Image-guided Surgery Research Articles

The Decompositions of Fluorescent Defects and Pristine Structure in (6,5) Carbon Nanotubes Using Various Oxidants

Fluorescent quantum defects in single-wall carbon nanotubes (SWCNTs) are outstanding candidates as fluorophores for in vivo biomedical imaging applications such as image-guided surgeries and single-cell tracking. Their longer wavelength emission in the short-wave infrared penetrates biological tissues deeper than visible and NIR light. In addition, fluorescent quantum defects can enhance fluorescence brightness by a factor of ~9 compared to the pristine SWCNT emission. Besides their exceeding optical properties, the degradations of SWCNTs in biological and environmental systems are also of importance, but still not well understood yet. This study utilizes sodium hypochlorite (NaClO) and hydrogen peroxide (H2O2) to examine the chemical decompositions of pristine and defect-containing SWCNTs. We found that the oxidation rate of NaClO is ~5 times faster than that of H2O2, showing an obvious oxidant-dependent degradation kinetics. It is also worth mentioning that when using NaClO as the oxidant, the oxidation rate is significantly increased under acidic conditions, probably due to the increased concentration of hypochlorous acid (HOCl). In contrast, H2O2 prefers to oxidize the pristine structure. It is also found that SWCNT coating materials including SDS, SC, and ssDNA might protect the surface structures, especially the defects, from oxidant attacks. We believe our study will lead to a better understanding of the SWCNT degradation, providing valuable insights for future clinical applications.

The Impact of Navigation in Lumbar Spine Surgery: A Study of Historical Aspects, Current Techniques and Future Directions.

Background/Objectives: We sought to improve accuracy while minimizing radiation hazards, improving surgical outcomes, and preventing potential complications. Despite the increasing popularity of these systems, a limited number of papers have been published addressing the historical evolution, detailing the areas of use, and discussing the advantages and disadvantages, of this increasingly popular system in lumbar spine surgery. Our objective was to offer readers a concise overview of navigation system history in lumbar spine surgeries, the techniques involved, the advantages and disadvantages, and suggestions for future enhancements to the system. Methods: A comprehensive review of the literature was conducted, focusing on the development and implementation of navigation systems in lumbar spine surgeries. Our sources include PubMed-indexed peer-reviewed journals, clinical trial data, and case studies involving technologies such as computer-assisted surgery (CAS), image-guided surgery (IGS), and robotic-assisted systems. Results: To develop more practical, effective, and accurate navigation techniques for spine surgery, consistent advancements have been made over the past four decades. This technological progress began in the late 20th century and has since encompassed image-guided surgery, intraoperative imaging, advanced navigation combined with robotic assistance, and artificial intelligence. These technological advancements have significantly improved the accuracy of implant placement, reducing the risk of misplacement and related complications. Navigation has also been found to be particularly useful in tumor resection and minimally invasive surgery (MIS), where conventional anatomic landmarks are lacking or, in the case of MIS, not visible. Additionally, these innovations have led to shorter operative times, decreased radiation exposure for patients and surgical teams, and lower rates of reoperation. As navigation technology continues to evolve, future innovations are anticipated to further enhance the capabilities and accessibility of these systems, ultimately leading to improved patient outcomes in lumbar spine surgery. Conclusions: The initial limited utilization of navigation system in spine surgery has further expanded to encompass almost all fields of lumbar spine surgeries. As the cost-effectiveness and number of trained surgeons improve, a wider use of the system will be ensured so that the navigation system will be an indispensable tool in lumbar spine surgery. However, continued research and development, along with training programs for surgeons, are essential to fully realize the potential of these technologies in clinical practice.

Imaging adjuvants in pediatric surgical oncology.

Surgery is a crucial component of pediatric cancer treatment, but conventional methods may lack precision. Image-guided surgery, including fluorescent and radioguided techniques, offers promise for enhancing tumor localization and facilitating precise resection. Intraoperative molecular imaging utilizes agents like indocyanine green to direct surgeons to occult deposits of tumor and to delineate tumor margins. Next-generation agents target tumors directly to improve specificity. Radioguided surgery, employing tracers like metaiodobenzylguanidine (MIBG), complements fluorescent techniques by allowing for detection of tumors at a greater depth. Dual-labeled agents combining both modalities are under development. Three-dimensional modeling and virtual/augmented reality aid in preoperative planning and intraoperative guidance. The above techniques show great promise to benefit patients with pediatric tumors, and their continued development will almost certainly improve surgical outcomes.

An Innovative Aggregation-Induced Emission-Based NIR Fluorescent Probe for Visualizing Carboxylesterases in Living Cells, Zebrafish, and Tumor-Bearing Mice.

In the human body, carboxylesterases (CEs) play crucial roles in xenobiotic metabolism and lipid homeostasis. But abnormal expression of CEs is highly associated with some diseases, such as hyperlipidemia, diabetes, and liver cancer. Therefore, it is of great importance to develop an efficient tool for the accurate detection of CEs in living organisms. Herein, an innovative near-infrared (NIR) fluorescent probe, TTAP-AB, was designed for CE detection based on the aggregation-induced emission (AIE) mechanism. This probe exhibits rapid response (2 min), excellent sensitivity (limit of detection = 8.14 × 10-6 U/mL), and high selectivity to CEs. Additionally, owing to its good biocompatibility, the TTAP-AB probe enables the monitoring of dynamic changes in CE levels under drug-induced modulation in living cells and zebrafish. More importantly, the TTAP-AB probe was successfully employed to image liver tumors and assist in tumor resection through the real-time monitoring of CEs, indicating that TTAP-AB is promising to guide liver cancer surgery. Therefore, the TTAP-AB probe can not only enrich the strategies for CE detection in biological systems but also has great potential for some clinical imaging applications, including medical diagnosis, preclinical research, and imaging-guided surgery.

Quenched Zwitterionic Cyclic Arg-Gly-Asp-Containing Pentapeptide Probe for Real-Time Brain Tumor Imaging.

The efficacy of glioblastoma treatment is closely associated with complete tumor resection. However, conventional surgical techniques often result in incomplete removal, leading to poor prognosis. A major challenge is the accurate delineation of tumor margins from healthy tissues. Imaging-guided surgery, particularly using fluorescent probes, is a promising solution for intraoperative guidance. The recently developed 'always-on' types of targeted fluorescence probes generate signals irrespective of their presence in tumor cells or in blood circulation, hampering their effectiveness. Here, we propose a novel activatable fluorescence imaging probe, Q-cRGD, that targets glioma cells via the specific binding of the cyclic Arg-Gly Asp-containing pentapeptide (cRGD) to integrins. The Q-cRGD probe was synthesized by conjugating a near-infrared (NIR) dye to a tryptophan quencher via a disulfide linkage, including a cRGD-targeting ligand. This activatable probe remained inactive until the redox-responsive cleavage of the disulfide linkage occurred within the target cell. The zwitterionic nature of NIR dyes minimizes nonspecific interactions with serum proteins, thereby enhancing the tumor-to-background signal ratio (TBR). An in vivo fluorescence imaging study demonstrated a TBR value of 2.65 within 3 h of the intravenous injection of Q-cRGD, confirming its potential utility in imaging-guided brain cancer surgery.

Erythrocyte nano-ghosts with dual optical and magnetic resonance characteristics.

Fluorescent organic dyes provide imaging capabilities at cellular and sub-cellular levels. However, a common problem associated with some of the existing dyes such as the US FDA-approved indocyanine green (ICG) is their weak fluorescence emission. Alternative dyes with greater emission characteristics would be useful in various imaging applications. Complementing optical imaging, magnetic resonance (MR) imaging enables deep tissue imaging. Nano-sized delivery systems containing dyes with greater fluorescence emission as well as MR contrast agents present a promising dual-mode platform with high optical sensitivity and deep tissue imaging for image-guided surgical applications. We have engineered a nano-sized platform, derived from erythrocyte ghosts (EGs), with dual near-infrared fluorescence and MR characteristics by co-encapsulation of a brominated carbocyanine dye and gadobenate dimeglumine (Gd-BOPTA). We have investigated the use of three brominated carbocyanine dyes (referred to as BrCy106, BrCy111, and BrCy112) with various degrees of bromination, structural symmetry, and acidic modifications for encapsulation by nano-sized EGs (nEGs) and compared their resulting optical characteristics with nEGs containing ICG. We find that asymmetric dyes (BrCy106 and BrCy112) with one dibromobenzene ring offer greater fluorescence emission characteristics. For example, the relative fluorescence quantum yield ( ) for nEGs fabricated using of BrCy112 is -fold higher than nEGs fabricated using the same concentrations of ICG. The dual-mode nEGs containing BrCy112 and Gd-BOPTA show a nearly twofold increase in their as compared with their single optical mode counterpart. Cytotoxicity is not observed upon incubation of SKOV3 cells with nEGs containing BrCy112. Erythrocyte nano-ghosts with dual optical and MR characteristics may ultimately prove useful in various biomedical imaging applications such as image-guided tumor surgery where MR imaging can be used for tumor staging and mapping, and fluorescence imaging can help visualize small tumor nodules for resection.

HHEPATO-Cy5, a Bimodal Tracer for Image-Guided Hepatobiliary Surgery.

Liver cancer is a leading cause of cancer deaths worldwide. Surgical resection of superficial hepatic lesions is increasingly guided by the disrupted bile excretion of the fluorescent dye indocyanine green (ICG). To extend this approach to deeper lesions, a dedicated bimodal tracer that facilitates both fluorescence guidance and radioguidance was developed. Methods: A tracer comprising a methylated cyanine-5 (Cy5) fluorescent dye and a mercaptoacetyltriserine chelate (hHEPATO-Cy5) was synthesized and characterized. Cellular uptake and excretion were evaluated in hepatocyte cultures (2-dimensional culture and invitro lesion model), using a fluorescent bile salt, MitoTracker dye, and methylated Cy5 as a control. After radiolabeling, the pharmacokinetics of 99mTc-hHEPATO-Cy5 were assessed in mice over 24 h (percentage injected dose and percentage injected dose per gram of tissue, SPECT/CT imaging and fluorescence imaging). The ability to provide real-time fluorescence guidance during robot-assisted hepatobiliary surgery was evaluated in a porcine model using ICG as a reference. Results: The unique molecular signature of hHEPATO-Cy5 promotes hepatobiliary excretion. In vitro studies on hepatocytes showed that where methylated Cy5 remained internalized, hHEPATO-Cy5 showed fast clearance (10 min) similar to that of fluorescent bile salt. In vivo use of 99mTc-hHEPATO-Cy5 in mice revealed liver accumulation and rapid biliary clearance. The effectiveness of bile clearance was best exemplified by the 2-orders-of-magnitude reduction in count rate for the gallbladder (P = 0.008) over time. During hepatobiliary surgery in a porcine model, hHEPATO-Cy5 enabled fluorescence-based lesion identification comparable to that of ICG. Conclusion: The bimodal 99mTc-hHEPATO-Cy5 provides an effective means to identify liver lesions. Uniquely, it helps overcome the shortcomings of fluorescence-only approaches by allowing for an extension to in-depth radioguidance.

Image-to-mesh conversion method for multi-tissue medical image computing simulations

AbstractConverting a three-dimensional medical image into a 3D mesh that satisfies both the quality and fidelity constraints of predictive simulations and image-guided surgical procedures remains a critical problem. Presented is an image-to-mesh conversion method called CBC3D. It first discretizes a segmented image by generating an adaptive Body-Centered Cubic mesh of high-quality elements. Next, the tetrahedral mesh is converted into a mixed element mesh of tetrahedra, pentahedra, and hexahedra to decrease element count while maintaining quality. Finally, the mesh surfaces are deformed to their corresponding physical image boundaries, improving the mesh’s fidelity. The deformation scheme builds upon the ITK open-source library and is based on the concept of energy minimization, relying on a multi-material point-based registration. It uses non-connectivity patterns to implicitly control the number of extracted feature points needed for the registration and, thus, adjusts the trade-off between the achieved mesh fidelity and the deformation speed. We compare CBC3D with four widely used and state-of-the-art homegrown image-to-mesh conversion methods from industry and academia. Results indicate that the CBC3D meshes: (1) achieve high fidelity, (2) keep the element count reasonably low, and (3) exhibit good element quality.

Polymer-Tethered Quenched Fluorescent Probes for Enhanced Imaging of Tumor-Associated Proteases.

Fluorescence-based contrast agents enable real-time detection of solid tumors and their neovasculature, making them ideal for use in image-guided surgery. Several agents have entered late-stage clinical trials or secured FDA approval, suggesting they are likely to become the standard of care in cancer surgeries. One of the key parameters to optimize in contrast agents is molecular size, which dictates much of the pharmacokinetic and pharmacodynamic properties of the agent. Here, we describe the development of a class of protease-activated quenched fluorescent probes in which a N-(2-hydroxypropyl)methacrylamide copolymer is used as the primary scaffold. This copolymer core provides a high degree of probe modularity to generate structures that cannot be achieved with small molecules and peptide probes. We used a previously validated cathepsin substrate and evaluated the effects of length and type of linker, as well as the positioning of the fluorophore/quencher pair on the polymer core. We found that the polymeric probes could be optimized to achieve increased overall signal and tumor-to-background ratios compared to the reference small molecule probe. Our results also revealed multiple structure-activity relationship trends that can be used to design and optimize future optical imaging probes. Furthermore, they confirm that a hydrophilic polymer is an ideal scaffold for use in optical imaging contrast probes, allowing a highly modular design that enables efficient optimization to maximize probe accumulation and overall biodistribution properties.

Targeting tumour surface collage with hydrogel probe: a new strategy to enhance intraoperative imaging sensitivity and stability of bladder cancer.

The incomplete resection of non-muscle invasive bladder cancer (NMIBC) augments the risk of disease recurrence. Imaging-guided surgery by molecular probes represents a pivotal strategy for mitigating postoperative recurrence. Traditional optical molecular probes, primarily composed of antibodies/peptides targeting tumour cells and fluorescent groups, are challenged by the high heterogeneity of NMIBC cells, leading to inadequate probe sensitivity. We have developed a collagen-adhesive probe (CA-P) to target the collagen within the tumour microenvironment, aiming to address the issue of insufficient imaging sensitivity. The distribution characteristics of collagen in animal bladder cancer models and human bladder cancer tissues were explored. The synthesis and properties of CA-P were validated. In animal models, the imaging performance of CA-P was tested and compared with our previously reported near-infrared probe PLSWT7-DMI. The clinical translational potential of CA-P was assessed using human ex vivo bladder tissues. The distribution of collagen on the surface of tumour cells is distinct from its expression in normal urothelium. In vitro studies have demonstrated the ability of the CA-P to undergo a "sol-gel" transition upon interaction with collagen. In animal models and human ex vivo bladder specimens, CA-P exhibits superior imaging performance compared to PLSWT7-DMI. The sensitivity of this probe is 94.1%, with a specificity of 81%. CA-P demonstrates the capability to overcome tumour cell heterogeneity and enhance imaging sensitivity, exhibiting favorable imaging outcomes in preclinical models. These findings provide a theoretical basis for the application of CA-P in intraoperative navigation for NMIBC.

PRSCS-Net: Progressive 3D/2D rigid Registration network with the guidance of Single-view Cycle Synthesis

The 3D/2D registration for 3D pre-operative images (computed tomography, CT) and 2D intra-operative images (X-ray) plays an important role in image-guided spine surgeries. Conventional iterative-based approaches suffer from time-consuming processes. Existing learning-based approaches require high computational costs and face poor performance on large misalignment because of projection-induced losses or ill-posed reconstruction. In this paper, we propose a Progressive 3D/2D rigid Registration network with the guidance of Single-view Cycle Synthesis, named PRSCS-Net. Specifically, we first introduce the differentiable backward/forward projection operator into the single-view cycle synthesis network, which reconstructs corresponding 3D geometry features from two 2D intra-operative view images (one from the input, and the other from the synthesis). In this way, the problem of limited views during reconstruction can be solved. Subsequently, we employ a self-reconstruction path to extract latent representation from pre-operative 3D CT images. The following pose estimation process will be performed in the 3D geometry feature space, which can solve the dimensional gap, greatly reduce the computational complexity, and ensure that the features extracted from pre-operative and intra-operative images are as relevant as possible to pose estimation. Furthermore, to enhance the ability of our model for handling large misalignment, we develop a progressive registration path, including two sub-registration networks, aiming to estimate the pose parameters via two-step warping volume features. Finally, our proposed method has been evaluated on a public dataset CTSpine1k and an in-house dataset C-ArmLSpine for 3D/2D registration. Results demonstrate that PRSCS-Net achieves state-of-the-art registration performance in terms of registration accuracy, robustness, and generalizability compared with existing methods. Thus, PRSCS-Net has potential for clinical spinal disease surgical planning and surgical navigation systems.

2D/3D deformable registration for endoscopic camera images using self-supervised offline learning of intraoperative pneumothorax deformation

Shape registration of patient-specific organ shapes to endoscopic camera images is expected to be a key to realizing image-guided surgery, and a variety of applications of machine learning methods have been considered. Because the number of training data available from clinical cases is limited, the use of synthetic images generated from a statistical deformation model has been attempted; however, the influence on estimation caused by the difference between synthetic images and real scenes is a problem. In this study, we propose a self-supervised offline learning framework for model-based registration using image features commonly obtained from synthetic images and real camera images. Because of the limited number of endoscopic images available for training, we use a synthetic image generated from the nonlinear deformation model that represents possible intraoperative pneumothorax deformations. In order to solve the difficulty in estimating deformed shapes and viewpoints from the common image features obtained from synthetic and real images, we attempted to improve the registration error by adding the shading and distance information that can be obtained as prior knowledge in the synthetic image. Shape registration with real camera images is performed by learning the task of predicting the differential model parameters between two synthetic images. The developed framework achieved registration accuracy with a mean absolute error of less than 10 mm and a mean distance of less than 5 mm in a thoracoscopic pulmonary cancer resection, confirming improved prediction accuracy compared with conventional methods.

Viscosity-activated carbon dots for noninvasive disease diagnosis, therapeutic efficacy assessment and anticancer drug screening

Abnormal levels of intracellular microviscosity have a close relationship with some diseases and pathologies. Therefore, quantitative imaging of viscosity at the cellular and organ levels is beneficial for disease diagnosis, curative effect evaluation, and anticancer drug screening. Herein, we synthesized viscosity-activated orange-red emitting carbon dots (named as LP-CDs) from lignin and p-phenylenediamine using a one-step method, whose fluorescence intensity, lifetime, and quantum yield significantly increase with rising viscosity. Meanwhile, the fluorescence intensity of LP-CDs also has a good linear relationship with the solution viscosity. Taking the advantages of high sensitivity, noninvasiveness, and rapid result output of fluorescence imaging, LP-CDs can visualize the cellular viscosity changes induced by inflammation and hyperglycemia, and image tumor evolution. More importantly, LP-CDs can be used as powerful sensors to screen anticancer drugs in vivo by evaluating therapeutic effects. This work provides a new scheme for constructing robust nanoprobes to achieve the diagnosis and imaging-guided surgery of viscosity related diseases.

Evaluation of a bimodal, matched pair theranostic agent targeting prostate-specific membrane antigen

BackgroundProstate cancer affects 1 in 6 men, and it is the second‑leading cause of cancer-related death in American men. Surgery is one of the main treatment modalities for prostate cancer, but it often results in incomplete resection margins or complete resection that leads to nerve damage and undesirable side effects. In the present work, we have developed a new bimodal tracer, NODAGA-sCy7.5 PSMAi (prostate-specific membrane antigen inhibitor), labeled with the true matched theranostic pair 64Cu/67Cu and a near-infrared fluorescent dye. This agent could potentially be used for concomitant PET imaging, optical surgical navigation, and targeted radiopharmaceutical therapy. MethodsA prostate-specific membrane antigen (PSMA)-targeting urea derivative was conjugated to NODAGA for copper radiolabeling and to the near-infrared fluorophore sulfo-Cy7.5 (sCy7.5). Binding studies were performed in PSMA-positive PC-3 PIP cells, as well as uptake and internalization assays in PC-3 PIP cells and PSMA-negative PC-3 wild type cells. Biodistribution studies of the 64Cu-labeled compound were performed in PC-3 PIP- and PC-3 tumor-bearing mice, and 67Cu biodistributions of the agent were obtained in PC-3 PIP tumor-carrying mice. PET imaging and fluorescence imaging were also performed, using the same molar doses, in the two mouse models. ResultsThe PSMA conjugate bound with high affinity to PSMA-positive prostate cancer cells, as opposed to cells that were PSMA-negative. Uptake and internalization were rapid and PSMA-mediated in PC-3 PIP cells, while only minimal non-specific uptake was observed in PC-3 cells. Biodistribution studies showed specific uptake in PC-3 PIP tumors, while accumulation in PC-3 tumor-bearing mice was low. Furthermore, tumor uptake of the 67Cu-labeled agent in the PC-3 PIP model was statistically equivalent to that of 64Cu. PET and fluorescence imaging at 0.5 nmol per mouse also demonstrated that PC-3 PIP tumors could be clearly detected, while PC-3 tumors showed no tumor accumulation. ConclusionsNODAGA-sCy7.5-PSMAi was specific and selective in detecting PSMA-positive, as opposed to PSMA-negative, tumors in mouse models of prostate cancer. This bioconjugate could potentially be used for PET staging with 64Cu, targeted radiopharmaceutical therapy with 67Cu, and/or image-guided surgery with sCy7.5.

The Rise of Molecular Image-Guided Robotic Surgery.

Following early acceptance by urologists, the use of surgical robotic platforms is rapidly spreading to other surgical fields. This empowerment of surgical perception via robotic advances occurs in parallel to developments in intraoperative molecular imaging. Convergence of these efforts creates a logical incentive to advance the decades-old image-guided robotics paradigm. This yields new radioguided surgery strategies set to optimally exploit the symbiosis between the growing clinical translation of robotics and molecular imaging. These strategies intend to advance surgical precision by increasing dexterity and optimizing surgical decision-making. In this state-of-the-art review, topic-related developments in chemistry (tracer development) and engineering (medical device development) are discussed, and future scientific robotic growth markets for molecular imaging are presented.

Task-based image quality assessment of an intraoperative CBCT for spine surgery compared with conventional CT

Purpose:To analyze the image quality of a novel, state-of-the art platform for CBCT image-guided spine surgery, focusing particularly on the dose–effectiveness compared with conventional CT (the gold standard for postoperative assessment). Methods:The ClarifEye platform (Philips Healthcare) with integrated augmented-reality surgical navigation, has been compared with a GE Revolution CT (GE Healthcare). The 3D spatial resolution (TTF) and noise (NPS) were evaluated considering relevant feature contrasts (200–900 HU) and background noise for differently sized patients (200–300 mm water-equivalent diameter). These measures were used to determine the noise equivalent quanta (NEQ) and observer model detectability. Results:The CBCT system exhibited a linear response with 50% TTF at 5.7 cycles/cm (10% TTF at 9.2 cycles/cm), and the axial noise power peaking at about 3.6 cycles/cm (average frequency of 4.1 cycles/cm). The noise magnitude and texture differed markedly compared to iteratively reconstructed CT images (GE ASiR-V). The CBCT system had 26% lower detectability for a high-frequency task (related to edge detection) compared with CT images reconstructed using the Bone kernel combined with ASiR-V 50%. Likewise, it had 18% lower detectability for low- and mid-frequency tasks compared with CT images reconstructed using the Standard kernel. This difference translates to 50%–80% higher CBCT imaging doses required to match the CT image quality. Conclusions:The ClarifEye platform demonstrates intraoperative CBCT-imaging capabilities that under certain circumstances are comparable with conventional CT. However, due to limited dose–effectiveness, a trade-off between timeliness and radiation exposure must be considered if end-of-procedure CBCT is to replace postoperative CT.

Nitroreductase-Triggered Fluorophore Labeling of Cells and Tissues under Hypoxia.

Several reductases, including nitroreductase, are upregulated under hypoxic conditions characterized by an oxygen-deficient microenvironment. Given that hypoxia is a prominent feature of solid tumors, our investigation focused on developing a bioconjugative probe designed for staining tissue under hypoxic conditions, particularly activated by nitroreductase. This probe, developed using our trigger-release-bioconjugation system rooted in the ortho-quinone methide chemistry, exhibited selective activation by nitroreductase and fluorophore labeling within mitochondria and endoplasmic reticulum. As a result, it displayed sustained fluorescence that persisted even after washing steps in cells and tissues. We applied this innovative probe to stain mouse kidney tissue in an acute kidney injury model induced by inadequate oxygen supply. Among various organ tissues examined, only kidney tissue showed significantly higher fluorescence in the injury model compared with the control tissue, as revealed by two-photon microscopic imaging. This research presents a promising avenue for the development of practical staining agents for image-guided tumor surgery.

Mitochondria-Targetable Near-Infrared Fluorescent Probe for Visualization of Hydrogen Peroxide in Lung Injury, Liver Injury, and Tumor Models.

Hydrogen peroxide (H2O2) overexpressed in mitochondria has been regarded as a key biomarker in the pathological processes of various diseases. However, there is currently a lack of suitable mitochondria-targetable near-infrared (NIR) probes for the visualization of H2O2 in multiple diseases, such as PM2.5 exposure-induced lung injury, hepatic ischemia-reperfusion injury (HIRI), nonalcoholic fatty liver (NAFL), hepatic fibrosis (HF), and malignant tumor tissues containing clinical cancer patient samples. Herein, we conceived a novel NIR fluorescent probe (HCy-H2O2) by introducing pentafluorobenzenesulfonyl as a H2O2 sensing unit into the NIR hemicyanine platform. HCy-H2O2 exhibits good sensitivity and selectivity toward H2O2, accompanied by a remarkable "turn-on" fluorescence signal at 720 nm. Meanwhile, HCy-H2O2 has stable mitochondria-targetable ability and permits monitoring of the up-generated H2O2 level during mitophagy. Furthermore, using HCy-H2O2, we have successfully observed an overproduced mitochondrial H2O2 in ambient PM2.5 exposure-induced lung injury, HIRI, NAFL, and HF models through NIR fluorescence imaging. Significantly, the visualization of H2O2 has been achieved in both tumor-bear mice as well as surgical specimens of cancer patients, making HCy-H2O2 a promising tool for cancer diagnosis and imaging-guided surgery.

Augmented Reality-Guided Extraction of Fully Impacted Lower Third Molars Based on Maxillofacial CBCT Scans

(1) Background: This study aimed to integrate an augmented reality (AR) image-guided surgery (IGS) system, based on preoperative cone beam computed tomography (CBCT) scans, into clinical practice. (2) Methods: In preclinical and clinical surgical setups, an AR-guided visualization system based on Microsoft’s HoloLens 2 was assessed for complex lower third molar (LTM) extractions. In this study, the system’s potential intraoperative feasibility and usability is described first. Preparation and operating times for each procedure were measured, as well as the system’s usability, using the System Usability Scale (SUS). (3) Results: A total of six LTMs (n = 6) were analyzed, two extracted from human cadaver head specimens (n = 2) and four from clinical patients (n = 4). The average preparation time was 166 ± 44 s, while the operation time averaged 21 ± 5.9 min. The overall mean SUS score was 79.1 ± 9.3. When analyzed separately, the usability score categorized the AR-guidance system as “good” in clinical patients and “best imaginable” in human cadaver head procedures. (4) Conclusions: This translational study analyzed the first successful and functionally stable application of the HoloLens technology for complex LTM extraction in clinical patients. Further research is needed to refine the technology’s integration into clinical practice to improve patient outcomes.

Neural Progenitor Cell-Mediated Magnetic Nanoparticles for Magnetic Resonance Imaging and Photothermal Therapy of Glioma.

Glioma is the most common primary malignant tumor in the brain. The diagnostic accuracy and treatment efficiency of glioma are facing great challenges due to the presence of the blood-brain barrier (BBB) and the high infiltration of glioma. There is an urgent need to explore the combination of diagnostic and therapeutic approaches to achieve a more accurate diagnosis, as well as guidance before and after surgery. In this work, we induced human induction of pluripotent stem cell into neural progenitor cells (NPCs) and synthesized nanoprobes labeled with enhanced green fluorescent protein (EGFP, abbreviated as MFe3O4-labeled EGFP-NPCs) for photothermal therapy. Nanoprobes carried by NPCs can effectively penetrate the BBB and target glioma for the purpose of magnetic resonance imaging and guiding surgery. More importantly, MFe3O4-labeled EGFP-NPCs can effectively induce local photothermal therapy, conduct preoperative tumor therapy, and inhibit the recurrence of postoperative glioma. This work shows that MFe3O4-labeled EGFP-NPCs is a promising nanoplatform for glioma diagnosis, accurate imaging-guided surgery, and effective photothermal therapy.