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

University Of Arkansas, Fayetteville AR

Investigators

Abstract

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.