Depth-Resolved Imaging of Alterations in Mucosal Microcirculation

粘膜微循环变化的深度分辨成像

• 批准号: 8307223
• 负责人: Sarah K Ruderman
• 金额: $ 3.49万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-15 至 2014-09-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8307223
• 关键词: Aberrant crypt foci; Adenomatous Polyps; American; Animal Model; Area; Azoxymethane; Biological; Blood; Blood Circulation; Blood capillaries; Cancer Detection; Cancer Etiology; Cessation of life; Clinical; Colon; Colon Carcinoma; Colonoscopy; Colorectal Cancer; Communities; Data; Dependence; Detection; Development; Diagnosis; Diagnostic; Discrimination; Early Diagnosis; Effectiveness; Event; Extravasation; Fingerprint; Fostering; Four-dimensional; Future; Goals; Gold; Health system; Hemoglobin; Image; Image Analysis; Imagery; Imaging Techniques; Immunohistochemistry; Lead; Lesion; Location; Malignant Neoplasms; Measurement; Measures; Methods; Microcirculation; Modeling; Molecular; Mucous Membrane; Nature; Neoplasms; Normal tissue morphology; Optics; Patients; Penetration; Polyps; Precancerous Conditions; Property; Rattus; Relative (related person); Research; Role; Series; Spectrum Analysis; Surface; System; Techniques; Technology; Testing; Texture; Time; Tissues; Universities; Vascular blood supply; Vasodilation; Work; acronyms; adenoma; angiogenesis; base; capillary; carcinogenesis; clinical application; clinically significant; colon carcinogenesis; colorectal cancer screening; design; flexibility; human NOS2A protein; image processing; imaging modality; imaging probe; improved; in vivo; insight; light scattering; neoplastic; neovascularization; new technology; novel; prototype; public health relevance; research study; simulation; tissue phantom; tumor progression; validation studies

DESCRIPTION (provided by applicant): Using a novel optical technique, polarization-gated spectroscopy, our group detected an early increase in blood supply (EIBS) prior to any morphological manifestation of colon carcinogenesis. The goal of this research plan is to extend previous work to enable a better understanding of the EIBS phenomenon. Developing an imaging based system will allow visualization of microvasculature changes beyond the capabilities of the current probe with single-point measurements. The project will utilize the azoxymethane (AOM) rat model of colon cancer to determine the biological mechanisms responsible for this increase in blood supply (neovascularization, vasodilation, and extravasation), and the optimal colonic depth to identify this effect. Future clinical applications will result from developing a novel imaging technique to detect this phenomenon. Initial designs of the imaging system will be guided through Monte Carlo simulations to determine the dependence of optical geometries on penetration depth. Contrast enhancement will be investigated for optimization through polarization gating and limited bandwidths or filtering. From these experiments, a prototype imaging system will be built and penetration depth validated on a series of tissue phantoms with tunable optical properties. Subsequently, the imaging technique will be refined and quantification of blood content, as well as roughness, homogeneity or other discriminating textures will be classified. Using the same animal model for validation studies, further refinement and image analysis will provide insight on specific differentiation between normal mucosa and the microvascular changes within the endoscopically-normal mucosa associated with carcinogenic events. This study will elucidate the biological mechanisms of EIBS, as well as explore the feasibility of imaging this phenomenon for more accurate detection and localization of colonic neoplasia. Accordingly, developing an imaging technique to explore visualization of superficial microcirculation will lead to an in vivo imaging application that would allow for accurately detecting structural changes of precancerous conditions from the endoscopically-normal tissue during a colonoscopy. Given the relative inexpensiveness of the technology and ease of use, this would be a clinically practical approach. If successful, depth-resolved imaging of colonic mucosa could foster the understanding of the origins of EIBS and possibly carcinogenesis, as well as improve polyp detection, providing a more reliable early detection method for colon cancer. PUBLIC HEALTH RELEVANCE: The objective of this project is to improve and extend the optical techniques developed by our lab for early detection of colon cancer. This requires design and implementation of a novel imaging technique capable of detecting blood supply, specifically pertaining to the superficial capillary network of the colon during the progression of cancer. Through optimization of the imaging system, visualization of these changes in vasculature can pave the road for clinical applications to improve cancer detection.

描述（由申请人提供）：使用一种新型的光学技术，极化门控光谱法，我们的小组在结肠癌发生的任何形态学表现之前都检测到了早期血液供应（EIBS）的早期增加。该研究计划的目的是扩展以前的工作，以更好地了解EIBS现象。开发基于成像的系统将允许通过单点测量的当前探针的能力来可视化微脉管系统的变化。该项目将利用结肠癌的甲氧基甲烷（AOM）大鼠模型来确定导致血液供应增加的生物学机制（新血管形成，血管舒张和渗出）以及最佳结肠深度以识别这种作用。未来的临床应用将是由于开发一种新型成像技术来检测这种现象而产生的。成像系统的初始设计将通过蒙特卡洛模拟引导，以确定光学几何形状对穿透深度的依赖性。对比度增强将通过极化门控和有限的带宽或过滤研究进行对比增强。从这些实验中，将建立一个原型成像系统，并在具有可调光学特性的一系列组织幻像上验证。随后，将对成像技术进行完善，并将血液含量的量化以及粗糙度，同质性或其他区分纹理进行分类。使用相同的动物模型进行验证研究，进一步的细化和图像分析将洞悉与致癌事件相关的内镜下正常粘膜内正常粘膜和微血管变化之间的特定区别。这项研究将阐明EIB的生物学机制，并探索成像这种现象以更准确检测和定位结肠肿瘤的可行性。 因此，开发一种成像技术来探索浅表微循环的可视化，将导致体内成像应用，该应用将允许在结肠镜检查过程中准确检测内镜下正常组织的癌前条件的结构变化。鉴于技术的相对便宜和易用性，这将是一种临床上实用的方法。如果成功，对结肠粘膜的深度分辨成像可能会促进对EIB的起源和可能的癌变的理解，并改善息肉检测，从而为结肠癌提供了更可靠的早期检测方法。 公共卫生相关性：该项目的目的是改善和扩展我们实验室为早期检测结肠癌开发的光学技术。这需要设计和实施一种能够检测血液供应的新型成像技术，特别是与癌症进展过程中结肠的表面毛细血管网络有关的。通过优化成像系统，脉管系统中这些变化的可视化可以为临床应用铺平道路，以改善癌症检测。