Optical Imaging  

Photoacoustic Tomography

Photoacoustic tomography has been developed for in vivo functional, metabolic, molecular, and histologic imaging by physically combining optical and ultrasonic waves. Broad applications include early-cancer detection and brain imaging. High-resolution optical imaging modalities, such as confocal microscopy, two-photon microscopy, and optical coherence tomography, are limited to superficial imaging within the optical diffusion limit (~1 mm in the skin) from the surface of scattering tissue. By synergistically combining light and sound, photoacoustic tomography provides deep penetration at high ultrasonic resolution and high optical contrast. Endogenous optical contrast can be used to quantify the concentrations of oxyhemoglobin, deoxyhemoglobin, melanin, lipids, water, cytochromes, DNA/RNA, bilirubin, etc. Exogenous optical contrast can be used to provide molecular imaging and reporter gene imaging as well as glucose-uptake imaging.

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 unscattered pulsed ultrasonic waves are then detected by ultrasonic transducers. High-resolution tomographic images of optical contrast are then formed through image reconstruction.

In photoacoustic microscopy, a pulsed laser beam is delivered 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.

Selected publications:

  • [Li, L.; Zhu, L.; Ma, C.; Lin, L.]; Yao, J.; Wang, L.; Maslov, K.; Zhang, R.; Chen, W.; Shi, J. H.; Wang, L. V.; "Single-impulse panoramic photoacoustic computed tomography of small-animal whole-body dynamics at high spatiotemporal resolution," Nature Biomedical Engineering 1 0071 (2017) [Request PDF]

  • Wong, T. T. W.; Zhang, R.; Hai, P.; Zhang, C.; Pleitez, M. A.; Aft, R. L.; Novack, D. V.; Wang, L. V.; "Fast label-free multilayered histology-like imaging of human breast cancer by photoacoustic microscopy," Science Advances 3(5) e1602168 (2017) [Request PDF]

  • [Yao, J.; Kaberniuk, A. A.; Li, L.]; Scherbakova, D. M.; Zhang, R.; Wang, L.; Li, G.; Verkhusha, V. V.; Wang, L. V.; "Multiscale photoacoustic tomography using reversibly switchable bacterial phytochrome as near-infrared photochromic probe," Nature Methods 13(1) 6773 (2016) [Request PDF]

  • Wang, L. V.; Yao, J.; "A practical guide to photoacoustic tomography in the life sciences," Nature Methods 13(8) 627637 (2016) [Request PDF]

  • Lai, P.; Wang, L.; Tay, J. W.; Wang, L. V.; "Photoacoustically guided wavefront shaping (PAWS) for enhanced optical focusing in scattering media," Nature Photonics 9 126-132 (2015) [PDF]

  • Yao, J.; Wang, L. ; Yang, J. M.; Maslov, K. I.; Wong, T. T. W.; Li, L.; Huang, C.; Zou, J.; Wang, L. V.; "High-speed label-free functional photoacoustic microscopy of mouse brain in action," Nature Methods 12(5) 407-10 (2015) [PDF]

  • Yao, J.; Wang, L.; Li, C.; Zhang, C.; Wang, L. V.; "Photoimprint photoacoustic microscopy for three-dimensional label-free sub-diffraction imaging," Physical Review Letters 112(1) 014302 (2014) [PDF]

  • Nasiriavanaki, M.; Xia, J.; Wan, H.; Bauer, A. Q.; Culver, J. P.; Wang, L. V.; "High-resolution photoacoustic tomography of resting-state functional connectivity in the mouse brain," PNAS 111(1) 2126 (2014) [PDF]

  • Wang, L.; Zhang, C.; Wang, L. V.; "Grueneisen relaxation photoacoustic microscopy," Physical Review Letters 113 174301 (2014) [PDF]

  • Wang, L.; Maslov, K.; Wang, L. V.; "Single-cell label-free photoacoustic flowoxigraphy in vivo," PNAS 110(15) 57595764 (2013) [PDF]

  • Wang, L.; Xia, J.; Yao, J.; Maslov, K. I.; Wang, L. V.; "Ultrasonically encoded photoacoustic flowgraphy in biological tissue," Physical Review Letters 111 204301 (2013) [PDF]

  • Yang, J. M.; Favazza, C.; Chen, R.; Yao, J.; Cai, X.; Maslov, K.; Zhou, Q.; Shung, K. K.; Wang, L. V.; "Simultaneous functional photoacoustic and ultrasonic endoscopy of internal organs in vivo," Nature Medicine 18(8) 1297-1303 (2012) [PDF]

  • Wang, L. V.; Hu, S.; "Photoacoustic tomography: in vivo imaging from organelles to organs," Science 335 1458-1462 (2012) [PDF]

  • Wang, L. V.; "Multiscale photoacoustic microscopy and computed tomography," Nature Photonics 3(9) 503-509 (2009) [PDF]

  • [Guo, Z.; Li, L.]; Wang, L. V.; "On the speckle-free nature of photoacoustic tomography," Medical Physics 36(9) 4084-4088 (2009) [PDF]

  • [Maslov, K.; Zhang, H. F.; Hu, S.]; Wang, L. V.; "Optical-resolution photoacoustic microscopy for in vivo imaging of single capillaries," Optics Letters 33(9) 929-931 (2008) [PDF]

  • Song, K. H.; Stein, E. W.; Margenthaler, J. A.; Wang, L. V.; "Noninvasive photoacoustic identification of sentinel lymph nodes containing methylene blue in vivo in a rat model," Journal of Biomedical Optics 13(5) 054033 (2008) [PDF]

  • Wang, L. V.; "Prospects of photoacoustic tomography," Medical Physics 35(12) 5758-5767 (2008) [PDF]

  • Zhang, H. F.; Maslov, K.; Wang, L. V.; "In vivo imaging of subcutaneous structures using functional photoacoustic microscopy," Nature Protocols 2(4) 797804 (2007) [PDF]

  • Zhang, H. F.; Maslov, K.; Stoica, G.; Wang, L. V.; "Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging," Nature Biotechnology 24(7) 848-851 (2006) [PDF]

  • Xu, M. H.; Wang, L. V.; "Photoacoustic imaging in biomedicine," Review of Scientific Instruments 77(4) 041101-(1-22) (2006) [PDF]

  • Xu, M. H.; Wang, L. V.; "Universal back-projection algorithm for photoacoustic computed tomography," Physical Review E 71(1) 016706-(1-7) (2005) [PDF]

  • Xu, Y.; Wang, L. V.; "Time reversal and its application to tomography with diffracting sources," Physical Review Letters 92(3) 033902-(1-4) (2004) [PDF]

  • Wang, X. D.; Pang, Y. J.; Ku, G.; Xie, X. Y.; Stoica, G.; Wang, L. V.; "Noninvasive laser-induced photoacoustic tomography for structural and functional in vivo imaging of the brain," Nature Biotechnology 21(7) 803-806 (2003) [PDF]

  • Xu, M. H.; Wang, L. V.; "Analytic explanation of spatial resolution related to bandwidth and detector aperture size in thermoacoustic or photoacoustic reconstruction," Physical Review E 67(5) 056605 (2003) [PDF]

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