Laser Optoacoustic Imaging System for Molecular and Functional Imaging Research in Small Animal Models

Optoacoustic tomography is an emerging field of medical imaging that is rapidly developing due to its unique capability to visualize and display molecular content of biological tissues with quantitative accuracy and excellent spatial resolution scalable with depth within live tissues. The main merit of optoacoustic tomography is in deep tissue imaging where resolution and contrast of pure optical imaging methods are limited by the strong optical scattering. The dominating tissue chromophores in the spectral range of laser wavelengths (650 nm to 1100 nm) that penetrate deep within tissues are hemoglobin and oxyhemoglobin of blood. Potential capability of functional optoacoustic tomography systems to measure concentrations of hemoglobin and oxyhemoglobin in humans provides for a variety of medical applications in the fields of diagnostics, therapeutic interventions and surgery. Using the methods of molecular imaging, it is also possible to visualize distribution of molecules that do not possess strong optical absorption in the near infrared spectral range, but can be targeted by special molecular and nano-particular contrast agents designed with strong optical absorption and high efficiency of acoustic wave emission through thermal expansion. In spite of great promises the full potential of optoacoustic tomography in functional and molecular imaging has not been realized yet. In order to achieve capabilities of functional and molecular imaging, the optoacoustic tomography system has to overcome the tradeoff between high sensitivity of detection and ultrawide-bandwidth of ultrasonic frequency detection. Furthermore, quantitative imaging is only possible with knowledge of the optical fluence distribution through the entire volume of interest at each of the multiple wavelengths of laser illumination. We took on a challenging task to develop such an advanced tomography system and enhance it with the methods of quantitative data analysis and image reconstruction. We designed and assembled a full view three-dimensional Laser Optoacoustic Imaging System (LOIS-3D) based on a 96-channel array of ultrawide band ultrasonic transducers and demonstrated its highest sensitivity to changes in the optical absorption coefficient ~0.03/cm compared with any academic or industrial system. We proposed and implemented a signal processing method of transducer impulse response deconvolution that enabled reversal of distortions in the detected optoacoustic signals, which in turn allowed the experimental approach to functional and molecular imaging in live laboratory animals. The system technical specifications were characterized in a number of molecular imaging experiments. Finally, we proposed and implemented a practical method of the optical fluence normalization through the entire imaged volume based on measurements of the voxel brightness in blood vessels with known optical absorption and without computations of light propagation through tissues with unknown optical properties. We reconstructed previously unattainable functional images of the total hemoglobin and blood oxygen saturation in a volume of live tissue showing separately arteries, veins and tissues.