Quantitative determination of chromophore concentrations from 2D photoacoustic images using a nonlinear model-based inversion scheme
TL;DR: A model-based inversion scheme was used to determine absolute chromophore concentrations from multiwavelength photoacoustic images, which incorporated a forward model, which predicted 2D images of the initial pressure distribution as a function of the spatial distribution of the chromophor concentrations.
Abstract: A model-based inversion scheme was used to determine absolute chromophore concentrations from multiwavelength photoacoustic images. The inversion scheme incorporated a forward model, which predicted 2D images of the initial pressure distribution as a function of the spatial distribution of the chromophore concentrations. It comprised a multiwavelength diffusion based model of the light transport, a model of acoustic propagation and detection, and an image reconstruction algorithm. The model was inverted by fitting its output to measured photoacoustic images to determine the chromophore concentrations. The scheme was validated using images acquired in a tissue phantom at wavelengths between 590 nm and 980 nm. The phantom comprised a scattering emulsion in which up to four tubes, filled with absorbing solutions of copper and nickel chloride at different concentration ratios, were submerged. Photoacoustic signals were detected along a line perpendicular to the tubes from which images of the initial pressure distribution were reconstructed. By varying the excitation wavelength, sets of multiwavelength photoacoustic images were obtained. The majority of the determined chromophore concentrations were within ±15% of the true value, while the concentration ratios were determined with an average accuracy of −1.2%.
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TL;DR: The underlying physical principles of the technique, its practical implementation, and a range of clinical and preclinical applications are reviewed.
Abstract: 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.
1,793 citations
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: Focusing on state-of-the-art developments in PAM, this Review discusses the key features of PAM implementations and their applications in biomedical studies.
Abstract: Photoacoustic microscopy (PAM) is a hybrid in vivo imaging technique that acoustically detects optical contrast via the photoacoustic effect. Unlike pure optical microscopic techniques, PAM takes advantage of the weak acoustic scattering in tissue and thus breaks through the optical diffusion limit (~1 mm in soft tissue). With its excellent scalability, PAM can provide high-resolution images at desired maximum imaging depths up to a few millimeters. Compared with backscattering-based confocal microscopy and optical coherence tomography, PAM provides absorption contrast instead of scattering contrast. Furthermore, PAM can image more molecules, endogenous or exogenous, at their absorbing wavelengths than fluorescence-based methods, such as wide-field, confocal, and multi-photon microscopy. Most importantly, PAM can simultaneously image anatomical, functional, molecular, flow dynamic and metabolic contrasts in vivo. Focusing on state-of-the-art developments in PAM, this Review discusses the key features of PAM implementations and their applications in biomedical studies.
391 citations
Cites methods from "Quantitative determination of chrom..."
...In addition, other model-based inversion methods have also been explored to mathematically reconstruct the tissue optical properties from the detected PA signals, which, however, are typically computationally intensive [139, 140]....
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TL;DR: In this article, a method to compensate for the effect of acoustic absorption on the measured time domain signals is described, where the reconstruction is regularized by filtering the absorption and dispersion terms in the spatial frequency domain using a Tukey window.
Abstract: The reconstruction of photoacoustic images typically neglects the effect of acoustic absorption on the measured time domain signals. Here, a method to compensate for acoustic absorption in photoacoustic tomography is described. The approach is based on time-reversal image reconstruction and an absorbing equation of state which separately accounts for acoustic absorption and dispersion following a frequency power law. Absorption compensation in the inverse problem is achieved by reversing the absorption proportionality coefficient in sign but leaving the equivalent dispersion parameter unchanged. The reconstruction is regularized by filtering the absorption and dispersion terms in the spatial frequency domain using a Tukey window. This maintains the correct frequency dependence of these parameters within the filter pass band. The method is valid in one, two and three dimensions, and for arbitrary power law absorption parameters. The approach is verified through several numerical experiments. The reconstruction of a carbon fibre phantom and the vasculature in the abdomen of a mouse are also presented. When absorption compensation is included, a general improvement in the image magnitude and resolution is seen, particularly for deeper features.
301 citations
TL;DR: In this paper, a wave equation that utilizes two lossy derivative operators based on the fractional Laplacian is derived, which can be efficiently incorporated into Fourier based pseudospectral and k-space methods without the increase in memory required by their time-domain fractional counterparts.
Abstract: The efficient simulation of wave propagation through lossy media in which the absorption follows a frequency power law has many important applications in biomedical ultrasonics. Previous wave equations which use time-domain fractional operators require the storage of the complete pressure field at previous time steps (such operators are convolution based). This makes them unsuitable for many three-dimensional problems of interest. Here, a wave equation that utilizes two lossy derivative operators based on the fractional Laplacian is derived. These operators account separately for the required power law absorption and dispersion and can be efficiently incorporated into Fourier based pseudospectral and k-space methods without the increase in memory required by their time-domain fractional counterparts. A framework for encoding the developed wave equation using three coupled first-order constitutive equations is discussed, and the model is demonstrated through several one-, two-, and three-dimensional simulations.
266 citations
References
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TL;DR: Extinction coefficients k(lambda) for water at 25 degrees C were determined through a broad spectral region by manually smoothing a point by point graph of k( lambda) vs wavelength lambda that was plotted for data obtained from a review of the scientific literature on the optical constants of water.
Abstract: Extinction coefficients k(lambda) for water at 25 degrees C were determined through a broad spectral region by manually smoothing a point by point graph of k(lambda) vs wavelength lambda that was plotted for data obtained from a review of the scientific literature on the optical constants of water. Absorption bands representing k(lambda) were postulated where data were not available in the vacuum uv and soft x-ray regions. A subtractive Kramers-Kronig analysis of the combined postulated and smoothed portions of the k(lambda) spectrum provided the index of refraction n(lambda) for the spectral region 200 nm
4,094 citations
01 Jan 1995
TL;DR: A Monte Carlo model of steady-state light transport in multi-layered tissues (MCML) has been coded in ANSI Standard C; therefore, the program can be used on various computers and has been in the public domain since 1992.
Abstract: A Monte Carlo model of steady-state light transport in multi-layered tissues (MCML) has been coded in ANSI Standard C; therefore, the program can be used on various computers. Dynamic data allocation is used for MCML, hence the number of tissue layers and grid elements of the grid system can be varied by users at run time. The coordinates of the simulated data for each grid element in the radial and angular directions are optimized. Some of the MCML computational results have been verified with those of other theories or other investigators. The program, including the source code, has been in the public domain since 1992.
2,889 citations
"Quantitative determination of chrom..." refers methods in this paper
...In order to validate this approach, comparisons were made with a 3D Monte Carlo model [17,18]....
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TL;DR: A Monte Carlo model of steady-state light transport in multi-layered tissues (MCML) has been coded in ANSI Standard C; therefore, the program can be used on various computers as mentioned in this paper.
2,678 citations
TL;DR: Functional photoacoustic microscopy (fPAM) is reported, which provides multiwavelength imaging of optical absorption and permits high spatial resolution beyond this depth limit with a ratio of maximum imaging depth to depth resolution greater than 100.
Abstract: Although optical absorption is strongly associated with the physiological status of biological tissue, existing high-resolution optical imaging modalities, including confocal microscopy, two-photon microscopy and optical coherence tomography, do not sense optical absorption directly. Furthermore, optical scattering prevents these methods from imaging deeper than ~1 mm below the tissue surface. Here we report functional photoacoustic microscopy (fPAM), which provides multiwavelength imaging of optical absorption and permits high spatial resolution beyond this depth limit with a ratio of maximum imaging depth to depth resolution greater than 100. Reflection mode, rather than orthogonal or transmission mode, is adopted because it is applicable to more anatomical sites than the others. fPAM is demonstrated with in vivo imaging of angiogenesis, melanoma, hemoglobin oxygen saturation (sO_2) of single vessels in animals and total hemoglobin concentration in humans.
1,766 citations
"Quantitative determination of chrom..." refers background in this paper
...The correction factors were obtained from measurements of the wavelength dependence of the photoacoustic signal amplitude detected in a black plastic absorber (of presumably known absorption spectrum) inserted beneath the skin [3,11], or from measurements of the optical attenuation of excised tissue samples [12]....
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TL;DR: In vivo noninvasive transdermal and transcranial imaging of the structure and function of rat brains by means of laser-induced photoacoustic tomography (PAT) is reported, which retains intrinsic optical contrast characteristics while taking advantage of the diffraction-limited high spatial resolution of ultrasound.
Abstract: Imaging techniques based on optical contrast analysis can be used to visualize dynamic and functional properties of the nervous system via optical signals resulting from changes in blood volume, oxygen consumption and cellular swelling associated with brain physiology and pathology. Here we report in vivo noninvasive transdermal and transcranial imaging of the structure and function of rat brains by means of laser-induced photoacoustic tomography (PAT). The advantage of PAT over pure optical imaging is that it retains intrinsic optical contrast characteristics while taking advantage of the diffraction-limited high spatial resolution of ultrasound. We accurately mapped rat brain structures, with and without lesions, and functional cerebral hemodynamic changes in cortical blood vessels around the whisker-barrel cortex in response to whisker stimulation. We also imaged hyperoxia- and hypoxia-induced cerebral hemodynamic changes. This neuroimaging modality holds promise for applications in neurophysiology, neuropathology and neurotherapy.
1,724 citations
"Quantitative determination of chrom..." refers background in this paper
...The chromophores that provide the strongest absorption in biological tissue are oxyand deoxyhemoglobin, and this has been exploited to obtain images of the vasculature in tumors and skin [1–3], and the brain [4,5] in small animals....
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