Objective: To develop CT/MRI dual modality imaging microspheres for embolization.Embolization has emerged as a highly effective interventional radiographic technique in a wide variety of diseases in current medical therapy.It is used for treatment of inoperable tumors, arterio-venous malformations (AVMs) and haemoptysis (excessive bleeding), etc.Embolic agents, such as microparticles, microspheres or beads have successfully employed in the embolization therapy for several decades.However, the commercial particles for embolization in current use are not visible under X-ray or magnetic resonance imaging (MRI), which means angiograms are needed to determine the position of embolic materials.In the process of angiography much X-ray contrast agents are used, which is costly and harmful to patients with impaired renal function.In order to solve the problem, "visible" embolic materials have been attracted attention, which mean directly detectable by computed tomography (CT) or MRI.Visible embolic agents provide obvious advantages over non-visible embolic agents, such as direct detection and immediate correction of non-targeted embolization in the interventional procedure, instant imaging of the successfully embolized tumor areas, assessing possible migration of the embolic agent over time and providing guidance in the follow-up treatment.Methods: To develop a CT/MRI dual modality imaging embolic agent, lipiodol and superparamagnetic iron oxide (SPIO) were loaded simultaneously in polyvinyl alcohol (PVA) microspheres by multiple emulsion chemical crosslinking method in this work.The dual modality imaging microspheres (DMIMs) were evaluated and characterized, including the morphology, the content of lipiodol and SPIO, and in vitro CT/MRI imaging, etc.The biocompatibility and CT/MRI imaging of DMIMs were investigated in mice immediately after subcutaneous injection and at 7, 14, 21 and 28 d.Then DMIMs of 100-300μm in diameter was embolized in a rabbit kidney and CT/MRI detection was followed at 4, 11, 20, 30, 37, 42, 45, and 90 d.After that, the rabbit was killed and both kidneys were removed for macroscopic and histopathology analysis.Results: Morphology of DMIMs observed by optical microscope and environmental scanning electron microscope (ESEM) revealed that DMIMs were spherical and well dispersed.The average content of lipiodol and SPIO in DMIMs were 261.1 ±-12.5 mg/ml and 2.57 ± 0.24 mg/ml, respectively.DMIMs provided a sufficient image compared to either the surrounding agar or the contrast of PVA microspheres on both CT and MRI in vitro scans.The CT/MRI images of mouse proved that DMIMs were CT/MRI dual visible and the visibility did not decrease at the end of experiment (28 d).And the DMIMs caused just a moderate inflammatory reaction according to the result of histopathological sections.Embolization was performed successfully in a rabbits left kidney, which was proved by the digital subtraction angiography (DSA) (Figure 1).Figure 1 showed the peripheral blood vessels of the kidney were occluded by DMIMs.Figure 2 gave the in vivo CT/MRI images of the kidney post embolization.DMIMs in peripheral blood vessels could be detected clearly under both CT and MRI, and the position of DMIMs monitored by CT and MRI were consistent with each other.The signals of DMIMs did not decrease on both CT and MRI till 45 d post embolization.Partial recanalization was found in the embolized kidney by CT/MRI at the 90th day after embolization and verified by follow-up angiography (figure was not shown here).Macroscopic examination showed the embolized kidney (left kidney) shrank to about 1/3 of the original size and compensatory renal hypertrophy was observed on the other kidney (right kidney).Hematoxylin and eosin stain of the embolized kidney showed the number of glomerular number was significantly reduced within partial area of renal cortex, tubular atrophy and renal interstitial collagen fibers hyperplasia, and the renal capsules were thickened.All these results proved a successful and visible embolization of DMIMs.Conclusion: DMIMs were CT/MRI visible embolic material with potential application for embolotherapy.