Delineation Of Tumor Margins Research Articles

Characterization of Polarimetric Properties in Various Brain Tumor Types Using Wide-Field Imaging Mueller Polarimetry.

Neuro-oncological surgery is the primary brain cancer treatment, yet it faces challenges with gliomas due to their invasiveness and the need to preserve neurological function. Hence, radical resection is often unfeasible, highlighting the importance of precise tumor margin delineation to prevent neurological deficits and improve prognosis. Imaging Mueller polarimetry, an effective modality in various organ tissues, seems a promising approach for tumor delineation in neurosurgery. To further assess its use, we characterized the polarimetric properties by analysing 45 polarimetric measurements of 27 fresh brain tumor samples, including different tumor types with a strong focus on gliomas. Our study integrates a wide-field imaging Mueller polarimetric system and a novel neuropathology protocol, correlating polarimetric and histological data for accurate tissue identification. An image processing pipeline facilitated the alignment and overlay of polarimetric images and histological masks. Variations in depolarization values were observed for grey and white matter of brain tumor tissue, while differences in linear retardance were seen only within white matter of brain tumor tissue. Notably, we identified pronounced optical axis azimuth randomization within tumor regions. This study lays the foundation for machine learning-based brain tumor segmentation algorithms using polarimetric data, facilitating intraoperative diagnosis and decision making.

Dual-Function Antibody Conjugate-Enabled Photoimmunotherapy Complements Fluorescence and Photoacoustic Imaging of Head and Neck Cancer Spheroids.

Several molecular-targeted imaging and therapeutic agents are in clinical trials for image-guided surgery and photoimmunotherapy (PIT) for head and neck cancers. In this context, we have previously reported the development, characterization, and specificity of a dual-function antibody conjugate (DFAC) for multimodal imaging and photoimmunotherapy (PIT) of EGFR-overexpressing cancer cells. The DFAC reported previously and used in the present study comprises an EGFR-targeted antibody, cetuximab, conjugated to benzoporphyrin derivative (BPD) for fluorescence imaging and PIT and a Si-centered naphthalocyanine dye for photoacoustic imaging. We report here the evaluation and performance of DFAC in detecting microscopic cancer spheroids by fluorescence and photoacoustic imaging along with their treatment by PIT. We demonstrate that while fluorescence imaging can detect spheroids with volumes greater than 0.049 mm3, photoacoustic imaging-based detection was possible even for the smallest spheroids (0.01 mm3) developed in the study. When subjected to PIT, the spheroids showed a dose-dependent response, with smaller spheroids (0.01 and 0.018 mm3) showing a complete response with no recurrence when treated with 100 J/cm2. Together our results demonstrate the complementary imaging and treatment capacity of DFAC. This potentially enables fluorescence imaging to assess the presence of tumor on a macroscopic scale, followed by photoacoustic imaging for delineating tumor margins guiding surgical resection and elimination of any residual microscopic disease by PIT, in a single intraoperative setting.

Advances in Intraoperative Glioma Tissue Sampling and Infiltration Assessment.

Gliomas are infiltrative brain tumors that often involve functional tissue. While maximal safe resection is critical for maximizing survival, this is challenged by the difficult intraoperative discrimination between tumor-infiltrated and normal structures. Surgical expertise is essential for identifying safe margins, and while the intraoperative pathological review of frozen tissue is possible, this is a time-consuming task. Advances in intraoperative stimulation mapping have aided surgeons in identifying functional structures and, as such, has become the gold standard for this purpose. However, intraoperative margin assessment lacks a similar consensus. Nonetheless, recent advances in intraoperative imaging techniques and tissue examination methods have demonstrated promise for the accurate and efficient assessment of tumor infiltration and margin delineation within the operating room, respectively. In this review, we describe these innovative technologies that neurosurgeons should be aware of.

Brachytherapy With 15- Versus 20-mm Ruthenium 106 Plaques Without Verification of Plaque Position Is Associated With Local Tumor Recurrence and Death in Posterior Uveal Melanoma

Brachytherapy with episcleral plaques is the most common primary tumor treatment for uveal melanoma. This study aims to compare the risk of tumor recurrence and metastatic death between two frequently used ruthenium-106 plaque designs: CCB (20.2 mm) and CCA (15.3 mm). Data were obtained from 1387 consecutive patients treated at XXX between 1981 and 2022 (439 with CCA and 948 with CCB plaques). During the period, scleral transillumination was performed to delineate tumor margins before plaque insertion, but no minimum scleral dose was used, and accurate plaque positioning was not verified after scleral attachment. Patients treated with CCA plaques had smaller tumors than those treated with CCB plaques (mean diameter 8.6 vs. 10.5 mm, P<0.001). There were no differences in patient sex, age, tumor distance to the optic disc, tumor apex dose, dose rate, or in rates of ciliary body involvement, eccentric plaque placement, or adjunct transpupillary thermotherapy. The average difference between plaque and tumor diameter was greater with the CCB plaque, and a smaller difference was an independent predictor of tumor recurrence. The 15-year incidence of tumor recurrence was 28% and 15% after treatment with CCA and CCB plaques, respectively (competing risk analysis, P<0.001). Multivariate Cox regression analysis revealed a lower risk for tumor recurrence with CCB plaques (HR 0.50). Similarly, patients treated with CCB plaques had a lower risk for uveal melanoma-related mortality (HR 0.77). Adjunct transpupillary thermotherapy did not reduce these risks. Uni- and multivariate time-dependent Cox regressions demonstrated that tumor recurrence was associated with uveal melanoma-related and all-cause mortality. Compared to 20 mm plaques, brachytherapy with 15 mm ruthenium plaques is associated with a higher risk for tumor recurrence and death. These adverse outcomes may be avoided by increasing safety margins and implementing effective methods to verify accurate plaque positioning.

NIRDye 812: A molecular platform tailored for multimodal bioimaging applications of targeted fluorescence- and photoacoustic-guided surgery.

The primary treatment for malignant tumors remains to be surgical removal of the diseased tissue. The presence or absence of residual diseased tissue at the tumor margin is the strongest predictor of postoperative prognosis and recurrence. Accordingly, reliance on the ability of surgeons to visually distinguish diseased tissue from healthy tissue unambiguously in real time is crucial. Near infrared-I (NIRI) fluorescence-emitting targeting biomolecular constructs such as anticancer antibody-fluorophore conjugates, namely cetuximab-IRDye® 800CW (CTB-IRDye® 800CW), are FDA-approved for clinical trial usage in the fluorescence-guided resection of diseased tissue due to affording improved direct visualization of tumor tissue when compared to the use of either the unaided eye under standard white light illumination (WLI) surgical techniques or non-targeting fluorophores. Unfortunately, though helpful, CTB-IRDye® 800CW affords limited (i) identification of diseased tissue and (ii) tumor margin delineation, because the immunoconjugate generates suboptimal tumor-to-background ratios (TBRs) as a result of its spectral/photophysical profiles poorly aligning with the fixed optical windows of pre-/clinical setups. As such, CTB-IRDye® 800CW is more prone to affording incomplete resection compared to if TBRs were higher due to otherwise. To aid in accurately identifying deep-seated diseased tissue, photoacoustic (PA) tomography has been implemented alongside CTB-IRDye® 800CW to achieve PA signals that could result in higher TBRs. However, in clinical trial practice, using IRDye® 800CW for PA imaging also yields subpar TBRs due to it affording low PA signals. To overcome such limitations, we developed NIRDye 812, a structurally-modified topological equivalent of IRDye® 800CW, to confer it the capability to yield both higher TBRs and superior PA signal than that of the equivalent CTB-conjugate and fluorophore IRDye® 800CW itself, respectively. To do so, we substituted the oxygen atom at its meso-position with a sulfur atom. CTB-NIRDye 812 demonstrated a red-shifted absorption wavelength at 796nm and a peak NIR-I fluorescence emission wavelength at 820nm, which better dovetails with the fixed windows of preinstalled fixed emission filters within commercial pre-/clinical NIR-I fluorescence imaging instruments. Overall, CTB-NIRDye 812 provided a∼2-fold increase in TBRs compared to those of CTB-IRDye® 800CW in vivo. Also, NIRDye 812 displayed an ∼60% higher PA signal than that of IRDye® 800CW. Collectively, we achieved our goal of improving upon the spectral/photophysical and PA properties of IRDye® 800CW via introducing a subtle modification to its electronic core such that its CTB immunoconjugate could potentially allow for fast track or breakthrough designation by the FDA due to its near-identical structure displaying considerably improved efficacy.

Precise tumor resection under the navigation of Tumor-Microenvironment pH-activated NIR-II fluorescence imaging via calcium Carbonate/Polydopamine Co-packed Nd-doped downshifting nanoprobes

Photobleaching resistance, high quantum yield and deep tissue imaging of Nd-doped nanocrystals with fluorescence in the second near infrared region (NIR-II, 1000–1700 nm) occupied an indispensable position for precisely navigating tumor resection. However, these NIR-II nanoprobes often encounter high passive accumulation in reticuloendothelial system (RES) organs that attenuates signal to background ratio (SBR), resulting in the impediment of their application for accurate tumor outline delineation. Herein, a hollow-structured CaCO3 and polydopamine co-packed shell has been co-cladded on the Nd-doped down-shifting nanocrystals (DSNCs@hPCa). After conjugating folic acid molecules on the hollowed surface (DSNCs@hPCa-FA), this fascinating NIR-II contrast nanoagent can further specifically enhance tumor targeting capacity and gratifyingly restrain the NIR-II fluorescence in the “OFF” state. It sensitively responds to the weak acid tumor microenvironment, consequently, the hybrid nanoshell is degraded and the NIR-II fluorescence is efficiently turn “ON”. Robust fluorescent imaging with the augmented SBR has been demonstrated to accurately identify tumor borderlines from normal tissue. Tumors were thoroughly removed under the navigation of this novel pH stimuli-responsive NIR-II fluorescence imaging with ignorable in situ recurrence or metastases after 28 days post-surgery. This strategy indicates the preclinical potential of tumor microenvironment activated nanoprobes for assisting the accurate delineation of tumor margins.

In Vivo Evaluation of a Gallium-68-Labeled Tumor-Tracking Cyanine Dye for Positron Emission Tomography/Near-Infrared Fluorescence Carcinoma Imaging, Image-Guided Surgery, and Photothermal Therapy.

Positron emission tomography (PET)/near-infrared fluorescence (NIRF) dual-modal imaging presents an enticing prospect for tumor diagnosis and surgical navigation. In this study, we developed a novel probe IR808-DOTA for tumor-targeted PET/NIRF imaging, image-guided surgery, and photothermal therapy. This construct had better water solubility and pharmacokinetics than IR808 and had similar photophysical properties, tumor targeting ability, and photothermal anticancer effect to IR808. By a simple labeling process, IR808-DOTA was labeled with gallium-68 and applied as a PET probe for tumor imaging in MCF-7 tumor xenografted mice. IR808-DOTA itself acted as an NIRF imaging agent in the following surgery for intraoperative navigation to aid surgeons in the delineation of tumor margins and visualizing sentinel lymph nodes to facilitate a more thorough tumor resection. Irradiation by laser, IR808-DOTA could prominently inhibit tumor growth in MCF-7 subcutaneous tumor model mice by directly ablating tumor cells, inhibiting tumor proliferation, and promoting tumor cell apoptosis. In summary, 68Ga-DOTA-IR808 could enable a convenient and user-friendly workflow for tumor imaging and guided surgery, and therefore, it may have great prospects for clinical translation as a PET/NIRF dual-modal probe.

Amino Acid Tracer PET MRI in Glioma Management: What a Neuroradiologist Needs to Know.

PET with amino acid tracers provides additional insight beyond MR imaging into the biology of gliomas that can be used for initial diagnosis, delineation of tumor margins, planning of surgical and radiation therapy, assessment of residual tumor, and evaluation of posttreatment response. Hybrid PET MR imaging allows the simultaneous acquisition of various PET and MR imaging parameters in a single investigation with reduced scanning time and improved anatomic localization. This review aimed to provide neuroradiologists with a concise overview of the various amino acid tracers and a practical understanding of the clinical applications of amino acid PET MR imaging in glioma management. Future perspectives in newer advances, novel radiotracers, radiomics, and cost-effectiveness are also outlined.

Intraoperative Assessment of Tumor Margins in Tissue Sections with Hyperspectral Imaging and Machine Learning

The intraoperative assessment of tumor margins of head and neck cancer is crucial for complete tumor resection and patient outcome. The current standard is to take tumor biopsies during surgery for frozen section analysis by a pathologist after H&E staining. This evaluation is time-consuming, subjective, methodologically limited and underlies a selection bias. Optical methods such as hyperspectral imaging (HSI) are therefore of high interest to overcome these limitations. We aimed to analyze the feasibility and accuracy of an intraoperative HSI assessment on unstained tissue sections taken from seven patients with oral squamous cell carcinoma. Afterwards, the tissue sections were subjected to standard histopathological processing and evaluation. We trained different machine learning models on the HSI data, including a supervised 3D convolutional neural network to perform tumor detection. The results were congruent with the histopathological annotations. Therefore, this approach enables the delineation of tumor margins with artificial HSI-based histopathological information during surgery with high speed and accuracy on par with traditional intraoperative tumor margin assessment (Accuracy: 0.76, Specificity: 0.89, Sensitivity: 0.48). With this, we introduce HSI in combination with ML hyperspectral imaging as a potential new tool for intraoperative tumor margin assessment.

Deploying Indocyanine Green Fluorescence-Guided Navigation System in Precise Laparoscopic Resection of Pediatric Hepatoblastoma.

Background: Hepatoblastoma (HB) is the most common form of liver cancer in children. To date, complete tumor resection is still the gold standard for treating HB. Indocyanine green (ICG) has been identified as a sensitive adjunct that is highly effective in the identification and surgical management of local and metastatic HB. It has thus becomes an increasingly popular choice among surgeons in HB resection surgeries that are fluorescence-guided. However, laparotomy remains the preferred choice in most cases since the applications and limitations of fluorescence-guided laparoscopic surgery in treating HB remain unclear. In this study, the characteristics and outcomes of laparoscopic HB resections that were guided by intraoperative ICG fluorescent imaging were investigated. Methods: Seven HB patients underwent ICG-guided laparoscopic HB resection surgery from August 2019 to December 2021. ICG was intravenously administered to the patients at a dosage of 0.5 mg/kg 48 h prior to the scheduled operation. During operation, tumor localization and resection boundary were guided by fluorescence visualization. The data on surgical and clinical features were collected retrospectively. Results: The resection area and tumor boundary could be clearly viewed in real-time under the ICG fluorescence imaging navigation system during operation, except for one patient who had received interventional chemoembolization before surgery. The image produced by laparoscopic fluorescence navigation was clear since it was not affected by ambient light. All tumors were completely resected as confirmed by negative margins for HB during postoperative pathological examination. No residual or recurrence were also found through computed tomography during follow-up visits from 9 to 37 months. Conclusions: ICG fluorescence-guided laparoscopic surgery is safe and effective in treating HB due to its ability to provide clear information on tumor localization and delineate tumor margins in real-time.

Boosting the Brightness of Thiolated Surface-Enhanced Raman Scattering Nanoprobes by Maximal Utilization of the Three-Dimensional Volume of Electromagnetic Fields.

Self-assembled monolayers (SAMs) of thiols on plasmonic nanoparticles constitute one of the most common methods for fabricating surface-enhanced Raman scattering (SERS) nanoprobes with wide applications. However, this method greatly limits the sufficient utilization of electromagnetic fields derived from plasmon excitation of the nanoparticles, because the thickness of SAMs (<1 nm) is usually much smaller than the attenuation length (>10 nm) of the fields. To overcome this, we propose a three-dimensional (3D) volume-active SERS (VASERS) technique to break the SAM limit, which integrates large amounts of thiol reporters into polydopamine shells on silver nanoparticles via Michael addition and allows sufficient utilization of 3D electromagnetic fields, leading to a dramatic increase in the intensity of the signal of the nanoprobes by about one order of magnitude. We demonstrate the universality of this strategy on various thiol reporters and plasmonic substrates. We also show that orthogonal VASERS nanoprobes with alkyne readout allow for high-precision in vivo tumor targeting and margin delineation.

Development and Evaluation of Targeted Optical Imaging Probes for Image‐Guided Surgery in Head and Neck Cancer

AbstractHead and neck cancer is the 7th most common cancer in the world and the primary treatment is surgical resection. Optical probes have shown great potential for application in image‐guided surgery to delineate tumor margins more accurately. Special biomarkers that are aberrant in tumors are considered in tumor‐targeting strategies. Targeted fluorescent probes can enable accurate visualization of tumor margins with appropriate targeting strategies, thereby providing better sensitivity and specificity. In this review, the preclinical evidence on optical probes that have been developed with specific targeting strategies is summarized and challenges in the clinical translation of novel targeted fluorescent probes are discussed.

Preoperative [11C]methionine PET to personalize treatment decisions in patients with lower-grade gliomas.

BackgroundPET with radiolabeled amino acids is used in the preoperative evaluation of patients with glial neoplasms. This study aimed to assess the role of [11C]methionine (MET) PET in assessing molecular features, tumor extent, and prognosis in newly diagnosed lower-grade gliomas (LGGs) surgically treated.MethodsOne hundred and fifty-three patients with a new diagnosis of grade 2/3 glioma who underwent surgery at our Institution and were imaged preoperatively using [11C]MET PET/CT were retrospectively included. [11C]MET PET images were qualitatively and semi-quantitatively analyzed using tumor-to-background ratio (TBR). Progression-free survival (PFS) rates were estimated using the Kaplan-Meier method and Cox proportional-hazards regression was used to test the association of clinicopathological and imaging data to PFS.ResultsOverall, 111 lesions (73%) were positive, while thirty-two (21%) and ten (6%) were isometabolic and hypometabolic at [11C]MET PET, respectively. [11C]MET uptake was more common in oligodendrogliomas than IDH-mutant astrocytomas (87% vs 50% of cases, respectively). Among [11C]MET-positive gliomas, grade 3 oligodendrogliomas had the highest median TBRmax (3.22). In 25% of patients, PET helped to better delineate tumor margins compared to MRI only. In IDH-mutant astrocytomas, higher TBRmax values at [11C]MET PET were independent predictors of shorter PFS.ConclusionsThis work highlights the role of preoperative [11C]MET PET in estimating the type of suspected LGGs, assessing tumor extent, and predicting biological behavior and prognosis of histologically confirmed LGGs. Our findings support the implementation of [11C]MET PET in routine clinical practice to better manage these neoplasms.

Insights and prospects for ion mobility-mass spectrometry in clinical chemistry

Introduction : Ion mobility-mass spectrometry is an emerging technology in the clinical setting for high throughput and high confidence molecular characterization from complex biological samples. Ion mobility spectrometry can provide isomer separations on the basis of molecular structure, the ability of which is increasing through technological developments that afford enhanced resolving power. Integrating multiple separation dimensions, such as liquid chromatography-ion mobility-mass spectrometry (LC-IM-MS) provide dramatic enhancements in the mitigation of molecular interferences for high accuracy clinical measurements. Areas covered : Multidimensional separations with LC-IM-MS provide better selectivity and sensitivity in molecular analysis. Mass spectrometry imaging of tissues to inform spatial molecular distribution is improved by complementary ion mobility analyses. Biomarker identification in surgical environments is enhanced by intraoperative biochemical analysis with mass spectrometry and holds promise for integration with ion mobility spectrometry. New prospects in high resolving power ion mobility are enhancing analysis capabilities, such as distinguishing isomeric compounds. Expert Opinion : Ion mobility-mass spectrometry holds many prospects for the field of isomer identification, molecular imaging, and intraoperative tumor margin delineation in clinical settings. These advantages are afforded while maintaining fast analysis times and subsequently high throughput. High resolving power ion mobility will enhance these advantages further, in particular for analyses requiring high confidence isobaric selectivity and detection.

Deep learning super-resolution magnetic resonance spectroscopic imaging of brain metabolism and mutant isocitrate dehydrogenase glioma.

BackgroundMagnetic resonance spectroscopic imaging (MRSI) can be used in glioma patients to map the metabolic alterations associated with IDH1,2 mutations that are central criteria for glioma diagnosis. The aim of this study was to achieve super-resolution (SR) MRSI using deep learning to image tumor metabolism in patients with mutant IDH glioma.MethodsWe developed a deep learning method based on generative adversarial network (GAN) using Unet as generator network to upsample MRSI by a factor of 4. Neural networks were trained on simulated metabolic images from 75 glioma patients. The performance of deep neuronal networks was evaluated on MRSI data measured in 20 glioma patients and 10 healthy controls at 3T with a whole-brain 3D MRSI protocol optimized for detection of d-2-hydroxyglutarate (2HG). To further enhance structural details of metabolic maps we used prior information from high-resolution anatomical MR imaging. SR MRSI was compared to ground truth by Mann–Whitney U-test of peak signal-to-noise ratio (PSNR), structure similarity index measure (SSIM), feature-based similarity index measure (FSIM), and mean opinion score (MOS).ResultsDeep learning SR improved PSNR by 17%, SSIM by 5%, FSIM by 7%, and MOS by 30% compared to conventional interpolation methods. In mutant IDH glioma patients proposed method provided the highest resolution for 2HG maps to clearly delineate tumor margins and tumor heterogeneity.ConclusionsOur results indicate that proposed deep learning methods are effective in enhancing spatial resolution of metabolite maps. Patient results suggest that this may have great clinical potential for image guided precision oncology therapy.

SERS Tags for Biomedical Detection and Bioimaging.

Surface-enhanced Raman scattering (SERS) has emerged as a valuable technique for molecular identification. Due to the characteristics of high sensitivity, excellent signal specificity, and photobleaching resistance, SERS has been widely used in the fields of environmental monitoring, food safety, and disease diagnosis. By attaching the organic molecules to the surface of plasmonic nanoparticles, the obtained SERS tags show high-performance multiplexing capability for biosensing. The past decade has witnessed the progress of SERS tags for liquid biopsy, bioimaging, and theranostics applications. This review focuses on the advances of SERS tags in biomedical fields. We first introduce the building blocks of SERS tags, followed by the summarization of recent progress in SERS tags employed for detecting biomarkers, such as DNA, miRNA, and protein in biological fluids, as well as imaging from in vitro cell, bacteria, tissue to in vivo tumors. Further, we illustrate the appealing applications of SERS tags for delineating tumor margins and cancer diagnosis. In the end, perspectives of SERS tags projecting into the possible obstacles are deliberately proposed in future clinical translation.

Terahertz dielectric spectroscopy and solid immersion microscopy of ex vivo glioma model 101.8: brain tissue heterogeneity.

Terahertz (THz) technology holds strong potential for the intraoperative label-free diagnosis of brain gliomas, aimed at ensuring their gross-total resection. Nevertheless, it is still far from clinical applications due to the limited knowledge about the THz-wave-brain tissue interactions. In this work, rat glioma model 101.8 was studied ex vivo using both the THz pulsed spectroscopy and the 0.15λ-resolution THz solid immersion microscopy (λ is a free-space wavelength). The considered homograft model mimics glioblastoma, possesses heterogeneous character, unclear margins, and microvascularity. Using the THz spectroscopy, effective THz optical properties of brain tissues were studied, as averaged within the diffraction-limited beam spot. Thus measured THz optical properties revealed a persistent difference between intact tissues and a tumor, along with fluctuations of the tissue response over the rat brain. The observed THz microscopic images showed heterogeneous character of brain tissues at the scale posed by the THz wavelengths, which is due to the distinct response of white and gray matters, the presence of different neurovascular structures, as well as due to the necrotic debris and hemorrhage in a tumor. Such heterogeneities might significantly complicate delineation of tumor margins during the intraoperative THz neurodiagnosis. The presented results for the first time pose the problem of studying the inhomogeneity of brain tissues that causes scattering of THz waves, as well as the urgent need to use the radiation transfer theory for describing the THz-wave - tissue interactions.

Fluorescent Imaging and Multifusion Segmentation for Enhanced Visualization and Delineation of Glioblastomas Margins

This study investigates the potential of fluorescence imaging in conjunction with an original, fused segmentation framework for enhanced detection and delineation of brain tumor margins. By means of a test bed optical microscopy system, autofluorescence is utilized to capture gray level images of brain tumor specimens through slices, obtained at various depths from the surface, each of 10 µm thickness. The samples used in this study originate from tumor cell lines characterized as Gli36ϑEGRF cells expressing a green fluorescent protein. An innovative three-step biomedical image analysis framework is presented aimed at enhancing the contrast and dissimilarity between the malignant and the remaining tissue regions to allow for enhanced visualization and accurate extraction of tumor boundaries. The fluorescence image acquisition system implemented with an appropriate unsupervised pipeline of image processing and fusion algorithms indicates clear differentiation of tumor margins and increased image contrast. Establishing protocols for the safe administration of fluorescent protein molecules, these would be introduced into glioma tissues or cells either at a pre-surgery stage or applied to the malignant tissue intraoperatively; typical applications encompass areas of fluorescence-guided surgery (FGS) and confocal laser endomicroscopy (CLE). As a result, this image acquisition scheme could significantly improve decision-making during brain tumor resection procedures and significantly facilitate brain surgery neuropathology during operation.

Diagnostic Ability of Magnifying Narrow-Band Imaging for the Extent of Early Gastric Cancer: A Systematic Review and Meta-Analysis

Background Accurate delineation of tumor margin is essential for complete resection of early gastric cancer (EGC). The objective of this study is to assess the performance of magnifying endoscopy with narrow-band imaging (ME-NBI) for the accurate demarcation of EGC margins. Methods We searched PubMed, EMBASE, Web of Science, and Cochrane Library databases up to March 2020 to identify eligible studies. The diagnostic accuracy of ME-NBI for EGC margins was calculated, and subgroup analyses were performed based on tumor size, depth of tumor invasion, tumor-occupied site, macroscopic type, histological type, Helicobacter pylori (H. pylori), and endoscopists' experience. Besides, we also evaluated the negative and positive resection rates of the horizontal margin (HM) of EGC after endoscopic submucosal dissection (ESD) and surgery. Results Ten studies comprising 1018 lesions were eligible in the databases. The diagnostic accuracy of ME-NBI for the demarcation of EGC margins was 92.4% (95% confidence interval (CI): 86.7%-96.8%). According to ME-NBI subgroup analyses, the rate of accurate evaluation of EGC margins was not associated with H. pylori infection status, tumor size, depth of tumor invasion, tumor-occupied site, macroscopic type, histological type, and endoscopists' experience, and no statistical differences were found in subgroup analyses. Moreover, the negative and positive resection rates of HM after ESD and surgery were 97.4% (95% CI: 92.1%-100%) and 2.6% (95% CI: 0.02%-7.9%), respectively. Conclusions ME-NBI enables a reliable delineation of the extent of EGC.

R11 Peptides Can Promote the Molecular Imaging of Spherical Nucleic Acids for the Bladder Cancer Margin Identification

One of the critical problems in bladder cancer (BC) management is local recurrence of disease. However, achieving accurate delineation of tumor margins intraoperatively remains extremely difficult due to the lack of effective tumor margin recognition technology. Herein, survivin molecular beacon (MB) and R11 peptides-linked spherical mucleic acids (SNAs) were synthesized as a nanoprobe (AuNP-MB@R11) for sensitive detection of BC margins. Physicochemical Properties proved that R11 peptides and survivin MB were successfully loaded onto the surface of SNAs. The AuNP-MB@R11 had good stability against nuclease, high sensitivity and specificity to detect survivin ssDNA in vitro experiment. In cytology, R11 peptides could increase BC targeting ability and membrane penetrability of SNAs. Notably, R11 peptides can significantly promote the disintegration of lysosome and release of SNAs to enhance the fluorescence imaging quality. The further RNA sequencing proved that some genes related with endocytosis and lysosome regulated significantly, such as AGPAT5, GPD1L, TREX1 and APEX1. In orthotopic BC models and a clinical sample from patient with BC, AuNP-MB@R11 showed a more legible cancerous fluorescence margin and offered remarkably improved detection effects compared to those achieved by SNAs. Thus, R11 peptides-linked SNAs presented a promising potential to identify the BC margin, which may help to improve the R0 resection rate in surgery and improve patient’s quality of life.