Neuroscience Seminar Series:
Lihong Wang, Washington University in St. Louis
‘Photoacoustic Tomography: Beat Optical Diffusion and Diffraction’
We develop photoacoustic tomography technologies for in vivo functional, metabolic, molecular, and histologic imaging by physically combining non-ionizing electromagnetic and ultrasonic waves. Broad applications include early-cancer detection and brain imaging. Unlike ionizing x-ray radiation, non-ionizing electromagnetic waves—such as optical and radio waves—pose no health hazard and reveal new contrast mechanisms. Unfortunately, electromagnetic waves in the non-ionizing spectral region do not penetrate biological tissue in straight paths as x-rays do. Consequently, high-resolution tomography based on non-ionizing electromagnetic waves alone—such as confocal microscopy, two-photon microscopy, and optical coherence tomography—is limited to superficial imaging within approximately one optical transport mean free path (~1 mm in the skin) of the surface of scattering tissue. Ultrasonic imaging, on the contrary, provides good image resolution but suffers strong speckle artifacts as well as poor contrast in early-stage tumors. Ultrasound-mediated imaging modalities that combine electromagnetic and ultrasonic waves can synergistically overcome the above limitations. The hybrid modalities provide relatively deep penetration at high ultrasonic resolution and yield speckle-free images with high electromagnetic contrast. In photoacoustic computed tomography, a pulsed broad laser beam illuminates the biological tissue to generate a small but rapid temperature rise, which leads to emission of ultrasonic waves due to thermoelastic expansion. The short-wavelength pulsed ultrasonic waves are then detected by unfocused ultrasonic transducers. High-resolution tomographic images of optical contrast are then formed through image reconstruction. Endogenous optical contrast can be used to quantify the concentration of total hemoglobin, the oxygen saturation of hemoglobin, and the concentration of melanin. Melanoma and other tumors have been imaged in vivo. Exogenous optical contrast can be used to provide molecular imaging and reporter gene imaging. In photoacoustic microscopy, a pulsed laser beam is focused into the biological tissue to generate ultrasonic waves, which are then detected with a focused ultrasonic transducer to form a depth resolved 1D image. Raster scanning yields 3D high-resolution tomographic images. Super-depths beyond the optical diffusion limit have been reached with high spatial resolution. Super-resolution beyond the optical diffraction limit has also been achieved recently. The following skin image was acquired in vivo in a mouse using optical-resolution photoacoustic microscopy.