Photoacoustic imaging (also called optoacoustic or thermoacoustic imaging) has the potential to image animal or human organs, such as the breast and the brain, with simultaneous high contrast and high spatial resolution. This article provides an overview of the rapidly expanding field of photoacoustic imaging for biomedical applications. Imaging techniques, including depth profiling in layered media, scanning tomography with focused ultrasonic transducers, image forming with an acoustic lens, and computed tomography with unfocused transducers, are introduced. Special emphasis is placed on computed tomography, including reconstruction algorithms, spatial resolution, and related recent experiments. Promising biomedical applications are discussed throughout the text, including (1) tomographic imaging of the skin and other superficial organs by laser-induced photoacoustic microscopy, which offers the critical advantages, over current high-resolution optical imaging modalities, of deeper imaging depth and higher absorptioncontrasts, (2) breast cancerdetection by near-infrared light or radio-frequency–wave-induced photoacoustic imaging, which has important potential for early detection, and (3) small animal imaging by laser-induced photoacoustic imaging, which measures unique optical absorptioncontrasts related to important biochemical information and provides better resolution in deep tissues than optical imaging.

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Photoacoustic imaging in biomedicine

Optical imaging of live animals has grown into an important tool in biomedical research as advances in photonic technology and reporter strategies have led to widespread exploration of biological processes in vivo. Although much attention has been paid to microscopy, macroscopic imaging has allowed small-animal imaging with larger fields of view (from several millimeters to several centimeters depending on implementation). Photographic methods have been the mainstay for fluorescence and bioluminescence macroscopy in whole animals, but emphasis is shifting to photonic methods that use tomographic principles to noninvasively image optical contrast at depths of several millimeters to centimeters with high sensitivity and sub-millimeter to millimeter resolution. Recent theoretical and instrumentation advances allow the use of large data sets and multiple projections and offer practical systems for quantitative, three-dimensional whole-body images. For photonic imaging to fully realize its potential, however, further progress will be needed in refining optical inversion methods and data acquisition techniques.

Looking and listening to light: the evolution of whole-body photonic imaging.

Photoacoustic tomography (PAT) is probably the fastest-growing area of biomedical imaging technology, owing to its capacity for high-resolution sensing of rich optical contrast in vivo at depths beyond the optical transport mean free path (~1 mm in human skin). Existing high-resolution optical imaging technologies, such as confocal microscopy and two-photon microscopy, have had a fundamental impact on biomedicine but cannot reach the penetration depths of PAT. By utilizing low ultrasonic scattering, PAT indirectly improves tissue transparency up to 1000-fold and consequently enables deeply penetrating functional and molecular imaging at high spatial resolution. Furthermore, PAT promises in vivo imaging at multiple length-scales; it can image subcellular organelles to organs with the same contrast origin — an important application in multiscale systems biology research.

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Multiscale photoacoustic microscopy and computed tomography.

Reconstruction-based microwave-induced thermoacoustic tomography in a spherical configuration is presented. Thermoacoustic waves from biological tissue samples excited by microwave pulses are measured by a wide-band unfocused ultrasonic transducer, which is set on a spherical surface enclosing the sample. Sufficient data are acquired from different directions to reconstruct the microwave absorption distribution. An exact reconstruction solution is derived and approximated to a modified backprojection algorithm. Experiments demonstrate that the reconstructed images agree well with the original samples. The spatial resolution of the system reaches 0.5 mm.

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Time-domain reconstruction for thermoacoustic tomography in a spherical geometry

The limited-view problem is studied for thermoacoustic tomography, which is also referred to as photoacoustic or optoacoustic tomography depending on the type of radiation for the induction of acoustic waves. We define a “detection region,” within which all points have sufficient detection views. It is explained analytically and shown numerically that the boundaries of any objects inside this region can be recovered stably. Otherwise some sharp details become blurred. One can identify in advance the parts of the boundaries that will be affected if the detection view is insufficient. If the detector scans along a circle in a two-dimensional case, acquiring a sufficient view might require covering more than a π-, or less than a π-arc of the trajectory depending on the position of the object. Similar results hold in a three-dimensional case. In order to support our theoretical conclusions, three types of reconstruction methods are utilized: a filtered backprojection (FBP) approximate inversion, which is shown to work well for limited-view data, a local-tomography-type reconstruction that emphasizes sharp details (e.g., the boundaries of inclusions), and an iterative algebraic truncated conjugate gradient algorithm used in conjunction with FBP. Computations are conducted for both numerically simulated and experimental data. The reconstructions confirm our theoretical predictions.

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Reconstructions in limited-view thermoacoustic tomography

Photoacoustic signal generation can be used for a new medical tomographic technique. This makes it possible to image optically different structures, such as the (micro)vascular system in tissues, by use of a transducer array for the detection of laser-generated wide-bandwidth ultrasound. A time-domain delay-and-sum focused beam-forming technique is used to locate the photoacoustic sources in the sample. To characterize the transducer response, simulations have been performed for a wide variety of parameter values and have been verified experimentally. With these data the weight factors for the spectrally and temporally filtered sensor signals are determined in order to optimize the signal-to-noise ratio of the beam former. The imaging algorithm is investigated by simulations and experiments. With this algorithm, for what is to our knowledge the first time, the three-dimensional photoacoustic imaging of complex optically absorbing structures located in a highly diffuse medium is demonstrated. When 200-mum-diameter hydrophone elements are used, the depth resolution is better than 20 mum, and the lateral resolution is better than 200 mum, independent of the depth for our range of imaging (to ~6 mm). Reduction of the transducer diameters and adaptation of the weight factors, at the cost of some increase of the noise level, will further improve the lateral resolution. The synthetic aperture algorithm used has been shown to be suitable for the new technique of photoacoustic tissue scanning.

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Papers

Image reconstruction for photoacoustic scanning of tissue structures.