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.

结肠内的早期癌症通常发生在组织的外层。随着癌症的发展并入侵下面的肠壁，细胞之间的信号会触发新的异常血管的形成。这些容器是扭曲的，其结构和组件有变化。与正常的血管和毛细血管相比，也存在显着差异。由于技术限制，现有的直接研究结肠组织结构和功能的技术受到限制。该项目将开发可用于内窥镜的探针，该探针可用于内窥镜，这是一种标准的手术设备，可以对组织特性的三维表示形象进行成像并重建三维表示。该技术将对多种类型和尺寸的解剖学“管”（包括消化道，胰管和其他结构）有用。这种新型装置将用于检验以下假设：结肠组织表面下的血管异常结构和组织与结直肠肿瘤的生长和发育有关。同样，可以预期有效的结直肠肿瘤将伴随着正常的血管结构和组织的回归。在该项目中，研究和教育组成部分是通过本科生和研究生指导和培训活动，课程开发以及特定于生物学特定的夏令营整合的。在夏令营中，学生将学习光的基础知识以及如何使用光来回答生命科学中的研究问题。该项目着重于开发一种新型的层析成像成像微观镜镜（TIME）平台，能够对组织结构和灌注的多模式表征。该研究计划建立在基于光纤图像指南的基于PI的基于图像指南的微观镜检查平台上，该平台能够在亚细胞（3.5微米）分辨率下对表面组织进行成像。提出的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，并能够在微脉管系统中进行多模式的实时实时实时成像，对组织灌注的光谱定量（血液蛋白含量和氧气饱和度）和高质量构造的图像的光谱定量。特定的设计目标包括：1）外径1mm； 2）没有复杂的电流法或谐振扫描系统； 3）具有成本效益的硬件（$ 20,000 USD），以促进转化为临床应用，4）层析成像分辨率，能够对地下容器的三维映射约为20微米直径，低至500微米的深度。研究计划围绕三个目标组织：1）使用纤维束图指南微观镜检查的层析成像图像重建 - 请求原型微观镜检查设备的开发以及PDMS Phantoms中的图像重建方法和图像重建方法和验证； 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治疗干预。该奖项反映了NSF的法定任务，并被认为是通过基金会的知识分子优点和更广泛的影响审查标准来评估值得支持的。