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（由申请人提供）：在此，我们提出开发一种高分辨率光学分子成像系统，其能够直接对大量内源性生物分子种类进行成像，这些生物分子种类目前无法进行高分辨率体积成像。我们计划建立在我们以前的成功集成泵浦探测吸收光谱与光学相干层析成像，开发泵浦探测光学相干显微镜（PPOCM）。所得到的成像系统将具有亚细胞分辨率，灵敏度为105 dB，假设反射器为-40 dB，细胞色素c的相应最小可检测浓度为1 μ M。我们预计组织穿透深度与标准光学相干显微镜相当，在850 nm处口腔上皮中>350 μ m。除了分子图像外，系统还将同时获取描绘组织超微结构的光学相干显微镜图像。我们将首先针对普遍存在的血红素蛋白，其在许多生理过程中发挥重要作用，包括氧转运（血红蛋白，肌红蛋白），细胞代谢（细胞色素c）和药物代谢（细胞色素P450）。许多血红素蛋白（包括列出的那些）以足够的局部浓度存在，以便能够用PPOCM进行检测。此外，它们丰富的吸收光谱在氧化和还原形式之间发生显著变化。这将使得能够测量相对浓度（氧化物/红色），从而直接测量血氧饱和度、细胞代谢和药物代谢。 公共卫生相关性：我们相信，这里提出的技术进步将提供一个宝贵的工具，在体内测量的生化浓度和动态的细胞和小动物亚细胞分辨率。利用开发的工具进行进一步的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非侵入性和微创诊断的发展。由于所提出的技术不需要标记的目标分子，无论是化学或遗传，它有一个强大的潜力，显着扩大光学分子成像在临床和研究环境的影响。