Study On Microbubbles With Gold Nanoparticles As Ultrasound And CT Dual-modality Contrast Agents

With the development of medical technology,ultrasound(US),computer tomography X-ray(CT),magnetic resonance imaging(MRI)and other imaging techniques have become the most commonly used medical imaging modalities.These diagnostic techniques have different principles and advantages.Because of its low cost,low damage to human tissues,and intuitive real-time imaging,ultrasound imaging has become one of the most commonly used approaches.However,each modality has different advantages and disadvantages,if they can be used complimentarily,more accurate and complete structural/functional information will be obtained.Due to this requirement,contrast-enhanced agents also evolve from a single modality to a multimodality.Lipid-shelled microbubbles are traditionally used as contrast agents in contrast-enhanced ultrasound imaging.The gold nanoparticles have been used as CT contrast agents in recent years.In this study,it has been attempted to combine gold nanoparticles with traditional lipid-shelled microbubble.The gold nanoparticles assembled on the shell of microbubbles make it possible to achieve a dual ultrasound-CT imaging.In this study,lipid-shelled microbubble contrast agents assembled with different shapes/concentration of gold nanoparticle were prepared,and their dual imaging functions on both ultrasound and CT were explored.The major contents are as follows:1.Firstly,both the gold nano-brick particles and spherical colloidal gold nanoparticles were selected to be assembled on the shell of lipid microbubbles.The results show that the gold nano-sized brick particles and spherical nano-particles could be successfully loaded on the shell of microbubbles.The structure of the nanoparticle-assembled microbubbles was confirmed by size and size distribution,Zeta-potentials,transmission electron microscopy,and scanning electron microscopy.The results showed that both nanostructured and spherical nanoparticles have been assembled on the microbubble membrane shell.The microbubbles with gold nano-sized bricks were less stable than shperical nanoparticle loading.The spherical colloidal gold nanoparticles assembled microbubbles arestable with its mean particle size of 1.1 ?m and the concentration of 109 bubbles per mL.2.Based on the successful fabrication of gold nanoparticle-assembled microbubbles,the in vitro ultrasound imaging has been used to evaluate contrast-enhanced effect by using the Vevo 2100 Small Animal Ultrasound Imaging System.It was found that the microbubbles assembled with gold particles could enhance the ultrasound imaging.For the gold nanobrick microbubbles,the mean contrast enhanement duration time was about 5 minutes.For spherical gold nanoparticle microbubbles,the contrast ultrasound enhancement effect decreased with the increase of nanoparticle contration.The contrast duration time was about 20-30 minutes.And the ultrasound contrast decreased to half of the initial value at 5-15 minutes.Furthermore,an in vitro CT reconstruction experiment was performed by using a Hiscan-M1000 In Vivo Micro-CT small animal imaging CT system.The results showed that the spherical gold nanoparticles assembled microbubbles had a CT value around-30,which was closed of water(-39).And clinically used iopromide(diluted 10 times to 37 mg/mL)has a CT value of 1882.The nanoparticle concentration need to be increased if the better CT enhancement effect could be obtained.3.Finally,the contrast-enhanced ultrasound is the commonly used imaging modality for the liver diagnosis in clinic because the microbubble enhanced imaging characterisitics is beneficial for the improvement of the diagnostic accuracy.Therefore,in this thesis,Based on the spherical gold nanoparticle-assembled microbubbles,the in vivo liver contrast-enhanced imaging experiments were performed by using the GE VIVID E9 Color Doppler System.At the same injection dose(0.8 mL),the contrast-enhanced ultrasound of the liver portal vein was good.Loading different concentration of the nanoparticles in microbubbles would result in different contrast enhancement for the liver portal vein.The result of the enhancement is as follows:9.01 mg/L colloidal gold particles(-33.9 dB)>controlled microbubbles(-36.7 dB)>the microbubbles with 2.23 mg/L colloidal gold particles(-41.9 dB).The duration contrast time was 1-2 minutes.