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Noninvasive laser-induced photoacoustic tomography for structural and functional in vivo imaging of the brain

Nature Biotechnology volume 21, pages 803–806 (2003)Cite this article

Abstract

Imaging techniques based on optical contrast analysis can be used to visualize dynamic and functional properties of the nervous system via optical signals resulting from changes in blood volume, oxygen consumption and cellular swelling associated with brain physiology and pathology. Here we report in vivo noninvasive transdermal and transcranial imaging of the structure and function of rat brains by means of laser-induced photoacoustic tomography (PAT). The advantage of PAT over pure optical imaging is that it retains intrinsic optical contrast characteristics while taking advantage of the diffraction-limited high spatial resolution of ultrasound. We accurately mapped rat brain structures, with and without lesions, and functional cerebral hemodynamic changes in cortical blood vessels around the whisker-barrel cortex in response to whisker stimulation. We also imaged hyperoxia- and hypoxia-induced cerebral hemodynamic changes. This neuroimaging modality holds promise for applications in neurophysiology, neuropathology and neurotherapy.

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Figure 1
Figure 2: PAT imaging of the rat brain in vivo.
Figure 3: PAT imaging of the rat brain lesion in situ.
Figure 4: Functional imaging of cerebral hemodynamic changes in response to whisker stimulation.

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References

  1. Grinvald, A., Frostig, R.D., Lieke, E. & Hildesheim, R. Optical imaging of neuronal activity. Physiol. Rev. 68, 1285–1365 (1988).

    Article  CAS  Google Scholar 

  2. Frostig, R.D., Lieke, E.E., Ts'o, D.Y. & Grinvald, A. Cortical functional architecture and local coupling between neuronal activity and the microcirculation revealed by in vivo high resolution optical imaging of intrinsic signals. Proc. Natl. Acad. Sci. USA 87, 6082–6086 (1990).

    Article  CAS  Google Scholar 

  3. MacVicar, B.A. & Hochman, D. Imaging of synaptically evoked intrinsic optical signals in hippocampal slices. J. Neurosci. 11, 1458–1469 (1991).

    Article  CAS  Google Scholar 

  4. Ebner, T.J. & Chen, G. Use of voltage-sensitive dyes and optical recordings in the central nervous system. Prog. Neurobiol. 46, 463–506 (1995).

    Article  CAS  Google Scholar 

  5. Villringer, A. & Chance, B. Non-invasive optical spectroscopy and imaging of human brain function. Trends. Neurosci. 20, 435–442 (1997).

    Article  CAS  Google Scholar 

  6. Mayhew, J. et al. Spectroscopic analysis of changes in remitted illumination: the response to increased neural activity in brain. Neuroimage 10, 304–326 (1999).

    Article  CAS  Google Scholar 

  7. Nemoto, M. et al. Analysis of optical signals evoked by peripheral nerve stimulation in rat somatosensory cortex: dynamic changes in hemoglobin concentration and oxygenation. J. Cereb. Blood Flow Metab. 19, 246–259 (1999).

    Article  CAS  Google Scholar 

  8. Gratton, G. & Fabiani, M. Dynamic brain imaging: event-related optical signals (EROS) measures of the time course and localization of cognitive-related activity. Psychon. Bull Rev. 5, 535–563 (1998).

    Article  Google Scholar 

  9. Grinvald, A., Lieke, E., Frostig, R.D., Gilbert, C.D. & Wiesel, T.N. Functional architecture of cortex revealed by optical imaging of intrinsic signals. Nature 324, 361–364 (1986).

    Article  CAS  Google Scholar 

  10. Haglund, M.M., Ojemann, G.A. & Hochman, D.W. Optical imaging of epileptiform and functional activity in human cerebral cortex. Nature 358, 668–671 (1992).

    Article  CAS  Google Scholar 

  11. Dowling, J.L., Henegar, M.M., Liu, D., Rovainen, C.M. & Woolsey, T.A. Rapid optical imaging of whisker responses in the rat barrel cortex. J. Neurosci. Meth. 66, 113–122 (1996).

    Article  CAS  Google Scholar 

  12. Jones, M., Berwick, J. & Mayhew, J. Changes in blood flow, oxygenation, and volume following extended stimulation of rodent barrel cortex. Neuroimage 15, 474–487 (2002).

    Article  Google Scholar 

  13. Hoelen, C.G.A., de Mul, F.F.M., Pongers, R. & Dekker, A. Three-dimensional photoacoustic imaging of blood vessels in tissue. Opt. Lett. 23, 648–650 (1998).

    Article  CAS  Google Scholar 

  14. Kruger, R.A., Reinecke, D.R. & Kruger, G.A. Thermoacoustic computed tomography–technical considerations. Med. Phys. 26, 1832–1837 (1999).

    Article  CAS  Google Scholar 

  15. Esenaliev, R.O., Karabutov, A.A. & Oraevsky, A.A. Sensitivity of laser opto-acoustic imaging in detection of small deeply embedded tumors. IEEE J. Sel. Top. Quant. 5, 981–988 (1999).

    Article  CAS  Google Scholar 

  16. Paltauf, G. & Schmidt-Kloiber, H. Optical method for two-dimensional ultrasonic detection. Appl. Phys. Lett. 75, 1048–1050 (1999).

    Article  CAS  Google Scholar 

  17. Karabutov, A.A., Savateeva, E. & Podymova, N.B. Backward mode detection of laser-induced wide-band ultrasonic transients with optoacoustic transducer. J. Appl. Phys. 87, 2003–2014 (2000).

    Article  CAS  Google Scholar 

  18. Köstli, K.P. et al. Optoacoustic imaging using a three-dimensional reconstruction algorithm. IEEE J. Sel. Top. Quant. 7, 918–923 (2001).

    Article  Google Scholar 

  19. Wang, X. et al. Photoacoustic tomography of biological tissues with high cross-section resolution: reconstruction and experiment. Med. Phys. 29, 2799–2805 (2002).

    Article  Google Scholar 

  20. Tokuno, H., Hatanaka, N., Takada, M. & Nambu, A. B-mode and color Doppler ultrasound imaging for localization of microelectrode in monkey brain. Neurosci. Res. 36, 335–338 (2000).

    Article  CAS  Google Scholar 

  21. Diebold, G.J., Sun, T. & Khan, M.I. in Photoacoustic and Photothermal Phenomena III (ed. Bicanic, D.) 263–296 (Springer, Berlin, Heidelberg, 1992).

    Book  Google Scholar 

  22. Sun, T. & Diebold, G.J. Generation of ultrasonic waves from a layered photoacoustic source. Nature 355, 806–808 (1992).

    Article  CAS  Google Scholar 

  23. Xu, M. & Wang, L.V. Time-domain reconstruction for thermoacoustic tomography in a spherical geometry. IEEE T. Med. Imaging 21, 814–822 (2002).

    Article  Google Scholar 

  24. Gerrits, R.J., Stein, E.A. & Greene, A.S. Blood flow increases linearly in rat somatosensory cortex with increased whisker movement frequency. Brain Res. 783, 151–157 (1998).

    Article  CAS  Google Scholar 

  25. Ogawa, S. et al. Intrinsic signal changes accompanying sensory stimulation: functional brain mapping with magnetic resonance imaging. Proc. Nat. Acad. Sci. USA 89, 5951–5955 (1992).

    Article  CAS  Google Scholar 

  26. Hoge, R.D. et al. Investigation of BOLD signal dependence on cerebral blood flow and oxygen consumption: the deoxyhemoglobin dilution model. Magn. Reson. Med. 42, 849–863 (1999).

    Article  CAS  Google Scholar 

  27. Kety, S.S. & Schmidt, C.F. The effects of altered arterial tensions of carbon dioxide and oxygen on cerebral blood flow and cerebral oxygen consumption of normal young men. J. Clin. Invest. 27, 484–491 (1948).

    Article  CAS  Google Scholar 

  28. Siesjo, B. Brain Energy Metabolism (John Wiley, New York, 1978).

    Google Scholar 

  29. Bereczki, D. et al. Hypoxia increases velocity of blood-flow through parenchymal microvascular systems in rat brain. Cerebr. Blood F. Met. 13, 475–486 (1993).

    Article  CAS  Google Scholar 

  30. Duong, T.Q., Iadecola, C. & Kim, S.G. Effect of hyperoxia, hypercapnia, and hypoxia on cerebral interstitial oxygen tension and cerebral blood flow. Magn. Reson. Med. 45, 61–70 (2001).

    Article  CAS  Google Scholar 

  31. Millikan, G.A. The oximeter, an instrument for measuring continuously the oxygen saturation of arterial blood in man. Rev. Sci. Instrum. 13, 434–444 (1942).

    Article  CAS  Google Scholar 

  32. Jöbsis, F.F. Noninvasive, infrared monitoring of cerebral and myocardial oxygen sufficiency and circulatory parameters. Science 198, 1264–1267 (1977).

    Article  Google Scholar 

  33. Mayevsky, A. & Chance, B. Intracellular oxidation-reduction state measured in situ by a multichannel fiberoptic surface fluorometer. Science 217, 537–540 (1982).

    Article  CAS  Google Scholar 

  34. Vanderlo, H. & Woolsey, T.A. Somatosensory cortex-structural alterations following early injury to sense organs. Science 179, 395–398 (1973).

    Article  Google Scholar 

  35. US National Institutes of Health. Guide for the Care and Use of Laboratory Animals, NIH Publication No. 86-23 (US Government Printing Office, Washington, DC, USA, 1985).

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Acknowledgements

This research was supported in part by the US Department of Defense, National Institutes of Health, National Science Foundation, and Texas Advanced Research Program.

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Authors and Affiliations

  1. Department of Biomedical Engineering, Optical Imaging Laboratory, Texas A&M University, College Station, Texas, 77843-3120, USA

    Xueding Wang, Yongjiang Pang, Geng Ku, Xueyi Xie & Lihong V Wang

  2. Department of Pathobiology, Texas A&M University, College Station, Texas, 77843-3120, USA

    George Stoica

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  1. Xueding Wang
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Correspondence to Lihong V Wang.

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Wang, X., Pang, Y., Ku, G. et al. Noninvasive laser-induced photoacoustic tomography for structural and functional in vivo imaging of the brain. Nat Biotechnol 21, 803–806 (2003). https://doi.org/10.1038/nbt839

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