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CAREER: Tomographic microendoscopy for characterization of epithelial tissue structure and function

职业：用于表征上皮组织结构和功能的断层显微内窥镜检查

基本信息

批准号：
1751554
负责人：
Timothy Muldoon
金额：
$ 50万
依托单位：
University of Arkansas
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-06-01 至 2024-12-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1751554&HistoricalAwards=false
关键词：
CAREER Tomographic microendoscopy characterization epithelial

项目摘要

Early cancer within the colon typically arises in the outer layers of the tissue. As cancer progresses and invades into the bowel wall beneath, a signals between cells trigger the formation of new, abnormal blood vessels. These vessels are twisted and have variations in their structure and components. There are also significant differences when compared to normal blood vessels and capillaries. Existing techniques to directly investigate the colon tissue's structure and function in a living subject are limited due to technological constraints. This project will develop a probe that can be used on an endoscope, a standard piece of surgical equipment, that can image the tissue and reconstruct a three-dimensional representation of the tissue properties. This technology will be useful for anatomical "tubes" of many types and sizes - including the digestive tract, pancreatic duct, and other structures. This novel device will be used to test the hypothesis that an abnormal structure and organization of blood vessels beneath the surface of the colon tissue is related to colorectal tumor growth and development. Similarly, it is expected that effective treatment of colorectal tumors will be accompanied by a return of normal blood vessel structure and organization. Within this project, research and educational components are integrated through undergraduate and graduate student mentoring and training activities, course development, and a Biophotonics-specific summer camp. In the summer camp, students will learn the fundamentals of light and how light can be used to answer research questions in the life sciences.The project focuses on developing a novel Tomographic Imaging MicroEndoscopy (TIME) platform, capable of multimodal characterization of tissue structure and perfusion. The Research Plan builds on an optical fiber bundle image guide-based microendoscopy platform, previously developed by the PI, capable of imaging superficial tissues at subcellular (3.5 micron) resolution. The proposed platform will be capable of deployment via endoscope (for gastrointestinal applications) or catheter (for intravascular applications) and be capable of multimodal real-time in vivo tomographic imaging of microvasculature, spectroscopic quantification of tissue perfusion (hemoglobin content and oxygen saturation) and high-resolution imaging of superficial tissue microarchitecture. Specific design goals include: 1) Outer diameter of 1mm; 2) No complex galvanometric or resonant scanning systems; 3) Cost-effective hardware ($20,000 USD) to facilitate translation to clinical applications and 4)Tomographic resolution capable of three dimensional mapping of subsurface vessels of ~20 micron diameter, down to 500 micron depth. The Research Plan is organized around three objectives: 1) Tomographic-image reconstruction using a fiber bundle image guide microendoscope--requiring development of the prototype microendoscopy device and image reconstruction methods and validation in PDMS phantoms; 2) Fluorescence-based tomographic microendoscopy (F-TIME) for angiographic applications--requiring development of image reconstruction methods and validation in optical phantoms and 3) Application of TIME for characterization of tumor vasculature and perfusion in an orthotopic mouse model of colorectal cancer--requiring mapping the in vivo microenvironment during tumor development and characterizing the tumor vasculature in response to a therapeutic intervention.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

早期结肠癌通常发生在组织的外层。当癌症进展并侵入下面的肠壁时，细胞之间的信号触发了新的异常血管的形成。这些血管是扭曲的，在结构和组成上有变化。与正常血管和毛细血管相比，也有显著差异。由于技术的限制，直接研究活体结肠组织结构和功能的现有技术受到限制。该项目将开发一种可用于内窥镜的探针，内窥镜是一种标准的外科设备，可以对组织成像并重建组织特性的三维表示。这项技术将适用于许多类型和大小的解剖“管道”，包括消化道、胰管和其他结构。这种新型装置将被用来检验结肠组织表面下血管的异常结构和组织与结直肠肿瘤的生长和发展有关的假设。同样，预期结肠肿瘤的有效治疗将伴随着正常血管结构和组织的恢复。在这个项目中，通过本科生和研究生的指导和培训活动、课程开发和生物光子学特定夏令营，研究和教育部分被整合在一起。在夏令营中，学生们将学习光的基础知识，以及如何利用光来回答生命科学中的研究问题。该项目致力于开发一种新型的层析成像显微内窥镜（TIME）平台，能够对组织结构和灌注进行多模态表征。该研究计划建立在先前由PI开发的基于光纤束图像导向的显微内窥镜平台上，能够以亚细胞（3.5微米）分辨率对表面组织进行成像。该平台将能够通过内窥镜（用于胃肠道应用）或导管（用于血管内应用）部署，并能够进行微血管的多模式实时体内断层成像，组织灌注的光谱定量（血红蛋白含量和氧饱和度）和表面组织微结构的高分辨率成像。具体设计目标包括：1)外径1mm；2)没有复杂的振镜或谐振扫描系统；3)具有成本效益的硬件（20,000美元），以促进转化为临床应用；4)层析成像分辨率能够对直径约20微米，深度至500微米的地下血管进行三维测绘。研究计划围绕三个目标组织：1)使用纤维束图像引导显微内窥镜进行断层成像重建-需要开发原型显微内窥镜设备和图像重建方法，并在PDMS幻影中进行验证；2)基于荧光的断层显微内窥镜（F-TIME）用于血管造影应用——需要开发图像重建方法并在光学成像中进行验证；3)TIME用于表征原位结直肠癌小鼠模型中的肿瘤血管和灌注——需要绘制肿瘤发展过程中的体内微环境，并表征肿瘤血管对治疗干预的反应。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。