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A) Photographs of the whole brain tissues before and 7 d after TBI. The dashed white box indicated the injured area. B) DAPI and immunohistochemical staining of brain sections for CD31 and CD44 in injured region after BMSC therapy of TBI. Blue, aubergine, and green fluorescence correspond to DAPI, CD44, and CD31, respectively. C) H&E staining of brain tissue slices during the recovery progress of TBI with or without intravenous administration of BMSCs.
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Stem cell migration and interaction with pathology are critical to understand the complexity and status of disease recovery progress. However, the dynamic visualization still remains a great challenge due to imaging technical limitation, cell labeling difficulty, or blood–brain barrier (BBB). Herein, fast photoacoustic tomography (PAT) with optical...
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Mesenchymal stromal cells (MSCs, known as mesenchymal stem cells) are considered to be a promising therapeutic tool for many diseases. But it is still unclear which cells are more efficient and safe for wound healing and tissue regeneration for clinical applications: undifferentiated, partially differentiated stem cells or differentiated cells. In...
Citations
... SPIO@Au 810 4 μg/ ml 3 days Brain lesion treatment [35] PAI, Two-photon microscopy AuNC 800 2.3×10 4 AuNCs/ cell Tracking cells [36] PAI Iron oxide (IO) 532, 700 20 μg/ ml --Delivery of resveratrol [37] US, PAI, MPI IO nanobubbles labelled with DiR 240 μg/ ml 3 days Cardiac therapy [38] PAI, MRI Fe 3+ -PEG-MNP 800 μg/ ml 35 days Tracking cells [39] PAI Prussian blue particles 701 0.2 mg/ ml 15 days Brain injury treatment [40] PAI Prussian blue nanoparticles 730 50 μg/ ml 14 days Ischemic brain damage [41] PAI Organic semiconducting polymer nanoparticle probes + 916, 1025 50 μg/ ml 14 days Tracking cells [42] PAI, MRI gadolinium loaded melanin nanoparticles 720-760 0.43 mg/ml --In vivo stem cell tracking [43] The future of Photoacoustic imaging ...
Photoacoustic imaging (PAI) is a rapidly growing biomedical imaging technique that combines the advantages of optical and acoustic imaging. This technique utilizes pulsed laser light to generate acoustic waves in biological tissue, which are then detected and used to create high-resolution images of tissue structure and function. PAI has several advantages over other imaging modalities, including its ability to provide functional information about tissue properties such as blood oxygenation and blood flow, as well as its ability to image tissue at greater depths than many other techniques. However, there are also challenges associated with PAI, including the need for specialized equipment and concerns regarding the potential for tissue damage due to laser exposure. Despite these challenges, PAI is a promising technique with many potential applications in biomedical research and clinical practice, and ongoing research in this area is likely to yield further advances in the coming years.
... In this study, we selected photoacoustic imaging (PAI) as a versatile imaging tool for multi-feature detection of GBM, which includes photoacoustic computed tomography (PACT) characterized as a large field of volume and photoacoustic microscopy (PAM) featured with high spatial resolution [28][29][30][31]. The PAI combines the abundant contrast of optical imaging with the high spatial resolution of ultrasonography, enabling structural, functional, and molecular imaging [32,33]. ...
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.
... There are some challenges for imaging neonatal mouse models. Previous studies have shown that PAT can be applied for dynamic imaging of adult mice/rat brains [22,[24][25][26]. The results show the major blood vessels and the dynamic change of the brain. ...
Neonatal brain hemorrhage (NBH) is the most common neurological disorder in neonates and its clinical interventions are very limited. Understanding the pathology of NBH by non-invasive in-vivo characterization of standardized animal models is essential for developing potential treatments. Currently, there is no suitable tool to provide non-invasive, non-ionizing dynamic imaging of neonatal mouse models with high resolution, high contrast, and deep imaging depth. In this study, we implemented a fast 3D photoacoustic tomography (PAT) system suitable for imaging neonatal mouse brains with good image quality and demonstrated its feasibility in non-invasive monitoring of the dynamic process of NBH in the whole neonatal mouse brain. The results present a high resolution and sensitivity for NBH detection. Both morphological and hemodynamic changes of the hematoma were accurately obtained. Our results demonstrated the potential of PAT as a powerful tool for the preclinical study of neonatal brain hemorrhage.
... 19,20 Photoacoustic imaging with exogenous molecules overcomes the limitation of imaging only blood, lipid, DNA, and RNA, which opens possibilities for imaging various physiological parameters, such as temperature, ion concentration, and pH values in tissues and organs. For example, dye molecules probes with photoacoustic signals depending on the pH value in the acidic environment of tumor can achieve an accurate photoacoustic imaging of mouse epidermal tumors; 21,22 molecular probes targeting the mouse brain can track bone marrow stem cells and image glioma in the mouse brain; 23,24 organic dye molecules can be used to monitor the H 2 S concentration and hypochlorite in mice through dualwavelength laser photoacoustic signal proportional imaging. 25 However, a low signal-to-noise level is a persistent problem in photoacoustic imaging based on exogenous molecular probes. ...
Plasmonic nanoparticles, such as Au nanoparticles, have been used as effective exogeneous contrast agents in photoacoustic imaging. However, using these particles to enhance photoacoustic wave generation from other light absorbers is difficult because the signal is overwhelmed by the signal from plasmonic nanoparticles themselves. In this study, we realized the surface-enhanced photoacoustic effect by using high-refractive-index dielectric nanoparticles in their ultralow light absorption Ohmic-loss wavelength band. We performed finite element method simulation on a model with gallium phosphide nanorod dimmer and light absorbers in the dimmer gap. The Au nanowire, carbon nanotube, and nanotube filled with melanin molecules were sequentially considered as the light absorber. It is found that a photoacoustic wave surface enhancement factor of approximately 10 was achieved and the enhanced photoacoustic wave ensures the photoacoustic spectral signature of the light absorber. The potential of optimization for boosting enhancement factors was further analyzed. These results can provide considerable insight into molecular photoacoustic sensing and imaging.
... Their results bring hopes for the high-resolution imaging of brain disease. 180 Liu et al. designed a micromolecule dye TFML, which can efficiently label neutrophile granulocyte and had high PA SNR, as shown in Figure 6e. 181 After labeling neutrophils with the TFML probe, the neutrophils were transferred to the recipient with active targeting, indicating a strong PA signal as shown in Figure 6f. ...
Photoacoustic imaging (PAI) has made great advances in availing the benefits for theragnostics with noninvasive, nonionizing and high-resolution features. However, PAI effectively visualizing tumors for the clinical practice is still lacking investigation. This review describes various integrated diagnostic strategies involving PAI for joint multimodel imaging combined with innovative contrast agents in five common cancer types. PAI combined multifunctional contrast agents in a second near-infrared (NIR-II, 1000−1700 nm) biological window, providing unprecedented sensitivity and translatability. We summarize the state-of-art status of PAI in the diagnosis of different types of cancers from ex vivo samples to in vivo humans. The detailed elucidation of the up-to-date advanced material science in NIR-II and versatile PAI-guided theragnostics is reviewed toward preclinical studies. Future perspective directions to establish all-in-one strategies to boost the clinical translation are highlighted.
... Primary injury, which is accompanied by cell death, occurs acutely as a result of the external impact. Secondary injury, for which effective treatments are lacking, involves a series of long-term cascade reactions [3,4]. Among these cascade reactions, excessive production of reactive oxygen species (ROS), including superoxide anion, hydrogen peroxide, hydroxyl radical, singlet oxygen, etc. is considered central to inducing proinflammatory cytokine release and neuronal loss, which ultimately leads to disability or death [5]. ...
Traumatic brain injury (TBI) is a cause of disability and death worldwide, but there are currently no specific treatments for this condition. Release of excess reactive oxygen species (ROS) in the injured brain leads to a series of pathological changes; thus, eliminating ROS could be a potential therapeutic strategy. Herein, we synthesized insulin-incubated ultrasmall palladium (Pd@insulin) clusters via green biomimetic chemistry. The Pd@insulin clusters, which were 3.2 nm in diameter, exhibited marked multiple ROS-scavenging ability testified by the theoretical calculation. Pd@insulin could be rapidly excreted via kidney-urine metabolism and induce negligible adverse effects after a long-time treatment in vivo. In a TBI mouse model, intravenously injected Pd@insulin clusters aggregated in the injured cortex, effectively suppressed excessive ROS production, and significantly rescued motor function, cognition and spatial memory. We found that the positive therapeutic effects of the Pd@insulin clusters were mainly attributed to their ROS-scavenging ability, as they inhibited excessive neuroinflammation, reduced cell apoptosis, and prevented neuronal loss. Therefore, the ability of Pd@insulin clusters to effectively eliminate ROS, as well as their simple structure, easy synthesis, low toxicity, and rapid metabolism may facilitate their clinical translation for TBI treatment.
... To overcome these dilemmas, we selected photoacoustic imaging (PAI) as a versatile imaging tool for multi-feature detection of GBM, which includes photoacoustic computed tomography (PACT) characterized as a large eld of volume and photoacoustic microscopy (PAM) featured with high spatial resolution [23][24][25][26]. The hybrid PAI combines the abundant contrast of optical imaging with the high spatial resolution of ultrasonography, enabling structural, functional, and molecular imaging [27,28]. ...
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-microenvironment visualization to systematically reveal the tumor infiltration, heterogeneity, and metastasis in intracranial tumors.
... Histochemical staining Prussian blue [48,49,51,[57][58][59]64,65,88,109,114,116,117,124,127,138,154,155,160,177,187,189,[209][210][211][212][213][214][215][216][217][218][219][220][221][222][223][224] Oil Red O [58,225] Alizarin red [225] Dyes for NP coating Propidium iodide (PI) [118] Nile red [89] Moreover, ex vivo checking, and quantification of cell uptake was performed by coating NPs with PI or Nile red dye. As example, NP coating with PI was successfully adopted to detect cells incorporating gold NPs through flow cytometry [118], whereas Nile red labeling of hybrid iron oxide/polymeric NPs was used to check in vitro uptake into macrophages [89]. ...
The usefulness of nanoparticles (NPs) in the diagnostic and/or therapeutic sector is derived from their aptitude for navigating intra- and extracellular barriers successfully and to be spatiotemporally targeted. In this context, the optimization of NP delivery platforms is technologically related to the exploitation of the mechanisms involved in the NP–cell interaction. This review provides a detailed overview of the available technologies focusing on cell–NP interaction/detection by describing their applications in the fields of cancer and regenerative medicine. Specifically, a literature survey has been performed to analyze the key nanocarrier-impacting elements, such as NP typology and functionalization, the ability to tune cell interaction mechanisms under in vitro and in vivo conditions by framing, and at the same time, the imaging devices supporting NP delivery assessment, and consideration of their specificity and sensitivity. Although the large amount of literature information on the designs and applications of cell membrane-coated NPs has reached the extent at which it could be considered a mature branch of nanomedicine ready to be translated to the clinic, the technology applied to the biomimetic functionalization strategy of the design of NPs for directing cell labelling and intracellular retention appears less advanced. These approaches, if properly scaled up, will present diverse biomedical applications and make a positive impact on human health.
... Tang et al. developed a wearable, multispectral, three-dimensional PA brain imaging system for rats with a resolution of 0.2 mm [6]. Subochev et al. [7], Yang et al. [8], and Li et al. [9] also reported outstanding works in the field of PA brain imaging. However, these studies focused on mice and rats with thin skulls (thickness: 0.3-0.8 ...
... Therefore, we believe that the method may be effective in solving the decoding problem of propagation of more broadband signal sources through complex paths. The high sensitivity of photoacoustic imaging to endogenous chromophores [60], [61] and exogenous probes [9], [62] of the brain gives this modality an unprecedented ability to interrogate the brain non-invasively in physiological and disease conditions [63]. For instance, Deliolanis et al. demonstrated the ability of photoacoustic imaging to visualize deep-seated glioma brain tumors for intraoperative depiction of tumor margins [64]. ...
Photoacoustic imaging is a promising approach used to realize
in vivo
transcranial cerebral vascular imaging. However, the strong attenuation and distortion of the photoacoustic wave caused by the thick porous skull greatly affect the imaging quality. In this study, we developed a convolutional neural network based on U-Net to extract the effective photoacoustic information hidden in the speckle patterns obtained from vascular network images datasets under porous media. Our simulation and experimental results show that the proposed neural network can learn the mapping relationship between the speckle pattern and the target, and extract the photoacoustic signals of the vessels submerged in noise to reconstruct high-quality images of the vessels with a sharp outline and a clean background. Compared with the traditional photoacoustic reconstruction methods, the proposed deep learning-based reconstruction algorithm has a better performance with a lower mean absolute error, higher structural similarity, and higher peak signal-to-noise ratio of reconstructed images. In conclusion, the proposed neural network can effectively extract valid information from highly blurred speckle patterns for the rapid reconstruction of target images, which offers promising applications in transcranial photoacoustic imaging.
... Due to its unique superiority in visualizing blood vessels, PAI has been widely exploited to investigate the vascular aberrations result from cerebral diseases [24][25][26][27][28]. Besides, the novel mechanism of optical absorption also enables PAI have a promising prospect in in vivo monitoring the BBB disruption, especially when combined with the specific CA [29]. As demonstrated in previous reports, photoacoustic computed tomography (PACT) and acoustic resolution photoacoustic microscopy (AR-PAM) have been reported for monitoring the impaired BBB induced by cerebral diseases with considerable penetration depth [30][31][32]. However, the limited spatial resolution prevents it capability of precisely evaluating the BBB disruption and disclosing the abnormal microvasculature. ...
The blood-brain barrier (BBB) strictly regulates the substance exchange between the vascular network and the central nervous system, and plays a critical role in maintaining normal brain homeostasis. Impaired BBB is often accompanied with the emergence of cerebral diseases and probably further leads to severe neuroinflammation or even neurological degeneration. Hence, there is an urgent need to precisely monitor the impaired BBB to understand its pathogenesis and better guide the enactment of therapeutic strategies. However, there is a lack of high-resolution imaging techniques to visualize and evaluate the large-scale BBB disruption in pre-clinical and clinical aspects. In this study, we propose a dual-wavelength photoacoustic imaging (PAI) methodology that simultaneously reveals the abnormal microvasculature and impaired BBB within the cerebral cortex. In in vivo studies, BBB disruption in both mice and rats were induced by local hot-water stimulation and unilateral carotid arterial perfusion of hyperosmolar mannitol, respectively. Subsequently, the exogenous contrast agent (CA) was injected into the microcirculation via the tail vein, and photoacoustic (PA) images of the microvasculature and leaked CA within the cerebral cortex were obtained by dual-wavelength photoacoustic microscopy to evaluate the BBB disruption. Besides, analysis of distribution and concentration of leaked CA in lesion region was further conducted to quantitatively reveal the dynamic changes of BBB permeability. Furthermore, we exploited this approach to investigate the reversibility of BBB disruption within the two distinct models. Based on the experimental results, this new proposed approach presents excellent performance in visualizing microvasculature and leaked CA, and enabling it possesses great potential in evaluating the abnormal microvasculature and impaired BBB result from cerebrovascular diseases.
