Image-guided Surgery Research Articles

Highly Sensitive Chemiluminescent Probe for CYP 2J2 Detection and Image-Guided Liver Cancer Surgery.

Developing chemiluminescent (CL) probes with a high tumor-to-normal tissue ratio is crucial for liver tumor visualization and image-guided surgery. Cytochrome P450 2J2 (CYP 2J2), an extrahepatic enzyme, is highly expressed in liver tumors but not in healthy tissues. However, no prior reports have documented the development of CL probes specifically targeting CYP 2J2. In this study, we designed a CYP 2J2-responsive CL probe, termed CYP-PD, by grafting methoxybenzyl alcohol onto Schaap's dioxetanes. In vitro and cellular experiments confirmed that CYP-PD selectively and sensitively responds to both exogenous and endogenous CYP 2J2, exhibiting an extraordinary limit of detection of 1.21 pM and a cellular detection threshold as low as 235 cells. Moreover, CYP-PD demonstrated the highest CL intensity in HepG-2 cells, with an ∼59.6-fold enhancement relative to normal liver cells (L02). Notably, the probe enabled a high tumor-to-normal tissue visualization ratio of tumor lesions from normal liver tissues (∼44.7-fold), successfully guiding the surgical resection of an orthotopic liver cancer mouse model. We envision that this work may provide a powerful tool for CYP 2J2 detection and image-guided liver cancer surgery in the future.

Awake versus asleep deep brain stimulation targeting the caudal zona incerta for essential tremor

To compare awake and asleep deep brain stimulation (DBS) surgery for Essential Tremor (ET), we conducted this retrospective cohort study of patients consecutively operated with DBS targeting the caudal Zona incerta (cZi). 37 underwent surgery awake and 55 asleep. Tremor before surgery and on/off stimulation one year after surgery were evaluated using the Essential Tremor Rating Scale (ETRS). Procedural time, electrode localization, stimulation parameters and adverse events were noted and compared. ETRS scores were similar at baseline between the groups except for contralateral arm tremor, which was slightly worse in the awake group. Total ETRS, contralateral arm tremor and activities of daily living scores showed no significant difference between the groups on-stimulation at one-year follow-up. Compared to the awake group, the asleep group had shorter procedural time and lower stimulation parameters. There were no intracranial haemorrhages nor surgery site-infections. Both groups showed a good improvement of tremor at one-year follow-up. Image-guided DBS surgery targeting the cZi enables safe and efficient asleep surgery for ET.

The safety of indocyanine green in patients with advanced chronic kidney disease or kidney transplantation – a scoping review

Near-infrared fluorescence imaging with indocyanine green (ICG) is increasingly being used in the field of image-guided surgery. Although ICG is considered non-nephrotoxic in current literature, caution is advised for the use of ICG in patients with advanced chronic kidney disease (CKD), including kidney transplant recipients. Therefore, a scoping review was performed to assess the safety of ICG in patients with advanced CKD or a renal allograft. This scoping review was guided by the PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-analyses extension for Scoping Reviews). Web of Science, PubMed, and Embase were searched for articles and abstracts in which ICG was administered in patients with CKD or a renal allograft. The extracted data included the incidence of adverse events, kidney function after injection of ICG, preservation of transplant function, and type of other possible complications. The initial search resulted in 635 records of which nineteen studies were found eligible for the review. ICG was used for multiple purposes but never specifically as an objective to investigate possible nephrotoxicity. No adverse events were reported in the transplant group (n=250) or the CKD group (n= 74). Despite ICG-injection, preservation of transplant function after transplantation surgery was 94% in 198 patients, and no increase in possible ICG-related other complications was reported. This scoping review found no evidence that ICG increases the risk of adverse events in patients with CKD, including kidney transplant recipients. Therefore, the administration of ICG should not be withheld from these patients.

Near-infrared fluorescent molecular probes with cetuximab in the in vivo fluorescence imaging for epithelial ovarian cancer

BackgroundNear-infrared fluorescence (NIRF) imaging is an excellent choice for image-guided surgery due to its simple operation and non-invasiveness. Developing tumor-specific fluorescent molecular probes is key to fluorescence imaging-guided surgery. EGFR (epidermal growth factor receptor) is closely related to the proliferation and growth of tumor cells and is highly expressed in epithelial ovarian cancer (EOC). The study aims to construct a NIR fluorescent molecular probe using cetuximab (an EGFR monoclonal antibody) and investigate its feasibility for targeting EOC in vivo through fluorescence imaging.MethodsWe determined the expression of EGFR in EOC. NIR fluorescent molecular probe with cetuximab (cetuximab-Cy7) was chemically engineered and identified. The subcutaneous xenografted tumor model of EOC was induced using SKOV3-Luc cell line with positive expression of EGFR. Cetuximab-Cy7 was used for in vivo fluorescence imaging, and phosphate-buffered saline, free Cy7 dye and mouse isotype immunoglobulin G-Cy7 were used as controls. NIRF imaging system was performed to study the distribution and targeting of the probes. Tumors were imaged in situ and ex vivo, and fluorescent intensity was quantified. Resected specimens were analyzed to confirm diagnosis, and immunohistochemical (IHC) staining was used to identify EGFR expression.ResultsEGFR expression was increased in EOC tissues than fallopian tube tissues. The high expression of EGFR was significantly correlated with well-differentiation, residual lesions ≤ 1 cm, no recurrence and increased survival. NIRF imaging showed that the cetuximab-Cy7 enabled detection of tumor lesions in EOC-bearing mice with the optimal dose of 30 µg. The suitable imaging time window may be 24–96 h post-injection. Ex vivo fluorescence imaging indicated that fluorescent signal was mainly detected in the tumor and the lung. IHC results confirmed that xenografts were EGFR positive.ConclusionCetuximab-Cy7 can specifically target the tumors of EOC xenografted nude mice. This research lays the foundation for future studies on EOC surgery navigation.

Tumor agnostic ultrasmall nanoprobes for fluorescence-guided surgical resection in peritoneal metastasis.

Surgical excision of metastases is the only curative treatment strategy in peritoneal carcinomatosis management, and the completeness of tumor resection determines the success of the surgery. Tumor-specific fluorescence-guided probes can improve the outcomes of cytoreductive surgery and thereby prognosis. This study aimed to develop and evaluate the feasibility of fluorescently labeled ultrasmall porous silica nanoparticles (UPSN) for image-guided resection of peritoneally disseminated tumors of different origins. Ultrasmall fluorescent nanoprobes were synthesized and characterized for their physicochemical properties and stability. Tumor-specific uptake and biodistribution profiles were evaluated in syngeneic CT26 colorectal and KPC-689 pancreatic cancer murine models. The practicability of real-time optical UPSN-guided resection was examined in the CT26 colorectal cancer model using a surgical stereomicroscope. Quantitative measurements of tumor sensitivity and specificity were performed. Histopathological examination validated in vivo findings about tumor-specific accumulation and safety of ultrasmall fluorescent probes. As-synthesized UPSNs were successfully surface modified with Cy5 or Cy3 dyes maintaining sub-15nm size and near neutral charge which is beneficial for optimized in vivo pharmacokinetics. UPSN-Cy5 demonstrated high tumor-specific uptake and favorable biodistribution profiles in peritoneal metastasis models of CT26 and KPC tumors. Dye-conjugated UPSN enabled resection of microscopic lesions and achieved a higher tumor-to-background ratios in comparison to FDA-approved indocyanine green (ICG) dye in both models. Microscopic evaluation showed tumor localization and off-target safety profile of the UPSN-Cy5. Ultrasmall fluorescent probes were effective in surgical resection of peritoneal metastases with high sensitivity and specificity, thus emerging as promising tumor agnostic agents for image-guided cancer surgery.

MULTIMODAL (5-ALA, TRACTOGRAPHY AND ULTRASOUND GUIDED) AWAKE CRANIOTOMY FOR GLIOBLASTOMA: MAXIMISING SAFE SURGICAL RESECTION

Abstract AIMS Maximising the extent of surgical resection of glioblastoma is a key prognostic factor for survival. This must be balanced against avoiding neurological deficit, which may delay or preclude adjuvant treatments. This is a particular challenge in eloquent tumours. Optimal surgical adjuncts to enable maximal resection of glioblastomas in eloquent brain regions, remain unclear. We present the first series assessing the safety and efficacy of multimodality image-guided, awake resection of IDH-wildtype glioblastoma, combining 5-aminolevulinic acid (5-ALA), diffusion tractography (DTI) and intraoperative ultrasound (USS). METHOD We present a single centre retrospective series of 175 patients undergoing awake craniotomy for primary resection of glioblastomas, between January 2014 and January 2023. Awake craniotomy was considered if tumours were in or adjacent to eloquent areas. Key outcomes assessed included post-operative neurological complications (classified into transient, if persisting <3 months and completely resolved, or permanent if persisting >3 months), extent of resection (EOR) and overall survival (OS). RESULTS 175 patients (103M:72F) were included, with a mean age of 58.2 years. All cases used neuronavigation, whilst 5- ALA and DTI were used in 98.9% and 97.1% of patients respectively. Intraoperative USS was used 88/175 (50.3%). Gross total resection (>98%) was achieved in 101/175 patients (64.7%). 83/175 patients (47.4%) experienced a post-operative neurological deficit, which was temporary in 84.3% (70/83) of cases. When transient deficits occurred, these were most often speech related (49/70). Subgroup analysis found left temporal tumours were highest risk for transient dysphasia (59.2%), followed by left frontal (21.7%) and left parietal (16.0%). The median percentage EOR with USS was 100%, whilst without USS was 97.8% (Wilcox, p=0.0004). CONCLUSION Patients should be counselled about the high risk of transient neurological complications following awake surgery, particularly speech deficit. Multimodal image-guided surgery can maximise the extent of safe resection for glioblastoma.

Vertebral cortical thickness and cortical bone density: an automated CT assessment - towards enhanced spine segmentation

ABSTRACT In this paper a non-invasive method using routine CT scan to assess the vertebral geometry through normalised Cortical Thickness (CTh) and Cortical Bone Density (CBD) is proposed. This paper aims to propose a new automated method to segment cortical bone and measure its thickness and local density. This method were then used as a tool to compare these parameters between different vertebra models (in-vivo, cadaver and swine) and vertebra levels. An automated technique to segment cortical bone was proposed, assuming a two Gaussian bone density distribution. 42 vertebrae (3 high-thoracic, 3 low-thoracic and 1 lumbar vertebra for each subject) from three sub-groups (human in-vivo, cadaver and swine) were investigated. In the human in-vivo sub-group, the vertebral level was shown to influence normalised CTh and CBD. The CBD was found uniform within all the functional areas of the vertebral body (p > 0.05), while the normalised CTh showed significant differences (p < 0.001). Both CBD and normalised CTh showed significantly different between the inferior articular processes area and the posterior arch area d (p < 0.02 *). In each of the three sub-groups (human in-vivo Vs cadaveric Vs swine), normalised CTh and CBD were found significantly different across most functional areas (p < 0.001 ***). The proposed method offers an automated and accurate way of measuring cortical thickness and cortical bone density. Vertebra level and vertebra function areas were found to have influences on both proposed cortical bone characteristics. The influence of the vertebral level and of the vertebral functional areas on normalised CTh and CBD were reported within in-vivo and two vertebral models. Such a methodology could be used as a tool for image-guided surgery.

Co-Assembled Nanosystems Exhibiting Intrinsic Fluorescence by Complexation of Amino Terpolymer and Its Quaternized Analog with Aggregation-Induced Emission (AIE) Dye.

Aggregation-induced emission dyes (AIEs) have gained significant interest due to their unique optical properties. Upon aggregation, AIEs can exhibit remarkable fluorescence enhancement. These systems are ideal candidates for applications in bioimaging, such as image-guided drug delivery or surgery. Encapsulation of AIEs in polymeric nanocarriers can result in biocompatible and efficient nanosystems. Herein, we report the fabrication of novel nanoaggregates formulated by amino terpolymer and tetraphenylethylene (TPE) AIE in aqueous media. Poly(di(ethylene glycol) methyl ether methacrylate-co-2-(dimethylamino)ethylmethacrylate-co-oligoethylene glycol methyl ether methacrylate), P(DEGMA-co-DMAEMA-co-OEGMA) hydrophilic terpolymer was utilized for the complexation of the sodium tetraphenylethylene 4,4',4″,4‴-tetrasulfonate AIE dye. Fluorescence spectroscopy, physicochemical studies, and self-assembly in aqueous and fetal bovine serum media were carried out. The finely dispersed nanoparticles exhibited enhanced fluorescence compared to the pure dye. To investigate the role of tertiary amino groups in the aggregation phenomenon, the polymer was quaternized, and quaternized polymer nanocarriers were fabricated. The increase in fluorescence intensity indicated stronger interaction between the cationic polymer analog and the dye. A stronger interaction between the nanoparticles and fetal bovine serum was observed in the case of the quaternized polymer. Thus, P(DEGMA-co-DMAEMA-co-OEGMA) formulations are better candidates for bioimaging applications than the quaternized ones, presenting both aggregation-induced emission and less interaction with fetal bovine serum.

Targeted blood-brain barrier penetration and precise imaging of infiltrative glioblastoma margins using hybrid cell membrane-coated ICG liposomes

Surgical resection remains the primary treatment modality for glioblastoma (GBM); however, the infiltrative nature of GBM margins complicates achieving complete tumor removal. Additionally, the blood-brain barrier (BBB) poses a formidable challenge to effective probe delivery, thereby hindering precise imaging-guided surgery. Here, we introduce hybrid cell membrane-coated indocyanine green (ICG) liposomes (HM-Lipo-ICG) as biomimetic near-infrared (NIR) fluorescent probes for targeted BBB penetration and accurate delineation of infiltrative GBM margins. HM-Lipo-ICG encapsulates clinically approved ICG within its core and utilizes a hybrid cell membrane exterior, enabling specific targeting and enhanced BBB permeation. Quantitative assessments demonstrate that HM-Lipo-ICG achieves BBB penetration efficiency 2.8 times higher than conventional ICG liposomes. Mechanistically, CD44 receptor-mediated endocytosis facilitates BBB translocation of HM-Lipo-ICG. Furthermore, HM-Lipo-ICG enables high-contrast NIR imaging, achieving a signal-to-background ratio of 6.5 in GBM regions of an orthotopic glioma mouse model, thereby improving tumor margin detection accuracy fourfold (84.4% vs. 22.7%) compared to conventional ICG liposomes. Application of HM-Lipo-ICG facilitates fluorescence-guided precision surgery, resulting in complete resection of GBM cells. This study underscores the potential of hybrid cell membrane-coated liposomal probes in precisely visualizing and treating infiltrative GBM margins.Graphical abstract

Robotic Surgery in Paediatric Oncology: Expanding Boundaries and Defining Relevant Indications

This article reviews the establishment and progress of the Multidisciplinary Paediatric Robotic Program in a high-volume paediatric surgery department at Hôpital Necker-Enfants Malades, Paris, France. A major foundational principle of the program was to establish a safe and secure environment for patients and staff, both pre-operatively, intra-operatively and post-operatively. This founding principle when applied systematically has allowed increasing confidence across the program and service. The robotic platform allows for precision surgery when approaching tumours, with freedom of movement adapted to meticulous vascular and organ dissection. Surgical feasibility is based on tumour characteristics, pre-operative imaging, with a focus on vascular and organ involvement, considering goals of surgery and surgical experience. Case complexity has been gradually increased (where appropriate) through an iterative process. The future of surgery is robotic, and even more so image-guided surgery, and this synergy has been instrumental when approaching tumour surgery in children. The current principles that guide application of robot-assisted surgery in paediatric tumours are presented. With this blueprint, excellent oncological outcomes can be achieved while utilising a minimally invasive approach in children with selected endocrine, neuroblastic and renal tumours.

Functional Endoscopic Sinus Surgery: Key Points for Safer Surgery.

Objectives: To review measures for safer functional endoscopic sinus surgery (FESS). Methods: PubMed, EBSCO, UpToDate, Proquest Central at Kırıkkale University, Google, and Google Scholar were used in the literature review. The search was performed using keywords of "functional endoscopic sinus surgery," "FESS," "Safety," "Image-Guided," and "complications" between 2000 and 2024. Results: Inflammatory and infectious sinus illnesses are the most prevalent indications for FESS. The 4 most common methods for FESS are endoscopic uncinectomy, maxillary antral ostomy/ethmoidectomy, anterior ethmoidectomy, and posterior ethmoidectomy. FESS has a complication rate of 0% to 1.5% for significant problems and 1.12% to 20.8% for minor issues. Sinus surgery outcomes can be improved and problems avoided with careful preoperative preparation. Powered instrumentation may enhance the severity of the problems rather than the number of occurrences. Intraoperative detection of cerebrospinal fluid leakage necessitates immediate localization and fixing of the leaking structure. The danger of infection increases and hospital stays are longer when investigation is delayed. In image-guided surgery, surgeons employ preoperative imaging data to pinpoint the exact position of a surgical tool concerning surrounding anatomical structures in real time. Although initially designed for use in neurosurgery, endoscopic sinus surgery has quickly become one of the most popular applications of this technique. Conclusion: Safer FESS can be accomplished with accurate CT scans, good patient preparation, surgical knowledge and training, and by using image guidance for endoscopic sinus surgery.

A near-infrared fluorescent probe with assembly/aggregation-induced retention effect for specific diagnosis of metastasis and image-guided surgery in breast cancer

Image-guided surgery is crucial for achieving complete tumor resection, reducing postoperative recurrence and improving patient survival. However, current clinical near-infrared fluorescent probes, such as indocyanine green (ICG), face two main limitations: 1) lack of active tumor targeting, and 2) short retention time in tumors, which restricts real-time imaging during surgery. To address these issues, we developed a near-infrared fluorescent probe capable of in situ nanofiber formation within tumor lesions. This probe actively targets the integrin αvβ3 receptors overexpressed on breast cancer cells and exhibits assembly/aggregation-induced retention effects at the tumor site, significantly extending the imaging time window. Additionally, we found that the probe's fluorescence intensity can be enhanced under receptor induction. Due to its excellent tumor specificity and sensitivity, 1FCG-FFGRGD not only identifies primary breast cancer but also precisely locates smaller lymph node metastases and detects sub-millimeter peritoneal metastases. In summary, this near-infrared probe, leveraging assembly/aggregation-induced retention effects, holds substantial potential for various biomedical applications.

MRI-compatible and sensorless haptic feedback for cable-driven medical robotics to perform teleoperated needle-based interventions.

Surgical robotics have demonstrated their significance in assisting physicians during minimally invasive surgery. Especially, the integration of haptic and tactile feedback technologies can enhance the surgeon's performance and overall patient outcomes. However, the current state-of-the-art lacks such interaction feedback opportunities, especially in robotic-assisted interventional magnetic resonance imaging (iMRI), which is gaining importance in clinical practice, specifically for percutaneous needle punctures. The cable-driven 'Micropositioning Robotics for Image-Guided Surgery' (µRIGS) system utilized the back-electromotive force effect of the stepper motor load to measure cable tensile forces without external sensors, employing the TMC5160 motor driver. The aim was to generate a sensorless haptic feedback (SHF) for remote needle advancement, incorporating collision detection and homing capabilities for internal automation processes. Three different phantoms capable of mimicking soft tissue were used to evaluate the difference in force feedback between manual needle puncture and the SHF, both technically and in terms of user experience. The SHF achieved a sampling rate of 800Hz and a mean force resolution of 0.26 ± 0.22N, primarily dependent on motor current and rotation speed, with a mean maximum force of 15N. In most cases, the SHF data aligned with the intended phantom-related force progression. The evaluation of the user study demonstrated no significant differences between the SHF technology and manual puncturing. The presented SHF of the µRIGS system introduced a novel MR-compatible technique to bridge the gap between medical robotics and interaction during real-time needle-based interventions.

Long-term reprojection loss for self-supervised monocular depth estimation in endoscopic surgery

Aim: Depth information plays a key role in enhanced perception and interaction in image-guided surgery. However, it is difficult to obtain depth information with monocular endoscopic surgery due to a lack of reliable cues for perceiving depth. Although there are reprojection loss-based self-supervised learning techniques to estimate depth and pose, the temporal information from the adjacent frames is not efficiently utilized to handle occlusion in surgery. Methods: We design long-term reprojection loss (LT-RL) self-supervised monocular depth estimation techniques by integrating longer temporal sequences into reprojection to learn better perception and to address occlusion artifacts in image-guided laparoscopic and robotic surgery. For this purpose, we exploit four temporally adjacent source frames before and after the target frame, where conventional reprojection loss uses two adjacent frames. The pixels that are visible in the target frame but occluded in the immediate two adjacent frames will produce the inaccurate depth but a higher chance to appear in the four adjacent frames during the calculation of minimum reprojection loss. Results: We validate LT-RL on the benchmark surgical datasets of Stereo correspondence and reconstruction of endoscopic data (SCARED) and Hamlyn to compare the performance with other state-of-the-art depth estimation methods. The experimental results show that our proposed technique yields 2%-4% better root-mean-squared error (RMSE) over the baselines of vanilla reprojection loss. Conclusion: Our LT-RL self-supervised depth and pose estimation technique is a simple yet effective method to tackle occlusion artifacts in monocular surgical video. It does not add any training parameters, making it flexible for integration with any network architecture and improving the performance significantly.

Tuning nanoparticle core composition drives orthogonal fluorescence amplification for enhanced tumour imaging

Tumour detection with high selectivity and sensitivity is crucial for delineating tumour margins and identifying metastatic foci during image-guided surgery. Optical nanoprobes with preferential tumour accumulation is often limited by inefficient amplification of biological signals. Here, we report the design of a library of hydrophobic core-tunable ultra-pH-sensitive nanoprobes (HUNPs) for orthogonally amplifying tumour microenvironmental signals on multiple tumour models. We find that tuning the hydrophobicity of nanoparticle core composition with non-ionizable monomers can enhance cellular association of HUNPs by more than ten-fold, resulting in a high cellular internalization efficiency of HUNPs with up to 50% in tumours. Combining high tumour accumulation and high cell internalization efficiency, HUNPs show orthogonally amplified fluorescence signals, permitting the precise locating and delineating margins between malignant lesions and normal tissues with high contrast-to-noise ratio and resolution. Our study provides key strategies to design nanomedicines with high intracellular bioavailability for cancer detection, drug/gene delivery, and therapy.

Multifaceted biomedical applications of bismuth oxide-doped bioactive glass: Synthesis challenges, characterization and potential clinical implications

Herewith, the present work reports a facile synthesis method of Bi2O3 doped 70 SiO2.30CaO binary bioactive glass system termed as modified Bi-BG (acronymed as mBi-BG) that indicates successful incorporation of Bi3+ into the silicate glassy network, on prior complex formation of the precursor bismuth nitrate salt with acetyl acetone to address the rapid decomposition rate of precursor bismuth nitrate. The binary bioactive glass composition as above mentioned (70 SiO2.30CaO) is named as BG/Control. The synthesis methodology addresses inherent challenges encountered in traditional sol-gel derived bismuth oxide incorporated bioactive glass (Bi-BG) synthesis wherein yellow coloured bismuth oxide gets separated from the glassy network as confirmed by XRD phase analysis. Next, mBi-BG (modified Bi-BG) was synthesized via modifying the sol gel method by introducing a chelating agent acetyl acetone to stabilize the precursor Bi (NO3)3 salt, and was characterized using XRD, FTIR, FESEM-EDX. TG-DSC and BET isotherm. In vitro bioactivity studies illustrate the formation of hydroxyapatite crystals on mBi-BG surface indicating its potential for bone repair and regeneration. Additionally, mBi-BG exhibits significant effect against Staphylococcus aureus (gram-positive) bacterial strain, highlighting its utility in preventing bacterial infections at surgical sites. Radiographic imaging of mBi-BG reveals excellent radiopacity comparable to human bone, rendering it suitable for image-guided surgeries and fluoroscopic procedures. In summary, mBi-BG emerges as a versatile biomaterial with enhanced bioactivity, antibacterial efficacy and radiopacity, thereby offering novel avenues in medical treatment modalities and patient care.

NIR‐II AIEgens nanosystem for fluorescence and chemiluminescence synergistic imaging‐guided precise resection in osteosarcoma surgery

AbstractOsteosarcoma (OS) is characterized by an unfavorable prognosis and high mortality rates, with the local recurrence attributed to residual lesions post‐surgery being a major reason for treatment failure. Precise and tumor‐specific resection guidance to minimize recurrence remains a significant challenge. In the present study, a nanosystem based on aggregation‐induced emission (AIE) molecules with emission in the second near‐infrared window is proposed for the synergistic fluorescence (FL) and chemiluminescence (CL) imaging‐guided surgical resection for the elimination of tumor foci. The designed AIE molecule, BBTD14, exhibits stable FL with a high quantum yield of up to 3.95%, which effectively matches the energy levels of CL high‐energy states, generating the longest emission wavelength of CL reported to date. Targeted tumor imaging‐guided surgery (IGS) is facilitated by FL and CL nanoprobes (FLNP and CLNP) constructed based on BBTD14. During OS surgery, the FLNP, with the stability of FL and a high targeting capability, was first intravenously used to guide the surgical removal of the main tumor. Subsequently, CLNP was locally incubated to facilitate rapid and accurate evaluation of residual tumors at the operative border. High signal‐to‐noise ratio CL imaging was achieved after spraying with hydrogen peroxide, thereby overcoming the limitations of intraoperative frozen sections. The proposed technique also significantly reduced the recurrence rates in OS mouse models and exhibited high marker specificity in ex vivo OS patient pathology samples, confirming its potential in clinical applications and providing a unique perspective for developing IGS.

The Current Status and Future Directions on Nanoparticles for Tumor Molecular Imaging.

Molecular imaging is an advanced technology that utilizes specific probes or markers in conjunction with cutting-edge imaging techniques to observe and analyze the localization, distribution, activity, and interactions of biomolecules within living organisms. Tumor molecular imaging, by enabling the visualization and quantification of molecular characteristics of tumor cells, facilitates a deeper and more comprehensive understanding of tumors, providing valuable insights for early diagnosis, treatment monitoring, and cancer biology research. However, the image quality of molecular imaging still requires improvement, and nanotechnology has significantly propelled the advancement of molecular imaging. Currently, nanoparticle-based tumor molecular imaging technologies encompass radionuclide imaging, fluorescence imaging, magnetic resonance imaging, ultrasound imaging, photoacoustic imaging, and multimodal imaging, among others. As our understanding of the tumor microenvironment deepens, the design of nanoparticle probes for tumor molecular imaging has also evolved, offering new perspectives and expanding the applications of tumor molecular imaging. Beyond diagnostics, there is a marked trend towards integrated diagnosis and therapy, with image-guided treatment playing a pivotal role. This includes image-guided surgery, photodynamic therapy, and chemodynamic therapy. Despite continuous advancements and innovative developments in molecular imaging, many of these remain in the experimental stage and require breakthroughs before they can be fully integrated into clinical practice.

Vacuum-based and body-mounted robotic-patient interface with an integrated metasurface for MRI-guided interventions

Abstract The increased clinical relevance of image-guided procedures, particularly of interventional magnetic resonance imaging (iMRI), highlights the need for advanced devices and robotics to optimize those procedures. To enable a realistic integration of robotics into the clinical workflow, robotic-patient interfaces (RPI) are required to ensure both functionality and usability. However, current concepts have issues with patient accessibility and safety, user handling, or performing interventions on versatile body regions. This work presents a novel silicone-based RPI to flexibly mount the ’Micropositioning Robotics for Image-Guided Surgery’ (μRIGS) system on differently shaped body regions through vacuum, regulated with an electronic miniature pump. Maximum holding forces of 60N at −0.1 bar and 66N at −0.2 bar relative vacuum pressure were reached depending on the applied human body area and tensile force angles. MRI with the integrated metasurface indicated up to 200% signal enhancement, enabling improved tissue contrast within the first 20mm in depth. The multifunctional design supported the incorporation of the sterile iMRI workflow concept. This RPI enables a realistic integration of future technologies such as miniature robots, tracking markers, and instrument holders into complex interventional workflows. Further long-term studies are needed to evaluate the effects of vacuum application lasting for 1-2 hours on different skin types.

Detection of Hepatocellular Carcinoma in an Orthotopic Patient-Derived Xenograft with an Epithelial Cell Adhesion Molecule-Specific Peptide.

Hepatocellular carcinoma (HCC) has emerged as a major contributor to the worldwide cancer burden. Improved methods are needed for early cancer detection and image-guided surgery. Peptides have small dimensions that can overcome delivery challenges to achieve high tumor concentrations and deep penetration. We used phage display methods to biopan against the extra-cellular domain of the purified EpCAM protein, and used IRDye800 as a near-infrared (NIR) fluorophore. The 12-mer sequence HPDMFTRTHSHN was identified, and specific binding to EpCAM was validated with HCC cells in vitro. A binding affinity of kd = 67 nM and onset of k = 0.136 min-1 (7.35 min) were determined. Serum stability was measured with a half-life of T1/2 = 2.6 h. NIR fluorescence images showed peak uptake in vivo by human HCC patient-derived xenograft (PDX) tumors at 1.5 h post-injection. Also, the peptide was able to bind to foci of local and distant metastases in liver and lung. Peptide biodistribution showed high uptake in tumor versus other organs. No signs of acute toxicity were detected during animal necropsy. Immunofluorescence staining of human liver showed specific binding to HCC compared with cirrhosis, adenoma, and normal specimens.