Page 25 - Volume 8, Issue 4 - Winter 2012

meability and retention effect. Additionally, the injected nanoparticles were bioconjugated to antibodies specific for cell receptors over-expressed on cell types used to initiate the tumors, thus it is likely that the active targeting improves the retention of the specific nanoparticles within the tumor region. This example demonstrates how the use of nanopar- ticles can provide molecular information about the cellular expression of the tumor. In this way, photoacoustics com- bines the benefits of high-contrast optical resolution of tar- getable light-interacting probes, with the imaging depth capabilities of ultrasound.
Conclusions
The strength of photoacoustic imaging is in its ability to image functional and molecular changes, at significant tissue depth, in living animals. Researchers have just begun to exploit photoacoustic imaging techniques to enable new dis- coveries of the functional and molecular characteristics of cancer, cardiovascular disease, and neurological diseases. We envision photoacoustic imaging becoming a critical tool in medical diagnostics and image-guided therapeutics in the future. While most photoacoustic functional imaging appli- cations thus far have used contrast sources which are natu- rally present, it is also possible to introduce biochemically triggered contrast agents for functional imaging. For exam- ple, many dyes exist which change their optical absorption spectra based on pH, or in the presence of an enzyme. By adding an activatable contrast agent, we can use the change in the multiwavelength photoacoustic signal intensity to pro- vide quantitative information about the biochemical envi- ronment within tissues, and monitor changes in this envi- ronment.
While this article focuses on imaging, it is also of note
that a natural synergy exists between photoacoustic imaging
and therapy. For example, thermal therapy can be achieved
by using a continuous light source to heat the optical
absorbers used for photoacoustic contrast, to a temperature
which can lead to the destruction of the cells and surround-
35
covalently-linked therapeutics.
Photoacoustic imaging is not without limitations. Like
ultrasound, the resolution will be physically limited by the inverse relationship between the imaging depth and the fre- quency of the ultrasound—as the frequency increases, reso- lution also increases, however the signal attenuation is greater at higher frequencies, leading to limitations in imag- ing depth. Sensitivity is impacted by the scattering of light within tissue, however new techniques to maximize the sig- nal to noise, including improved contrast agents, and varying the laser light characteristics, can help to minimize back- ground signal. Other limitations include the time required to scan—achieving high lateral resolution is dependent upon a narrow beam, which means that the receiving transducer (in scanning systems) or object being imaged (in tomographic systems) must be scanned in a third dimension to widen the field of view. This time limitation does limit the temporal res-
olution of the functional and molecular information which can be obtained to the timescale of minutes. Currently, only preclinical photoacoustic imaging systems are available com- mercially, but the additional functional and molecular infor- mation available through this imaging modality will mean its increasing use in preclinical studies, providing the needed research background necessary for clinical adaptations.AT
Acknowledgements
The authors acknowledge support from the National Institutes of Health (NIH) under grants F32CA159913 (C.L. Bayer), and F31CA168168 (G.P. Luke). We thank Juili Kevlar for providing the silica-coated gold nanorod TEM images, and Dr. Kimberly Homan for providing the silver plate TEM images. We also thank Shailja Tewari of VisualSonics, Christian Wiest of iThera Medical, and Richard Moss of Endra Life Sciences for providing the pictures compiled in Fig. 3.
References
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3
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A. A. Oraevsky, S. L. Jacques, R. O. Esenaliev, and F. K. Tittel “Time-resolved optoacoustic imaging in layered biological tis- sues,” OSA Proc.Advances in Optical Imaging and Photon
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Additionally, multimodal photoacoustic contrast agents can be designed to provide laser-activated delivery of therapeutic molecules, such as by using a temperature- responsive polymer coating,36 or by using the heat to release
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