Integrated photoacoustic and fluorescence imaging system for anatomical, functional, and molecular characterization of murine models

SUMMARY PhotoSound Technologies, Inc. proposes to develop a novel imaging modality for characterization and preclinical research of small animal models. The technology will be capable of three-dimensional functional and molecular imaging of fluorescent labels and reporter genes mapped with high fidelity over robust anatomical structures, such as skin, central and peripheral vasculature, and internal organs. The Phase II commercial instrument is designed to perform high-throughput whole body imaging of rodent models. It could be used in broad spectrum of preclinical research applications including cancer, toxicology, tissue engineering and regeneration, cardiovascular and developmental biology. In addition to qualitatively superior performance characteristics, the proposed multimodality imaging platform will significantly reduce space and funds required to house and operate a whole-body imaging platform at an animal research facility. Optical in vivo imaging methods (fluorescence and bioluminescence) found great popularity among researchers as affordable, convenient, and very sensitive molecular imaging tools for preclinical studies and development of animal models. However, their stand-alone application is impeded by poor spatial resolution and limitations imposed by two-dimensionality of the images. A fast and high-resolution in vivo 3D imaging method, which could be easily integrated with optical imaging in a single instrument, would have a great impact on the entire field of small animal research. Photoacoustic tomography is an emerging whole body 3D imaging modality capable of 200-500 µm resolution. It can also use the same components for excitation of fluorescence and generation of photoacoustic effect. However, its in vivo application for detection of fluorophores is impeded by strong background generated by native blood. Also, there are no commercial or research photoacoustic whole- body imaging instrument that could work with high-throughput imaging procedures (lt5 min per animal). Our proposal shows a way to defeat shortcomings of each individual technology and enable fast high-resolution whole body 3D imaging of fluorescent biomarkers by integrating robotic scanning and multi-view orthogonal fluorescence and photoacoustics in a single co-registered modality (PAFT). The Phase II project is focused on development of a commercial PAFT instrument and is organized in three specific aims: (1) Develop, fabricate, and assess the performance of a commercial PAFT instrument; (2) Develop and implement high-throughput PAFT image reconstruction method; (3) Field-test the commercial PAFT instrument. Ultimate commercial system will enable high-throughput in vivo 3D visualization and analysis of native hemoglobin, fluorophores, nanoparticles, and other photosensitive constructs used for molecular and functional mapping and longitudinal studies. Such an instrument would alleviate subjective interpretation of missing and misregistered imaging data and would streamline the preclinical phase of development, leading to a higher success rate and lower costs of drug development.