Convolutional sparse coding for compressed sensing photoacoustic CT reconstruction with partially known support.

In photoacoustic tomography (PAT), imaging speed is an essential metric that is restricted by the pulse laser repetition rate and the number of channels on the data acquisition card (DAQ). Reconstructing the initial sound pressure distribution with fewer elements can significantly reduce hardware costs and back-end acquisition pressure. However, undersampling will result in artefacts in the photoacoustic image, degrading its quality. Dictionary learning (DL) has been utilised for various image reconstruction techniques, but they disregard the uniformity of pixels in overlapping blocks. Therefore, we propose a compressive sensing (CS) reconstruction algorithm for circular array PAT based on gradient domain convolutional sparse coding (CSCGR). A small number of non-zero signal positions in the sparsely encoded feature map are used as partially known support (PKS) in the reconstruction procedure. The CS-CSCGR-PKS-based reconstruction algorithm can use fewer ultrasound transducers for signal acquisition while maintaining image fidelity. We demonstrated the effectiveness of this algorithm in sparse imaging through imaging experiments on the mouse torso, brain, and human fingers. Reducing the number of array elements while ensuring imaging quality effectively reduces equipment hardware costs and improves imaging speed.

Visual Perception and Convolutional Neural Network-Based Robotic Autonomous Lung Ultrasound Scanning Localization System.

Under the situation of severe COVID-19 epidemic, lung ultrasound (LUS) has been proved to be an effective and convenient method to diagnose and evaluate the extent of respiratory disease. However, the traditional clinical ultrasound (US) scanning requires doctors not only to be in close contact with patients but also to have rich experience. In order to alleviate the shortage of medical resources and reduce the work stress and risk of infection for doctors, we propose a visual perception and convolutional neural network (CNN)-based robotic autonomous LUS scanning localization system to realize scanned target recognition, probe pose solution and movement, and the acquisition of US images. The LUS scanned targets are identified through the target segmentation and localization algorithm based on the improved CNN, which is using the depth camera to collect the image information; furthermore, the method based on multiscale compensation normal vector is used to solve the attitude of the probe; finally, a position control strategy based on force feedback is designed to optimize the position and attitude of the probe, which can not only obtain high-quality US images but also ensure the safety of patients and the system. The results of human LUS scanning experiment verify the accuracy and feasibility of the system. The positioning accuracy of the scanned targets is 15.63 ± 0.18 mm, and the distance accuracy and rotation angle accuracy of the probe position calculation are 6.38 ± 0.25 mm and 8.60° ±2.29° , respectively. More importantly, the obtained high-quality US images can clearly capture the main pathological features of the lung. The system is expected to be applied in clinical practice.

Multi-Wavelength Photoacoustic Temperature Feedback Based Photothermal Therapy Method and System.

Photothermal therapy (PTT) is a new type of tumor treatment technology that is noninvasive, repeatable, and does not involve radiation. Owing to the lack of real-time and accurate noninvasive temperature measurement technology in current PTT surgical procedures, empirical and open-loop treatment laser power control mode inevitably leads to overtreatment. Thermal radiation causes irreversible damage to normal tissue around cancer tissue and seriously affects the therapeutic effect of PTT and other therapies conducted at the same time. Therefore, real-time measurement and control of the temperature and thermal damage of the therapeutic target are critical to the success of PTT. To improve the accuracy and safety of PTT, we propose a multi-wavelength photoacoustic (PA) temperature feedback based PTT method and system. PA thermometry information at different wavelengths is mutually corrected, and the therapeutic light dose is regulated in real time to accurately control the treatment temperature. The experimental results on the swine blood sample confirm that the proposed method can realize real-time temperature measurement and control of the target area with an accuracy of 0.56 °C and 0.68 °C, demonstrating its good prospects for application.

Combined effects of vitamin C and cold atmospheric plasma-conditioned media against glioblastoma via hydrogen peroxide.

Glioblastoma is the most lethal intracranial malignant tumor, for which the five-year overall survival rate is approximately 5%. Here we explored the therapeutic combination of vitamin C and plasma-conditioned medium on glioblastoma cells in culture and as subcutaneous or intracranial xenografts in mice. The combination treatment reduced cell viability and proliferation while promoting apoptosis, and the effects were significantly stronger than with either treatment on its own. Similar results were obtained in the two xenograft models. Vitamin C appeared to upregulate aquaporin-3 and enhance the uptake of extracellular H2O2, while the combination treatment increased intracellular levels of reactive oxygen species including H2O2 and activated the JNK signaling pathway. The cytotoxic effects of the combination treatment were partially reversed by the specific JNK signaling inhibitor SP600125. Our results suggest that the combination of vitamin C and plasma-conditioned medium has therapeutic potential against glioblastoma, and they provide mechanistic insights that may help investigate this and other potential therapies in greater depth.

IL-12 nanochaperone-engineered CAR T cell for robust tumor-immunotherapy.

Although chimeric antigen receptor T (CAR T) cell immunotherapy has demonstrated remarkable success in clinical, therapeutic effects are still limited in solid tumor due to lack of activated T cell infiltration in immunosuppression of tumor microenvironment. Herein, we develop IL-12 nanostimulant-engineered CAR T cell (INS-CAR T) biohybrids for boosting antitumor immunity of CAR T cells via immunofeedback. As stimulating nanochaperone, IL-12-loaded human serum albumin (HSA) nanoparticles are effectively conjugated onto CAR T cells via bioorthogonal chemistry without influencing their antitumor capabilities. IL-12 is responsively released from INS-CAR T biohybrids in presence of the increased thiol groups on cell-surface triggered by tumor antigens. In return, released IL-12 obviously promotes the secretion of CCL5, CCL2 and CXCL10, which further selectively recruits and expands CD8+ CAR T cells in tumors. Ultimately, the immune-enhancing effects of IL-12 nanochaperone significantly boost CAR T cell antitumor capabilities, dramatically eliminated solid tumor and minimized unwanted side effects. Hence, immunofeedback INS-CAR T biohybrids, which include INS that serves as an intelligent 'nanochaperone', could provide a powerful tool for efficient and safe antitumor immunotherapy.

Synthesis and Characterization of Polyvinylpyrrolidone-Modified ZnO Quantum Dots and Their In Vitro Photodynamic Tumor Suppressive Action.

Despite the numerous available treatments for cancer, many patients succumb to side effects and reoccurrence. Zinc oxide (ZnO) quantum dots (QDs) are inexpensive inorganic nanomaterials with potential applications in photodynamic therapy. To verify the photoluminescence of ZnO QDs and determine their inhibitory effect on tumors, we synthesized and characterized ZnO QDs modified with polyvinylpyrrolidone. The photoluminescent properties and reactive oxygen species levels of these ZnO/PVP QDs were also measured. Finally, in vitro and in vivo experiments were performed to test their photodynamic therapeutic effects in SW480 cancer cells and female nude mice. Our results indicate that the ZnO QDs had good photoluminescence and exerted an obvious inhibitory effect on SW480 tumor cells. These findings illustrate the potential applications of ZnO QDs in the fields of photoluminescence and photodynamic therapy.

Photoacoustic Mouse Brain Imaging Using an Optical Fabry-Pérot Interferometric Ultrasound Sensor.

Photoacoustic (PA, or optoacoustic, OA) mesoscopy is a powerful tool for mouse cerebral imaging, which offers high resolution three-dimensional (3D) images with optical absorption contrast inside the optically turbid brain. The image quality of a PA mesoscope relies on the ultrasonic transducer which detects the PA signals. An all-optical ultrasound sensor based on a Fabry-Pérot (FP) polymer cavity has the following advantages: broadband frequency response, wide angular coverage and small footprint. Here, we present 3D PA mesoscope for mouse brain imaging using such an optical sensor. A heating laser was used to stabilize the sensor's cavity length during the imaging process. To acquire data for a 3D angiogram of the mouse brain, the sensor was mounted on a translation stage and raster scanned. 3D images of the mouse brain vasculature were reconstructed which showed cerebrovascular structure up to a depth of 8 mm with high quality. Imaging segmentation and dual wavelength imaging were performed to demonstrate the potential of the system in preclinical brain research.

Full three-dimensional segmentation and quantification of tumor vessels for photoacoustic images.

Quantitative analysis of tumor vessels is of great significance for tumor staging and diagnosis. Photoacoustic imaging (PAI) has been proven to be an effective way to visualize comprehensive tumor vascular networks in three-dimensional (3D) volume, while previous studies only quantified the vessels projected in one plane. In this study, tumor vessels were segmented and quantified in a full 3D framework. It had been verified in the phantom experiments that the 3D quantification results have better accuracy than 2D. Furthermore, in vivo vessel images were quantified by 2D and 3D quantification methods respectively. And the difference between these two results is significant. In this study, complete vessel segmentation and quantification method within a 3D framework was implemented, which showed obvious advantage in the analysis accuracy of 3D photoacoustic images, and potentially improve tumor study and diagnosis.

Photoacoustic visualization of the fluence rate dependence of photodynamic therapy.

This study investigates the fluence rate effect, an essential modulating mechanism of photodynamic therapy (PDT), by using photoacoustic imaging method. To the best of our knowledge, this is the first time that the fluence rate dependence is investigated at a microscopic scale, as opposed to previous studies that are based on tumor growth/necrosis or animal surviving rate. This micro-scale examination enables subtle biological responses, including the vascular damage and the self-healing response, to be studied. Our results reveal the correlations between fluence rate and PDT efficacy/self-healing magnitude, indicating that vascular injuries induced by high fluence rates are more likely to recover and by low fluence rates (≤126 mW/cm2) are more likely to be permanent. There exists a turning point of fluence rate (314 mW/cm2), above which PDT practically produces no permanent therapeutic effect and damaged vessels can fully recover. These findings have practical significance in clinical setting. For cancer-related diseases, the 'effective fluence rate' is useful to provoke permanent destruction of tumor vasculature. Likewise, the 'non effective range' can be applied when PDT is used in applications such as opening the blood brain barrier to avoid permanent brain damage.

Ultracompact biosensor based on a metalens with a longitudinally structured vector beam.

The refractive index is one of the essential parameters in describing biochemical reactions and biomedical diagnostics, and in situ measurement of the refractive index is very important for the micro total analysis system. We proposed an ultracompact biosensor based on a high numerical aperture metalens that was designed as two parts for generating the Pancharatnam-Berry phase and propagation phase, respectively, by using zinc sulfide nanofins, and nanopillars. Then incident light was modulated into a right-circularly polarized vortex beam and a left-circularly polarized vortex beam in the focal spot. The superposition of both beams can generate a structured vector beam with various polarization states along the focus direction. The polarization is sensitive to the difference of optical path, which has a potential application in index detection and biochemical analysis.

Chiral optical field generated by an annular subzone vortex phase plate.

We proposed and experimentally demonstrated a novel method for generating a chiral beam with controllable intensity twist lobes and direction by using annular subzone (AS) vortex phase plates, which is composed of different ASs and different vortex phases. The phase distribution continuity between two adjacent ASs determines the intensity distribution of the light field. The rotated direction of the optical filed is determined by the topological charge sign. The number of intensity twist lobes is determined by the topological charge gradient between adjacent subzones. The experimental results show that this method is effective and practical, which offers broad potential applications in particle manipulation, chiral microstructure fabrication, and optical tweezers.

Highly Sensitive Fluorescence and Photoacoustic Detection of Metastatic Breast Cancer in Mice Using Dual-Modal Nanoprobes.

The biomedical imaging of metastatic breast cancer, especially in lymphatic and lung metastasis, is highly significant in cancer staging as it helps assess disease prognosis and treatment. Using an albumin-indocyanine green dual-modal nanoprobe developed in our laboratory, in vivo fluorescence imaging and photoacoustic imaging of metastatic breast cancer tumors were performed separately. Fluorescence imaging at the near-infrared window features high imaging sensitivity but is generally limited by a low imaging depth. Thus, tumors can only be observed in situ whereas tumor cells in the lymph nodes and lung cannot be imaged in a precise manner. In contrast, photoacoustic imaging often helps overcome the limitations of imaging depth with high acoustic spatial resolution, which could provide complementary information for imaging cancer metastases. Ex vivo fluorescence and photoacoustic imaging were also performed to verify the tumor metastatic route. This study may not only provide insights into the design of dual-modal nanoprobes for breast cancer diagnosis but may also demonstrate the superiority of combined fluorescence imaging and photoacoustic imaging for guiding, monitoring, and evaluating lymphatic and lung metastatic stages of breast cancer with a high imaging specificity as well as sensitivity.

Dual-foci detection in photoacoustic computed tomography with coplanar light illumination and acoustic detection: a phantom study.

A dual-foci transducer with coplanar light illumination and acoustic detection was applied for the first time. It overcame the small directivity angle, low-sensitivity, and large datasets in conventional circular scanning or array-based photoacoustic computed tomography (PACT). The custom-designed transducer is focused on both the scanning plane with virtual-point detection and the elevation direction for large field of view (FOV) cross-sectional imaging. Moreover, a coplanar light illumination and acoustic detection configuration can provide ring-shaped light irradiation with highly efficient acoustic detection, which in principle has a better adaptability when imaging samples of irregular surfaces. Phantom experiments showed that our PACT system can achieve high resolution (∼0.5 mm), enhanced signal-to-noise ratio (16-dB improvement), and a more complete structure in a greater FOV with an equal number of sampling points compared with the results from a flat aperture transducer. This study provides the proof of concept for the fabrication of a sparse array with the dual-foci property and large aperture size for high-quality, low-cost, and high-speed photoacoustic imaging.

Topological charge measurement of concentric OAM states using the phase-shift method.

We proposed a method to measure orbital angular momentum (OAM) states by using a multi-zone pure phase grating with the phase-shift technique. In free-space optical communication systems, the topological charges (TCs) of concentric OAM beams are usually detected for decoding, since the diameter of the OAM beam relates to the transmission distance. Two typical concentric OAM beams, concentric Laguerre-Gaussian beams and perfect vortex beams, were generated as incident beams, and the diffraction patterns can be separated by implementing a pure phase grating in the Fourier plane of a 4-f system. By counting the corresponding diffraction fringes, we can identify the TCs of the two OAM states. The simulation results show that the diffraction angles of the concentric OAM beams can be controlled and two concentric OAM states can be measured simultaneously.

Highly specific noninvasive photoacoustic and positron emission tomography of brain plaque with functionalized croconium dye labeled by a radiotracer.

Highly-efficient targeting probes are desirable for disease diagnosis and functional imaging. However, most of the current near-infrared (NIR) probes suffer from low signal conversion, insufficient photostability, poor probe specificity, and limited functions. Herein, an NIR ultrahigh absorbing croconium dye for amyloid (CDA) was designed and synthesized to specifically bind to cerebrovascular amyloid without antibody linkage. This unique CDA is able to strongly bind the hydrophobic channels of amyloid beta (Aß) fiber with a very strong binding energy of -9.3 kcal mol-1. Our experimental results demonstrate that the amphipathic dye with an intense absorption peak at 800 nm generated a significant local temperature surge under low-power laser irradiation. Compared with representative prominent indocyanine green, Prussian blue, and gold nanorods, this probe can produce the strongest photoacoustic signal based on the same mass concentration. Labeled with radioactive 18F, this multifunctional probe allowed for the ultrasensitive photoacoustic tomography (PAT)/positron emission tomography (PET)/fluorescence imaging of Aß plaques in the brain cortex. Featured with high spatial resolution and optical specificity, PAT was intrinsically suitable for imaging pathological sites on cortical vessels, whereas PET revealed whole-body anatomy with quantitative biodistribution information. Our study shows that a CDA-based functionalized dye aided with PAT and PET is capable of plaque diagnosis and localization.

High-speed, sparse-sampling three-dimensional photoacoustic computed tomography in vivo based on principal component analysis.

Photoacoustic computed tomography (PACT) has emerged as a unique and promising technology for multiscale biomedical imaging. To fully realize its potential for various preclinical and clinical applications, development of systems with high imaging speed, reasonable cost, and manageable data flow are needed. Sparse-sampling PACT with advanced reconstruction algorithms, such as compressed-sensing reconstruction, has shown potential as a solution to this challenge. However, most such algorithms require iterative reconstruction and thus intense computation, which may lead to excessively long image reconstruction times. Here, we developed a principal component analysis (PCA)-based PACT (PCA-PACT) that can rapidly reconstruct high-quality, three-dimensional (3-D) PACT images with sparsely sampled data without requiring an iterative process. In vivo images of the vasculature of a human hand were obtained, thus validating the PCA-PACT method. The results showed that, compared with the back-projection (BP) method, PCA-PACT required ∼50% fewer measurements and ∼40% less time for image reconstruction, and the imaging quality was almost the same as that for BP with full sampling. In addition, compared with compressed sensing-based PACT, PCA-PACT had approximately sevenfold faster imaging speed with higher imaging accuracy. This work suggests a promising approach for low-cost, 3-D, rapid PACT for various biomedical applications.

Photoacoustic imaging method based on arc-direction compressed sensing and multi-angle observation.

In photoacoustic imaging (PAI), the photoacoustic (PA) signal can be observed only from limit-view angles due to some structure limitations. As a result, data incompleteness artifacts appear and some image details lose. An arc-direction mask in PA data acquisition and arc-direction compressed sensing (CS) reconstruction algorithm are proposed instead of the conventional rectangle CS methods for PAI. The proposed method can effectively realize the compression of the PA data along the arc line and exactly recover the PA images from multi-angle observation. Simulation results demonstrate that it has the potential of application in high-resolution PAI for obtaining highly resolution and artifact-free PA images.