Fluorescence and photoacoustic (FL/PA) dual-modal probe: Responsive to reactive oxygen species (ROS) for atherosclerotic plaque imaging.

Accurate and early detection of atherosclerosis (AS) is imperative for their effective treatment. However, fluorescence probes for efficient diagnosis of AS often encounter insufficient deep tissue penetration, which hinders the reliable assessment of plaque vulnerability. In this work, a reactive oxygen species (ROS) activated near-infrared (NIR) fluorescence and photoacoustic (FL/PA) dual model probe TPA-QO-B is developed by conjugating two chromophores (TPA-QI and O-OH) and ROS-specific group phenylboronic acid ester. The incorporation of ROS-specific group not only induces blue shift in absorbance, but also inhibits the ICT process of TPA-QO-OH, resulting an ignorable initial FL/PA signal. ROS triggers the convertion of TPA-QO-B to TPA-QO-OH, resulting in the concurrent amplification of FL/PA signal. The exceptional selectivity of TPA-QO-B towards ROS makes it effectively distinguish AS mice from the healthy. The NIR emission can achieve a tissue penetration imaging depth of 0.3 cm. Moreover, its PA775 signal possesses the capability to penetrate tissues up to a thickness of 0.8 cm, ensuring deep in vivo imaging of AS model mice in early stage. The ROS-triggered FL/PA dual signal amplification strategy improves the accuracy and addresses the deep tissue penetration problem simultaneously, providing a promising tool for in vivo tracking biomarkers in life science and preclinical applications.

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.

Nanoprobe Based on Novel NIR-II Quinolinium Cyanine for Multimodal Imaging.

NIR-II imaging has the advantages of high sensitivity, spatiotemporal resolution, and high penetration depth, thereby serving as a potential alternative to conventional imaging methods. Herein, a novel NIR-II dye IR-1010 (λex/λem = 1010/1058 nm) is reported with high quantum yield (3.08%) and good stability, by incorporating p-methoxyphenyl groups into a quinolinium cyanine dye. Then a multifunctional nanoprobe, termed IUFP NPs, is developed by the incorporation of upconversion (UC) nanoparticles (NPs), perfluoro-15-crown-5-ether (PFCE), and IR-1010, to display the novel performance of multimodal imaging. Under the single-wavelength excitation (980 nm), IUFP NPs simultaneously emit the NIR-II fluorescence of IR-1010 and visible UC luminescence of UCNPs, and thus realize the UC imaging for cells, and NIR-II fluorescence/photoacoustic/19F magnetic resonance imaging for blood vessels, lymph nodes and tumor in mice. This work affords a novel approach to NIR-II dyes and a general strategy for the design of multimodal imaging probes.

Performance evaluation of image co-registration methods in photoacoustic mesoscopy of the vasculature.

Objective:The formation of functional vasculature in solid tumours enables delivery of oxygen and nutrients, and is vital for effective treatment with chemotherapeutic agents. Longitudinal characterisation of vascular networks can be enabled using mesoscopic photoacoustic imaging, but requires accurate image co-registration to precisely assess local changes across disease development or in response to therapy. Co-registration in photoacoustic imaging is challenging due to the complex nature of the generated signal, including the sparsity of data, artefacts related to the illumination/detection geometry, scan-to-scan technical variability, and biological variability, such as transient changes in perfusion. To better inform the choice of co-registration algorithms, we compared five open-source methods, in physiological and pathological tissues, with the aim of aligning evolving vascular networks in tumours imaged over growth at different time-points.Approach:Co-registration techniques were applied to 3D vascular images acquired with photoacoustic mesoscopy from murine ears and breast cancer patient-derived xenografts, at a fixed time-point and longitudinally. Images were pre-processed and segmented using an unsupervised generative adversarial network. To compare co-registration quality in different settings, pairs of fixed and moving intensity images and/or segmentations were fed into five methods split into the following categories: affine intensity-based using 1)mutual information (MI) or 2)normalised cross-correlation (NCC) as optimisation metrics, affine shape-based using 3)NCC applied to distance-transformed segmentations or 4)iterative closest point algorithm, and deformable weakly supervised deep learning-based using 5)LocalNet co-registration. Percent-changes in Dice coefficients, surface distances, MI, structural similarity index measure and target registration errors were evaluated.Main results:Co-registration using MI or NCC provided similar alignment performance, better than shape-based methods. LocalNet provided accurate co-registration of substructures by optimising subfield deformation throughout the volumes, outperforming other methods, especially in the longitudinal breast cancer xenograft dataset by minimising target registration errors.Significance:We showed the feasibility of co-registering repeatedly or longitudinally imaged vascular networks in photoacoustic mesoscopy, taking a step towards longitudinal quantitative characterisation of these complex structures. These tools open new outlooks for monitoring tumour angiogenesis at the meso-scale and for quantifying treatment-induced co-localised alterations in the vasculature.

Identification of the Vulnerability of Atherosclerotic Plaques by a Photoacoustic/Ultrasonic Dual-Modal cRGD Nanomolecular Probe.

Objective: To explore the feasibility of using cRGD-GNR-PFP-NPs to assess plaque vulnerability in an atherosclerotic plaque mouse model by dual-modal photoacoustic/ultrasonic imaging. Methods: A nanomolecular probe containing gold nanorods (GNRs) and perfluoropentane (PFP) coated with the cyclic Arg-Gly-Asp (cRGD) peptide were prepared by double emulsion solvent evaporation and carbodiimide methods. The morphology, particle size, potential, cRGD conjugation and absorption features of the nanomolecular probe were characterized, along with its in vitro phase transformation and photoacoustic/ultrasonic dual-modal imaging properties. In vivo fluorescence imaging was used to determine the distribution of cRGD-GNR-PFP-NPs in vivo in apolipoprotein E-deficient (ApoE-/-) atherosclerotic plaque model mice, the optimal imaging time was determined, and photoacoustic/ultrasonic dual-modal molecular imaging of integrin αvß3 expressed in atherosclerotic plaques was performed. Pathological assessments verified the imaging results in terms of integrin αvß3 expression and plaque vulnerability. Results: cRGD-GNR-PFP-NPs were spherical with an appropriate particle size (average of approximately 258.03±6.75 nm), a uniform dispersion, and a potential of approximately -9.36±0.53 mV. The probe had a characteristic absorption peak at 780~790 nm, and the surface conjugation of the cRGD peptide reached 92.79%. cRGD-GNR-PFP-NPs were very stable in the non-excited state but very easily underwent phase transformation under low-intensity focused ultrasound (LIFU) and had excellent photoacoustic/ultrasonic dual-modal imaging capability. Mice fed a high-fat diet for 20 weeks had obvious hyperlipidemia with larger, more vulnerable plaques. These plaques could be specifically targeted by cRGD-GNR-PFP-NPs as determined by in vivo fluorescence imaging, and the enrichment of nanomolecular probe increased with the increasing of plaque vulnerability; the photoacoustic/ultrasound signals of the plaques in the high-fat group were stronger. The pathological assessments were in good agreement with the cRGD-GNR-PFP-NPs plaque accumulation, integrin αvß3 expression and plaque vulnerability results. Conclusion: A phase variant photoacoustic/ultrasonic dual-modal cRGD nanomolecular probe was successfully prepared and can be used to identify plaque vulnerability safely and effectively.

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.

Development of a Controllable Intelligent Drug Delivery System for Efficient Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a complex inflammatory disease of the joints, which is often accompanied by degeneration of articular cartilage and bone erosion, seriously affecting the quality of life and psychological state of patients. RA is difficult to be cured completely, and currently the main purpose of relief is through the use of anti-inflammatory and antirheumatic drugs, hormones, and biological agents. Tofacitib is a new type of small molecule inhibitor, which has a good effect in the treatment of RA. The current direct drug delivery method has serious side effects caused by the systemic distribution of the drug, so there is a need to develop an intelligent drug delivery system to realize precise treatment. In this work, tofacitib, gallic acid, targeted molecule folic acid, and Fe(III) were selected to assemble a novel type of artificial controllable nanodrug GF-TF. The self-photoacoustic/magnetic resonance imaging (self-PA/MRI) monitored the enrichment of GF-TF in the lesion in real-time, and artificially regulated the addition of deferoxamine (DFO) at the optimal enrichment. DFO strongly chelates Fe(III) in GF-TF and causes its structure to disintegrate gradually, and the self-PA/MRI signal of GF-TF became weaker while tofacitib began to be released, thus realizing the precise and artificially controlled release of the drug under the guidance of imaging. This nanodrug not only achieves efficient aggregation of drugs in inflamed joints, but also achieves real-time monitoring and precise control of drug release through self-PA/MRI, providing a new strategy for the precise treatment of RA.

Advancements in photoacoustic imaging for cancer diagnosis and treatment.

Photoacoustic imaging provides in vivo morphological and functional information about tumors within surrounding tissue. By integrating ultrasound guidance, this technique enables precise localization and characterization of tumors. Moreover, the introduction of targeted contrast agents has further expanded the capabilities of photoacoustic imaging in the realm of in vivo molecular imaging. These contrast agents facilitate enhanced molecular and cellular characterization of cancer, enabling detailed insights into the disease. This review aims to provide a concise summary of the extensive research conducted in the field of Photoacoustic imaging for cancer management. It encompasses the development of the technology, its applications in clinical settings, and the advancements made in molecular imaging. By consolidating and synthesizing the existing knowledge, this review contributes to a better understanding of the potential of photoacoustic imaging in cancer care. In conclusion, photoacoustic imaging has emerged as a non-ionizing and noninvasive modality with the ability to visualize tissue's optical absorption properties while maintaining ultrasound's spatial resolution. Its integration with targeted contrast agents has enhanced molecular and cellular characterization of cancer. This review serves as a succinct overview of the extensive research conducted in the field, shedding light on the potential of photoacoustic imaging in the management of cancer.

Optical Transmission in Single-Layer Brain Tissues under Different Optical Source Types: Modelling and Simulation.

The human brain is a complex organ controlling daily activity. Present technique models have mostly focused on multi-layer brain tissues, which lack understanding of the propagation characteristics of various single brain tissues. To better understand the influence of different optical source types on individual brain tissues, we constructed single-layer brain models and simulated optical propagation using the Monte Carlo method. Based on the optical simulation results, sixteen optical source types had different optical energy distributions, and the distribution in cerebrospinal fluid had obvious characteristics. Five brain tissues (scalp, skull, cerebrospinal fluid, gray matter, and blood vessel) had the same set of the first three optical source types with maximum depth, while white matter had a different set of the first three optical source types with maximum depth. Each brain tissue had different optical source types with the maximum and minimum full width at half maximum. The study on single-layer brain tissues under different optical source types lays the foundation for constructing complex brain models with multiple tissue layers. It provides a theoretical reference for optimizing the selection of optical source devices for brain imaging.

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.

Activatable Photoacoustic/Near-Infrared Probes for the Detection of Copper Ions of Cardiovascular Disease In Vivo and in Urine.

Copper ions, implicated in processes such as oxidative stress and inflammation, are believed to play a crucial role in cardiovascular disease, a prevalent and deadly disease. Despite this, current diagnostic methods fail to detect early stage cardiovascular disease or track copper ion accumulation, limiting our understanding of the disease's progression. Therefore, the development of noninvasive techniques to image copper ions in cardiovascular disease is urgently needed to enhance diagnostic precision and therapeutic strategies. In this study, we report the successful synthesis and application of a copper ion-activated photoacoustic probe, CS-Cu, which exhibits high sensitivity and selectivity toward copper ions both in vitro and in vivo. CS-Cu was able to noninvasively monitor the changes in copper ion levels and differentiate between different mice based on copper ions in urine. Furthermore, the probe demonstrated good photoacoustic stability and exhibited no significant toxicity in the mice. These findings suggest that CS-Cu could be a promising tool for early detection and monitoring of Cu2+ levels in vivo and urine, providing a new perspective on the role of copper ions in cardiovascular disease.

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.

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.

High performance filtering and high-sensitivity concentration retrieval of methane in photoacoustic spectroscopy utilizing deep learning residual networks.

A novel method is introduced to improve the detection performance of photoacoustic spectroscopy for trace gas detection. For effectively suppressing various types of noise, this method integrates photoacoustic spectroscopy with residual networks model which encompasses a total of 40 weighted layers. Firstly, this approach was employed to accurately retrieve methane concentrations at various levels. Secondly, the analysis of the signal-to-noise ratio (SNR) of multiple sets of photoacoustic spectroscopy signals revealed significant enhancement. The SNR was improved from 21 to 805, 52-962, 98-944, 188-933, 310-941, and 587-936 across the different concentrations, respectively, as a result of the application of the residual networks. Finally, further exploration for the measurement precision and stability of photoacoustic spectroscopy system utilizing residual networks was carried out. The measurement precision of 0.0626 ppm was obtained and the minimum detectable limit was found to be 1.47 ppb. Compared to traditional photoacoustic spectroscopy method, an approximately 46-fold improvement in detection limit and 69-fold enhancement in measurement precision were achieved, respectively. This method not only advances the measurement precision and stability of trace gas detection but also highlights the potential of deep learning algorithms in spectroscopy detection.

In vivo targeted-imaging of mitochondrial acidification in an aristolochic acid I-induced nephrotoxicity mouse model by a fluorescent/photoacoustic bimodal probe.

Aristolochic acid I (AAI), a natural compound in aristolochia type Chinese medicinal herb, is generally acknowledged to have nephrotoxicity, which may be associated with mitophagy. Mitophagy is a cellular process with important functions that drive AAI-induced renal injury. Mitochondrial pH is currently measured by fluorescent probes in cell culture, but existing probes do not allow for in situ imaging of AAI-induced mitophagy in vivo. We developed a ratiometric fluorescent/PA dual-modal probe with a silicon rhodamine fluorophore and a pH-sensitive hemicyanine dye covalently linked via a short chain to obtain a FRET type probe. The probe was used to measure AAI-mediated mitochondrial acidification in live cells and in vivo. The Förster resonance energy transfer (FRET)-mediated ratiometric and bimodal method can efficiently eliminate signal variability associated with the commonly used one-emission and single detection mode by ratiometric two channels of the donor and acceptor. The probe has good water-solubility and low molecular weight with two positively charged, facilitating its precise targeting into renal mitochondria, where the fluorescent/PA changes in response to mitochondrial acidification, enabling dynamic and semi-quantitative mapping of subtle changes in mitochondrial pH in AAI-induced nephrotoxicity mouse model for the first time. Also, the joint use of L-carnitine could mitigate the mitophagy in AAI-induced nephrotoxicity.

Molecular imaging nanoprobes and their applications in atherosclerosis diagnosis.

Molecular imaging has undergone significant development in recent years for its excellent ability to image and quantify biologic processes at cellular and molecular levels. Its application is of significance in cardiovascular diseases, particularly in diagnosing them at early stages. Atherosclerosis is a complex, chronic, and progressive disease that can lead to serious consequences such as heart strokes or infarctions. Attempts have been made to detect atherosclerosis with molecular imaging modalities. Not only do imaging modalities develop rapidly, but research of relevant nanomaterials as imaging probes has also been increasingly studied in recent years. This review focuses on the latest developments in the design and synthesis of probes that can be utilized in computed tomography, positron emission tomography, magnetic resonance imaging, ultrasound imaging, photoacoustic imaging and combined modalities. The challenges and future developments of nanomaterials for molecular imaging modalities are also discussed.

Could exhaled methane be used as a possible indicator for hemodynamic changes in trauma induced hemorrhagic shock? Scientific basis supported by a case study.

INTRODUCTION: Identification of severe blood loss and hemorrhagic shock in polytrauma patients poses a key challenge for trauma teams across the world, as there are just a few objective parameters, on which clinicians can rely. We investigated the relationship between exhaled air methane (CH4) concentration and blood loss in a polytrauma patient. Decreased blood flow in the superior mesenteric artery (SMA) is one of the first compensatory responses to blood loss. Gases produced by the anaerobic flora of the intestinal segment supplied by the SMA are the primary source of exhaled CH4, which diffuses through the intestinal microvessels into the circulation and is finally eliminated through the lungs. We hypothesized that diminution of exhaled CH4 indicates blood loss and tested our theory in a severely injured patient. METHODS: Exhaled CH4 concentrations of a severely injured patient were measured using a photoacoustic spectroscope (PAS) attached to the exhalation side of the breathing circuit. The primary objective was to investigate the relationship between exhaled CH4 and conventional indicators of hemorrhage including hemoglobin (Hb) levels, base deficit (BD) values and vital parameters (heart rate and systolic blood pressure) in the early phase of in-hospital care (first 4 h). RESULTS: A severely injured patient was admitted with unstable hemodynamic parameters and incomplete left lower limb amputation, (Injury Severity Score: 38, 74/36 mmHg, 76 bpm). At the time of arrival, considerably lower CH4 levels were detected (22,800 PAU) in the exhaled air. During the first 4 h fluid and massive blood resuscitation, the exhaled CH4 levels were continuously rising in parallel with Htc and Hb values. Corresponding to these changes, BD values displayed a decreasing tendency. DISCUSSION: Our study was conducted to characterize the changes in exhaled air CH4 concentration in response to hemorrhagic shock and to provide data on a viable clinical use of an experimental technique. According to our results, the real-time detection of exhaled air CH4 concentration is an applicable and promising technique for the early detection of bleeding and hemorrhagic shock in severely injured patients. Further research on large sample size and refinement of the PAS technique is required.

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-1ß). 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.

High-fidelity imaging of drug-induced acute gastritis by using a fluorescent and photoacoustic dual-modal probe with good stability in stomach acid.

In consideration of deep tissue imaging and signal fidelity, fluorescent-photoacoustic (PA) dual-modal probes are much more desirable. However, dual-modal imaging of gastritis using molecular probes remains a challenge due to the harsh gastric acid environment in the stomach. Based on the positive correlation between gastritis and cell viscosity, stomach acid-stable and viscosity-activated probes could potentially diagnose gastritis. As a proof of concept, herein, a fluorescent and photoacoustic dual-modal probe (named WSP-1) is revealed for the imaging of drug-induced acute gastritis in vivo. WSP-1 exhibits viscosity-dependent fluorescence emission and photoacoustic signals. A rotatable C-C single bond is incorporated into the D-π-A structure of WSP-1, which could facilitate the formation of the twisted intramolecular charge transfer (TICT) state in a low-viscosity environment (weak fluorescence/PA signal) and the intramolecular charge transfer (ICT) state in a high-viscosity environment (strong fluorescence/PA signal). WSP-1 has demonstrated the capability to target mitochondria and can be utilized to monitor the viscosity enhancement of cells during inflammation. Most importantly, WSP-1 exhibits good optical and structural stability in gastric acid. By leveraging these desirable features of WSP-1, we have achieved fluorescent and 3D photoacoustic in situ imaging of drug-induced acute gastritis following oral administration of WSP-1.

From Morphology to Therapeutic Strategies: Exploring New Applications of Ultrasound for Diabetic Peripheral Neuropathy Diagnosis and Management.

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes that can result in severe lower limb pain and amputation. Early detection and treatment of DPN are vital, but this condition is often missed due to a lack of symptoms and the insensitivity of testing methods. This article reviews various ultrasound imaging modalities in the direct and indirect evaluation of peripheral neuropathy. Moreover, how ultrasound-related therapeutic strategies are playing a role in clinical treatment is discussed. Finally, the application of innovative methodologies in the diagnosis of DPN, including ultrasound attenuation, photoacoustic imaging, and artificial intelligence, is described.