Functional endoscopic fournier domain optical coherence tomography and nano-optical systems for integrated biomedical microscopy

利用光的生物医学成像是一个令人兴奋的研究领域，用于体内细胞和组织的高分辨率结构和功能可视化。光学相干断层扫描（OCT）提供了直接与组织学相当的非破坏性微米级分辨率组织横截面图像。最近，通过使用光谱分辨傅立叶域（FD）检测，已经确定了可获得的OCT系统灵敏度的显著增加。除了功能成像的系统级优势外，FD OCT还可在保持高图像质量的同时实现高速扫描。 本研究提案的目的是使用傅立叶域检测实现的新系统和技术，进一步扩展OCT在眼科传统利基应用之外的用途。FD OCT作为一种光学成像模式，具有很强的潜力，可用于小模型动物和发育生物学的生物医学成像。为了作为首选成像方式获得广泛接受，需要对OCT进行功能扩展，以实现组织识别和生物过程的可视化。提出了利用光谱技术、荧光自干涉和傅里叶域检测相结合的分子衬度成像方法。还将研究用于专门临床应用的最小直径光纤内窥镜探头。 由FD OCT实现的另一功能扩展是纳米级轴向分辨率，在文献中称为谱域相位显微术（SDPM）。本研究提案的第二个分支研究了SDPM与纳米光学显微镜的集成，提供了一种在所有三个维度上提高图像分辨率的途径。纳米孔径成像系统测量由与样品的相互作用引起的通过亚波长直径孔的光透射的差异。微机电系统（MEMS）将被研究用于细胞的操纵和定位，以开发高度集成的芯片上显微镜成像系统。

Biomedical imaging using light is an exciting area of research for high resolution structural and functional visualization of cells and tissues in vivo. Optical coherence tomography (OCT) provides non-destructive micrometer scale resolution cross sectional images of tissue which are directly comparable to histology. Recently, a significant increase in attainable OCT system sensitivity has been identified by the use of spectrally resolved Fourier domain (FD) detection. In addition to novel system level benefits for functional imaging, FD OCT facilitates high speed scanning while maintaining high image quality.     The objective of this research proposal is to further extend the uses of OCT outside its traditional niche application in ophthalmology using novel systems and techniques enabled by Fourier domain detection. FD OCT has strong potential as an optical imaging modality both for biomedical imaging of small model animals and developmental biology. To achieve wide acceptance as the preferred imaging modality, functional extensions are required for OCT to enable tissue identification and visualization of biological processes. Investigation of molecular contrast imaging is proposed using spectroscopic techniques and fluorescence self-interference in combination with Fourier domain detection. Research into minimum diameter fiber-based endoscopic probes for light delivery in specialized clinical applications will also be investigated.     Another functional extension enabled by FD OCT is nanometer-scale axial resolution, referred to in the literature as Spectral Domain Phase Microscopy (SDPM). The second branch of this research proposal investigates integration of SDPM with nano-optical microscopy, providing an avenue to improve image resolution in all three dimensions. The nano-aperture imaging system measures differences in light transmission through a sub-wavelength diameter hole caused by interaction with a sample. Micro-electro-mechanical systems (MEMS) will be investigated for the manipulation and positioning of cells to develop a highly integrated microscope-on-a-chip imaging system.