Score-based generative model-assisted information compensation for high-quality limited-view reconstruction in photoacoustic tomography.

Photoacoustic tomography (PAT) regularly operates in limited-view cases owing to data acquisition limitations. The results using traditional methods in limited-view PAT exhibit distortions and numerous artifacts. Here, a novel limited-view PAT reconstruction strategy that combines model-based iteration with score-based generative model was proposed. By incrementally adding noise to the training samples, prior knowledge can be learned from the complex probability distribution. The acquired prior is then utilized as constraint in model-based iteration. The information of missing views can be gradually compensated by cyclic iteration to achieve high-quality reconstruction. The performance of the proposed method was evaluated with the circular phantom and in vivo experimental data. Experimental results demonstrate the outstanding effectiveness of the proposed method in limited-view cases. Notably, the proposed method exhibits excellent performance in limited-view case of 70° compared with traditional method. It achieves a remarkable improvement of 203% in PSNR and 48% in SSIM for the circular phantom experimental data, and an enhancement of 81% in PSNR and 65% in SSIM for in vivo experimental data, respectively. The proposed method has capability of reconstructing PAT images in extremely limited-view cases, which will further expand the application in clinical scenarios.

Unsupervised disentanglement strategy for mitigating artifact in photoacoustic tomography under extremely sparse view.

Traditional methods under sparse view for reconstruction of photoacoustic tomography (PAT) often result in significant artifacts. Here, a novel image to image transformation method based on unsupervised learning artifact disentanglement network (ADN), named PAT-ADN, was proposed to address the issue. This network is equipped with specialized encoders and decoders that are responsible for encoding and decoding the artifacts and content components of unpaired images, respectively. The performance of the proposed PAT-ADN was evaluated using circular phantom data and the animal in vivo experimental data. The results demonstrate that PAT-ADN exhibits excellent performance in effectively removing artifacts. In particular, under extremely sparse view (e.g., 16 projections), structural similarity index and peak signal-to-noise ratio are improved by ∼188 % and ∼85 % in in vivo experimental data using the proposed method compared to traditional reconstruction methods. PAT-ADN improves the imaging performance of PAT, opening up possibilities for its application in multiple domains.

High-resolution iterative reconstruction at extremely low sampling rate for Fourier single-pixel imaging via diffusion model.

The trade-off between imaging efficiency and imaging quality has always been encountered by Fourier single-pixel imaging (FSPI). To achieve high-resolution imaging, the increase in the number of measurements is necessitated, resulting in a reduction of imaging efficiency. Here, a novel high-quality reconstruction method for FSPI imaging via diffusion model was proposed. A score-based diffusion model is designed to learn prior information of the data distribution. The real-sampled low-frequency Fourier spectrum of the target is employed as a consistency term to iteratively constrain the model in conjunction with the learned prior information, achieving high-resolution reconstruction at extremely low sampling rates. The performance of the proposed method is evaluated by simulations and experiments. The results show that the proposed method has achieved superior quality compared with the traditional FSPI method and the U-Net method. Especially at the extremely low sampling rate (e.g., 1%), an approximately 241% improvement in edge intensity-based score was achieved by the proposed method for the coin experiment, compared with the traditional FSPI method. The method has the potential to achieve high-resolution imaging without compromising imaging speed, which will further expanding the application scope of FSPI in practical scenarios.

Accelerated model-based iterative reconstruction strategy for sparse-view photoacoustic tomography aided by multi-channel autoencoder priors.

Photoacoustic tomography (PAT) commonly works in sparse view due to data acquisition limitations. However, reconstruction suffers from serious deterioration (e.g., severe artifacts) using traditional algorithms under sparse view. Here, a novel accelerated model-based iterative reconstruction strategy for sparse-view PAT aided by multi-channel autoencoder priors was proposed. A multi-channel denoising autoencoder network was designed to learn prior information, which provides constraints for model-based iterative reconstruction. This integration accelerates the iteration process, leading to optimal reconstruction outcomes. The performance of the proposed method was evaluated using blood vessel simulation data and experimental data. The results show that the proposed method can achieve superior sparse-view reconstruction with a significant acceleration of iteration. Notably, the proposed method exhibits excellent performance under extremely sparse condition (e.g., 32 projections) compared with the U-Net method, with an improvement of 48% in PSNR and 12% in SSIM for in vivo experimental data.

Sparse-view reconstruction for photoacoustic tomography combining diffusion model with model-based iteration.

As a non-invasive hybrid biomedical imaging technology, photoacoustic tomography combines high contrast of optical imaging and high penetration of acoustic imaging. However, the conventional standard reconstruction under sparse view could result in low-quality image in photoacoustic tomography. Here, a novel model-based sparse reconstruction method for photoacoustic tomography via diffusion model was proposed. A score-based diffusion model is designed for learning the prior information of the data distribution. The learned prior information is utilized as a constraint for the data consistency term of an optimization problem based on the least-square method in the model-based iterative reconstruction, aiming to achieve the optimal solution. Blood vessels simulation data and the animal in vivo experimental data were used to evaluate the performance of the proposed method. The results demonstrate that the proposed method achieves higher-quality sparse reconstruction compared with conventional reconstruction methods and U-Net. In particular, under the extreme sparse projection (e.g., 32 projections), the proposed method achieves an improvement of ∼ 260 % in structural similarity and ∼ 30 % in peak signal-to-noise ratio for in vivo data, compared with the conventional delay-and-sum method. This method has the potential to reduce the acquisition time and cost of photoacoustic tomography, which will further expand the application range.

Noise insensitive volumetric fusion method for enhanced photoacoustic microscopy.

Significance: Photoacoustic imaging is an emerging imaging modality that combines the high contrast of optical imaging and the high penetration of acoustic imaging. However, the strong focusing of the laser beam in optical-resolution photoacoustic microscopy (OR-PAM) leads to a limited depth-of-field (DoF). Aim: Here, a volumetric photoacoustic information fusion method was proposed to achieve large volumetric photoacoustic imaging at low cost. Approach: First, the initial decision map was built through the focus detection based on the proposed three-dimensional Laplacian operator. Majority filter-based consistency verification and Gaussian filter-based map smoothing were then utilized to generate the final decision map for the construction of photoacoustic imaging with extended DoF. Results: The performance of the proposed method was tested to show that our method can expand the limited DoF by a factor of 1.7 without the sacrifice of lateral resolution. Four sets of multi-focus vessel data at different noise levels were fused to verify the effectiveness and robustness of the proposed method. Conclusions: The proposed method can efficiently extend the DoF of OR-PAM under different noise levels.

Noise-insensitive defocused signal and resolution enhancement for optical-resolution photoacoustic microscopy via deep learning.

Optical-resolution photoacoustic microscopy suffers from narrow depth of field and a significant deterioration in defocused signal intensity and spatial resolution. Here, a method based on deep learning was proposed to enhance the defocused resolution and signal-to-noise ratio. A virtual optical-resolution photoacoustic microscopy based on k-wave was used to obtain the datasets of deep learning with different noise levels. A fully dense U-Net was trained with randomly distributed sources to improve the quality of photoacoustic images. The results show that the PSNR of defocused signal was enhanced by more than 1.2 times. An over 2.6-fold enhancement in lateral resolution and an over 3.4-fold enhancement in axial resolution of defocused regions were achieved. The large volumetric and high-resolution imaging of blood vessels further verified that the proposed method can effectively overcome the deterioration of the signal and the spatial resolution due to the narrow depth of field of optical-resolution photoacoustic microscopy.

High-speed real 3D scene acquisition and 3D holographic reconstruction system based on ultrafast optical axial scanning.

The lack of three-dimensional (3D) content is one of the challenges that have been faced by holographic 3D display. Here, we proposed a real 3D scene acquisition and 3D holographic reconstruction system based on ultrafast optical axial scanning. An electrically tunable lens (ETL) was used for high-speed focus shift (up to 2.5 ms). A CCD camera was synchronized with the ETL to acquire multi-focused image sequence of real scene. Then, the focusing area of each multi-focused image was extracted by using Tenengrad operator, and the 3D image were obtained. Finally, 3D holographic reconstruction visible to the naked eye can be achieved by the layer-based diffraction algorithm. The feasibility and effectiveness of the proposed method have been demonstrated by simulation and experiment, and the experimental results agree well with the simulation results. This method will further expand the application of holographic 3D display in the field of education, advertising, entertainment, and other fields.

Bessel acoustic-beam acoustic lens for extending the depth of field of detection in optical-resolution photoacoustic microscopy.

As an important part of optical-resolution photoacoustic microscopy, the acoustic lens is responsible for efficient collection of photoacoustic signals. The spherical focused acoustic lens is commonly used in photoacoustic microscopy because of its efficient detection of the photoacoustic signal in the focus area. However, the narrow depth of field of the spherical focused acoustic lens limits the expansion of the depth of field of the photoacoustic microscopy. To solve this problem, a Bessel acoustic-beam acoustic lens is proposed. The Bessel acoustic-beam acoustic lens replaces the spherical concave surface with a conical concave surface to generate a Bessel acoustic beam with non-diffraction. Using the simulation model of Bessel acoustic-beam acoustic lens constructed by COMSOL Multiphysics, it is verified theoretically that the Bessel acoustic-beam acoustic lens can improve the depth of field of detection by ∼2 times. The Bessel acoustic-beam acoustic lens can further promote the capability of high-speed and large volumetric imaging of optical-resolution photoacoustic microscopy and will be helpful in the acquisition of physiological and pathological processes.

High-resolution volumetric information fusion for depth of field enhancement in photoacoustic microscopy.

Optical-resolution photoacoustic microscopy suffers from limited depth of field due to the strongly focused laser beam. Here, a novel volumetric information fusion is proposed to achieve large volumetric and high-resolution imaging. First, three-dimensional stationary wavelet transform was performed on the multi-focus data to obtain eight wavelet coefficients. Differential evolution based on joint weighted evaluation was then employed to optimize the block size of division for each wavelet coefficient. The proposed fusion rule using standard deviation for focus detection was used to fuse the corresponding sub-coefficients. Finally, photoacoustic imaging with large depth of field can be achieved by the inverse stationary wavelet transform. Performance test shows that the depth of field of photoacoustic imaging can be doubled without sacrificing lateral resolution. The proposed volumetric information fusion can further promote the capability of volumetric imaging of optical-resolution photoacoustic microscopy and will be helpful in the acquisition of physiological and pathological process.

Multiscale photoacoustic imaging without motion using single-pixel imaging.

The conventional photoacoustic microscopy usually uses mechanical raster scanning to obtain three-dimensional information, and the imaging speed is limited. Meanwhile, the conventional photoacoustic microscopy can only be performed at one single scale due to fixed resolution, it cannot make full use of multiscale information for integrated imaging. Here, we proposed a multiscale photoacoustic microscopy based on single-pixel imaging. A sequence of sinusoidal fringes with varying spatial frequencies is used to obtain the Fourier coefficients in the case of a single ultrasonic transducer. By controlling the spatial frequency of fringe, the acquisition of Fourier coefficients can be controlled and multiscale imaging can be achieved. The feasibility of this method is verified by theory and simulation. The results show that the lateral resolution can be tuned from several microns to tens of microns without mechanical scanning. This method will expand the application of photoacoustic imaging in biomedical research.

Controllable axial optical chain beams using a holographic method.

Axial optical chain (optical bottle beams) beams are widely used in optical micromanipulation, atom trapping, guiding and binding of microparticles and biological cells, etc. However, the generation of axial optical chain beams are not very flexible at present, and its important characteristics such as periodicity and phase shift cannot be easily regulated. Here, we propose a holographic method to achieve the axial optical chain beams with controllable periodicity and phase. A double annular phase diagram is generated based on the gratings and lenses algorithms. The beam incident to the double annular slits was tilted from the optical axis to produce concentric double annular beams. The annular beam with different radius will produce the zero-order Bessel beam with different axial wave vector. Axial optical chain beams is produced by interference of two zero-order Bessel beams with different axial wave vectors. The phase and periodicity of the axial optical chain beams can be changed by changing the initial phase difference and radius of the double annular slits of the double annular phase diagram, respectively. The feasibility and effectiveness of the proposed method are demonstrated by theoretical numerical analysis and experiments. This method will further expand the application of axial optical chain beams in optical tweezers, optical modulation and other fields.

Virtual optical-resolution photoacoustic microscopy using the k-Wave method.

Deep learning has been widely used in image processing, quantitative analysis, and other applications in optical-resolution photoacoustic microscopy (OR-PAM). It requires a large amount of photoacoustic data for training and testing. However, due to the complex structure, high cost, slow imaging speed, and other factors of OR-PAM, it is difficult to obtain enough data required by deep learning, which limits the research of deep learning in OR-PAM to a certain extent. To solve this problem, a virtual OR-PAM based on k-Wave is proposed. The virtual photoacoustic microscopy mainly includes the setting of excitation light source and ultrasonic probe, scanning and signal processing, which can realize the common Gaussian-beam and Bessel-beam OR-PAMs. The system performance (lateral resolution, axial resolution, and depth of field) was tested by imaging a vertically tilted fiber, and the effectiveness and feasibility of the virtual simulation platform were verified by 3D imaging of the virtual vascular network. The ability to the generation of the dataset for deep learning was also verified. The construction of the virtual OR-PAM can promote the research of OR-PAM and the application of deep learning in OR-PAM.

Graded peripheral nerve injury creates mechanical allodynia proportional to the progression and severity of microglial activity within the spinal cord of male mice.

The reactivity of microglia within the spinal cord in response to nerve injury, has been associated with the development and maintenance of neuropathic pain. However, the temporal changes in microglial reactivity following nerve injury remains to be defined. Importantly, the magnitude of behavioural allodynia displayed and the relationship to the phenotypic microglial changes is also unexplored. Using a heterozygous CX3CR1gfp+ transgenic mouse strain, we monitored microglial activity as measured by cell density, morphology, process movement and process length over 14 days following chronic constriction of the sciatic nerve via in vivo confocal microscopy. Uniquely this relationship was explored in groups of male mice which had graded nerve injury and associated graded behavioural mechanical nociceptive sensitivity. Significant mechanical allodynia was quantified from the ipsilateral hind paw and this interacted with the extent of nerve injury from day 5 to day 14 (p < 0.009). The extent of this ipsilateral allodynia was proportional to the nerve injury from day 5 to 14 (Spearman rho = -0.58 to -0.77; p < 0.002). This approach allowed for the assessment of the association of spinal microglial changes with the magnitude of the mechanical sensitivity quantified behaviourally. Additionally, the haemodynamic response in the somatosensory cortex was quantified as a surrogate measure of neuronal activity. We found that spinal dorsal horn microglia underwent changes unilateral to the injury in density (Spearman rho = 0.47; p = 0.01), velocity (Spearman rho = -0.68; p = 0.00009), and circularity (Spearman rho = 0.55; p = 0.01) proportional to the degree of the neuronal injury. Importantly, these data demonstrate for the first time that the mechanical allodynia behaviour is not a binary all or nothing state, and that microglial reactivity change proportional to this behavioural measurement. Increased total haemoglobin levels in the somatosensory cortex of higher-grade injured animals was observed when compared to sham controls suggesting increased neuronal activity in this brain region. The degree of phenotypic microglial changes quantified here, may explain how microglia can induce both rapid onset and sustained functional changes in the spinal cord dorsal horn, following peripheral injury.

Prospective Respiration-Gated Photoacoustic Microscopy.

OBJECTIVE: Photoacoustic microscopy (PAM) is a promising biomedical imaging technique that relies on sequential excitation to generate three-dimensional images. It combines the high contrast of optical imaging with high penetration depth of ultrasound imaging. The normal respiration rate of mice is greater than 3 Hz, which leads to motion artifacts in most reported PAM for in vivo imaging. METHODS: Here, we introduce a prospective respiratory gating (PRG) method for PAM to address this problem. We captured the mouse's respiratory signal with a laser displacement sensor, and the photoacoustic signal was acquired at specific phase points of the respiratory signal. The scanning mode and the scanning timing were also designed and evaluated. We combined this method with our PAM to demonstrate its feasibility. RESULTS: Our experiments show that the proposed method can help remove motion artifacts well, and the subcutaneous vascular imaging results of the mouse abdominal region with PRG are much better than those without any gating.

A near-infrared light-controlled smart nanocarrier with reversible polypeptide-engineered valve for targeted fluorescence-photoacoustic bimodal imaging-guided chemo-photothermal therapy.

Despite burgeoning development of nanoplatform made in the past few years, it remains a challenge to produce drug nanocarrier that enables requested on/off drug release. Thus, this study aimed to develop an ideal near-infrared light-triggered smart nanocarrier for targeted imaging-guided treatment of cancer that tactfully integrated photothermal therapy with chemotherapy to accurately control drug release time and dosage. Methods: This delivery system was composed of Ag2S QD coating with dendritic mesoporous silica (DMSN), which acted as nanocarrier of doxorubicin localized inside pores. To provide the nanocarrier with controlled release capability, a polypeptide-engineered that structure was reversible to photothermal effect of Ag2S QD, was covalently grafted to the external surface of drug-loaded DMSN. Results: This nanocarrier with the size of 40~60 nm had satisfactory biocompatibility and photothermal conversion efficiency up to 28.35%. Due to acidity-triggered charge reversal of polypeptide, which significantly extended circulation time and improved targeting ability, fluorescence and photoacoustic signals were still obvious at tumor site post-24 h by tail vein injection and chemo-photothermal synergistic therapy obviously enhanced antitumor efficacy. Mild PTT with multiple short-term exposures not only reduced the side effect of overdose drug but also avoided skin damage caused by long-term irradiation. Conclusion: By adjusting irradiation time and on/off cycle, multiple small amount local drug release reduced the side effect of overdose drug and skin damage. This novel approach provided an ideal near-infrared light-triggered nanocarrier with accurate control of area, time, and especially dosage.

An injectable hybrid hydrogel based on a genetically engineered polypeptide for second near-infrared fluorescence/photoacoustic imaging-monitored sustained chemo-photothermal therapy.

An injectable multifunctional hydrogel based on an engineered coiled-coil polypeptide, Ag2S quantum dots (QDs), and paclitaxel (PTX) has been developed for sustained chemo-photothermal therapy. Oil-soluble Ag2S QDs and PTX were first loaded into nanogels formed with engineered polypeptide PC10A by ultrasonic treatment to prepare PC10A/Ag2S QD/PTX nanogels. The multifunctional PC10A/Ag2S QD/PTX hydrogels were prepared by dissolving the PC10A/Ag2S QD/PTX nanogels into the PC10A hydrogel. The PC10A/Ag2S QD/PTX hydrogel can be injected directly into the site of tumors. In vitro and in vivo toxicity results showed that the PC10A/Ag2S QD/PTX hydrogel presented excellent biocompatibility. Compared with single near-infrared photothermal therapy and chemotherapy, the combined therapy could effectively suppress the growth of SKOV3 ovarian carcinoma tumor. In addition, real-time monitoring of the in vivo degradation of the PC10A/Ag2S QD/PTX hydrogel was achieved by near-infrared fluorescence imaging and photoacoustic imaging. These results demonstrated that this injectable multifunctional PC10A/Ag2S QD/PTX hydrogel has the potential as a theranostic platform for sustained cancer treatments.

A Simple Glutathione-Responsive Turn-On Theranostic Nanoparticle for Dual-Modal Imaging and Chemo-Photothermal Combination Therapy.

Constructing a tumor microenvironment stimuli activatable theranostic nanoparticle with simple components and preparation procedures for multimodality imaging and therapy remains a major challenge for current theranostic systems. Here we report a novel and simple glutathione (GSH)-responsive turn-on theranostic nanoparticle for dual-modal imaging and combination therapy. The theranostic nanoparticle, DHP, consisting of a disulfide-bond-linked hydroxyethyl starch paclitaxel conjugate (HES-SS-PTX) and a near-infrared (NIR) cyanine fluorophore DiR, is prepared with a simple one-step dialysis method. As DiR is encapsulated within the hydrophobic core formed by HES-SS-PTX, the fluorescence of DiR is quenched by the aggregation-caused quenching (ACQ) effect. Nonetheless, once DHP is internalized by cancer cells, the disulfide bond of HES-SS-PTX can be cleaved by intracellular GSH, leading to the synchronized release of conjugated PTX and loaded DiR. The released PTX could exert its therapeutic effect, while DiR could adsorb onto nearby endosome/lysosome membranes and regain its fluorescence. Thus, DHP could monitor the release and therapeutic effect of PTX through the fluorescence recovery of DiR. Remarkably, DHP can also be used as an in vivo probe for both fluorescent and photoacoustic imaging and at the same time achieves potent antitumor efficacy through chemo-photothermal combination therapy. This study provides novel insights into designing clinically translatable turn-on theranostic systems.

Self-Assembled "Off/On" Nanopomegranate for In Vivo Photoacoustic and Fluorescence Imaging: Strategic Arrangement of Kupffer Cells in Mouse Hepatic Lobules.

Kupffer cells (KCs), potent scavenger cells located in hepatic sinusoids, constantly phagocytize and degrade foreign materials to maintain metabolism and clearance. Understanding the strategic KC arrangement which links to their spatial location and function in hepatic lobules, the basic functional unit in the liver, is highly valuable for characterizing liver function. However, selectively labeling KCs and characterizing their function in vivo remains challenging. Herein, a fast self-assembled pomegranate structure-like nanoparticle with "nanopomegranate seeds" of dye aggregates has been developed, which has dual-modality "off/on" capability. This nanopomegranate shows good photostability, a high extinction coefficient, a high KC labeling efficiency (98.8%), and better visualization of KC morphology than commercial FluoSpheres. In vivo photoacoustic (PA) and fluorescence imaging consistently visualize that KCs are strategically distributed along the central vein (CV)-portal triad (PT) axis in each liver lobule: more and larger KCs exist in areas closer to the PTs. The high-resolution PA quantitative data further revealed that the density of KCs was linearly dependent on the r n/ rmax ratio (their relative location along the CV-PT axis) ( R2 = 0.7513), and the KC density at the outermost layer is almost 246-fold that at the innermost layer (each layer is 8 µm). Notably, the phagocytic ability of KCs located in layers with r n/ rmax ratios of 0.167-0.3 varies in a zigzag pattern, as evidenced by their different PA intensities. Additionally, the fluorescence imaging quantitation suggests similar fluorescence activation of nanopomegranate in KCs. Nanopomegranates combined with dual-modality imaging reveal the strategic arrangement of KCs in vivo, greatly extending our understanding of liver physiology.

In situ aqueous synthesis of genetically engineered polypeptide-capped Ag2S quantum dots for second near-infrared fluorescence/photoacoustic imaging and photothermal therapy.

Ag2S quantum dots have received extensive attention as theranostic agents for second near-infrared (NIR-II) fluorescence and photoacoustic dual-mode imaging, and photothermal therapy. However, it is still greatly challenging to synthesize Ag2S quantum dots using aqueous synthesis. In this study, genetically engineered polypeptide-capped Ag2S quantum dots were successfully synthesized. Three cysteines were integrated to the C-terminal and N-terminal of RGDPC10A to enhance the stability and brightness of the synthesized Ag2S quantum dots. The RGDPC10A-capped Ag2S quantum dots exhibited excellent stability, outstanding resistance to photobleaching, and a superior quantum yield of up to 3.78% in the NIR-II biological window. The in vitro and in vivo results showed that the RGDPC10A-capped Ag2S quantum dots possessed typical NIR-II fluorescence, photoacoustic imaging, and photothermal therapeutic effectiveness against tumors. Moreover, the results of toxicity assays suggested that the RGDPC10A-capped Ag2S quantum dots have negligible long-term toxicity. These findings open up the possibility for synthesizing theranostic agents by using this aqueous method.