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射线发光计算机层析成像(XLCT)是一种新型的、有发展前途的分子成像手段。在……里面 XLCT，准直X射线光子激发纳米磷光体，可以功能化以诱导发光 为层析成像而测量的光子。因此，XLCT有望将X-空间分辨率 射线显微CT和分子光学成像的灵敏度。然而，这一潜力尚未实现。 然而，由于以下两个挑战。首先，将发散的X射线准直成一支细铅笔是相当困难的 即使是这么窄的光束，数据采集过程也需要很长时间。第二，它 如何开发明亮、安全和生物相关的X射线可激发纳米荧光粉仍然是一个悬而未决的问题。 在这个项目中，我们将建立一个聚焦x射线发光层析成像(Fxlt)系统的原型。 分辨率为150微米，分子灵敏度约为5微米，穿透深度足以容纳小动物 成像。每个横截面的成像时间是&lt；2分钟，辐射剂量在典型的 微型CT扫描。我们的试验结果表明，我们可以使用多毛细管透镜聚焦来自焦点的X射线。 在聚焦区，55微米的光斑进入78微米的双锥形铅笔束，变得更薄，也更 比文献中报道的XLCT实验中的准直X射线束更强。因此， FXLT的空间分辨率至少可以提高到~150微米。我们将使用8个光电倍增管(PMT)来 同时测量两个发射波长的小鼠体表面发射的光学光子。这个 并行使用这些单光子计数PMT将大大缩短测量时间和 辐射剂量。我们将把一个带有透镜的X射线管安装在一个线性工作台上，而这个工作台又安装在一个旋转的龙门上。 在同一机架上，我们将安装另一台X射线管和一台用于混合X-CT的X射线光子探测器。 光线和光学成像。我们将开发用于从微观图像重建图像的压缩传感算法 CT和FXLT数据，借助稀疏性和相关性先验的优化组合，例如通过最小化 图像的面片流形的维度。显微CT图像将指导区域的选择 感兴趣，并允许衰减的准确性为定量FXLT。以启用和演示临床前 FXLT的可行性和优点，我们将合成多个发射波长的明亮纳米荧光粉 和表面功能化。我们将从它们的角度来表征和优化这些纳米荧光粉 发射效率、发射波长、毒性和特异性。最后，我们将进行活体老鼠研究 使用我们的FXLT系统，重点是对深部肿瘤的EGFR密度进行纵向成像。 在这个项目完成后，我们将对第一款同类混合动力车进行优化和表征 分子成像系统FXLT。此外，我们还将展示FXLT在临床前的优势 分子成像。FXLT将X射线聚焦和光学标记结合在一起，以实现Micro-CT分辨率和光学 高灵敏度，并将成为精密医学的重要分子成像工具。