent. We characterized the resolution of our system using different types of focused transducers and a 1 m toner particle as optoacoustic source. The lateral -6 dB width of the pointspread-function was found to be in the range of 5 m. Further, we investigated the possibility of optoacoustic imaging of cell monolayers incubated with gold nanoshells. The resulting optoacoustic image was compared to pure optical microscope data and a clear correlation was found.