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。但它们的应用受到深目标空间分辨率低的限制。x射线成像因其高分辨率而常被用作解剖成像工具。但其对比度较低，限制了其在分子成像中的应用。我们提出了一种混合成像方式，x射线发光光学断层扫描（XLOT），在浑浊介质中成像x射线可激发纳米颗粒，具有高分子对比灵敏度和良好的空间分辨率，与目标深度无关。利用高分辨率x射线束沿着单线激发Gd2O2S:Eu （GOS）等磷光纳米粒子穿过物体。利用灵敏的电子倍增电荷耦合器件（EMCCD）检测受激GOS发射的光子。通过扫描x射线束穿过受试者，利用EMCCD测量数据，利用基于模型的重建方法，利用已知的激发位置重建颗粒浓度。同时也可以产生结构x射线图像。我们建立了一个直径为2mm的准直x射线束和EMCCD相机的XLOT原型系统。x射线束扫描了幻影的横切面。利用XLOT成功重建了直径4.8 mm、深5.7 mm、浓度分别为1.0 mg/mL和0.2 mg/mL的微尺度GOS颗粒的圆柱形目标，但由于x射线成像的对比灵敏度较低，无法检测到。本提案的目标是开发和表征适合体内成像研究的XLOT系统，该系统也可以同时产生解剖x射线CT图像。第二个目标是优化平台荧光粉纳米颗粒核心，该核心可以功能化并与XLOT成像一起使用，以支持快速扩展的纳米医学领域的广泛研究和开发。

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.