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

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.

The detection and measurement of gas concentrations using the characteristic optical absorption of the gas species is important for both understanding and monitoring a variety of phenomena from industrial processes to environmental change. This study reviews the field, covering several individual gas detection techniques including non-dispersive infrared, spectrophotometry, tunable diode laser spectroscopy and photoacoustic spectroscopy. We present the basis for each technique, recent developments in methods and performance limitations. The technology available to support this field, in terms of key components such as light sources and gas cells, has advanced rapidly in recent years and we discuss these new developments. Finally, we present a performance comparison of different techniques, taking data reported over the preceding decade, and draw conclusions from this benchmarking.

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Optical gas sensing: a review

We review recent advances in laser cell surgery, and investigate the working mechanisms of femtosecond laser nanoprocessing in biomaterials with oscillator pulses of 80-MHz repetition rate and with amplified pulses of 1-kHz repetition rate. Plasma formation in water, the evolution of the temperature distribution, thermoelastic stress generation, and stress-induced bubble formation are numerically simulated for NA=1.3, and the outcome is compared to experimental results. Mechanisms and the spatial resolution of femtosecond laser surgery are then compared to the features of continuous-wave (cw) microbeams. We find that free electrons are produced in a fairly large irradiance range below the optical breakdown threshold, with a deterministic relationship between free-electron density and irradiance. This provides a large ‘tuning range’ for the creation of spatially extremely confined chemical, thermal, and mechanical effects via free-electron generation. Dissection at 80-MHz repetition rate is performed in the low-density plasma regime at pulse energies well below the optical breakdown threshold and only slightly higher than used for nonlinear imaging. It is mediated by free-electron-induced chemical decomposition (bond breaking) in conjunction with multiphoton-induced chemistry, and hardly related to heating or thermoelastic stresses. When the energy is raised, accumulative heating occurs and long-lasting bubbles are produced by tissue dissociation into volatile fragments, which is usually unwanted. By contrast, dissection at 1-kHz repetition rate is performed using more than 10-fold larger pulse energies and relies on thermoelastically induced formation of minute transient cavities with lifetimes <100 ns. Both modes of femtosecond laser nanoprocessing can achieve a 2–3 fold better precision than cell surgery using cw irradiation, and enable manipulation at arbitrary locations.

Mechanisms of femtosecond laser nanosurgery of cells and tissues

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

Introduction to Environmental Sensing (M. Sigrist). Differential Optical Absorption Spectroscopy (DOAS) (U. Platt). Differential Absorption Lidar (DIAL) (S. Svanberg). Air Monitoring by Laser Photoacoustic Spectroscopy (M. Sigrist). The Use of Tunable Diode Laser Absorption Spectroscopy for Atmospheric Measurements (H. Schiff, et al.). Gas Measurement in the Fundamental Infrared Region (P. Hanst & S. Hanst). Matrix Isolation Spectroscopy in Atmospheric Chemistry (D. Griffith). Index.

Air monitoring by spectroscopic techniques

The laser generation of sound in liquids and gases is reviewed. The sound‐generating mechanisms of laser interaction with matter are discussed with emphasis on the thermoelastic process. The studies on strongly absorbing liquids include detailed theoretical considerations of the thermoelastic sound generation with pulsed lasers. Acoustic waveforms for H2O and D2O are calculated analytically on the basis of a model laser‐pulse shape. Both free and rigid boundaries on the surface of the liquid are considered. Good agreement between theory and experiments with respect to waveforms and amplitudes is obtained. The experiments are performed with a hybrid CO2 laser and piezoelectric or optical detection of the acoustic transients. In view of a present controversy, special emphasis is put on the temperature dependence of the acoustic amplitudes in H2O, D2O, and in aqueous MgSO4 solutions. Good agreement is found between experimental data and a new, pure thermal model which takes heat conduction into account. The distortion of the acoustic waveform during the propagation through the liquid is treated in terms of sound absorption, diffraction, and nonlinear acoustics. A simple experimental method for the determination of Beyer’s nonlinearity parameter B/A is presented. In the last section some characteristics of photoacoustic spectroscopy (PAS) in gaseous media are reviewed. This method has been demonstrated to be highly sensitive. The measurement of absorption coefficients as low as 10− 8 cm− 1 is possible. PA studies on H2O vapor are discussed with new results on line and continuum absorption in the 9–11‐μm wavelength range. Finally, the impact of PAS on trace gas analysis is demonstrated. With PAS the detection of gas concentrations in the ppb range is feasible. The operational characteristics of a stationary CO laser and a mobile CO2 laser‐PAS system are presented, including first results on continuous i n s i t u air pollution monitoring.

Laser generation of acoustic waves in liquids and gases

The generation of laser‐induced stress waves in liquids by the vaporization process and the thermoelastic effect was studied experimentally. A high‐speed camera and special high‐sensitivity stress transducers with a response time of a few nanoseconds have been used for these investigations. The experimental results obtained for water, n‐heptane, and carbon tetrachloride are discussed. For the first time, the individual contributions of vaporization and the thermoelastic effect on stress generation are separated. In addition, tunable high‐frequency acoustic waves, with frequencies up to 60 MHz, have been generated in water by the impact of a laser pulse exhibiting longitudinal mode beating. Since existing theories on the thermoelastic generation of acoustic waves do not yield satisfactory agreement with our experimental data, a new spherical model is proposed, where the transient heating caused by the laser impact, is represented by the three‐dimensional heat pole. This solution of the equation of heat conduction corresponds to a Gaussian distribution of the excessive temperature in space, and thus to the TEM00 mode of the incident laser beam. An analytical solution of the thermoelastic pressure wave is derived for this case of temperature distribution. Its good agreement with the experiment is discussed for various liquids and for two different laser characteristics.

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Laser‐generated stress waves in liquids

The success of laser-based trace gas sensing techniques crucially depends on the availability and performance of tunable laser sources combined with appropriate detection schemes. Besides near-infrared diode lasers, continuously tunable midinfrared quantum cascade lasers and nonlinear optical laser sources are preferentially employed today. Detection schemes are based on sensitive absorption measurements and comprise direct absorption in multi-pass cells as well as photoacoustic and cavity ringdown techniques in various configurations. We illustrate the performance of several systems implemented in our laboratory. These include time-resolved multicomponent traffic emission measurements with a mobile CO2-laser photoacoustic system, a diode-laser based cavity ringdown device for measurements of impurities in industrial process control, isotope ratio measurements with a difference frequency (DFG) laser source combined with balanced path length detection, detection of methylamines for breath analysis with both a near-IR diode laser and a DFG source, and finally, acetone measurements with a heatable multipass cell intended for vapor phase studies on doping agents in urine samples.

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Trace gas monitoring with infrared laser-based detection schemes

Trace gas sensing systems have to meet several requirements like high detection sensitivity and selectivity, multicomponent capability, field suitability, etc. In this respect devices based on tunable lasers combined with appropriate detection schemes are attracting great interest. This report reviews recent developments demonstrating the potential of such systems. The performance of various spectroscopic systems with different lasers (gas lasers, nonlinear optical sources like optical parametric oscillators and difference frequency generation, near-infrared external cavity diode lasers, quantum cascade lasers) and different detection schemes (photoacoustic, multipass transmission, cavity ringdown) is discussed and illustrated with examples from various areas. Applications include laboratory analyses of multicomponent samples with isotopic selectivity, field measurements in ambient urban and rural air or even at volcanic sites, as well as investigations in the area of biology and medical diagnostics.

Markus W. Sigrist

Papers

Air monitoring by spectroscopic techniques

Laser generation of acoustic waves in liquids and gases

Laser‐generated stress waves in liquids

Trace gas monitoring with infrared laser-based detection schemes

Trace gas monitoring by laser photoacoustic spectroscopy and related techniques (plenary)