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

Acoustic holograms can be used to form complex distributions of pressure in 3D at MHz frequencies from simple inexpensive ultrasound sources. The generation of such fields is vital to a diverse range of applications in physical acoustics. However, at present, the application of acoustic holograms is severely hindered by the static nature of the resulting fields. In this work, it is shown that by intentionally reducing the diffraction efficiency of each hologram, it is possible to create stackable acoustic holograms that can be repositioned to reconfigure the combined acoustic field. An experimental test-case consisting of two holograms, each designed to generate a distinct distribution of acoustic foci, is used to demonstrate the feasibility of this approach. Field scans taken for four different positions of the two holograms confirm that the individual patterns for each hologram can be arbitrary translated relative to one another. This allows for the generation of a much greater range of fields from a single transducer than could be created using a single hologram.

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Stackable acoustic holograms

For many engineers and acousticians, the boundary element method (BEM) provides an invaluable tool in the analysis of complex problems. It is particularly well suited for the examination of acoustical problems within large domains. Unsurprisingly, the widespread application of the BEM continues to produce an academic interest in the methodology. New algorithms and techniques are still being proposed, to extend the functionality of the BEM, and to compute the required numerical tasks with greater accuracy and efficiency. However, for a given global error constraint, the actual computational accuracy that is required from the various numerical procedures is not often discussed. Within this context, this paper presents an investigation into the discretisation and computational errors that arise in the BEM for acoustic scattering. First, accurate routines to compute regular, weakly singular, and nearly weakly singular integral kernels are examined. These are then used to illustrate the effect of the requisite boundary discretisation on the global error. The effects of geometric and impedance singularities are also considered. Subsequently, the actual integration accuracy required to maintain a given global error constraint is established. Several regular and irregular scattering examples are investigated, and empirical parameter guidelines are provided.

http://users.cecs.anu.edu.au/~btreeby/papers/JOURN_06_2009_Treeby_EABE_ErrorsBoundaryElementMethod.pdf

A practical examination of the errors arising in the direct collocation boundary element method for acoustic scattering

In this work, the use of binary amplitude holography is investigated as a mechanism to focus broadband acoustic pulses generated by high peak-power pulsed lasers. Two algorithms are described for the calculation of the binary holograms; one using ray-tracing, and one using an optimization based on direct binary search. It is shown using numerical simulations that when a binary amplitude hologram is excited by a train of laser pulses at its design frequency, the acoustic field can be focused at a pre-determined distribution of points, including single and multiple focal points, and line and square foci. The numerical results are validated by acoustic field measurements from binary amplitude holograms, excited by a high peak-power laser.

Control of broadband optically generated ultrasound pulses using binary amplitude holograms.

Simulating the propagation of nonlinear ultrasound waves is computationally difficult because of the dense grids needed to capture high-frequency harmonics Here, a mapped k-space pseudospectral method is presented which allows the use of nonuniform grid spacings This enables grid points to be clustered around steep regions of the wave field Compared with using a uniform grid, this significantly reduces the total number of grid points needed for accurate simulations Two methods for selecting a suitable nonuniform grid mapping are discussed

Modeling nonlinear wave propagation on nonuniform grids using a mapped k-space pseudospectral method

Reconstructing images from measured time domain signals is an essential step in tomography-mode photoacoustic imaging. However, in practice, there are many complicating factors that make it difficult to obtain high-resolution images. These include incomplete or undersampled data, filtering effects, acoustic and optical attenuation, and uncertainties in the material parameters. Here, the processing and image reconstruction steps routinely used by the Photoacoustic Imaging Group at University College London are discussed. These include correction for acoustic and optical attenuation, spatial resampling, material parameter selection, image reconstruction, and log compression. The effect of each of these steps is demonstrated using a representative in vivo dataset. All of the algorithms discussed form part of the open-source k-Wave toolbox (available from http://www.k-wave.org).

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Bradley E. Treeby

Papers

Stackable acoustic holograms

A practical examination of the errors arising in the direct collocation boundary element method for acoustic scattering

Control of broadband optically generated ultrasound pulses using binary amplitude holograms.

Modeling nonlinear wave propagation on nonuniform grids using a mapped k-space pseudospectral method

Advanced photoacoustic image reconstruction using the k-Wave toolbox