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  • 1
    Keywords: IN-VITRO ; AGENTS ; IN-VIVO ; PERFUSION ; THERAPY ; CT ; HEPATOCELLULAR-CARCINOMA ; liver ; TISSUE ; MRI ; CATHETER ; embolization ; X-RAY ; ARTERIOVENOUS-MALFORMATIONS ; MICROSPHERES ; ARTERY EMBOLIZATION ; ENDOVASCULAR EMBOLIZATION ; multimodal ; THERAPEUTIC EMBOLIZATION ; UTERINE FIBROID EMBOLIZATION
    Abstract: Objectives: 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. Materials and Methods: 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 mu m). 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. 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 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. 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
    Type of Publication: Journal article published
    PubMed ID: 21263332
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  • 2
    Keywords: CANCER ; CELLS ; AGENTS ; CT ; PARTICLES ; CONJUGATION ; BIOMEDICAL APPLICATIONS ; MICROSPHERES ; PARTICULATE EMBOLI ; RADIOPAQUE POLYMERIC BIOMATERIALS
    Abstract: Bismuth oxide nanoparticles of 12.1 +/- 3.0 nm diameter were prepared by thermal decomposition of bismuth acetate dissolved in ethylene glycol in the presence of an oxidizing agent. Functionalization and stabilization of the hydrophobic Bi(2) O(3) nanoparticles was accomplished by coating these core nanoparticles with human serum albumin (HSA), via a precipitation process. The formed Bi(2) O(3) /HSA core-shell nanoparticles were of 15.2 +/- 3.5 nm diameter. Elemental analysis measurements indicated that the bismuth weight % of the Bi(2) O(3) /HSA core-shell nanoparticles is 72.9. The crystalline structure of these nanoparticles was examined by XRD. The radiopacity of these nanoparticles was demonstrated in vitro and in vivo by a CT scanner. In ovo and in vivo trials proved the safety of these Bi(2) O(3) /HSA core-shell nanoparticles. In the future, we plan to extend this study particularly for molecular imaging applications. (c) 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 101B: 131-138, 2013.
    Type of Publication: Journal article published
    PubMed ID: 23090940
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