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

4. Survey of Novel Multiphoton Active Materials 1257 4.1. Multiphoton Absorbing Systems 1257 4.2. Organic Molecules 1257 4.3. Organic Liquids and Liquid Crystals 1259 4.4. Conjugated Polymers 1259 4.4.1. Polydiacetylenes 1261 4.4.2. Polyphenylenevinylenes (PPVs) 1261 4.4.3. Polythiophenes 1263 4.4.4. Other Conjugated Polymers 1265 4.4.5. Dendrimers 1265 4.4.6. Hyperbranched Polymers 1267 4.5. Fullerenes 1267 4.6. Coordination and Organometallic Compounds 1271 4.6.1. Metal Dithiolenes 1271 4.6.2. Pyridine-Based Multidentate Ligands 1272 4.6.3. Other Transition-Metal Complexes 1273 4.6.4. Lanthanide Complexes 1275 4.6.5. Ferrocene Derivatives 1275 4.6.6. Alkynylruthenium Complexes 1279 4.6.7. Platinum Acetylides 1279 4.7. Porphyrins and Metallophophyrins 1279 4.8. Nanoparticles 1281 4.9. Biomolecules and Derivatives 1282 5. Nonlinear Optical Characterizations of Multiphoton Active Materials 1282

Multiphoton Absorbing Materials : Molecular Designs, Characterizations, and Applications

Author(s): Vogel, Alfred; Venugopalan, Vasan | Abstract: The mechanisms of pulsed laser ablation of biological tissues were studied. The transiently empty space created between the fiber tip and the tissue surface improved the optical transmission to the target and thus increased the ablation efficiency. It was found that the structure and morphology also affect the energy transport among tissue constituents.

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Mechanisms of pulsed laser ablation of biological tissues.

Photoacoustic (PA) imaging, also called optoacoustic imaging, is a new biomedical imaging modality based on the use of laser-generated ultrasound that has emerged over the last decade. It is a hybrid modality, combining the high-contrast and spectroscopic-based specificity of optical imaging with the high spatial resolution of ultrasound imaging. In essence, a PA image can be regarded as an ultrasound image in which the contrast depends not on the mechanical and elastic properties of the tissue, but its optical properties, specifically optical absorption. As a consequence, it offers greater specificity than conventional ultrasound imaging with the ability to detect haemoglobin, lipids, water and other light-absorbing chomophores, but with greater penetration depth than purely optical imaging modalities that rely on ballistic photons. As well as visualizing anatomical structures such as the microvasculature, it can also provide functional information in the form of blood oxygenation, blood flow and temperature. All of this can be achieved over a wide range of length scales from micrometres to centimetres with scalable spatial resolution. These attributes lend PA imaging to a wide variety of applications in clinical medicine, preclinical research and basic biology for studying cancer, cardiovascular disease, abnormalities of the microcirculation and other conditions. With the emergence of a variety of truly compelling in vivo images obtained by a number of groups around the world in the last 2–3 years, the technique has come of age and the promise of PA imaging is now beginning to be realized. Recent highlights include the demonstration of whole-body small-animal imaging, the first demonstrations of molecular imaging, the introduction of new microscopy modes and the first steps towards clinical breast imaging being taken as well as a myriad of in vivo preclinical imaging studies. In this article, the underlying physical principles of the technique, its practical implementation, and a range of clinical and preclinical applications are reviewed.

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Biomedical photoacoustic imaging

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

The authors discuss the theory and experiments dealing with the pulsed optoacoustic effect (i.e., generation of a transient acoustic wave by absorption of an optical pulse) in condensed matter. Their primary interest lies in the measurement of small absorption coefficients (\ensuremath{\ll}${10}^{\ensuremath{-}1}$ ${\mathrm{cm}}^{\ensuremath{-}1}$). At present an experimental capability of measuring absorption coefficients as small as ${10}^{\ensuremath{-}6}$ ${\mathrm{cm}}^{\ensuremath{-}1}$ has been demonstrated, and further improvement is foreseen. The pulsed optoacoustic absorption measurement technique has been applied to the following linear spectroscopic studies: (1) precise measurements of the optical absorption spectra of ${\mathrm{H}}_{2}$O and ${\mathrm{D}}_{2}$O; (b) accurate determination of absorption strengths and profiles of high harmonics ($n=6, 7, \mathrm{and} 8$) of vibrational modes in transparent organic liquids (e.g., benzene); (c) quantitative absorption spectra of thin (\ensuremath{\sim} 1-10 \ensuremath{\mu}m) liquid films; and (d) quantitative absorption spectra of solids and finely powdered crystals. The usefulness of the pulsed optoacoustic technique to nonlinear spectroscopy has been demonstrated in the following studies: (a) quantitative two-photon absorption spectroscopy of the weak two-photon ($^{1}B_{2\ensuremath{\mu}}\ensuremath{\leftarrow}^{1}A_{1g}$) transition in benzene; and (b) optoacoustic Raman-gain spectra for a variety of liquids where an ability to measure Raman gains as small as ${10}^{\ensuremath{-}5}$ ${\mathrm{cm}}^{\ensuremath{-}1}$ has been demonstrated. In addition to reviewing the above studies the authors discuss future possible applications and compare the pulsed optoacoustic spectroscopy technique with other optoacoustic absorption measurement techniques.

Pulsed optoacoustic spectroscopy of condensed matter

Flash laser heating using short‐pulsed laser irradiation of a surface is demonstrated to be a promising new approach for effective removal of particulate contaminations of sizes as small as 0.1 μm. This is very useful because micron‐ and submicron‐sized particulates adhere tenaciously onto a solid surface, and conventional cleaning techniques are inadequate for removal. Several varieties of the new laser‐cleaning techniques have been developed by us as well as by others. For example, the pulsed laser irradiation can be used with or without the simultaneous deposition of a thin liquid film on the surface to be laser cleaned. The laser wavelength can also be chosen so that absorption occurs mainly at the sample surface, or in the liquid, or in the particulate, or in a combination of these. In this paper, we discuss and compare examples of these different approaches. We find that laser cleaning with highest efficiency is achieved by choosing a laser wavelength that is strongly absorbed by the surface together with pulse depositing a water film of thickness on the order of microns on the surface momentarily before the pulsed laserirradiation. This permits the effective removal of particles smaller than ∼20 μm, down to as small as 0.1 μm, from a solid surface using a modest ultraviolet laser fluence of ∼0.1 J/cm2.

Laser‐cleaning techniques for removal of surface particulates

Laser cleaning with pulsed ultraviolet and infrared lasers is successfully employed to remove particulate contamination from silicon wafer surfaces and from delicate lithography membrane masks. Particulate material investigated include latex, alumina, silicon, and gold. Gold particles as small as 0.2 μm can be effectively removed. This new and highly efficient laser cleaning is achieved by choosing a pulsed laser with short pulse duration (without causing substrate damage), and a wavelength that is strongly absorbed by the surface; the removal efficiency is further enhanced by depositing a liquid film of thickness on the order of micron on the surface just before the pulsed laser irradiation.

Efficient pulsed laser removal of 0.2 μm sized particles from a solid surface

A method and device for detecting a narrow acoustic spectral feature in a sample as described. The method uses an electrical frequency modulated (FM) signal that is obtained from a voltage controlled oscillator. The Fourier spectrum of this wave is a main frequency fc with two small sidebands at frequencies fc ±fs. This whole triplet is slowly swept in frequency by a slow sawtooth generator. The electrical signal is fed into a flat acoustic transducer; the acoustic wave is then transmitted through an acoustically active medium, i.e. the sample, and detected by another flat acoustic transducer which produces an FM signal with a superposed amplitude modulated (AM) signal if one of the sidebands overlaps an acoustic feature. This electrical signal is then demodulated to give a pure AM signal which can be phase sensitive detected by using a lock-in amplifier. By suitable adjustment of the phase setting of the lock-in amplifier both the "in-phase" and "out-of-phase" signals of the detected acoustic signal can be detected.

Andrew C. Tam

Papers

Applications of photoacoustic sensing techniques

Pulsed optoacoustic spectroscopy of condensed matter

Laser‐cleaning techniques for removal of surface particulates

Efficient pulsed laser removal of 0.2 μm sized particles from a solid surface

Method and device for detecting a specific acoustic spectral feature