3D Time Domain Molecular Imaging

描述(由申请人提供)： 最近出现的新的分子荧光探针和蛋白质使分子功能的体内询问成为可能，并极大地提高了我们研究体内发病机制的能力。虽然荧光探头的发展很快，但相应的体内成像技术在很大程度上局限于接近表面事件的定性摄影方法(反射成像)。为了更深入地成像组织中的分子事件，我们最近开发了一台原型扫描仪，用于小动物的荧光介导分子层析成像(FMT)和分子靶标的成像。在活体中仍然存在的主要挑战是a)提高分辨率，b)对特定分子标记的全身分布进行定量成像，以及c)将分子重建与高分辨率表面特征相结合以实现高位置精度渲染。在这项提议中，我们寻求开发一种高度优化的成像系统，具有前所未有的三维探测能力。特别是，我们提出了使用时间门控增强型CCD摄像机对荧光信号进行高空间和时间采样，并将其与非接触检测几何结构、并行反射成像和高分辨率三维边界提取相结合。此外，我们的目标是开发适用于获取的大数据集和非接触几何结构的快速重建方案，以解析和量化荧光染料的浓度、激活和荧光寿命。FMT是为数不多的真正使分子成像成为可能的技术之一，因为它利用了信号放大和荧光激活(分子开关或信标)、高检测灵敏度和化学特异性。此外，它使用稳定的报告器，非电离辐射，可以通过光谱微分同时对多个目标成像。最近的研究也显示了使用这项技术来审问人体组织的潜力。FMT有望增强我们研究分子途径、进行疾病早期检测、实时分子药物以及最终为患者量身定做治疗的能力。

DESCRIPTION (provided by applicant): The recent emergence of novel molecular fluorescent probes and proteins has enabled the in-vivo interrogation of molecular function and significantly enhanced our ability to study pathogenesis in vivo. While advances in fluorochrome probe development have been rapid, the corresponding technologies for in-vivo imaging have been largely limited to qualitative photographic approaches of close to the surface events (reflectance imaging). In order to image molecular events deeper in tissue, we have recently developed a prototype scanner for fluorescence-mediated molecular tomography (FMT) of small animals and imaging of molecular targets. Major challenges that remain in vivo are a) to improve resolution, b) to quantitatively image the full-body distribution of specific molecular markers and c) to merge molecular reconstructions with high-resolution surface features for high positional accuracy rendering. In this proposal we seek to develop a highly optimized imaging system with unprecedented three-dimensional detection capacity. In particular we propose the use of a time-gated intensified CCD camera for high spatial and temporal sampling of fluorescent signals and combine it with non-contact detection geometries, concurrent reflectance imaging and high-resolution three-dimensional boundary extraction. Furthermore, we aim at developing fast reconstruction schemes, appropriate for the large data-sets acquired and for non-contact geometries, in order to resolve and quantify fluorochrome concentration, activation and fluorescence lifetime. FMT is one of the few truly enabling technologies for molecular imaging since it capitalizes on signal amplification and fluorescence activation (molecular switches or beacons), high detection sensitivity and chemical specificity. Furthermore, it uses stable reporters, non-ionizing radiation and can simultaneously image multiple targets by spectral differentiation. Recent studies have also shown the potential of using this technology to interrogate human tissues. FMT is expected to enhance our ability to study molecular pathways, perform early detection of disease, real time molecular medicine and ultimately patient-tailored treatment.