X-ray Luminescence Optical Tomography for Small Animal Imaging

描述（由申请人提供）：体内荧光和生物发光光学成像在基因和蛋白质表达以及其他细胞水平活动的研究中发挥着越来越重要的作用，具有非常高的测量灵敏度。但由于其对深部目标的空间分辨率较低，限制了其应用。由于其高分辨率，X射线成像通常用作解剖成像工具。但由于其对比灵敏度较低，限制了其在分子成像中的应用。我们提出了一种混合成像模式，X射线发光光学断层扫描（XLOT），图像X射线可激发的纳米粒子在混浊介质中具有高分子对比灵敏度和良好的空间分辨率，独立于目标深度。使用高分辨率X射线束来沿着沿着穿过物体的单条线激发诸如Gd 2 O 2 S：Eu（GOS）的磷光体纳米颗粒。由激发的GOS发射的可见光子用灵敏的电子倍增电荷耦合器件（EMCCD）检测。通过在受试者上扫描X射线束，EMCCD测量用于使用基于模型的重建方法使用已知的激发位置来重建颗粒浓度。同时还可以生成结构X射线图像。我们已经建立了一个XLOT原型系统与2毫米直径的准直X射线束和EMCCD相机。X射线束扫描了体模的横切面。用浓度为1.0 mg/mL和0.2 mg/mL的微尺度GOS颗粒嵌入的圆柱形靶（直径4.8 mm，深5.7 mm）用XLOT成功地重建，但由于其低对比敏感度，单独的X射线成像不能检测到它们。该提案的目标是开发和表征适用于体内成像研究的XLOT系统，该系统还可以同时产生解剖X射线CT图像。第二个目标是优化平台磷光体纳米颗粒核心，其可以被功能化并与XLOT成像一起使用，以支持在迅速扩展的纳米医学领域中的广泛研究和开发。

DESCRIPTION (provided by applicant): In vivo fluorescence and bioluminescence optical imaging are playing an increasing important role in studies of gene and protein expression, and other cellular level activities with very high measurement sensitivity. But their applications are limited by low spatial resolution for deep targets. X-ray imaging is often used as an anatomical imaging tool because of its high resolution. But its application in molecular imaging is limited because of its low contrast sensitivity. We propose a hybrid imaging modality, X-ray luminescence optical tomography (XLOT), to image X-ray excitable nanoparticles in turbid media with both high molecular contrast sensitivity and good spatial resolution, independent of the target depth. A high resolution X-ray beam is used to excite phosphor nanoparticles such as Gd2O2S:Eu (GOS) along a single line through the object. Optical photons emitted by the excited GOS are detected with a sensitive electron-multiplying charge coupled device (EMCCD). By scanning the x-ray beam across the subject, the EMCCD measurements are used to reconstruct the particle concentration using the known excitation locations with a model based reconstruction method. Structural x-ray images also can be produced at the same time. We have built a XLOT prototype system with 2 mm diameter collimated X-ray beam and an EMCCD camera. The X-ray beam scanned a transverse section of phantoms. Embedded cylindrical targets (4.8 mm diameter, 5.7 mm deep) with microscale GOS particles at concentrations of 1.0 mg/mL and 0.2 mg/mL were reconstructed successfully with XLOT but X-ray imaging alone could not detect them due to its low contrast sensitivity. The goal of this proposal is to develop and characterize a XLOT system suitable for in vivo imaging studies, that also can concurrently produce anatomic X-ray CT images. A second goal is to optimize platform phosphor nanoparticle cores that can be functionalized and used with XLOT imaging in support of a broad range of research and development in the rapidly expanding field of nanomedicine.