Photoacoustic tomography (PAT) can create multiscale multicontrast images of living biological structures ranging from organelles to organs. This emerging technology overcomes the high degree of scattering of optical photons in biological tissue by making use of the photoacoustic effect. Light absorption by molecules creates a thermally induced pressure jump that launches ultrasonic waves, which are received by acoustic detectors to form images. Different implementations of PAT allow the spatial resolution to be scaled with the desired imaging depth in tissue while a high depth-to-resolution ratio is maintained. As a rule of thumb, the achievable spatial resolution is on the order of 1/200 of the desired imaging depth, which can reach up to 7 centimeters. PAT provides anatomical, functional, metabolic, molecular, and genetic contrasts of vasculature, hemodynamics, oxygen metabolism, biomarkers, and gene expression. We review the state of the art of PAT for both biological and clinical studies and discuss future prospects.

Photoacoustic Tomography: In Vivo Imaging from Organelles to Organs

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

Medical Image Computing and Computer-Assisted Intervention

The diffraction tomography theorem is adapted to one-dimensional length measurement. The resulting spectral interferometry technique is described and the first length measurements using this technique on a model eye and on a human eye in vivo are presented.

Measurement of intraocular distances by backscattering spectral interferometry

A k-space pseudospectral model is developed for the fast full-wave simulation of nonlinear ultrasound propagation through heterogeneous media. The model uses a novel equation of state to account for nonlinearity in addition to power law absorption. The spectral calculation of the spatial gradients enables a significant reduction in the number of required grid nodes compared to finite difference methods. The model is parallelized using a graphical processing unit (GPU) which allows the simulation of individual ultrasound scan lines using a 256 × 256 × 128 voxel grid in less than five minutes. Several numerical examples are given, including the simulation of harmonic ultrasound images and beam patterns using a linear phased array transducer.

http://www.k-wave.org/papers/2011-Treeby-MICCAI.pdf

Time domain simulation of harmonic ultrasound images and beam patterns in 3d using the k-space pseudospectral method

Attenuation effects can be significant in photoacoustic tomography since the generated pressure signals are broadband, and ignoring them may lead to image artifacts and blurring. La Riviere et al. [Opt. Lett. 31(6), pp. 781-783, (2006)] had previously derived a method for modeling the attenuation effect and correcting for it in the image reconstruction. This was done by relating the ideal, unattenuated pressure signals to the attenuated pressure signals via an integral operator. We derive an integral operator relating the attenuated pressure signals to the absorbed optical energy for a planar measurement geometry. The matrix operator relating the two quantities is a function of the temporal frequency, attenuation coefficient and the two-dimensional spatial frequency. We perform singular-value decomposition (SVD) of this integral operator to study the problem further. We find that the smallest singular values correspond to wavelet-like eigenvectors in which most of the energy is concentrated at times corresponding to greater depths in tissue. This allows us to characterize the ill-posedness of recovering the absorbed optical energy distribution at different depths in an attenuating medium. This integral equation can be inverted using standard SVD methods, and the initial pressure distribution can be recovered. We conduct simulations and derive an algorithm for image reconstruction using SVD for a planar measurement geometry. We also study the noise and resolution properties of this image-reconstruction method.

https://www.spiedigitallibrary.org/journals/Journal-of-Biomedical-Optics/volume-17/issue-6/061204/Photoacoustic-image-reconstruction-in-an-attenuating-medium-using-singular-value/10.1117/1.JBO.17.6.061204.pdf

Photoacoustic image reconstruction in an attenuating medium using singular-value decomposition.

Previous empirical and analytical investigations into human sound localization have illustrated that the head-related transfer function (HRTF) and interaural cues are affected by the acoustic material properties of the head. This study utilizes a recent analytical treatment of the sphere scattering problem (which accounts for a hemispherically divided surface boundary) to investigate the contribution of hair to the auditory cues below 5 kHz. The hair is modeled using a locally reactive equivalent impedance parameter, and cue changes are discussed for several cases of measured hair impedance. The hair is shown to produce asymmetric perturbations to the HRTF and the interaural time and level differences. The changes in the azimuth plane are explicated via analytical examination of the surface pressure variations with source angle. Experimental HRTFs obtained using a sphere with and without a hemispherical covering of synthetic hair show a good agreement with analytical results. Additional experimental and analytical investigations illustrate that the relative contribution of the hair remains robust, regardless of the placement of the pinnas, or inclusion of a cylindrical neck.

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The effect of hair on auditory localization cues

Erratum: Modeling power law absorption and dispersion for acoustic propagation using the fractional Laplacian [J. Acoust. Soc. Am. 127, 2741–2748 (2010)]

Previous analytical and empirical studies of the human auditory system have shown that the cues used for localization are modified by the inclusion of nonrigid scattering surfaces (clothing, hair etc). This paper presents an investigation into the acoustic impedance properties of human hair. The legitimacy of a locally reactive surface assumption is investigated, and an appropriate boundary condition is formulated to account for the physiological composition of a human head with hair. This utilizes an equivalent impedance parameter to allow the scattering boundary to be defined at a reference plane coincident with the inner rigid surface of the head. Experimental examination of a representative synthetic hair material at oblique incidence is used to show that a locally reactive surface assumption is legitimate. Additional experimental analysis of a simple scattering problem illustrates that the equivalent impedance must be used in favor of the traditional surface impedance to yield physically correct pressure magnitudes. The equivalent acoustic impedance properties of a representative range of human hair samples are discussed, including trends with sample thickness, fiber diameter, bulk density, and mass.

http://users.cecs.anu.edu.au/~btreeby/papers/JOURN_03_2007_Treeby_JASA_AcousticImpedanceHumanHair.pdf

Bradley E. Treeby

Papers

Time domain simulation of harmonic ultrasound images and beam patterns in 3d using the k-space pseudospectral method

Photoacoustic image reconstruction in an attenuating medium using singular-value decomposition.

The effect of hair on auditory localization cues

Erratum: Modeling power law absorption and dispersion for acoustic propagation using the fractional Laplacian [J. Acoust. Soc. Am. 127, 2741–2748 (2010)]

An experimental study of the acoustic impedance characteristics of human hair