CN102824648A - 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 - Google Patents

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 Download PDF

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CN102824648A
CN102824648A CN2012103467295A CN201210346729A CN102824648A CN 102824648 A CN102824648 A CN 102824648A CN 2012103467295 A CN2012103467295 A CN 2012103467295A CN 201210346729 A CN201210346729 A CN 201210346729A CN 102824648 A CN102824648 A CN 102824648A
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contrast agent
many performances
mri
plga
multipurpose
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郑元义
孙阳
王志刚
冉海涛
李攀
牛诚诚
宫玉萍
赵雅静
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Chongqing Medical University
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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

Many performances contrast agent that the potentiation high intensity focused ultrasound melts under a kind of US/MRI of being applied to guiding and preparation method thereof
Technical field
The invention belongs to the ultrasound medicine field, be specifically related to a kind of US of enhancing, the video picture of MRI bimodal, and can be used for year Fe that the potentiation high intensity focused ultrasound melts 3O 4Many performances contrast agent and preparation method thereof.
Background technology
Along with the fast development of molecule imaging technique, the contrast agent of simple function and imaging pattern can not satisfy growing medical science variation and hommization demand.Imaging technique advantages such as the comprehensive US of many performances contrast agent, CT, MRI, optics; Can take place, develop pathological changes and carry out various modes and show at body; Can under multiple imaging monitoring, carry out targeted therapy again, for early discovery, the Clinics and Practices of disease are taken a firm foundation.
High intensity focused ultrasound (High-intensity focused ultrasound; HIFU) be the new technique of fast-developing in recent years Noninvasive local ablation tumor, the HIFU therapy system is made up of image (US or MRI) supervising device and focused ultrasonic treating head.In image (US or MRI) the supervising device guiding HIFU therapeutic process pathological changes is accurately located, and can be in treating back Real-Time Evaluation ablation effect; HIFU treatment head adopts the high-energy focusing device; The external supersonic energy focusing is organized in in-vivo tumour; Produce the moment high-temperature effect more than 60 ℃ through the along high strength supersonic, cause protein denaturation, make tumor tissues generation irreversible coagulation property downright bad; And progressively be absorbed or scarring, thereby reach the therapeutic effect that can match in excellence or beauty and perform the operation.
At present, have two problems in the HIFU treatment: 1. image (US or MRI) supervising device can not accurate, clear location to small lesion and is presented its edge; 2. ultrasound wave has attenuation characteristic in biological tissue's communication process, and ultrasonic energy increases decay significantly with distance, and tissue blood flows and also can take away portion of energy, weakens the target area energy deposition, greatly reduces the HIFU therapeutic efficiency.
Summary of the invention
The present invention is directed to the problem that exists in the HIFU treatment, select inorganic SPIO (Fe 3O 4) nano-particle; And high-molecular organic material lactic acid/co-glycolic acid [poly (lactic-co-glycolic acid) of good biocompatibility; PLGA] be filmogen; And give full play to the advantage separately of above-mentioned two kinds of materials, a kind of US/MRI of being applied to guiding many performances contrast agent of melting of potentiation high intensity focused ultrasound, i.e. Fe down are provided 3O 4Many performances of/PLGA contrast agent, and in external, body, tentatively probed into its development and potentiation HIFU effect in the experiment.
The present invention also provides preparation said Fe 3O 4The method for preparing of many performances of/PLGA contrast agent.
For realizing above-mentioned purpose, technical scheme provided by the present invention is such:
The present invention is applied to the Fe that the potentiation high intensity focused ultrasound melts under the US/MRI guiding 3O 4Many performances of/PLGA contrast agent, for having the polymer microsphere of core-shell structure, the shell membrane material is by PLGA and magnetic Fe 3O 4Nano-particle is by weight being 30-70:1 composition, wherein magnetic Fe 3O 4Nano-particle is embedded on the shell membrane, contrast agent core parcel distilled water; Said magnetic Fe 3O 4The particle diameter of nano-particle is 10-20 nm; The particle diameter of said many performances contrast agent is 750-1050 nm.
Above-mentioned Fe 3O 4The method for preparing of many performances of/PLGA contrast agent adopts two emulsion processes, at first PLGA is dissolved in the organic solvent chloroform, treat that PLGA dissolves fully after, slow dropping magnetic Fe in supersonic oscillations and before adding polyvinyl alcohol (PVA) solution 3O 4Nano-particle, this kind method for preparing makes PLGA and Fe 3O 4Common formation Fe 3O 4The housing parts of many performances of/PLGA contrast agent is beneficial to Fe 3O 4Many performances of/PLGA contrast agent plays a role in bimodal video picture and potentiation HIFU treatment.
More particularly, above-mentioned Fe 3O 4The method for preparing of many performances of/PLGA contrast agent may further comprise the steps: 0.8-1.2 g PLGA is added in the 17-28 ml chloroform, be stirred well to after the dissolving fully slowly to wherein dripping 1.8-2.3 ml Fe 3O 4With 1.6-3 ml distilled water, adopt the vibration of sonic oscillation appearance subsequently, get brown W/O emulsion, hunting power is 130 W in the said sonic oscillation process, duration of oscillation is 30-45 s; PVA is dissolved in to be mixed with the PVA percentage by weight in the distilled water be 5% poly-vinyl alcohol solution; Above-mentioned brown emulsion and poly-vinyl alcohol solution are mixed for 1:5 by volume; Adopt high speed dispersion homogenizer homogenizing 5-6 min to prepare the W/O/W microsphere, under room temperature, stir 1.5-2 h again, chloroform is fully volatilized; After 3-5 distilled water washing, centrifugal after; Collecting precipitation is many performances contrast agent of the present invention, and said homogenizer rotating speed is 9000-10000 rpm.Adopt light microscopic, Electronic Speculum, laser particle size analyzer, PPMS etc. that sample is carried out the observation of characteristics such as form, particle diameter, magnetic respectively then.
Preferably, lactic acid monomer and the monomeric mol ratio of hydroxyacetic acid are 50:50 among the above-mentioned PLGA.
High, the good biocompatibility of high-molecular organic material PLGA stability according to the invention, and have degradable in vivo property and good acoustic characteristic, can prolong blood circulation time, often be used to the preparation of imaging agent for ultrasonic diagnosis; Said superparamagnetism Fe 3O 4Nano-particle is that a kind of particle diameter is little, toxicity is low, highly sensitive, targeting property is good, surface modificability is strong inorganic magnetic nano meter biomaterial, Fe 3O 4Shown special advantages at biomedical sector, because Fe 3O 4Nano-particle is adding under the action of a magnetic field and can induced the stronger local magnetic field of generation, and then influences the relaxation process of hydrogen proton in the granule ambient water molecule consumingly, shortens the T2 relaxation time effectively, makes resulting T2WI deepening, so Fe 3O 4Show the negative imaging results that strengthens as the MRI contrast medium.With PLGA and Fe 3O 4Combine, be expected to synthetic a kind of multi-modal contrast agent that can be used for US and MRI video picture simultaneously.In addition, Fe 3O 4Belong to the acoustic impedance material, in the HIFU treatment, Fe 3O 4Arrive behind the target tissue and organize acoustic impedance difference remarkable, interior the not matching property of acoustic impedance height of intensifier target tissue can improve ultrasonic energy and assemble in the target area, excites target area high temperature; Simultaneously, ferrite is a kind of ultrasonic absorption material, and when HIFU irradiation target area, absorbing material absorbs ultrasound wave in a large number, and the absorption of sound wave is converted into heat energy with acoustic energy, strengthens the target area energy deposition, potentiation HIFU.
Also that is to say Fe according to the invention 3O 4Many performances of/PLGA contrast agent has the iconography characteristic that strengthens rabbit VX2 hepatocarcinoma MRI T2WI in external enhancing US, MRI video picture and the body.
Wherein, Fe of the present invention 3O 4The observational technique of many performances of/PLGA contrast agent US/MRI video picture characteristics comprises: with above-mentioned Fe 3O 4Many performances of/PLGA contrast agent places external imaging model, and using ultrasound diagnostic apparatus and magnetic resonance scanner are to variable concentrations Fe 3O 4Many performances of/PLGA contrast agent carries out US and MRI imaging respectively; Further the rabbit ear edge vein through the VX2 liver cancer model injects Fe 3O 4Many performances of/PLGA contrast agent, it is machine-processed to observe also preliminary its video picture of discussion of MRI imaging effect through the variations such as signal intensity that contrast injection front and back liver parenchyma and tumor.
Further, Fe according to the invention 3O 4That many performances of/PLGA contrast agent has is external, strengthen the biological property that HIFU melts effect in the body.
Wherein, Fe of the present invention 3O 4The observational technique of many performances of/PLGA contrast agent potentiation HIFU ablation effect comprises: respectively at carrying out above-mentioned Fe in external fresh in vitro Hepar Bovis seu Bubali and the rabbit VX2 mammary gland corpus carcinosus 3O 4Many performances of/PLGA contrast agent potentiation HIFU experiment, local injection Fe 3O 4Behind many performances of/PLGA contrast agent, give certain parameter HIFU irradiation, change through methods such as naked eyes, light microscopic, Electronic Speculum, immunohistochemistry observation irradiated site coagulation necrosis volume and organizational structure and estimate ablation effect.
The above-mentioned Fe of the present invention 3O 4Many performances of/PLGA contrast agent potentiation HIFU melts the treatment parameter of selecting in the experiment and is: radiation mode is fixed point irradiation, a treatment frequency 0.94 MHz, focal length 145 mm, and irradiation acoustical power 150 W, exposure time is respectively 5 s in external 2 s, the body.
Fe according to the invention 3O 4Many performances of/PLGA contrast agent embodies huge using value in the HIFU treatment:
(1) accurately locatees: Fe 3O 4Many performances of/PLGA contrast agent has the characteristic that strengthens US and MRI video picture, before the HIFU treatment, and Fe 3O 4Many performances of/PLGA contrast agent accumulates in target tissue through blood circulation; Through US and the MRI image of strengthening; But clear view supplies situation to tumor number, position, size, edge, blood; The guided focused ultrasound therapy focus accurately is positioned tumor tissues, thereby guarantees not damage normal surrounding tissue in the ablation procedure;
(2) potentiation research: Fe 3O 4Many performances of/PLGA contrast agent can improve energy and assemble in the target area through changing the local organization acoustic environment, excites target area high temperature, improves the HIFU therapeutic efficiency, is expected to become new HIFU synergist.
Description of drawings
Fig. 1 Fe 3O 4Many performances of/PLGA contrast agent sem photograph;
Fig. 2 Fe 3O 4Many performances of/PLGA contrast agent hysteresis curve figure;
Fig. 3 variable concentrations Fe 3O 4The external US of many performances of/PLGA contrast agent, the MRI figure that develops;
Fig. 4 Fe 3O 4Many performances of/PLGA contrast agent rabbit VX2 hepatocarcinoma MRI develops and schemes (arrow indication tumor);
Fig. 5 is external, Intrabody HIFU melts the downright bad volume comparison diagram of after coagulation property (simple HIFU melts and is matched group, and arrow is depicted as the coagulation necrosis district);
Fig. 6 HIFU unites Fe 3O 4After many performances of/PLGA contrast agent melts, histopathology (HE), SABC (PCNA) and transmission electron microscope (TEM) figure.
The specific embodiment
Below in conjunction with the specific embodiment the present invention is done further explain, but content of the present invention is not limited to the embodiment that lifted.
Embodiment 1 Fe of the present invention 3O 4The method for preparing of many performances of/PLGA contrast agent
Material: lactic acid/co-glycolic acid (PLGA, 50:50, Mount Tai, a Jinan handle of the Big Dipper), SPIO nano-particle (Fe 3O 4, 10-20 nm, 10 mg/ml, Ocean), polyvinyl alcohol (PVA, Sigma), chloroform, distilled water.
Instrument: electronic balance, sonic oscillation appearance (SONICS, USA), high speed dispersion homogenizer (FJ300-SH, Shanghai), high speed centrifuge, Electronic Speculum (Hitachi), laser diameter measuring instrument (Zeta SIZER 3000HS; Malvern, USA), comprehensive rerum natura measuring system (PPMS Model 6000).
Adopt two emulsion processes: (1) adds 0.8 g PLGA in the 17 ml chloroform, is stirred well to after the dissolving fully slowly to wherein dripping 1.8 ml Fe 3O 4With 1.6 ml distilled waters;
Or (2) add 1.2 g PLGA in the 28 ml chloroform, is stirred well to after the dissolving fully slowly to wherein dripping 2.3 ml Fe 3O 4With 3 ml distilled waters;
Or (3) add 0.8 g PLGA in the 21 ml chloroform, is stirred well to after the dissolving fully slowly to wherein dripping 2.3 ml Fe 3O 4With 2.5 ml distilled waters;
Or (4) add 1.2 g PLGA in the 25 ml chloroform, is stirred well to after the dissolving fully slowly to wherein dripping 1.8 ml Fe 3O 4With 1.9 ml distilled waters;
Or (5) add 1 g PLGA in the 20 ml chloroform, is stirred well to after the dissolving fully slowly to wherein dripping 2 ml Fe 3O 4With the 2ml distilled water;
To be adopted the vibration of sonic oscillation appearance by arbitrary mixed solution that above-mentioned (1) to (5) obtain subsequently, and get brown W/O emulsion, hunting power is 130 W in the said sonic oscillation process, and duration of oscillation is 30-45s; PVA is dissolved in to be mixed with the PVA percentage by weight in the distilled water be 5% poly-vinyl alcohol solution; Above-mentioned brown emulsion and poly-vinyl alcohol solution are the 1:5 mixing by volume, adopt high speed dispersion homogenizer homogenizing 5-6 min to prepare the W/O/W microsphere, under room temperature, stir 1.5-2 h again; Chloroform is fully volatilized; After 3-5 distilled water washing, centrifugal after, collecting precipitation promptly gets Fe 3O 4Many performances of/PLGA contrast agent, said homogenizer rotating speed is 9000-10000 rpm.
Observe visible Fe under the Electronic Speculum by embodiment 1 preparation 3O 4Many performances of/PLGA contrast agent is spherical in shape, the form rule, and size is even, good dispersion degree (Fig. 1), it is (885.6 ± 133.2) nm that the Malvern laser analyzer records its particle diameter; Hysteresis curve shows, Fe under the room temperature 3O 4Many performances of/PLGA contrast agent does not have hysteresis, is superparamagnetism, and saturation magnetization is 1.0 emu/g (Fig. 2).
Embodiment 2 Fe of the present invention 3O 4Many performances of/PLGA contrast agent US, MRI bimodal developing method
⑴ external US imaging is with the Fe of embodiment 1 preparation 3O 4Many performances of/PLGA contrast agent and PBS are diluted to by a certain percentage that to contain PLGA amount be 100,50,25; 12.5 5 mg/ml insert respectively in the hole model of processing with gel (1%); Do contrast with simple PBS; Adopt Philips iU22 diasonograph, the Fundamental Imaging pattern is gathered the ultrasonoscopy in each hole.The result shows, with PBS contrast, Fe 3O 4Many performances of/PLGA contrast agent shows high echo, and echo intensity reduces to be reduction trend (Fig. 3) with PLGA concentration.
⑵ external MR imaging is with the Fe of embodiment 1 preparation 3O 4It is 0,2.5,5,10 that many performances of/PLGA contrast agent and gel are diluted to iron-holder by a certain percentage, and 25,50 μ g/ml put into the EP pipe of 2.0 ml sealing respectively, are fixed on the perforated plastic plate after vibration shakes up, and are dipped in the water container.Using P hilips Achieva 3.0T TX magnetic resonance scanner, scanning sequence are FFE (TR 72 ms, TE 9 ms; Flip 45o, FOV 180 mm, bed thickness 3.0 mm); Obtain T2*WI, measure each hole sample signal intensity (signal intensity, SI).Visible by Fig. 3, Fe 3O 4Many performances of/PLGA contrast agent is the negative video picture that strengthens at T2*WI, promptly increases with Fe content, and the MRI signal intensity significantly reduces.
⑶ rabbit VX2 hepatocarcinoma MR imaging
The VX2 tumor inoculation carries out the MRI imaging behind rabbit liver 21d.Experimental rabbit gave the anesthesia of 3% pentobarbital sodium before MRI developed, and dorsal position is fixed on the MRI gantry.Abdominal part MRI is flat in advance sweeps, and injects Fe through rabbit ear edge vein then 3O 4Diluent 1 ml/kg of many performances of/PLGA contrast agent, wherein dilution process is the Fe with embodiment 1 preparation 3O 4Many performances of/PLGA contrast agent and normal saline are diluted to Fe in proportion 3O 4Concentration is 3.1mg/ml, carries out the MRI enhanced ct scans respectively at injection back 30 s, 5 min, gathers T2WI.The MRI sweep parameter is: TSE sequence, TR 2500 ms, TE 80 ms, Flip 90o, FOV 160 mm, bed thickness 4.0 mm.The result shows, injection Fe 3O 430 s behind many performances of/PLGA contrast agent, though liver tumor SI does not see significant change, liver parenchyma SI significantly reduces around the tumor, has improved signal intensity contrast between tumor tissues and the normal liver tissue, improves the tumor recall rate; The 5min in injection back, liver parenchyma signal intensity raise gradually (Fig. 4).
Embodiment 3 Fe of the present invention 3O 4Many performances of/PLGA contrast agent potentiation HIFU experiment
⑴ external potentiation HIFU experiment
JC200 type focus supersonic tumor therapy system (Chongqing Haifu's production) is used in experiment.Fresh in vitro Hepar Bovis seu Bubali (10 cm * 7 cm * 5 cm) rewarming outgases behind 25 min, places the methyl methacrylate container, and de aerated water covers to the Glisson's capsule surface, with 200 μ l Fe 3O 4The diluent of many performances of/PLGA contrast agent directly injects degassing Hepar Bovis seu Bubali, and wherein dilution process is the Fe with embodiment 1 preparation 3O 4Many performances of/PLGA contrast agent and normal saline are diluted to Fe in proportion 3O 4Concentration is 0.5mg/ml.Injection site is monitored with the HIFU diagnostic ultrasound in real time, gives acoustical power 150 W after the injection immediately, and the HIFU of exposure time 2 s melts once.Irradiation finishes the back to be measured and also calculates target area coagulation necrosis volume, V=P (long * wide * thick)/6, and with simple HIFU treatment group contrast.After HIFU melted, the coagulation necrosis district was canescence, and is clear with the surrounding tissue boundary.Can know by Fig. 5, under the identical condition of treatment a frequency, irradiation power, exposure time, injection Fe 3O 4Behind many performances of/PLGA contrast agent, the simple HIFU treatment group of Hepar Bovis seu Bubali coagulation necrosis volume obviously increases.
⑵ rabbit VX2 breast tumor potentiation HIFU experiment
14d carries out the HIFU treatment to experimental rabbit behind the VX2 tumor inoculation.Before the HIFU treatment, experimental rabbit depilation, anesthesia, the HIFU therapeutic bed is fixed in the ventricumbent position, and abdominal part is soaked in the degassing water-bath.Airborne ultrasonic auxiliary HIFU will treat focus and be positioned in the tumor, and real-time monitor treatment process.The HIFU predose, the local Fe that injects of breast tumor 3O 4Diluent 0.5 ml of many performances of/PLGA contrast agent, wherein dilution process is the Fe with embodiment 1 preparation 3O 4Many performances of/PLGA contrast agent and normal saline are diluted to Fe in proportion 3O 4Concentration is 1mg/ml, carries out HIFU irradiation after massaging 1 min.HIFU treats parameter: fixed point irradiation, a treatment frequency 0.94 MHz, focal length 145 mm, irradiation acoustical power 150 W, exposure time 5 s.After HIFU irradiation finished, the anatomy experiment rabbit was taken out tumor tissues, and lamellar is cut, and showed that as far as possible tumor damages maximum aspect, observed, measured and calculate and respectively organize breast tumor coagulation necrosis volume after being dipped in 1% TTC solution, 15 min; Get 1cm 3The size tumor tissues places 10% formalin fixing; Routine paraffin wax embedding, section, HE dyeing, row PCNA (Proliferating Cell Nuclear Antigen; PCNA) detect, light microscopic observes its histopathology down and immunohistochemistry changes; Other gets 1mm 3Tumor tissues, 2% glutaraldehyde solution is fixed, tissues observed ultrastructural change under the transmission electron microscope, overall merit Fe 3O 4Many performances of/PLGA contrast agent enhanced HIFU therapeutic effect.
After HIFU melted, breast tumor coagulation necrosis district was canescence, and is clear with the surrounding tissue boundary, and TTC dyeing back contrast is more obvious.Visible by Fig. 5, behind the simple HIFU irradiation, breast tumor tissues is not seen obvious coagulation necrosis, associating Fe 3O 4Many performances of/PLGA contrast agent irradiation group, the visible obviously coagulation necrosis district of tumor tissues.HIFU unites Fe 3O 4Many performances of/PLGA contrast agent group, the HE demonstration of dyeing, necrotic area and surrounding tissue boundary are clear; The PCNA positive expression rate obviously descends, and PCNA is positioned nucleus, and the pale brown color colour developing of homogenizing occurs and be the PCNA positive cell, during the nucleus structural damage, the negative expression of PCNA; Transmission electron microscope is observed down, and the irradiated site cellularity owes clear, and cell membrane and nuclear membrane lose seriality, chromatin pyknosis, the cracked lumps that is, and visible Fe particle deposition distributes along the nuclear membrane outside (Fig. 6) in endochylema.

Claims (6)

1. one kind is applied to many performances contrast agent that the potentiation high intensity focused ultrasound melts under the US/MRI guiding; It is characterized in that: said many performances contrast agent is the polymer microsphere with core-shell structure; The shell membrane material by lactic acid/co-glycolic acid and magnetic ferroferric oxide nanometer granule by weight forming for 30-70:1; Wherein magnetic ferroferric oxide nanometer is particle studded on shell membrane, contrast agent core parcel distilled water; Said magnetic ferroferric oxide nanometer particle grain size is 10-20 nm; The particle diameter of said many performances contrast agent is 750-1050 nm.
2. one kind is applied to the US/MRI guiding method for preparing of many performances contrast agent of melting of potentiation high intensity focused ultrasound down; It is characterized in that; May further comprise the steps: 0.8-1.2 g lactic acid/co-glycolic acid is added in the 17-28 ml chloroform, be stirred well to after the dissolving fully slowly to wherein dripping 1.8-2.3 ml Fe 3O 4With 1.6-3 ml distilled water, adopt the vibration of sonic oscillation appearance subsequently, get brown W/O emulsion, hunting power is 130 W in the said sonic oscillation process, duration of oscillation is 30-45 s; Polyvinyl alcohol is dissolved in to be mixed with the polyvinyl alcohol percentage by weight in the distilled water be 5% poly-vinyl alcohol solution; Above-mentioned brown emulsion and poly-vinyl alcohol solution are mixed for 1:5 by volume; Adopt high speed dispersion homogenizer homogenizing 5-6 min to prepare the W/O/W microsphere, under room temperature, stir 1.5-2 h again, chloroform is fully volatilized; After 3-5 distilled water washing, centrifugal after; Collecting precipitation promptly gets many performances contrast agent, and said homogenizer rotating speed is 9000-10000 rpm.
3. many performances contrast agent according to claim 1 and 2 is characterized in that: the monomeric mol ratio of lactic acid monomer and hydroxyacetic acid is 50:50 in said lactic acid/co-glycolic acid.
4. claim 1 or 2 described many performances contrast agent are used for strengthening in external enhancing US, MRI video picture and the body purposes of rabbit VX2 hepatocarcinoma MRI T2WI image.
5. claim 1 or 2 described many performances contrast agent are used for purposes external, that the interior potentiation high intensity focused ultrasound of body melts.
6. many performances contrast agent according to claim 5; It is characterized in that: the treatment parameter when said many performances contrast agent is used for the potentiation high intensity focused ultrasound and melts is: radiation mode is fixed point irradiation; A treatment frequency 0.94 MHz, focal length 145 mm; Irradiation acoustical power 150 W, exposure time is respectively 5 s in external 2 s, the body.
CN2012103467295A 2012-09-19 2012-09-19 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 Pending CN102824648A (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105641704A (en) * 2015-12-30 2016-06-08 上海理工大学 Bubble-producing polylactide acid-glycolic acid effervescence drug and preparation method and application thereof
CN107007835A (en) * 2017-05-31 2017-08-04 重庆医科大学 Carry Prussian blue targeted nano compound and preparation method thereof

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
孙阳等: "多功能超声造影剂体外超声-磁共振双模态显像及增效HIFU实验", 《第十一届全国超声医学学术大会 论文汇编》 *
孙阳等: "载超顺磁性氧化铁高分子微球对兔肝癌MR成像效果的影响", 《中国医学影像技术》 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105641704A (en) * 2015-12-30 2016-06-08 上海理工大学 Bubble-producing polylactide acid-glycolic acid effervescence drug and preparation method and application thereof
CN107007835A (en) * 2017-05-31 2017-08-04 重庆医科大学 Carry Prussian blue targeted nano compound and preparation method thereof

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Application publication date: 20121219