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Special Semester on Quantitative Biology analyzed by Mathematical Methods
Linz, October 1, 2007 - January 27, 2008
Photoacoustic tomography: structural, functional, and molecular imaging of biological tissue

Workshop on Bioimaging I, Thu, 15 Nov, 2007

Speaker: Lihong Wang

Abstract

The field of biomedical photoacoustic tomography has experienced considerable growth in the past few years. Although several commercially available pure optical imaging modalities, including confocal microscopy, two-photon microscopy, and optical coherence tomography, have been highly successful, none of these technologies can penetrate beyond ~1 mm into scattering biological tissues because all of them are based on ballistic and quasi-ballistic photons. Consequently, heretofore there has been a void in high-resolution optical imaging beyond this depth limit (quasi-ballistic regime). Photoacoustic tomography has filled this void by combining high ultrasonic resolution and strong optical contrast in a single modality.
In photoacoustic imaging, an expanded pulsed laser beam diffuses into the biological tissue and generates a small but rapid temperature rise, which causes the emission of ultrasonic waves as a result of thermoelastic expansion. The short-wavelength ultrasonic waves are then detected to form high-resolution tomographic images. Because any absorbed photons that cause heating can produce photoacoustic signals, photoacoustic imaging does not depend on ballistic or quasi-ballistic photons. As a result, photoacoustic imaging can work in the quasi-diffusive (1-10 mm) or diffusive regimes (>10 mm). Using near-infrared light, photoacoustic imaging has been demonstrated to image as deep as ~30-50 mm into biological tissue.
Photoacoustic imaging has been implemented in various modes. Working at high ultrasonic frequency (50-MHz), dark-field confocal photoacoustic microscopy is able to penetrate 3 mm into biological tissue. The axial resolution is ~15 micrometers, whereas the lateral resolution is ~45 micrometers. The depth-to-resolution ratio is ~200, which indicates the effective number of pixels in the depth direction. Functional imaging has been demonstrated by quantifying the total concentration of hemoglobin and the oxygen saturation of hemoglobin. Melanoma has also been imaged with high resolution.
Photoacoustic imaging is scalable with the ultrasound bandwidth. By scaling the 50 MHz ultrasound frequency of the photoacoustic microscope down by a factor of ~10, we constructed another system for deeper imaging. This new system is able to image ~30 mm deep while maintaining a similar depth-to-resolution ratio.
In parallel with laser-induced photoacoustic imaging, radiofrequency-induced thermoacoustic tomography is on the horizon. Thermoacoustic tomography can potentially penetrate deeper than photoacoustic tomography while providing radiofrequency-based contrast.

1. X. Wang, Y. Pang, G. Ku, X. Xie, G. Stoica, and L. V. Wang, Nature Biotechnology 21 (7), 803–806 (2003).
2. Y. Xu and L. V. Wang, Physical Review Letters 92 (3), 033902 (2004).
3. H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, Nature Biotechnology 24, 848–851 (2006).
4. H. F. Zhang, K. Maslov, and L. V. Wang, Nature Protocols (in press, 2007).

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