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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 Media Coverage

June, 2021 Caltech: Recording Brain Activity with Laser Light

A Caltech professor, in collaboration with researchers at the University of Southern California, has demonstrated for the first time a new technology for imaging the human brain using laser light and ultrasonic sound waves.... More>>

Feb, 2019 SPIE: Photons Plus Ultrasound: 25 years at Photonics West

In 2003, Lihong Wang, then at Texas A&M University, US, delivered images of brains in living rats that well and truly moved the field of photoacoustic imaging into the fast lane. Revealing intricate networks of blood vessels in the rat cerebral cortex - acquired with the skin and skull intact - the tomograms represented a massive leap forward for functional imaging using photoacoustics, also known as optoacoustics, and stunned researchers worldwide... More>>

October, 2018 SPIE: Man Makes PACT

An innovative breast-imaging technique offers noninvasive options for multiple biomedical applications... More>>

June, 2018 NIBIB: Light-Based, 15-Second Scan Aims to Replace Painful Mammograms

Up to 50% of women skip potentially life-saving mammograms often because the procedure can cause extreme discomfort and pain. Now researchers have developed a painless, light-based, non-radioactive, 15-second procedure that could revolutionize breast cancer screening and save lives... More>>

May, 2017 New Atlas: New Cancer Imaging Technique to Help Removal of Tumors in One Go

For many patients diagnosed with cancer, the primary treatment plan is surgery to remove the tumor, but in the quest to retain as much healthy tissue as possible, it's impossible for surgeons to know if they've removed all traces of the cancerous tissue while in the operating room. A new imaging technique would give doctors this ability, thus avoiding having the patient return to surgery weeks later for a second procedure... More>>

July, 2015 National Public Radio: A Scientist Deploys Light and Sound to Reveal the Brain

Wang, a professor of biomedical engineering at Washington University in St. Louis, has already helped develop instruments that can detect individual cancer cells in the bloodstream and oxygen consumption deep within the body... More>>

June, 2009 The Economist: The Sound of Light

A novel scanning technique that combines optics with ultrasound could provide detailed images at greater depths... More>>

Selected Foundational, Tutorial, and Review Papers

  1. 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]
  2. Xu, Y.; Wang, L. V.; Ambartsoumian, G.; Kuchment, P.; "Reconstructions in limited-view thermoacoustic tomography," Medical Physics 31(4) 724-733 (2004) [PDF]
  3. Xu, M. H.; Wang, L. V.; "Universal back-projection algorithm for photoacoustic computed tomography," Physical Review E 71(1) 016706-(1-7) (2005) [PDF]
  4. Wang, L. V.; "Tutorial on photoacoustic microscopy and computed tomography," IEEE Journal of Selected Topics in Quantum Electronics 14(1) 171-179 (2008) [PDF]
  5. Wang, L. V.; Hu, S.; "Photoacoustic tomography: in vivo imaging from organelles to organs," Science 335 1458-1462 (2012) [PDF]
  6. Hu, P.; Li, L.; Lin, L.; Wang, L. V.; "Spatiotemporal antialiasing in photoacoustic computed tomography," IEEE Transactions on Medical Imaging 39(11) 3535-3547 (2020) [PDF]
  7. [Park, J.; Choi, S.; Knieling, F.]; Clingman, B.; Bohndiek, S.; Wang, L. V.; Kim, C.; "Clinical translation of photoacoustic imaging," Nature Reviews Bioengineering 3 193–212 (2024) [PDF]

Selected Publications

  1. [Zhang, Y.; Na, S.; Russin, J. J.]; Sastry, K.; Lin, L.; Zheng, J.; Luo, Y.; Tong, X.; An, Y.; Hu, P.; Maslov, K.; Tan, T.; Liu, C. Y.; Wang, L. V.; "Rotational ultrasound and photoacoustic tomography of the human body," Nature Biomedical Engineering (2026) [PDF]
  2. [Park, B.; Cao, R.; Luo, Y.; Liu, C.]; Zeng, Y.; Zhang, Y.; Zhou, Q.; Davis, S.; D'Apuzzo, M.; Wang, L. V.; "Rapid cancer diagnosis using deep learning–powered label-free subcellular-resolution photoacoustic histology," Science Advances 11(47) (2025) [PDF]
  3. [Tong, X.; Liu, C. Z.; Luo, Y.; Lin, L.]; Dzubnar, J.; Invernizzi, M.; Santos, S. D.; Zhang, Y.; Cao, R.; Hu, P.; Zheng, J.; Torres, J.; Kasabyan, A.; Lai, L. L.; Yee, L. D.; Wang, L. V.; "Panoramic photoacoustic computed tomography with learning-based classification enhances breast lesion characterization," Nature Biomedical Engineering (2025) [PDF]
  4. Cao, R.; Luo, Y.; Zhao, J.; Zeng, Y.; Zhang, Y.; Zhou, Q.; le da Zerda, A.; Wang, L. V.; "Optical-resolution parallel ultraviolet photoacoustic microscopy for slide-free histology," Science Advances 10(50) (2024) [PDF]
  5. [Zhang, Y.; Hu, P.]; Li, L.; Cao, R.; Khadria, A.; Maslov, K.; Tong, X.; Zeng, Y.; Jiang, L.; Zhou, Q.; Wang, L. V.; "Ultrafast longitudinal imaging of haemodynamics via single-shot volumetric photoacoustic tomography with a single-element detector," Nature Biomedical Engineering 8(6) 712–725 (2024) [PDF]
  6. [Zhang, Y.; Olick-Gibson, J.]; Khadria, A.; Wang, L. V.; "Photoacoustic vector tomography for deep haemodynamic imaging," Nature Biomedical Engineering 8(6) 701–711 (2024) [PDF]
  7. [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]
  8. 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]
  9. Lin, L.; Wang, L, V.; "The emerging role of photoacoustic imaging in clinical oncology," Nature Reviews Clinical Oncology 365-384 (2022) [PDF]
  10. [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]
  11. Garrett, D. C.; Wang, L. V.; "Acoustic sensing with light," Nature Photonics (2021) [PDF]
  12. [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]
  13. [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]
  14. [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]
  15. [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]
  16. 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]
  17. [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]
  18. 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]
  19. 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]
  20. 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]
  21. 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]
  22. [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]
  23. Wang, L. V.; Yao, J.; "A practical guide to photoacoustic tomography in the life sciences," Nature Methods 13(8) 627â€"637 (2016) [PDF]
  24. [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]
  25. 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]
  26. 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]
  27. Wang, L.; Zhang, C.; Wang, L. V.; "Grueneisen relaxation photoacoustic microscopy," Physical Review Letters 113 174301 (2014) [PDF]
  28. 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]
  29. 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]
  30. 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]
  31. 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]
  32. Wang, L. V.; Hu, S.; "Photoacoustic tomography: in vivo imaging from organelles to organs," Science 335 1458-1462 (2012) [PDF]
  33. 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]
  34. Hu, S.; Maslov, K.; Wang, L. V.; "Three-dimensional optical-resolution photoacoustic microscopy," Journal of Visualized Experiments 51 (2011) [PDF]
  35. [Guo, Z.; Li, L.]; Wang, L. V.; "On the speckle-free nature of photoacoustic tomography," Medical Physics 36(9) 4084-4088 (2009) [PDF]
  36. Wang, L. V.; "Multiscale photoacoustic microscopy and computed tomography," Nature Photonics 3(9) 503-509 (2009) [PDF]
  37. Wang, L. V.; "Prospects of photoacoustic tomography," Medical Physics 35(12) 5758-5767 (2008) [PDF]
  38. 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]
  39. [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]
  40. 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]
  41. Xu, M. H.; Wang, L. V.; "Photoacoustic imaging in biomedicine," Review of Scientific Instruments 77(4) 041101-(1-22) (2006) [PDF]
  42. 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]
  43. Xu, M. H.; Wang, L. V.; "Universal back-projection algorithm for photoacoustic computed tomography," Physical Review E 71(1) 016706-(1-7) (2005) [PDF]
  44. 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]
  45. 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]
  46. 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]