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

生物医学成像利用光是一个令人兴奋的研究领域，高分辨率的结构和功能可视化的细胞和组织在体内。光学相干断层扫描（OCT）提供非破坏性微米级分辨率的组织横截面图像，直接与组织学相比较。最近，通过使用光谱分辨傅立叶域（FD）检测，可以显著提高OCT系统的灵敏度。除了功能成像的新系统级优势外，FD OCT还有助于高速扫描，同时保持高图像质量。本研究计划的目标是利用傅立叶域检测的新系统和技术，进一步扩展OCT在眼科传统应用领域之外的应用。FD OCT在小型模型动物和发育生物学的生物医学成像中具有很强的潜力。为了作为首选成像方式得到广泛接受，OCT需要功能扩展，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和荧光自干涉结合傅立叶域检测技术进行分子对比成像的研究。研究最小直径光纤内窥镜探针的光传输在专门的临床应用也将进行调查。FD OCT的另一个功能扩展是纳米尺度的轴向分辨率，在文献中称为光谱域相显微镜（SDPM）。本研究计划的第二个分支研究了SDPM与纳米光学显微镜的集成，为提高所有三个维度的图像分辨率提供了一条途径。纳米孔径成像系统测量由与样品相互作用引起的亚波长直径孔的光透射差异。将研究微机电系统（MEMS）用于细胞的操作和定位，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.