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(申请人提供)：胆管癌(胆管癌)是最常见的胆道恶性肿瘤，在全球范围内发病率和死亡率都在增加。它通常是在晚期被诊断出来的，在这个时候总体预后很差。然而，接受手术切除的早期肿瘤患者的预后很好。相反，胆管上皮内瘤变(BLIN)是胆管癌的一种，其病变通常表现为不确定的胆管狭窄，由于难以获得足够的人体组织进行组织学分析，临床诊断往往不确定。结果，很大一部分患者接受了大手术，结果发现狭窄是良性的，或者等待了太长时间才进行根治性手术。合作的目标是开发一种基于图像的诊断方法，使用荧光染色的探针和一种新的内窥镜设备来映射探针。使用这种方法，可以从以下几个方面缩短癌症检测的时间并提高诊断的准确性：胆管上皮生物标记物的定量映射有望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，并可能识别癌症治疗的分子靶点。高对比度荧光分子探针也可以用来对整个不确定的胆管狭窄进行成像，并可用于指导活检。由于胆管细胞癌的分子生物学具有高度的异质性，因此需要一种检测多分子靶点的方法。研究人员将使用已知的与不同癌症靶点结合的多个探针，并将在现有原型的基础上开发能够对荧光探针进行广域成像的多模多光谱扫描光纤内窥镜(MmSFE)。这些探针将进行优化和验证，并将在小鼠体内用验证过的探针测试MmSFE。在小鼠研究后，将使用局部应用荧光分子探针和微创内窥镜在试点人类受试者试验中测试MmSFE。定量测试也将在体外人体组织和模体胰胆器官中进行。体内和体外图像将与病理结果进行比较，以开发基于图像的诊断工具，这些工具可以单独使用，也可以与组织和细胞样本结合使用。最近的研究表明，开发的早期检测胆道癌的方法将适用于其他胰胆器官的癌症，特别是胰腺癌，这是美国癌症死亡的第四大原因。该项目具有长期潜力，可以减少胰胆癌的晚期诊断，从而改善预后，并减少对不确定胆管狭窄的过度诊断，从而防止不必要的大手术和创伤。