Influence factors of metagenomic next-generation sequencing negative results in diagnosed patients with spinal infection.

The aim of this study was to evaluate the influence factors of metagenomic next-generation sequencing (mNGS) negative results in the diagnosed patients with spinal infection. mNGS test was applied in a cohort of 114 patients with suspected spinal infection, among which 56 patients had a final diagnosis of spinal infection. mNGS achieved a sensitivity of 75.0% (95% CI, 61.6% to 85.6%) and a specificity of 84.5% (95% CI, 72.6% to 92.7%), using histopathology and culture results as reference. Diagnosed patients with a negative culture result had lower white blood cell account, percentage of neutrophilic granulocyte, C-reactive protein (all P<0.05) and relatively higher rate of prior antimicrobial treatment history (P=0.059). However, diagnosed patients with a negative mNGS result did not have such difference with mNGS-positive patients, suggesting that mNGS was not strictly limited by the above indicators, which presented the advantages of this technique from another point of view.

Joint extraction of wheat germplasm information entity relationship based on deep character and word fusion.

The verified text data of wheat varieties is an important component of wheat germplasm information. To automatically obtain a structured description of the phenotypic and genetic characteristics of wheat varieties, the aim at solve the issues of fuzzy entity boundaries and overlapping relationships in unstructured wheat variety approval data, WGIE-DCWF (joint extraction model of wheat germplasm information entity relationship based on deep character and word fusion) was proposed. The encoding layer of the model deeply fused word semantic information and character information using the Transformer encoder of BERT. This allowed for the cascading fusion of contextual semantic feature information to achieve rich character vector representation and improve the recognition ability of entity features. The triple extraction layer of the model established a cascading pointer network, extracted the head entity, extracted the tail entity according to the relationship category, and decoded the output triplet. This approach improved the model's capability to extract overlapping relationships. The experimental results demonstrated that the WGIE-DCWF model performed exceptionally well on both the WGD (wheat germplasm dataset) and the public dataset DuIE. The WGIE-DCWF model not only achieved high performance on the evaluation datasets but also demonstrated good generalization. This provided valuable technical support for the construction of a wheat germplasm information knowledge base and is of great significance for wheat breeding, genetic research, cultivation management, and agricultural production.

Genetic relatedness, antibiotic resistance, and virulence of Klebsiella pneumoniae isolated from healthcare and food sources in Wuhan, China.

OBJECTIVE: To investigate genetic relatedness and antibiotic resistance of Klebsiella pneumoniae from retail meat samples, clinical source samples, and hospital environmental samples in Wuhan, China. METHODS: The hypermucoviscosity phenotypes and biofilm formation ability of K. pneumoniae were determined by string test and crystalline violet staining. The minimal inhibitory concentrations of 18 antimicrobial agents were determined by the broth microdilution test, and PCR assays were performed to detect 14 genes associated with antibiotic resistance. Pulsed-field gel electrophoresis (PFGE) analysis was used to assess the genetic relatedness and clonal dissemination. RESULTS: Among the 5730 samples analyzed, 46 tested positive for K. pneumoniae, with higher rates observed in meat (23.4%, CI: 12.8-38.4%) than in clinical samples (0.6%, CI: 0.4-0.8%) and hospital environmental samples (8.0%, CI: 2.6-20.1%). Meat-derived isolates showed high resistance to tetracycline (36.4%, 4/11, CI: 12.4-68.4%), sulphonamide (27.3%, 3/11, CI: 7.3-60.7%), and gentamicin (27.3%, 3/11, CI: 7.3-60.7%), whereas clinical isolates exhibited significant resistance to ampicillin-sulbactam (32.3%, 10/31, CI: 17.3-51.5%). Multidrug resistance was observed in 17.4% (8/46, CI:8.3-32.0%) of the isolates, particularly in hospital environmental samples (3/4, CI: 21.9-98.7%). Biofilm production was observed in 88.1% (37/42, CI: 73.6-95.6%) of K. pneumoniae, with varying degrees of strength. PFGE analysis revealed patient-to-patient K. pneumoniae transmission, transmission between patients and hospital environment, as well as cross-contamination between markets. CONCLUSION: The findings underscore the importance of comprehensive surveillance, infection control and judicious antibiotic use in mitigating the impact of K. pneumoniae on public health, especially in food chain and healthcare settings.

RETRACTED: Serebrovska et al. Intermittent Hypoxia-Hyperoxia Training Improves Cognitive Function and Decreases Circulating Biomarkers of Alzheimer's Disease in Patients with Mild Cognitive Impairment: A Pilot Study. Int. J. Mol. Sci. 2019, 20, 5405.

The journal Int [...].

Non-telecentric photoacoustic microscopy for multi-scale imaging.

Optical-resolution photoacoustic microscopy (OR-PAM) excels in precisely imaging a biological tissue based on absorption contrast. However, existing OR-PAMs are confined by fixed compromises between spatial resolution and field of view (FOV), preventing the integration of large FOV and local high-resolution within one system. Here, we present a non-telecentric OR-PAM (nTC-PAM) that empowers efficient adaptation of FOV and spatial resolution to match the multi-scale requirement of diverse biological imaging. Our method allows for a large-scale transformation in FOV and even surpassing the nominal FOV of the objective with minimal marginal degradation of the lateral resolution. We demonstrate the advantage of nTC-PAM through multi-scale imaging of the leaf phantom, mouse ear, and cortex. The results reveal that nTC-PAM can switch the FOV and spatial resolution to meet the requirements of different biological tissues, such as large-scale imaging of the whole cerebral cortex and high-resolution imaging of microvascular structures in local brain regions.

High spatiotemporal mapping of cortical blood flow velocity with an enhanced accuracy.

Cerebral blood flow velocity is one of the most essential parameters related to brain functions and diseases. However, most existing mapping methods suffer from either inaccuracy or lengthy sampling time. In this study, we propose a particle-size-related calibration method to improve the measurement accuracy and a random-access strategy to suppress the sampling time. Based on the proposed methods, we study the long-term progress of cortical vasculopathy and abnormal blood flow caused by glioma, short-term variations of blood flow velocity under different anesthetic depths, and cortex-wide connectivity of the rapid fluctuation of blood flow velocities during seizure onset. The experimental results demonstrate that the proposed calibration method and the random-access strategy can improve both the qualitative and quantitative performance of velocimetry techniques and are also beneficial for understanding brain functions and diseases from the perspective of cerebral blood flow.

YOLOv8s-CGF: a lightweight model for wheat ear Fusarium head blight detection.

Fusarium head blight (FHB) is a destructive disease that affects wheat production. Detecting FHB accurately and rapidly is crucial for improving wheat yield. Traditional models are difficult to apply to mobile devices due to large parameters, high computation, and resource requirements. Therefore, this article proposes a lightweight detection method based on an improved YOLOv8s to facilitate the rapid deployment of the model on mobile terminals and improve the detection efficiency of wheat FHB. The proposed method introduced a C-FasterNet module, which replaced the C2f module in the backbone network. It helps reduce the number of parameters and the computational volume of the model. Additionally, the Conv in the backbone network is replaced with GhostConv, further reducing parameters and computation without significantly affecting detection accuracy. Thirdly, the introduction of the Focal CIoU loss function reduces the impact of sample imbalance on the detection results and accelerates the model convergence. Lastly, the large target detection head was removed from the model for lightweight. The experimental results show that the size of the improved model (YOLOv8s-CGF) is only 11.7 M, which accounts for 52.0% of the original model (YOLOv8s). The number of parameters is only 5.7 × 106 M, equivalent to 51.4% of the original model. The computational volume is only 21.1 GFLOPs, representing 74.3% of the original model. Moreover, the mean average precision (mAP@0.5) of the model is 99.492%, which is 0.003% higher than the original model, and the mAP@0.5:0.95 is 0.269% higher than the original model. Compared to other YOLO models, the improved lightweight model not only achieved the highest detection precision but also significantly reduced the number of parameters and model size. This provides a valuable reference for FHB detection in wheat ears and deployment on mobile terminals in field environments.

Antibiotic-Resistance Profiles and Genetic Diversity of Shigella Isolates in China: Implications for Control Strategies.

The urgent need for comprehensive and systematic analyses of Shigella as the key pathogen led us to meticulously explore the epidemiology and molecular attributes of Shigella isolates. Accordingly, we procured 24 isolates (10 from Xinjiang and 14 from Wuhan, China) and performed serotype identification and antimicrobial susceptibility testing. Resistance gene detection and homology analysis by polymerase chain reaction and pulsed-field gel electrophoresis (PFGE), respectively, were performed for genetic diversity analysis. All isolates were identified as Shigella flexneri, with 70% (35.4-91.9%) and 30% (8.1-64.6%) of the Xinjiang isolates and 85.7% (56.2-97.5%) and 14.3% (2/14, 2.5-43.9%) of the Wuhan isolates belonging to serotype 2a and serotype 2b, respectively. All isolates displayed resistance to at least two antibiotics and complete resistance to ampicillin. Multidrug resistance (MDR) was recorded in 70.8% (48.8-86.6%) of isolates, with Xinjiang isolates exhibiting relatively higher resistance to ampicillin-sulbactam, piperacillin, ceftriaxone, and aztreonam. Conversely, Wuhan isolates displayed higher MDR and resistance to tetracycline, ciprofloxacin, levofloxacin, and cefepime relative to Xinjiang isolates. Molecular scrutiny of antibiotic-resistance determinants revealed that blaTEM was the main mechanism of ampicillin resistance, blaCTX-M was the main gene for resistance to third- and fourth-generation cephalosporins, and tetB was the predominant gene associated with tetracycline resistance. Four Xinjiang and seven Wuhan isolates shared T1-clone types (>85%), and two Xinjiang and one Wuhan isolates were derived from the T6 clone with a high similarity of 87%. Six PFGE patterns (T1, T2, T5, T6-3, T8, and T10) of S. flexneri were associated with MDR. Thus, there is a critical need for robust surveillance and control strategies in managing Shigella infections, along with the development of targeted interventions and antimicrobial stewardship programs tailored to the distinct characteristics of Shigella isolates in different regions of China.

Wearable photoacoustic watch for humans.

Longitudinal detection of hemodynamic changes based on wearable devices is imperative for monitoring human healthcare. Photoacoustic effect is extremely sensitive to variations in hemoglobin. Therefore, wearable photoacoustic devices are apt to monitor human healthcare via the observation of hemodynamics. However, the bulky system and difficulties in miniaturizing and optimizing the imaging interface restrict the development of wearable photoacoustic devices for human use. In this study, we developed a wearable photoacoustic watch with a fully integrated system in a backpack that has a size of 450 mm × 300 mm × 200 mm and an affordable weight of 7 kg for an adult to wear. The watch has a size of 43 mm × 30 mm × 24 mm, weighs 40 g, and features a lateral resolution of 8.7 µm, a field of view (FOV) of 3 mm in diameter, and a motorized adjustable focus for optimizing the imaging plane for different individuals. We recruited volunteers to wear the watch and the backpack and performed in vivo imaging of the vasculatures inside human wrists under the conditions of walking and human cuff occlusion to observe hemodynamic variations during different physiological states. The results suggest that the focus shifting capability of the watch makes it suitable for different individuals, and the compact and stable design of the entire system allows free movements of humans.

Photoacoustic expansion microscopy of melanosomes.

Optical resolution photoacoustic microscopy (OR-PAM) is a hybrid imaging method for visualizing organelles due to the high spatial resolution and abundant optical contrast. Usually, OR-PAM employs high numerical aperture (NA) objectives and high-frequency ultrasonic detectors to resolve three-dimensional (3D) microstructures of cells. Expansion microscopy (ExM) provides a nanoscale resolution by isotropically enlarging cells instead of utilizing ultrahigh NA objectives. In this Letter, we report the development of photoacoustic expansion microscopy (PA-ExM) that combines the advantages of OR-PAM and ExM for 3D organelle imaging using near-infrared light. We evaluate the performance of PA-ExM using label-free melanoma cells, where the image quality of melanosome distributions in expanded cells using a 40× objective is comparable to that of unexpanded cells using an oil-immersed 100× objective. The results suggest that PA-ExM possesses the great potential to study organelles.

Infant and Adult Human Intestinal Enteroids are Morphologically and Functionally Distinct.

Background & Aims: Human intestinal enteroids (HIEs) are gaining recognition as physiologically relevant models of the intestinal epithelium. While HIEs from adults are used extensively in biomedical research, few studies have used HIEs from infants. Considering the dramatic developmental changes that occur during infancy, it is important to establish models that represent infant intestinal characteristics and physiological responses. Methods: We established jejunal HIEs from infant surgical samples and performed comparisons to jejunal HIEs from adults using RNA sequencing (RNA-Seq) and morphologic analyses. We validated differences in key pathways through functional studies and determined if these cultures recapitulate known features of the infant intestinal epithelium. Results: RNA-Seq analysis showed significant differences in the transcriptome of infant and adult HIEs, including differences in genes and pathways associated with cell differentiation and proliferation, tissue development, lipid metabolism, innate immunity, and biological adhesion. Validating these results, we observed a higher abundance of cells expressing specific enterocyte, goblet cell and enteroendocrine cell markers in differentiated infant HIE monolayers, and greater numbers of proliferative cells in undifferentiated 3D cultures. Compared to adult HIEs, infant HIEs portray characteristics of an immature gastrointestinal epithelium including significantly shorter cell height, lower epithelial barrier integrity, and lower innate immune responses to infection with an oral poliovirus vaccine. Conclusions: HIEs established from infant intestinal tissues reflect characteristics of the infant gut and are distinct from adult cultures. Our data support the use of infant HIEs as an ex-vivo model to advance studies of infant-specific diseases and drug discovery for this population.

Grafting a Polymer Coating Layer onto Li1.2 Ni0.13 Co0.13 Mn0.54 O2 Cathode by Benzene Diazonium Salts to Facilitate the Cycling Performance and High-Voltage Stability.

Li-rich Mn-based cathodes have been regarded as promising cathodes for lithium-ion batteries because of their low cost of raw materials (compared with Ni-rich layer structure and LiCoO2 cathodes) and high energy density. However, for practical application, it needs to solve the great drawbacks of Li-rich Mn-based cathodes like capacity degradation and operating voltage decline. Herein, an effective method of surface modification by benzene diazonium salts to build a stable interface between the cathode materials and the electrolyte is proposed. The cathodes after modification exhibit excellent cycling performance (the retention of specific capacity is 84.2% after 350 cycles at the current density of 1 C), which is mainly attributed to the better stability of the structure and interface. This work provides a novel way to design the coating layer with benzene diazonium salts for enhancing the structural stability under high voltage condition during cycling.

Rotavirus-mediated DGAT1 degradation: A pathophysiological mechanism of viral-induced malabsorptive diarrhea.

Gastroenteritis is among the leading causes of mortality globally in infants and young children, with rotavirus (RV) causing ~258 million episodes of diarrhea and ~128,000 deaths annually in infants and children. RV-induced mechanisms that result in diarrhea are not completely understood, but malabsorption is a contributing factor. RV alters cellular lipid metabolism by inducing lipid droplet (LD) formation as a platform for replication factories named viroplasms. A link between LD formation and gastroenteritis has not been identified. We found that diacylglycerol O-acyltransferase 1 (DGAT1), the terminal step in triacylglycerol synthesis required for LD biogenesis, is degraded in RV-infected cells by a proteasome-mediated mechanism. RV-infected DGAT1-silenced cells show earlier and increased numbers of LD-associated viroplasms per cell that translate into a fourfold-to-fivefold increase in viral yield (P < 0.05). Interestingly, DGAT1 deficiency in children is associated with diarrhea due to altered trafficking of key ion transporters to the apical brush border of enterocytes. Confocal microscopy and immunoblot analyses of RV-infected cells and DGAT1-/- human intestinal enteroids (HIEs) show a decrease in expression of nutrient transporters, ion transporters, tight junctional proteins, and cytoskeletal proteins. Increased phospho-eIF2α (eukaryotic initiation factor 2 alpha) in DGAT1-/- HIEs, and RV-infected cells, indicates a mechanism for malabsorptive diarrhea, namely inhibition of translation of cellular proteins critical for nutrient digestion and intestinal absorption. Our study elucidates a pathophysiological mechanism of RV-induced DGAT1 deficiency by protein degradation that mediates malabsorptive diarrhea, as well as a role for lipid metabolism, in the pathogenesis of gastroenteritis.

Human intestinal organoids from Cronkhite-Canada syndrome patients reveal link between serotonin and proliferation.

Cronkhite-Canada Syndrome (CCS) is a rare, noninherited polyposis syndrome affecting 1 in every million individuals. Despite over 50 years of CCS cases, the etiopathogenesis and optimal treatment for CCS remains unknown due to the rarity of the disease and lack of model systems. To better understand the etiology of CCS, we generated human intestinal organoids (HIOs) from intestinal stem cells isolated from 2 patients. We discovered that CCS HIOs are highly proliferative and have increased numbers of enteroendocrine cells producing serotonin (also known as 5-hydroxytryptamine or 5HT). These features were also confirmed in patient tissue biopsies. Recombinant 5HT increased proliferation of non-CCS donor HIOs and inhibition of 5HT production in the CCS HIOs resulted in decreased proliferation, suggesting a link between local epithelial 5HT production and control of epithelial stem cell proliferation. This link was confirmed in genetically engineered HIOs with an increased number of enteroendocrine cells. This work provides a new mechanism to explain the pathogenesis of CCS and illustrates the important contribution of HIO cultures to understanding disease etiology and in the identification of novel therapies. Our work demonstrates the principle of using organoids for personalized medicine and sheds light on how intestinal hormones can play a role in intestinal epithelial proliferation.

The Role of OCTA in Evaluating Diabetic Retinopathy Progression: A Meta-Analysis.

Background: Diabetic retinopathy (DR) substantially threatens ocular health, necessitating the accurate and prompt assessment of its onset and progression. Optical coherence tomography angiography (OCTA) is a valuable tool for evaluating periocular microvascular indicators, offering insights crucial for diagnosing and treating DR. Objective: This meta-analysis aims to evaluate the progression of diabetic retinopathy (DR) by examining periocular microvascular indicators using optical coherence tomography angiography (OCTA). The objective is to provide substantive evidence for the future diagnosis and treatment of DR. Methods: We analyzed the relevant research retrieved from PubMed and Web of Science until January 2023. The inclusion and exclusion criteria were carefully applied to select eligible studies. Quality assessment was performed using the Newcastle-Ottawa Scale, with studies scoring 4 or less excluded. Meta-analysis was conducted using Revman 5.3 software and focused on key indicators, including peripapillary vascular length density (pVLD) and peripapillary vascular density (pVD). Heterogeneity was assessed using I2 and P values, with effect sizes determined via fixed-effect or random-effects models based on heterogeneity levels. Results: Six studies involving 839 DR-afflicted eyes and 3209 non-DR eyes were included after screening. All selected articles exhibited high reference value, with quality scores ranging from 5 to 8 points. The meta-analysis demonstrated that DR patients displayed significantly lower pVD and pVLD in the superficial (SCP) and deep capillary plexus (DCP) compared to non-DR patients (P < .05). These findings remained consistent across different effect models, reaffirming their validity. Conclusions: Patients with DR exhibit reduced levels of pVD and pVLD in the SCP and DCP compared to non-DR individuals. OCTA examination of periocular microvascular indicators emerges as an effective tool for assessing the onset and progression of DR.

Long-term assessment of cutaneous inflammation and treatment using optical resolution photoacoustic microscopy.

Cutaneous inflammation is an acute skin disease characterized by edema and vascular hyperplasia. Longitudinal monitoring of vasculature is crucial for studying the development of inflammation and evaluating the therapeutic efficacy of drugs. Optical-resolution photoacoustic microscopy (OR-PAM) is a hybrid imaging tool for non-invasive and label-free visualization of microcirculations with a capillary-scale spatial resolution. In this study, we assess the feasibility of OR-PAM for long-term monitoring of vascular changes in 12-O-Tetradecanoylphorbol-13-Acetate (TPA)-induced mouse models, as well as the corresponding treatment process. Quantitative vascular evaluation is conducted based on derived key parameters, including vessel length, branchpoint number, vessel area fraction, vessel diameter, fractal dimension, vessel tortuosity and ear thickness, which reveal that vascular morphological changes are highly dependent on the concentration of TPA and existence of therapeutic drugs. Furthermore, the results show the potential of OR-PAM in the clinical management of inflammation and as an effective tool to evaluate vascular responses to pharmacological interventions in vivo.

Chronic Exposure to Environmental Pollutant Ammonia Causes Damage to the Olfactory System and Behavioral Abnormalities in Mice.

Ammonia (NH3) is a major air pollutant. However, few studies have been extended beyond the histopathological changes in the olfactory mucosa to the impact of NH3 exposure on other parts of the olfactory system and olfactory functioning. Therefore, we assessed the effects of exogenous NH3 (either 20 ppm for the low exposure group or 200 ppm for the high exposure group) on the various parts of the olfactory system by histological observation, gene expression, immunochemistry, and chemical analyses. A total of 140 Institute of Cancer Research mice (4 weeks old), 70 females and 70 males (average body weight at the start: 21.5 ± 1.9 g), were used. The exposure lasted for 4 weeks, and the mice were exposed to the NH3 for 4 h per day. Our results showed that chronic exposure to NH3 damaged the olfactory system, with consequences for changing the foraging behavior and anxiety behavior. Our results also suggest that it is plausible that NH3 recruited T cells and activated microglia cells and astrocytes, leading to inflammation in the olfactory system. Increased release of proinflammatory cytokines (TNF-α, IL-1ß, IL-6, and interferon-γ) and reduced release of anti-inflammatory cytokines (IL-4 and IFN-beta) led to tissue damage and compromised the functions of the olfactory system.

Biomimetic Structural Protein Based Magnetic Responsive Scaffold for Enhancing Bone Regeneration by Physical Stimulation on Intracellular Calcium Homeostasis.

The bone matrix has distinct architecture and biochemistry which present a barrier to synthesizing bone-mimetic regenerative scaffolds. To mimic the natural structures and components of bone, biomimetic structural decellularized extracellular matrix (ECM)/regenerated silk fibroin (RSF) scaffolds incorporated with magnetic nanoparticles (MNP) are prepared using a facile synthetic methodology. The ECM/RSF/MNP scaffold is a hierarchically organized and interconnected porous structure with silk fibroin twined on the collagen nanofibers. The scaffold demonstrates saturation magnetization due to the presence of MNP, along with good cytocompatibility. Moreover, the ß-sheet crystalline domain of RSF and the chelated MNP could mimic the deposition of hydroxyapatite and enhance compressive modulus of the scaffold by ≈20%. The results indicate that an external static magnetic field (SMF) with a magnetic responsive scaffold effectively promotes cell migration, osteogenic differentiation, neogenesis of endotheliocytes in vitro, and new bone formation in a critical-size femur defect rat model. RNA sequencing reveals that the molecular mechanisms underlying this osteogenic effect involve calsequestrin-2-mediated Ca2+ release from the endoplasmic reticulum to activate Ca2+ /calmodulin/calmodulin-dependent kinase II signaling axis. Collectively, bionic magnetic scaffolds with SMF stimulation provide a potent strategy for bone regeneration through internal structural cues, biochemical composition, and external physical stimulation on intracellular Ca2+ homeostasis.

Eutectic-Based Polymer Electrolyte with the Enhanced Lithium Salt Dissociation for High-Performance Lithium Metal Batteries.

The deployment of lithium metal anode in solid-state batteries with polymer electrolytes has been recognized as a promising approach to achieving high-energy-density technologies. However, the practical application of the polymer electrolytes is currently constrained by various challenges, including low ionic conductivity, inadequate electrochemical window, and poor interface stability. To address these issues, a novel eutectic-based polymer electrolyte consisting of succinonitrile (SN) and poly (ethylene glycol) methyl ether acrylate (PEGMEA) is developed. The research results demonstrate that the interactions between SN and PEGMEA promote the dissociation of the lithium difluoro(oxalato) borate (LiDFOB) salt and increase the concentration of free Li+ . The well-designed eutectic-based PAN1.2 -SPE (PEGMEA: SN=1: 1.2 mass ratio) exhibits high ionic conductivity of 1.30 mS cm-1 at 30 °C and superior interface stability with Li anode. The Li/Li symmetric cell based on PAN1.2 -SPE enables long-term plating/stripping at 0.3 and 0.5 mA cm-2 , and the Li/LiFePO4 cell achieves superior long-term cycling stability (capacity retention of 80.3 % after 1500 cycles). Moreover, Li/LiFePO4 and Li/LiNi0.6 Co0.2 Mn0.2 O2 pouch cells employing PAN1.2 -SPE demonstrate excellent cycling and safety characteristics. This study presents a new pathway for designing high-performance polymer electrolytes and promotes the practical application of high-stable lithium metal batteries.

Near-Infrared II Semiconducting Polymer Dots: Chain Packing Modulation and High-Contrast Vascular Imaging in Deep Tissues.

Fluorescence imaging in the second near-infrared (NIR-II) window has attracted considerable interest in investigations of vascular structure and angiogenesis, providing valuable information for the precise diagnosis of early stage diseases. However, it remains challenging to image small blood vessels in deep tissues because of the strong photon scattering and low fluorescence brightness of the fluorophores. Here, we describe our combined efforts in both fluorescent probe design and image algorithm development for high-contrast vascular imaging in deep turbid tissues such as mouse and rat brains with intact skull. First, we use a polymer blending strategy to modulate the chain packing behavior of the large, rigid, NIR-II semiconducting polymers to produce compact and bright polymer dots (Pdots), a prerequisite for in vivo fluorescence imaging of small blood vessels. We further developed a robust Hessian matrix method to enhance the image contrast of vascular structures, particularly the small and weakly fluorescent vessels. The enhanced vascular images obtained in whole-body mouse imaging exhibit more than an order of magnitude improvement in the signal-to-background ratio (SBR) as compared to the original images. Taking advantage of the bright Pdots and Hessian matrix method, we finally performed through-skull NIR-II fluorescence imaging and obtained a high-contrast cerebral vasculature in both mouse and rat models bearing brain tumors. This study in Pdot probe development and imaging algorithm enhancement provides a promising approach for NIR-II fluorescence vascular imaging of deep turbid tissues.