Focused-x-ray Luminescence at uCT Resolution and uM-level Sensitivity

uCT 分辨率和 uM 级灵敏度的聚焦 X 射线发光

• 批准号: 9891055
• 负责人: Changqing Li
• 金额: $ 60.88万
• 依托单位: UNIVERSITY OF CALIFORNIA, MERCED
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9891055
• 关键词: 3-Dimensional; Algorithms; Animal Model; Animals; Area; Biological; Biophotonics; Body Surface; Characteristics; Collection; Color; Cone; Coupled; Couples; Data; Diagnostic radiologic examination; Diffusion; Dimensions; Drug Delivery Systems; Epidermal Growth Factor Receptor; Fc Receptor; Fiber; Financial compensation; Goals; Hybrids; Image; Imaging Device; Individual; Label; Lead; Libraries; Light; Literature; Location; Longitudinal Studies; Malignant Neoplasms; Maps; Measures; Modeling; Molecular; Monitor; Mus; Optics; Penetration; Performance; Photons; Process; Protocols documentation; Radiation Dose Unit; Reporting; Research; Resolution; Roentgen Rays; Scanning; Scheme; Slice; Specificity; Speed; Spottings; Surface; System; Thinness; Three-Dimensional Image; Time; Tissues; Toxic effect; Tube; Universities; Update; Work; X-Ray Computed Tomography; algorithm development; animal imaging; anticancer research; attenuation; base; cancer cell; cellular imaging; data acquisition; data format; data sharing; density; design; detector; experimental study; genetic disorder diagnosis; image reconstruction; imaging modality; imaging platform; imaging system; improved; in vivo; insight; instrumentation; interest; lens; light emission; luminescence; microCT; millimeter; molecular imaging; multidisciplinary; nanomedicine; novel; operation; optical imaging; optical spectra; outcome forecast; particle; personalized medicine; photomultiplier; pre-clinical; precision medicine; preclinical study; prototype; receptor density; reconstruction; response; scale up; serial imaging; simulation; temporal measurement; tomography; tumor; tumor growth; tumor heterogeneity

X-ray luminescence computed tomography (XLCT) is a novel and promising molecular imaging modality. In XLCT, collimated X-ray photons excite nanophosphors that can be functionalized to induce luminescence light photons that are measured for tomographic imaging. Thus, XLCT promises to integrate spatial resolution of X- ray micro-CT and molecular sensitivity of optical imaging. However, this potential has not been implemented yet due to the following two challenges. First, it is rather difficult to collimate divergent X-rays into a thin pencil beam, and even with such a narrow beam the data acquisition process would take long time. Second, it remains an open question how to develop bright, safe and biologically relevant X-ray excitable nanophosphors. In this project, we will prototype a focused X-ray luminescence tomography (FXLT) system for spatial resolution of 150µm, molecular sensitivity around 5µM, and penetration depth sufficient for small animal imaging. The imaging time per transverse section is <2 minute with the radiation dose in the range of a typical micro-CT scan. Our pilot results demonstrate that we can use a polycapillary lens to focus X-rays from a focal spot of 55µm into a dual-cone-shaped pencil beam of 78 µm in the focused region, much thinner and much more intense than a collimated X-ray beam in the XLCT experiments reported in the literature. Hence, the spatial resolution of FXLT can be at least improved to ~150µm. We will use 8 photomultiplier tubes (PMTs) to measure emitted optical photons on the mouse body surface at two emission wavelengths simultaneously. The parallel use of these single-photon-counting PMTs will substantially reduce the measurement time and the radiation dose. We will mount an X-ray tube with its lens on a linear stage which is in turn on a rotary gantry. On the same gantry, we will mount another X-ray tube and an X-ray photon detector for micro-CT for hybrid X- ray and optical imaging. We will develop compressed sensing algorithms for image reconstruction from micro- CT and FXLT data, aided by optimized combination of sparsity and correlation priors such as by minimizing dimensionality of the patch manifold of an image. The micro-CT images will guide the selection of regions of interest and allow attenuation correctness for quantitative FXLT. To enable and demonstrate the preclinical feasibility and merits of FXLT, we will synthesize bright nanophosphors with multiple emission wavelengths and surface functionalization. We will characterize and optimize these nanophosphors in terms of their emission efficiency, emission wavelengths, toxicity, and specificity. Finally, we will perform live mouse studies using our FXLT system, with an emphasis on longitudinal imaging of the EGFR density in deep tumor. Upon the completion of this project, we will have optimized and characterized the first-of-its-kind hybrid molecular imaging system FXLT. Also, we will have demonstrated the advantages of FXLT for preclinical molecular imaging. FXLT couples X-ray focusing and optical labeling for micro-CT resolution and optical sensitivity, and will be a vital molecular imaging tool for precision medicine.

X射线发光计算机断层扫描（XLCT）是一种新颖而有望的分子成像方式。在 XLCT，对X射线照片的X射线照片激发了可以功能诱导发光光的纳米磷酸 用于层析成像的照片。 XLCT有望整合X-的空间分辨率 光学成像的射线微CT和分子灵敏度。但是，这种潜力尚未实施 然而，由于以下两个挑战。首先，很难将X射线分散成薄铅笔很难 梁，即使有如此狭窄的光束，数据采集过程也需要很长时间。第二，它 仍然是一个悬而未决的问题，如何发展明亮，安全和生物学上相关的X射线激动人心的纳米流圈。 在这个项目中，我们将原型用于空间的X射线发光断层扫描（FXLT）系统 分辨率为150µm，分子敏感性在5µm附近的分子敏感性和足够的小动物的穿透深度 成像。每个横截面的成像时间小于2分钟，辐射剂量在典型的范围内 Micro-CT扫描。我们的飞行员结果表明，我们可以使用多毛细管镜头从焦点进行X射线 在聚焦区域中，55µm的斑点置于78 µm的双锥形铅笔梁中，较薄且多大 在文献中报道的XLCT实验中，比对X射线的X射线束更强烈。因此， FXLT的空间分辨率至少可以提高到〜150µm。我们将使用8个Photolultiplier管（PMT） 简单地在两个发射波长下在小鼠体表面上测量发射的光学照片。这 并行使用这些单光子计数PMT将大大减少测量时间和 辐射剂量。我们将在线性舞台上安装带有镜头的X射线管，然后又在旋转龙门上。 在同一龙门上，我们将安装另一台X射线管和一个用于混合X-的Micro-CT的X射线光子检测器 射线和光学成像。我们将开发从微型重建图像重建的压缩传感算法 CT和FXLT数据，通过优化的稀疏性和相关先验的组合，例如通过最小化 图像的补丁歧管的维度。 Micro-CT图像将指导选择区域的选择 兴趣并允许定量FXLT的衰减正确性。启用和演示临床前 FXLT的可行性和优点，我们将综合具有多个发射波长的明亮纳米磷酸 和表面功能化。我们将根据其表征和优化这些纳米磷 发射效率，发射波长，毒性和特异性。最后，我们将进行现场鼠标研究 使用我们的FXLT系统，重点是深肿瘤中EGFR密度的纵向成像。 该项目完成后，我们将优化和表征首先的混合动力 分子成像系统FXLT。另外，我们将证明FXLT在临床前的优势 分子成像。 FXLT情侣X射线聚焦和光学标记，用于微分离和光学 灵敏度，将是精确药物的重要分子成像工具。