Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Heidelberg University, Mannheim, Germany.
Invest Radiol. 2011 Mar;46(3):178-86. doi: 10.1097/RLI.0b013e318205af53.
Embolization therapy is gaining importance in the treatment of malignant lesions, and even more in benign lesions. Current embolization materials are not visible in imaging modalities. However, it is assumed that directly visible embolization material may provide several advantages over current embolization agents, ranging from particle shunt and reflux prevention to improved therapy control and follow-up assessment. X-ray- as well as magnetic resonance imaging (MRI)-visible embolization materials have been demonstrated in experiments. In this study, we present an embolization material with the property of being visible in more than one imaging modality, namely MRI and x-ray/computed tomography (CT). Characterization and testing of the substance in animal models was performed.
To reduce the chance of adverse reactions and to facilitate clinical approval, materials have been applied that are similar to those that are approved and being used on a routine basis in diagnostic imaging. Therefore, x-ray-visible Iodine was combined with MRI-visible Iron (Fe3O4) in a macroparticle (diameter, 40-200 μm). Its core, consisting of a copolymerized monomer MAOETIB (2-methacryloyloxyethyl [2,3,5-triiodobenzoate]), was coated with ultra-small paramagnetic iron oxide nanoparticles (150 nm). After in vitro testing, including signal to noise measurements in CT and MRI (n = 5), its ability to embolize tissue was tested in an established tumor embolization model in rabbits (n = 6). Digital subtraction angiography (DSA) (Integris, Philips), CT (Definition, Siemens Healthcare Section, Forchheim, Germany), and MRI (3 Tesla Magnetom Tim Trio MRI, Siemens Healthcare Section, Forchheim, Germany) were performed before, during, and after embolization. Imaging signal changes that could be attributed to embolization particles were assessed by visual inspection and rated on an ordinal scale by 3 radiologists, from 1 to 3. Histologic analysis of organs was performed.
Particles provided a sufficient image contrast on DSA, CT (signal to noise [SNR], 13 ± 2.5), and MRI (SNR, 35 ± 1) in in vitro scans. Successful embolization of renal tissue was confirmed by catheter angiography, revealing at least partial perfusion stop in all kidneys. Signal changes that were attributed to particles residing within the kidney were found in all cases in all the 3 imaging modalities. Localization distribution of particles corresponded well in all imaging modalities. Dynamic imaging during embolization provided real-time monitoring of the inflow of embolization particles within DSA, CT, and MRI. Histologic visualization of the residing particles as well as associated thrombosis in renal arteries could be performed. Visual assessment of the likelihood of embolization particle presence received full rating scores (153/153) after embolization.
Multimodal-visible embolization particles have been developed, characterized, and tested in vivo in an animal model. Their implementation in clinical radiology may provide optimization of embolization procedures with regard to prevention of particle misplacement and direct intraprocedural visualization, at the same time improving follow-up examinations by utilizing the complementary characteristics of CT and MRI. Radiation dose savings can also be considered. All these advantages could contribute to future refinements and improvements in embolization therapy. Additionally, new approaches in embolization research may open up.
栓塞治疗在恶性病变的治疗中变得越来越重要,在良性病变中更是如此。目前的栓塞材料在影像学检查中不可见。然而,人们认为直接可见的栓塞材料可能具有优于当前栓塞剂的多种优势,范围从颗粒分流和反流预防到改善治疗控制和随访评估。已经在实验中证明了 X 射线和磁共振成像(MRI)可见的栓塞材料。在这项研究中,我们提出了一种具有在多种成像模式下可见的特性的栓塞材料,即 MRI 和 X 射线/计算机断层扫描(CT)。在动物模型中对该物质进行了特性和测试。
为了降低不良反应的机会并促进临床批准,应用了类似于在诊断成像中批准和常规使用的材料。因此,X 射线可见的碘与 MRI 可见的铁(Fe3O4)结合在大颗粒(直径 40-200μm)中。其核心由共聚单体 MAOETIB(2-甲基丙烯酰氧基乙基[2,3,5-三碘苯甲酸酯])组成,并用超小顺磁氧化铁纳米颗粒(150nm)涂覆。在进行体外测试,包括 CT 和 MRI 中的信噪比测量(n=5)后,在兔建立的肿瘤栓塞模型中测试了其栓塞组织的能力(n=6)。在栓塞前、栓塞期间和栓塞后进行数字减影血管造影(DSA)(Integris,Philips)、CT(Definition,Siemens Healthcare Section,Forchheim,德国)和 MRI(3 Tesla Magnetom Tim Trio MRI,Siemens Healthcare Section,Forchheim,德国)。通过视觉检查评估栓塞颗粒引起的成像信号变化,并由 3 位放射科医生对其进行等级评定,从 1 到 3。对器官进行组织学分析。
在体外扫描中,颗粒在 DSA、CT(信噪比[SNR],13±2.5)和 MRI(SNR,35±1)上提供了足够的图像对比度。通过导管血管造影术证实了肾组织的成功栓塞,所有肾脏均至少部分灌注停止。在所有三种成像方式中,均发现与驻留在肾脏内的颗粒有关的信号变化。颗粒在所有成像方式中的定位分布都很好地对应。栓塞过程中的动态成像在 DSA、CT 和 MRI 中提供了栓塞颗粒流入的实时监测。可以对驻留在肾动脉中的颗粒进行组织学可视化以及相关的血栓形成。栓塞后,栓塞颗粒存在的可能性的视觉评估获得了完整的评分(153/153)。
已经开发、表征并在动物模型中体内测试了多模态可见的栓塞颗粒。它们在临床放射学中的应用可能会优化栓塞程序,预防颗粒错位,并直接在程序内可视化,同时利用 CT 和 MRI 的互补特性改进随访检查。还可以考虑节省辐射剂量。所有这些优势都可能有助于未来改进栓塞治疗。此外,栓塞研究的新方法可能会出现。