Three-dimensional Deep-tissue Functional and Molecular Imaging by Integrated Photoacoustic, Ultrasound, and Angiographic Tomography (PAUSAT)

Abstract

Non-invasive small-animal imaging technologies, such as optical imaging, magnetic resonance imaging and x-ray computed tomography, have enabled researchers to study normal biological phenomena or disease progression in their native conditions. However, existing small-animal imaging technologies often lack either the penetration capability for interrogating deep tissues (e.g., optical microscopy), or the functional and molecular sensitivity for tracking specific activities (e.g., magnetic resonance imaging). To achieve functional and molecular imaging in deep tissues, we have developed an integrated photoacoustic, ultrasound and angiographic tomography (PAUSAT) system by seamlessly combining light and ultrasound in a non-invasive manner. PAUSAT can perform three imaging functions simultaneously with complementary contrast: high-frequency B-mode ultrasound imaging of tissue morphology, microbubble-enabled acoustic angiography of vasculature, and multi-spectral photoacoustic imaging of molecular probes. PAUSAT can provide three-dimensional (3D) multi-contrast images that are automatically co-registered, with high spatial resolutions at large depth. Using PAUSAT, we conducted proof-of-concept in vivo experiments on various small animal models: monitoring longitudinal development of placenta and embryo during mouse pregnancy, tracking biodistribution and metabolism of near-infrared organic dye on the whole-body scale, and detecting genetically-encoded breast tumor expressing photoswitchable phytochromes. These results have collectively demonstrated that PAUSAT has broad applicability in biomedical research, providing comprehensive structural, functional, and molecular imaging of small animal models.

Three-dimensional non-invasive brain imaging of ischemic stroke by integrated photoacoustic, ultrasound and angiographic tomography (PAUSAT)

“…A control box with an FPGA (myRIO, National Instruments, USA) is programmed to synchronize the motorized stage motion, laser firing, and PA data acquisition. 2D PACT images are generated using a dual speed-of-sound delay-and-sum reconstruction method [16] . Stacks of 2D PA images are then combined to create a 3D PACT volume.…”

“…However, AA lacks information on the functional status of the vessels such as blood oxygenation. Thus, taking advantage of the complementary imaging contrast of PACT and AA, we have recently developed a new PAUSAT imaging system that integrates PACT, AA, and high-frequency B-mode ultrasound imaging, simultaneously providing morphological, functional, and molecular imaging on the same animals [16] .…”