X-ray Luminescence Optical Tomography for Small Animal Imaging

描述(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具有非常高测量灵敏度的细胞水平活动的研究中发挥着越来越重要的作用。但由于深部目标空间分辨率低，限制了它们的应用。X射线成像因其高分辨率而经常被用作解剖成像工具。但由于其对比度灵敏度较低，限制了其在分子成像中的应用。我们提出了一种混合成像方式，即X射线发光光学层析成像(XLOT)，用于成像混浊介质中的X射线可激发纳米颗粒，具有高分子对比度灵敏度和良好的空间分辨率，与靶深度无关。高分辨率的X射线束被用来激发荧光粉纳米颗粒，如Gd2O2S：Eu(GOS)，沿着穿过物体的一条线。用灵敏的电子倍增电荷耦合器件(EMCCD)探测被激发的GOS发出的光光子。通过扫描穿过受试者的X射线束，EMCCD测量被用来利用基于模型的重建方法利用已知的激发位置来重建粒子浓度。还可以同时产生结构X射线图像。我们用直径为2 mm的准直X射线束和一台EMCCD摄像机搭建了XLOT原型系统。X射线束扫描了模体的横截面。用XLOT成功地重建了直径4.8 mm、深度5.7 mm、GOS浓度为1.0 mg/m L和0.2 mg/m L微米级GOS颗粒的圆柱形靶标，但由于其对比度低，仅用X射线成像不能检测到它们。这项建议的目标是开发和表征一种适用于活体成像研究的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荧光粉纳米颗粒核心，这些核心可以功能化并与XLOT成像一起使用，以支持快速扩张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.