Computed tomography (CT) is one of the most widely used clinical imaging modalities. In order to increase the sensitivity of CT, small iodinated compounds are used as injectable contrast agents. However, the iodinated contrast agents are excreted through the kidney and have short circulation times. This rapid renal clearance not only restricts in vivo applications that require long circulation times but also sometimes induces serious adverse effects related to the excretion pathway. In addition, the X-ray attenuation of iodine is not efficient for clinical CT that uses high-energy X-ray. Due to these limitations, nano-sized iodinated CT contrast agents have been developed that can increase the circulation time and decrease the adverse effects. In addition to iodine, nanoparticles based on heavy atoms such as gold, lanthanides, and tantalum are used as more efficient CT contrast agents. In this review, we summarize the recent progresses made in nano-sized CT contrast agents.
Highly versatile nanocomposite nanoparticles were synthesized by decorating the surface of mesoporous dye-doped silica nanoparticles with multiple magnetite nanocrystals. The superparamagnetic property of the magnetite nanocrystals enabled the nanoparticles to be used as a contrast agent in magnetic resonance (MR) imaging, and the dye molecule in the silica framework imparted optical imaging modality. Integrating a multitude of magnetite nanocrystals on the silica surface resulted in remarkable enhancement of MR signal due to the synergistic magnetism. An anticancer drug, doxorubicin (DOX), could be loaded in the pores and induced efficient cell death. In vivo passive targeting and accumulation of the nanoparticles at the tumor sites was confirmed by both T2 MR and fluorescence imaging. Furthermore, apoptotic morphology was clearly detected in tumor tissues of mice treated with DOX loaded nanocomposite nanoparticles, demonstrating that DOX was successfully delivered to the tumor sites and its anticancer activity was retained.
Core/shell upconverting nanoparticles (UCNPs) of NaGdF4:Er3+,Yb3+/NaGdF4 (see figure) are shown to serve as a multimodal imaging probe that works for both background‐free optical imaging and magnetic resonance imaging (MRI). The nonblinking and nonbleaching properties of UCNPs can contribute to minimization of possible artifacts in long‐term imaging experiments. Owing to Gd3+ ions in the host matrix, contrast is enhanced in T1‐weighted MRI.
Histogram analysis of ADC maps based on entire tumor volume can be a useful tool for grading gliomas. The fifth percentile of the cumulative ADC histogram obtained at a high b value was the most promising parameter for differentiating high- from low-grade gliomas.
Ever since Au nanoparticles were developed as X-ray contrast agents, researchers have actively sought alternative nanoparticle-based imaging probes that are not only inexpensive but also safe for clinical use. Herein, we demonstrate that bioinert tantalum oxide nanoparticles are suitable nanoprobes for high-performance X-ray computed tomography (CT) imaging while simultaneously being cost-effective and meeting the criteria as a biomedical platform. Uniformly sized tantalum oxide nanoparticles were prepared using a microemulsion method, and their surfaces were readily modified using various silane derivatives through simple in situ sol-gel reaction. The silane-modified surface enabled facile immobilization of functional moieties such as polyethylene glycol (PEG) and fluorescent dye. PEG was introduced to endow the nanoparticles with biocompatibility and antifouling activity, whereas immobilized fluorescent dye molecules enabled simultaneous fluorescence imaging as well as X-ray CT imaging. The resulting nanoparticles exhibited remarkable performances in the in vivo X-ray CT angiography and bimodal image-guided lymph node mapping. We also performed an extensive study on in vivo toxicity of tantalum oxide nanoparticles, revealing that the nanoparticles did not affect normal functioning of organs.
Background and PurposeTo apply a texture analysis of apparent diffusion coefficient (ADC) maps to evaluate glioma heterogeneity, which was correlated with tumor grade.Materials and MethodsForty patients with glioma (WHO grade II (n = 8), grade III (n = 10) and grade IV (n = 22)) underwent diffusion-weighted imaging (DWI), and the corresponding ADC maps were obtained. Regions of interest containing the lesions were drawn on every section of the ADC map containing the tumor, and volume-based data of the entire tumor were constructed. Texture and first order features including entropy, skewness and kurtosis were derived from the ADC map using in-house software. A histogram analysis of the ADC map was also performed. The texture and histogram parameters were compared between low-grade and high-grade gliomas using an unpaired student’s t-test. Additionally, a one-way analysis of variance analysis with a post-hoc test was performed to compare the parameters of each grade.ResultsEntropy was observed to be significantly higher in high-grade gliomas than low-grade tumors (6.861±0.539 vs. 6.261±0.412, P = 0.006). The fifth percentiles of the ADC cumulative histogram also showed a significant difference between high and low grade gliomas (836±235 vs. 1030±185, P = 0.037). Only entropy proved to be significantly different between grades III and IV (6.295±0.4963 vs. 7.119±0.3165, P<0.001). The diagnostic accuracy of ADC entropy was significantly higher than that of the fifth percentile of the ADC histogram (P = 0.0034) in distinguishing high- from low-grade glioma.ConclusionA texture analysis of the ADC map based on the entire tumor volume can be useful for evaluating glioma grade, which provides tumor heterogeneity.
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