CN105427725B - A kind of imitative body Model for ultrasonic single mode image co-registration assessment tumour ablation range - Google Patents
A kind of imitative body Model for ultrasonic single mode image co-registration assessment tumour ablation range Download PDFInfo
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Abstract
The invention belongs to medical domains, are related to a kind of imitative body Model for ultrasonic single mode image co-registration assessment tumour ablation range, tumour glue is embedded in normal tissue glue, the model before forming ablation is melted；After ablation, the normal tissue glue that the tumour glue and peripheral part that dissolution is sucked out melt, Reperfu- sion melts glue, the model after forming ablation, assesses tumour ablation range for ultrasonic single mode image co-registration.Normal tissue glue contains carragheen, is in equal echo under two-dimensional ultrasonic imaging mode.Tumour glue is in Gao Huisheng under two-dimensional ultrasonic imaging mode.It melts glue and contains carragheen, particular dye, acoustic contrast agent, be in Gao Huisheng under two-dimensional ultrasonic imaging mode.Naked eyes gross examination of skeletal muscle sheet imitates body Model, and normal tissue glue is semi-transparent clear, and tumour glue is White-opalescent, ablation glue be it is coloured opaque, comparison is strong, easily distinguishable.Therefore this imitative body Model can accurately assess tumour ablation range, be suitable as the teaching and training of tumour ablation technology.
Description
Technical field
The invention belongs to medical domain, the ultrasonic contrast and liver cancer by US-guided related in particular in ultrasound medicine is examined
Disconnected and interventional therapy field, is related to a kind of teaching and training for ultrasonic single mode image fusion technology and tumour ablation technology
Model.
Technical background
Ablation is a kind of minimally invasive, easy, safe therapeutic modality, and it is swollen clinically to have become a kind of common treatment
The mode of tumor.Basic operation is to penetrate an aciculiform utensil in tumor tissues, issues radio frequency by needle point or microwave generates heat,
Lead to that the moisture inside and outside tumor tissues evaporates rapidly, albuminous degeneration and coagulation necrosis occurs in histocyte.Currently, clinically leading
To judge whether ablation is complete using Imaging Method.Ultrasound due to noninvasive radiationless, economical and convenient, can Real-time and Dynamic Detection,
There is significant advantage in art and in bedside application.But since ultrasonic space resolution ratio is lower, make it in assessment ablation range
When be very restricted.
In recent years, the rapid development of medical image integration technology overcomes the limitation of ordinary ultrasonic to a certain extent.
Studying at present more is CT/MR-US image fusion technology, by CT/MR good spatial resolution and the good real-time of ultrasound into
Row has complementary advantages, and then guidance ultrasound positions liver lesion, punctures, treating and curative effect evaluation.However different imaging
Mode is from different inspections, and different operations is likely to result in anatomical position and changes precisely to melt, and not
It will also result in error with the conversion of modality images format, therefore CT/MR-US image fusion technology is difficult to accurate fusion.With
The maturation of three-dimensional ultrasound is expected to overcome CT/MR-US image by using the automatic integration technology of three-D ultrasonic single mode image
The deficiency of integration technology.Although single mode ultrasound integration technology is in art and bedside is applied with significant advantage, exist
The strong deficiency of operating experience dependence, needs operator skillfully to grasp ultrasonic imaging technique and interventional procedure technology.Young doctor
By the constraint of medical ethical moral and medical care precess specification, operation practice can not be carried out with patient, makes the hair of new technology
Exhibition and popularization are by huge limitation.Therefore, the simulation training platform that human body can be simulated for young doctor building, makes ultrasonic doctor
Operating technology in training process fast lifting, be urgent being essential for single mode image co-registration assessment tumour ablation technology development
It asks.
The ultrasound for imparting knowledge to students and training existing a small amount of at present imitates body Model, wherein also include tumour imitate body class model,
The model of Ultrasound-guided Biopsy class.The authorized patent ZL 201010281470.1 of this seminar discloses a kind of for void
The imitative body Model for the tumor tissue biopsy process that quasi- navigation assisting ultrasonic can not be shown, for training ultrasonic doctor in conventional two dimension
Ultrasound can not find the technology for precisely puncturing tumour in the case where tumor focus using virtual navigation technology.Using external model into
Row ablation practice can directly cut model after the evaluation of ultrasonic single mode image co-registration, verify evaluation result.However state so far
It inside there is no the relevant report of ultrasonic single mode image co-registration evaluation tumour ablation security boundary model.
Clinically ultrasonic single mode image co-registration assessment ablation range mainly carries out Image Acquisition using ultrasonic contrast, comments
Valence disappears according to the high enhancing and low enhancement region for being former lesion, becomes the ablation stove of no enhancing and covers former lesion.Therefore, it establishes
A kind of imitative body Model that can be used for ultrasonic single mode image co-registration assessment tumour ablation range, needs to solve following problem: 1. can
It is imaged under two-dimensional ultrasound and harmonic wave contrast-enhanced ultrasound mode；2. the high enhancing table of contrast-enhanced ultrasound of primary hepatocellular carcinoma arterial phase can be simulated
It is existing；3. can simulate former focal area after liver cancer ablation becomes no enhancement region；4. can be imaged after ablation using ultrasound；5. imitating
The tumor model of body is generally convenient for observation.
Summary of the invention
One of the object of the invention is that providing one kind can be used for ultrasound for the problems of imitative body Model of ultrasound at present
The imitative body Model of single mode image fusion assessment tumour ablation range.
The second purpose of the present invention is to provide the formulas and preparation method of above-mentioned imitative body Model.
Invention is achieved through the following technical solutions above-mentioned purpose:
Invention provides a kind of imitative body Model for ultrasonic single mode image co-registration assessment tumour ablation range, feature
It is containing the tumour glue for simulating tumour and the normal tissue glue for simulating normal surrounding tissue；
The tumour glue contains microcapsular ultrasound contrast agent；More preferable nanometer microcapsular ultrasound contrast agent；
And the imitative body Model is accompanied by after ablation for injecting the ablation glue formula in ablation space, the ablation glue formula
Contain carragheen, stomach window acoustic contrast and dyestuff；
Preferably, the dyestuff is Congo red, methyl blue or carbon black；It is most preferably Congo red.
The imitative body Model includes containing normal tissue glue and tumour glue in model before melting, and extracts the tumour of melting after ablation out
The normal tissue glue that glue and peripheral part melt, Reperfu- sion melt glue, make in model comprising normal tissue glue and ablation glue.Tumour
Glue is in first Gao Huisheng under two-dimensional ultrasonic imaging mode, becomes equal echo after ablation；Normal tissue glue and ablation glue are super in two dimension
Respectively always it is in equal echo and Gao Huisheng under acoustic imaging mode, assesses tumour ablation range for ultrasonic single mode image co-registration.
Alternatively, microcapsular ultrasound contrast agent or nanometer microcapsular ultrasound contrast agent that the imitative body Model uses
For protide, carbohydrate, nonionic surfactants, lipid or polymeric vesicle acoustic contrast agent；
But preferably lipid microbubble ultrasonic contrast agent；
It is highly preferred that being nano-lipid microcapsular ultrasound contrast agent；
It is highly preferred that the partial size of the nanometer microcapsular ultrasound contrast agent is 300~500nm.
Alternatively, tumor stroma glue is also contained in tumour glue, it is preferable that the tumor stroma glue contains OK a karaoke club
Glue, stomach window acoustic contrast；Preferably also contain mammal milk/milk powder；It is highly preferred that mammal milk/the milk powder
For milk.Contain carragheen, stomach window acoustic contrast in normal tissue glue；It is accompanied by marker material.
Present invention simultaneously provides for ultrasonic single mode image co-registration assessment tumour ablation range imitative body Model formula,
Contain microcapsular ultrasound contrast agent or nanometer microcapsular ultrasound contrast agent, carragheen, stomach window acoustic contrast；Preferably also contain lactation
Animal milk/milk powder；
Preferably, the mammal milk/milk powder is milk；
Except this, also containing ablation glue formula, the ablation glue formula contains carragheen, stomach window acoustic contrast and dyestuff；
Preferably, the dyestuff is Congo red, methyl blue or carbon black；It is most preferably Congo red.
Optionally, contain in the tumour glue formula:
The content of microcapsular ultrasound contrast agent or nanometer microcapsular ultrasound contrast agent with phosphatide Mass Calculation be 0.005%~
0.009% (w/v), more preferable 0.0056~0.0084% (w/v),
Carragheen 0.5%~5% (w/v),
Stomach window acoustic contrast 0.05% to 0.2% (w/v),
Preferably also contain milk 2%~10% (v/v).
Optionally, contain in normal tissue glue formula:
Carragheen 0.5%~5% (w/v),
Stomach window acoustic contrast 0.05%~0.2% (w/v).
Optionally, it melts and contains in glue formula:
Carragheen 0.5%~5% (w/v),
Stomach window acoustic contrast 0.5%~5% (w/v)；
Dyestuff 0.03~0.1% (w/v).
Carragheen, stomach window acoustic contrast, milk is selected to be as the reason of matrigel: firstly, food-grade carragheen
It is the hydrophilic colloid extracted from plant or algae, hydrothermal solution forms stable translucent at room temperature after cooling
Gel state.Concentration by adjusting carragheen can prepare the gel of different hardness, advantageous as the primary structure of model.
Along with food-grade carragheen has no toxic and side effect to human body, the safety of user can be ensured.And using carragheen as matrix group
Divide suitable for ablation, ablation can reach the ablation range of about 4 × 3cm for 4 minutes, and the saving time is particularly suited for experiment mould
The production of type.And the high stability of agar, the agar model after solidification are not easy to melt in RF ablation, ablation 12 minutes
Ablation range only has about 3 × 2cm.Second, stomach window acoustic contrast is a kind of clinically common gastrointestinal tract contrast medium, main
Ingredient is various plants and algae, cellulose, is in Gao Huisheng in two-dimensional ultrasonic imaging.Stomach window acoustics is added in matrigel to make
Shadow agent can provide certain echo intensity for model, thus acoustics performance of the simulated tissue in two-dimensional ultrasonic imaging.Third, will
Milk is added in matrigel, can effectively change the opacity of matrigel.According to different needs, the concentration for adjusting milk can make
Different opacities is presented in different tissues ingredient in imitative body, is conducive to visually observe.In addition, milk itself has in two-dimensional ultrasound
There is certain echo intensity, milk is added can also change the acoustic characteristic of imitative body simultaneously.
The history in the research of microcapsular ultrasound contrast agent existing more than 30 years.Recent domestic successfully has developed albumen in succession
The ultrasonic microbubble of a variety of coatings such as class, carbohydrate, nonionic surfactants, lipid, macromolecule.Studies have shown that nanoscale
Lipid microbubble contrast agent partial size is small, penetration power is strong, good dispersion, sound field stability are good.
And the present invention is then used for the imitative body Model of preparation simulation tumour for the first time.Inventors have found that using nanoscale
Lipid microbubble ultrasonic contrast agent makes an addition in tumour glue, can prepare the imitative body Model for being very suitable for tumor diagnosis and treatment research.It is logical
The content and solution temperature of crossing control nanometer microcapsular ultrasound contrast agent can control the imaging time of tumour rubber moulding type in imitative body,
Regulated and controled convenient for user according to the training goal of oneself.Microcapsular ultrasound contrast agent returns under two-dimensional ultrasonic imaging mode in high
Sound, it is often more important that be also in Gao Huisheng under harmonic contrast's ultrasound imaging mode, therefore, microcapsular ultrasound be added in tumour glue and makes
(two-dimensional ultrasound and harmonic wave contrast echo imaging pattern are in for shadow agent, i.e. the acoustics performance of analog contrast-enhanced ultrasound of primary hepatocellular carcinoma arterial phase
Height enhancing).Further, since nanometer microcapsular ultrasound contrast agent and unstable, slowly destroyed in tumour glue or due to ablation and
It is destroyed, therefore the echo meeting automatic descending of tumour rubber moulding type, until subsiding completely.
The tumour glue provided in the present invention program is first first under two-dimensional ultrasonic imaging mode and harmonic wave ultrasound imaging mode
It is respectively in high echo and Gao Huisheng, subsequent (such as within 30~240min time, most preferably in 45~60min or so) becomes automatically
For equal echo and echoless；Normal tissue glue under two-dimensional ultrasonic imaging mode and harmonic wave ultrasound imaging mode always respectively in etc.
Echo and echoless.
In a particularly preferred embodiment of the invention, the nanometer microcapsular ultrasound contrast agent of use is that nano-lipid is micro-
Steep acoustic contrast agent.At this time in most suitable additive amount (such as 0.005~0.008%, especially 0.007% or so) range
It is interior, can obtain simultaneously imaging session time the most suitable and imaging effect (duration at 45~60min or so (Fig. 3),
And imaging effect is optimal (Fig. 2)).
Most suitable additive amount is 0.007% or so.Not only imaging time is suitble to (just be suitable for imitative body Model at this time
For training purposes), and either two-dimensional model or harmonic mode, imaging effect are optimal (Fig. 2).It is such skilful
It is very favorable for closing for the production for imitating body Model.
It is prepared by known method currently, nano-lipid microcapsular ultrasound contrast agent can only be adopted.For example, Wang Ping can be used
The method of equal reports prepares (king's equality, the preparation of novel nano microcapsular ultrasound contrast agent and ultrasonic image research, Zhongshan University
Report (medical science version), 2011,32 (3), 327-330) or the method for the reports such as Yin Tinghui prepare (Yin Tinghui etc.,
Nanobubbles for enhanced ultrasound imaging of tumors, Int J Nanomedicine,
2012,7:895-904).
The main component and formula of normal tissue glue include the food-grade OK a karaoke club of proportion identical as the matrigel of tumor model
Glue, stomach window acoustic contrast.Its object is to so that the normal tissue glue of imitative body is disappeared in the microcapsular ultrasound contrast agent of tumour rubber moulding type
It steps back, forms acoustic feature identical with tumour glue.Marker material is accompanied by normal tissue glue, it on the ultrasound image can be clear
It has been shown that, as ablation front and back alignment mark.
The component for melting glue includes food-grade carragheen, stomach window acoustic contrast and color dye.Carragheen proportion with just
Normal tissue glue is identical, and the proportion of stomach window acoustic contrast is 20 times of normal tissue glue.Its object is to make to melt glue and normal
The echo comparison of tissue glue is strong, is convenient for ultrasound observation.It is to distinguish the tumour glue and dye of white using the purpose of color dye
The ablation glue of color is convenient for gross examination of skeletal muscle.
Dyestuff in ablation glue is especially Congo red particularly preferably from Congo red, methyl blue or carbon black.
Congo red is a kind of red-brown powder, odorless, is dissolved in water, is slightly soluble in ethyl alcohol, is practically insoluble in chloroform, ether, often
It is used as dyestuff diagnosticum, for checking renal function, amyloidosis etc..The present invention is for the first time by the Congo red carragheen of being used for
In dyeing.The reason of selecting the Congo red color dye as tumour rubber moulding type is: it is Congo red well dispersed in carragheen,
So that ablation glue is taken on a red color, is conducive to visually observe, and distinguish with tumour glue.
Since concretionary model at least contains ablation glue and normal tissue glue after perfusion ablation glue after present invention ablation,
And easily distinguish different colloids and be important in the present invention, because thus could effectively judge ablation effect.
If using general dyestuff, it is easy to generate the phenomenon that dyestuff interpenetrates, lead to the color between different glue
Boundary is unclear.For example, inventor once attempted a variety of dyestuffs, it further include peacock other than Congo red, methyl blue, carbon black
Malachite green, eosin, rose red b etc., still, after tumour gelling is solid further by normal tissue glue package after, many dyestuffs can be from
It is penetrated into tumour glue in normal tissue glue, so that normal tissue glue is with corresponding color.This will obscure two kinds of rubber moulding types,
Extremely it is unfavorable for correctly assessing.
And it is amazing be, inventor use it is Congo red this usually as diagnostic reagent dyestuff as tumour glue
Dyestuff when, after tumour gelling is solid, can effectively adsorb and lock onto tumour glue, even if tumour glue outer layer coats one again
Layer normal tissue glue, in the course that long-time is placed or is impregnated, dyestuff is still steadily existed only in tumour glue, so that swollen
Stable clearly boundary is formed between tumor glue and normal tissue glue.Therefore, the present invention is using the Congo red dye as ablation glue
Material exists only in ablation glue to dyestuff all-the-time stable during injecting ablation glue to long-time placement to normal tissue glue
In, it is suitable for ablation model, assessment ablation range is able to lucidly judge very much.
Invention provides simultaneously a kind of to be carried out ultrasonic single mode image co-registration using imitative body Model and assesses tumour ablation range
Method, comprising the following steps:
S1. body Model is imitated before preparing ablation；
S11. prepare normal tissue sol solution and tumour sol solution；Wherein tumour sol solution contain microcapsular ultrasound contrast agent or
Nanometer microcapsular ultrasound contrast agent；
S12. tumour sol solution is injected into tumour sealing rubber die, cooled and solidified is at tumour rubber moulding type；
S13. tumour rubber moulding type is fixed in imitative mould with silk thread, is placed in marker material in a mold, poured into normal
Sol solution is organized, then cooled and solidified is at imitative body Model；The marker material is sutures or bamboo, wooden or plastic class
Like the article of toothpick shape.
S2. after being melted, melted liquid will be melted and be sucked out, ablation glue is reinjected；The ablation glue contains dyestuff,
Preferably Congo red, methyl blue or carbon black；It is most preferably Congo red；
S3. after gelling to be ablated is solid, the coverage area by melting glue can be used for assessing ablation range.
Preferably, the tumour sol solution is carragheen, stomach window acoustic contrast, the dissolution of nanometer microcapsular ultrasound contrast agent
It is obtained in water, is preferably also added with milk or milk powder, and the temperature of solution is maintained into 50 DEG C~70 DEG C, preferably 60 DEG C；
The normal tissue sol solution is that carragheen stomach function regulating window acoustic contrast is dissolved in water acquisition, and by the temperature of solution
Degree maintains 50 DEG C~70 DEG C, preferably 60 DEG C.
The ablation sol solution is that carragheen, stomach window acoustic contrast and dyestuff are dissolved in water acquisition, and by solution
Temperature maintains 50 DEG C~70 DEG C, preferably 60 DEG C.
The normal tissue sol solution contains:
Carragheen 0.5%~5% (w/v),
Stomach window acoustic contrast 0.05% to 0.2% (w/v).
The tumour glue sol solution contains:
Carragheen 0.5%~5% (w/v),
Stomach window acoustic contrast 0.05% to 0.2% (w/v).
The content of microcapsular ultrasound contrast agent or nanometer microcapsular ultrasound contrast agent with phosphatide Mass Calculation be 0.005%~
0.009% (w/v), more preferable 0.0056%~0.0084% (w/v)；
Preferably also contain mammal milk 2%~10% (v/v), more preferable milk.
The ablation sol solution contains:
Carragheen 0.5%~5% (w/v),
Stomach window acoustic contrast 0.5%~5% (w/v)；
Dyestuff 0.03~0.1% (w/v).
More specifically ultrasound single mode image co-registration assessment tumour ablation range method the following steps are included:
S1. body Model is imitated before preparing ablation:
Normal tissue glue component is dissolved in the distilled water of heat, and is kept the temperature in 50 DEG C to 70 DEG C thermostat water baths, shape
At normal tissue sol solution.
Tumour glue, which is fixed on a height of 10cm diameter with silk thread, is in the cylinder mold of 9cm, and merging mark in a mold
Remember material, normal tissue sol solution is then added and embeds tumour glue, imitative body is placed in -18 DEG C of refrigerators and is quickly cooled down, is frozen into
Imitative body Model, can be used for melting.
S2. the ablation glue perfusion after being melted and melted:
Radio frequency ablation needle is inserted into inside tumour glue and is melted, automatic catch melts 4-6 minutes, the tumour glue after ablation
And peripheral part normal tissue glue is become liquid by thermal melting, and after this liquid is fully drawn out with syringe, injection ablation peptization
Liquid；
S3. at body Model is imitated after ablation after gelling to be ablated is solid, for assessing tumour ablation range.
Preferably, the distilled water temperature that normal tissue glue ingredient is dissolved in step S1 is 50 DEG C to 70 DEG C, thermostat water bath
Temperature be 50 DEG C to 70 DEG C.
It is highly preferred that the distilled water temperature that normal tissue glue ingredient is dissolved in step S1 is 60 DEG C, the temperature of thermostat water bath
Degree is 60 DEG C.
Specifically, marker material described in step S1 is sutures or bamboo, wooden or plastic similar toothpick
The article of shape.Preferred marker material is sutures, convenient fixed in advance.
Preferably, the cooling time in step S1 is 15min to 60min.
It is highly preferred that the cooling time in step S1 is 40min.
Specifically, in step S1 tumour rubber moulding type preparation method the following steps are included:
S11. tumor stroma glue component is dissolved in the distilled water of heat, and is protected in 50 DEG C to 70 DEG C thermostat water baths
Temperature forms matrix sol solution.
S12. acoustic contrast agent is added in matrix sol solution and forms tumour sol solution.
S13., after tumour sol solution to be placed in the spherical die of diameter 3cm, it is placed in ice water and is quickly cooled down, be frozen into tumour
Rubber moulding type.
Preferably, in step S11 tumor stroma glue constituent content be respectively food-grade carragheen content be 0.5% to
5% (w/v), stomach window acoustic contrast content be 0.05% to 0.2% (w/v), the content of milk is 2% to 10% (v/v).
It is 2% (w/ that tumor stroma glue constituent content, which is respectively the content of food-grade carragheen, in more preferably step S11
V), the content of stomach window acoustic contrast is 0.1% (w/v), the content of milk is 5% (v/v).
Specifically, in step S12 nanoscale ultrasound contrast agents preparation method the following steps are included:
S121. by two palm phosphatidylcholine of phospholipid composition, Distearoyl Phosphatidylethanolamine and two palmityl phosphatide
Acid is dissolved in chloroform.
S122. glycerol (v/v) and 2mg/mL Pu Lang containing 10% are added after chloroform volatilizees naturally and forms phospholipid membrane
The distilled water of Buddhist nun gram F68 in 37 DEG C after aquation 1 hour, is passed through octafluoropropane gas and carries out gas displacement, sound and vibration instrument probe is placed in
Gas-liquid intersection carries out sound and vibration 5min.
S123. 50 × g of microvesicle liquid is centrifuged 5min, draws lower layer's milky white liquid tube, 805 × g is centrifuged 30min, abandons
Lower liquid and is resuspended to get nanoscale lipid microbubble ultrasonic contrast agent is arrived with PBS.
Preferably, two palm phosphatidylcholine, Distearoyl Phosphatidylethanolamine and two palmityl phosphorus in step S121
Mass parts ratio 18:1:1~5 of resin acid.
It is highly preferred that two palm phosphatidylcholine, Distearoyl Phosphatidylethanolamine and two palmityls in step S121
The mass parts ratio 18:1:3 of phosphatidic acid.
Preferably, the content of nanoscale lipid microbubble ultrasonic contrast agent is in step S12 tumour glue with phosphatide Mass Calculation
0.0056% to 0.0084% (w/v).
It is highly preferred that the content of nanoscale lipid microbubble ultrasonic contrast agent is in step S12 tumour glue with phosphatide Mass Calculation
For 0.007% (w/v).
Preferably, the cooling time in step S13 is 1min to 10min.
It is highly preferred that the cooling time in step S13 is 5min.
Preferably, the cooling time in step S2 is 15min to 60min.
It is highly preferred that the cooling time in step S2 is 40min.
Specifically, in step S2 melt rubber moulding type preparation method the following steps are included:
S21. matrigel component will be melted to be dissolved in the distilled water of heat, and protected in 50 DEG C to 70 DEG C thermostat water baths
Temperature forms matrix sol solution.
S22. congo red is added in matrix sol solution and forms ablation sol solution.
S23. the liquid that melts after being fully drawn out ablation with syringe, injection ablation sol solution, room temperature cooled and solidified is at disappearing
Melt rubber moulding type.
Preferably, in step S21 melt matrigel constituent content be respectively food-grade carragheen content be 0.5% to
5% (w/v), stomach window acoustic contrast content be 0.5% to 5% (w/v).
It is 2% (w/ that the content that matrigel constituent content is respectively food-grade carragheen is melted in more preferably step S21
V), the content of stomach window acoustic contrast is 2% (w/v).
Preferably, it is 0.03~0.1% (w/v) that step S22, which melts the content of congo red in glue,.
Preferably, the cooling time in step S23 is 1min to 10min.
It is highly preferred that the cooling time in step S23 is 5min.
The beneficial effects of the present invention are:
Tumour glue is embedded in normal tissue glue by this imitative body, and the imitative body rubber moulding type before forming ablation is melted；Ablation
Afterwards, it extracts the tumour glue of melting out and the normal tissue glue of peripheral part dissolution, Reperfu- sion melts glue, the imitative body glue after forming ablation
Model assesses tumour ablation range for ultrasonic single mode image co-registration.Normal tissue glue ingredient containing carragheen, in two-dimensional ultrasound
It is in equal echo under imaging pattern.Tumour glue contains carragheen, acoustic contrast agent, is in Gao Huisheng under two-dimensional ultrasonic imaging mode.Disappear
Melt glue containing carragheen, Congo red, acoustic contrast agent, is in Gao Huisheng under two-dimensional ultrasonic imaging mode.Naked eyes gross examination of skeletal muscle sheet is imitative
Body Model, normal tissue glue are semi-transparent clear, and tumour glue is White-opalescent, and ablation glue is that red is opaque, and comparison is strong,
It is easily distinguishable.Therefore this imitative body Model can accurately assess tumour ablation range, be suitable as the teaching of tumour ablation technology
With training.
This acoustic feature of imitative body analog liver cancer under ultrasonic contrast, i.e. tumour glue are harmonious in two-dimensional ultrasonic imaging mode
It is in respectively first high echo and Gao Huisheng under wave contrast echo imaging pattern, then automatically becomes equal echo and echoless.Normal group
Glue is knitted under two-dimensional ultrasonic imaging mode and harmonic wave contrast echo imaging pattern always respectively in equal echo and echoless.More attach most importance to
It wants, nano-lipid microvesicle is evenly distributed, good dispersion, inside and outside imaging results are strong, stablizes in high/low frequency ultrasonic sound field
Property is more preferable, is more advantageous to user's ultrasonic contrast checking method and high/low frequency ultrasound guidance tumor aspiration biopsy and tumour disappears
Melt the practice for the treatment of
Nano-lipid microvesicle destroys in tumour rubber moulding type when this imitative body is due to ablation, makes tumour glue in two-dimensional ultrasound
It is in dynamic changing process in imaging pattern, preferably simulates the acoustic feature of tumour before and after clinical ablation, be conducive to user
Carry out the practice of skill.
This imitative body is generally being easy to distinguish tumor model, normal tissue model and ablation range, is conducive to user couple
The objective evaluation of tumour ablation treating effect.
The material of this imitative body is simple, is easily obtained, cheap, and preparation method is easy, and the consistency of finished product is controllable.
Detailed description of the invention
Fig. 1 present invention imitates the tumour glue of body Model and the center sectional view of normal tissue glue.Its center is diameter 3cm's
Positive sphere tumour blob of viscose, tumour glue are outside normal tissue glue.
The nanoscale lipid microbubble ultrasonic contrast agent of Fig. 2 various concentration prepare imitative body Model ultrasonic imaging effect (left side:
Two-dimensional ultrasonic imaging mode；Right side: harmonic contrast's ultrasound imaging mode).NB, nanobubble, nanometer microvesicle.
Fig. 3 imitates the ultrasonic imaging effect (left side: two-dimensional ultrasonic imaging mode of body Model in different time points；Right side: humorous
Wave contrast echo imaging pattern).
The two-dimensional ultrasonic imaging figure of Fig. 4 tumour glue.Wherein hyperechoic circular is tumour blob of viscose, in normal tissue
Implantation surgery suture (arrow is signified) is used as alignment mark in glue.
The three-dimensional volume figure of imitative body Model before Fig. 5 ablation.Ultrasonic scan imitates body Model and acquires image, and sketches the contours lesion.It is left
Upper, lower-left and bottom right are followed successively by the tumour glue image that coronal, crosscutting and sagittal section sketches the contours, and upper right is the three-dimensional of multiplanar reconstruction
Volume diagram.
The ultrasound figure of ablation stove of Fig. 6 tumour glue after melting.The echo of ablation stove is identical as normal tissue glue, ultrasound
It cannot be distinguished.Arrow meaning is ablation needle.
Fig. 7 ultrasound single mode image co-registration assessment tumour melts completely.A figure is the preoperative 3 d ultrasonography of tumour glue and art
Gained image after the real-time scanning ultrasound figure fusion of ablation stove afterwards.B figure is that the standard type section of ablation stove of the tumour glue after melting is seen,
Wherein blob of viscose red in normal tissue glue is the ablation glue of Reperfu- sion.
Fig. 8 ultrasound single mode image co-registration assessment tumour not exclusively melts.A figure be the preoperative 3 d ultrasonography of tumour glue with
Gained image after the postoperative real-time scanning ultrasound figure fusion of ablation stove.B figure is the standard type section of ablation stove of the tumour glue after melting
It sees, wherein blob of viscose white in normal tissue glue is tumour glue, and red blob of viscose is the ablation glue of Reperfu- sion, and boundary is obvious.
Specific embodiment
The invention will be further described below, but embodiments of the present invention are not limited to embodiment introduction below,
It is all that the scope that the present invention protects is regarded as according to variation or accommodation equivalent made by the principle of the present invention or theory.
The preparation of 1 nano-lipid microcapsular ultrasound contrast agent of embodiment
1. Distearoyl Phosphatidylethanolamine and dipalmitophosphatidic acid are molten by two palm phosphatidylcholine of phospholipid composition
In chloroform.Two palm phosphatidylcholine, the mass parts ratio of Distearoyl Phosphatidylethanolamine and dipalmitophosphatidic acid
For 18:1:3.5.
2. glycerol (v/v) and 2mg/mL pluronic containing 10% are added after chloroform volatilizees naturally and forms phospholipid membrane
The distilled water of F68, in 37 DEG C after aquation 1 hour, sound and vibration instrument probe is placed in gas-liquid intersection and carries out sound and vibration 5min, while being passed through eight
Fluoro-propane gas.
3. 50 × g of microvesicle liquid is centrifuged 5min, lower layer's milky white liquid tube is drawn, 805 × g is centrifuged 30min, abandons lower layer
Liquid, and be resuspended with PBS to get the nano-lipid microcapsular ultrasound contrast agent for being about 5.6mg/mL to phospholipid concentration.
Partial size through laser particle instrument detection nano-lipid microcapsular ultrasound contrast agent is 300~500nm.
The preparation of the imitative body Model before melting of embodiment 2
With electronic balance weigh carragheen 20g, stomach window acoustic contrast 1g is placed in a beaker, be added 60 DEG C of 1000mL
Distilled water.It places the beaker in 60 DEG C of thermostat water bath, stirs with glass rod to solute to be completely dissolved to form normal tissue matrix
Glue.Matrigel 38mL is taken with small beaker, 2mL milk is added and forms tumour gel matrix glue, adds nano-lipid microcapsular ultrasound and makes
Shadow agent stirs evenly to form tumour glue.The present embodiment prepares the concentration of nanoscale lipid microbubble ultrasonic contrast agent (with phosphatide respectively
Mass Calculation) be 0.0042%, 0.0056%, 0.007%, 0.0084% and 0.0098% (w/v) tumour rubber moulding type.It will swell
It after tumor glue is placed in the sphere mold that diameter is 3cm, is placed in ice water and is quickly cooled down 5min, up to tumour rubber moulding type after taking.
Tumour rubber moulding type is fixed in the mold for the cylindrical body that a height of 10cm diameter is 9cm with silk thread, implantation surgery seam
Line pours into normal tissue matrix sol solution as alignment mark.Mold is placed in -18 DEG C of refrigerators cooling 40min, can be obtained
Imitative body Model.Imitative body Model is splitted along tumour center, observes imitative body general form, as shown in Figure 1.
The ultrasonic imaging effect detection of imitative body Model before the ablation of embodiment 3
By the imitative body Model Contrast-enhanced ultrasonography of different study on nano-scale contrast agents concentration.The present embodiment Bai Sheng MyLab
Twice model clinical ultrasound diagnostic equipment and linear array probe detect imitative body, and imaging frequency range is 3~11MHz, and focus point is placed in
Tumour middle position, gain 0.5.It the use of mechanical index is 0.03 for harmonic contrast's ultrasound imaging mode, gain 0.38.It is imitative
Body Model 10min after taking out in refrigerator is defined as 0min, carries out two-dimensional ultrasound and harmonic wave to imitative body Model in different time points
Contrast echo imaging.
As a result as shown in Fig. 2, at the time point of 0min, the imitative body Model of the study on nano-scale contrast agents preparation of various concentration is presented
Different imaging effects.When nanoscale ultrasound contrast agents concentration is lower, tumour glue and normal tissue glue are almost in equal echo；With
Concentration increase to 0.0084% from 0.0056%, tumour glue and normal tissue glue are in two-dimensional ultrasonic imaging mode and harmonic contrast
Contrast enhanced under ultrasound imaging mode；When the content of study on nano-scale contrast agents in tumour glue is 0.007%, imitate swollen in body Model
Tumor glue imaging effect is best；And when the content of study on nano-scale contrast agents increases to 0.0098%, the tumour glue in imitative body Model exists
Visible strong echo light blob rear sound shadow, can not observe the tumour glue of ball-type form under ultrasound imaging mode.
Nanometer acoustic contrast agent is conducive to simulate tumour ultrasonic contrast for being added in tumour glue.0.0056~
Under 0.0084% content, two-dimensional ultrasound and the imaging of harmonic wave contrast echo can be achieved at the same time.The optimal effectiveness being wherein imaged occurs
It is 0.007% or so in microcapsular ultrasound contrast agent mass content.From Figure 2 it can be seen that being 0.007% in nanometer ultrasonic contrast agent content
When, imaging effect is the most suitable, and 0.006~0.008% is also acceptable.Imaging effect is both not at this time
Echo compares inadequate strong defect when 0.0056% or so, the lacking too long of imaging time when 0.0084% or so will not occurs
It falls into.Therefore the content (with phosphatide Mass Calculation) of nanometer acoustic contrast agent is preferably 0.0056~0.007% in tumour glue.It is more excellent
Select 0.005~0.009%, more preferable 0.0056~0.0084%, more preferable 0.006~0.008%, most preferably 0.007%.
It is noted that can satisfy imaging time substantially under 0.0056~0.0084% content and continue 30min
~240min (table 1).(Consideration is the dress of the instruments such as practice, puncture and the ablation of trainee in actual practice operation
Match and debug time), imaging time is 45~60min or so the most suitable.Seen from table 1, in nanometer ultrasonic contrast agent content
When being 0.007%, imaging effect is also proper.
The consistency that this imaging time optimization is optimized with imaging effect, which overlaps, selects nano-lipid grade ultrasound to make
Occur when shadow agent.From this perspective, nano-lipid acoustic contrast agent is selected to be also advantageous in the present invention program.
In addition, the ultrasonic imaging effect such as Fig. 3 institute changed over time with imitative body Model prepared by 0.007% nano-contrast agent
Show.With the growth of time, tumour glue and normal tissue glue are under two-dimensional ultrasonic imaging and harmonic wave contrast echo imaging pattern
Comparison weakens, until disappear, it is similar with the dynamic acoustic feature of clinical tumor ultrasonic contrast.
Further, the imitative body Model containing SonoVue or nano-lipid microcapsular ultrasound contrast agent is compared.Firstly,
From the point of view of Contrast-enhanced Ultrasound, nano-contrast agent echo uniformity is good, and regression time is long, and sound field stability is good.Secondly,
The content of phospholipid of SonoVue is 4.2mg/mL, and preferred concentration is 10% (i.e. 16.7mg phosphatide), and the cost for making imitative body is 427
Member/time；And the content of phospholipid of nano-lipid microcapsular ultrasound contrast agent is 5.6mg/mL, preferred concentration is 1.25% (i.e. 2.8mg phosphorus
Rouge), make imitative body cost be dozens of yuan/time, therefore more economical using study on nano-scale contrast agents, cost is lower.In conclusion receiving
Meter level acoustic contrast agent is particularly suited for the imitative body Model of simulation contrast-enhanced ultrasound of primary hepatocellular carcinoma performance.
Imitative body Model preparation temperature before embodiment 4 melts controls
When making imitative body Model, the temperature of solution is adjusted in the range of 50~70 DEG C in a certain range.As shown in table 1.
When temperature is 50 DEG C, occurs to subside for the echo of tumour glue the latest the time occurred, but solution is easy solidification at this time, therefore preferably
Temperature be 60 ° or so, such as 57~65 DEG C.The temperature that trainer can adjust water-bath according to their own needs carries out corresponding
Adjustment.
The tumour glue imaging time of different nanometer ultrasonic contrast agent contents under 1. different temperatures of table
The three-dimensional ultrasonography volume Image Acquisition of the ablation pre-neoplastic blob of viscose of embodiment 5
The present embodiment detects imitative body with Bai Sheng MyLab twice model clinical ultrasound diagnostic equipment, is equipped with three-dimensional hold
The correlations such as product probe (frequency range 1-8MHz is imaged in BC441), linear array probe (3~11MHz of frequency range is imaged in LA332), magnetic locator
Hardware and image fusion software.B-ultrasound examination is carried out using linear array probe first, as shown in figure 4, being then switched to three
Volume probe is tieed up, image is acquired, solid sketches the contours tumour, as shown in Figure 5.Using gained three-dimensional ultrasonography volume image as reference map
Picture, for image registration after melting.
The imaging effect of body Model is imitated after 6 ablation operation of embodiment and ablation
The present embodiment uses the Cool-tip cool-tip circulation ablation system of Radionics company, and radio-frequency ablation electrode is naked
Dew end is 3cm.RF ablation will be carried out inside radio frequency ablation needle insertion tumour glue, automatic catch melts 4-6 minutes.Ablation stove
Echo is identical as normal tissue glue, and ultrasound cannot be distinguished, as shown in Figure 6.
Embodiment 7 imitates body Model assessment ablation operation effect
Weighing carragheen 2g, stomach window 2g, Congo red 0.1g with electronic balance and being dissolved in 60 DEG C of 100mL of distilled water becomes
Sol solution is melted, and the beaker equipped with solution is placed in 60 DEG C of thermostat water bath.Tumour glue and peripheral part after ablation
Normal tissue glue is become liquid by thermal melting, this liquid is fully drawn out with syringe.Ablation sol solution is then injected into, after 5min
Solidification.
The present embodiment detects imitative body with Bai Sheng MyLab twice model clinical ultrasound diagnostic equipment, is equipped with three-dimensional hold
The correlations such as product probe (frequency range 1-8MHz is imaged in BC441), linear array probe (3~11MHz of frequency range is imaged in LA332), magnetic locator
Hardware and image fusion software.With three-dimensional volume probe scanning ablation stove, and real-time ultrasonoscopy data are left and taken, utilizes ultrasound
Single mode image co-registration, using the sutures that are placed in advance as alignment mark, by the real-time scanning image and art after ablation
Preceding three dimensional volumetric image compares, and whether observation ablation glue image is completely covered tumour glue image, so that evaluating ablation is
It is no complete.As shown in Figure 7 A, this ablation is complete.As shown in Figure 8 A, this ablation is incomplete, and measurement is aobvious on the ultrasound image
Show, not up to the maximum distance of tumor boundaries is 4mm.
Cut sample after the evaluation of ultrasonic single mode image co-registration, visually observe ablation effect, and with ultrasonic single mode image
Fusion rules Comparative result.If red ablation glue (Fig. 7 B) is only observed in ablation completely；If ablation is not exclusively,
The tumour glue for having partial white is remaining (Fig. 8 B and 8C).In addition, generally measuring display, the not up to maximum of tumor boundaries
Distance is 5mm (Fig. 8 C), almost the same with ultrasonic single mode image co-registration assessment result.As it can be seen that the model is suitable for practice
Ultrasonic single mode image co-registration assesses tumour ablation range, and can generally be verified.
The comparative experiments of 8 dyestuff of embodiment
The dyestuff of ablation glue has Congo red, methyl blue, carbon black, malachite green, eosin, rose red b, tonyred respectively.Institute
Manufactured model places 1 hour and 24 as a child observation infiltration situations respectively.The results are shown in Table 2.
Table 2 melts model character pair ratio when glue uses different dyes
As can be seen from the results, Congo red effect is best, is much superior to other dyestuffs, and edge is very clear, and dyestuff is complete
It is complete impermeable to normal tissue glue, it melts glue and normal tissue glue contrast very strongly (Fig. 7 B and 8B), places 24 hours very
To after week age, good state is still maintained.
Methyl blue effect is taken second place, and is placed the basic discrimination of back boundary energy in 1 hour, cannot then be met the requirements after placing 24 hours；
Carbon black effect is taken second place, and is placed 1 hour back boundary and is obscured, 24 as a child, diffuses to the dyestuff of normal tissue glue due to further expanding
It dissipates so that more shallow when the dye colour of normal tissue glue was than 1 hour, it can discrimination boundary to a certain extent.
When using malachite green, eosin, rose red b, the color for melting glue seriously diffuses to normal tissue glue, module of boundary
Paste is not able to satisfy the demand of ultrasound training and judgement completely.
The above embodiment is a preferred embodiment of the present invention, but embodiments of the present invention are not by above-described embodiment
Limitation, other any changes, modifications, substitutions, combinations, simplifications made without departing from the spirit and principles of the present invention,
All without departing from the contents of the present invention, it is included in protection scope of the present invention.
Claims (30)
1. a kind of imitative body Model for ultrasonic single mode image co-registration assessment tumour ablation range, it is characterised in that containing being used for
The tumour glue of tumour and the normal tissue glue for simulating normal surrounding tissue are simulated, contains matrigel in normal tissue glue, institute
Matrigel is stated containing carragheen 0.5%~5% (w/v), stomach window acoustic contrast 0.05% to 0.2% (w/v)；The tumour glue contains
There is microcapsular ultrasound contrast agent, content, for 0.005%~0.009% (w/v), also contains tumor stroma glue with phosphatide Mass Calculation,
The tumor stroma glue contains carragheen 0.5%~5% (w/v), stomach window acoustic contrast 0.05% to 0.2% (w/v)；
And the imitative body Model is accompanied by after ablation for injecting the ablation glue formula in ablation space, and the ablation glue formula contains
Carragheen 0.5%~5% (w/v), stomach window acoustic contrast 0.5%~5% (w/v) and dyestuff 0.03~0.1% (w/v).
2. imitative body Model as described in claim 1, it is characterised in that the microcapsular ultrasound contrast agent is that a nanometer microcapsular ultrasound is made
Shadow agent.
3. imitative body Model as described in claim 1, it is characterised in that the microcapsular ultrasound contrast agent is protide, carbohydrate, non-
Nonionic surfactant class, lipid or polymeric vesicle acoustic contrast agent.
4. imitative body Model as claimed in claim 3, it is characterised in that the microcapsular ultrasound contrast agent is made for lipid microvesicle ultrasound
Shadow agent.
5. imitative body Model as claimed in claim 4, it is characterised in that the lipid microbubble ultrasonic contrast agent is that nano-lipid is micro-
Steep acoustic contrast agent.
6. imitative body Model as claimed in claim 5, it is characterised in that the partial size of the nano-lipid microcapsular ultrasound contrast agent is
300~500nm.
7. imitative body Model as claimed in claim 6, it is characterised in that in the tumor stroma glue also containing mammal milk/
Milk powder.
8. imitative body Model as claimed in claim 7, it is characterised in that the mammal milk/milk powder is milk/milk milk
Powder.
9. imitative body Model as claimed in any one of claims 1 to 6, it is characterised in that the dyestuff be Congo red, methyl blue or
Carbon black.
10. imitative body Model as claimed in claim 9, it is characterised in that it is characterized in that the dyestuff is Congo red.
11. a kind of formula of the imitative body Model for ultrasonic single mode image co-registration assessment tumour ablation range, contains tumour glue
Formula, tumour glue formula contain microcapsular ultrasound contrast agent content with phosphatide Mass Calculation be 0.005%~0.009% (w/v), card
Draw glue 0.5%~5% (w/v), stomach window acoustic contrast 0.05% to 0.2% (w/v)；Except this, also containing ablation glue formula, institute
It states ablation glue formula and contains carragheen 0.5%~5% (w/v), stomach window acoustic contrast 0.05% to 5% (w/v) and dyestuff
0.03~0.1% (w/v).
12. formula as claimed in claim 11, it is characterised in that the tumour glue formula also contains mammal milk/milk powder.
13. formula as claimed in claim 12, it is characterised in that the mammal milk/milk powder is milk/milk powder.
14. formula as claimed in claim 11, it is characterised in that the dyestuff is Congo red, methyl blue or carbon black.
15. formula as claimed in claim 14, it is characterised in that the dyestuff is Congo red.
16. the formula as described in claim 11-15 any one, it is characterised in that the content of the microcapsular ultrasound contrast agent with
Phosphatide Mass Calculation is 0.0056~0.0084% (w/v).
17. formula as claimed in claim 16, it is characterised in that the microcapsular ultrasound contrast agent is a nanometer microvesicle ultrasound angiography
Agent.
18. formula as claimed in claim 17, it is characterised in that the tumour glue formula also contains 2%~10% (v/ of milk
v)。
19. a kind of method for carrying out ultrasonic single mode image co-registration assessment tumour ablation range using imitative body Model, feature exist
In the following steps are included:
S1. body Model is imitated before preparing ablation；
S11. prepare normal tissue sol solution and tumour sol solution；Wherein tumour sol solution contain microcapsular ultrasound contrast agent content with
Phosphatide Mass Calculation is 0.005%~0.009% (w/v), carragheen 0.5%~5% (w/v), stomach window acoustic contrast
0.05% to 0.2% (w/v)；Normal tissue sol solution contains matrigel, the matrigel 0.5%~5% (w/ containing carragheen
V), stomach window acoustic contrast 0.05% to 0.2% (w/v)；
S12. tumour sol solution is injected into tumour sealing rubber die, cooled and solidified is at tumour rubber moulding type；
S13. tumour rubber moulding type is fixed in imitative mould, pours into normal tissue sol solution, then cooled and solidified into imitative body Model；
S2. after being melted, melted liquid will be melted and be sucked out, ablation glue is reinjected；The ablation glue contains dyestuff 0.03
~0.1% (w/v), carragheen 0.5%~5% (w/v), stomach window acoustic contrast 0.05% to 5% (w/v)；
S3. after gelling to be ablated is solid, by melting the coverage area of glue for assessing ablation range.
20. method as claimed in claim 19, it is characterised in that the dyestuff is Congo red.
21. method as claimed in claim 19, it is characterised in that the tumour sol solution is carragheen, stomach window acoustic contrast
Agent, nanometer microcapsular ultrasound contrast agent are dissolved in water acquisition, and the temperature of solution is maintained 50 DEG C~70 DEG C；
The normal tissue sol solution is that carragheen stomach function regulating window acoustic contrast is dissolved in water acquisition, and the temperature of solution is tieed up
It holds at 50 DEG C~70 DEG C；
The ablation sol solution is that carragheen, stomach window acoustic contrast and dyestuff are dissolved in water acquisition, and by the temperature of solution
Maintain 50 DEG C~70 DEG C.
22. method as claimed in claim 21, it is characterised in that the tumour sol solution is also added with milk or milk powder.
23. method as claimed in claim 21, it is characterised in that the temperature of the tumour sol solution is maintained 60 DEG C.
24. method as claimed in claim 21, it is characterised in that the temperature of the normal tissue sol solution maintains 60 DEG C.
25. method as claimed in claim 21, it is characterised in that the temperature of the ablation sol solution maintains 60 DEG C.
26. the method as described in claim 19-25 any one, it is characterised in that the content of the microcapsular ultrasound contrast agent with
Phosphatide Mass Calculation is 0.0056%~0.0084% (w/v).
27. method as claimed in claim 26, it is characterised in that the microcapsular ultrasound contrast agent is a nanometer microvesicle ultrasound angiography
Agent.
28. the method as described in claim 19-25 any one, it is characterised in that the tumour sol solution is also dynamic containing lactation
Object milk 2%~10% (v/v).
29. method as claimed in claim 28, it is characterised in that the mammal milk is milk.
30. method as claimed in claim 29, it is characterised in that the microcapsular ultrasound contrast agent is a nanometer microvesicle ultrasound angiography
Agent.
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| CN111724666A (en) * | 2020-07-01 | 2020-09-29 | 天津市第三中心医院 | A imitative body model for simulating clinical tumour heat ablation treatment |
| CN113593386A (en) * | 2021-07-01 | 2021-11-02 | 中山大学附属第一医院 | Multi-modal phantom model and preparation method and application thereof |
| CN117379170B (en) * | 2023-12-13 | 2024-04-12 | 北京北琪医疗科技股份有限公司 | Special phantom capable of displaying radio frequency thermal field and preparation method and application thereof |
| CN117683273B (en) * | 2023-12-18 | 2024-07-23 | 北京曦健科技有限公司 | Bionic body model and preparation method thereof |
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