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Spectral Imaging of Iodine and Gadolinium Nanoparticles Using Dual-Energy CT

机译：双能CT对碘和d纳米粒子的光谱成像

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Advances in CT hardware have propelled the development of novel CT contrast agents. Combined with the spectral capabilities of X-ray CT, molecular imaging is possible using multiple heavy-metal contrast agents. Nanoparticle platforms make particularly attractive agents because of (1) their ability to carry a large payload of imaging moieties, and (2) their ease of surface modification to facilitate molecular targeting. While several novel imaging moieties based on high atomic number elements are being explored, iodine (I) and gadolinium (Gd) are particularly attractive because they are already in clinical use. In this work, we investigate the feasibility for in vivo discrimination of iodine and gadolinium nanoparticles using dual energy micro-CT. Phantom experiments were performed to measure the CT enhancement for I and Gd over a range of voltages from 40 to 80 kVp using a dual-source micro-CT system with energy integrating detectors having cesium iodide scintillators. The two voltages that provide maximum discrimination between I and Gd were determined to be 50 kVp with Cu filtration and 40 kVp without any filtration. Serial dilutions of I and Gd agents were imaged to determine detection sensitivity using the optimal acquisition parameters. Next, an in vivo longitudinal small animal study was performed using Liposomal I (Lip-I) and Liposomal Gd (Lip-Gd) nanoparticles. The mouse was intravenously administered Lip-Gd and imaged within 1 h post-contrast to visualize Gd in the vascular compartment. The animal was re-imaged at 72 h post-contrast with dual-energy micro-CT at 40 kVp and 50 kVp to visualize the accumulation of Lip-Gd in the liver and spleen. Immediately thereafter, the animal was intravenously administered Lip-I and re-imaged. The dual energy sets were used to estimate the concentrations of Gd and I via a two-material decomposition with a non-negativity constraint. The phantom results indicated that the relative contrast enhancement per mg/ml of I to Gd was 0.85 at 40 kVp and 1.79 at 50 kVp. According to the Rose criterion (CNR>5), the detectability limits were 2.67 mg/ml for I and 2.46 mg/ml for Gd. The concentration maps confirmed the expected biodistribution, with Gd concentrated in the spleen and with I in the vasculature of the kidney, liver, and spleen. Iterative reconstruction provided higher sensitivity to detect relatively low concentrations of gadolinium. In conclusion, dual energy micro-CT can be used to discriminate and simultaneously image probes containing I and Gd.
机译：CT硬件的进步推动了新型CT造影剂的发展。结合X射线CT的光谱功能，可以使用多种重金属造影剂进行分子成像。纳米粒子平台之所以成为极具吸引力的试剂，是因为（1）它们能够携带大量成像部分有效载荷，以及（2）它们易于进行表面修饰以促进分子靶向。虽然正在探索基于高原子序数元素的几种新颖的成像部分，但是碘（I）和ado（Gd）特别有吸引力，因为它们已经在临床中使用。在这项工作中，我们调查使用双能微型CT在体内区分碘和g纳米颗粒的可行性。进行了幻影实验，使用带能量整合探测器和碘化铯闪烁体的双源微型CT系统，在40至80 kVp的电压范围内测量了I和Gd的CT增强。提供I和Gd之间最大区别的两个电压经Cu过滤确定为50 kVp，不进行任何过滤的确定为40 kVp。对I和Gd试剂的系列稀释液进行成像，以使用最佳采集参数确定检测灵敏度。接下来，使用脂质体I（Lip-I）和脂质体Gd（Lip-Gd）纳米粒子进行了体内纵向小动物研究。给小鼠静脉内施用Lip-Gd并在造影后1小时内成像以可视化血管腔室中的Gd。对比后72 h，用40 kVp和50 kVp的双能微型CT对动物重新成像，以观察Lip-Gd在肝脏和脾脏中的蓄积情况。此后立即给动物静脉内施用Lip-1并重新成像。双能量集用于通过具有非负约束的两种材料分解来估算Gd和I的浓度。幻影结果表明，每毫克/毫升I与Gd的相对对比度增强在40 kVp时为0.85，在50 kVp时为1.79。根据Rose标准（CNR> 5），I的可检测限为Gd的2.67 mg / ml，Gd的可检测限为2.46 mg / ml。浓度图证实了预期的生物分布，其中Gd集中在脾脏中，I集中在肾脏，肝脏和脾脏的脉管系统中。迭代重建提供更高的灵敏度来检测相对较低浓度的g。总之，双能微型CT可以用于区分和同时成像包含I和Gd的探针。

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