CN100581596C - Tissue mould for evaluating focusing performance of high strength focusing ultra sonic in tissue and its preparation method - Google Patents
Tissue mould for evaluating focusing performance of high strength focusing ultra sonic in tissue and its preparation method Download PDFInfo
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Abstract
A tissue body model used for evaluating the focusing performance of high-intensity ultrasonic waves in tissue is proportionally prepared from solidifying agent, biologic tissue material and aquatic medium through preparing aquatic medium, preparing the solution of solidifying agent, mixing them together, sufficient expanding, dissolving and degassing, preparing the homogeneous tissue, adding it to the solution of solidifying agent, stirring, and shaping.
Description
Technical field
The invention belongs to biological technical field, relate to a kind of estimate high intensity focused ultrasound in tissue focusing performance organize phantom and preparation method thereof.
Background technology
The high-strength focusing ultrasonic therapy technology has obtained clinical approval as a kind of new technique of non-invasive, suitable shape heat " excision " treatment lesion tissue of rising in recent years, but in clinical practice, must check, especially the focusing performance that focuses on focused transducer be estimated the effect that just can ensure treatment effectiveness, safety and the reliability of treatment.
At present, (Acoustic Focal Region is an acoustic pressure AFR) is used as the detection index of estimating the focused transducer focusing performance in the zone of space 6dB decay in sound burnt territory.The sound field of the focused transducer under the form of AFR and size can drive with the hydrophone scanning low-power of calibrating distributes quantitative description.Yet, when high power (for example output acoustic power is more than 100 watts) drives, the acoustic pressure of focused transducer Jiao Yuchu in water very high (can reach tens megapascal (MPa)s), existing hydrophone is difficult to bear high pressure like this, therefore is difficult to describe the focusing performance of the focused transducer under the high power driving at present with hydrophone scanning sound field method.
Yet it is different with traditional thermotherapy, the key of high-strength focusing ultrasonic therapy technology is at first will form one coagulation necrosis in tissue, also be called as " Biological Focal Region " (Biological Focal Region, BFR), moving by BFR in the suitable shape scanning strip kinetoplast of external focusing ultrasonic transducer again, to reach the effect of complete treatment lesion tissue, so for the high-strength focusing ultrasonic therapy technology, estimate the focusing performance of focused transducer, than AFR, that we more are concerned about is the BFR that focused transducer forms in tissue, be the focusing performance of focused transducer in tissue, and for a definite focused transducer, the form of the BFR that forms in tissue and size depend primarily on aspect two: the one, and the biological characteristics of biological tissue itself, comprise that organizational structure is (as density, elasticity etc.) and functional status (supplying etc.) as blood, the 2nd, the therapeutic dose of focused transducer, i.e. output acoustic power and exposure time.Studies show that: the biological characteristics of biological tissue itself is very big to the influence of BFR.Therefore, be difficult to up to now the focusing performance of focused transducer be estimated with the biological tissue of nonstandardized technique, so, set up a kind of as far as possible with biological tissue, biological tissue's phantom that thermal characteristics is consistent just becomes exigence.
Summary of the invention
Technical problem to be solved by this invention is at estimating the above-mentioned shortcoming that the focused transducer focusing performance exists in the prior art, a kind of and biological tissue sound, biological tissue's phantom that thermal characteristics is consistent are provided, and the preparation method of this biological tissue's phantom and the application in estimating the focused transducer focusing performance.
The technical scheme that solution the technology of the present invention problem is adopted is that this biological tissue's phantom comprises shape-fixing agent, biological organization material and aqueous medium, the percentage ratio that accounts for this tissue phantom cumulative volume respectively is: shape-fixing agent 3%-60%, biological organization material 30%-80%, aqueous medium 1%-40%, this tissue phantom can produce the biological effect result's who shows that high intensity focused ultrasound produces in biological tissue the coagulation necrosis or the change of color behind high intensity focused ultrasound irradiation.
Described shape-fixing agent can be among gelatin, acrylamide, Ammonium Persulfate 98.5 or the TEMED one or several and mixes, for make that the organizer mold forming of making is good, even structure, good springiness, described preferred gelatin is as shape-fixing agent.
Described biological tissue raw material is selected the Ovum Gallus domesticus album of laying eggs from animal that can conveniently obtain, pluck tissue (as liver), serum, macromolecular material etc. for use, and the change of coagulation necrosis or color can take place under 45 ℃ of-80 ℃ of temperature this biological organization material.
Described aqueous medium is distilled water, normal saline or the APS solution that does not have bubble.
Can be anti-for the phantom of making of organizing in preservation, in this organizer film, can also add antiseptic, described antiseptic is selected from 3～30% formaldehyde or 3～10% paraformaldehyde, accounts for and organizes 1%～10% of phantom cumulative volume.
The present invention also provides and prepares the above-mentioned method of organizing phantom of high intensity focused ultrasound at the tissue focusing performance that be used for estimating, and may further comprise the steps:
(1), determine the component in the organizer film: comprise shape-fixing agent, biological organization material and aqueous medium, the percentage ratio that each component accounts for this tissue phantom cumulative volume respectively is: shape-fixing agent 3%-60%, biological organization material 30%-80%, aqueous medium 1%-40%;
(2), the preparation of aqueous medium: remove the bubble in the aqueous medium;
(3), the preparation of shape-fixing agent solution: the shape-fixing agent of (1) determined percent by volume is sneaked in the aqueous medium of determined percent by volume set by step, fully expands, and is warmed to 30 ℃-50 ℃ and makes shape-fixing agent dissolve, outgas;
(4), the preparation of homogenate tissue: biological organization material is removed connective tissue, is pulverized, removes bubble, separation, and obtaining not having bubble does not have connective tissue homogenate;
(5), mix: resulting homogenate tissue of step (4) and the abundant mix homogeneously of the resulting shape-fixing agent solution of step (3);
(6), be shaped: mixture is carried out moulding processing promptly finalize the design and solidify typing in the container.
The above shape-fixing agent is that among gelatin, acrylamide, Ammonium Persulfate 98.5 or the TEMED (stock solution) one or several mix.
The above biological organization material is Ovum Gallus domesticus album, pluck tissue, serum, the macromolecular material of laying eggs from animal for the biological organization material of coagulation necrosis or color change can take place under 45 ℃ of-80 ℃ of temperature.
The above aqueous medium is distilled water, normal saline or APS solution.
For the organizer film that makes anti-in preservation, preferably the component in the organizer film also comprises antiseptic in the above-mentioned steps (1), account for and organize 1%～10% of phantom cumulative volume, described antiseptic is selected from 3%～30% formaldehyde or 3%～10% paraformaldehyde, adds antiseptic and other component mix homogeneously in step (5).
The organizer film that makes according to the method described above, consistent with the sound characteristics and the hot rerum natura of biological tissue, thereby the focusing performance and the Biological Focal Region for measuring focused transducer of success provide a test carrier, for the quality guarantee of high-strength focusing ultrasonic therapy provides a Controllable evaluation material.
Description of drawings:
Fig. 1 is the picture after biological tissue of the present invention body film is shaped
Fig. 2 left side is to organize the B ultrasonic image of phantom behind high intensity focused ultrasound irradiation for B ultrasonic image, the right side of organizing the phantom predose
The Biological Focal Region that Fig. 3 forms in organizing phantom for high intensity focused ultrasound (BFR)
The Biological Focal Region (BFR) that Fig. 4 forms in the Hepar Bovis seu Bubali that exsomatizes for high intensity focused ultrasound.
The specific embodiment
Below in conjunction with embodiment and accompanying drawing, the technology of the present invention is described in further detail.
Embodiment 1:
Utilization is boiled, condensation, the mode of taking out negative pressure, high speed centrifugation (4000-12000ram) obtain degassing distilled water; Take by weighing gelatin 40g, add 200ml degassing distilled water heating for dissolving gelatin, gelatin is put into water-bath and is cooled to 35-40 ℃, discharges bubble in the gelatin solution with the mode of taking out negative pressure or high speed centrifugation (4000-12000ram) then.
The preparation of homogenate tissue.Remove the connective tissue in the Hepar Bovis seu Bubali, pulverize Hepar Bovis seu Bubali, remove simultaneously connective tissue again, remove out the bubble of homogenate tissue with the mode of taking out negative pressure or high speed centrifugation (4000-12000ram), separate no bubble and do not have the homogenate of connective tissue, measure the homogenate tissue, simultaneously rewarming (temperature is controlled at 30 ℃-40 ℃) is organized in homogenate.
Ready gelatin solution 200ml is added ready Hepar Bovis seu Bubali homogenate organize among the 600ml, fully add 25% formaldehyde 10ml behind the mixing, abundant again mixing is poured at last in the typing container and is finalized the design.
Embodiment 2: utilize boil, condensation, the mode of taking out negative pressure, high speed centrifugation (4000-12000ram) obtain degassing distilled water; Take by weighing by gelatin 60g, add 300ml degassing distilled water heating for dissolving gelatin, gelatin is put into water-bath and is cooled to 35-40 ℃, discharges bubble in the gelatin solution with the mode of taking out negative pressure or high speed centrifugation (4000-12000ram) then.
The preparation of homogenate tissue.Remove the connective tissue in the Hepar Sus domestica, pulverize Hepar Sus domestica, remove simultaneously connective tissue again, take out negative pressure or high speed centrifugation (4000-12000ram) and get rid of the bubble of homogenate tissue, separate no bubble and do not have the homogenate of connective tissue, measure the homogenate tissue, simultaneously rewarming (temperature is controlled at 30 ℃-40 ℃) is organized in homogenate.
Ready gelatin solution 300ml is added ready Hepar Sus domestica homogenate organize among the 600ml, fully add 10% paraformaldehyde 15ml behind the mixing, abundant again mixing is poured at last in the typing container and is finalized the design.
According to embodiment 1 described identical method and step, use the biological organization material of liver tissue homogenate as the focusing performance that shows focus supersonic, use gelatin solution as shape-fixing agent, obtained high-strength focusing ultrasonic therapy of the present invention with organizing phantom according to the listed proportioning of table 1 (embodiment 2).Institute obtains and organizes phantom is the bronzing solid, is applicable to the focusing performance that detects focused transducer.
Embodiment 3: determine component thing and consumption according to the listed proportioning of table 1 (embodiment 3); Utilization is boiled, condensation, the mode of taking out negative pressure, high speed centrifugation (4000-12000ram) obtain degassing normal saline; By taking by weighing acrylamide 200g, add in the 200ml degassing normal saline and dissolve acrylamide, discharge bubble in the acrylamide solution with the mode of taking out negative pressure or high speed centrifugation (4000-12000ram) then.
The preparation of homogenate tissue.Get egg white 600ml, remove impurity wherein, remove bubble in the Ovum Gallus domesticus album with the mode of taking out negative pressure or high speed centrifugation (4000-12000ram).
Ready acrylamide solution 400ml is added among the ready Ovum Gallus domesticus album 600ml, fully add 10% paraformaldehyde solution 25ml behind the mixing, abundant again mixing is poured at last in the typing container and is finalized the design.
Embodiment 4: determine component thing and consumption according to the listed proportioning of table 1 (among the embodiment 4); Utilization is boiled, condensation, the mode of taking out negative pressure, high speed centrifugation (4000-12000ram) obtain degassing normal saline; By taking by weighing acrylamide 400g, add in the 300ml degassing normal saline and dissolve acrylamide, discharge bubble in the acrylamide solution with the mode of taking out negative pressure or high speed centrifugation (4000-12000ram) then.
The preparation of homogenate tissue.Get calf serum 300ml, remove impurity wherein, use the mode of taking out negative pressure or high speed centrifugation (4000-12000ram) except that the bubble in the serum deprivation.
Ready acrylamide solution 700ml is added among the ready serum 300ml, fully add 10% paraformaldehyde solution 50ml behind the mixing, abundant again mixing is poured at last in the typing container and is finalized the design.
Test example 1: the JC type focus supersonic tumor therapy system irradiation of the biological tissue's phantom that makes by embodiment 1 with Haifu's production, irradiation parameters is selected frequency 1.6MHz, focal length 110mm, diameter 120mm, fixed point irradiation power 200W, time 10S, irradiation degree of depth 20mm, B ultrasonic image behind the predose and the BFR that forms in phantom be as shown in Figure 2: certain irradiation dose (200W, high intensity focused ultrasound 10s) forms (Fig. 2 left side) before the BFR in organizing phantom, back (Fig. 2 right side) target area B ultrasonic ultrasonogram and gross examination of skeletal muscle, visible tissue phantom ultrasonogram is very consistent with the ultrasonogram of animal tissue, and can form the coagulation necrosis that the border is perfectly clear.
The BFR that Fig. 3 forms in organizing phantom for high intensity focused ultrasound, the BFR that Fig. 4 forms in the fresh in vitro Hepar Bovis seu Bubali for high intensity focused ultrasound.
The result shows: organize phantom to can be used for detecting to focus on the focusing performance of focused transducer in tissue by what embodiment 1 made, its produces coagulation necrosis and is exsomatizing, conforming on the live body with ultrasonic.Final result of the test shows: the phantom of organizing that embodiment 1 makes can be effective, detects the focusing performance that focuses on focused transducer accurately.
The present invention can be used for the demand in a large amount of high intensity focused ultrasound related basic researches the focusing performance of focused transducer accurately estimated, can be used for that high intensity focused ultrasound device fabrication unit accurately comments properties of product and, can be used for the foundation of high intensity focused ultrasound technical standard the demand of high intensity focused ultrasound clinicist's training.
Table 1
| Embodiment 2 | Embodiment 3 | Embodiment 4 | |
| Liver tissue homogenate | 600ml | ||
| Egg white | 600ml | ||
| Serum | 300ml | ||
| 20% gelatin solution | 300ml | ||
| Acrylamide | 200 grams | 400 grams | |
| De aerated water | 200ml | 300ml | |
| 10% paraformaldehyde solution | 15ml | 25ml | |
| 25% formalin | 50ml |
Claims (7)
1, a kind of estimate high intensity focused ultrasound in tissue focusing performance organize phantom, it is characterized in that this organizer film comprises shape-fixing agent, biological organization material and aqueous medium, the percentage ratio that accounts for this tissue phantom cumulative volume respectively is: shape-fixing agent 3%-60%, biological organization material 30%-80%, aqueous medium 1%-40%; Wherein, described shape-fixing agent is that among gelatin, acrylamide, Ammonium Persulfate 98.5 or the TEMED one or several mix; The biological organization material of coagulation necrosis or color change for taking place in described biological organization material under 45 ℃ of-80 ℃ of temperature; Described aqueous medium is distilled water, normal saline or APS solution.
2, evaluation high intensity focused ultrasound according to claim 1 in tissue focusing performance organize phantom, it is characterized in that described biological organization material is Ovum Gallus domesticus album or pluck tissue or the serum that animal is laid eggs.
3, evaluation high intensity focused ultrasound according to claim 1 and 2 in tissue focusing performance organize phantom, it is characterized in that this organizer film also includes antiseptic, it accounts for 1%～10% of this organizer film cumulative volume.
4, evaluation high intensity focused ultrasound according to claim 3 in tissue focusing performance organize phantom, it is characterized in that described antiseptic is selected from 3%～30% formaldehyde or 3%～10% paraformaldehyde.
5, a kind of preparation method of organizing phantom as claimed in claim 1 may further comprise the steps:
(1), determine the component in the organizer film: comprise shape-fixing agent, biological organization material and aqueous medium, the percentage ratio that each component accounts for this tissue phantom cumulative volume respectively is: shape-fixing agent 3%-60%, biological organization material 30%-80%, aqueous medium 1%-40%; Wherein, described shape-fixing agent is that among gelatin, acrylamide, Ammonium Persulfate 98.5 or the TEMED one or several mix; The biological organization material of coagulation necrosis or color change for taking place in described biological organization material under 45 ℃ of-80 ℃ of temperature; Described aqueous medium is distilled water, normal saline or APS solution;
(2), the preparation of aqueous medium: remove the bubble in the aqueous medium;
(3), the preparation of shape-fixing agent solution: the shape-fixing agent of (1) determined percent by volume is sneaked in the aqueous medium of determined percent by volume set by step, fully expands, and is warmed to 30 ℃-50 ℃ and makes shape-fixing agent dissolve, outgas;
(4), the preparation of homogenate tissue: biological organization material is removed connective tissue, is pulverized, removes bubble, separation, and obtaining not having bubble does not have connective tissue homogenate;
(5), mix: resulting homogenate tissue of step (4) and the abundant mix homogeneously of the resulting shape-fixing agent solution of step (3);
(6), be shaped: mixture is carried out moulding processing.
6, preparation method according to claim 5 is characterized in that Ovum Gallus domesticus album or pluck tissue or the serum of described biological organization material for laying eggs from animal.
7, preparation method according to claim 5, it is characterized in that the component in the organizer film also comprises antiseptic in the step (1), it accounts for organizes 1%～10% of phantom cumulative volume, described antiseptic is selected from 3%～30% formaldehyde or 3%～10% paraformaldehyde, adds antiseptic and other component mix homogeneously in step (5).
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| 一种评价HIFU聚焦性能的仿组织体模的建立. 敬宗玉.中国优秀博硕士学位论文全文数据库. 2005 |
| 一种评价HIFU聚焦性能的仿组织体模的建立. 敬宗玉.中国优秀博硕士学位论文全文数据库. 2005 * |
| 超声体模及性能测试. 李国伟，陈亚珠.声学学术，第37卷第4期. 1990 |
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