Multipurpose contrast agent applied to ultrasonography/magnetic resonance imaging (US/MRI) guidance synergistic high-intensity focused ultrasound ablation and preparation method for multipurpose contrast agent

A focused ultrasound and contrast agent technology, applied in the field of ultrasound medicine, can solve the problems of reducing the efficiency of HIFU treatment, weakening the energy deposition in the target area, and inaccurate small lesions, etc., to achieve enhanced energy deposition in the target area, strong surface modification, and shortened The effect of relaxation time

Inactive Publication Date: 2012-12-19
CHONGQING MEDICAL UNIVERSITY
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] At present, there are two problems in HIFU treatment: ① Imaging (US or MRI) monitoring devices cannot accurately and clearly locate small lesions and present their edges; ② Ultrasonic waves have attenuation characteristics during the propagation of biological tissues, and ultrasonic energy attenuates with distance Significantly, and tissue blood flow will also take away part of the energy, weaken the energy deposition in the target area, and greatly reduce the efficiency of HIFU treatment

Method used

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  • Multipurpose contrast agent applied to ultrasonography/magnetic resonance imaging (US/MRI) guidance synergistic high-intensity focused ultrasound ablation and preparation method for multipurpose contrast agent
  • Multipurpose contrast agent applied to ultrasonography/magnetic resonance imaging (US/MRI) guidance synergistic high-intensity focused ultrasound ablation and preparation method for multipurpose contrast agent
  • Multipurpose contrast agent applied to ultrasonography/magnetic resonance imaging (US/MRI) guidance synergistic high-intensity focused ultrasound ablation and preparation method for multipurpose contrast agent

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Example 1 Fe of the present invention 3 o 4 Preparation method of / PLGA multi-performance contrast agent

[0029] Materials: lactic acid / glycolic acid copolymer (PLGA, 50:50, Jinan Daigang), superparamagnetic iron oxide nanoparticles (Fe 3 o 4 , 10-20 nm, 10 mg / ml, Ocean), polyvinyl alcohol (PVA, Sigma), chloroform, double distilled water.

[0030] Instruments: electronic balance, ultrasonic oscillator (SONICS, USA), high-speed dispersion homogenizer (FJ300-SH, Shanghai), high-speed centrifuge, electron microscope (Hitachi), laser caliper (Zeta SIZER 3000HS; Malvern, USA), Comprehensive physical property measurement system (PPMS Model 6000).

[0031] Using the double emulsification method: (1) Add 0.8 g PLGA into 17 ml chloroform, stir well until it is completely dissolved, then slowly add 1.8 ml Fe 3 o 4 and 1.6 ml double distilled water;

[0032] Or (2) Add 1.2 g PLGA into 28 ml chloroform, stir well until completely dissolved, then slowly add 2.3 ml Fe 3 o 4...

Embodiment 2

[0038] Example 2 Fe of the present invention 3 o 4 / PLGA multi-performance contrast agent US, MRI dual-modal imaging method

[0039] (1) In vitro US imaging The Fe prepared in Example 1 3 o 4 / PLGA multi-performance contrast agent and PBS were diluted in a certain proportion to contain PLGA at 100, 50, 25, 12.5, and 5 mg / ml, which were respectively placed in hole models made of gel (1%). As a control, a Philips iU22 ultrasonic diagnostic instrument was used in fundamental wave imaging mode to collect ultrasonic images in each well. The results showed that, compared with PBS, Fe 3 o 4 / PLGA multi-performance contrast agent showed hyperecho, and the echo intensity decreased with the decrease of PLGA concentration ( image 3 ).

[0040] (2) In vitro MR imaging The Fe prepared in Example 1 3 o 4 / PLGA multi-performance contrast agent and gel are diluted in a certain proportion so that the iron content is 0, 2.5, 5, 10, 25, 50 μg / ml, put them into 2.0 ml sealed EP tubes re...

Embodiment 3

[0043] Example 3 Fe of the present invention 3 o 4 / PLGA multi-performance contrast agent synergistic HIFU experiment

[0044] ⑴ In vitro synergistic HIFU experiment

[0045] The experiment used JC200 focused ultrasound tumor therapy system (produced by Chongqing Haifu Technology Co., Ltd.). Fresh isolated bovine liver (10 cm × 7 cm × 5 cm) was rewarmed and degassed for 25 min, placed in a methyl methacrylate container, covered with degassed water to the surface of the liver capsule, and 200 μl Fe 3 o 4 The diluent of / PLGA multi-performance contrast agent is directly injected in the degassed bovine liver, wherein the dilution method is the Fe prepared in Example 1 3 o 4 / PLGA multi-performance contrast agent is diluted proportionally with normal saline to form Fe 3 o 4 The concentration is 0.5mg / ml. The injection site was monitored in real time by HIFU diagnostic ultrasound. Immediately after the injection, HIFU was ablated once with an acoustic power of 150 W and an ...

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Abstract

The invention relates to a multipurpose contrast agent applied to ultrasonography/magnetic resonance imaging (US/MRI) guidance synergistic high-intensity focused ultrasound ablation and a preparation method for the multipurpose contrast agent and belongs to the field of ultrasonic medicine. The multipurpose contrast agent is a polymer microsphere with a core-shell structure. A shell membrane consists of lactic acid/poly lactic-co-glycolic acid (PLGA) and magnetic ferroferric oxide (Fe3O4) nano-particles in weight ratio of (30-70):1 in material, wherein the magnetic Fe3O4 nano-particles are inlaid onto the shell membrane. Double distilled water is coated on the core of the contrast agent. By taking the inorganic superparamagnetic ferroferric oxide nano-particles and the organic high polymer material lactic acid/PLGA as membrane-forming materials and by combining the respective advantages of the two materials, US in-vivo displaying and MRI in-vivo displaying can be performed on tumorigenesis and tumor progression by the multipurpose contrast agent. US/MRI monitoring synergistic high-intensity focused ultrasound ablation treatment can also be performed, and thereby, a solid foundation is laid for early discovery, early diagnosis and early treatment on tumors.

Description

technical field [0001] The invention belongs to the field of ultrasound medicine, and in particular relates to a Fe-loaded material that can enhance US and MRI dual-mode imaging and can be used for synergistic high-intensity focused ultrasound ablation 3 o 4 Multifunctional contrast agent and its preparation method. Background technique [0002] With the rapid development of molecular imaging technology, contrast agents with a single function and imaging mode can no longer meet the growing needs of medical diversification and humanization. The multi-functional contrast agent integrates the advantages of US, CT, MRI, optical and other imaging technologies. It can display the occurrence and development of lesions in multiple modes in vivo, and can carry out targeted therapy under various image monitoring. Lay a solid foundation for diagnosis and treatment. [0003] High-intensity focused ultrasound (HIFU) is a new technology for non-invasive local ablation of tumors that ha...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/22
Inventor 郑元义孙阳王志刚冉海涛李攀牛诚诚宫玉萍赵雅静
Owner CHONGQING MEDICAL UNIVERSITY
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