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.

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

A new, freely available third party MATLAB toolbox for the simulation and reconstruction of photoacoustic wave fields is described. The toolbox, named k-Wave, is designed to make realistic photoacoustic modeling simple and fast. The forward simulations are based on a k-space pseudo-spectral time domain solution to coupled first-order acoustic equations for homogeneous or heterogeneous media in one, two, and three dimensions. The simulation functions can additionally be used as a flexible time reversal image reconstruction algorithm for an arbitrarily shaped measurement surface. A one-step image reconstruction algorithm for a planar detector geometry based on the fast Fourier transform (FFT) is also included. The architecture and use of the toolbox are described, and several novel modeling examples are given. First, the use of data interpolation is shown to considerably improve time reversal reconstructions when the measurement surface has only a sparse array of detector points. Second, by comparison with one-step, FFT-based reconstruction, time reversal is shown to be sufficiently general that it can also be used for finite-sized planar measurement surfaces. Last, the optimization of computational speed is demonstrated through parallel execution using a graphics processing unit.

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k-Wave: MATLAB toolbox for the simulation and reconstruction of photoacoustic wave fields

The life sciences can benefit greatly from imaging technologies that connect microscopic discoveries with macroscopic observations. One technology uniquely positioned to provide such benefits is photoacoustic tomography (PAT), a sensitive modality for imaging optical absorption contrast over a range of spatial scales at high speed. In PAT, endogenous contrast reveals a tissue's anatomical, functional, metabolic, and histologic properties, and exogenous contrast provides molecular and cellular specificity. The spatial scale of PAT covers organelles, cells, tissues, organs, and small animals. Consequently, PAT is complementary to other imaging modalities in contrast mechanism, penetration, spatial resolution, and temporal resolution. We review the fundamentals of PAT and provide practical guidelines for matching PAT systems with research needs. We also summarize the most promising biomedical applications of PAT, discuss related challenges, and envision PAT's potential to lead to further breakthroughs.

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A practical guide to photoacoustic tomography in the life sciences

Two universal reconstruction methods for photoacoustic (also called optoacoustic or thermoacoustic) computed tomography are derived, applicable to an arbitrarily shaped detection surface. In photoacoustic tomography acoustic pressure waves are induced by illuminating a semitransparent sample with pulsed electromagnetic radiation and are measured on a detection surface outside the sample. The imaging problem consists in reconstructing the initial pressure sources from those measurements. The first solution to this problem is based on the time reversal of the acoustic pressure field with a second order embedded boundary method. The pressure on the arbitrarily shaped detection surface is set to coincide with the measured data in reversed temporal order. In the second approach the reconstruction problem is solved by calculating the far-field approximation, a concept well known in physics, where the generated acoustic wave is approximated by an outgoing spherical wave with the reconstruction point as center. Numerical simulations are used to compare the proposed universal reconstruction methods with existing algorithms.

Exact and approximative imaging methods for photoacoustic tomography using an arbitrary detection surface.

For photoacoustic imaging, usually point-like detectors are used. As a special sensing technology for photoacoustic imaging, integrating detectors have been investigated that integrate the acoustic pressure over an area or line that is larger than the imaged object. Different kinds of optical fiber-based detectors are compared regarding their sensitivity and resolution in three-dimensional photoacoustic tomography. In the same type of interferometer, polymer optical fibers yielded much higher sensitivity than glass fibers. Fabry-Perot glass-fiber interferometers in turn gave higher sensitivity than Mach-Zehnder-type interferometers. Regarding imaging resolution, the single-mode glass fiber showed the best performance. Last, three-dimensional images of phantoms and insects using a glass-fiber-based Fabry-Perot interferometer as integrating line detector are presented.

https://www.spiedigitallibrary.org/journals/Journal-of-Biomedical-Optics/volume-15/issue-2/021306/Three-dimensional-photoacoustic-imaging-using-fiber-based-line-detectors/10.1117/1.3381186.pdf

Three-dimensional photoacoustic imaging using fiber-based line detectors.

Photoacoustic tomography (PAT) is based on the generation of ultrasound waves by heating an object with short light pulses. A three-dimensional image of the distribution of absorbed energy within the object is reconstructed from signals measured around the object with either point-like or extended, linear sensors. Limited angle artefacts arise when the curve or surface connecting neighbouring detectors is not closed around the object. For this case, there exists a 'detection region' in which all boundaries of an object are visible in the reconstruction. All straight lines passing through each point in this region intersect the detection curve or surface at least once. Although for these points an accurate reconstruction is possible, direct back projection leads to artefacts when some of the straight lines intersect the detection surface twice and others just once. In this work, special weight functions for direct, non-iterative back projection are presented that reduce these kinds of artefacts. A clear improvement in image quality is shown in simulations for three-dimensional (3D) imaging with point detectors and for two-dimensional (2D) imaging using line detectors compared to reconstruction without weight factors. For the 2D case also an experiment is shown. The presented weight factors make commonly used back projection formulae suitable for a more accurate reconstruction of the initial pressure distribution in cases where the detection aperture only covers a limited angle, and the region of interest lies within the detection region.

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Weight factors for limited angle photoacoustic tomography.

Photoacoustic imaging is based on the generation of acoustic waves in a semitransparent sample after illumination with short pulses of light or radio waves. The goal is to recover the spatial distribution of absorbed energy density inside the sample from acoustic pressure signals measured outside the sample (photoacoustic inverse problem). We have proposed a numerical method to calculate directly the time reversed field by retransmitting the measured pressure on the detection surface in reversed temporal order. This model-based time reversal method can solve the photoacoustic inverse problem exactly for an arbitrary closed detection surface. Recently we presented a set up which requires a single rotation axis and line detectors perpendicular to the rotation axis. Using a two-dimensional reconstruction method, such as time reversal in two dimensions, and applying the inverse two-dimensional radon transform afterwards gives an exact reconstruction of a three-dimensional sample with this set up. The resolution in photoacoustic imaging is limited by the acoustic bandwidth and therefore by acoustic attenuation, which can be substantial for high frequencies. This effect is usually ignored in reconstruction algorithms but has a strong impact on the resolution of small structures. It is demonstrated that the model based time reversal method allows to partly compensate this effect.

Compensation of acoustic attenuation for high-resolution photoacoustic imaging with line detectors

A device for three-dimensional (3-D) photoacoustic tomography with resolution in the range of tens of micrometers is presented that uses a light beam for interferometric detection of acoustic waves. Reconstruction of the 3-D initial pressure distribution from the signals representing line integrals of the acoustic field is a two-step process. It uses an inversion of 2-D wave propagation to obtain line projections of the initial pressure distribution and the inverse Radon transform. The light beam, propagating freely in a water bath, is scanned either in an πarc- or box-shaped curve around the object. Simulations are performed to compare the two scanning procedures. The projection images are obtained either using the filtered back projection algorithm for the -arc scanning mode or the frequency domain algorithm for the box scanning mode. While the former algorithm provides slightly better image quality, the latter is about 20 times faster. The ability of the photoacoustic tomography device to create 3-D images with constant resolution throughout the reconstruction volume is demonstrated experimentally using a human hair phantom. These measurements revealed a 3-D resolution below 100 µm. In a second experiment, 3-D imaging of an isolated mouse heart is demonstrated to show the applicability for preclinical and biological research.

Günther Paltauf

Papers

Exact and approximative imaging methods for photoacoustic tomography using an arbitrary detection surface.

Three-dimensional photoacoustic imaging using fiber-based line detectors.

Weight factors for limited angle photoacoustic tomography.

Compensation of acoustic attenuation for high-resolution photoacoustic imaging with line detectors

Photoacoustic microtomography using optical interferometric detection