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Long-distance tracing of the lymphatic system with a CT/fluorescence dual-modality nanoprobe for surveying tumor lymphatic metastasis
摘要： Noninvasive visualization of deep tissue lymphatic metastasis is crucial for diagnosing malignant tumors and predicting prognosis. However, the limited diffusivity and specificity of imaging contrast agents that are transported in lymph vessels (LVs), even for those agents delivered by nanocarriers, make long-distance tracing of the lymphatic system in vivo challenging. Here, we develop a CT/fluorescence dual-modality phospholipid nanoprobe (PL(I/D)NP) with a negative charge and sub-60 nm size. By using micro-CT, we noninvasively traced the LVs from the subcutaneous injection site in feet to the thoracic ducts with an entire length of ~68 mm and measured the volume of the lymph nodes (LNs) and their separation distance along the LVs. For diagnostic imaging of tumor lymphatic metastasis, all LNs with metastasis were identified in vivo. Thus, with their long-distance diffusivity, high lymphatic capillary specificity and quantifiability, the PL(I/D)NPs combined with noninvasive imaging accurately depicted the changes in the lymphatic system under pathologic conditions, especially cancer metastasis, which indicates their high potential for clinical applicability.
关键词： lymphatic system,nanoparticle,fluorescent imaging,micro-CT,lymphatic metastasis
更新于2025-11-21 11:08:12
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Fast ScanNet: Fast and Dense Analysis of Multi-Gigapixel Whole-Slide Images for Cancer Metastasis Detection
摘要： Lymph node metastasis is one of the most important indicators in breast cancer diagnosis, that is traditionally observed under the microscope by pathologists. In recent years, with the dramatic advance of high-throughput scanning and deep learning technology, automatic analysis of histology from whole-slide images has received a wealth of interest in the field of medical image computing, which aims to alleviate pathologists’ workload and simultaneously reduce misdiagnosis rate. However, automatic detection of lymph node metastases from whole-slide images remains a key challenge because such images are typically very large, where they can often be multiple gigabytes in size. Also, the presence of hard mimics may result in a large number of false positives. In this paper, we propose a novel method with anchor layers for model conversion, which not only leverages the efficiency of fully convolutional architectures to meet the speed requirement in clinical practice, but also densely scans the whole-slide image to achieve accurate predictions on both micro- and macro-metastases. Incorporating the strategies of asynchronous sample prefetching and hard negative mining, the network can be effectively trained. The efficacy of our method are corroborated on the benchmark dataset of 2016 Camelyon Grand Challenge. Our method achieved significant improvements in comparison with the state-of-the-art methods on tumour localization accuracy with a much faster speed and even surpassed human performance on both challenge tasks.
关键词： metastasis detection,Histopathology image analysis,deep learning,whole-slide image,computational pathology
更新于2025-09-23 15:23:52
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A Nanoprobe for Diagnosing and Mapping Lymphatic Metastasis of Tumor Using 3D Multispectral Optoacoustic Tomography Owing to Aggregation/Deaggregation Induced Spectral Change
摘要： Lymphatic metastasis of tumor is one of leading causes of cancer-related death, and diagnosing lymphatic metastasis is of significance in terms of optimal disease management and possible better outcomes for patients. Herein a turn-on optoacoustic nanoprobe is reported for noninvasively diagnosing and locating lymphatic metastasis in vivo. A positively charged tricyanofuran-containing polyene chromophore (TCHM) with high extinction coefficient is designed, synthesized, and allowed to form the nanoprobe with a negatively charged hyaluronan. The TCHMs take an aggregated state within the nanoprobe and exhibit weak absorption at 882 nm, the overexpressed hyaluronidase in cancer cells specifically degrades hyaluronan into small fragments and disaggregates TCHMs, thereby greatly enhancing the absorption at 882 nm and generating prominent optoacoustic signals. For multispectral optoacoustic tomography (MSOT) imaging in vivo, mice models with subcutaneous tumor and orthotopic bladder tumor are imaged first to demonstrate the nanoprobe’s capability for detecting HAase-overexpressing tumors. A mouse model of lymphatic metastasis of tumor is then established and the lymphatic metastasis is successfully imaged and tracked optoacoustically. The imaging results were verified using multiple biochemical assays. Moreover, 3D MSOT renderings are obtained for precisely locating and tracking the metastasis of tumor in lymphatic system in a spatiotemporal manner.
关键词： lymphatic metastasis,imaging,multispectral,nanoprobe,3D,optoacoustic tomography,aggregation
更新于2025-09-23 15:23:52
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[IEEE 2018 IEEE/CVF Conference on Computer Vision and Pattern Recognition (CVPR) - Salt Lake City, UT, USA (2018.6.18-2018.6.23)] 2018 IEEE/CVF Conference on Computer Vision and Pattern Recognition - Crafting a Toolchain for Image Restoration by Deep Reinforcement Learning
摘要： Background: Malignant insulinoma is extremely rare and accounts for only 10% of total insulinoma cases. The goal of this study is to retrospectively analyze clinical data from 15 patients with malignant insulinoma treated at Peking Union Medical College Hospital (PUMCH) from 1984 to April 2017. Methods: “Malignant insulinoma” was used as the keywords in the PUMCH medical record retrieval system to search and obtain patients’ clinical information. We identified subjects diagnosed with malignant insulinoma based on clinical or surgical pathological signs and subsequently analyzed their clinical data. Results: Eight males and seven females with a median age at diagnosis of 40 years (38–54 years) were included. Eight patients (53%) had developed metastases at diagnosis, while the others (46.67%) developed metastases during the follow-up visits. The major sites of metastasis were the liver (86.7%), local tissues and blood vessels (33%) and abdominal lymph nodes (13%). All patients displayed neuroglycopenic (100%) and/or autonomic (60%) symptoms, mostly during fasting periods (73.3%), with an average blood glucose level of 1.66 ± 0.51 mmol/L. A total of 93% of the patients had one primary pancreatic lesion, 53% had a lesion in the head of the pancreas, and 47% had a lesion in the tail of the pancreas, with diameters ranging between 0.9 and 6.0 cm. Most liver metastases were multiple lesions. Selective celiac arteriography yielded 100% sensitivity for both primary pancreatic lesions and liver metastases. Most patients received synthetical treatments, including surgery, chemoembolization, and octreotide. Conclusions: Malignant insulinomas have a similar diagnostic process to that of benign insulinomas but require far more comprehensive therapies to alleviate hypoglycemic symptoms and extend patients’ survival.
关键词： Hypoglycemia,Hyperinsulinism,Malignant insulinoma,Metastasis,Therapeutics,Diagnosis
更新于2025-09-23 15:23:52
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In Search for Optimal Targets for Intraoperative Fluorescence Imaging of Peritoneal Metastasis From Colorectal Cancer
摘要： Peritoneal metastasis (PM) occurs in about 10% of patients with colorectal cancer (CRC). Fluorescence imaging can enhance contrast between cancerous and benign tissue, enabling the surgeon to clearly visualize PM during cytoreductive surgery. This study assessed the suitability of different biomarkers as potential targets for tumor-targeted imaging of PM of CRC. Tissue samples from primary tumor and PM from patients with CRC were obtained from the pathology archives and immunohistochemical stainings were performed. Overexpression of the epithelial cell adhesion molecule (EpCAM) and carcinoembryonic antigen (CEA) was seen in 100% of PM samples and the expression was strong in >70% of samples. Tyrosine-kinase Met (C-Met) and folate receptor α overexpression was seen in 20% of PM samples. For successful application of tumor-targeted intraoperative fluorescence imaging of PM, biomarkers need to be identified. We demonstrated that both EpCAM and CEA are suitable targets for fluorescence imaging of PM in patients with CRC.
关键词： peritoneal metastasis,biomarkers,colorectal cancer,metastasis,Image-guided surgery,fluorescence
更新于2025-09-23 15:22:29
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Detection of Metastasis in a Patient-derived Orthotopic Xenograft (PDOX) Model of Undifferentiated Pleomorphic Sarcoma with Red Fluorescent Protein
摘要： Background/Aim: Undifferentiated pleomorphic sarcoma (UPS) is a common soft tissue sarcoma and highly recalcitrant. We have previously developed patient-derived orthotopic xenograft (PDOX) mouse models of UPS and other major sarcoma types. Unlike PDOX models of other cancer types, it has been difficult to demonstrate metastasis in the sarcoma PDOX models. Materials and Methods: To visualize metastasis at high resolution in the UPS PDOX model, established tumor fragments were implanted in transgenic nude mice expressing red fluorescent protein (RFP) for one passage. The tumors acquired RFP-expressing stroma from transgenic host. UPS tumor with RFP stromal cells were harvested and implanted orthotopically in non-transgenic nude mice. After six weeks of UPS tumor growth in the PDOX model, the primary tumor was imaged non-invasively and lung, liver, and spleen were resected and imaged ex-vivo in order to visualize the presence of RFP, with a FluorVivo? imaging system and FV1000? confocal laser microscope, respectively. Results: The primary tumor was imaged non-invasively. Confocal microscopy visualized the presence of RFP in the lung and liver indicating metastases in these organs. This is the first report of metastasis in a sarcoma PDOX model. Conclusion: This study should prove very useful to screen for anti-metastatic drugs for the PDOX donor patients and to understand the metastatic process in sarcoma.
关键词： PDOX,patient-derived orthotopic xenograft,red fluorescent protein,soft-tissue,stromal cell,Undifferentiated pleomorphic sarcoma,metastasis
更新于2025-09-23 15:22:29
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Polydopamine-Coated Gold Core/Hollow Mesoporous Silica Shell Particles as a Nanoplatform for Multimode Imaging and Photothermal Therapy of Tumors
摘要： It is highly desirable to develop a new hybrid nanoplatform that integrates diagnosis and treatment elements for effective theranostics of tumors. Herein, we have skillfully designed a nanoplatform of polydopamine (PDA)-coated and perfluorohexane (PFH)-filled gold core/hollow mesoporous silica shell (Au@mSiO2-PFH-PDA, ASPP for short) particles for photoacoustic (PA)/ultrasound (US)/computed tomography (CT)/thermal imaging and photothermal therapy (PTT) of tumors. In this work, we first synthesized Au seed particles with a diameter of 15.8 nm using a sodium citrate reduction method, and coated Au seeds with polyvinylpyrrolidone for further growth of solid silica shell/mesoporous silica shell onto the Au seeds. After treatment via selective etching to remove solid silica shell, amination of surface of the particles, and filling of PFH into the internal cavity of the spheres with a diameter of 182.1 nm, PDA coating was performed to render the particles with an external shell thickness of 15.1 nm. The formed hybrid particles with a size of 212.2 nm are colloidally stable and exhibit good cytocompatibility, and display excellent PA/US/CT/thermal imaging property due to the co-presence of PDA, PFH, and Au nanoparticles. Furthermore, the PDA coating renders the platform with a photothermal conversion efficiency of 61.2%, enabling effective photothermal ablation of cancer cells in vitro and a xenografted 4T1 tumor model in vivo under irradiation with an 808 nm laser. More importantly, in the primary 4T1 tumor model, intratumoral injection of the ASPP and irradiation with an 808 nm laser can also completely inhibit the occurrence lung metastasis induced by the 4T1 tumor. The as-prepared hybrid nanoplatform may hold a great promise to be adopted for multimode imaging and PTT of tumors and inhibition of tumor metastasis.
关键词： Tumor metastasis inhibition,Multimode imaging,Photothermal therapy,Polydopamine NPs,Hollow mesoporous silica,Surface modification
更新于2025-09-23 15:22:29
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Expression of peptide transporter 1?has a positive correlation in protoporphyrin IX accumulation induced by 5-aminolevulinic acid with photodynamic detection of non-small cell lung cancer and metastatic brain tumor specimens originating from non-small cell lung cancer
摘要： BACKGROUND: Recently, 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX fluorescence was reported to be an useful tool during total surgical resection of high-grade gliomas. However, the labeling efficacy of protoporphyrin IX fluorescence is lower in metastatic brain tumors compared to that in high-grade gliomas, and the mechanism underlying protoporphyrin IX fluorescence in metastatic brain tumors remains unclear. Lung cancer, particularly non-small cell lung cancer (NSCLC), is the most common origin for metastatic brain tumor. Therefore, we investigated the mechanism of protoporphyrin IX fluorescence in NSCLC and associated metastatic brain tumors. METHODS: Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) was employed to evaluate the protein and mRNA levels of five transporters and enzymes involved in the porphyrin biosynthesis pathway: peptide transporter 1 (PEPT1), hydroxymethylbilane synthase (HMBS), ferrochelatase (FECH), ATP-binding cassette 2 (ABCG2), and heme oxygenase 1 (HO-1). The correlation between protein, mRNA, and protoporphyrin IX levels in NSCLC cells were evaluated in vitro. Immunohistochemistry was used to determine proteins that played a key role in intraoperative protoporphyrin IX fluorescence in clinical samples from patients with NSCLC and pathologically confirmed metastatic brain tumors. RESULTS: A significant correlation between PEPT1 expression and protoporphyrin IX accumulation in vitro was identified by western blotting (P = 0.003) and qRT-PCR (P = 0.04). Immunohistochemistry results indicated that there was a significant difference in PEPT1 between the intraoperative protoporphyrin IX fluorescence-positive and protoporphyrin IX fluorescence-negative groups (P = 0.009). CONCLUSION: Expression of PEPT1 was found to be positively correlated with 5-ALA-induced protoporphyrin IX accumulation detected by photodynamic reaction in metastatic brain tumors originating from NSCLC.
关键词： protoporphyrin IX,brain metastasis,non-small lung cancer,peptide transporter 1
更新于2025-09-23 15:22:29
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Cutaneous erysipeloid metastasis of cholangiocarcinoma and evaluation by in?vivo reflectance confocal microscopy
摘要： Cutaneous metastases are relatively uncommon, occurring in only 0.7% to 9% of all internal malignancies. Cholangiocarcinoma is a rare bile duct neoplasm that accounts for less than 2% of malignancies. Although it is well known that cholangiocarcinoma metastasizes to the lungs, liver, peritoneum, and retroperitoneal lymph nodes, a retrospective review of the literature from 1978 to 2014 indicates only 30 cases of cutaneous cholangiocarcinoma, with 17 cases presenting without concurrent metastasis in other sites. Among these patients, the cutaneous metastatic disease occurred evenly at adjacent and distant sites, presenting as 0.3-cm to 4-cm erythematous papules or nodules with or without ulceration. The median overall survival after diagnosis of cutaneous cholangiocarcinoma metastasis is 4 months. Paradoxically, single-site metastases carry a significantly worse prognosis than multiple-site metastases and may be attributed to difficulty in identifying a singular lesion. In vivo reflectance confocal microscopy (RCM) is a novel, noninvasive diagnostic alternative to skin biopsy with comparable insurance reimbursement that captures real-time, high-resolution, cellular-level images from the skin surface down to the reticular dermis (up to 300 μm depth). This modality forgoes traumatic biopsy and has been used for diagnosis and monitoring of skin cancers and inflammatory dermatoses.
关键词： cholangiocarcinoma,erysipeloid,cutaneous metastasis,reflectance confocal microscopy
更新于2025-09-23 15:21:21
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One-stop radiotherapeutic targeting of primary and distant osteosarcoma to inhibit cancer progression and metastasis using 2DG-grafted graphene quantum dots
摘要： The application of radiotherapy (RT) to treat osteosarcoma (OS) has been limited, but this is starting to change as the ability to target radiation energy to niches improves. Further, lung cancer from highly metastatic OS is a major cause of death, so it is critical to explore new strategies to tackle metastasis. In this study, we designed a nanoscale radiosensitizer by grafting 2-deoxy-d-glucose (2DG) on to graphene quantum dots (GQD) to achieve OS targeting and boost RT efficacy. Combining the use of 2DG-grafted GQDs (2DG-g-GQD) with RT produced a significant increase in oxidative stress response and DNA damage in the 143B OS cell line compared with RT alone. Moreover, 2DG-g-GQDs selectively associated with 143B cells, and demonstrated inhibition of migration in a scratch assay. We also demonstrated remarkable improvement in ability to inhibit tumour progression and lung metastasis in an OS xenograft mouse model. Our results show that the use of 2DG-g-GQDs as an OS-targeting radiosensitizer improves the therapeutic outcome and exhibits potential for use in low-dose precision RT for OS.
关键词： osteosarcoma,radiotherapy,metastasis,2-deoxy-d-glucose,graphene quantum dots
更新于2025-09-23 15:19:57