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

Although optical absorption is strongly associated with the physiological status of biological tissue, existing high-resolution optical imaging modalities, including confocal microscopy, two-photon microscopy and optical coherence tomography, do not sense optical absorption directly. Furthermore, optical scattering prevents these methods from imaging deeper than ~1 mm below the tissue surface. Here we report functional photoacoustic microscopy (fPAM), which provides multiwavelength imaging of optical absorption and permits high spatial resolution beyond this depth limit with a ratio of maximum imaging depth to depth resolution greater than 100. Reflection mode, rather than orthogonal or transmission mode, is adopted because it is applicable to more anatomical sites than the others. fPAM is demonstrated with in vivo imaging of angiogenesis, melanoma, hemoglobin oxygen saturation (sO_2) of single vessels in animals and total hemoglobin concentration in humans.

Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging

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.

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

Noble metal nanoparticles are capable of confining resonant photons in such a manner as to induce coherent surface plasmon oscillation of their conduction band electrons, a phenomenon leading to two important properties. Firstly, the confinement of the photon to the nanoparticle's dimensions leads to a large increase in its electromagnetic field and consequently great enhancement of all the nanoparticle's radiative properties, such as absorption and scattering. Moreover, by confining the photon's wavelength to the nanoparticle's small dimensions, there exists enhanced imaging resolving powers, which extend well below the diffraction limit, a property of considerable importance in potential device applications. Secondly, the strongly absorbed light by the nanoparticles is followed by a rapid dephasing of the coherent electron motion in tandem with an equally rapid energy transfer to the lattice, a process integral to the technologically relevant photothermal properties of plasmonic nanoparticles. Of all the possible nanoparticle shapes, gold nanorods are especially intriguing as they offer strong plasmonic fields while exhibiting excellent tunability and biocompatibility. We begin this review of gold nanorods by summarizing their radiative and nonradiative properties. Their various synthetic methods are then outlined with an emphasis on the seed-mediated chemical growth. In particular, we describe nanorod spontaneous self-assembly, chemically driven assembly, and polymer-based alignment. The final section details current studies aimed at applications in the biological and biomedical fields.

Gold Nanorods: From Synthesis and Properties to Biological and Biomedical Applications

This paper reviews the theory and applications of photoacoustic (also called optoacoustic) methods belonging to the more general area of photothermal measurement techniques. The theory covers excitation of gaseous or condensed samples with modulated continuous light beams or pulsed light beams. The applications of photoacoustic methods include spectroscopy, monitoring deexcitation processes, probing physical properties of materials, and generating mechanical motions. Several other related photothermal methods, as well as particle-acoustics and wave-acoustics methods are also described. This review complements an earlier and narrower review [Rev. Mod. Phys. 53, 517 (1981)] that is mainly concerned with sensitive detection by pulsed photoacoustic spectroscopy in condensed matter.

Applications of photoacoustic sensing techniques

We show that the photoacoustic pressure in one, two, and three dimensions can be found as mappings of the optical deposition of heat in space for short optical radiation pulses. In addition, we find the photoacoustic pressure to be proportional to the zeroth derivative in one dimension, the one-half derivative in two dimensions, and the first derivative in three dimensions of the optical radiation intensity for long pulses. Experiments with fluid layers, cylinders, and droplets give ultrasonic wave forms that are in general agreement with the theorems.

Photoacoustic monopole radiation in one, two, and three dimensions.

The use of high-pressure liquid chromatographic separation in conjunction with laser-induced fluorescence detection permits the analysis of trace fluorescent species at new limits of sensitivity. This technique was applied to the carcinogens aflatoxins B1, B2, G1, and G2, which were linearly quantitated to 7.5 x 10(-13) gram. The procedure consists of forming more fluorescent aflatoxin derivatives, eluting the aflatoxins from a reverse-phase column, focusing the 325-nanometer output of a helium-cadmium ion laser into a suspended droplet of the eluent, and measuring the resulting fluorescence using phase-sensitive detection.

Laser fluorimetry: subpicogram detection of aflatoxins using high-pressure liquid chromatography

We investigate the photoacoustic effect generated by heat deposition at a point in space in an inviscid fluid. Delta-function and long Gaussian optical pulses are used as sources in the wave equation for the displacement potential to determine the fluid motion. The linear sound-generation mechanism gives bipolar photoacoustic waves, whereas the nonlinear mechanism produces asymmetric tripolar waves. The salient features of the photoacoustic point source are that rapid heat deposition and nonlinear thermal expansion dominate the production of ultrasound.

Photoacoustic point source.

Properties of photoacoustic waves in one, two, and three dimensions

Absorption of pulsed laser radiation by a single particle generates a photoacoustic wave whose time profile can be measured with a wideband pressure transducer. Solution of the wave equation for pressure in one, two, and three dimensions shows that the photoacoustic wave is determined by the geometry and dimensions of the particle, and by its sound speed and density relative to the fluid that surrounds it. Photoacoustic waves, referred to here as signatures, are reported in experiments in which fluid droplets, cylinders, and layers are irradiated with 10-nanosecond laser pulses.

http://science.sciencemag.org/content/sci/250/4977/101.full.pdf

Gerald J. Diebold

Papers

Photoacoustic monopole radiation in one, two, and three dimensions.

Laser fluorimetry: subpicogram detection of aflatoxins using high-pressure liquid chromatography

Photoacoustic point source.

Properties of photoacoustic waves in one, two, and three dimensions

Photoacoustic "signatures" of particulate matter: optical production of acoustic monopole radiation.