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Photoacoustic Tomography (PAT)

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

  1. [Cao, R.; Zhao, J.]; Li, L.; Du, L.; Zhang, Y.; Luo, Y.; Jiang, L.; Davis, S.; Zhou, Q.; de la Zerda, A.; Wang, L. V.; "Optical-resolution photoacoustic microscopy with a needle-shaped beam," Nature Photonics 17 89-95 (2023) [PDF]
  2. Cao, R.; Nelson, S. D.; Davis, S.; Liang, Y.; Luo, Y.; Zhang, Y.; Crawford, B.; Wang, L. V.; "Label-free intraoperative histology of bone tissue via deep-learning-assisted ultraviolet photoacoustic microscopy," Nature Biomedical Engineering (2022) [PDF]
  3. Lin, L.; Wang, L, V.; "The emerging role of photoacoustic imaging in clinical oncology," Nature Reviews Clinical Oncology 365-384 (2022) [PDF]
  4. [Na, S; Russin, J. J.; Lin, L; Yuan, X]; Hu, P; Jann, K. B.; Yan, L; Maslov, K; Shi, J; Wang, D. J.; Liu, C. Y.; Wang, L. V.; "Massively parallel functional photoacoustic computed tomography of the human brain," Nature Biomedical Engineering 584-592 (2021) [PDF]
  5. Garrett, D. C.; Wang, L. V.; "Acoustic sensing with light," Nature Photonics (2021) [PDF]
  6. [Li, L; Li, Y]; Zhang, Y; Wang, L. V.; "Snapshot photoacoustic topography through an ergodic relay of optical absorption in vivo," Nature Protocols (2021) [PDF]
  7. [Lin, L.; Hu, P.; Tong, X.; Na, S.]; Cao, R.; Yuan, X.; Garrett, D. C.; Shi, J.; Maslov, K.; Wang, L. V.; "High-speed three-dimensional photoacoustic computed tomography for preclinical research and clinical translation," Nature Communications 12(1) 882 (2021) [PDF]
  8. [Li, Y.; Li, L.; Zhu, L. R.]; Maslov, K.; Shi, J. H.; Hu, P.; Bo, E.; Yao, J. J.; Liang, J. Y.; Wang, L. D.; Wang, L. V.; "Snapshot photoacoustic topography through an ergodic relay for high-throughput imaging of optical absorption," Nature Photonics 14(3) 164-170 (2020) [PDF]
  9. [Wu, Z.; Li, L]; Yang, Y.; Hu, P.; Li, Y.; Yang, S.-Y.; Wang, L. V.; Gao, W.; "A microrobotic system guided by photoacoustic computed tomography for targeted navigation in intestines in vivo," Science Robotics 4(32) eaax0613 (2019) [PDF]
  10. Shi, J.; Wong, T. T. W.; He, Y.; Li, L.; Zhang, R.; Yung, C. S.; Hwang, J.; Maslov, K.; Wang, L. V.; "High-resolution, high-contrast mid-infrared imaging of fresh biological samples with ultraviolet-localized photoacoustic microscopy," Nature Photonics 13 609-615 (2019) [PDF]
  11. [Hai, P.; Imai, T.]; Xu, S.; Zhang, R.; Aft, R. L.; Zou, J.; Wang, L. V.; "High-throughput, label-free, single-cell photoacoustic microscopy of intratumoral metabolic heterogeneity," Nature Biomedical Engineering 3(5) 381-391 (2019) [PDF]
  12. Li, L.; Shemetov, A. A.; Baloban, M.; Hu, P.; Zhu, L.; Shcherbakova, D. M.; Zhang, R.; Shi, J.; Yao, J.; Wang, L. V.; Verkhusha, V. V.; "Small near-infrared photochromic protein for photoacoustic multi-contrast imaging and detection of protein interactions in vivo," Nature Communications 9(1) 2734 (2018) [PDF]
  13. Lin, L.; Hu, P.; Shi, J.; Appleton, C. M.; Maslov, K.; Li, L.; Zhang, R.; Wang, L. V.; "Single-breath-hold photoacoustic computed tomography of the breast," Nature Communications 9(1) 2352 (2018) [PDF]
  14. Wong, T. T. W.; Zhang, R.; Zhang, C.; Hsu, H. C.; Maslov, K. I.; Wang, L.; Shi, J.; Chen, R.; Shung, K. K.; Zhou, Q.; Wang, L. V.; "Label-free automated three-dimensional imaging of whole organs by microtomy-assisted photoacoustic microscopy," Nature Communications 8(1) 1386 (2017) [PDF]
  15. 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) [PDF]
  16. [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) [PDF]
  17. Wang, L. V.; Yao, J.; "A practical guide to photoacoustic tomography in the life sciences," Nature Methods 13(8) 627â€"637 (2016) [PDF]
  18. [Yao, J.; Kaberniuk, A. A.; Li, L.]; Shcherbakova, 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) 67-73 (2016) [PDF]
  19. 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]
  20. Lai, P.; Wang, L.; Tay, J. W.; Wang, L. V.; "Photoacoustically guided wavefront shaping for enhanced optical focusing in scattering media," Nature Photonics 9 126-132 (2015) [PDF]
  21. Wang, L.; Zhang, C.; Wang, L. V.; "Grueneisen relaxation photoacoustic microscopy," Physical Review Letters 113 174301 (2014) [PDF]
  22. 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," Proceedings of the National Academy of Sciences 111(1) 21-26 (2014) [PDF]
  23. 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]
  24. 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]
  25. Wang, L.; Maslov, K.; Wang, L. V.; "Single-cell label-free photoacoustic flowoxigraphy in vivo," Proceedings of the National Academy of Sciences 110(15) 5759-5764 (2013) [PDF]
  26. Wang, L. V.; Hu, S.; "Photoacoustic tomography: in vivo imaging from organelles to organs," Science 335 1458-1462 (2012) [PDF]
  27. 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]
  28. Hu, S.; Maslov, K.; Wang, L. V.; "Three-dimensional optical-resolution photoacoustic microscopy," Journal of Visualized Experiments 51 (2011) [PDF]
  29. [Guo, Z.; Li, L.]; Wang, L. V.; "On the speckle-free nature of photoacoustic tomography," Medical Physics 36(9) 4084-4088 (2009) [PDF]
  30. Wang, L. V.; "Multiscale photoacoustic microscopy and computed tomography," Nature Photonics 3(9) 503-509 (2009) [PDF]
  31. Wang, L. V.; "Prospects of photoacoustic tomography," Medical Physics 35(12) 5758-5767 (2008) [PDF]
  32. 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]
  33. [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]
  34. Zhang, H. F.; Maslov, K.; Wang, L. V.; "In vivo imaging of subcutaneous structures using functional photoacoustic microscopy," Nature Protocols 2(4) 797-804 (2007) [PDF]
  35. Xu, M. H.; Wang, L. V.; "Photoacoustic imaging in biomedicine," Review of Scientific Instruments 77(4) 041101-(1-22) (2006) [PDF]
  36. 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]
  37. Xu, M. H.; Wang, L. V.; "Universal back-projection algorithm for photoacoustic computed tomography," Physical Review E 71(1) 016706-(1-7) (2005) [PDF]
  38. 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]
  39. 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]
  40. 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]