Photoacoustic imaging with deconvolution algorithm

The impulse response of the ultrasonic transducer used for detection is crucial for photoacoustic imaging with high resolution. We demonstrate a reconstruction method that allows the optical absorption distribution of a sample to be reconstructed without knowing the impulse response of the ultrasonic transducer. A convolution relationship between photoacoustic signals measured by an ultrasound transducer and optical absorption distribution is developed. Based on this theory, the projection of the optical absorption distribution of a sample can be obtained directly by deconvolving the recorded PA signal originating from a point source out of that from the sample. And a modified filtered back projection algorithm is used to reconstruct the optical absorption distribution. We constructed a photoacoustic imaging system to validate the reconstruction method and the experimental results demonstrated that the reconstructed images agreed well with the original phantom samples. The spatial resolution of the system reaches 0.3 mm.     

Photoacoustic tomography of biological tissues with high cross-section resolution: reconstruction and experiment

A modified back-projection approach deduced from an exact reconstruction solution was applied to our photoacoustic tomography of the optical absorption in biological tissues. Pulses from a Ti:sapphire laser (4.7 ns FWHM at 789.2 nm) were employed to generate a distribution of photoacoustic sources in a sample. The sources were detected by a wide-band nonfocused ultrasonic transducer at different positions around the imaging cross section perpendicular to the axis of the laser irradiation. Reconstructed images of phantoms made from chicken breast tissue agreed well with the structures of the samples. The resolution in the imaging cross section was experimentally demonstrated to be better than 60 microm when a 10 MHz transducer (140% bandwidth at -60 dB) was employed, which was nearly diffraction limited by the detectable photoacoustic waves of the highest frequency.     

Non-contact biomedical photoacoustic and ultrasound imaging

The detection of ultrasound in photoacoustic tomography (PAT) usually relies on ultrasonic transducers in contact with the biological tissue through a coupling medium. This is a major drawback for important potential applications such as surgery. Here we report the use of a remote optical method, derived from industrial laser-ultrasonics, to detect ultrasound in tissues. This approach enables non-contact PAT (NCPAT) without exceeding laser exposure safety limits. The sensitivity of the method is based on the use of suitably shaped detection laser pulses and a confocal Fabry-Perot interferometer in differential configuration. Reliable image reconstruction is obtained by measuring remotely the surface profile of the tissue with an optical coherence tomography system. The proposed method also allows non-contact ultrasound imaging (US) by applying a second reconstruction algorithm to the data acquired for NCPAT. Endogenous and exogenous inclusions exhibiting optical and acoustic contrasts were detected ex vivo in chicken breast and calf brain specimens. Inclusions down to 0.3 mm in size were detected at depths exceeding 1 cm. The method could expand the scope of photoacoustic and US to in-vivo biomedical applications where contact is impractical.     

Optical coherence photoacoustic microscopy: accomplishing optical coherence tomography and photoacoustic microscopy with a single light source

We developed optical coherence photoacoustic microscopy (OC-PAM) to demonstrate that the functions of optical coherence tomography (OCT) and photoacoustic microscopy (PAM) can be achieved simultaneously by using a single illuminating light source. We used a pulsed broadband laser centered at 580 nm and detected the absorbed photons through photoacoustic detection and the back-scattered photons with an interferometer. In OC-PAM, each laser pulse generates both one OCT A-line and one PAM A-line simultaneously; as a result, the two imaging modalities are intrinsically co-registered in the lateral directions. In vivo images of the mouse ear were acquired to demonstrate the capabilities of OC-PAM.     

Photoacoustic imaging of blood vessels with a double-ring sensor featuring a narrow angular aperture

A photoacoustic double-ring sensor, featuring a narrow angular aperture, is developed for laser-induced photoacoustic imaging of blood vessels. An integrated optical fiber enables reflection-mode detection of ultrasonic waves. By using the cross-correlation between the signals detected by the two rings, the angular aperture of the sensor is reduced by a factor of 1.9, from 1.5 to 0.8 deg. Consequently, photoacoustic images could be obtained in a manner analogous to the ultrasound B-scan mode. Next, the cross section of artificial blood vessels is visualized by reconstruction of the absorbed energy distribution. Finally, in vivo imaging and the subsequent reconstruction of the absorbed energy distribution is demonstrated for superficial blood vessels in the human wrist.     

Three-dimensional finite-element-based photoacoustic tomography: reconstruction algorithm and simulations

In this paper, a finite element reconstruction algorithm for three-dimensional photoacoustic tomography is described. The algorithm is based on rigorous iterative solution to the Helmholtz photoacoustic wave equation coupled with regularization techniques and is able to recover both the images of absorbed optical energy density and acoustic speed simultaneously. The algorithm is tested using various numerical examples that mimic cancer detection and joint imaging. The results show that the algorithm is able to reconstruct photoacoustic images quantitatively in terms of the location, size, optical and acoustic properties of the target, and background media for various examples examined.     

Aberration correction for transcranial photoacoustic tomography of primates employing adjunct image data

A challenge in photoacoustic tomography (PAT) brain imaging is to compensate for aberrations in the measured photoacoustic data due to their propagation through the skull. By use of information regarding the skull morphology and composition obtained from adjunct x-ray computed tomography image data, we developed a subject-specific imaging model that accounts for such aberrations. A time-reversal-based reconstruction algorithm was employed with this model for image reconstruction. The image reconstruction methodology was evaluated in experimental studies involving phantoms and monkey heads. The results establish that our reconstruction methodology can effectively compensate for skull-induced acoustic aberrations and improve image fidelity in transcranial PAT.     

Blood oxygen flux estimation with a combined photoacoustic and high-frequency ultrasound microscopy system: a phantom study

The metabolic rate of oxygen consumption, an important indicator of tissue metabolism, can be expressed as the change of net blood oxygen flux into and out of a tissue region per 100 g of tissue. In this work, we propose a photoacoustic and Doppler ultrasound method for imaging local blood oxygen flux of a single vessel. An imaging system for combined photoacoustic and high-frequency ultrasound microscopy is presented. This system uses a swept-scan 25-MHz ultrasound transducer with confocal dark-field laser illumination optics. A pulse-sequencer enables ultrasonic and laser pulses to be interlaced so that photoacoustic and Doppler ultrasound images are co-registered. Since the mean flow speed can be measured by color Doppler ultrasound, the vessel cross-sectional area can be measured by power Doppler or structural photoacoustic imaging, and multi-wavelength photoacoustic methods can be used to estimate oxygen saturation (sO(2)) and total concentration of haemoglobin (C(Hb)), all of the parameters necessary for oxygen flux estimation can be provided. The accuracy of the flow speed and sO(2) estimation has been investigated. In vitro sheep blood phantom experiments have been performed at different sO(2) levels and mean flow speeds. Blood oxygen flux has been estimated, and the uncertainty of the measurement has been quantified.     

Photoacoustic tomography of ex vivo mouse hearts with myocardial infarction

In the present study, we evaluated the applicability of ex vivo photoacoustic imaging (PAI) on small animal organs. We used photoacoustic tomography (PAT) to visualize infarcted areas within murine hearts and compared these data to other imaging techniques [magnetic resonance imaging (MRI), micro-computed tomography] and histological slices. In order to induce ischemia, an in vivo ligation of the left anterior descending artery was performed on nine wild-type mice. After varying survival periods, the hearts were excised and fixed in formaldehyde. Samples were illuminated with nanosecond laser pulses delivered by a Nd:YAG pumped optical parametric oscillator. Ultrasound detection was achieved using a Mach-Zehnder interferometer (MZI) working as an integrating line detector. The voxel data were computed using a Fourier-domain based reconstruction algorithm, followed by inverse Radon transforms. The results clearly showed the capability of PAI to visualize myocardial infarction and to produce three-dimensional images with a spatial resolution of approximately 120 μm. Regions of affected muscle tissue in PAI corresponded well with the results of MRI and histology. Photoacoustic tomography utilizing a MZI for ultrasound detection allows for imaging of small tissue samples. Due to its high spatial resolution, good soft tissue contrast and comparatively low cost, PAT offers great potentials for imaging.     

Investigation of iterative image reconstruction in three-dimensional optoacoustic tomography

Iterative image reconstruction algorithms for optoacoustic tomography (OAT), also known as photoacoustic tomography, have the ability to improve image quality over analytic algorithms due to their ability to incorporate accurate models of the imaging physics, instrument response and measurement noise. However, to date, there have been few reported attempts to employ advanced iterative image reconstruction algorithms for improving image quality in three-dimensional (3D) OAT. In this work, we implement and investigate two iterative image reconstruction methods for use with a 3D OAT small animal imager: namely a penalized least-squares (PLS) method employing a quadratic smoothness penalty and a PLS method employing a total variation norm penalty. The reconstruction algorithms employ accurate models of the ultrasonic transducer impulse responses. Experimental data sets are employed to compare the performances of the iterative reconstruction algorithms to that of a 3D filtered backprojection (FBP) algorithm. By the use of quantitative measures of image quality, we demonstrate that the iterative reconstruction algorithms can mitigate image artifacts and preserve spatial resolution more effectively than FBP algorithms. These features suggest that the use of advanced image reconstruction algorithms can improve the effectiveness of 3D OAT while reducing the amount of data required for biomedical applications.     

Spectrally encoded photoacoustic microscopy using a digital mirror device

We have developed spectrally encoded photoacoustic microscopy using a digital mirror device for multi-wavelength tomography, which enables fast spectral imaging of optical absorption. The optical illumination wavelengths are multiplexed at a laser pulse repetition rate of ≈ 2 kHz. Liquid samples, whole blood, and blood vessels in mouse ears were imaged. Compared with internal wavelength tuning of a narrow-band laser, external wavelength tuning based on a digital mirror device improves the data acquisition speed of spectral photoacoustic microscopy. Compared with external wavelength scanning of a wide-band laser with the same pulse energy, spectral encoding improves the signal-to-noise ratio.     

Photoacoustic microscopy of tyrosinase reporter gene in vivo

Photoacoustic tomography is a hybrid modality based on optical absorption excitation and ultrasonic detection. It is sensitive to melanin, one of the primary absorbers in skin. For cells that do not naturally contain melanin, melanin production can be induced by introducing the gene for tyrosinase, the primary enzyme responsible for expression of melanin in melanogenic cells. Optical resolution photoacoustic microscopy was used in the ex vivo study reported here, where the signal from transfected cells increased by more than 10 times over wild-type cells. A subsequent in vivo experiment was conducted to demonstrate the capability of photoacoustic microscopy to spectrally differentiate between tyrosinase-catalyzed melanin and various other absorbers in tissue.     

Comparisons of hybrid radiosity-diffusion model and diffusion equation for bioluminescence tomography in cavity cancer detection

Bioluminescence tomography (BLT) has been successfully applied to the detection and therapeutic evaluation of solid cancers. However, the existing BLT reconstruction algorithms are not accurate enough for cavity cancer detection because of neglecting the void problem. Motivated by the ability of the hybrid radiosity-diffusion model (HRDM) in describing the light propagation in cavity organs, an HRDM-based BLT reconstruction algorithm was provided for the specific problem of cavity cancer detection. HRDM has been applied to optical tomography but is limited to simple and regular geometries because of the complexity in coupling the boundary between the scattering and void region. In the provided algorithm, HRDM was first applied to three-dimensional complicated and irregular geometries and then employed as the forward light transport model to describe the bioluminescent light propagation in tissues. Combining HRDM with the sparse reconstruction strategy, the cavity cancer cells labeled with bioluminescent probes can be more accurately reconstructed. Compared with the diffusion equation based reconstruction algorithm, the essentiality and superiority of the HRDM-based algorithm were demonstrated with simulation, phantom and animal studies. An in vivo gastric cancer-bearing nude mouse experiment was conducted, whose results revealed the ability and feasibility of the HRDM-based algorithm in the biomedical application of gastric cancer detection.     

Application of the photon average trajectories method to real-time reconstruction of tissue inhomogeneities in diffuse optical tomography of strongly scattering media

The possibility of application of the photon average trajectories (PAT) method to real-time reconstruction of tissue inhomogeneities in diffuse optical tomography of strongly scattering media has been substantiated. By this method, the inverse problem is reduced to solution of the integral equation with integration along a conditional PAT. Such an approach allows the standard fast algebraic algorithms commonly used in projection computed tomography to be applied to diffuse optical image reconstruction. To demonstrate the capabilities of the PAT method, a numerical experiment on cross-sectional reconstruction of cylindrical strongly scattering objects with absorbing inhomogeneities has been done. Relative shadows caused by inhomogeneities are simulated via numerical solution of the non-stationary diffusion equation. To solve the inverse problem, the QR-factorization least-squares algorithm and the multiplicative algebraic reconstruction technique are used. The results are compared with those obtained by a well-known software package for temporal optical absorption and scattering tomography based on multiple solution of the diffusion equation. It is shown that the PAT method allows reconstruction of the optical structure of objects with comparable accuracy while saving reconstruction time considerably.     

Sentinel lymph node detection ex vivo using ultrasound-modulated optical tomography

We apply ultrasound-modulated optical tomography (UOT) to image ex-vivo methylene-blue-dyed sentinel lymph nodes embedded in 3.2-cm-thick chicken breast tissues. The UOT system is implemented for the first time using ring-shaped light illumination, intense acoustic bursts, and charge-coupled device (CCD) camera-based speckle contrast detection. Since the system is noninvasive, nonionizing, portable, relatively cost effective, and easy to combine with photoacoustic imaging and single element ultrasonic pulse-echo imaging, UOT can potentially be a good imaging modality for the detection of sentinel lymph nodes in breast cancer staging in vivo.     

Three-dimensional photoacoustic tomography based on the focal-line concept

A full ring ultrasonic array-based photoacoustic tomography system was recently developed for small animal brain imaging. The 512-element array is cylindrically focused in the elevational direction, and can acquire a two-dimensional (2D) image in 1.6 s. In this letter, we demonstrate the three-dimensional (3D) imaging capability of this system. A novel 3D reconstruction algorithm was developed based on the focal-line concept. Compared to 3D images acquired simply by stacking a series of 2D images, the 3D focal-line reconstruction method renders images with much less artifacts, and improves the elevational resolution by 30% and the signal-to-noise ratio by two times. The effectiveness of the proposed algorithm was first validated by numerical simulations and then demonstrated with a hair phantom experiment and an ex vivo mouse embryo experiment.     

Whole-body Cerenkov luminescence tomography with the finite element SP(3) method

Generation of an accurate Cerenkov luminescence imaging model is a current issue of nuclear tomography with optical techniques. The article takes a pro-active approach toward whole-body Cerenkov luminescence tomography. The finite element framework employs the equation of radiative transfer via the third-order simplified spherical harmonics approximation to model Cerenkov photon propagation in a small animal. After this forward model is performed on a digital mouse with optical property heterogeneity and compared with the Monte Carlo method, we investigated the whole body reconstruction algorithm along a regularization path via coordinate descent. The endpoint of the follow-up study is the in vivo application, which provides three-dimensional biodistribution of the radiotracer uptake in the mouse from measured partial boundary currents. The combination of the forward and inverse model with elastic-net penalties is not only validated by numerical simulation, but it also effectively demonstrates in vivo imaging in small animals. Our exact reconstruction method enables optical molecular imaging to best utilize Cerenkov radiation emission from the decay of medical isotopes in tissues.     

Photoacoustic section imaging using an elliptical acoustic mirror and optical detection

A method is proposed that utilizes the advantages of optical ultrasound detection in two-dimensional photoacoustic section imaging, combining an optical interferometer with an acoustic mirror. The concave mirror has the shape of an elliptical cylinder and concentrates the acoustic wave generated around one focal line in the other one, where an optical beam probes the temporal evolution of acoustic pressure. This yields line projections of the acoustic sources at distances corresponding to the time of flight, which, after rotating the sample about an axis perpendicular to the optical detector, allows reconstruction of a section using the inverse Radon transform. A resolution of 120 [micro sign]m within and 1.5 mm between the sections can be obtained with the setup. Compared to a bare optical probe beam, the signal-to-noise ratio (SNR) is seven times higher with the mirror. Furthermore, the imaging system is tested on a biological sample.     

基于滤波反投影算法的血管内光声图像重建

将目前在光声断层（PAT）成像中得到广泛应用的滤波反投影（FBP）重建算法应用到血管内光声（IVPA）成像中,提出一种简单快速的二维图像重建方法。首先,对组织产生的光声信号进行滤波、逆卷积和时域一阶求导的预处理;然后,针对IVPA在血管腔内封闭成像的特殊性,采用权重法将预处理后的光声信号数据对导管以外的成像区域沿弧线进行反投影,得到成像平面内每个网格点处的初始光声压。最后,得到反映血管壁组织结构形态的横截面灰阶图像。对仿真血管模型的实验表明,采用所提出的方法重建IVPA图像的结构,相似性指标（SSIM）可达到 0.571 7。合理选择滤波函数、滤波截止频率以及测量位置数,可以提高IVPA重建图像的质量;对光声信号进行时域一阶求导处理,能有效地突出重建图像中的组织结构信息。该方法为后续图像重建算法的优化奠定基础。     

Photoacoustic and high-frequency power Doppler ultrasound biomicroscopy: a comparative study

Both photoacoustic imaging and power Doppler ultrasound are capable of producing images of the vasculature of living subjects, however, the contrast mechanisms of the two modalities are very different. We present a quantitative and objective comparison of the two methods using phantom data, highlighting relative merits and shortcomings. An imaging system for combined photoacoustic and high-frequency power Doppler ultrasound microscopy is presented. This system uses a swept-scan 25-MHz ultrasound transducer with confocal dark-field laser illumination optics. A pulse-sequencer enables ultrasonic and laser pulses to be interlaced so that photoacoustic and power Doppler ultrasound images can be coregistered. Experiments are performed on flow phantoms with various combinations of vessel size, flow velocity, and optical wavelength. For the task of blood volume detection, power Doppler is seen to be advantageous for large vessels and high flow speeds. For small vessels with low flow speeds, photoacoustic imaging is seen to be more effective than power Doppler at the detection of blood as quantified by receiver operating characteristic analysis. A combination of the two modes could provide improved estimates of fractional blood volume in comparison with either mode used alone.