Development of high-resolution molecular imaging of endogenous chromophores with

内源性发色团高分辨率分子成像的发展

• 批准号: 7845631
• 负责人: Brian E. Applegate
• 金额: $ 17.25万
• 依托单位: TEXAS ENGINEERING EXPERIMENT STATION
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-15 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7845631
• 关键词: Algorithms; Animals; Biochemical; Biometry; Blood; Cells; Clinical Research; Collagen; Color; Cytochrome P450; Data Collection; Detection; Development; Diagnostic; Environment; Hemeproteins; Hemoglobin; Human; Image; Lead; Measurement; Measures; Metabolism; Microscopy; Myoglobin; Optical Coherence Tomography; Optics; Oxygen; Penetration; Physiological Processes; Play; Principal Investigator; Process; Pump; Recovery; Relative (related person); Resolution; Role; Scanning; Scheme; Sensitivity and Specificity; Specificity; Spectrum Analysis; System; Techniques; Testing; Time; Tissues; absorption; base; chromophore; cytochrome c; design; drug metabolism; human disease; improved; in vivo; minimally invasive; molecular imaging; oral cavity epithelium; oxygen transport; programs; public health relevance; research and development; success; tissue phantom; tool

DESCRIPTION (provided by applicant): Here we propose to develop a high-resolution optical molecular imaging system capable of directly imaging a large pool of endogenous biomolecular species, which are currently inaccessible to high-resolution volumetric imaging. We plan to build on our previous success in integrating pump-probe absorption spectroscopy with optical coherence tomography to develop pump-probe optical coherence microscopy (PPOCM). The resulting imaging system will have subcellular resolution with a sensitivity of 105 dB and a corresponding minimum detectable concentration of 1 ¿M of cytochrome c assuming a -40 dB reflector. We expect the tissue penetration depth to be comparable to standard optical coherence microscopy, which is >350 ¿m in oral epithelium at 850 nm. In addition to the molecular image the system will simultaneously acquire the optical coherence microscopy image depicting tissue ultrastructure. We will initially target the ubiquitous heme proteins, which play an important role in numerous physiological processes including oxygen transport (hemoglobin, myoglobin), cellular metabolism (cytochrome c) and drug metabolism (cytochrome P450). Many of the heme proteins (including those listed) exist in sufficient local concentrations to enable detection with PPOCM. In addition, their rich absorption spectra change significantly between oxidized and reduced forms. This will enable the measurement of relative concentrations (oxid/red) leading to direct measures of blood oxygen saturation, cellular metabolism, and drug metabolism. PUBLIC HEALTH RELEVANCE: We believe the technological advances proposed here will provide an invaluable tool for the in vivo measure of biochemical concentration and dynamics in cells and small animals with subcellular resolution. Further research and development utilizing the developed tools may lead to advances in the understanding of the origins and treatment of human disease as well the development of noninvasive and minimally invasive diagnostics in humans. Since the proposed technique does not require tagging of target molecules either chemically or genetically it has a strong potential for dramatically extending the impact of optical molecular imaging in both the clinical and research environment.

描述（由适用提供）：在这里，我们建议开发一种能够直接成像大量内源性生物分子物种的高分辨率光学分子成像系统，目前无法访问高分辨率体积成像。我们计划基于以前在将泵探针抽象光谱与光学相干断层扫描相结合以开发泵浦探针光学相干显微镜（PPOCM）方面的成功。所得的成像系统将具有105 dB的敏感性的亚细胞分辨率，并假设一个-40 dB反射器的敏感性为105 dB和相应的最小可检测浓度。我们期望组织渗透深度与标准的光学相干显微镜相当，在850 nm处的口服上皮中> 350€。除了分子图像外，系统还将轻松获取描绘组织超微结构的光学相干显微镜图像。我们最初将靶向普遍存在的血红素蛋白，该蛋白在包括氧气转运（血红蛋白，肌红蛋白），细胞代谢（细胞色素C）和药物代谢（细胞染料P450）在内的许多物理过程中起着重要作用。许多血红素蛋白（包括列出的蛋白质）都以足够的局部浓度存在，可以通过PPOCM检测。此外，它们富含氧化和还原形式之间的富苦难光谱发生了显着变化。这将实现对相对浓度（氧化/红色）的测量，导致直接测量血氧饱和，细胞代谢和药物代谢。 公共卫生相关性：我们认为，此处提出的技术进步将为体内测量具有亚细胞分辨率的细胞和小动物的生化浓度和动力学提供宝贵的工具。利用已开发工具的进一步研究和开发可能会导致对人类疾病起源和治疗的理解以及人类无创和微创诊断的发展。由于所提出的技术不需要化学或一般对靶标分子进行标记，因此具有巨大的潜力，可以显着扩展光学分子成像在临床和研究环境中的影响。