In-vivo optical molecular imaging with Dynamic Contrast Enhancement (DyCE)

描述（由申请人提供）：小动物中基于荧光的分子成像对药物开发和疾病研究产生重大影响。然而，在体内成像靶向荧光标记物的一个重大挑战仍然存在：除非标记的区域位于表面;定位，定量和宿主器官鉴定受到光散射和吸收的影响。原位肿瘤和疾病模型越来越优选于生物学相关性较低的皮下异种移植物。在这样的研究中，在纵向研究中遇到了很大的困难，因为动物正在生长，每次测量的位置都不同。我们相信，一个单一的成像进步可以解决许多这些问题，并推进体内分子成像的实用性：一个精确的解剖配准技术，不依赖于多模态技术。该提案描述了动态分子成像（DIM），一种可以通过以简单且廉价的方式利用染料在小动物体内的药代动力学来提供共配准的解剖信息的方法。我们证明，通过在注射惰性染料过程中获得一个时间序列的光学图像，我们可以重复和准确地描绘出小鼠的主要内部器官单独使用光学成像。这是可能的，因为每个主要器官都被染料通过它的动力学“照亮”，从而使它与其他结构区分开来。时空分析可以利用这些特征时间过程，以允许每个器官的体表表示被可视化。这些体内解剖图可以叠加到同时采集的靶向分子探针的图像上（如果需要，通过多光谱成像技术检测并与映射染料区分开），以显著帮助识别探针的解剖和物理位置。使用CRi现有的和原型的2D，“2.5D”和真正的3D多光谱鼠标成像系统，我们建议测试和完善一个可扩展的方法。基于我们迄今为止的发现，我们将研究和利用近红外染料吲哚菁绿色的体内药代动力学，以生成各个器官的描绘表面投影。将该表面图与检测到的靶向标记的表面投影共配准将允许推断靶向探针的3D空间位置。该信息可进一步用于提高深部靶的纵向分子成像研究的定量准确性。

DESCRIPTION (provided by applicant): Fluorescence-based molecular Imaging in small animals is having a major impact on drug development and disease research. However, a significant challenge to imaging targeted fluorescent markers in vivo remains: unless the labeled regions are located superficially; localization, quantitation and host organ identification are impeded by the effects of light scattering and absorption. Orthotopic tumor and disease models are increasingly preferred over less biologically relevant subcutaneous xenografts. In such studies, substantial difficulties are encountered in longitudinal studies where animals are growing and are positioned differently for each measurement. We believe that a single imaging advance could address many of these issues, and advance the utility of in-vivo molecular imaging: an exact anatomical co-registration technique that does not rely on multimodal techniques. This proposal describes dynamic molecular imaging (DMI), an approach that can provide co-registered anatomical information by exploiting in-vivo pharmacokinetics of dyes in small animals in a simple and inexpensive way. We demonstrate that by acquiring a time-series of optical images during injection of an inert dye, we can repeatably and accurately delineate the major internal organs of mice using optical imaging alone. This is possible because each major organ is "illuminated" by the kinetics of dye passing through it in such a manner as to make it distinguishable from other structures. Spatiotemporal analysis can exploit these characteristic time courses to allow the body-surface representation of each organ to be visualized. These in- vivo anatomical maps can be overlaid onto simultaneously acquired images of a targeted molecular probe (detected and distinguished from the mapping dye via multispectral imaging techniques, if necessary) to significantly aid in identification of the probe's anatomical and physical location. Using CRi's existing and prototype 2D, "2.5D" and true 3D multispectral mouse imaging systems, we propose to test and refine a DMI approach. Based on our findings to date, we will examine and exploit in-vivo pharmacokinetics of the near-infrared dye, indocyanine green, to generate delineated surface projections of individual organs. Co-registering this surface map with surface projections of detected targeted labels will allow the targeted probe's 3D spatial location to be inferred. This information can further be used to improve quantitative accuracy in longitudinal molecular imaging studies of deep targets.