[show abstract][hide abstract] ABSTRACT: Objectives: Embolization therapy is gaining importance in the treatment of malignant 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 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/CT. Characterization and testing of the substance in animal models was performed.
Materials and Methods: In order 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. Herefore X- ray visible Iodine was combined with MRI visible Iron (Fe3+O4) 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 (USPIO, 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, Philipps), 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 three radiologists from 1 to 3. Histological analysis of organs was performed. Results: 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 three 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. Histological 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.
Conclusions: 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.