Deeply penetrating photoacoustic imaging in animals, with clinical potential

This study is focused on the development of two deeply penetrating photoacoustic (PA) imaging systems and their application on small and large animals, with the long term goal of achieving clinical applications. PA imaging is an emerging hybrid technology, combining the merits of optical and ultrasonic imaging modalities: it overcomes the poor spatial resolution of purely optical imaging methods, but retains optical sensitivity and specificity as well as ultrasonic imaging depth scalability. In this study, two PA imaging systems were designed and developed, in the mode of computed tomography and in the mode of reflection, respectively. The first developed system was a noninvasive in vivo three-dimensional photoacoustic tomography (PAT) system to visualize the vasculature of the whole head of a small animal. The system produced in vivo three-dimensional PAT images of the vasculature of a nude mouse head and in vivo three-dimensional images of brain tumors deeply situated in a nude mouse brain.;In addition to the PAT system, a deeply penetrating reflection mode PA imaging system was developed to visualize deeply located biological structures, improve spatial resolution in the depth direction, and extend the versatility of PA imaging systems. The imaging depth of the system was proven to be ∼38 mm in chicken breast tissue. This imaging system could noninvasively image the vasculature in the brain cortex of rats and the internal organs of rats and rabbits in vivo or in situ. It is believed that this work lays a foundation for studying internal organs using PA imaging in small animals.;For the development of clinical applications of this technique, noninvasive sentinel lymph node (SLN) identification using clinically available methylene blue was performed. The system imaged the SLN of a rat with good optical contrast and good spatial resolution. To evaluate the clinical potential, up to 31 mm imaging depth was also demonstrated. This depth was beyond the mean depth of SLNs in human beings. Since the PA SLN mapping is completely noninvasive, this technique can potentially allow minimally invasive sentinel lymph node biopsy (SLNB) with the aid of fine needle aspiration biopsy.;As new lymph node tracers, nanoparticles (5 nm-100 nm) could be good alternatives to current tracers, such as methylene blue and/or radioactive colloids, since nanoparticles can provide diagnostic information (imaging contrast or specific targeting) and therapeutic functions (targeted drug delivery). For noninvasive PA SLN mapping, Au nanocages were chosen as a lymph node tracer. With chicken breast tissues placed on the axillary region, the SLN of a rat was successfully identified with good contrast at about 33 mm depth. Au nanocages have a distinctive advantage over methylene blue: antibodies can be attached to their surface, making them a molecular biomarker. With this feature, PA imaging can potentially not only identify SLNs but also evaluate the metastasis in SLNs simultaneously. Au nanocage based PA mapping would greatly benefit breast cancer patients, once it is approved by the FDA.