Photoacoustic Imaging Research Articles

Multi-parametric Photoacoustic Imaging Combined with Acoustic Radiation Force Impulse Imaging for Applications in Tissue Engineering.

Tissue engineering is a dynamic field focusing on the creation of advanced scaffolds for tissue and organ regeneration. These scaffolds are customized to their specific applications and are often designed to be complex, large structures to mimic tissues and organs. This study addresses the critical challenge of effectively characterizing these thick, optically opaque scaffolds that traditional imaging methods fail to fully image due to their optical limitations. We introduce a novel multi-modal imaging approach combining ultrasound, photoacoustic, and acoustic radiation force impulse imaging. This combination leverages its acoustic-based detection to overcome the limitations posed by optical imaging techniques. Ultrasound imaging is employed to monitor the scaffold structure, photoacoustic imaging is employed to monitor cell proliferation, and acoustic radiation force impulse imaging is employed to evaluate the homogeneity of scaffold stiffness. We applied this integrated imaging system to analyze melanoma cell growth within silk fibroin protein scaffolds with varying pore sizes and therefore stiffness over different cell incubation periods. Among various materials, silk fibroin was chosen for its unique combination of features including biocompatibility, tunable mechanical properties, and structural porosity which supports extensive cell proliferation. The results provide a detailed mesoscale view of the scaffolds' internal structure, including cell penetration depth and biomechanical properties. Our findings demonstrate that the developed multimodal imaging technique offers comprehensive insights into the physical and biological dynamics of tissue-engineered scaffolds. As the field of tissue engineering continues to advance, the importance of non-ionizing and non-invasive imaging systems becomes increasingly evident, and by facilitating a deeper understanding and better characterization of scaffold architectures, such imaging systems are pivotal in driving the success of future tissue-engineering solutions.

Tailoring Plasmonic Nanoheaters Size for Enhanced Theranostic Agent Performance.

The introduction of optimized nanoheaters, which function as theranostic agents integrating both diagnostic and therapeutic processes, holds significant promise in the medical field. Therefore, developing strategies for selecting and utilizing optimized plasmonic nanoheaters is crucial for the effective use of nanostructured biomedical agents. This work elucidates the use of the Joule number (Jo) as a figure of merit to identify high-performance plasmonic theranostic agents. A framework for optimizing metallic nanoparticles for heat generation was established, uncovering the size dependence of plasmonic nanoparticles optical heating. Gold nanospheres (AuNSs) with a diameter of 50 nm and gold nanorods (AuNRs) with dimensions of 41×10 nm were identified as effective nanoheaters for visible (530 nm) and infrared (808 nm) excitation. Notably, AuNRs achieve higher Jo values than AuNSs, even when accounting for the possible orientations of the nanorods. Theoretical results estimate that 41×10 nm gold nanorods have an average Joule number of 80, which is significantly higher compared to larger rods. The photothermal performance of optimal and suboptimal nanostructures was evaluated using photoacoustic imaging and photothermal therapy procedures. The photoacoustic images indicate that, despite having larger absorption cross-sections, the large nanoparticle volume of bigger particles leads to less efficient conversion of light into heat, which suggests that the use of optimized nanoparticles promotes higher contrast, benefiting photoacoustic-based procedures in diagnostic applications. The photothermal therapy procedure was performed on S180-bearing mice inoculated with 41×10 nm and 90×25 nm PEGylated AuNRs. Five minutes of laser irradiation of tumor tissue with 41×10 nm produced an approximately 9.5% greater temperature rise than using 90×25 AuNRs in the therapy trials. Optimizing metallic nanoparticles for heat generation may reduce the concentration of the nanoheaters used or decrease the light fluence for bioscience applications, paving the way for the development of more economical theranostic agents.

Advances in Photoacoustic Endoscopic Imaging Technology for Prostate Cancer Detection

The rapid progress in biomedical imaging technology has generated considerable interest in new non-invasive photoacoustic endoscopy imaging techniques. This emerging technology offers significant benefits, including high spectral specificity, strong tissue penetration, and real-time multidimensional high-resolution imaging capabilities, which enhance clinical diagnosis and treatment of prostate cancer. This paper delivers a thorough review of current prostate cancer screening techniques, the core principles of photoacoustic endoscopy imaging, and the latest research on its use in detecting prostate cancer. Additionally, the limitations of this technology in prostate cancer detection are discussed, and future development trends are anticipated.

Nanocrystallized copper phosphate endowed with photothermal conversion and photoacoustic imaging capabilities

Copper-based nanomaterials have garnered significant attention for their potential applications in photothermal (PT) conversion and photoacoustic (PA) imaging due to their unique optical properties. However, current strategies often involve complex synthesis processes and the incorporation of additional materials, which limit their practical applicability. Here, we employed a straightforward nanocrystallization method to synthesize copper phosphate nanoparticles (Cu3(PO4)2 NPs), converting free copper ions into solid-phase nano-sized particles. This approach not only simplifies the synthesis process but also enhances the optical and thermal properties of the resulting Cu3(PO4)2 NPs. The Cu3(PO4)2 NPs achieved a temperature increase of over 20∘C and a PT conversion efficiency of 10.5% under 808 nm laser irradiation. Furthermore, Cu3(PO4)2 NPs exhibited strong, concentration-dependent PA signals, which enabled effective deep tissue imaging in vivo. The enhanced properties of Cu3(PO4)2 NPs can be attributed to the nanocrystallization of the particles, which alters the local environment of copper ions and enhances d−d transitions through specific ligand field effects. These effects increase light absorption, particularly in the NIR region, by facilitating better overlap of electronic states and enabling more efficient non-radiative relaxation processes. This highlights the significance of nano-structuring in developing advanced nanomaterials with tailored functionalities for biomedical applications.

Novel Metal-Free Nanozyme for Targeted Imaging and Inhibition of Atherosclerosis via Macrophage Autophagy Activation to Prevent Vulnerable Plaque Formation and Rupture.

Atherosclerosis is a primary cause of cardiovascular and cerebrovascular diseases, with the unpredictable rupture of vulnerable atherosclerotic plaques enriched with lipid-laden macrophages being able to lead to heart attacks and strokes. Activating macrophage autophagy presents itself as a promising strategy for preventing vulnerable plaque formation and reducing the risk of rupture. In this study, we have developed a novel metal-free nanozyme (HCN@DS) that integrates the functions of multimodal imaging-guided therapy for atherosclerosis. HCN@DS has demonstrated high macrophage-targeting abilities due to its affinity toward scavenger receptor A (SR-A), along with excellent photoacoustic and photothermal imaging capabilities for guiding the precise treatment. It combines mild photothermal effects with moderate reactive oxygen species (ROS) generation to treat atherosclerosis. This controlled approach activates autophagy in atherosclerotic macrophages, inhibiting foam cell formation by reducing the uptake of oxidized low-density lipoproteins (oxLDL) and promoting efferocytosis and cholesterol efflux in macrophages. Additionally, it prevents plaque rupture by inhibiting apoptosis and inflammation within the plaque. Therefore, this metal-free nanozyme holds great potential for reducing the risk of atherosclerosis due to its high biosafety, excellent targeting ability, dual-modality imaging capability, and appropriate modulation of autophagy.

Evaluation of Postoperative Anastomotic Patency in Lymphaticovenular Anastomosis Using Photoacoustic Imaging.

Lymphaticovenular anastomosis (LVA) is a surgical technique used to alleviate lymphedema by bypassing the lymphatic and venous vessels and facilitating lymphatic fluid drainage. Accurate evaluation of anastomotic patency is crucial for assessing LVA outcomes. Traditional near-infrared fluorescence lymphography has limitations, including fluorescence diffusion in subcutaneous fat and difficulty evaluating areas beneath the dermal backflow. Photoacoustic imaging (PAI) is a potential alternative for high-resolution visualization of lymphatic and blood vessels. We aimed to evaluate the utility of PAI for assessing LVA patency. Using the LUB0 PAI system, we examined patients who underwent LVA. Imaging was conducted using subcutaneously injected indocyanine green (ICG) to visualize lymphatic vessels. Results showed clear patency in some cases, inability to evaluate it in others, and confirmed occlusion in certain instances. While PAI provides valuable insights, challenges remain, including the potential for ambiguous results from the intermittent nature of lymphatic flow and difficulty visualizing low-ICG-concentration lymphatic vessels. Nonetheless, PAI offers a promising method for detailed 3D evaluation of anastomoses. It may improve surgical outcomes and contribute to future evidence in the field. Further advancements, including real-time video assessment, may enhance the accuracy and reliability of LVA patency evaluation.

Rational Design of a Hetero-multinuclear Gadolinium(III)-Copper(II) Complex: Integrating Magnetic Resonance Imaging, Photoacoustic Imaging, Mild Photothermal Therapy, Chemotherapy and Immunotherapy of Cancer.

For more accurate diagnosis and effective treatment of cancer, we proposed to develop a hetero-multinuclear metal complex based on the property of apoferritin (AFt) for targeting tumor theranostics by integrating dual-modality imaging diagnosis and multimodality therapy. To this end, we rational designed and synthesized a trinuclear Gd(III)-Cu(II) thiosemicarbazone complex (Gd-2Cu) and then constructed a Gd-2Cu@AFt nanoparticle (NP) delivery system. Gd-2Cu/Gd-2Cu@AFt NPs not only had significant T1-weighted magnetic resonance imaging and photoacoustic imaging of the tumor but also effectively inhibited tumor growth through a combination of mild photothermal therapy, chemotherapy, and immunotherapy. Gd-2Cu@AFt NPs optimized the behavior of imaging diagnosis and therapy of Gd-2Cu, improved its targeting ability, and reduced the side effects in vivo. Besides, we revealed and clarified the anticancer mechanism of Gd-2Cu: interrupting energy metabolism of the tumor cell, inducing apoptosis of the tumor cell, and activating a systemic immune response by inducing immunogenic cell death of cancer cells.

Picosecond photoacoustic generation of ultrasounds with composites of graphene-decorated gold nanoparticles

Photoacoustic or light-to-pressure transducer materials exhibit tremendous potential across various disciplines and applications, embracing theragnostic ultrasounds and permeabilization of biological barriers for drug delivery or for gene transfection. Here, we report the photoacoustic response in the picosecond excitation regime of graphene and gold nanoparticles decorated graphene dispersed in a polydimethylsiloxane polymer matrix. A novel decoration method was developed to nucleate Au nanoparticles of 25 nm on the graphene surface without reducing agent. We observed that the picosecond excitation enforced by the stress confinement generates high-frequency waves, with bandwidths of −6 dB and −20 dB of around 70 MHz and 130 MHz respectively, and peak pressure > 5 MPa. Further, the presence of gold surface decoration leads to a better dispersibility of the flake into the polymer matrix and to an increasing bandwidth at −6 dB up to 85 MHz. The decrease in source thickness leads to an increase in ultrasound frequency, which retains its value even when the laser fluence is increased up to 150 mJ cm –2. This enables the generation of high pressures while keeping the same bandwidth. We experimentally show that the photoacoustic waveform can be tailored by changing the temporal duration of the laser light, the geometry of the acoustic source, and the nature of the graphene absorber. Flexible decoration and fabrication methods of thin films, along with the generation of high-frequency and high-pressure ultrasound waves, offer new perspectives for the use of physical methods to permeabilize biological barriers and develop high-resolution photoacoustic imaging systems.

JQR-Net: joint quantitative reconstruction network for dual-modal photoacoustic imaging and optical coherence tomography

JQR-Net: joint quantitative reconstruction network for dual-modal photoacoustic imaging and optical coherence tomography

Joint segmentation and image reconstruction with error prediction in photoacoustic imaging using deep learning

Deep learning has been used to improve photoacoustic (PA) image reconstruction. One major challenge is that errors cannot be quantified to validate predictions when ground truth is unknown. Validation is key to quantitative applications, especially using limited-bandwidth ultrasonic linear detector arrays. Here, we propose a hybrid Bayesian convolutional neural network (Hybrid-BCNN) to jointly predict PA image and segmentation with error (uncertainty) predictions. Each output pixel represents a probability distribution where error can be quantified. The Hybrid-BCNN was trained with simulated PA data and applied to both simulations and experiments. Due to the sparsity of PA images, segmentation focuses Hybrid-BCNN on minimizing the loss function in regions with PA signals for better predictions. The results show that accurate PA segmentations and images are obtained, and error predictions are highly statistically correlated to actual errors. To leverage error predictions, confidence processing created PA images above a specific confidence level.

The global uniqueness of a dissipative fractional Helmholtz equation

In this paper, we consider the Dirichlet problem for the fractional Helmholtz equation with dissipation, and study the inverse problem of determining the source function, potential function and dissipation of the equation using the Dirichlet-to-Neumann map and Runge approximation. We prove the global uniqueness of these three functions of the equation under low-frequency conditions. As the main result, this implies that one can use the external data to uniquely recover the unknown functions of the equation in the low-frequency case, which will be of great significance in photoacoustic tomography and thermoacoustic tomography.

Enhancing photoacoustic imaging for lung diagnostics and BCI communication: simulation of cavity structures artifact generation and evaluation of noise reduction techniques.

Pandemics like COVID-19 have highlighted the potential of Photoacoustic imaging (PAI) for Brain-Computer Interface (BCI) communication and lung diagnostics. However, PAI struggles with the clear imaging of blood vessels in areas like the lungs and brain due to their cavity structures. This paper presents a simulation model to analyze the generation and propagation mechanism within phantom tissues of PAI artifacts, focusing on the evaluation of both Anisotropic diffusion filtering (ADF) and Non-local mean (NLM) filtering, which significantly reduce noise and eliminate artifacts and signify a pivotal point for selecting artifact-removal algorithms under varying conditions of light distribution. Experimental validation demonstrated the efficacy of our technique, elucidating the effect of light source uniformity on artifact-removal performance. The NLM filtering simulation and ADF experimental validation increased the peak signal-to-noise ratio by 11.33% and 18.1%, respectively. The proposed technique adds a promising dimension for BCI and is an accurate imaging solution for diagnosing lung diseases.

Photoacoustic Imaging Sensors Based on Integrated Photonics: Challenges and Trends

AbstractUltrasound and photoacoustic imaging are important imaging modalities with significant applications in clinical diagnosis and biomedical research. However, current capacitive and piezoelectric ultrasound detectors face challenges related to sensitivity and bandwidth, particularly at higher frequencies. These challenges can hinder their ability to achieve high spatial resolution and deep penetration for imaging purposes. Optical ultrasound sensors offer high sensitivity and show great potential for developing ultrasound/photoacoustic imaging systems. Among all methods of optical ultrasound detection, integrated photonics, with its superior advantages in miniaturization, sensitivity, and integration capability with electronics, could be next‐generation photoacoustic/ultrasound imaging technology. This review explores the device structure designs and applications of ultrasound/photoacoustic sensing based on integrated photonics, analyzes their performance metrics as ultrasound detectors, and discusses some perspectives on future developments and trends in this field.

Non-invasive optoacoustic imaging of glycogen-storage and muscle degeneration in late-onset Pompe disease

Pompe disease (PD) is a rare autosomal recessive glycogen storage disorder that causes proximal muscle weakness and loss of respiratory function. While enzyme replacement therapy (ERT) is the only effective treatment, biomarkers for disease monitoring are scarce. Following ex vivo biomarker validation in phantom studies, we apply multispectral optoacoustic tomography (MSOT), a laser- and ultrasound-based non-invasive imaging approach, in a clinical trial (NCT05083806) to image the biceps muscles of 10 late-onset PD (LOPD) patients and 10 matched healthy controls. MSOT is compared with muscle magnetic resonance imaging (MRI), ultrasound, spirometry, muscle testing and quality of life scores. Next, results are validated in an independent LOPD patient cohort from a second clinical site. Our study demonstrates that MSOT enables imaging of subcellular disease pathology with increases in glycogen/water, collagen and lipid signals, providing higher sensitivity in detecting muscle degeneration than current methods. This translational approach suggests implementation in the complex care of these rare disease patients.

Noninvasive visualization of the midline-crossing arterial variation in the deep inferior epigastric artery perforator flap using photoacoustic tomography for application in patients with abdominal scars

BackgroundThe importance of the subcutaneous arterial network crossing the midline in transverse abdominal flaps has been reported. Photoacoustic tomography can be used to noninvasively visualize subcutaneous vascular networks. We applied this novel technology preoperatively in patients undergoing breast reconstruction to detect individual variations in the midline-crossing arteries. MethodsSix patients scheduled to undergo breast reconstruction using free deep inferior epigastric artery perforator flaps were examined. Each scan of the 12×8-cm region took approximately 8min. The accuracy of the tentative arteries evaluation defined by photoacoustic tomography was compared with the arterial phase detected by intraoperative indocyanine green angiography. The number of perforator vessels used for the flap, surgical time for flap elevation, and perfusion area ratio were compared with those of the control group. ResultsThe average match rate between tentative arteries prediction by photoacoustic tomography and arterial-phase assessment by intraoperative angiography in 5 patients was 79.8%. Each midline crossing artery showed individual variations. The photoacoustic tomography group (PAT-1 to 5) showed 1.8 perforators per flap, 163minutes for flap elevation, and 93% perfusion area, with no significant differences from the control group (N=5). A 63-year-old woman (PAT-6) with abdominal scars, including a midline abdominal incision, showed a preserved midline crossing artery. The planned single perforator deep inferior epigastric perforator flap was successfully applied to the contralateral perfusion area. ConclusionsPhotoacoustic tomography noninvasively visualizes the subcutaneous midline-crossing arterial networks. Understanding individual vascular variations can support preoperative planning and surgical indication of abdominal flaps, especially in patients with postsurgical scars.

In vivo spatiotemporal characterizing diverse body transportation of optical labeled high immunity aluminium adjuvants with photoacoustic tomography

Vaccine development requires high-resolution, in situ, and visual adjuvant technology. To address this need, this work proposed a novel adjuvant labeling that involved indocyanine green (ICG) and bovine serum albumin (BSA) with self-assembled aluminium adjuvant (Alum), which was called BSA@ICG@Alum. This compound exhibited excellent photoacoustic properties and has been confirmed its safety, biocompatibility, high antigen binding efficiency, and superior induction of immune response. Photoacoustic tomography (PAT) tracked the distribution of Alum in lymph nodes (LNs) and lymphatic vessels in real time after diverse injection modalities. The non-invasive imaging approach revealed that BSA@ICG@Alum was transported to the draining LNs 60 min after intramuscular injection and to distal LNs within 30 min after lymph node injection. In conclusion, PAT enabled real-time three-dimensional and quantitative visualization, thus offering a powerful tool for advancing vaccine design by providing critical insights into adjuvant transport and immune system activation.

Glutathione-responsive biodegradable nanohybrid for cancer photoacoustic imaging and gas-assisted photothermal therapy

Photothermal therapy (PTT), particularly in the near-infrared-II (NIR-II) range, has attracted widespread attention over the past years. However, the accompanied inflammatory responses can result in undesirable side effects and contribute to treatment ineffectiveness. Herein, we introduced a novel biodegradable nanoplatform (CuS/HMON-PEG) capable of PTT and hydrogen sulfide (H2S) generation, aimed at modulating inflammation for improved cancer treatment outcomes. The embedded ultrasmall copper sulphide (CuS) nanodots (1–2 nm) possessed favorable photoacoustic imaging (PAI) and NIR-II photothermal capabilities, rendering CuS/HMON-PEG an ideal phototheranostic agent. Upon internalization by 4T1 cancer cells, the hollow mesoporous organosilica nanoparticle (HMON) component could react with the overproduced glutathione (GSH) to produce H2S. In addition to the anticipated photothermal tumor ablation and H2S-induced mitochondrial dysfunction, the anti-inflammatory regulation was also been demonstrated by the downregulation of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1beta (IL-1β). More importantly, the modulation of inflammation also promoted wound healing mediated by PTT. This work not only presents a H2S-based nanomodulator to boost NIR-II PTT but also provides insights into the construction of novel organic/inorganic hybrid nanosystems.

An Oxidative Stress Nano-Amplifier for Improved Tumor Elimination and Combined Immunotherapy.

Amplifying oxidative stress to disrupt intracellular redox homeostasis can accelerate tumor cell death. In this work, an oxidative stress amplifier (PP@T) is prepared for enhanced tumor oxidation therapy to reduce tumor growth and metastases. The nano-amplifier has been successfully constructed by embedding MTH1 inhibitor (TH588) in the PDA-coated porphyrin metal-organic framework PCN-224. The controllable-released TH588 is demonstrated from pores can hinder MTH1-mediated damage-repairing process by preventing the hydrolysis of 8-oxo-dG, thereby amplifying oxidative stress and exacerbating the oxidative DNA damage induced by the sonodynamic therapy of PP@T under ultrasound irradiation. Furthermore, PP@T can effectively induce immunogenic cell death to trigger systemic anti-tumor immune response. When administered in combination with immune checkpoint blockade, PP@T not only impedes the progression of the primary tumor but also achieves obvious antimetastasis in breast cancer murine models, including orthotopic and artificial whole-body metastasis models. Furthermore, the nanoplatform also provides photoacoustic imaging for in vivo treatment guidance. In conclusion, by amplifying oxidative stress and reactive oxygen species sensitized immunotherapy, this image-guided nanosystem shows potential for highly specific, effective combined therapy against tumor cells with negligible side-effects to normal cells which will provide a new insight for precise tumor treatment.

Multi-focus Image Fusion via Blind Deconvolution and Registration based on Photoacoustic Microscopy

Abstract Optical resolution photoacoustic microscopy (OR-PAM), which can present the microstructure of biological tissues is useful in the disease diagnosis. However, conventional OR-PAM can only obtain images with high resolution in a narrow range of depths around the focal plane. In this study, we proposed a multi-focus photoacoustic image fusion method based on the blind deconvolution. This method is divided into two steps. First, we used the method of blind deconvolution to obtain an approximate point spread function (PSF) for each photoacoustic images obtained from multiple layers, and then got the corresponding deblurred photoacoustic images. Second, we used the method of multi-focus images registration and fusion to accurately align the multi-focus photoacoustic images and effectively fuse the features of different images. Finally, the proposed method was applied to process the photoacoustic images obtained from photoacoustic imaging experiments on ants with irregular morphology using fast controllable confocal focus PAM (FC-PAM). The results show that our method improves the quality of photoacoustic images, and can quickly obtain multi-focus fused photoacoustic images with high resolution. It indicates that the proposed multi-focus photoacoustic image fusion method based on FC-PAM has great potential in fast imaging of living biological tissues at multiple imaging depths.

Ex vivo human teeth imaging with various photoacoustic imaging systems.

Dental caries cause pain and if not diagnosed, it may lead to the loss of teeth in extreme cases. Dental X-ray imaging is the gold standard for caries detection; however, it cannot detect hidden caries. In addition, the ionizing nature of X-ray radiation is another concern. Hence, other alternate imaging modalities like photoacoustic (PA) imaging are being explored for dental imaging. Here, we demonstrate the feasibility of acoustic resolution photoacoustic microscopy (ARPAM) to image a tooth with metal filling, circular photoacoustic computed tomography (cPACT) to acquire images of teeth with caries and pigmentation, and linear array-based photoacoustic imaging (lPACT) of teeth with caries and pigmentation. The cavity measured with lPACT imaging is compared with the X-ray computed tomography image. The metal filling and its boundaries are clearly seen in the ARPAM image. cPACT images at 1064 nm were a better representative of the tooth surface compared to the images acquired at 532 nm. It was possible to detect the cavities present in the dentine when lPACT imaging was used. The PA signal from the pigmented caries on the lateral surface (occlusion view) of the tooth was high when imaged using the lPACT system.