Quantitative photoacoustic tomography with multiple optical sources
TL;DR: A noniterative reconstruction technique for producing quantitative photoacoustic images of absorption perturbations is introduced for the case when the optical properties of the turbid background are known and when multiple optical illumination locations are used.
Abstract: Quantitative imaging of optical properties of biological tissues with high resolution has been a long-sought-after goal of many research groups. Photoacoustic imaging is a hybrid bio-optical imaging technique offering optical absorption contrast with ultrasonic spatial resolution. While photoacoustic methods offer significant promise for high-resolution optical imaging, quantification has thus far proved challenging. In this paper, a noniterative reconstruction technique for producing quantitative photoacoustic images of absorption perturbations is introduced for the case when the optical properties of the turbid background are known and when multiple optical illumination locations are used. Through theoretical developments and computational examples it is demonstrated that multiple-optical-source photoacoustic imaging can produce quantitative optical absorption reconstructions. The combination of optical and photoacoustic measurements is shown to yield improved reconstruction stability.
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TL;DR: This topic, known as quantitative photoacoustic imaging, is reviewed here and the inverse problems involved are described, their nature is discussed, proposed solution techniques and their limitations are explained, and the remaining unsolved challenges are introduced.
Abstract: Obtaining absolute chromophore concentrations from photoacoustic images obtained at multiple wavelengths is a nontrivial aspect of photoacoustic imaging but is essential for accurate functional and molecular imaging. This topic, known as quantitative photoacoustic imaging, is reviewed here. The inverse problems involved are described, their nature (nonlinear and ill-posed) is discussed, proposed solution techniques and their limitations are explained, and the remaining unsolved challenges are introduced.
602 citations
TL;DR: In this article, a regularized, adjoint-assisted gradient inversion using a finite element model of the RTE was used to determine the optical absorption and scattering coefficients, and the acoustic pressure time series were simulated using a k-space, pseudo-spectral time domain model, and a time-reversal reconstruction algorithm were used to form a set of photoacoustic images corresponding to four illumination positions.
Abstract: Quantitative photoacoustic tomography (QPAT) offers the possibility of high-resolution molecular imaging by quantifying molecular concentrations in biological tissue. QPAT comprises two inverse problems: (1) the construction of a photoacoustic image from surface measurements of photoacoustic wave pulses over time, and (2) the determination of the optical properties of the imaged region. The first is a well-studied area for which a number of solution methods are available, while the second is, in general, a nonlinear, ill-posed inverse problem. Model-based inversion techniques to solve (2) are usually based on the diffusion approximation to the radiative transfer equation (RTE) and typically assume the acoustic inversion step has been solved exactly. Here, neither simplification is made: the full RTE is used to model the light propagation, and the acoustic propagation and image reconstruction are included in the simulations of measured data. Since Hessian- and Jacobian-based minimizations are computationally expensive for the large data sets typically encountered in QPAT, gradient-based minimization schemes provide a practical alternative. The acoustic pressure time series were simulated using a k-space, pseudo-spectral time domain model, and a time-reversal reconstruction algorithm was used to form a set of photoacoustic images corresponding to four illumination positions. A regularized, adjoint-assisted gradient inversion using a finite element model of the RTE was then used to determine the optical absorption and scattering coefficients.
138 citations
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...This has been highlighted recently in [2, 3, 7, 33], where it has been demonstrated that a set of PAT images obtained using multiple illumination positions can ensure a unique solution....
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TL;DR: In this article, the authors present a review of hybrid inverse problems, which are also referred to as coupled-physics inverse problems of multi-wave inverse problems and multi-modal inverse problems.
Abstract: This paper reviews recent results on hybrid inverse problems, which are also called coupled-physics inverse problems of multi-wave inverse problems. Inverse problems tend to be most useful in, e.g., medical and geophysical imaging, when they combine high contrast with high resolution. In some settings, a single modality displays either high contrast or high resolution but not both. In favorable situations, physical effects couple one modality with high contrast with another modality with high resolution. The mathematical analysis of such couplings forms the class of hybrid inverse problems.
Hybrid inverse problems typically involve two steps. In a first step, a well-posed problem involving the high-resolution low-contrast modality is solved from knowledge of boundary measurements. In a second step, a quantitative reconstruction of the parameters of interest is performed from knowledge of the point-wise, internal, functionals of the parameters reconstructed during the first step. This paper reviews mathematical techniques that have been developed in recent years to address the second step.
Mathematically, many hybrid inverse problems find interpretations in terms of linear and nonlinear (systems of) equations. In the analysis of such equations, one often needs to verify that qualitative properties of solutions to elliptic linear equations are satisfied, for instance the absence of any critical points. This paper reviews several methods to prove that such qualitative properties hold, including the method based on the construction of complex geometric optics solutions.
135 citations
TL;DR: In this article, a non-iterative procedure was proposed to reconstruct the optical coefficients from the absorbed radiation map, namely diffusion and absorption coefficients, and the Gruneisen coefficient when the propagation of radiation is modeled by a second-order elliptic equation.
Abstract: Photoacoustic tomography (PAT) is a novel hybrid medical imaging technique that aims to combine the large contrast of optical coefficients with the high-resolution capabilities of ultrasound. We assume that the first step of PAT, namely the reconstruction of a map of absorbed radiation from ultrasound boundary measurement, has been done. We focus on quantitative photoacoustic tomography, which aims at quantitatively reconstructing the optical coefficients from knowledge of the absorbed radiation map. We present a non-iterative procedure to reconstruct such optical coefficients, namely the diffusion and absorption coefficients, and the Gruneisen coefficient when the propagation of radiation is modeled by a second-order elliptic equation. We show that PAT measurements allow us to uniquely reconstruct only two out of the above three coefficients, even when data are collected using an arbitrary number of radiation illuminations. We present uniqueness and stability results for the reconstructions of two such parameters and demonstrate the accuracy of the reconstruction algorithm with numerical reconstructions from two-dimensional synthetic data.
129 citations
TL;DR: It is experimentally demonstrated that combining DOT with PA imaging can significantly reduce fluence-related errors in PA images, while producing quantitatively accurate, high-resolution images of the optical absorption coefficient.
Abstract: The specificity of molecular and functional photoacoustic (PA) images depends on the accuracy of the photoacoustic absorption spectroscopy. The PA signal is proportional to the product of the optical absorption coefficient and local light fluence; quantitative PA measurements of the optical absorption coefficient therefore require an accurate estimation of optical fluence. Light-modeling aided by diffuse optical tomography (DOT) can be used to map the required fluence and to reduce errors in traditional PA spectroscopic analysis. As a proof-of-concept, we designed a tissue-mimicking phantom to demonstrate how fluence-related artifacts in PA images can lead to misrepresentations of tissue properties. To correct for these inaccuracies, the internal fluence in the tissue phantom was estimated by using DOT to reconstruct spatial distributions of the absorption and reduced scattering coefficients of multiple targets within the phantom. The derived fluence map, which only consisted of low spatial frequency components, was used to correct PA images of the phantom. Once calibrated to a known absorber, this method reduced errors in estimated absorption coefficients from 33% to 6%. These results experimentally demonstrate that combining DOT with PA imaging can significantly reduce fluence-related errors in PA images, while producing quantitatively accurate, high-resolution images of the optical absorption coefficient.
118 citations
References
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TL;DR: An overview of the rapidly expanding field of photoacoustic imaging for biomedical applications can be found in this article, where a number of imaging techniques, including depth profiling in layered media, scanning tomography with focused ultrasonic transducers, image forming with an acoustic lens, and computed tomography using unfocused transducers are introduced.
Abstract: 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.
2,343 citations
TL;DR: The absorption and effective scattering coefficients of beef liver, dog prostate, and human aortic atheroma at three wavelengths, 1064 nm (in near infrared), 532 nm (visible), and 355 nm (near UV), were deduced from laser-induced stress profiles with additional measurements of total diffuse reflectance.
Abstract: We report on a technique utilizing time-resolved detection of laser-induced stress transients for the measurement of optical properties in turbid media specifically suitable for biological tissues. The method was tested initially in nonscattering absorbing media so that it could be compared with spectrophotometry. The basis of this method is provided by the conditions of temporal stress confinement in the irradiated volume where the pressure generated in tissues heated instantly by laser pulses is proportional to the absorbed laser energy density, and the exponential profile of the initial stress distribution in the irradiated volume corresponds to thez-axial distribution of the absorbed laser fluence. Planar thermoelastic waves can propagate in water-containing media with minimal distortion, and their axial profiles can be detected by an acoustic transducer with sufficient temporal resolution. The acoustic waves induced by14-ns laser pulses in nonscattering media, turbid gels, and tissues were measured by a piezoelectric transducer with a 3-ns response time. Temporal profiles of stress transients yielded z-axial distributions of the absorbed laser energy in turbid and opaque media, provided that the speed of sound in these media was known. The absorption and effective scattering coefficients of beef liver, dog prostate, and human aortic atheroma at three wavelengths, 1064 nm (in near infrared), 532 nm(visible), and 355 nm (near UV), were deduced from laser-induced stress profiles with additional measurements of total diffuse reflectance.
322 citations
TL;DR: A simple iterative algorithm is described to recover the distribution of optical absorption coefficients from the image of the absorbed optical energy, which incorporates a diffusion-based finite-element model of light transport.
Abstract: Photoacoustic imaging is a noninvasive biomedical imaging modality for visualizing the internal structure and function of soft tissues. Conventionally, an image proportional to the absorbed optical energy is reconstructed from measurements of light-induced acoustic emissions. We describe a simple iterative algorithm to recover the distribution of optical absorption coefficients from the image of the absorbed optical energy. The algorithm, which incorporates a diffusion-based finite-element model of light transport, converges quickly onto an accurate estimate of the distribution of absolute absorption coefficients. Two-dimensional examples with physiologically realistic optical properties are shown. The ability to recover optical properties (which directly reflect tissue physiology) could enhance photoacoustic imaging techniques, particularly methods based on spectroscopic analysis of chromophores.
273 citations
TL;DR: In this paper, the theory of laser excitation of acoustic waves by absorbing of light in particles, dispersed in transparent, light-absorbing or scattering media, is developed and the distribution of light absorption can be obtained from the temporal course of acoustic pressure.
Abstract: The methods of time-resolved laser optoacoustic tomography of inhomogeneous media and related problems are reviewed. Time-resolved laser optoacoustic tomography allows one to measure the distribution of light absorption in turbid media with depth resolution up to several microns in real time. The theory of laser excitation of acoustic waves by absorbing of light in particles, dispersed in transparent, light-absorbing or scattering media, is developed. The distribution of light absorption can be obtained from the temporal course of acoustic pressure. Two schemes of acoustic wave detection — in the medium under testing (direct detection) and in transparent medium, coupled to the investigated one (indirect detection) — are discussed. In both cases the reconstruction of light absorption can be made by simple calculations. Test experiments with homogeneous and layered media confirm the proposed theoretical models and the possibility of using the proposed experimental schemes. Light absorption in homogeneous, inhomogeneous media and in absorbing particles dispersed in turbid media was investigated. The experimental setup allows one to measure the absorption coefficients over the range 1-500 cm−1 with the depth resolution 10–15 μm over the depth 1–1.5 mm.
167 citations
TL;DR: This work describes a framework for obtaining accurate quantitative estimates of the spatially varying concentrations of the sources of photoacoustic contrast-endogenous or exogenous chromophores and shows that prior knowledge of the wavelength dependence of the scattering is shown to be sufficient to overcome the absorption-scattering nonuniqueness.
Abstract: Biomedical photoacoustic tomography (PAT) can provide qualitative images of biomedical soft tissue with high spatial resolution. However, whether it is possible to give accurate quantitative estimates of the spatially varying concentrations of the sources of photoacoustic contrast—endogenous or exogenous chromophores—remains an open question. Even if the chromophores' absorption spectra are known, the problem is nonlinear and ill-posed. We describe a framework for obtaining such quantitative estimates. When the optical scattering distribution is known, adjoint and gradient-based optimization techniques can be used to recover the concentration distributions of the individual chromophores that contribute to the overall tissue absorption. When the scattering distribution is unknown, prior knowledge of the wavelength dependence of the scattering is shown to be sufficient to overcome the absorption-scattering nonuniqueness and allow both distributions of chromophore concentrations and scattering to be recovered from multiwavelength photoacoustic images.
157 citations