Therapy management and outcome of acute hydrocephalus secondary to intraventricular hemorrhage in adults.

BACKGROUND: Intraventricular hemorrhage (IVH) refers to bleeding within the brain's ventricular system, and hydrocephalus is a life-threatening complication of IVH characterized by increased cerebrospinal fluid accumulation in the ventricles resulting in elevated intracranial pressure. IVH poses significant challenges for healthcare providers due to the complexity of the underlying pathophysiology and lack of standardized treatment guidelines. Herein, we performed a systematic review of the treatment strategies for hydrocephalus secondary to IVH. METHODS: This systematic review was prospectively registered with PROSPERO (CRD42023450786). The search was conducted in PubMed, Cochrane Library, and Web of Science on July 15, 2023. We included original studies containing valid information on therapy management and outcome of hydrocephalus secondary to primary, spontaneous, and subarachnoid or intracranial hemorrhage following IVH in adults that were published between 2000 and 2023. Glasgow Outcome Scale (GOS) or modified Ranking Scale (mRS) scores during follow-up were extracted as primary outcomes. The risk of bias was assessed using the Newcastle-Ottawa Scale for Cohort Studies or Cochrane Risk of Bias 2.0 Tool. RESULTS: Two hundred and seven patients from nine published papers, including two randomized controlled trials, were included in the analysis. The GOS was used in five studies, while the mRS was used in four. Seven interventions were applied, including craniotomy for removal of hematoma, endoscopic removal of hematoma with/without endoscopic third ventriculostomy (ETV), traditional external ventricular drainage (EVD), and various combinations of EVD, lumbar drainage (LD), and intraventricular fibrinolysis (IVF). Endoscopic removal of hematoma was performed in five of nine studies. Traditional EVD had no obvious benefit compared with new management strategies. Three different combinations of EVD, LD, and IVF demonstrated satisfactory outcomes, although more studies are required to confirm their reliability. Removal of hematoma through craniotomy generated reliable result. Generally, endoscopic removal of hematoma with ETV, removal of hematoma through craniotomy, EVD with IVF, and EVD with early continuous LD were useful. CONCLUSION: EVD is still crucial for the management of IVH and hydrocephalus. Despite a more reliable result from the removal of hematoma through craniotomy, a trend toward endoscopic approach was observed due to a less invasive profile.

VX-765 Alleviates Circadian Rhythm Disorder in a Rodent Model of Traumatic Brain Injury Plus Hemorrhagic Shock and Resuscitation.

Severe traumatic brain injury (TBI) can result in persistent complications, including circadian rhythm disorder, that substantially affect not only the injured people, but also the mood and social interactions with the family and the community. Pyroptosis in GFAP-positive astrocytes plays a vital role in inflammatory changes post-TBI. We determined whether VX-765, a low molecular weight caspase-1 inhibitor, has potential therapeutic value against astrocytic inflammation and pyroptosis in a rodent model of TBI plus hemorrhagic shock and resuscitation (HSR). A weight-drop plus bleeding and refusion model was used to establish traumatic exposure in rats. VX-765 (50 mg/kg) was injected via the femoral vein after resuscitation. Wheel-running activity was assessed, brain magnetic resonance images were evaluated, the expression of pyroptosis-associated molecules including cleaved caspase-1, gasdermin D (GSDMD), and interleukin-18 (IL-18) in astrocytes in the region of anterior hypothalamus, were explored 30 days post-trauma. VX-765-treated rats had significant improvement in circadian rhythm disorder, decreased mean diffusivity (MD) and mean kurtosis (MK), increased fractional anisotropy (FA), an elevated number and branches of astrocytes, and lower cleaved caspase-1, GSDMD, and IL-18 expression in astrocytes than TBI + HSR-treated rats. These results demonstrated that inhibition of pyroptosis-associated astrocytic activations in the anterior hypothalamus using VX-765 may ameliorate circadian rhythm disorder after trauma. In conclusion, we suggest that interventions targeting caspase-1-induced astrocytic pyroptosis by VX-765 are promising strategies to alleviate circadian rhythm disorder post-TBI.

HBOT has a better cognitive outcome than NBH for patients with mild traumatic brain injury: A randomized controlled clinical trial.

BACKGROUND: Normobaric hyperoxia (NBH) and hyperbaric oxygen therapy (HBOT) are effective treatment plan for traumatic brain injury (TBI). The aim of this study was to compare cognitive outcome after mild TBI between NBH and HBOT so as to provide a more suitable treatment strategy for patients with mild TBI. METHODS: A prospective research was conducted between October 2017 and March 2023, enrolling patients with mild TBI (Glasgow coma scale score: 13-15 points) within 24 hours of injury in Cangzhou Central Hospital. Patients were randomized into 3 groups: group control (C), group NBH and group HBOT. The patients in HBOT group received hyperbaric oxygen therapy in high pressure oxygen chamber and patients in NBH group received hyperbaric oxygen therapy. at 0 minute before NBH or HBOT (T1), 0 minute after NBH or HBOT (T2) and 30 days after NBH or HBOT (T3), level of S100ß, NSE, GFAP, HIF-1α, and MDA were determined by ELISA. At the same time, the detection was performed for MoCA and MMSE scores, along with rSO2. RESULTS: The results showed both NBH and HBOT could improve the score of MoCA and MMSE, as well as the decrease the level of S100ß, NSE, GFAP, HIF-1α, MDA, and rSO2 compared with group C. Furthermore, the patients in group HBOT have higher score of MoCA and MMSE and lower level of S100ß, NSE, GFAP, HIF-1α, MDA, and rSO2. CONCLUSION: Both NBH and HBOT can effectively improve cognitive outcome for patients with mild TBI by improving cerebral hypoxia and alleviating brain injury, while HBOT exert better effect than NBH.

CORM-3 alleviates the intestinal injury in a rodent model of hemorrhage shock and resuscitation: roles of GFAP-positive glia.

Hemorrhagic shock and resuscitation (HSR) can induce severe intestinal damages, thereby leading to sepsis and long-term complications including dysbacteriosis and pulmonary injury. The NOD-like receptor protein 3 (NLRP3) inflammasome facilitates inflammation-associated cell recruitment in the gastrointestinal tract, and participates in many inflammatory bowel diseases. Previous studies have shown that exogenous carbon monoxide (CO) exerts neuroprotective effects against pyroptosis after HSR. We aimed to investigate whether carbon monoxide-releasing molecules-3 (CORM-3), an exogenous CO compound, could attenuate HSR-induced intestinal injury and the potential underlying mechanism.Rats were subjected to a HSR model by bleeding and re-infusion. Following resuscitation, 4 mg/kg of CORM-3 was administered intravenously into femoral vein. At 24 h and 7 d after HSR modeling, the pathological changes in intestinal tissues were evaluated by H&E staining. The intestinal pyroptosis, glial fibrillary acidic protein (GFAP)-positive glial pyroptosis, DAO (diamine oxidase) content, intestine tight junction proteins including zonula occludens-1 (ZO-1) and claudin-1 were further detected by immunofluorescence, western blot and chemical assays at 7 d after HSR. CORM-3 administration led to significantly mitigated HSR-induced intestinal injury, aggravation of intestinal pyroptosis indicated by cleaved caspase-1, IL-1ß and IL-18, upregulation of GFAP-positive glial pyroptosis, decreased intensity of ZO-1 and claudin-1 in the jejunum, and increased of DAO in the serum. Nigericin, an agonist of NLRP3, significantly reversed the protective effects of CORM-3. CORM-3 alleviates the intestinal barrier dysfunction in a rodent model of HSR, and the potential mechanism may be associated with inhibition of NLRP3-associated pyroptosis. CORM-3 administration could be a promising therapeutic strategy for intestinal injury after hemorrhagic shock.

In vivo characterization and analysis of glioblastoma at different stages using multiscale photoacoustic molecular imaging.

Simultaneous spatio-temporal description of tumor microvasculature, blood-brain barrier, and immune activity is pivotal to understanding the evolution mechanisms of highly aggressive glioblastoma, one of the most common primary brain tumors in adults. However, the existing intravital imaging modalities are still difficult to achieve it in one step. Here, we present a dual-scale multi-wavelength photoacoustic imaging approach cooperative with/without unique optical dyes to overcome this dilemma. Label-free photoacoustic imaging depicted the multiple heterogeneous features of neovascularization in tumor progression. In combination with classic Evans blue assay, the microelectromechanical system based photoacoustic microscopy enabled dynamic quantification of BBB dysfunction. Concurrently, using self-fabricated targeted protein probe (αCD11b-HSA@A1094) for tumor-associated myeloid cells, unparalleled imaging contrast of cells infiltration associated with tumor progression was visualized by differential photoacoustic imaging in the second near-infrared window at dual scale. Our photoacoustic imaging approach has great potential for tumor-immune microenvironment visualization to systematically reveal the tumor infiltration, heterogeneity, and metastasis in intracranial tumors.

Spautin-1 Protects Against Mild TBI-Induced Anxiety-Like Behavior in Mice via Immunologically Silent Apoptosis.

Anxiety is reportedly one of the most common mental changes after traumatic brain injury (TBI). Perineuronal nets (PNNs) produced by astrocytes in the lateral hypothalamus (LHA) that surround gamma-aminobutyric acid-ergic (GABAergic) neurons have been associated with anxiety. The potent anti-tumor effects of Spautin-1, a novel autophagy inhibitor, have been documented in malignant melanoma; moreover, the inhibition of autophagy is reported to mitigate anxiety disorders. However, little is known about the ability of spautin-1 to alleviate anxiety. In this study, we sought to investigate whether spautin-1 could alleviate anxiety-like behaviors post-TBI by reducing the loss of PNNs in the LHA. A mild TBI was established in mice through Feeney's weight-drop model. Then, Spautin-1 (20 mmol/2 µl) was immediately administered into the left lateral ventricle. Behavioral and pathological changes were assessed at 24 h, 7 days, 30 days, 31 days and 32 days after TBI by the neurological severity scores (NSS), open field test (OFT), elevated plus-maze (EPM) test, western blot, immunofluorescence assays and electron microscopy. Spautin-1 significantly reversed TBI-induced decreased time in the central zone during OFT and in the open-arm during the EPM test. Spautin-1 also increased PNNs around GABAergic neurons indicated by WFA- plus GAD2- positive A2-type astrocytes and attenuated M1-type microglia in the LHA 32 days after TBI compared to TBI alone. Moreover, compared to mice that only underwent TBI, spautin-1 downregulated autophagic vacuoles, abnormal organelles, the expression of Beclin 1, USP13, phospho-TBK1, and phospho-IRF3 and upregulated the levels of cleaved caspase-3, -7 and -9, but failed to increase TUNEL-positive cells in the LHA at 24 h. Spautin-1 alleviated anxiety-like behavior in mice exposed to mild TBI; this protective mechanism may be associated with decreased PNNs loss around GABAergic neurons via immunologically silent apoptosis induced by the caspase cascade.

Subanesthetic dose of S-ketamine improved cognitive dysfunction via the inhibition of hippocampal astrocytosis in a mouse model of post-stroke chronic stress.

Post-stroke chronic stress (PSCS) is generally associated with the poorer recovery and more pronounced cognitive dysfunction. Recent evidence has implied that S-ketamine can reduce suicidal ideation in treatment-resistant depression. In this current study, we aimed to investigate whether the administration of S-ketamine ameliorated cognitive deficits under PSCS conditions, which was established by a model combining middle cerebral artery occlusion (MCAO) and chronic restraint stress. Our data suggested that mice exposed to PSCS exhibited depression-like behavior and cognitive impairment, which coincided with astrocytosis as indicated by increased GFAP-positive cells and impairment of long-time potentiation (LTP) in the hippocampal CA1. Subanesthetic doses (10 mg/kg) of S-ketamine have significantly mitigated depression-like behaviors, cognitive deficits and LTP impairment, reduced astrocytosis, excessive GABA, and inflammatory factors, including NLRP3 and IL-18 in astrocytes in the CA1. Besides, neuroprotective effects induced by S-ketamine administration were found in vitro but could be partially reversed by an agonist of the NLRP3 nigericin. Our current data also suggests that the subanesthetic doses of S-ketamine improved cognitive dysfunction via the inhibition of hippocampal astrocytosis in a mouse model of PSCS.

IL-18BP Alleviates Anxiety-Like Behavior Induced by Traumatic Stress via Inhibition of the IL-18R-NLRP3 Signaling Pathway in a Mouse Model of Hemorrhagic Shock and Resuscitation.

Psychological distress and posttraumatic stress, including anxiety, severely influence life quality. Previously, we reported that interleukin-18 (IL-18) was involved in pyroptosis-induced emotional changes in a rodent model of hemorrhagic shock and resuscitation (HSR). Here, we aimed to continue our investigation on the role of IL-18 binding protein (IL-18BP), which exhibits excellent anti-inflammatory effects as an IL-18 negative regulator. Mice were administered with an intraperitoneal injection of IL-18BP after HSR exposure and anxiety-like behavior was examined using the open-field test and elevated plus maze test. Moreover, the following variables post-HSR were measured: (1) the activation of astrocytes; (2) pyroptosis-associated factors including cleaved caspase-1, GSDMD, IL-18; (3) the roles of IL-18 receptor (IL-18R)-NOD-like receptor pyrin domain-containing-3 (NLRP3) signal with the application of the NLRP3 specific agonist or astrocyte-specific NLRP3 knockout mice. IL-18BP administration remarkably alleviated HSR-induced anxiety-like behavior, astrocytic activation, and increases in pyroptosis-associated factors, while NLRP3 agonist nigericin partially reversed IL-18BP-induced neuroprotective effects. Astrocyte-specific NLRP3 knockout mice exhibited relatively less anxiety-like behavior. Similarly, IL-18BP exhibited an anti-pyroptosis effect in astrocytes in an in vitro model of low oxygen-glucose deprivation. These findings offer unique perspectives on HSR-induced posttraumatic stress and indicate that inhibition of IL-18R-NLRP3 signal via IL-18BP can attenuate astrocytic activation and pyroptosis, broadening the therapeutic landscape for patients with psychological distress and posttraumatic stress.

STING mediates neuroinflammatory response by activating NLRP3-related pyroptosis in severe traumatic brain injury.

Long-term neurological deficits after severe traumatic brain injury (TBI), including cognitive dysfunction and emotional impairments, can significantly impair rehabilitation. Glial activation induced by inflammatory response is involved in the neurological deficits post-TBI. This study aimed to investigate the role of the stimulator of interferon genes (STING)-nucleotide-binding oligomerization domain-like receptor pyrin domain-containing-3 (NLRP3) signaling in a rodent model of severe TBI. Severe TBI models were established using weight-drop plus blood loss reinfusion model. Selective STING agonist ADU-S100 or antagonist C-176 was given as a single dose after modeling. Further, NLRP3 inhibitor MCC950 or activator nigericin, or caspase-1 inhibitor VX765, was given as an intracerebroventricular injection 30 min before modeling. After that, a novel object recognition test, open field test, force swimming test, western blot, and immunofluorescence assays were used to assess behavioral and pathological changes in severe TBI. Administration of C-176 alleviated TBI-induced cognitive dysfunction and emotional impairments, neuronal loss, and inflammatory activation of glia cells. However, the administration of STING agonist ADU-S100 exacerbated TBI-induced behavioral and pathological changes. In addition, STING activation exacerbated pyroptosis-associated neuroinflammation via promoting glial activation, as evidenced by increased cleaved caspase-1 and GSDMD N-terminal expression. In contrast, the administration of C-176 showed anti-pyroptotic effects. The neuroprotective effects of C-176 were partially reversed by the NLRP3 activator, nigericin. Collectively, glial STING is responsible for neuroinflammation post-TBI. However, pharmacologic inhibition of STING led to a remarkable improvement of neuroinflammation partly through suppressing NLRP3 signaling. The STING-NLRP3 signaling is a potential therapeutic target in TBI-induced neurological dysfunction.

Esketamine alleviates postoperative cognitive decline via stimulator of interferon genes/ TANK-binding kinase 1 signaling pathway in aged rats.

BACKGROUND: Postoperative cognitive decline (POCD) is a common complication after surgery and anesthesia among the elderly. Yet the potential mechanism of POCD remains ambiguous, with limited therapeutic measures currently available. Ketamine has been reported to attenuate POCD after cardiac surgery. Herein, we tried to determine the effect of esketamine (the S-enantiomer of ketamine) on POCD and the possible molecular mechanisms. METHODS: We investigated the effects of esketamine (10 mg/kg) on POCD using an exploratory laparotomy model in aged SD rats (24 months). Open field, novel object recognition, and morris water maze tests were performed on day 30 post-surgery. 24 h or 30 d post-surgery, brain tissue from the hippocampus and ventromedial prefrontal cortex (vmPFC) was harvested and subjected to histopathology and molecular biology analysis. During the in vitro experiment, primary astrocytes from the hippocampus and vmPFC were exposed to lipopolysaccharide (LPS) to investigate the pathological changes in astrocytes during the process of POCD. RESULTS: Our results indicated that exploratory laparotomy could induce significant cognitive and memory decline, accompanied by A2-type astrocytes phenotype loss and increased expression of neuron Aß-42, astrocytes GABA, stimulator of interferon genes (STING) and TANK-binding kinase 1 (TBK1). In addition, LPS exposure significantly decreased the mitochondrial membrane potential and upregulated the level of pyroptosis-associated proteins, including cleaved caspase-1 and IL-18. Notably, treatment with esketamine reversed these abnormalities in vivo and vitro. However, ADU-S100, a special STING activator, suppressed the protective effects of esketamine to a certain extent. Finally, C-176, an antagonist of STING, further enhanced the protective effects of esketamine against POCD. CONCLUSIONS: Findings of our study suggest that esketamine can alleviate surgery-induced POCD in rats via inhibition of the STING/TBK1 signaling pathway.

Improving the adversarial transferability with relational graphs ensemble adversarial attack.

In transferable black-box attacks, adversarial samples remain adversarial across multiple models and are more likely to attack unknown models. From this view, acquiring and exploiting multiple models is the key to improving transferability. For exploiting multiple models, existing approaches concentrate on differences among models but ignore the underlying complex dependencies. This exacerbates the issue of unbalanced and inadequate attacks on multiple models. To this problem, this paper proposes a novel approach, called Relational Graph Ensemble Attack (RGEA), to exploit the dependencies among multiple models. Specifically, we redefine the multi-model ensemble attack as a multi-objective optimization and create a sub-optimization problem to compute the optimal attack direction, but there are serious time-consuming problems. For this time-consuming problem, we define the vector representation of the model, extract the dependency matrix, and then equivalently simplify the sub-optimization problem by utilizing the dependency matrix. Finaly, we theoretically extend to investigate the connection between RGEA and the traditional multiple gradient descent algorithm (MGDA). Notably, combining RGEA further enhances the transferability of existing gradient-based attacks. The experiments using ten normal training models and ten defensive models on the labeled face in the wild (LFW) dataset demonstrate that RGEA improves the success rate of white-box attacks and further boosts the transferability of black-box attacks.

Online Learning Algorithm for Distributed Convex Optimization With Time-Varying Coupled Constraints and Bandit Feedback.

This article focuses on multiagent distributed-constrained optimization problems in a dynamic environment, in which a group of agents aims to cooperatively optimize a sum of time-changing local cost functions subject to time-varying coupled constraints. Both the local cost functions and constraint functions are unrevealed to an individual agent until an action is submitted. We first investigate a gradient-feedback scenario, where each agent can access both values and gradients of cost functions and constraint functions owned by itself at the chosen action. Then, we design a distributed primal-dual online learning algorithm and show that the proposed algorithm can achieve the sublinear bounds for both the regret and constraint violations. Furthermore, we extend the gradient-feedback algorithm to a gradient-free setup, where an individual agent has only attained the values of local cost functions and constraint functions at two queried points near the selected action. We develop a bandit version of the previous method and give the explicitly sublinear bounds on the expected regret and expected constraint violations. The results indicate that the bandit algorithm can achieve almost the same performance as the gradient-feedback algorithm under wild conditions. Finally, numerical simulations on an electric vehicle charging problem demonstrate the effectiveness of the proposed algorithms.

Instant Ultrasound-Evoked Precise Nanobubble Explosion and Deep Photodynamic Therapy for Tumors Guided by Molecular Imaging.

Nanobubbles (NBs) have recently gained interest in cancer imaging and therapy due to the fact that nanoparticles with the size range of 1-1000 nm can extravasate into permeable tumor types through the enhanced permeability and retention (EPR) effect. However, the therapeutic study of NBs was only limited to drug delivery or cavitation. Herein, we developed ultrasound-evoked massive NB explosion to strikingly damage the surrounding cancer. The dual-function agent allows synergistic mechanical impact and photodynamic therapy of the tumors and enhances imaging contrast. Moreover, the mechanical explosion improved the light delivery efficiency in biological tissue to promote the effect of photodynamic therapy. Under ultrasound/photoacoustic imaging guidance, we induced on-the-spot bubble explosion and photodynamic therapy of tumors at a depth of centimeters in vivo. The mechanical impact of the explosion can enhance delivery of the photosensitizers. Ultrasound explicitly revealed the cancer morphology and exhibited fast NB perfusion. Generated mechanical damage and release of mixture agents demonstrated remarkable synergetic anticancer effects on deep tumors. This finding also offers a new approach and insight into treating cancers.

In vivo photoacoustic imaging dynamically monitors the structural and functional changes of ischemic stroke at a very early stage.

Ischemic stroke (IS) is one of the leading causes of death and accounts for 85% of stroke cases. Since the symptoms are not obvious, diagnosis of IS, particularly at an early stage, is a great challenge. Photoacoustic imaging combines high sensitivity of optical imaging and fine resolution of ultrasonography to non-invasively provide structural and functional information of IS. Methods: We adopted three rapid photoacoustic imaging systems with varying characteristics, including a portable handheld photoacoustic system, high-sensitivity bowl-shaped array photoacoustic computed tomography (PACT), and high-resolution photoacoustic microscopy (PAM) to assess the stereoscopic and comprehensive pathophysiological status of IS at an early stage. Two representative models of IS, referring to photothrombosis and middle cerebral artery occlusion (MCAO) models, were established to verify the feasibility of photoacoustic imaging detection. Results: Non-invasive, rapid PACT of the IS model in mouse provided structural information of the brain lesion, achieving early disease identification (5 min after the onset of disease). Moreover, it was able to dynamically reflect disease progression. Quantitative high-resolution PAM allowed observation of pathological changes in the microvascular system of mouse brain. In terms of functional imaging, significant differences in oxygen saturation (sO2) levels between infarcted and normal areas could be observed by PACT, permitting effective functional parameters for the diagnosis of IS. Conclusions: We used PACT to perform full-view structural imaging and functional imaging of sO2 in IS at the macroscopic level, and then observed the microvascular changes in the infarcted area at the microscopic level by using PAM. This work may provide new tools for the early diagnosis of IS and its subsequent complications as well as assessment of disease progression.

Label-Free Visualization of Early Cancer Hepatic Micrometastasis and Intraoperative Image-Guided Surgery by Photoacoustic Imaging.

The detection of cancer micrometastasis for early diagnosis and treatment poses a great challenge for conventional imaging techniques. The aim of our study was to evaluate the performance of photoacoustic imaging (PAI) in detecting hepatic micrometastases from melanoma at a very early stage and in aiding tumor resection by intraoperative guidance. Methods: In vivo studies were performed by following protocols approved by the Ethical Committee for Animal Research at Xiamen University. First, a mouse model of B16 melanoma metastatic to the liver (n = 10) was established to study the development of micrometastases in vivo. Next, the mice were imaged by a scalable PAI instrument, ultrasound, 9.4-T high-resolution MRI, PET/CT, and bioluminescence imaging. PAI scans acquired with optical wavelengths of 680-850 nm were kept spectrally unmixed by using a linear least-squares method to differentiate various components. Differences in signal-to-background ratios among different modalities were determined with the 2-tailed paired t test. The diagnostic results were assessed with histologic examination. Excised liver samples from patients diagnosed with hepatic cancer were also examined to identify the tumor boundaries. Surgical removal of metastatic melanoma was precisely guided in vivo by the portable PAI system. Results: PAI was able to detect metastases as small as approximately 400 µm at a depth of up to 7 mm in vivo-a size that is smaller than can be detected with ultrasound and MRI. The tumor-to-liver ratio for PAI at 8 d (4.2 ± 0.2, n = 6) and 14 d (9.2 ± 0.4, n = 5) was significantly higher than for PET/CT (1.8 ± 0.1, n = 5, and 4.5 ± 0.2, n = 5, respectively; P < 0.001 for both). Functional PAI revealed dynamic oxygen saturation changes during tumor growth. The limit of detection was approximately 219 cells/µL in vitro. We successfully performed intraoperative PAI-guided surgery in vivo using the portable PAI system. Conclusion: Our findings offer a rapid and effective complementary clinical imaging application to noninvasively detect micrometastases and guide intraoperative resection.

In vivo dual-scale photoacoustic surveillance and assessment of burn healing.

Accurate diagnoses of superficial and deep dermal burns are difficult to make even by experienced investigators due to slight differences in dermis damage. Many imaging technologies have been developed to improve the burn depth assessment. But these imaging tools have limitations in deep imaging or resolving ability. Photoacoustic imaging is a hybrid modality combining optical and ultrasound imaging that remains high resolution in deep imaging depth. In this work, we used dual-scale photoacoustic imaging to noninvasively diagnose burn injury and monitor the burn healing. Real-time PACT provided cross-sectional and volumetric images of the burn region. High-resolution PAM allowed for imaging of angiogenesis on the hyperemic ring. A long-term surveillance was also performed to assess the difference between the two damage degrees of burn injuries. Our proposed method suggests an effective tool to diagnose and monitor burn injury.

Ag-Hybridized plasmonic Au-triangular nanoplates: highly sensitive photoacoustic/Raman evaluation and improved antibacterial/photothermal combination therapy.

Core-shell metal nanostructures with versatile functions have attracted extensive attention and are highly desirable for imaging and therapeutic purposes. Among them, gold and silver nanomaterials are widely explored for biological applications due to their unique properties. Despite a wide range of applications, limited enhancement ability and insufficient photothermal performance have hampered their further development. In this work, a novel multifunctional nanoprobe, a Au@Ag nanoplate (NP), is fabricated with a biocompatible surface in the aqueous phase. The as-obtained nanocomposite possesses a unique core-shell triangular configuration, sharp apexes, and a large specific surface area, exhibiting strong absorption at 780 nm. PEG-Au@Ag NPs depict highly sensitive photoacoustic imaging (PAI) capacity and extraordinary photothermal conversion efficiency (η = 73%) under 808 nm laser irradiation. Raman signals are multiplied benefitting from the enhanced surface plasma resonance contributed by the silver layer and sharp spears. PAI provides deeper pathological information while Raman detection presents superficial optical properties. Their union forms comprehensive scale coverage for disease imaging and localization. Outstanding photothermal therapy and antibacterial efficacy are observed on animal disease models. This novel multifunctional nanocomposite not only holds great potential as an excellent contrast agent for the combination of PAI and Raman evaluation, but also allows tumor and infection therapy as well as the corresponding therapeutic monitoring.