Med Phys. 2013 Aug;40(8):080702. doi: 10.1118/1.4816297.
To develop a proof-of-principle L-shell x-ray fluorescence (XRF) imaging system that locates and quantifies sparse concentrations of gold nanoparticles (GNPs) using a benchtop polychromatic x-ray source and a silicon (Si)-PIN diode x-ray detector system.
12-mm-diameter water-filled cylindrical tubes with GNP concentrations of 20, 10, 5, 0.5, 0.05, 0.005, and 0 mg∕cm3 served as calibration phantoms. An imaging phantom was created using the same cylindrical tube but filled with tissue-equivalent gel containing structures mimicking a GNP-loaded blood vessel and approximately 1 cm3 tumor. Phantoms were irradiated by a 3-mm-diameter pencil-beam of 62 kVp x-rays filtered by 1 mm aluminum. Fluorescence∕scatter photons from phantoms were detected at 90° with respect to the beam direction using a Si-PIN detector placed behind a 2.5-mm-diameter lead collimator. The imaging phantom was translated horizontally and vertically in 0.3-mm steps to image a 6 mm×15 mm region of interest (ROI). For each phantom, the net L-shell XRF signal from GNPs was extracted from background, and then corrected for detection efficiency and in-phantom attenuation using a fluorescence-to-scatter normalization algorithm.
XRF measurements with calibration phantoms provided a calibration curve showing a linear relationship between corrected XRF signal and GNP mass per imaged voxel. Using the calibration curve, the detection limit (at the 95% confidence level) of the current experimental setup was estimated to be a GNP mass of 0.35 μg per imaged voxel (1.73×10(-2) cm3). A 2D XRF map of the ROI was also successfully generated, reasonably matching the known spatial distribution as well as showing the local variation of GNP concentrations.
L-shell XRF imaging can be a highly sensitive tool that has the capability of simultaneously imaging the spatial distribution and determining the local concentration of GNPs presented on the order of parts-per-million level within subcentimeter-sized ex vivo samples and superficial tumors during preclinical animal studies.
开发一种基于原理验证的 L 壳层 X 射线荧光（XRF）成像系统，该系统使用台式多色 X 射线源和硅（Si）-PIN 二极管 X 射线探测器系统定位和定量稀疏浓度的金纳米颗粒（GNPs）。
使用浓度为 20、10、5、0.5、0.05、0.005 和 0mg/cm3 的直径为 12mm 的装满水的圆柱形管作为校准体模。使用相同的圆柱形管创建成像体模，但充满组织等效凝胶，其中包含模拟载有金纳米颗粒的血管和大约 1cm3 肿瘤的结构。体模用 3mm 直径的 62kVp X 射线铅笔束照射，并用 1mm 厚的铝过滤。使用放置在 2.5mm 直径铅准直器后面的 Si-PIN 探测器，以相对于光束方向 90°检测来自体模的荧光/散射光子。将成像体模以 0.3mm 的步长水平和垂直平移，以对感兴趣区域（ROI）的 6mm×15mm 区域进行成像。对于每个体模，从背景中提取 GNPs 的净 L 壳层 XRF 信号，然后使用荧光与散射归一化算法对检测效率和体模内衰减进行校正。
校准体模的 XRF 测量提供了一条校准曲线，显示校正后的 XRF 信号与每个成像体素中的 GNP 质量之间存在线性关系。使用校准曲线，估计当前实验装置的检测限（置信水平为 95%）为每个成像体素中 0.35μg 的 GNP 质量（1.73×10(-2)cm3）。还成功生成了 ROI 的 2D XRF 图，与已知的空间分布相当吻合，并且显示了 GNP 浓度的局部变化。
L 壳层 XRF 成像可以成为一种高度灵敏的工具，具有在亚厘米级离体样本和临床前动物研究中对表面肿瘤内以百万分之几的量级同时成像 GNP 空间分布和确定局部浓度的能力。
