High-precision tumor resection down to few-cell level guided by NIR-IIb molecular fluorescence imaging.

In vivo fluorescence/luminescence imaging in the near-infrared-IIb (NIR-IIb, 1,500 to 1,700 nm) window under <1,000 nm excitation can afford subcentimeter imaging depth without any tissue autofluorescence, promising high-precision intraoperative navigation in the clinic. Here, we developed a compact imager for concurrent visible photographic and NIR-II (1,000 to 3,000 nm) fluorescence imaging for preclinical image-guided surgery. Biocompatible erbium-based rare-earth nanoparticles (ErNPs) with bright down-conversion luminescence in the NIR-IIb window were conjugated to TRC105 antibody for molecular imaging of CD105 angiogenesis markers in 4T1 murine breast tumors. Under a ∼940 ± 38 nm light-emitting diode (LED) excitation, NIR-IIb imaging of 1,500- to 1,700-nm emission afforded noninvasive tumor­to­normal tissue (T/NT) signal ratios of ∼40 before surgery and an ultrahigh intraoperative tumor-to-muscle (T/M) ratio of ∼300, resolving tumor margin unambiguously without interfering background signal from surrounding healthy tissues. High-resolution imaging resolved small numbers of residual cancer cells during surgery, allowing thorough and nonexcessive tumor removal at the few-cell level. NIR-IIb molecular imaging afforded 10-times-higher and 100-times-higher T/NT and T/M ratios, respectively, than imaging with IRDye800CW-TRC105 in the ∼900- to 1,300-nm range. The vastly improved resolution of tumor margin and diminished background open a paradigm of molecular imaging-guided surgery.

A Dual-Cascade Activatable Near-Infrared Fluorescent Probe for Precise Intraoperative Imaging of Tumor.

Accurate intraoperative tumor delineation is critical to achieving successful surgical outcomes. However, conventional techniques typically suffer from poor specificity and low sensitivity and are time-consuming, which greatly affects intraoperative decision-making. Here, we report a cascade activatable near-infrared fluorescent (NIRF) probe IR780SS@CaP that can sequentially respond to tumor acidity and elevated glutathione levels for accurate intraoperative tumor localization. Compared with nonactivatable and single-factor activatable probes, IR780SS@CaP with a cascade strategy can minimize nonspecific activation and false positive signals in a complicated biological environment, affording a superior tumor-to-normal tissue ratio to facilitate the delineation of abdominal metastases. Small metastatic lesions that were less than 1 mm in diameter can be precisely identified by IR780SS@CaP and completely excised under NIRF imaging guidance. This study could benefit tumor diagnosis and image-guided tumor surgery by providing real-time information and reliable decision support, thus reducing the risk of both recurrence and complications to improve patient outcomes.

Visualization of Brain Tumors with Infrared-Labeled Aptamers for Fluorescence-Guided Surgery.

Gliomas remain challenging brain tumors to treat due to their infiltrative nature. Accurately identifying tumor boundaries during surgery is crucial for successful resection. This study introduces an innovative intraoperative visualization method utilizing surgical fluorescence microscopy to precisely locate tumor cell dissemination. Here, the focus is on the development of a novel contrasting agent (IR-Glint) for intraoperative visualization of human glial tumors comprising infrared-labeled Glint aptamers. The specificity of IR-Glint is assessed using flow cytometry and microscopy on primary cell cultures. In vivo effectiveness is studied on mouse and rabbit models, employing orthotopic xenotransplantation of human brain gliomas with various imaging techniques, including PET/CT, in vivo fluorescence visualization, confocal laser scanning, and surgical microscopy. The experiments validate the potential of IR-Glint for the intraoperative visualization of gliomas using infrared imaging. IR-Glint penetrates the blood-brain barrier and can be used for both intravenous and surface applications, allowing clear visualization of the tumor. The surface application directly to the brain reduces the dosage required and mitigates potential toxic effects on the patient. The research shows the potential of infrared dye-labeled aptamers for accurately visualizing glial tumors during brain surgery. This novel aptamer-assisted fluorescence-guided surgery (AptaFGS) may pave the way for future advancements in the field of neurosurgery.

Unfolded Protein-Based Sandwich AIE Probe Imparts High Fluorescent Contrast for Pan-Cancer Surgical Navigation.

Fluorescence imaging-guided navigation for cancer surgery has a promising clinical application. However, pan-cancer encompasses a wide variety of cancer types with significant heterogeneity, resulting in the lack of universal and highly contrasted fluorescent probes for surgical navigation. Here, we developed an aggregation-induced emission (AIE) probe (MI-AIE-TsG, MAT) with dual activation for pan-cancer surgical navigation. MAT weakly activates fluorescence by targeting the SUR1 protein on the endoplasmic reticulum (ER) through the TsG group. Subsequently, the sulfhydryl groups on the unfolded proteins, which are highly enriched in cancer ER, react with the maleimide (MI) of MAT through the thiol-ene click reaction, further enhancing the fluorescence. The formation of a SUR1-MAT-unfolded protein sandwich complex reinforces the restriction of intramolecular motion and eliminates photoinduced electron transfer of MAT, leading to high signal-to-noise (9.2) fluorescence imaging and use for surgical navigation of pan-cancer. The generally high content of unfolded proteins in cancer cells makes MAT imaging generalizable, and it currently has proven feasibility in ovarian, cervical, and breast cancers. Meanwhile, MAT promotes cellular autophagy by hindering protein folding, thereby inhibiting cancer cell proliferation. This generalizable, high-contrast AIE fluorescent probe spans the heterogeneity of pancreatic cancer, enabling precise pancreatic cancer surgery navigation and treatment.

Surgical marker navigation system in breast conserving surgery and excision of non-palpable lesions: first Spanish single-center experience.

BACKGROUND: Due to the establishment of screening mammography for breast cancer detection, the number of non-palpable lesions has increased. Thus, an optimal localization system is mandatory for the excision of non-palpable breast tumors. OBJECTIVE: The aim of the study is to report the feasibility Surgical Marker Navigation (SMN) system Sirius Pintuition® for the excision of non-palpable breast tumors and non-palpable axillary lymph nodes. METHODS: A retrospective observational study of patients undergoing breast-conserving surgery and lymph node excision guided by SMN between December 2022 and May 2023 was performed. RESULTS: A total of 84 patients underwent excision of non-palpable breast tumors (77; 91.7%) or non-palpable axillary lymph-nodes (7; 8.3%) using SMN. In total, 94 markers were placed, in 74 patients (88.1%) only one marker was placed, whereas in 10 patients (11.9%) two markers were placed to correctly localize the lesion in the operating room. Most markers were placed using ultrasonographic guidance (69; 82.1%). Seventy-seven patients underwent breast-conserving surgery (91.7%) and 7 (8.3%) lymph node excision. In 10 cases (11.9%), the marker was accidentally displaced during surgery due to the use of magnetized instruments, although the specimen could be removed. In sum, all the markers were removed from the patients, although the marker retrieval rate, as we defined it (percentage of patients in whom the initial excised specimen contained the marker divided by the total number of patients), was 88.1%. CONCLUSION: The use of Sirius Pintuition® SMN for non-palpable breast tumors and non-palpable lymph nodes is feasible, with a retrieval rate of 88.1%.

Polystyrene-Based Matrix to Enhance the Fluorescence of Aggregation-Induced Emission Luminogen for Fluorescence-Guided Surgery.

Achieving ultrabright fluorogens is a key issue for fluorescence-guided surgery (FGS). Fluorogens with aggregation-induced emission (AIEgens) are potential agents for FGS on the benefit of the bright fluorescence in physiological conditions. Herein, the fluorescence brightness of AIEgen is further improved by preparing the nanoparticle using a polystyrene-based matrix and utilizing it for tumor FGS with a high signal-to-background ratio. After encapsulating AIEgen into polystyrene-poly (ethylene glycol) (PS-PEG), the fluorescence intensity of the prepared AIE@PS-PEG nanoparticles is multiple times that of nanoparticles in 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-poly (ethylene glycol) (DSPE-PEG), a commonly used polymer matrix for nanoparticle preparation. Molecular dynamics simulations suggest that higher free energy is required for the outer rings of AIEgen to rotate in polystyrene than in the DSPE, indicating that the benzene rings in polystyrene can restrict the intramolecular motions of AIEgen better than the alkyl chain in DSPE-PEG. Fluorescence correlation microscopy detections suggest that the triplet excited state of AIEgens is less in PS-PEG than in DSPE-PEG. The restricted intramolecular motions and suppressed triplet excited state result in ultrabright AIE@PS-PEG nanoparticles, which are more conducive to illuminating tumor tissues in the intestine for FGS. The illumination of metastatic tumors in lungs by AIE@PS-PEG nanoparticles is also tried.

Fully automated quantitative coronary angiography versus optical coherence tomography guidance for coronary stent implantation (FLASH): Study protocol for a randomized controlled noninferiority trial.

BACKGROUND: Artificial intelligence-based quantitative coronary angiography (AI-QCA) has been developed to provide a more objective and reproducible data about the severity of coronary artery stenosis and the dimensions of the vessel for intervention in real-time, overcoming the limitations of significant inter- and intraobserver variability, and time-consuming nature of on-site QCA, without requiring extra time and effort. Compared with the subjective nature of visually estimated conventional CAG guidance, AI-QCA guidance provides a more practical and standardized angiography-based approach. Although the advantage of intravascular imaging-guided PCI is increasingly recognized, their broader adoption is limited by clinical and economic barriers in many catheterization laboratories. METHODS: The FLASH (fully automated quantitative coronary angiography versus optical coherence tomography guidance for coronary stent implantation) trial is a randomized, investigator-initiated, multicenter, open-label, noninferiority trial comparing the AI-QCA-assisted PCI strategy with optical coherence tomography-guided PCI strategy in patients with significant coronary artery disease. All operators will utilize a novel, standardized AI-QCA software and PCI protocol in the AI-QCA-assisted group. A total of 400 patients will be randomized to either group at a 1:1 ratio. The primary endpoint is the minimal stent area (mm2), determined by the final OCT run after completion of PCI. Clinical follow-up and cost-effectiveness evaluations are planned at 1 month and 6 months for all patients enrolled in the study. RESULTS: Enrollment of a total of 400 patients from the 13 participating centers in South Korea will be completed in February 2024. Follow-up of the last enrolled patients will be completed in August 2024, and primary results will be available by late 2024. CONCLUSION: The FLASH is the first clinical trial to evaluate the feasibility of AI-QCA-assisted PCI, and will provide the clinical evidence on AI-QCA assistance in the field of coronary intervention. CLINICAL TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT05388357.

3D Specimen Scanning and Mapping in Musculoskeletal Oncology: A Feasibility Study.

BACKGROUND: Surgical resection is the primary treatment for bone and soft tissue tumors. Negative margin status is a key factor in prognosis. Given the three-dimensional (3D) anatomic complexity of musculoskeletal tumor specimens, communication of margin results between surgeons and pathologists is challenging. We sought to perform ex vivo 3D scanning of musculoskeletal oncology specimens to enhance communication between surgeons and pathologists. METHODS: Immediately after surgical resection, 3D scanning of the fresh specimen is performed prior to frozen section analysis. During pathologic grossing, whether frozen or permanent, margin sampling sites are annotated on the virtual 3D model using computer-aided design (CAD) software. RESULTS: 3D scanning was performed in seven cases (six soft tissue, one bone), with specimen mapping on six cases. Intraoperative 3D scanning and mapping was performed in one case in which the location of margin sampling was shown virtually in real-time to the operating surgeon to help achieve a negative margin. In six cases, the 3D model was used to communicate final permanent section analysis. Soft tissue, cartilage, and bone (including lytic lesions within bone) showed acceptable resolution. CONCLUSIONS: Virtual 3D scanning and specimen mapping is feasible and may allow for enhanced documentation and communication. This protocol provides useful information for anatomically complex musculoskeletal tumor specimens. Future studies will evaluate the effect of the protocol on positive margin rates, likelihood that a re-resection contains additional malignancy, and exploration of targeted adjuvant radiation protocols using a patient-specific 3D specimen map.

Indocyanine Green Fluorescence-Guided Laparoscopic Anatomical Segmentectomy of Liver Segment 6: Surgical Strategy and Technical Details.

BACKGROUND: Because of the complex anatomy of the right posterior hepatic pedicle, there have been few reports on standardized laparoscopic portal territory staining-guided anatomical resection of liver segment 6 (LPTAR-S6). This study aimed to elucidate the indocyanine green (ICG) fluorescence staining methods for LPTAR-S6. PATIENTS AND METHODS: LPTAR-S6 can be performed using positive and negative fluorescence staining approaches. We implemented these two approaches for patients with hepatocellular carcinoma. Descriptions of the surgical strategy and technical details are presented. RESULTS: Two patients safely underwent LPTAR-S6 using a preoperative three-dimensional reconstruction plan. The intraoperative ICG fluorescence staining effect was satisfactory, and the anatomical landmarks were fully exposed. CONCLUSIONS: A detailed preoperative three-dimensional reconstruction plan, complete intraoperative application of real-time laparoscopic ultrasound guidance, and ICG fluorescence staining can result in accurate transection of the liver parenchyma during LPTAR-S6.

Cost-Effectiveness of Radar Localisation Versus Wire Localisation for Wide Local Excision of Non-palpable Breast Cancer.

BACKGROUND: Wire localisation (WL) is the "gold standard" localisation technique for wide local excision (WLE) of non-palpable breast lesions but has disadvantages that have led to the development of wireless techniques. This study compared the cost-effectiveness of radar localisation (RL) to WL. METHODS: This was a single-institution study of 110 prospective patients with early-stage breast cancer undergoing WLE using RL with the SCOUT® Surgical Guidance System (2021-2023) compared with a cohort of 110 patients using WL. Margin status, re-excision rates, and surgery delays associated with preoperative localisation were compared. Costs from a third-party payer perspective in Australian dollars (AUD$) calculated by using microcosting, break-even point, and cost-utility analyses. RESULTS: A total of 110 WLEs using RL cost a total of AUD$402,281, in addition to the device cost of AUD$77,150. The average additional cost of a surgery delay was AUD$2318. Use of RL reduced the surgery delay rate by 10% (p = 0.029), preventing 11 delays with cost savings of AUD$25,496. No differences were identified in positive margin rates (RL: 11.8% vs. WL: 17.3%, p = 0.25) or re-excision rates (RL: 14.5% vs. WL: 21.8%, p = 0.221). In total, 290 RL cases are needed to break even. The cost of WLE using RL was greater than WL by AUD$567. There was a greater clinical benefit of 1.15 quality-adjusted life-years (QALYs) and an incremental cost-utility ratio of AUD$493 per QALY favouring RL. CONCLUSIONS: Routine use of RL was a more cost-effective intervention than WL. Close to 300 RL cases are likely needed to be performed to recover costs of the medical device. CLINICAL TRIAL REGISTRATION: ACTRN12624000068561.

Radio-Guided Surgery with a New-Generation ß-Probe for Radiolabeled Somatostatin Analog, in Patients with Small Intestinal Neuroendocrine Tumors.

BACKGROUND: Radio-guided surgery (RGS) holds promise for improving surgical outcomes in neuroendocrine tumors (NETs). Previous studies showed low specificity (SP) using γ-probes to detect radiation emitted by radio-labeled somatostatin analogs. OBJECTIVE: We aimed to assess the sensitivity (SE) and SP of the intraoperative RGS approach using a ß-probe with a per-lesion analysis, while assessing safety and feasibility as secondary objectives. METHODS: This prospective, single-arm, single-center, phase II trial (NCT05448157) enrolled 20 patients diagnosed with small intestine NETs (SI-NETs) with positive lesions detected at 68Ga-DOTA-TOC positron emission tomography/computed tomography (PET/CT). Patients received an intravenous injection of 1.1 MBq/Kg of 68Ga-DOTA-TOC 10 min prior to surgery. In vivo measurements were conducted using a ß-probe. Receiver operating characteristic (ROC) analysis was performed, with the tumor-to-background ratio (TBR) as the independent variable and pathology result (cancer vs. non-cancer) as the dependent variable. The area under the curve (AUC), optimal TBR, and absorbed dose for the surgery staff were reported. RESULTS: The intraoperative RGS approach was feasible in all cases without adverse effects. Of 134 specimens, the AUC was 0.928, with a TBR cut-off of 1.35 yielding 89.3% SE and 86.4% SP. The median absorbed dose for the surgery staff was 30 µSv (range 12-41 µSv). CONCLUSION: This study reports optimal accuracy in detecting lesions of SI-NETs using the intraoperative RGS approach with a novel ß-probe. The method was found to be safe, feasible, and easily reproducible in daily clinical practice, with minimal radiation exposure for the staff. RGS might potentially improve radical resection rates in SI-NETs. CLINICAL TRIALS REGISTRATION: 68Ga-DOTATOC Radio-Guided Surgery with ß-Probe in GEP-NET (RGS GEP-NET) [NCT0544815; https://classic. CLINICALTRIALS: gov/ct2/show/NCT05448157 ].

Comparison of Postoperative Outcomes Between Near-Infrared Fluorescent Imaging-Guided Mediastinal Lymphadenectomy and Conventional Surgery for Esophageal Cancer.

BACKGROUND: The study aimed to evaluate the efficacy of using near-infrared fluorescent imaging (NIRF) imaging with indocyanine green as an intraoperative tool for achieving complete mediastinal lymph node (LN) resection. PATIENTS AND METHODS: Between September 2019 and July 2021, patients with potential for esophagectomy due to middle and lower thoracic esophageal cancer were enrolled in this study. All patients were scheduled for NIRF-guided mediastinal lymphadenectomy during esophageal cancer surgery and were appropriately assigned to the NIRF group. Patients who underwent esophagectomy between September 2017 and September 2019 were assigned to the historical control group upon satisfying the inclusion/exclusion criteria. Surgical outcomes and the number of removed LNs were compared between the two groups using 1:1 propensity score matching. RESULTS: Of 67 eligible patients, 59 patients were included in the NIRF group after postsurgical exclusions. The operative time was significantly shorter in the NIRF group than in the historical control group [180 (140-420) min versus 202 (137-338) min; P < 0.001]. The incidence of postoperative chylothorax and hoarseness were significantly lower in the NIRF group than in the historical control group (0% versus 10.2 %; P = 0.036, 3.4% versus 13.6%; P = 0.047). The number of dissected total LNs, mediastinal LNs, and negative LNs was significantly larger in the NIRF group than in the historical control group. The number of overall metastatic LNs and abdominal LNs was comparable between the two groups. CONCLUSIONS: NIRF imaging can assist in the thorough and complete mediastinal LNs dissections without increasing complications in patients undergoing esophagectomy.

Laparoscopic Right Hemi-hepatectomy of the Bile Duct-Obstructed Area Guided by Real-Time Fluorescence Imaging.

BACKGROUND: The regions of the liver with cholestasis caused by biliary tumors or thrombosis can be distinctly identified using indocyanine green (ICG) fluorescence imaging.1 The authors' team reported the application of bile-duct obstructed area imaging (BOAI) to assist open hepatectomy for intrahepatic cholangiocarcinoma (ICC) combined with intrahepatic bile duct obstruction previously.2 This video is the first report of real-time BOAI-guided three-dimensional (3D) laparoscopic hepatectomy using a 3D-4K fluorescence imaging system. METHODS: A 65-year-old man was admitted to the authors' institution with clonorchiasis. Preoperative computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP) showed an obstruction and diffuse dilation of the right hepatic duct. A 15-min retention of ICG (ICG R15) was performed 5 days before the operation, with a 3.3% result. Preoperative planning involved performing laparoscopic right hemi-hepatectomy with regional lymph node dissection assisted by visualization technology.3 During the procedure, significant fluorescence accumulation in the right liver was shown by fluorescence imaging. With the guidance of real-time BOAI (Fig. 1), the regions of biliary obstruction were precisely resected, and the middle hepatic vein (MHV) was passively and adequately exposed on the cutting plane. Fig. 1 Administration steps for real-time bile duct-obstructed area imaging. A ICG is injected intravenously 3-5 days before operation at a dose of 0.5 mg/kg. B ICG is accumulated in the whole liver within a few minutes after injection. C ICG is selectively absorbed by the liver and excreted into the intestines, whereby it is retained in areas of biliary obstruction RESULTS: The histopathologic diagnosis indicated high-grade intraepithelial neoplasia of the right bile duct tumor without lymph node metastases and clonorchiasis. The duration of the operation was 300 min, with an intraoperative blood loss of 50 ml. No postoperative complications occurred, and the patient was discharged after 7 days. CONCLUSION: Laparoscopic right hemi-hepatectomy for the bile-duct obstructed area with the guidance of real-time BOAI is feasible and effective.

Intraoperative Image Guidance in Orbital and Lacrimal Surgery: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the efficacy and safety of the use of intraoperative image guidance (IIG) in orbital and lacrimal surgery. METHODS: A literature search of the PubMed database was last conducted in November 2023 for English-language original research that assessed the use of any image guidance system in orbital and lacrimal surgery that included at least 5 patients. The search identified 524 articles; 94 were selected for full-text analysis by the panel. A total of 32 studies met inclusion criteria. The panel methodologist assigned a level II rating to 2 studies and a level III rating to 30 studies. No study met the criteria for level I evidence. RESULTS: Procedures reported on were as follows: fracture repair (n = 14), neoplasm and infiltrate biopsy or excision (n = 6), orbital decompression for Graves ophthalmopathy (n = 3), dacryocystorhinostomy (n = 1), and mixed etiology and procedures (n = 8). Four studies used more than one IIG system. One study that met level II evidence criteria compared the outcomes of orbital fracture repair with IIG (n = 29) and without IIG (n = 29). Borderline better outcomes were reported in the IIG group: 2% versus 10% with diplopia (P = 0.039) and 3% versus 10% with enophthalmos (P = 0.065). The other level II study compared the repair of fractures with navigation (n = 20) and without (n = 20). The group in which navigation was used had a measured mean volume reduction of 3.82 cm3 compared with 3.33 cm3 (P = 0.02), and there was a greater measured reduction in enophthalmos in the navigation group of 0.72 mm (P = 0.001). Although the remaining 30 assessed articles failed to meet level II criteria, all alleged a benefit from IIG. No complications were reported. CONCLUSIONS: A small number of comparative studies suggest that there are improved outcomes when IIG is used in orbital fracture repair, but each study suffers from various limitations. No high-quality comparative studies exist for the management of lacrimal surgery, neoplastic disease, or decompression. Complications attributable to the use of IIG have not been identified, and IIG has not been analyzed for cost savings. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Visual extended reality tools in image-guided surgery in urology: a systematic review.

PURPOSE: The aim of this systematic review is to assess the clinical implications of employing various Extended Reality (XR) tools for image guidance in urological surgery. METHODS: In June 2023, a systematic electronic literature search was conducted using the Medline database (via PubMed), Embase (via Ovid), Scopus, and Web of Science. The search strategy was designed based on the PICO (Patients, Intervention, Comparison, Outcome) criteria. Study protocol was registered on PROSPERO (registry number CRD42023449025). We incorporated retrospective and prospective comparative studies, along with single-arm studies, which provided information on the use of XR, Mixed Reality (MR), Augmented Reality (AR), and Virtual Reality (VR) in urological surgical procedures. Studies that were not written in English, non-original investigations, and those involving experimental research on animals or cadavers were excluded from our analysis. The quality assessment of comparative and cohort studies was conducted utilizing the Newcastle-Ottawa scale, whilst for randomized controlled trials (RCTs), the Jadad scale was adopted. The level of evidence for each study was determined based on the guidelines provided by the Oxford Centre for Evidence-Based Medicine. RESULTS: The initial electronic search yielded 1,803 papers after removing duplicates. Among these, 58 publications underwent a comprehensive review, leading to the inclusion of 40 studies that met the specified criteria for analysis. 11, 20 and 9 studies tested XR on prostate cancer, kidney cancer and miscellaneous, including bladder cancer and lithiasis surgeries, respectively. Focusing on the different technologies 20, 15 and 5 explored the potential of VR, AR and MR. The majority of the included studies (i.e., 22) were prospective non-randomized, whilst 7 and 11 were RCT and retrospective studies respectively. The included studies that revealed how these new tools can be useful both in preoperative and intraoperative setting for a tailored surgical approach. CONCLUSIONS: AR, VR and MR techniques have emerged as highly effective new tools for image-guided surgery, especially for urologic oncology. Nevertheless, the complete clinical advantages of these innovations are still in the process of evaluation.

Lessons learned in application driven imaging agent design for image-guided surgery.

To meet the growing demand for intraoperative molecular imaging, the development of compatible imaging agents plays a crucial role. Given the unique requirements of surgical applications compared to diagnostics and therapy, maximizing translational potential necessitates distinctive imaging agent designs. For effective surgical guidance, exogenous signatures are essential and are achievable through a diverse range of imaging labels such as (radio)isotopes, fluorescent dyes, or combinations thereof. To achieve optimal in vivo utility a balanced molecular design of the tracer as a whole is required, which ensures a harmonious effect of the imaging label with the affinity and specificity (e.g., pharmacokinetics) of a pharmacophore/targeting moiety. This review outlines common design strategies and the effects of refinements in the molecular imaging agent design on the agent's pharmacological profile. This includes the optimization of affinity, pharmacokinetics (including serum binding and target mediated background), biological clearance route, the achievable signal intensity, and the effect of dosing hereon.

Intraoperative image-guidance during robotic surgery: is there clinical evidence of enhanced patient outcomes?

BACKGROUND: To date, the benefit of image guidance during robot-assisted surgery (IGS) is an object of debate. The current study aims to address the quality of the contemporary body of literature concerning IGS in robotic surgery throughout different surgical specialties. METHODS: A systematic review of all English-language articles on IGS, from January 2013 to March 2023, was conducted using PubMed, Cochrane library's Central, EMBASE, MEDLINE, and Scopus databases. Comparative studies that tested performance of IGS vs control were included for the quantitative synthesis, which addressed outcomes analyzed in at least three studies: operative time, length of stay, blood loss, surgical margins, complications, number of nodal retrievals, metastatic nodes, ischemia time, and renal function loss. Bias-corrected ratio of means (ROM) and bias-corrected odds ratio (OR) compared continuous and dichotomous variables, respectively. Subgroup analyses according to guidance type (i.e., 3D virtual reality vs ultrasound vs near-infrared fluoresce) were performed. RESULTS: Twenty-nine studies, based on 11 surgical procedures of three specialties (general surgery, gynecology, urology), were included in the quantitative synthesis. IGS was associated with 12% reduction in length of stay (ROM 0.88; p = 0.03) and 13% reduction in blood loss (ROM 0.87; p = 0.03) but did not affect operative time (ROM 1.00; p = 0.9), or complications (OR 0.93; p = 0.4). IGS was associated with an estimated 44% increase in mean number of removed nodes (ROM 1.44; p < 0.001), and a significantly higher rate of metastatic nodal disease (OR 1.82; p < 0.001), as well as a significantly lower rate of positive surgical margins (OR 0.62; p < 0.001). In nephron sparing surgery, IGS significantly decreased renal function loss (ROM 0.37; p = 0.002). CONCLUSIONS: Robot-assisted surgery benefits from image guidance, especially in terms of pathologic outcomes, namely higher detection of metastatic nodes and lower surgical margins. Moreover, IGS enhances renal function preservation and lowers surgical blood loss.

Molecular image-guided surgery in gynaecological cancer: where do we stand?

PURPOSE: The aim of this review is to give an overview of the current status of molecular image-guided surgery in gynaecological malignancies, from both clinical and technological points of view. METHODS: A narrative approach was taken to describe the relevant literature, focusing on clinical applications of molecular image-guided surgery in gynaecology, preoperative imaging as surgical roadmap, and intraoperative devices. RESULTS: The most common clinical application in gynaecology is sentinel node biopsy (SNB). Other promising approaches are receptor-target modalities and occult lesion localisation. Preoperative SPECT/CT and PET/CT permit a roadmap for adequate surgical planning. Intraoperative detection modalities span from 1D probes to 2D portable cameras and 3D freehand imaging. CONCLUSION: After successful application of radio-guided SNB and SPECT, innovation is leaning towards hybrid modalities, such as hybrid tracer and fusion of imaging approaches including SPECT/CT and PET/CT. Robotic surgery, as well as augmented reality and virtual reality techniques, is leading to application of these innovative technologies to the clinical setting, guiding surgeons towards a precise, personalised, and minimally invasive approach.

Surgical radioguidance with beta-emitting radionuclides; challenges and possibilities: A position paper by the EANM.

Radioguidance that makes use of ß-emitting radionuclides is gaining in popularity and could have potential to strengthen the range of existing radioguidance techniques. While there is a strong tendency to develop new PET radiotracers, due to favorable imaging characteristics and the success of theranostics research, there are practical challenges that need to be overcome when considering use of ß-emitters for surgical radioguidance. In this position paper, the EANM identifies the possibilities and challenges that relate to the successful implementation of ß-emitters in surgical guidance, covering aspects related to instrumentation, radiation protection, and modes of implementation.

An ultra-small organic dye nanocluster for enhancing NIR-II imaging-guided surgery outcomes.

PURPOSE: The accuracy of surgery for patients with solid tumors can be greatly improved through fluorescence-guided surgery (FGS). However, existing FGS technologies have limitations due to their low penetration depth and sensitivity/selectivity, which are particularly prevalent in the relatively short imaging window (< 900 nm). A solution to these issues is near-infrared-II (NIR-II) FGS, which benefits from low autofluorescence and scattering under the long imaging window (> 900 nm). However, the inherent self-assembly of organic dyes has led to high accumulation in main organs, resulting in significant background signals and potential long-term toxicity. METHODS: We rationalize the donor structure of donor-acceptor-donor-based dyes to control the self-assembly process to form an ultra-small dye nanocluster, thus facilitating renal excretion and minimizing background signals. RESULTS: Our dye nanocluster can not only show clear vessel imaging, tumor and tumor sentinel lymph nodes definition, but also achieve high-performance NIR-II imaging-guided surgery of tumor-positive sentinel lymph nodes. CONCLUSION: In summary, our study demonstrates that the dye nanocluster-based NIR-II FGS has substantially improved outcomes for radical lymphadenectomy.