Photoacoustic Tomography: High-resolution Imaging of Optical Contrast in Vivo at New Depths

Lihong Wang
Gene K. Beare Distinguished Professor
Optical Imaging Laboratory
Department of Biomedical Engineering
Washington University in St. Louis

Monday, May 18, 2009 at 1:00PM
54-134 Engineering IV Building
Refreshments Served

Abstract: We develop photoacoustic imaging technologies for in vivo early-cancer detection and functional imaging by physically combining non-ionizing electromagnetic and ultrasonic waves. Unlike ionizing x-ray radiation, non-ionizing electromagnetic waves, such as optical and radio waves, pose no health hazard and, at the same time, 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, as demonstrated by confocal microscopy and two-photon microscopy as well as optical coherence tomography, is limited to superficial imaging within about one optical transport mean free path (~1 mm in the skin) of the surface of biological tissue. Ultrasonic imaging, on the contrary, provides good image resolution but has strong speckle artifacts as well as poor contrast in early-stage tumors. We have developed ultrasound-mediated imaging modalities by combining electromagnetic and ultrasonic waves synergistically to 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 in small animals. 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. The ultrasonic waves are then detected with a focused ultrasonic transducer to form a depth resolved 1D image directly. Raster scanning yields 3D high-resolution tomographic images. Super-depth beyond the optical transport mean free path has been reached with high spatial resolution.

Thermoacoustic tomography is similar to photoacoustic tomography except that low-energy microwave pulses, instead of laser pulses, are used. Although long-wavelength microwaves diffract rapidly, the short-wavelength microwave-induced ultrasonic waves provide high spatial resolution. Microwave contrast measures the concentrations of water and ions.

Biography: Dr. Lihong Wang studied for his Ph.D. degree at Rice University, Houston, Texas under the tutelage of Drs. Robert Curl, Richard Smalley and Frank Tittel. He currently holds the Gene K. Beare Distinguished Professorship in the Department of Biomedical Engineering at Washington University in St. Louis. He has authored and co-authored two books, including one of the first textbooks in the field of biomedical optics. He is the editor for the first comprehensive book on biomedical photoacoustic tomography. He has published 168 peer-reviewed journal articles and delivered 198 keynote, plenary, and invited talks. He received the Outstanding Young Scientist Award sponsored by Johnson & Johnson Medical, Inc. and the Houston Society for Engineering in Medicine and Biology. He is a fellow of the American Institute for Medical and Biological Engineering, the Optical Society of America, the Institute of Electrical and Electronics Engineers, and the Society of Photo-Optical Instrumentation Engineers. He serves on the editorial board for the Journal of Biomedical Optics and also served for Applied Optics. He has reviewed for more than 30 scientific journals. He serves as an equal co-chair for the annual conference on Photons plus Ultrasound, the 2010 Gordon Conference on Lasers in Medicine and Biology, and the 2010 OSA Topical Meeting on Biomedical Optics. He also serves as an equal co-chair for the International Biomedical Optics Society. He has served as a study section chair or grant reviewer for NIH, NSF, etc. He is currently a chartered member on an NIH study section. He serves as the founding chair for the scientific advisory board of a company commercializing his invention. His research on non-ionizing biophotonic imaging has been funded by NIH (principal investigator for 12 NIH grants, totaling >$21M), NSF, and other funding agencies. He was a recipient of the NIH FIRST award and NSF CAREER award. His laboratory invented or discovered frequency-swept ultrasound-modulated optical tomography, dark-field confocal photoacoustic microscopy (PAM), optical-resolution PAM, photoacoustic Doppler sensing, photoacoustic reporter gene imaging, focused scanning microwave-induced thermoacoustic tomography, exact reconstruction algorithms for photoacoustic or thermoacoustic tomography, sonoluminescence tomography, Mueller-matrix optical coherence tomography, optical coherence computed tomography, and oblique-incidence reflectometry. In particular, PAM broke through the long-standing penetration limit and reached super-depth for noninvasive biochemical, functional, and molecular imaging in living tissue at high resolution. His Monte Carlo model of photon transport in scattering media has been used worldwide.