Advances in Clinical and Biomedical Applications of Photoacoustic Imaging

Abstract

IMPORTANCE OF THE FIELD: Photoacoustic imaging is an imaging modality that derives image contrast from the optical absorption coefficient of the tissue being imaged. The imaging technique is able to differentiate between healthy and diseased tissue with either deeper penetration or higher resolution than other functional imaging modalities currently available. From a clinical standpoint, photoacoustic imaging has demonstrated safety and effectiveness in diagnosing diseased tissue regions using either endogenous tissue contrast or exogenous contrast agents. Furthermore, the potential of photoacoustic imaging has been demonstrated in various therapeutic interventions ranging from drug delivery and release to image-guided therapy and monitoring. AREAS COVERED IN THIS REVIEW: This article reviews the current state of photoacoustic imaging in biomedicine from a technological perspective, highlights various biomedical and clinical applications of photoacoustic imaging, and gives insights on future directions. WHAT THE READER WILL GAIN: Readers will learn about the various applications of photoacoustic imaging, as well as the various contrast agents that can be used to assist photoacoustic imaging. This review will highlight both pre-clinical and clinical uses for photoacoustic imaging, as well as discuss some of the challenges that must be addressed to move photoacoustic imaging into the clinical realm. TAKE HOME MESSAGE: Photoacoustic imaging offers unique advantages over existing imaging modalities. The imaging field is broad with many exciting applications for detecting and diagnosing diseased tissue or processes. Photoacoustics is also used in therapeutic applications to identify and characterize the pathology and then to monitor the treatment. Although the technology is still in its infancy, much work has been done in the pre-clinical arena, and photoacoustic imaging is fast approaching the clinical setting.

Figure 1

(a) Optical absorption spectrum of different tissue types which could be used as endogenous contrast agents in vivo. (b) Exogenous contrast agents such as gold nanospheres (16 nm diameter), silver nanotriangles (200 nm on edge), and gold nanorods (10 nm by 40 nm) and their corresponding extinction spectrum. Tunable peaks show that nanoparticles can be used as contrast agents in various applications.

Figure 2

Lipid regions (orange color) were demonstrated on top of the IVUS images for diseased (a) and control (d) rabbit aorta. (b, e) Oil Red O stain for lipid and (c, f) H&E stain closed to the imaged cross-section of diseased and control rabbit aortas. Reproduced with permission from Wang B, Su JL, Amirian J, et al. Detection of lipid in atherosclerotic vessels using ultrasound-guided spectroscopic intravascular photoacoustic imaging. Opt Express 2010 Mar 1;18(5):4889–97. [11].

Figure 3

(a) Silica-coated gold nanorods with enhanced thermal stability. Reproduced with permission from[69]. (b) cTEM image of a dual ultrasound and photoacoustic contrast agent. Perfluorocarbon droplets loaded with silver nanotriangles. Reproduced with permission from Wilson K, Homan K, Emelianov S. Synthesis of a dual contrast agent for ultrasound and photoacoustic imaging. In: Samuel A, Ramesh R, editors. Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications II; 2010; San Francisco, CA, USA; 2010. p. 75760M [53]. (b) Silica-coated gold nanorods with enhanced thermal stability. Reproduced with permission from Chen YS, Frey W, Kim S, et al. Enhanced thermal stability of silica-coated gold nanorods for photoacoustic imaging and image-guided therapy. Opt Express 2010 Apr 26;18(9):8867–78. [69].

Figure 4

Darkfield, ultrasound and photoacoustic images (λ = 532 nm and 680 nm) of control, targeted and non-targeted tissue phantoms. The darkfield images measure 440 μm by 340 μm field of view. The ultrasound and optoacoustic images measure 2 mm by 1.67 mm. The targeted EGFR cells show high photoacoustic signal due to the plasmon resonance coupling resulting from clustering gold nanoparticles. Reproduced from Mallidi S, Larson T, Aaron J, et al. Molecular specific optoacoustic imaging with plasmonic nanoparticles. Opt Express 2007 May 28;15(11):6583–8 with permission of the Optical Society of America. [27]

Figure 5

(a) Ultrasound, (b) photoacoustic and (c) thermal image of a subcutaneous tumor in nude mouse. Reprinted with permission from Mallidi S, Wang B, Mehrmohammadi M, et al. Ultrasound-based imaging of nanoparticles: from molecular and cellular imaging to therapy guidance. Proceedings of the 2009 IEEE Ultrasonics Symposium 2009:27–36 (2009) [81].

Figure 6

Examples of several multiplexed nanoparticles used as an imaging contrast agent, as a drug delivery vehicle, and/or for image-guided therapy. (a)_SEM image of hollow nanocages used to contain therapy products. Reproduced with permission from Skrabalak SE, Chen J, Sun Y, et al. Gold nanocages: synthesis, properties, and applications. Acc Chem Res 2008 Dec;41(12):1587–95 [86] (b) Gold nanoshells for use in photothermal applications. Reproduced with permission from Loo C, Lowery A, Halas N, et al. Immunotargeted Nanoshells for Integrated Cancer Imaging and Therapy. Nano Letters 2005;5(4):709–11. [87]. (c) Diagram demonstrating a multifunctional nanosystem platform utilizing a silver cage with a silica core. Reproduced with permission from Homan K, Shah J, Gomez S, et al. Silver nanosystems for photoacoustic imaging and image-guided therapy. J Biomed Opt 2010 Mar-Apr;15(2):021316 [92]. (d) Silver coated PLGA as a carrier for imaging contrast agents. Image courtesy of K.A. Homan. All figures used with permission.

Figure 7

3D-reconstruction of a stent embedded in a PVA phantom. Individual cross sections can show the position of the stent within the vessel. (a) Ultrasound 3D reconstruction of the phantom showing the structure of the vessel. (b) Photoacoustic reconstruction of the stent structure which can be used to assess the condition of the stent. (c) Photoacoustic image of the stent overlaid with the ultrasound image of the vessel can show the position of both. (d) Cutaway image of the reconstruction, allowing for accurate assessment of the stent within the vessel. Reproduced with permission from Su JL, Wang B, Emelianov SY. Photoacoustic imaging of coronary artery stents. Opt Express 2009 Oct 26;17(22):19894–901 [97].