Photoacoustic Imaging System Research Articles

Tissue-mimicking phantoms for performance evaluation of photoacoustic microscopy systems.

Phantom-based performance test methods are critically needed to support development and clinical translation of emerging photoacoustic microscopy (PAM) devices. While phantoms have been recently developed for macroscopic photoacoustic imaging systems, there is an unmet need for well-characterized tissue-mimicking materials (TMMs) and phantoms suitable for evaluating PAM systems. Our objective was to develop and characterize a suitable dermis-mimicking TMM based on polyacrylamide hydrogels and demonstrate its utility for constructing image quality phantoms. TMM formulations were optically characterized over 400-1100 nm using integrating sphere spectrophotometry and acoustically characterized using a pulse through-transmission method over 8-24 MHz with highly confident extrapolation throughout the usable band of the PAM system. This TMM was used to construct a spatial resolution phantom containing gold nanoparticle point targets and a penetration depth phantom containing slanted tungsten filaments and blood-filled tubes. These phantoms were used to characterize performance of a custom-built PAM system. The TMM was found to be broadly tunable and specific formulations were identified to mimic human dermis at an optical wavelength of 570 nm and acoustic frequencies of 10-50 MHz. Imaging results showed that tungsten filaments yielded 1.1-4.2 times greater apparent maximum imaging depth than blood-filled tubes, which may overestimate real-world performance for vascular imaging applications. Nanoparticles were detectable only to depths of 120-200 µm, which may be due to the relatively weaker absorption of single nanoparticles vs. larger targets containing high concentration of hemoglobin. The developed TMMs and phantoms are useful tools to support PAM device characterization and optimization, streamline regulatory decision-making, and accelerate clinical translation.

Transparent Flexible Piezoelectric Ultrasound Transducer for Photoacoustic Imaging System

Photoacoustic imaging (PAI) has become a popular technique for biomedical diagnosis. However, current systems are overly complex or use bulky piezoelectric materials, necessitating options other than these methods for future PAI systems. In this study, a wearable transparent ultrasonic transducer was developed and applied in a PAI system with excellent performance. The acoustic sensor was fabricated with a sandwich structure consisting of 150 nm thick amorphous indium tin oxide on both sides of a <inline-formula> <tex-math notation="LaTeX">$110~\mu \text{m}$ </tex-math></inline-formula> commercial polyvinylidene fluoride film. This single-element sensor exhibited the performance of a 6.7 MHz center frequency, an 86.3&#x0025; &#x2212;3 dB fractional bandwidth, and a <inline-formula> <tex-math notation="LaTeX">$20\times20\,\,\times $ </tex-math></inline-formula> 36 mm³ volumetric imaging field. Modified imaging phantoms were made to evaluate the lateral resolution, imaging depth, ability to make a convex photoacoustic image, quality of 3D imaging, and capability to perform PAI directly in the ambient environment with a customized phantom. In summary, the study has demonstrated the sensor&#x2019;s potential for large-field PAI application in wearable health devices at a low cost.

Photoacoustic imaging systems based on clinical ultrasound platform.

Photoacoustic imaging has drawn a significant amount of attention due to its unique capacity for functional, metabolic, and molecular imaging, which is achieved by the combination of optical excitation and acoustic detection. With both strengths of light and ultrasound, photoacoustic images can provide strong optical contrast at high ultrasound resolution in deep tissue. As photoacoustic imaging can be used to visualize complementary information to ultrasound imaging using the same data acquisition process, several studies have been conducted on combining photoacoustic imaging with existing clinical ultrasound systems. This review highlights our development of a photoacoustic/ultrasound dual-modal imaging system, various features and functionalities implemented for clinical translation, and preclinical/clinical studies performed by using the systems.

A Fabry–Perot Fiber-Optic Array for Photoacoustic Imaging

Photoacoustic imaging is an emerging noninvasive and nonionizing imaging modality with high contrast and high resolution, which originates from the photoabsorption selectivity and the broadband response of the photoacoustic signals. However, sensing of the photoacoustic signal is currently limited by the bandwidth of piezoelectric ultrasound transducers. The optical ultrasound sensors based on Fabry–Perot (F–P) interference exhibit broader bandwidth than piezoelectric transducers, which is expected to be a promising alternative. At present, nevertheless, the parallel sensing and processing of ultrasound signals using the fiber-optic ultrasound sensor is still a challenge. Here, we propose a <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$4\times16$ </tex-math></inline-formula> fiber-optic array based on F–P interference, which enables parallel sensing for imaging with a volume rate of 10 Hz. We experimentally demonstrated that the fiber-optic array ultrasound sensor exhibited a pressure nonlinearity of <3.64%, and −6 dB bandwidth from ~0 to 18.3 MHz. High-definition imaging is achieved by this sensing array without mechanical scanning. As the ultrasound sensing realized by optics, the photoacoustic imaging system is potentially an all-optic system with broadband response.

Simplified-Delay-Multiply-and-Sum-Based Promising Beamformer for Real-Time Photoacoustic Imaging

Photoacoustic imaging (PAI) using a traditional delay-and-sum (DAS) beamformer suffers from various limitations such as low contrast, low signal-to-noise ratio (SNR) and strong side-lobe influence. Consequently, reconstructed image quality dramatically degrades. The present work improves reconstructed image quality by the use of a novel adaptive weighting algorithm named simplified-delay-multiply-and-standard-deviation (SDMASD). SDMASD combined with established DAS and delay-multiply-and-sum (DMAS) methodologies are presented in this article. This present method can efficiently improve the achievable resolution, contrast and SNR and conquer all the persisting drawbacks present in the DAS and DMAS beamformers. Computational complexity in this method, is reduced from <i>O</i>(<i>N</i>²) to <i>O</i>(<i>N</i>) by using a unique mathematical tool. Therefore, it can be programmable for real-time PA image reconstruction. The performance of the algorithm has been accelerated using GPU programming. It executes 50 times faster than the standard CPU based DAS method. A validation study of the algorithm was carried out both numerically and experimentally. In experimental study, a low-cost (16-elements) linear array transducer in a home-built PAI system was employed to acquire the PA signals. All the results illustrate an excellent capability of the proposed algorithm in improving image quality metrics. The quantitative evaluation of the agar phantom shows that SDMASD leads to an improvement of &#x007E; 45% and &#x007E; 40% in SNR, &#x007E; 20% and &#x007E; 30% in full-width-half-maximum (FWHM) compared to DAS and DMAS respectively. Conclusively, the study demonstrates that the proposed algorithm is very much powerful and promising for a cost-effective PAI system using a low-cost linear array transducer.

Intelligent Denoising Algorithm for Signals Based on Three-Dimensional Photoacoustic Tomography System

Intelligent Denoising Algorithm for Signals Based on Three-Dimensional Photoacoustic Tomography System

Back-projection method with fast time-delay correction for photoacoustic tomography reconstruction based on a focused sound field model

Photoacoustic tomography is a rapidly developing imaging technology, which can provide structural and functional information of biological tissues. It can integrate the advantage of high optical contrast from optical imaging with those from high penetration depth from ultrasound imaging. However, the existing back-projection algorithm in photoacoustic tomography equates the ultrasonic transducer scanning around the target to a point detector, which leads to a notable tangential blur in the eccentric imaging regions, and thus seriously degrading the image quality. In this paper, we propose a novel photoacoustic tomography reconstruction algorithm, which employs a focused sound field equivalent model to overcome the sound field distortion caused by the transducer’ finite aperture effect and can quickly and effectively restore the elongated tangential resolution in the eccentric imaging regions. Simulation results show that for the target with a diameter of 5 mm and a distance of 6 mm from the rotation center, the tangential resolution is improved by at least twice. Experimental results show that this method can effectively restore the image tangential blur in the off-center regions, where the tiny structures of complex targets can be detected. This new method provides a valuable alternative to the conventional back-projection method and plays an important guiding role in the design of photoacoustic tomography systems based on circle/sphere scanning.

Automatic 3-D segmentation and volumetric light fluence correction for photoacoustic tomography based on optimal 3-D graph search.

Preclinical imaging with photoacoustic tomography (PAT) has attracted wide attention in recent years since it is capable of providing molecular contrast with deep imaging depth. The automatic extraction and segmentation of the animal in PAT images is crucial for improving image analysis efficiency and enabling advanced image post-processing, such as light fluence (LF) correction for quantitative PAT imaging. Previous automatic segmentation methods are mostly two-dimensional approaches, which failed to conserve the 3-D surface continuity because the image slices were processed separately. This discontinuity problem further hampers LF correction, which, ideally, should be carried out in 3-D due to spatially diffused illumination. Here, to solve these problems, we propose a volumetric auto-segmentation method for small animal PAT imaging based on the 3-D optimal graph search (3-D GS) algorithm. The 3-D GS algorithm takes into account the relation among image slices by constructing a 3-D node-weighted directed graph, and thus ensures surface continuity. In view of the characteristics of PAT images, we improve the original 3-D GS algorithm on graph construction, solution guidance and cost assignment, such that the accuracy and smoothness of the segmented animal surface were guaranteed. We tested the performance of the proposed method by conducting in vivo nude mice imaging experiments with a commercial preclinical cross-sectional PAT system. The results showed that our method successfully retained the continuous global surface structure of the whole 3-D animal body, as well as smooth local subcutaneous tumor boundaries at different development stages. Moreover, based on the 3-D segmentation result, we were able to simulate volumetric LF distribution of the entire animal body and obtained LF corrected PAT images with enhanced structural visibility and uniform image intensity.

Application of Photoacoustic Imaging for Lymphedema Treatment

Background Lymphatic vessels are difficult to identify using existing modalities as because of their small diameter and the transparency of the lymph fluid flowing through them. Methods Here, we introduce photoacoustic lymphangiography (PAL), a new modality widely used for lymphedema treatment, to observe limb lymphatic vessels. The photoacoustic imaging system used in this study can simultaneously visualize lymphatic vessels and veins with a high resolution (0.2 mm) and can also observe their three-dimensional relationship with each other. Results High-resolution images of the lymphatic vessels, detailed structure of the dermal back flow, and the three-dimensional positional relationship between the lymphatic vessels and veins were observed by PAL. Conclusion The clear image provided by PAL could have a major application in pre- and postoperative use during lymphaticovenular anastomosis for lymphedema treatment.

Photoacoustic Imaging System based on Diode Laser and Condenser Microphone for Characterization of Dental Anatomy

The feasibility of a diode laser and condenser microphone-based photoacoustic imaging system for dental anatomy characterization has been investigated. The sample of this study was human teeth illuminated by a diode laser with a wavelength of 532 nm. The laser and detector were fixed in a static position while the sample was moved in the X-Y direction. A laser diode illuminated the sample at 17-20 kHz frequencies combined with 30%, 35%, 40%, 45%, 50%, and 55% of the duty cycles to investigate optimal laser irradiation for dental anatomy imaging. The acoustic intensity was measured ten times to investigate the characterization of dental anatomical structure, <em>i.e.,</em> enamel, dentin, and pulp. The sample was then scanned using the system to determine the characterization of the dental structure in the photoacoustic image. The results of this study reveal that the optimal frequency and duty cycle of laser exposure to produce the photoacoustic image of the sample are 19 kHz and 50%, respectively. The maximum acoustic intensities of enamel, dentin and pulp are -71,8 dB, -70,8 dB, -70,5 dB, respectively. Whereas the minimum acoustic intensities of enamel, dentin and pulp are -72,0 dB, -70,9 dB, -70,6 dB respectively. In this study, a photoacoustic imaging system based on a diode laser and a condenser microphone can generate photoacoustic images of dental anatomical structures. The optical absorption of pulp is stronger than the dentin and enamel layer. Hence the pulp area emits the highest acoustic intensity and emerges as a red area in the photoacoustic image.

Suite of 3D test objects for performance assessment of hybrid photoacoustic-ultrasound breast imaging systems

.SignificanceDuring the development and early testing phases of new photoacoustic (PA) breast imaging systems, several choices need to be made in aspects of system design and measurement sequences. Decision-making can be complex for state-of-the-art systems such as 3D hybrid photoacoustic-ultrasound (PA-US) breast imagers intended for multispectral quantitative imaging. These systems have a large set of design choices and system settings that affect imaging performance in different ways and often require trade-offs. Decisions have to be made carefully as they can strongly influence the imaging performance.AimA systematic approach to assess the influence of various choices on the imaging performance in carefully controlled laboratory situations is crucial before starting with human studies. Test objects and phantoms are used for first imaging studies, but most reported structures have a 2D geometry and are not suitable to assess all the image quality characteristics (IQCs) of 3D hybrid PA-US systems.ApproachOur work introduces a suite of five test objects designed for hybrid PA-US systems with a 3D detection aperture. We present the test object designs and production protocols and explain how they can be used to study various performance measures. To demonstrate the utility of the developed objects, measurements are made with an existing tomographic PA system.ResultsTwo test objects were developed for measurements of the US detectors’ impulse responses and light distribution on the breast surface. Three others were developed to assess image quality and quantitative accuracy of the PA and US modes. Three of the five objects were imaged to demonstrate their use.ConclusionsThe developed test objects allow one to study influences of various choices in design and system settings. With this, IQCs can be assessed as a function of measurement sequence settings for the PA and US modes in a controlled way. Systematic studies and measurements using these objects will help to optimize various system settings and measurement protocols in laboratory situations before embarking on human studies.

Double-Clad Optical Fiber-Based Multi-Contrast Noncontact Photoacoustic and Fluorescence Imaging System

A noncontact photoacoustic and fluorescence dual-modality imaging system is proposed, which integrates a fiber-based fluorescence imaging system with noncontact photoacoustic imaging using a specially fabricated double-cladding fiber (DCF) coupler and a DCF lens. The performance of the DCF coupler and lens was evaluated, and the feasibility of this new imaging system was demonstrated using simple tubing phantoms with black ink and fluorophore. Our imaging results demonstrated that the multimodal imaging technique can simultaneously acquire photoacoustic and fluorescence images without coming into contact with the sample. Consequently, the developed method is the first noncontact scheme among multimodal imaging systems that is integrated with a photoacoustic imaging system, which can provide varied and complementary information about the sample.

Development of a Compact Photoacoustic Tomography Imaging System with Dual Single-Element Transducers for Image Enhancement

ObjectiveThis paper proposes a new photoacoustic computed tomography (PACT) imaging system employing dual ultrasonic transducers with different frequencies. When imaging complex biological tissues, photoacoustic (PA) signals with multiple frequencies are produced simultaneously; however, due to the limited bandwidth of a single-frequency transducer, the received PA signals with specific frequencies may be missing, leading to a low imaging quality.MethodsIn contrast to our previous work, the proposed system has a compact volume as well as specific selection of the detection center frequency of the transducer, which can provide a comprehensive range for the detection of PA signals. In this study, a series of numerical simulation and phantom experiments were performed to validate the efficacy of the developed PACT system.ResultsThe images generated by our system combined the advantages of both high resolution and ideal brightness/contrast.ConclusionThe interchangeability of transducers with different frequencies provides potential for clinical deployment under the circumstance where a single frequency transducer cannot perform well.

An Excitation-Reception Collinear Probe for Ultrasonic, Photoacoustic, and Thermoacoustic Tri-Modal Volumetric Imaging.

Imaging systems that integrate multiple modalities can reveal complementary anatomic and functional information as they exploit different contrast mechanisms, which have shown great application potential and advantages in preclinical studies. A portable and easy-to-use imaging probe will be more conducive to transfer to clinical practice. Here, we present a tri-modal ultrasonic (US), photoacoustic (PA), and thermoacoustic (TA) imaging system with an excitation-reception collinear probe. The acoustic field, light field, and electric field of the probe were designed to be coaxial, realizing homogeneous illumination and high-sensitivity detection at the same detection position. US images can provide detailed information about structures, PA images can delineate the morphology of blood vessels in tissues, and TA images can reveal dielectric properties of the tissues. Moreover, phantoms and in vivo human finger experiments were performed by the tri-modal imaging system to demonstrate its performance. The results show that the tri-modal imaging system with the proposed probe has the ability to detect small breast tumors with a radius of only 2.5 mm and visualize the anatomical structure of the finger in three dimensions. Our work confirms that the tri-modal imaging system equipped with a collinear probe can be applied to a variety of different scenarios, which lays a solid foundation for the application of the tri-modality system in clinical trials.

Characteristics of megahertz resonant platform for evaluating sensitivity of photoacoustic contrast agent

A platform designed exclusively for evaluating photoacoustic contrast agents is required to prevent deviations in the results caused by differences in the architecture of photoacoustic imaging systems. In this paper, we managed to develop an evaluation system using a cost-efficient laser diode running in megahertz frequency band. To increase the output signal, an acoustic resonance structure is introduced where the sample liquid is filled in a glass capillary embedded in a soft phantom. The optimal width and interval of the excitation pulse were investigated and found to be 230 ns and 4.92 μs, respectively. Experimental results on inks and Indocyanine green verified the feasibility and effectiveness of the platform. Next, as a non-resonant platform, the glass capillary was replaced with a soft tube to examine the signal enhancement effect of the resonance. The signal-to-noise ratio was on average improved 2.5-fold by the resonance occurring in the glass capillary. The success in improving the signal-to-noise ratio may ensure the lower requirement on the laser power, which could consequently suppress the cost of the evaluation platform.

A High Sensitivity Transparent Ultrasound Transducer based on PMN-PT for Ultrasound and Photoacoustic Imaging.

We recently introduced piezoelectric lithium niobate (LN) based transparent ultrasound transducers (TUT) as a new platform for developing multimodal optical, ultrasound and photoacoustic imaging systems. However, LN based TUT is limited in its signal-to-noise ratio due to material's low piezoelectricity (d 33). In this paper, we report, for the first time, a 0.2 mm thick transparent lead magnesium niobate-lead titanate (PMN-PT) based TUT (PMN-PT-TUT) for ultrasound and photoacoustic applications and compared its performance with a 0.25 mm thick transparent LN based TUT (LN-TUT). To improve the ultrasound energy transmission efficiency, TUTs were fabricated with a two-matching-layer design. This resulted in a dual frequency response with center frequencies of 7.8 MHz/13.2 MHz and corresponding bandwidths of 28.2%/66.67% for PMN-PT-TUT, and center frequencies of 7.2 MHz/11.8 MHz and bandwidths of 36.1%/62.7% for LN-TUT. The optical transmission rate of PMN-PT-TUTs and LN-TUTs are measured as ~73% and ~91% respectively at 532 nm optical wavelength. The PMN-PT-TUT exhibited higher sensitivity compared to LN-TUT with a nearly three-fold higher pulse echo amplitude and more than two-fold higher photoacoustic amplitude. Furthermore, optical resolution photoacoustic microscopy (ORPAM) experiments on phantom targets demonstrated lateral resolutions of 7 μm and 5.1 μm, and axial resolutions of 285.6 μm and 375.9 μm for PMN-PT-TUT and LN-TUT respectively. These results indicated that PMN-PT is a viable alternative to LN for developing TUT based multimodal ultrasound and photoacoustic imaging systems.

Assessment of Brain Functional Activity Using a Miniaturized Head-Mounted Scanning Photoacoustic Imaging System in Awake and Freely Moving Rats.

Understanding the relationship between brain function and natural behavior remains a significant challenge in neuroscience because there are very few convincing imaging/recording tools available for the evaluation of awake and freely moving animals. Here, we employed a miniaturized head-mounted scanning photoacoustic imaging (hmPAI) system to image real-time cortical dynamics. A compact photoacoustic (PA) probe based on four in-house optical fiber pads and a single custom-made 48-MHz focused ultrasound transducer was designed to enable focused dark-field PA imaging, and miniature linear motors were included to enable two-dimensional (2D) scanning. The total dimensions and weight of the proposed hmPAI system are only approximately 50 × 64 × 48 mm and 58.7 g (excluding cables). Our ex vivo phantom experimental tests revealed that a spatial resolution of approximately 0.225 mm could be achieved at a depth of 9 mm. Our in vivo results further revealed that the diameters of cortical vessels draining into the superior sagittal sinus (SSS) could be clearly imaged and continuously observed in both anesthetized rats and awake, freely moving rats. Statistical analysis showed that the full width at half maximum (FWHM) of the PA A-line signals (relative to the blood vessel diameter) was significantly increased in the selected SSS-drained cortical vessels of awake rats (0.58 ± 0.17 mm) compared with those of anesthetized rats (0.31 ± 0.09 mm) (p < 0.01, paired t-test). In addition, the number of pixels in PA B-scan images (relative to the cerebral blood volume (CBV)) was also significantly increased in the selected SSS-drained blood vessels of awake rats (107.66 ± 23.02 pixels) compared with those of anesthetized rats (81.99 ± 21.52 pixels) (p < 0.01, paired t-test). This outcome may result from a more active brain in awake rats than in anesthetized rats, which caused cerebral blood vessels to transport more blood to meet the increased nutrient demand of the tissue, resulting in an obvious increase in blood vessel volume. This hmPAI system was further validated for utility in the brains of awake and freely moving rats, showing that their natural behavior was unimpaired during vascular imaging, thereby providing novel opportunities for studies of behavior, cognition, and preclinical models of brain diseases.

Sparsity-Based Recovery of Three-Dimensional Photoacoustic Images from Compressed Single-Shot Optical Detection.

Photoacoustic (PA) imaging combines optical excitation with ultrasonic detection to achieve high-resolution imaging of biological samples. A high-energy pulsed laser is often used for imaging at multi-centimeter depths in tissue. These lasers typically have a low pulse repetition rate, so to acquire images in real-time, only one pulse of the laser can be used per image. This single pulse necessitates the use of many individual detectors and receive electronics to adequately record the resulting acoustic waves and form an image. Such requirements make many PA imaging systems both costly and complex. This investigation proposes and models a method of volumetric PA imaging using a state-of-the-art compressed sensing approach to achieve real-time acquisition of the initial pressure distribution (IPD) at a reduced level of cost and complexity. In particular, a single exposure of an optical image sensor is used to capture an entire Fabry–Pérot interferometric acoustic sensor. Time resolved encoding as achieved through spatial sweeping with a galvanometer. This optical system further makes use of a random binary mask to set a predetermined subset of pixels to zero, thus enabling recovery of the time-resolved signals. The Two-Step Iterative Shrinking and Thresholding algorithm is used to reconstruct the IPD, harnessing the sparsity naturally occurring in the IPD as well as the additional structure provided by the binary mask. We conduct experiments on simulated data and analyze the performance of our new approach.

Predicting intestinal viability by consecutive photoacoustic monitoring of oxygenation recovery after reperfusion in acute mesenteric ischemia in rats

The purpose was to assess whether consecutive monitoring of oxygenation by photoacoustic imaging (PAI) can objectively predict intestinal viability during surgery for acute mesenteric ischemia (AMI). PAI uses laser light to detect relative amounts of oxygenated and deoxygenated hemoglobin in intestinal tissue. In 30 rats, AMI was induced by clamping the mesenteric and marginal vessels of the ileum for 0 min in the control group, 30 min in the mild group, and 180 min in the severe group (10 rats per group). After 60 min of reperfusion, intestinal damage was evaluated pathologically. Oxygenation of the intestine was monitored throughout the procedure in real time by a commercially available PAI system and compared among the groups. All rats showed irreversible (i.e. transmucosal or transmural infarction) damage in the severe group. After reperfusion, the oxygenation in the mild group recovered immediately and was significantly higher than in the severe group at 1, 5, 10, 30, and 60 min (P = .011, 002, < .001, 001, and 001, respectively). Oxygenation showed a significant strong negative correlation with pathological severity (rs = − 0.7783, − 0.7806, − 0.7422, − 0.7728, and − 0.7704, respectively). In conclusion, PAI could objectively predict irreversible ischemic damage immediately after reperfusion, which potentially prevents inadequate surgery.

Recent Progress on Molecular Photoacoustic Imaging with Carbon-Based Nanocomposites.

For biomedical imaging, the interest in noninvasive imaging methods is ever increasing. Among many modalities, photoacoustic imaging (PAI), which is a combination of optical and ultrasound imaging techniques, has received attention because of its unique advantages such as high spatial resolution, deep penetration, and safety. Incorporation of exogenous imaging agents further amplifies the effective value of PAI, since they can deliver other specified functions in addition to imaging. For these agents, carbon-based materials can show a large specific surface area and interesting optoelectronic properties, which increase their effectiveness and have proved their potential in providing a theragnostic platform (diagnosis + therapy) that is essential for clinical use. In this review, we introduce the current state of the PAI modality, address recent progress on PAI imaging that takes advantage of carbon-based agents, and offer a future perspective on advanced PAI systems using carbon-based agents.