Real-time Intraoperative Imaging Research Articles

A handheld device for intra-cavity and ex vivo fluorescence imaging of breast conserving surgery margins with 5-aminolevulinic acid

BackgroundVisualization of cancer during breast conserving surgery (BCS) remains challenging; the BCS reoperation rate is reported to be 20-70% of patients. An urgent clinical need exists for real-time intraoperative visualization of breast carcinomas during BCS. We previously demonstrated the ability of a prototype imaging device to identify breast carcinoma in excised surgical specimens following 5-aminolevulinic acid (5-ALA) administration. However, this prototype device was not designed to image the surgical cavity for remaining carcinoma after the excised lumpectomy specimen is removed. A new handheld fluorescence (FL) imaging prototype device, designed to image both excised specimens and within the surgical cavity, was assessed in a clinical trial to evaluate its clinical utility for first-in-human, real-time intraoperative imaging during index BCS.ResultsThe imaging device combines consumer-grade imaging sensory technology with miniature light-emitting diodes (LEDs) and multiband optical filtering to capture high-resolution white light (WL) and FL digital images and videos. The technology allows for visualization of protoporphyrin IX (PpIX), which fluoresces red when excited by violet-blue light. To date, n=17\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$n = 17$$\\end{document} patients have received 20mgkg\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$20\\frac{\ ext {mg}}{\ extrm{kg}}$$\\end{document} bodyweight (BW) 5-ALA orally 2-4 h before imaging to facilitate the accumulation of PpIX within tumour cells. Tissue types were identified based on their colour appearance. Breast tumours in sectioned lumpectomies appeared red, which contrasted against the green connective tissues and orange-brown adipose tissues. In addition, ductal carcinoma in situ (DCIS) that was missed during intraoperative standard of care was identified at the surgical margin at <1 mm depth. In addition, artifacts due to the surgical drape, illumination, and blood within the surgical cavity were discovered.ConclusionsThis study has demonstrated the detection of a grossly occult positive margin intraoperatively. Artifacts from imaging within the surgical cavity have been identified, and potential mitigations have been proposed.Trial RegistrationClinicalTrials.gov Identifier: NCT01837225 (Trial start date is September 2010. It was registered to ClinicalTrials.gov retrospectively on April 23, 2013, then later updated on April 9, 2020, to reflect the introduction of the new imaging device.)

Comparison of indocyanine green angiography vs intraoperative parathyroid hormone in early prediction of risk of post-thyroidectomy hypocalcemia: a prospective cohort study

Introduction: Indocyanine green (ICG) angiography is the ‘real-time intraoperative imaging’ technique used to reduce the chances of hypoparathyroidism in post-thyroidectomy patients. In our study, the authors predicted the risk of early post-thyroidectomy hypocalcemia by intraoperative evaluation of parathyroid gland perfusion by ICG angiography. Materials and methods: In patients who underwent total thyroidectomy, ICG angiography was done using the SPY PHI imaging system (Stryker). Post-thyroid specimen removal, scoring of parathyroids was done in spy contrast mode. All 4 or &lt;4 visualized parathyroids were scored for vascularity with the highest score of 8. Serum ionized calcium was done 6 h postsurgery and on the morning and evening of postoperative days 1 and 2. Calcium supplements were given to only those who developed clinical or severe biochemical hypocalcemia. Results: Out of 60, postoperative hypocalcemia was noted in 41 patients. Total ICG score ≤5 was seen in 34 patients, out of which 28 developed postoperative hypocalcemia showing PPV 82.3% and diagnostic accuracy of 68.3% while iPTH (4.28 pmol/l) showed PPV 76.7 and diagnostic accuracy 70 %. In eight patients, none of the glands was scored as 2 (White) and all these patients developed hypocalcemia requiring calcium infusion. Conclusion: The absence of visualization of at least 1 well-perfused (score 2) gland on ICG angiography is highly predictive of hypocalcemia and the majority of patients with total ICG score ≤5 developed hypocalcemia in the immediate postoperative period. ICG is a good predictor of the absence of hypoparathyroidism after thyroidectomy and is comparable to iPTH in the prediction of post-thyroidectomy hypocalcemia.

Intraoperative in vivo confocal laser endomicroscopy imaging at glioma margins: can we detect tumor infiltration?

Confocal laser endomicroscopy (CLE) is a US Food and Drug Administration-cleared intraoperative real-time fluorescence-based cellular resolution imaging technology that has been shown to image brain tumor histoarchitecture rapidly in vivo during neuro-oncological surgical procedures. An important goal for successful intraoperative implementation is in vivo use at the margins of infiltrating gliomas. However, CLE use at glioma margins has not been well studied. Matching in vivo CLE images and tissue biopsies acquired at glioma margin regions of interest (ROIs) were collected from 2 institutions. All images were reviewed by 4 neuropathologists experienced in CLE. A scoring system based on the pathological features was implemented to score CLE and H&E images from each ROI on a scale from 0 to 5. Based on the H&E scores, all ROIs were divided into a low tumor probability (LTP) group (scores 0-2) and a high tumor probability (HTP) group (scores 3-5). The concordance between CLE and H&E scores regarding tumor probability was determined. The intraclass correlation coefficient (ICC) and diagnostic performance were calculated. Fifty-six glioma margin ROIs were included for analysis. Interrater reliability of the scoring system was excellent when used for H&E images (ICC [95% CI] 0.91 [0.86-0.94]) and moderate when used for CLE images (ICC [95% CI] 0.69 [0.40-0.83]). The ICCs (95% CIs) of the LTP group (0.68 [0.40-0.83]) and HTP group (0.68 [0.39-0.83]) did not differ significantly. The concordance between CLE and H&E scores was 61.6%. The sensitivity and specificity values of the scoring system were 79% and 37%. The positive predictive value (PPV) and negative predictive value were 65% and 53%, respectively. Concordance, sensitivity, and PPV were greater in the HTP group than in the LTP group. Specificity was higher in the newly diagnosed group than in the recurrent group. CLE may detect tumor infiltration at glioma margins. However, it is not currently dependable, especially in scenarios where low probability of tumor infiltration is expected. The proposed scoring system has excellent intrinsic interrater reliability, but its interrater reliability is only moderate when used with CLE images. These results suggest that this technology requires further exploration as a method for consistent actionable intraoperative guidance with high dependability across the range of tumor margin scenarios. Specific-binding and/or tumor-specific fluorophores, a CLE image atlas, and a consensus guideline for image interpretation may help with the translational utility of CLE.

NIR-II fluorescence imaging in liver tumor surgery: A narrative review

In liver tumor surgery, the recognition of tumor margin and radical resection of microcancer focis have always been the crucial points to reduce postoperative recurrence of tumor. However, naked-eye inspection and palpation have limited effectiveness in identifying tumor boundaries, and traditional imaging techniques cannot consistently locate tumors in real time. As an intraoperative real-time navigation imaging method, NIR fluorescence imaging has been extensively studied for its simplicity, reliable safety, and superior sensitivity, and is expected to improve the accuracy of liver tumor surgery. In recent years, the research focus of NIR fluorescence has gradually shifted from the first near-infrared window (NIR-I, 700–900 nm) to the second near-infrared window (NIR-II, 1000–1700[Formula: see text]nm). Fluorescence imaging in NIR-II reduces the scattering effect of deep tissue, providing a preferable detection depth and spatial resolution while significantly eliminating liver autofluorescence background to clarify tumor margin. Developing fluorophores combined with tumor antibodies will further improve the precision of fluorescence-guided surgical navigation. With the development of a bunch of fluorophores with phototherapy ability, NIR-II can integrate tumor detection and treatment to explore a new therapeutic strategy for liver cancer. Here, we review the recent progress of NIR-II fluorescence technology in liver tumor surgery and discuss its challenges and potential development direction.

3D/2D Vessel Registration Based on Monte Carlo Tree Search and Manifold Regularization.

The augmented intra-operative real-time imaging in vascular interventional surgery, which is generally performed by projecting preoperative computed tomography angiography images onto intraoperative digital subtraction angiography (DSA) images, can compensate for the deficiencies of DSA-based navigation, such as lack of depth information and excessive use of toxic contrast agents. 3D/2D vessel registration is the critical step in image augmentation. A 3D/2D registration method based on vessel graph matching is proposed in this study. For rigid registration, the matching of vessel graphs can be decomposed into continuous states, thus 3D/2D vascular registration is formulated as a search tree problem. The Monte Carlo tree search method is applied to find the optimal vessel matching associated with the highest rigid registration score. For nonrigid registration, we propose a novel vessel deformation model based on manifold regularization. This model incorporates the smoothness constraint of vessel topology into the objective function. Furthermore, we derive simplified gradient formulas that enable fast registration. The proposed technique undergoes evaluation against seven rigid and three nonrigid methods using a variety of data - simulated, algorithmically generated, and manually annotated - across three vascular anatomies: the hepatic artery, coronary artery, and aorta. Our findings show the proposed method's resistance to pose variations, noise, and deformations, outperforming existing methods in terms of registration accuracy and computational efficiency. The proposed method demonstrates average registration errors of 2.14 mm and 0.34 mm for rigid and nonrigid registration, and an average computation time of 0.51 s.

Feasibility of novel intraoperative navigation for anatomical liver resection using real-time virtual sonography combined with indocyanine green fluorescent imaging technology.

To analyze the feasibility and clinical effect of novel intraoperative navigation of real-time virtual sonography (RVS) combined with indocyanine green (ICG) fluorescent imaging technology in anatomical liver resection (ALR) for hepatocellular carcinoma. The clinical data of 41 patients who underwent ALR using RVS intraoperative navigation combined with ICG fluorescent imaging technology in the Department of Hepatobiliary Surgery of Peking University International Hospital from January 2020 to May 2022 were retrospectively analyzed. RVS was applied to guide the surgical plane through fusing real-time intraoperative ultrasound images with corresponding preoperative CT or MRI images. Operation methods, operation time, intraoperative blood loss, operative margin, hospital stay and postoperative complications were analyzed. The 1-year overall survival rate and tumor-free survival rate of patients were followed up by outpatient review or telephone calls. ALR surgery was performed on each of 41 patients. There were no deaths during perioperative period and postoperative complications occurred in 7 cases (17.1%). The postoperative pathological examinations demonstrated all cases of hepatocellular carcinoma and negative operative margins. The 41 patients were followed up for 12 to 20 months, with a median follow-up time of 14 months. The overall survival rate 1 year after surgery was 100.0% (41/41), 3 patients (7.3%) experienced tumor recurrence, and the tumor-free survival rate of 1 year after surgery was 92.7% (38/41). In conclusion, novel intraoperative navigation of RVS combined with ICG fluorescent imaging technology is safe and feasible in anatomical segmental hepatectomy of hepatocellular carcinoma.

Rational design of NIR-II molecule-engineered nanoplatform for preoperative downstaging and imaging-guided surgery of orthotopic hepatic tumor

Orthotopic advanced hepatic tumor resection without precise location and preoperative downstaging may cause clinical postoperative recurrence and metastasis. Early accurate monitoring and tumor size reduction based on the multifunctional diagnostic-therapeutic integration platform could improve real-time imaging-guided resection efficacy. Here, a Near-Infrared II/Photoacoustic Imaging/Magnetic Resonance Imaging (NIR-II/PAI/MRI) organic nanoplatform IRFEP-FA-DOTA-Gd (IFDG) is developed for integrated diagnosis and treatment of orthotopic hepatic tumor. The IFDG is designed rationally based on the core “S-D-A-D-S” NIR-II probe IRFEP modified with folic acid (FA) for active tumor targeting and Gd-DOTA agent for MR imaging. The IFDG exhibits several advantages, including efficient tumor tissue accumulation, good tumor margin imaging effect, and excellent photothermal conversion effect. Therefore, the IFDG could realize accurate long-term monitoring and photothermal therapy non-invasively of the hepatic tumor to reduce its size. Next, the complete resection of the hepatic tumor in situ lesions could be realized by the intraoperative real-time NIR-II imaging guidance. Notably, the preoperative downstaging strategy is confirmed to lower the postoperative recurrence rate of the liver cancer patients under middle and advanced stage effectively with fewer side effects. Overall, the designed nanoplatform demonstrates great potential as a diagnostic-therapeutic integration platform for precise imaging-guided surgical navigation of orthotopic hepatic tumors with a low recurrence rate after surgery, providing a paradigm for diagnosing and treating the advanced tumors in the future clinical translation application.Graphical

Technical evolution of pediatric neurosurgery: the evolution of intraoperative imaging.

Imaging has always been fundamental to neurosurgery, and its evolution over the last century has made a dramatic transformation in the ability of neurosurgeons to define pathology and preserve normal tissue during their operations. In the mid-70s, the development of computerized cross-sectional imaging with CT scan and subsequently MRI have revolutionized the practice of neurosurgery. Later, further advances in computer technology and medical engineering have allowed the combination of many modalities to bring them into the operating theater. This evolution has allowed real-time intraoperative imaging, in the hope of helping neurosurgeons achieve accuracy, maximal safe resection, and the implementation of minimally invasive techniques in brain and spine pathologies. Augmented reality and robotic technologies are also being applied as useful intra-operative techniques that will improve surgical planning and outcomes in the future. In this article, we will review imaging modalities and provide our institutional perspective on how we have integrated them into our practice.

Robot-Guided Ultrasonography in Surgical Interventions.

The introduction of robotic-guided procedures in surgical techniques has brought an increase in the accuracy and control of resections. Surgery has evolved as a technique since the development of laparoscopy, which has added to the visualisation of the peritoneal cavity from a different perspective. Multi-armed robot associated with real-time intraoperative imaging devices brings important manoeuvrability and dexterity improvements in certain surgical fields. The present study is designed to synthesise the development of imaging techniques with a focus on ultrasonography in robotic surgery in the last ten years regarding abdominal surgical interventions. All studies involved abdominal surgery. Out of the seven studies, two were performed in clinical trials. The other five studies were performed on organs or simulators and attempted to develop a hybrid surgical technique using ultrasonography and robotic surgery. Most studies aim to surgically identify both blood vessels and nerve structures through this combined technique (surgery and imaging). Ultrasonography is often used in minimally invasive surgical techniques. This adds to the visualisation of blood vessels, the correct identification of tumour margins, and the location of surgical instruments in the tissue. The development of ultrasound technology from 2D to 3D and 4D has brought improvements in minimally invasive and robotic surgical techniques, and it should be further studied to bring surgery to a higher level.

Wide-field optical coherence tomography for microstructural analysis of key tissue types: a proof-of-concept evaluation.

Introduction: The presence of positive margins following tumor resection is a frequent cause of re-excision surgery. Nondestructive, real-time intraoperative histopathological imaging methods may improve margin status assessment at the time of surgery; optical coherence tomography (OCT) has been identified as a potential solution but has not been tested with the most common tissue types in surgical oncology using a single, standardized platform. Methods: This was a proof-of-concept evaluation of a novel device that employs wide-field OCT (WF-OCT; OTIS 2.0 System) to image tissue specimens. Various cadaveric tissues were obtained from a single autopsy and were imaged with WF-OCT then processed for permanent histology. The quality and resolution of the WF-OCT images were evaluated and compared to histology and with images in previous literature. Results: A total of 30 specimens were collected and tissue-specific microarchitecture consistent with previous literature were identified on both WF-OCT images and histology slides for all specimens, and corresponding sections were correlated. Application of vacuum pressure during scanning did not affect specimen integrity. On average, specimens were scanned at a speed of 10.3s/cm2 with approximately three features observed per tissue type. Conclusion: The WF-OCT images captured in this study displayed the key features of the most common human tissue types encountered in surgical oncology with utility comparable to histology, confirming the utility of an FDA-cleared imaging platform. With further study, WF-OCT may have the potential to bridge the gap between the immediate information needs of the operating room and the longer timeline inherent to histology workflow.

Tailoring albumin-based theranostic PROTACs nanoparticles for enhanced NIR-II bioimaging and synergistic cancer chemo-phototherapy

PROteolysis TArgeting Chimeras (PROTACs), a developing therapeutic tool designed to dictate target proteins for proteolysis through hijacking the ubiquitin–proteasome system, show potential for cancer therapy. However, unfavorable solubility and poor permeability of traditional PROTACs lead to low bioavailability and insufficient tumor distribution, which limit their clinical applications. Herein, we report a tridentate molecular probe (PROTAC-Cy7) by a three-in-one molecular designing strategy, which integrated a warhead that binds to MCL-1, the E3 ligase ligand pomalidomide and a heptamethine cyanine linker connecting the warhead and the ligand into the same scaffold. Then, bovine serum albumin (BSA) nanoparticles (NPs) with excellent biocompatibility, nonantigenic and biosafety were utilized to manufacture water-insoluble PROTAC-Cy7. The prepared PROTAC-Cy7@BSA NPs demonstrated tumor targeting and efficient degradation of MCL-1 through specific binding to MCL-1 receptors, which are overexpressed in multiple tumors. Moreover, PROTAC-Cy7@BSA NPs can be successfully used for near-infrared-II (NIR-II) noninvasively biomedical vascular imaging and to perform tumor resection guided by intraoperative real-time imaging. Under 808 nm laser irradiation, PROTAC-Cy7@BSA NPs exhibited synergistic Chemo-Phototherapy and showed perfect tumor suppression with 100% survival rate throughout the course of 60-day monitoring period. Our work provides a simple and feasible strategy for designing multifunctional drugs to have imaging-guided tumor-targeted multimodal therapy.

The Value of Indocyanine Green Image-Guided Surgery in Patients with Primary Liver Tumors and Liver Metastases.

Successful R0 resection is crucial for the survival of patients with primary liver cancer (PLC) or liver metastases. Up to date, surgical resection lacks a sensitive, real-time intraoperative imaging modality to determine R0 resection. Real-time intraoperative visualization with near-infrared light fluorescence (NIRF) using indocyanine green (ICG) may have the potential to meet this demand. This study evaluates the value of ICG visualization in PLC and liver metastases surgery regarding R0 resection rates. Patients with PLC or liver metastases were included in this prospective cohort study. ICG 10 mg was administered intravenously 24 h before surgery. Real-time intraoperative NIRF visualization was created with the SpectrumTM fluorescence imaging camera system. First, all liver segments were inspected with the fluorescence imaging system and intraoperative ultrasound for identification of the known tumor, as well as additional lesions, and were compared to preoperative MRI images. PLC, liver metastases, and additional lesions were then resected according to oncological principles. In all resected specimens, the resection margins were analyzed with the fluorescence imaging system for ICG-positive spots immediately after resection. Histology of additional detected lesions, as well as ICG fluorescence compared to histological resection margins, were assessed. Of the 66 included patients, median age was 65.5 years (IQR 58.7-73.9), 27 (40.9%) were female, and 18 (27.3%) were operated on laparoscopically. Additional ICG-positive lesions were detected in 23 (35.4%) patients, of which 9 (29%) were malignant. In patients with no fluorescent signal at the resection margin, R0 rate was 93.9%, R1 rate was 6.1%, and R2 rate was 0% compared to an ICG-positive resection margin with an R0 rate of 64.3%, R1 rate of 21.4%, and R2 rate of 14.3% (p = 0.005). One- and two-year overall survival rates were 95.2% and 88.4%, respectively. The presented study provides significant evidence that ICG NIRF guidance helps to identify R0 resection intraoperatively. This offers true potential to verify radical resection and improve patient outcomes. Furthermore, implementation of NIRF-guided imaging in liver tumor surgery allows us to detect a considerable amount of additional malignant lesions.

Intraoperative ultrasound in recurrent gliomas surgery: Impact on residual tumor volume and patient outcomes.

Reoperation may be beneficial for patients with recurrent gliomas. Minimizing the residual tumor volume (RTV) while ensuring the functionality of relevant structures is the goal of the reoperation of recurrent gliomas. Intraoperative ultrasound (IoUS) may be helpful for intraoperative tumor localization, intraoperative real-time imaging to guide surgical resection, and postoperative evaluation of the RTV in the reoperation for recurrent gliomas. To assess the effect of real-time ioUS on minimizing RTV in recurrent glioma surgery compared to Non-ioUS. We retrospectively analyzed the data from 92 patients who had recurrent glioma surgical resection: 45 were resected with ioUS guidance and 47 were resected without ioUS guidance. RTV, Karnofsky Performance Status (KPS) at 6 months after the operation, the number of recurrent patients, and the time to recurrence were evaluated. The average RTV in the ioUS group was significantly less than the Non-ioUS group (0.27 cm3 vs. 1.33 cm3, p = 0.0004). Patients in the ioUS group tended to have higher KPS scores at 6 months of follow-up after the operation than those in the Non-ioUS group (70.00 vs. 60.00, p = 0.0185). More patients in the Non-ioUS group experienced a recurrence than in the ioUS group (43 (91.49%) vs. 32 (71.11%), p = 0.0118). The ioUS group had a longer mean time to recurrence than the Non-ioUS group (7.9 vs. 6.3 months, p = 0.0013). The use of ioUS-based real-time for resection of recurrent gliomas has been beneficial in terms of both RTV and postoperative outcomes, compared to the Non-ioUS group.

Commentary: Scleral penetration or perforation during strabismus surgery.

Commentary: Scleral penetration or perforation during strabismus surgery.

Functionalized polydopamine nanospheres as in situ spray for photothermal image-guided tumor precise surgical resection

Surgical resection is a critical procedure for treatment of solid tumor, which commonly suffers from postoperative local recurrence due to the possibility of positive surgical margin. Although the widely used clinical imaging techniques (CT, MRI, PET, etc.) show beneficial effects in providing a macroscopic view of preoperative tumor position, they are still failing to provide intraoperative real-time imaging navigation during the surgery and need oral or intravenous injection contrast agents with risk of adverse effects. In this work, we present a nano-spray assisted photothermal imaging system for in vitro cells discrimination as well as in vivo visualization of tumor position and border that guides real-time precise tumor resection during surgery (even for tiny tumor less than 3 mm). Herein, the nano-spray were prepared by RGD peptide functionalized polydopamine (PDA-RGD) nanospheres with excellent photothermal conversion efficiency (54.27%), stability and reversibility, which target ανβ3 integrin overexpressed tumor cells. Such PDA-RGD serve as nanothermometers that convert and amplify biological signal to intuitive thermal image signal, depicting the tumor margin in situ. In comparison to conventional imaging techniques, our approach through topical spraying together with portable infrared camera has the characteristics of low cost, convenient, no radiation hazard, real-time intraoperative imaging-guidance and avoiding the adverse effects risk of oral or intravenous contrast agent. This technology provides a new universal tool for potentially assisting surgeons’ decision in real-time during surgery and aiding to improved outcome.

Near-infrared-dye labeled tumor vascular-targeted dimer GEBP11 peptide for image-guided surgery in gastric cancer.

Positive resection margins occur in about 2.8%-8.2% gastric cancer surgeries and is associated with poor prognosis. Intraoperative guidance using Nearinfrared (NIR) fluorescence imaging is a promising technique for tumor detection and margin assessment. The goal of this study was to develop a tumor-specific probe for real-time intraoperative NIR fluorescence imaging guidance. The tumor vascular homing peptide specific for gastric cancer, GEBP11, was conjugated with a near-infrared fluorophore, Cy5.5. The binding specificity of the GEBP11 probes to tumor vascular endothelial cells were confirmed by immunofluorescent staining. The ability of the probe to detect tumor lesions was evaluated in two xenograft models. An orthotopic gastric cancer xenograft model was used to evaluate the efficacy of the GEBP11 NIR probes in real-time surgical guidance. In vitro assay suggested that both mono and dimeric GEBP11 NIR probes could bind specifically to tumor vascular epithelial cells, with dimeric peptides showed better affinity. In tumor xenograft mice, live imaging suggested that comparing with free Cy5.5 probe, significantly stronger NIR signals could be detected at the tumor site at 24-48h after injection of mono or dimeric GEBP11 probes. Dimeric GEBP11 probe showed prolonged and stronger NIR signals than mono GEBP11 probe. Biodistribution assay suggested that GEBP11 NIR probes were enriched in gastric cancer xenografts. Using dimeric GEBP11 NIR probes in real-time surgery, the tumor margins and peritoneal metastases could be clearly visualized. Histological examination confirmed the complete resection of the tumor. (GEBP11)2-ACP-Cy5.5 could be a potential useful probe for intraoperative florescence guidance in gastric cancer surgery.

Confocal laser imaging in neurosurgery: A comprehensive review of sodium fluorescein-based CONVIVO preclinical and clinical applications.

Given the established direct correlation that exists among extent of resection and postoperative survival in brain tumors, obtaining complete resections is of primary importance. Apart from the various technological advancements that have been introduced in current clinical practice, histopathological study still remains the gold-standard for definitive diagnosis. Frozen section analysis still represents the most rapid and used intraoperative histopathological method that allows for an intraoperative differential diagnosis. Nevertheless, such technique owes some intrinsic limitations that limit its overall potential in obtaining real-time diagnosis during surgery. In this context, confocal laser technology has been suggested as a promising method to have near real-time intraoperative histological images in neurosurgery, thanks to the results of various studies performed in other non-neurosurgical fields. Still far to be routinely implemented in current neurosurgical practice, pertinent literature is growing quickly, and various reports have recently demonstrated the utility of this technology in both preclinical and clinical settings in identifying brain tumors, microvasculature, and tumor margins, when coupled to the intravenous administration of sodium fluorescein. Specifically in neurosurgery, among different available devices, the ZEISS CONVIVO system probably boasts the most recent and largest number of experimental studies assessing its usefulness, which has been confirmed for identifying brain tumors, offering a diagnosis and distinguishing between healthy and pathologic tissue, and studying brain vessels. The main objective of this systematic review is to present a state-of-the-art summary on sodium fluorescein-based preclinical and clinical applications of the ZEISS CONVIVO in neurosurgery.

Indocyanine Green-Guided Intraoperative Imaging to Facilitate Video-Assisted Retroperitoneal Debridement for Treating Acute Necrotizing Pancreatitis.

Video-assisted retroperitoneal debridement (VARD) is a feasible, minimally invasive necrosectomy method for treating severe acute necrotizing pancreatitis, if it does not resolve or is accompanied with infected necrosis in the retroperitoneum. As there are rarely any visually clear separating surface in white light image between necrotic debris and adjacent inflammatory normal tissues due to extensive retroperitoneal adhesions, VARD is accompanied with the risk of vascular injury, external pancreatico-cutaneous or enterocutaneous fistulae. In view of the above disadvantages, we apply real-time intraoperative near-infrared fluorescence imaging with indocyanine green (ICG) during VARD, which enables visualization of the well-perfused adjacent normal tissues. This modified technique (ICG-guided VARD) can provide a clear separating surface during debridement and reduce the risk of vascular or enteric injury. ICG-guided VARD may facilitate surgeons to perform safer debridement in treating severe acute necrotizing pancreatitis.

Real-time intraoperative near-infrared autofluorescence imaging to locate the parathyroid glands: A preliminary report.

Identification and localization of parathyroid glands (PGs) remains a challenge for surgeons. The aim of this study was to evaluate the efficiency of intraoperative near-infrared autofluorescence (NIRAF) imaging to detect PGs in thyroid and parathyroid diseases. Seventy-six patients undergoing surgery for thyroid or parathyroid diseases between July 9, 2020 and August 20, 2021 were retrospectively analyzed. Intraoperative carbon nanoparticle (CN) negative imaging and handheld NIRAF imaging were successively performed for each patient. Of 206 PGs that needed to be identified for surgery, 162 were identified by NIRAF imaging, with a theoretical rate of identification of 78.64%. This was higher than the rate of identification with CN negative imaging, which was 75.73%. The number of PGs identified by NIRAF imaging and CN negative imaging did not differ significantly in either total thyroidectomy or thyroid lobectomy. In addition, the autofluorescence (AF) intensity of secondary parathyroid adenoma was weaker than that of normal PGs. NIRAF imaging is potentially a more efficient tool for identification of PGs than CN negative imaging, with a shorter learning curve and lower risk. It may not be well-suited to secondary hyperthyroidism or adenoma, but it was more efficient at identifying excised specimens than visual identification by a surgeon.

Long-term safety of MRI-guided administration of AAV2-GDNF and gadoteridol in the putamen of individuals with Parkinson’s disease

Direct putaminal infusion of adeno-associated virus vector (serotype 2) (AAV2) containing the human glial cell line-derived neurotrophic factor (GDNF) transgene was studied in a phase I clinical trial of participants with advanced Parkinson's disease (PD). Convection-enhanced delivery of AAV2-GDNF with a surrogate imaging tracer (gadoteridol) was used to track infusate distribution during real-time intraoperative magnetic resonance imaging (iMRI). Pre-, intra-, and serial postoperative (up to 5 years after infusion) MRI were analyzed in 13 participants with PD treated with bilateral putaminal co-infusions (52 infusions in total) of AAV2-GDNF and gadoteridol (infusion volume, 450mL per putamen). Real-time iMRI confirmed infusion cannula placement, anatomic quantification of volumetric perfusion within the putamen, and direct visualization of off-target leakage or cannula reflux (which permitted corresponding infusion rate/cannula adjustments). Serial post-treatment MRI assessment (n= 13) demonstrated no evidence of cerebral parenchyma toxicity in the corresponding regions of AAV2-GDNF and gadoteridol co-infusion or surrounding regions over long-term follow-up. Direct confirmation of key intraoperative safety and efficacy parameters underscores the safety and tissue targeting value of real-time imaging with co-infused gadoteridol and putative therapeutic agents (i.e., AAV2-GDNF). This delivery-imaging platform enhances safety, permits delivery personalization, improves therapeutic distribution, and facilitates assessment of efficacy and dosing effect.