Real-time Photoacoustic Imaging Research Articles

A model-based image reconstruction algorithm for near real-time transcranial photoacoustic imaging

Photoacoustic imaging is a promising hybrid imaging modality that can visualize both microscopic and macroscopic structures and oxygenation changes in brain function. Phase aberration caused by the skull is a major barrier for high-quality photoacoustic imaging of the brain. Time-reversal methods have been used to address this issue, though they rely on solving the full-wave equation, and is therefore computationally heavy and slow. Herein, a near real-time model-based image reconstruction algorithm is proposed. The acoustic forward model is mathematically described as a model matrix and image reconstructions are performed by employing the pseudoinverse of the model matrix and calculating the initial pressure distribution. The pseudoinverse matrix only needs to be computed once for the same experimental setup and acoustic medium and is obtained offline prior to imaging. The proposed algorithm shows equivalent image quality but considerably faster reconstruction time (>40 times faster), compared to the time-reversal method and therefore could potentially enable near real-time photoacoustic imaging.

Higher-order correlation based real-time beamforming in photoacoustic imaging.

Although a delay-and-sum (DAS) beamformer is best suited for real-time photoacoustic (PA) image formation, the reconstructed images are often afflicted by noises, sidelobes, and other intense artifacts due to inaccurate assumptions in PA signal correlation. The present work aims to develop a reconstruction method that reduces the occurrence of sidelobes and artifacts and thus improves the reconstructed image quality or imaging performance. This beamformer is fundamentally based on higher-order signal correlation wherein a higher number of delayed PA signals-compared to conventional delay-multiply-and-sum (DMAS)-are combined and summed up. The proposed technique provides significant improvements in resolution, contrast, and signal-to-noise ratio (SNR) compared to traditional beamformers. For real-time implementation, the proposed algorithms were simplified, and their computational complexities were shrunk to the order of DAS [O(N)]. A GPU based study was also performed to validate the real-time capability of the proposed beamformers. For validation studies, both numerical simulation and experiments were conducted. Quantitative evaluation studies involving SNR, contrast ratio, generalized contrast-to-noise ratio, and FWHM demonstrate that the proposed higher-order DMAS beamformer is superior in PA image reconstruction. Conclusively, the proposed beamformer uniquely facilitates real-time PA image reconstruction with an achievable frame rate close to DAS and DMAS but with better imaging performance, which holds promise for real-time PA imaging and its clinical applications.

Ultra-homogeneous Cu2−xSe nanoparticles as near-infrared II plasmonic phototheranstics for photothermal/chemodynamic synergistic therapy of liver cancer

Laser mediated photothermal/chemodynamic co-therapy is widely applied for anti-cancer treatment due to its good therapeutic effect. However, the laser wavelength for effectively targeting deep tumor tissues can decide whether or not it is a key premise of irradiation treatment. In this study, a super-homogenous and highly dispersive spherical nanoparticle Cu2-XSe was prepared, which displayed a strong surface plasmon resonance (SPR) peak in the near-infrared region (NIR)-II and high Fenton catalytic efficiency. The results of in vitro experiments showed that Cu2-XSe nanoparticles exhibited high photothermal conversion efficiency under the excitation of NIR-II laser irradiation, which significantly improved its ability to produce ·OH. In a tumor-bearing mouse model, the combination of Cu2-XSe and photothermal/chemodynamic co-therapy guided by the real-time photoacoustic imaging in the NIR-II could effectively inhibit tumor growth and exhibit good in vivo/in vitro biocompatibility. In summary, this Cu2-XSe nanoparticle-based NIR-II laser-mediated photothermal/chemodynamic co-therapy strategy is expected to provide a new option for the diagnosis and treatment of liver cancer.

A Two-In-One Nanoprodrug for Photoacoustic Imaging-Guided Enhanced Sonodynamic Therapy.

Sonodynamic therapy (SDT) is garnering considerable attention in cancer treatment due to its non-invasive nature and the potential of spatiotemporal control. However, the high level of glutathione (GSH) in cancer cells can alleviate the SDT-mediated ROS-damages, resulting in a reduced SDT effect. Here, a two-in-one nano-prodrug for photoacoustic imaging-guided enhanced SDT against skin cancers is synthesized. A dual-prodrug molecule (DOA) of sulfide dioxide (SO2 ) and 5-aminolevulinic acid (ALA) is first synthesized and then co-assembled with methoxyl poly(ethylene glycol)-b-poly(l-lysine) (mPEG-b-PLL) to generate the two-in-one prodrug nanoparticles (P-DOA NPs). The P-DOA NPs simultaneously released ALA and SO2 in response to the overexpressed GSH in tumor cells. The released ALA is metabolically converted into protoporphyrin IX (PpIX) in tumor cells for SDT and photoacoustic imaging. Meanwhile, the released SO2 , together with the consumption of GSH based on the reaction of DOA in P-DOA NPs with intracellular GSH, can significantly increase the intracellular ROS content, leading to enhanced SDT. As a result, the P-DOA NPs significantly inhibited the growth of melanoma and squamous cell carcinoma xenografts in mouse models under the guidance of real-time photoacoustic imaging. Therefore, this novel two-in-one nano-prodrug is promising for effective SDT against skin cancers.

Synchronization of RF Data in Ultrasound Open Platforms (UOPs) for High-Accuracy and High-Resolution Photoacoustic Tomography Using the "Scissors" Programming Method.

Synchronization is important for photoacoustic (PA) tomography, but some fixed delays between the data acquisition (DAQ) and the light pulse are a common problem degrading imaging quality. Here, we present a simple yet versatile method named "Scissors" to help synchronize ultrasound open platforms (UOPs) for PA imaging. Scissors is a programed function that can cut or add a fixed delay to radio frequency (RF) data and, thus, synchronize it before reconstruction. Scissors applies the programmable metric of UOPs and has several advantages. It is compatible with many setups regardless of the synchronization methods, light sources, transducers, and delays. The synchronization is adjustable in steps reciprocal to the UOPs' sampling rate (20-ns step with a 50-MHz sampling rate). Scissors works in real-time PA imaging, and no extra hardware is needed. We programed Scissors in Vantage UOP (Verasonics, Inc., Kirkland, WA, USA) and then imaged two 30- [Formula: see text] nichrome wires with a 20.2-MHz central frequency transducer. The PA image was severely distorted by an 828-ns delay; over 90% delay was caused by our Q -switch laser. The axial and lateral resolutions are 112 and [Formula: see text], respectively, after using Scissors. We imaged a human finger in vivo, and the imaging quality is tremendously improved after solving the 828-ns delay by using Scissors.

The researches on convolutional beamforming for linear-array photoacoustic tomography

The convolutional beamforming algorithm (COBA) which can be easily implemented by fast Fourier transform (FFT) and is suitable for real-time photoacoustic tomography (PAT) is introduced. In order to reveal the imaging effects of COBA, the photoacoustic images reconstructed by COBA, delay-and-sum algorithm (DAS), and minimum variance (MV) are investigated. The results demonstrate that the COBA significantly improves the lateral resolution and the contrast of the photoacoustic images. Moreover, the coherence factor (CF) as an adaptive weighting is used in COBA, the combined method shows that better lateral resolution and contrast of photoacoustic images can be obtained, which can be a potential imaging method for linear-array PAT.

Photoacoustic image-guided corpus cavernosum intratunical injection of adipose stem cell-derived exosomes loaded polydopamine thermosensitive hydrogel for erectile dysfunction treatment

Stem cell-derived exosomes (SC-EXO) was an emerging therapeutic agent in regenerative medicine. Intratunical injection of SC-EXO is considered as a prospective approach for erectile dysfunction (ED) treatment. However, high vascularization of cavernous body makes effective retention a major challenge for SC-EXO intratunical injection. In this study, a Polydopamine nanoparticles (PDNPs) incorporated poly (ethylene glycol)-poly(ε-caprolactone-co-lactide) (PDNPs-PELA) thermosensitive hydrogels were fabricated by a facile in situ polymerization for intratunical administration of adipose stem cell-derived exosomes (EXO). The hydrogels exhibited sol-gel transition at body temperature. Moreover, the in-situ polymerization of PDNPs using poly (ethylene glycol)-poly(ε-caprolactone-co-lactide) (PELA) block copolymer as a template was found to be more stable dispersion in the gel system. After being encapsulated into the hydrogel, EXO shows sustained release behavior within two weeks. In vivo animal experiments revealed that exosomes released from hydrogel lead to the healing of endothelial cells and neurons, increase of the cavity's pressure, thereby restoring the erectile function. In particular, since the PDNPs in thermosensitive gels have excellent photoacoustic performance, the hydrogel can be accurately delivered into the tunica albuginea by the guidance of real-time photoacoustic imaging. These results suggest that the as-prepared PDNPs-PELA has a promising future as an injectable exosome carrier for ED treatment.

Deep learning enabled real-time photoacoustic tomography system via single data acquisition channel

Photoacoustic computed tomography (PACT) combines the optical contrast of optical imaging and the penetrability of sonography. In this work, we develop a novel PACT system to provide real-time imaging, which is achieved by a 120-elements ultrasound array only using a single data acquisition (DAQ) channel. To reduce the channel number of DAQ, we superimpose 30 nearby channels’ signals together in the analog domain, and shrinking to 4 channels of data (120/30 = 4). Furthermore, a four-to-one delay-line module is designed to combine these four channels’ data into one channel before entering the single-channel DAQ, followed by decoupling the signals after data acquisition. To reconstruct the image from four superimposed 30-channels’ PA signals, we train a dedicated deep learning model to reconstruct the final PA image. In this paper, we present the preliminary results of phantom and in-vivo experiments, which manifests its robust real-time imaging performance. The significance of this novel PACT system is that it dramatically reduces the cost of multi-channel DAQ module (from 120 channels to 1 channel), paving the way to a portable, low-cost and real-time PACT system.

Low-intensity focused ultrasound-augmented Cascade chemodynamic therapy via boosting ROS generation

Fenton reaction-mediated chemodynamic therapy (CDT), which destroys tumor cells by converting H2O2 into cytotoxic hydroxyl radical (OH) and singlet oxygen (1O2) species, is a promising field. However, Fenton-based CDT is severely impaired by the inappropriate tumor environment associated with undesirable intratumoral acidity and insufficient H2O2 supply in tumor microenvironment (TME). Therefore, a strategy that can address these concerns is highly desired and beneficial for boosting such treatment. Herein, a magnetic nanoreactor system (denoted as poly (lactic-co-glycolic acid) (PLGA)–superparamagnetic iron oxide (SPIO)&vitamin C (Vc) was constructed with Vc in the core, SPIO on the shell, and PLGA as the building carrier. Upon low-intensity focused ultrasound irradiation, on-demand Vc release can locally decompose into H2O2, which can generate a favorable condition for facilitating SPIO-based Fenton-like reaction and result in continuous O2 and OH/1O2 generation. The TME modulation-augmented CDT by this nanoreactor based on the reinforced Fenton reaction tremendously improved the antitumor outcomes, especially under increased accumulation contributed by magnetic targeting combined with enhanced permeability and retention effect. Moreover, the explosive production of oxygen can be monitored by real-time photoacoustic imaging, offering a noninvasive means to forecast the treatment efficacy. Therefore, this established microenvironment modulation strategy for augmenting Fenton reaction-based CDT paves a new avenue to realize highly efficient cancer theranostics.

Polydopamine-Coated Laponite Nanoplatforms for Photoacoustic Imaging-Guided Chemo-Phototherapy of Breast Cancer.

Theranostic nanoplatforms combining photosensitizers and anticancer drugs have aroused wide interest due to the real-time photoacoustic (PA) imaging capability and improved therapeutic efficacy by the synergistic effect of chemotherapy and phototherapy. In this study, polydopamine (PDA) coated laponite (LAP) nanoplatforms were synthesized to efficiently load indocyanine green (ICG) and doxorubicin (DOX), and modified with polyethylene glycol-arginine-glycine-aspartic acid (PEG-RGD) for PA imaging-guided chemo-phototherapy of cancer cells overexpressing αvβ3 integrin. The formed ICG/LAP-PDA-PEG-RGD/DOX nanoplatforms showed significantly higher photothermal conversion efficiency than ICG solution and excellent PA imaging capability, and could release DOX in a pH-sensitive and NIR laser-triggered way, which is highly desirable feature in precision chemotherapy. In addition, the ICG/LAP-PDA-PEG-RGD/DOX nanoplatforms could be uptake by cancer cells overexpressing αvβ3 integrin with high specificity, and thus serve as a targeted contrast agent for in vivo PA imaging of cancer. In vivo experiments with 4T1 tumor-bearing mouse model demonstrated that ICG/LAP-PDA-PEG-RGD/DOX nanoplatforms exhibited much stronger therapeutic effect and higher survival rate than monotherapy due to the synergetic chemo-phototherapy under NIR laser irradiation. Therefore, the reported ICG/LAP-PDA-PEG-RGD/DOX represents a promising theranostic nanoplatform for high effectiveness PA imaging-guided chemo-phototherapy of cancer cells overexpressing αvβ3 integrin.

A Deep Learning Approach to Photoacoustic Wavefront Localization in Deep-Tissue Medium.

Optical photons undergo strong scattering when propagating beyond 1-mm deep inside biological tissue. Finding the origin of these diffused optical wavefronts is a challenging task. Breaking through the optical diffusion limit, photoacoustic (PA) imaging (PAI) provides high-resolution and label-free images of human vasculature with high contrast due to the optical absorption of hemoglobin. In real-time PAI, an ultrasound transducer array detects PA signals, and B-mode images are formed by delay-and-sum or frequency-domain beamforming. Fundamentally, the strength of a PA signal is proportional to the local optical fluence, which decreases with the increasing depth due to depth-dependent optical attenuation. This limits the visibility of deep-tissue vasculature or other light-absorbing PA targets. To address this practical challenge, an encoder-decoder convolutional neural network architecture was constructed with custom modules and trained to identify the origin of the PA wavefronts inside an optically scattering deep-tissue medium. A comprehensive ablation study provides strong evidence that each module improves the localization accuracy. The network was trained on model-based simulated PA signals produced by 16 240 blood-vessel targets subjected to both optical scattering and Gaussian noise. Test results on 4600 simulated and five experimental PA signals collected under various scattering conditions show that the network can localize the targets with a mean error less than 30 microns (standard deviation 20.9 microns) for targets below 40-mm imaging depth and 1.06 mm (standard deviation 2.68 mm) for targets at a depth between 40 and 60 mm. The proposed work has broad applications such as diffused optical wavefront shaping, circulating melanoma cell detection, and real-time vascular surgeries (e.g., deep-vein thrombosis).

Dual Raster-Scanning Photoacoustic Small-Animal Imager for Vascular Visualization.

Imaging of vascular networks on small animals has played an important role in basic biomedical research. Photoacoustic imaging technology has great potential for application in the imageology of small animals. The wide-field photoacoustic imaging of small animals can provide images with high spatiotemporal resolution, deep penetration, and multiple contrasts. Also, the real-time photoacoustic imaging system is desirable to observe the hemodynamic activities of small-animal vasculature, which can be used to research the dynamic monitoring of small-animal physiological features. Here, a dual-raster-scanning photoacoustic imager is presented, featuring a switchable double-mode imaging function. The wide-field imaging is driven by a two-dimensional motorized translation stage, while the real-time imaging is realized with galvanometers. By setting different parameters and imaging modes, in vivo visualization of small-animal vascular network can be performed. The real-time imaging can be used to observe pulse change and blood flow change of drug-induced, etc. The wide-field imaging can be used to track the growth change of tumor vasculature. These are easy to be adopted in various areas of basic biomedicine research.

Assessment of liver function reserve by photoacoustic tomography: a feasibility study.

Assessment of liver function reserve (LFR) is essential to determine liver resection scope and predict prognosis for patients with liver disease. Indocyanine green (ICG) concentration change is a classic marker to reflect liver function reserve as ICG is selectively taken up and eliminated by liver. Here we proposed a noninvasive approach for LFR assessment based on a real-time photoacoustic tomography (PAT) system. This feasibility study was to detect ICG concentration change by PAT in phantom and in vivo using both normal and partial hepatectomy (PH) rabbits. A linear relationship between photoacoustic signal intensity of ICG and ICG concentration was found in vitro. In vivo ICG concentration change over time after ICG injection was observed by PAT in normal rabbits, which was consistent with the findings measured by invasive spectrophotometry. Finally, clear difference in ICG clearance between the control and PH models was identified by PAT. Taken together, our study indicated the clinical potential of PAT to in vivo evaluate LFR noninvasively.

Limited-View and Sparse Photoacoustic Tomography for Neuroimaging with Deep Learning

Photoacoustic tomography (PAT) is a non-ionizing imaging modality capable of acquiring high contrast and resolution images of optical absorption at depths greater than traditional optical imaging techniques. Practical considerations with instrumentation and geometry limit the number of available acoustic sensors and their “view” of the imaging target, which result in image reconstruction artifacts degrading image quality. Iterative reconstruction methods can be used to reduce artifacts but are computationally expensive. In this work, we propose a novel deep learning approach termed pixel-wise deep learning (Pixel-DL) that first employs pixel-wise interpolation governed by the physics of photoacoustic wave propagation and then uses a convolution neural network to reconstruct an image. Simulated photoacoustic data from synthetic, mouse-brain, lung, and fundus vasculature phantoms were used for training and testing. Results demonstrated that Pixel-DL achieved comparable or better performance to iterative methods and consistently outperformed other CNN-based approaches for correcting artifacts. Pixel-DL is a computationally efficient approach that enables for real-time PAT rendering and improved image reconstruction quality for limited-view and sparse PAT.

Targeted imaging of orthotopic prostate cancer by using clinical transformable photoacoustic molecular probe

BackgroundTo obtain high-yield histological samples by targeted prostate cancer (PCa) biopsy is the current trend compared with transrectal ultrasound (TRUS)-guided systematic histological biopsy, which is regarded as the gold standard for prostate cancer (PCa) diagnosis. In this paper, we present a targeted PCa imaging strategy using a real-time molecular photoacoustic imaging system integrated with a handheld US probe (PAI/US) and synthesized an integrin αvβ3 targeted probe based on ICG (cRGD–ICG).MethodsTo prepare cRGD–ICG, ICG-NHS was linked to cRGD through carboxyl-co-reaction. In vitro PA imaging ability of cRGD–ICG was tested. Orthotopic PCa-bearing rats were used as animal models. After injected with either cRGD–ICG or non-targeted probe, rats were implemented with PA imaging to confirm the specific accumulation of cRGD–ICG at tumor region. Moreover, pathological frozen slices were made to observe distribution of the probe in prostate tissue ex vivo.ResultsA small molecular PAI probe was synthesized and exhibited excellent targeted imaging ability in vitro. In vivo photoacoustic imaging was carried out after intravenous injection of cRGD-ICG in orthotopic PCa-bearing rats under the facilitation of the PAI/US system. Maximum molecular photoacoustic signals were observed in the tumor area in vivo after the probe injection, which showed 3.8-fold higher signal enhancement than that in the control group (P < 0.05). Significantly higher cRGD-ICG accumulation was observed under confocal microscopy in the tumor region than in normal prostate tissue.ConclusionsAll our results showed that the comprehensive strategy provided a high-yield and reliable method for PCa diagnosis and targeted prostate biopsy, with great clinical translation potential.

Scalable dextran-polypyrrole nano-assemblies with photothermal/photoacoustic dual capabilities and enhanced biocompatibility

Polypyrroles have shown great potential in photoacoustic imaging and photothermal therapy owing to its excellent photothermal conversion capabilities. However, the synthesis of polypyrrole-based nano-assemblies which have colloidal stability in biological buffers requires a number of steps, including the polymerization of pyrrole monomers, self-assembly of polypyrrole-based copolymers, and even an additional step to increase the biocompatibility of the nano-assemblies. Herein, a “polymerization/assembly” two-in-one synthesis is proposed for the first time to achieve the one-step synthesis of a new family of polypyrrole-based nano-assemblies, dextran-polypyrrole nano-assemblies (Dex-PPy NAs), under ambient conditions and in aqueous media. In addition, the approach employs tetravalent cerium ions as initiators which can initiate the polymerization of pyrrole monomers through the initiation of free radicals from dextran molecular chains. The resultant Dex-PPy NAs have a photothermal conversion efficiency reaching as high as 41 % and an excellent photostability. More importantly, the NAs with controllable nanoscale dimensions display no signs of cytotoxicity in both in vitro and in vivo studies owing to their biocompatible dextran “shell”. An in vivo study further confirmed that the Dex-PPy NAs have excellent real-time photoacoustic imaging and photothermal therapy capabilities for malignant tumors. Therefore, this study represents an important step towards the scalable synthesis of polypyrrole-based nano-assemblies with photothermal/photoacoustic dual capabilities and enhanced biocompatibility.

In-vivo hemodynamic imaging of acute prenatal ethanol exposure in fetal brain by photoacoustic tomography.

Prenatal ethanol exposure (PEE) can lead to structural and functional abnormalities in fetal brain. Although neural developmental deficits due to PEE have been recognized, the immediate effects of PEE on fetal brain vasculature and hemodynamics remain poorly understood. One of the major obstacles that preclude the rapid advancement of studies on fetal vascular dynamics is the limitation of the imaging techniques. Thus, a technique for noninvasive in-vivo imaging of fetal vasculature and hemodynamics is desirable. In this study, we explored the dynamic changes of the vessel dimeter, density and oxygen saturation in fetal brain after acute maternal ethanol exposure in the second-trimester equivalent murine model using a real-time photoacoustic tomography system we developed for imaging embryo of small animals. The results indicate a significant decrease in fetal brain vessel diameter, perfusion and oxygen saturation. This work demonstrated that PAT can provide high-resolution noninvasive imaging ability to monitor fetal vascular dynamics.

Effect of Amplifier Gain on Photoacoustic SNR (Signal to Noise Ratio) in an LED-based Photoacoustic Imaging System.

The possibility of using photoacoustic imaging for functional diagnosis has attracted much attention especially in the clinical field. Among such imaging systems, a system, which offers real-time imaging using compact and low-priced LEDs as a light source, has appeared. Compared to solid state lasers, the LED pulse energy was extremely small, so it had been thought that imaging would be extremely difficult, but by adding a pre-amplifier, real time photoacoustic imaging became possible. However the signal-to-noise ratio (SNR) and the amplifier gain needed for making real time imaging possible have remained unclear. The present study was designed to clarify these data. The results showed that, using a tissue phantom and human fingers, an SNR > 4 and amplifier gain > 80dB were required, and demonstrated why making an image without a pre-amplifier had proved difficult.

Toroidally focused sensor array for real-time laser-ultrasonic imaging: The first experimental study

In this paper we report on the first toroidally focused 2D real-time laser-ultrasonic imaging system and a modified filtered back projection algorithm that can be used in the region near the waist of the astigmatic laser-ultrasonic probe beam. The system is capable of visualizing an acupuncture needle 0.2 mm in diameter located at ∼4 cm depth in water. The lateral spatial resolution is better than ∼0.32 mm and axial spatial resolution is ∼30 μm. The achieved frame rate is up to 30 Hz. The depth dependency of the sensitivity region width and lateral resolution are experimentally measured and discussed. The array is intended to be used as a part of combined real-time photoacoustic and laser-ultrasonic imaging system.

Accelerated Photoacoustic Tomography Reconstruction via Recurrent Inference Machines.

Accelerated photoacoustic tomography (PAT) reconstruction is important for real-time photoacoustic imaging (PAI) applications. PAT requires a reconstruction algorithm to reconstruct the detected photoacoustic signal in order to obtain the detected image of the tissue, which is usually an inverse problem. Different from the typical method for solving the inverse problems that defines a model and chooses an inference procedure, we propose to use the Recurrent Inference Machines (RIM) as a framework for PAT reconstruction. Our model performs an accelerated iterative reconstruction, and directly learns to solve the inverse problem in PAT using the information from a forward model that is based on k-space methods. As shown in experiments, our method achieves faster high-resolution PAT reconstruction, and outperforms another method based on deep neural network in some respects.