Multiplexed imaging of biliary intra-epithelial neoplasia

胆道上皮内瘤变的多重成像

• 批准号: 9110227
• 负责人: Eric J Seibel
• 金额: $ 58.91万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-14 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9110227
• 关键词: Affinity; Benign; Bile duct carcinoma; Biliary; Biliary Tract Cancer; Biliary Tract Neoplasm; Binding; Biological Markers; Biopsy; Caliber; Cancer Detection; Cancer Etiology; Cell surface; Cells; Cessation of life; Cholangiocarcinoma; Clinical; Collaborations; Curative Surgery; Cytology; Detection; Devices; Diagnosis; Diagnostic; Diagnostic Neoplasm Staging; Diagnostic Procedure; Disease; Duct (organ) structure; Early Diagnosis; Endoscopes; Endoscopy; Epidermal Growth Factor Receptor; Epithelial; Epithelium; Excision; Fiber; Fluorescence; Gallbladder; Gastrointestinal tract structure; Goals; Health; Histology; Human; Image; Imaging Device; Imaging Techniques; In Vitro; Incidence; Individual; Intraepithelial Neoplasia; Label; Lead; Lesion; Light; Liver; Main pancreatic duct; Malignant Neoplasms; Malignant neoplasm of pancreas; Maps; Methods; Michigan; Molecular; Molecular Biology; Molecular Probes; Molecular Target; Mus; Neoplasms; Operative Surgical Procedures; Organ; Outcome; Pancreas; Pancreatic Adenocarcinoma; Pancreatic duct; Pancreaticoduodenectomy; Pathology; Pathway interactions; Patients; Peptides; Performance; Physicians; Procedures; Protocols documentation; Research; Research Personnel; Resected; Sampling; Scanning; Screening for cancer; Sensitivity and Specificity; Specificity; Specimen; Staging; Staining method; Stains; Structural Models; System; Testing; Therapeutic; Time; Tissues; Topical application; Trauma; Tumor stage; United States; Universities; Unnecessary Surgery; Washington; Work; animal imaging; base; bile duct; biliary tract; cancer biomarkers; chemotherapy; claudin-1 protein; clinical Diagnosis; diagnostic accuracy; flexibility; fluorescence imaging; fluorophore; human subject; human tissue; imaging agent; imaging modality; improved; in vivo; in vivo imaging; innovation; millimeter; minimally invasive; mortality; neoplastic; novel; optical imaging; outcome forecast; overexpression; patient population; prevent; prototype; targeted cancer therapy; time use; tissue phantom; tool

 DESCRIPTION (provided by applicant): Cholangiocarcinoma (bile duct cancer) is the most common malignancy of the biliary tract, and is increasing in incidence and mortality worldwide. It is usually diagnosed at an advanced stage, at which point the overall prognosis is poor. However, patients with early stage tumors who undergo resection have excellent outcomes. Conversely, lesions of biliary intraepithelial neoplasia (BilIN), a type of cholangiocarcinoma, frequently appear as indeterminate biliary strictures, and because of the difficulty obtaining enough human tissue for histological analysis, clinical diagnosis is often inconclusive. As a result, a large fraction of patients undergo major surgery only to find that the strictures are benign, or wait too long to have curative surgery. The goal of the collaboration is to develop an image-based diagnostic method that uses fluorescently stained probes and a novel endoscopy device to map the probes. With this method, the time to cancer detection could be reduced and the accuracy of diagnosis improved in the following ways: Quantitative mapping of biomarkers of the biliary epithelium is expected to enable detection of molecular changes before structural changes are apparent - it should improve the ability to distinguish cancer from nonlethal disease, and it may be able to identify molecular targets for cancer therapy. High-contrast fluorescence molecular probes can also be used to image the entire indeterminate biliary stricture and can be used to guide biopsy. Because the molecular biology of cholangiocarcinoma is highly heterogeneous, a method of detecting multiple molecular targets is needed. The researchers will use multiple probes known to bind with different cancer targets and, from an existing prototype, will develop a multimodal multispectral scanning fiber endoscope (mmSFE) capable of wide-field imaging of the fluorescence probes. The probes will be optimized and validated, and the mmSFE will be tested with the validated probes in vivo in mice. After the mouse studies, the mmSFE will be tested in pilot human subject trials using topical application of the fluorescence molecular probes and minimally invasive endoscopy. Quantitative tests will also be performed with ex vivo human tissue and phantom pancreatobiliary organs. In vivo and ex vivo images will be compared with pathology findings in order to develop image-based diagnostic tools that can be used alone or combined with tissue and cell samples. Recent research indicates that methods developed for early detection of biliary cancer will be applicable to cancers of other pancreatobiliary organs, specifically cancer of the pancreas, and the fourth leading cause of cancer deaths in the United States. This project has the long-term potential to reduce late-stage diagnoses of pancreatobiliary cancer, thereby improving prognoses, as well as to reduce overdiagnosis of indeterminate biliary strictures, thereby preventing unnecessary major surgery and trauma.

 描述（由申请人提供）：胆管癌（胆管癌）是最常见的胆道恶性肿瘤，其发病率和死亡率在全球范围内不断增加，通常在晚期才被诊断出来，此时总体预后较差。然而，接受切除术的早期肿瘤患者通常会获得良好的离线预后，胆管上皮内瘤变（BilIN）（一种胆管癌）的病变经常发生。表现为不确定的胆管狭窄，并且由于难以获得足够的人体组织进行组织学分析，临床诊断常常是不确定的，因此，很大一部分患者接受大手术后才发现狭窄是良性的，或者等待太久。此次合作的目标是开发一种基于图像的诊断方法，该方法使用荧光染色探针和新型内窥镜设备来绘制探针图，从而可以缩短癌症检测的时间，并提高癌症检测的效率。通过以下方式提高诊断的准确性：胆道上皮生物标志物的定量图谱预计能够在结构变化明显之前检测到分子变化 - 它应该提高区分癌症和非致命性疾病的能力，并且可能能够确定癌症治疗的分子靶点 高对比度荧光分子探针还可用于对整个不确定的胆管狭窄进行成像，并可用于指导活检，因为胆管癌的分子生物学具有高度的特异性。异质性，需要一种检测多个分子靶标的方法，研究人员将使用已知与不同癌症靶标结合的多种探针，并将从现有原型开发出能够对癌症进行宽视野成像的多模态多光谱扫描纤维内窥镜（mmSFE）。探针将被优化和验证，mmSFE 将在小鼠体内使用经过验证的探针进行测试。在小鼠研究之后，mmSFE 将在人体试验中使用局部应用进行测试。荧光分子探针和微创内窥镜检查还将对离体人体组织和模型胰胆器官进行定量测试，将体内和离体图像与病理结果进行比较，以开发可单独使用的基于图像的诊断工具。或与组织和细胞样本相结合，最近的研究表明，为早期检测胆道癌而开发的方法将适用于其他胰胆器官的癌症，特别是胰腺癌，这是癌症死亡的第四大原因。该项目具有减少胰胆癌晚期诊断的长期潜力，从而改善预后，并减少对不确定性胆管狭窄的过度诊断，从而防止不必要的大手术和创伤。