Utilization of nanoparticles as X‐ray contrast agents for diagnostic imaging applications

Among all the diagnostic imaging modalities, X‐ray imaging techniques are the most commonly used owing to their high resolution and low cost. The improvement of these techniques relies heavily on the development of novel X‐ray contrast agents, which are molecules that enhance the visibility of internal structures within the body in X‐ray imaging. To date, clinically used X‐ray contrast agents consist mainly of small iodinated molecules that might cause severe adverse effects (e.g. allergies, cardiovascular diseases and nephrotoxicity) in some patients owing to the large and repeated doses that are required to achieve good contrast. For this reason, there is an increasing interest in the development of alternative X‐ray contrast agents utilizing elements with high atomic numbers (e.g. gold, bismuth, ytterbium and tantalum), which are well known for exhibiting high absorption of X‐rays. Nanoparticles (NPs) made from these elements have been reported to have better imaging properties, longer blood circulation times and lower toxicity than conventional iodinated X‐ray contrast agents. Additionally, the combination of two or more of these elements into a single carrier allows for the development of multimodal and hybrid contrast agents. Herein, the limitations of iodinated X‐ray contrast agents are discussed and the parameters that influence the efficacy of X‐ray contrast agents are summarized. Several examples of the design and production of both iodinated and iodine‐free NP‐based X‐ray contrast agents are then provided, emphasizing the studies performed to evaluate their X‐ray attenuation capabilities and their toxicity in vitro and in vivo. Copyright © 2014 John Wiley & Sons, Ltd.     

Real‐time 3D MRI of contrast agents in whole living mice

A specific mouse whole body coil and a dedicated gradient system at 4.7 T were coupled with an ultra‐fast 3D gradient echo MRI and keyhole reconstruction technique to obtain 3D whole‐body dynamic T₁‐weighted or T₂*‐weighted imaging. The technique was used to visualize the real‐time distribution of non‐targeting T₁ and T₂* contrast agent (CA) in a glioma‐bearing mouse model. T₁ dynamic contrast‐enhancement imaging was performed with a fast imaging with steady‐state precession sequence [echo time/repetition time (TE/TR), 1.32/3.7 ms] before and after CA injection (Gd–DOTA and BSA–Gd–DOTA) for 21 min. The temporal resolution was 1 image/6.5 s. T₂* imaging (TE/TR, 4/8 ms) was performed before and after iron‐based (small and ultra‐small particles of iron oxide) CA injection for 45 min. The temporal resolution was 1 image/14 s. Signal‐to‐noise ratio curves were determined in various mouse organs. The whole‐body coil and gradient systems made it possible to acquire data with sufficient and homogeneous signal‐to‐noise ratio on the whole animal. The spatial resolution allowed adequate depiction of the major organs, blood vessels and brain glioma. The distribution and the time‐course of T₁ and T₂* contrasts upon contrast agent injection were also assessed. 3D whole‐body mouse MRI is feasible at high spatial resolution in movie mode and can be applied successfully to visualize real‐time contrast agent distribution. This method should be effective in future preclinical molecular imaging studies. Copyright © 2011 John Wiley & Sons, Ltd.     

超声造影评估脑血流循环时间在无创颅内压监测中的应用

目的:应用超声造影评估脑血流循环时间(cerebral blood flow circulation time,CCT)探索不同程度颅内压时CCT的变化规律,为无创颅内压监测提供新方法。方法:选取2019年1-12月空军军医大学唐都医院的10例颅内压增高的出血性脑卒中或急性颅脑创伤患者,在有创颅内压(invasive ...     

光热型纳米金-共聚物超声造影剂的制备和体内外显像

目的 制备外包纳米金壳内载全氟丙烷(C₃F₈)的聚乳酸羟基乙酸(PLGA)光热型超声造影剂,观察其在体内外的超声显像效果及体外的光热效能。方法 通过改进的乳化溶剂挥发法制备PLGA纳米粒子,包载C₃F₈气体后,再用种子生长法在PLGA表面形成纳米金壳,制备C₃F₈@PLGA@Au纳米粒子;检测其一般特性,并用近红外激光和超声成像仪评估其体外光热效能及体内外成像效果。结果 成功制备C₃F₈@PLGA@Au纳米粒子,该粒子的平均直径为268.2±80.5 nm,分散性好,无明显细胞毒性;在808 nm激光辐照下,粒子有很好的溶液光热效果;体内外超声成像实验中均有增强显像。结论 成功制备了光热型纳米超声造影剂,其有良好的体外光热性能和体内外超声显像效果,为乳腺癌疾病诊治提供了新思路。     

In vitro and in vivo characterization of several functionalized ultrasmall particles of iron oxide,vectorized against amyloid plaques and potentially able to cross the blood–brain barrier: toward earlier diagnosis of Alzheimer's disease by molecular imaging

Alzheimer's disease (AD) is a neurodegenerative disorder most often diagnosed 10 years after its onset and development. It is characterized by the accumulation of amyloid‐β peptide (ABP) into amyloid plaques between nerve cells, which produces a massive local neurodegeneration. Molecular magnetic resonance imaging allows diagnosis of AD by showing ABP accumulation in the brain. The ultrasmall particles of iron oxide (USPIO) derivatives proposed in the present work were functionalized with peptides that present an affinity for ABP, independently of its state of aggregation. Their nanomolar K_d* confirms the high affinity of our vectorized contrast agents (VCA) for ABP and therefore their high labeling potential, specificity and sensitivity. Their lack of toxicity has been demonstrated, both by in vitro studies using the MTT method on several cell types, and by in vivo investigations with assessment of renal and hepatic biomarkers and by histopathology evaluation. The results of biodistribution studies corroborated by MRI demonstrate that USPIO‐PHO (USPIO coupled to peptide C‐IPLPFYN‐C) are able to cross the blood–brain barrier without any facilitating strategy, and accumulates in the brain 90 min after its injection in NMRI mice. None of the USPIO derivatives were found in any organs one week after administration. To conclude, USPIO‐PHO seems to have a genuine potential for labeling amyloid plaques in the brain; it has a nanomolar binding affinity, no toxic effects, and its elimination half‐life is about 3 h. Further tests will be made on transgenic mice, aimed at confirming the potential of early AD diagnosis using our VCA. Copyright © 2014 John Wiley & Sons, Ltd.     

Preclinical ex vivo expansion of cord blood hematopoietic stem and progenitor cells: duration of culture; the media, serum supplements, and growth factors used; and engraftment in NOD/SCID mice

BACKGROUND: Ex vivo expansion of cord blood (CB) hematopoietic stem and progenitor cells increases cell dose and may reduce the severity and duration of neutropenia and thrombocytopenia after transplantation. This study's purpose was to establish a clinically applicable culture system by investigating the use of cytokines, serum-free media, and autologous plasma for the expansion of CB cells and the engraftment of expanded product in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. STUDY DESIGN AND METHODS: Enriched CB CD34+ cells were cultured in four media (Iscove's modified Dulbecco's medium with FCS, Gibco; X-Vivo-10, BioWhittaker; QBSF-60, Quality Biological; and StemSpan SFEM, Stem Cell Technologies) with four cytokine combinations (thrombopoietin [TPO], SCF, Flt-3 ligand [FL] with and without G-CSF, and/or IL-6). The effect of autologous CB plasma was also investigated. The read-out measures were evaluated on Days 8 and 12. After expansion at the optimized condition, cultured cells were transplanted into sublethally irradiated NOD/SCID mice. The engraftment of human CD45+ cells and subsets in the bone marrow, spleen, and peripheral blood was determined. RESULTS: QBSF-60 or StemSpan SFEM supported high yields of early progenitors (CD34+ cells, 相似文献