Integrated Optical Needle (ION) for Cellular and Molecular Imaging of Cancer

用于癌症细胞和分子成像的集成光针 (ION)

• 批准号: 7526818
• 负责人: Rebecca R. Richards-Kortum
• 金额: $ 35.36万
• 依托单位: RICE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7526818
• 关键词: Address; Anatomy; Animal Model; Architecture; Area; Biological Markers; Biomedical Engineering; Biopsy; Biopsy Specimen; Caliber; Cancer Center; Caring; Cells; Cellular Morphology; Class; Clinical; Clinical Trials; Collaborations; Color; Columnar Epithelium; Commit; Communicable Diseases; Computer Systems Development; Confocal Microscopy; Contrast Media; Coupled; Cultured Cells; Custom; Data; Depth; Detection; Development; Device Designs; Devices; Diagnosis; Disadvantaged; Discipline; Disease; Distal; Dose; Dyes; Early Diagnosis; Endoscopes; Engineering; Epithelial; Evaluation; Excision; Faculty; Fiber; Fiber Optics; Figs - dietary; Finland; Fluorescence; Functional Imaging; Gel; Goals; Head and Neck Surgery; Human; Image; Image Guided Biopsy; Imaging Device; Imaging technology; Inflammatory; Institution; Invasive; Ions; Laboratories; Lateral; Lead; Length; Light; Lighting; Location; Magnetic Resonance Imaging; Malignant Neoplasms; Measures; Mechanics; Metabolic; Methods; Metric; Microscope; Modality; Molecular; Molecular Target; Monitor; Morphology; Names; Needles; Neoplasms; Operative Surgical Procedures; Optical Coherence Tomography; Optics; Pain; Patients; Penetration; Performance; Phase II Clinical Trials; Photons; Pliability; Positron-Emission Tomography; Pre-Clinical Model; Preclinical Testing; Principal Investigator; Process; Productivity; Puncture biopsy; Range; Relative (related person); Research; Research Design; Resistance; Resolution; Rice; Sampling; Sampling Errors; Sectioning technique; Site; Source; Squamous Epithelium; Staining method; Stains; Standards of Weights and Measures; Structure; System; Systems Integration; Techniques; Technology; Testing; Time; Tissues; Translations; Ultrasonography; Universities; University of Texas M D Anderson Cancer Center; Walking; Work; base; cellular imaging; clinical Diagnosis; clinical application; concept; cost; design; detector; dosage; human subject; human tissue; image processing; improved; in vivo; interdisciplinary collaboration; lens; lithography; member; molecular imaging; molecular/cellular imaging; neoplastic; oncology; optical imaging; preclinical study; professor; programs; prototype; response; sensor; size; therapeutic target; time use; tissue culture; tool; tumor

DESCRIPTION (provided by applicant): Recent advances in confocal microscopy have demonstrated the potential of optical imaging to provide molecular images with sub-cellular resolution. In this proposal, we extend our work in high resolution confocal microscopy, based on a much simpler alternative, based on our observation that high resolution optical images of the top 1-2 layers of cells can be obtained without the need for a confocal imaging gate if the cells are placed in direct contact with a flat optical window. Here we propose a new class of optical imaging device - the integrated optical needle (ION) - which can be inserted into a small gauge needle and advanced through tissue to acquire images of tissue at the distal tip of the needle with sub-cellular resolution in real time; the use of targeted contrast agents or vital stains can yield additional contrast as well as functional and/or molecular imaging capability. The first version of the optical needle, described in Aim 1, is based on a flexible, coherent fiber-optic bundle coupled to macroscopic imaging optics and a CCD image sensor. The under-sampling associated with the structure of the fiber bundle used in Aim 1 limits the spatial resolution. The second approach, an integrated optical needle (ION) described in Aims 2 and 3, uses LIGA technology to integrate miniature lenses fabricated using grayscale lithography, together with the light source and image sensor to yield a miniature microscope which can be inserted through a needle. This ION consists of a NA = 0.4 microscope that can image with 1 micron lateral resolution from a 250 um field of view; it is designed to fit within a needle that has an inner diameter of 1 mm. We will carry out a variety of preclinical tests using cell culture, tissue culture, animal models and pilot clinical trials to evaluate the relative performance of these systems. The question to be addressed is whether imaging without a pinhole or other depth-sectioning technique yields images of sufficient quality to appreciate cellular detail required clinically, and to determine whether out-of-focus and scattered photons reduce contrast to too large a degree. Our preliminary results indicate that it is possible to obtain good images of cellular detail in human subjects using contrast agents in routine clinical use. However, to judge image quality with the various devices and contrast agents, we will use quantitative measures of image resolution, image contrast and image SNR. Research proposed here will develop a new tool for image guided tissue assessment in real time, and confirmatory biopsy at image directed locations. The ION can image a broad range of contrast agents enabling molecular information from specific sites. The cost of the integrated optical needle will be low even in small quantities (below $2,300) but there is great potential to further reduce this cost when manufactured in quantity.

描述（由申请人提供）：共焦显微镜的最新进展已经证明了光学成像提供具有亚细胞分辨率的分子图像的潜力。在本提案中，我们基于一种更简单的替代方案，扩展了我们在高分辨率共焦显微镜方面的工作，基于我们的观察，如果细胞与平面光学窗口直接接触，则无需共焦成像门即可获得顶部 1-2 层细胞的高分辨率光学图像。在这里，我们提出了一种新型光学成像设备——集成光学针（ION）——它可以插入小规格针中并穿过组织，以实时获取针远端组织的亚细胞分辨率图像；使用靶向造影剂或活体染色剂可以产生额外的对比度以及功能和/或分子成像能力。目标 1 中描述的第一个版本的光针基于与宏观成像光学器件和 CCD 图像传感器耦合的柔性相干光纤束。与目标 1 中使用的光纤束结构相关的欠采样限制了空间分辨率。第二种方法是目标 2 和 3 中描述的集成光针 (ION)，它使用 LIGA 技术将使用灰度光刻制造的微型透镜与光源和图像传感器集成在一起，形成可以通过针插入的微型显微镜。该 ION 由 NA = 0.4 显微镜组成，可以在 250 微米视场中以 1 微米横向分辨率进行成像；它设计用于安装内径为 1 毫米的针。我们将利用细胞培养、组织培养、动物模型和预临床试验进行各种临床前测试，以评估这些系统的相对性能。要解决的问题是，没有针孔或其他深度切片技术的成像是否能产生足够质量的图像来欣赏临床所需的细胞细节，并确定离焦和散射光子是否会在很大程度上降低对比度。我们的初步结果表明，在常规临床使用中使用造影剂可以获得人类受试者细胞细节的良好图像。然而，为了判断不同设备和造影剂的图像质量，我们将使用图像分辨率、图像对比度和图像信噪比的定量测量。这里提出的研究将开发一种新工具，用于实时图像引导组织评估，并在图像引导位置进行验证性活检。 ION 可以对多种造影剂进行成像，从而获得特定位点的分子信息。即使是小批量（低于 2,300 美元），集成光针的成本也很低，但大批量生产时，进一步降低成本的潜力巨大。