Development of a preclinical optical frequency domain angiography instrument

描述(申请人提供)：肿瘤诱导的血管生成在肿瘤向恶性肿瘤的发展过程中起着核心作用，为血液来源的治疗提供进入肿瘤空间的关键运输，并提供氧气以实现氧气依赖的放射和基于光的治疗。肿瘤血管生成和肿瘤微血管功能的临床前研究传统上依赖于组织学方法，这些方法存在众所周知的局限性，或者基于荧光的共聚焦和多光子显微镜，它们提供多参数的高分辨率三维成像，但支持有限视野和穿透深度的成像。相比之下，光学相干断层扫描方法支持相对更大的视野和穿透深度，如果转化到生物实验室，有可能揭示肿瘤微血管系统的关键和以前隐藏的方面。在我们的实验室中，我们已经演示了一种独特的临床前光学成像技术的原理，该技术将成为研究体内血管和生物微环境的强大工具。这项名为光学频域血管成像(OFDA)的技术支持类似于多光子和共聚焦显微镜的高分辨率三维成像。在这份提案中，我们提出了光学、工程、计算和软件解决方案，这些解决方案将需要实现实用和健壮的OFDA仪器，以便转化为生物实验室。我们的方法将联合马萨诸塞州综合医院(MGH)和物理科学公司(PSI)的研究人员和资源。OFDA仪器和核心算法的创新将由MGH团队进行，而改善处理所需的计算硬件和软件的构建将由PSI团队执行。我们的目标是将OFDA的技术从工程转移到生物实验室，这可能会催化对基础癌症生物学和癌症治疗的研究。

DESCRIPTION (provided by applicant): Tumor-induced angiogenesis plays a central role in the progression of tumors to malignancy, provides the critical transport of blood-born therapies into the tumor space, and supplies oxygen to effectuate oxygen-dependent radiological and light-based therapies. Pre-clinical research in tumor angiogenesis and tumor microvascular function has traditionally relied on histological methods, which suffer from well-known limitations, or fluorescence-based confocal and multiphoton microscopy, which provide high- resolution three-dimensional mapping of multiple parameters but support imaging over limited fields of view and depths of penetration. By contrast, optical coherence tomography approaches support a relatively larger field of view and depth of penetration and have the potential, if translated into the biological laboratory, to reveal critical and previously hidden aspects of the tumor microvasculature. In our laboratory, we have demonstrated the principles of a unique preclinical optical imaging technology that will be a powerful tool for investigating blood vessels and the biological microenvironment in vivo. The technology, optical frequency domain angiography (OFDA), supports high- resolution three-dimensional imaging similar to multiphoton and confocal microscopy. In this proposal, we propose optical, engineering, computational, and software solutions that will be required to realize a practical and robust OFDA instrument for translation into the biological laboratory. Our approach will unite investigators and resources at the Massachusetts General Hospital (MGH) and Physical Sciences, Incorporated (PSI). Innovations to the OFDA instrumentation and core algorithms will be performed by the MGH team, while construction of the computational hardware and software that is needed to improve processing will be performed by the PSI team. Our goal is to move OFDA technology from the engineering to the biological laboratory, which may catalyze research into basic cancer biology and cancer therapeutics.