New Technologies for high resolution optical molecular imaging

描述(申请人提供)：在这里，我们建议采用一种众所周知的和公认的技术，双色泵浦-探测吸收光谱学，用于生物系统的高分辨率三维光学分子成像。泵浦探测吸收光谱在实验分子物理中被广泛用于测量弱荧光分子物种的分子性质。光学相干层析成像(OCT)是一种新兴的高分辨率光学成像手段，它利用低相干干涉测量技术来测量组织样品的三维空间分辨反射率。通过这两种技术的融合，我们将建立一种新的高分辨率三维光学分子成像技术，可以直接探测大量荧光较差的生物分子物种。这项新技术的早期应用是组织微血管系统中血氧饱和度的标测和监测，这是一个很好的试验台。氧合和脱氧血红蛋白都是极差的荧光团，这使得这对于基于荧光的技术来说是一个艰巨的任务，如果不是不可能的话。血氧饱和度是许多人类疾病和条件的重要生物测量指标，包括肿瘤生长和治疗反应、神经系统疾病和伤口愈合。此外，我们还计划将开发的技术与多普勒OCT相结合，以便同时测量血流速度。总之，这里提出的混合成像系统将具有无创和无分子标记的能力，绘制组织形态和微血管的地图，直到最小的血管(~10？m)，测量生理相关水平的血氧饱和度，并测量生理相关流速的血流。我们相信，这里提出的技术进步将为体内测量细胞和小动物的生化浓度和动力学提供宝贵的工具，这可能会促进对人类疾病起源和治疗的了解。它还有可能应用于人类，对发生在上皮和视网膜上的疾病和状况进行非侵入性监测和诊断。由于所提出的技术不需要在化学或遗传上标记目标分子，因此它具有极大地扩展光学分子成像在临床和研究环境中的影响的强大潜力。

DESCRIPTION (provided by applicant): Here we propose to adapt a well known and well established technique, two-color pump-probe absorption spectroscopy, for high resolution 3-D optical molecular imaging of biological systems. Pump-probe absorption spectroscopy has been used extensively in experimental molecular physics to measure the molecular properties of poorly fluorescing molecular species. Optical coherence tomography (OCT) is an emerging high resolution optical imaging modality which harnesses the power of low coherence interferometry to measure the 3-D spatially resolved reflectivity of a tissue sample. By melding these two techniques we will establish a new high resolution 3-D optical molecular imaging technique which can directly probe the large number of poorly fluorescing biomolecular species. An early application of this new technology and an excellent test bed is the mapping and monitoring of blood oxygen saturation in tissue microvasculature. Both oxy and deoxy hemoglobin are extremely poor fluorophores making this a formidable if not impossible task for fluorescence based techniques. Blood oxygen saturation is an important biometric for numerous human diseases and conditions including tumor growth and response to treatment, diseases of the nervous system, and wound healing. In addition we plan to combine the developed technique with Doppler OCT, in order to simultaneously measure the blood flow rate. In summary, the hybrid imaging system proposed here will have the capacity to noninvasively and without molecular tags, map the tissue morphology and microvasculature down to the smallest vessels (~10 ¿m), measure the blood oxygen saturation at physiologically relevant levels, and measure blood flow at physiologically relevant flow rates 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 which may lead to advances in the understanding of the origins and treatment of human disease. There is also the potential for application in humans for noninvasive monitoring and diagnosis of diseases and conditions which occur in the epithelium and retina. 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.