Preparation And Performance Studies Of Chitosan Ultrasound-magnetic Resonance Dual Mode Contrast Agents

In the process of diagnosis of various diseases,medical imaging technology is playing an increasingly important role.The combined application of ultrasound and magnetic resonance imaging technology can take the advantages of both technologies and achieve better diagnostic results.In this paper,on the basis of chitosan blank microspheres prepared by emulsification method,chitosan ultrasound-magnetic resonance dual mode contrast agents were further desinged and prepared.The structure,content,stability,cytotoxicity and blood compatibility,enhanced ability of ultrasound and magnetic resonance imaging of the dual-mode contrast agents were investigated.The main research contents are as follows:Firstly,the chitosan/liquid paraffin biphasic stratification system was desinged,and Span80 was used as surfactant to construct water/oil system,micrometer scale chitosan blank microspheres were successfully prepared.The effects of chitosan concentration,stirring speed and chitosan/liquid paraffin ratio on the size of chitosan blank microspheres were investigated by single factor experiments respectively.The results showed that with the increase of chitosan concentration,the average particle size of chitosan blank microspheres increased.With the increase of stirring speed,the average particle size of chitosan blank microspheres decreased.With the decrease of chitosan/liquid paraffin ratio,the average particle size of chitosan blank microspheres decreased.Subsequently,on the basis of chitosan blank microspheres,ultrasound-magnetic resonance dual mode contrast agents were prepared by adding perfluoropentane and Fe₃O₄.Using infrared spectrum and X-ray diffraction to confirm the exist of perfluoropentane and Fe₃O₄.The effects of Fe₃O₄/perfluoropentane ratio on the composition and particle size of the dual mode contrast agents were analyzed.The results showed that the content of Fe₃O₄ in the contrast agents increased with the increase of Fe₃O₄/perfluoropentane ratio,but the content of perfluoropentane was almost the same.With the increase of Fe₃O₄/perfluoropentane ratio on the dual mode contrast agents,the average particle size decreased and then increased.Then,stability,cytotoxicity and blood compatibility of ultrasound-magnetic resonance dual mode contrast agents were investigated.The results showed that chitosan dual mode contrast agents'stability increased with the increase of Fe₃O₄/perfluoropentane ratio.Cytotoxicity and blood compatibility of dual-mode contrast agents were studied.The results showed dual mode contrast agents had less cytotoxicity after 24 and 48 hours.Dual mode contrast agents had few effects on the blood coagulation time,erythrocyte sedimentation rate,blood components and hemolysis rate,dual mode contrast agents has good blood compatibility.Finally,the enhanced ability of imaging of ultrasound-magnetic resonance dual mode contrast agents was investigated.The effects of concentration and temperature on the enhanced ability of ultrasound imaging were investigated.The results showed that the enhanced ability of ultrasound imaging of dual mode contrast agents increased with the increase of concentration.After treatment at different water bath,the enhanced ability of ultrasound imaging of dual mode contrast agents decreased.The effects of concentration and temperature on the enhanced ability of magnetic resonance imaging were investigated.The results showed that the enhanced ability of magnetic resonance imaging increased with the increase of the concentration of dual mode contrast agents.Temperature had no effects on the enhanced ability of magnetic resonance imaging.In the combined ultrasound and magnetic resonance imaging,changing the imaging sequence,chitosan ultrasound-magnetic resonnance dual mode contrast agents still had the enhanced ability of ultrasound and magnetic resonance imaging.In conclusion,this paper had successfully prepared micron sized chitosan ultrasound-magnetic resonance dual mode contrast agents by emulsification method.The chitosan ultrasound-magnetic resonance dual mode contrast agents can be applied to ultrasound imaging and magnetic resonance imaging,and lays a certain foundation for the application of dual-mode contrast agents in clinical diagnosis and treatment.