Peripheral vascular embolization efficiency evaluation method, system and application

Abstract

The application discloses a peripheral vascular embolization efficiency evaluation method, and comprises the following steps: ear general appearance, ear angiography, pathological staining, and rabbit ear artery embolization efficiency score. The application further discloses a peripheral vascular embolization efficiency evaluation system. The application discloses a quantitative index for judging embolization efficiency, and comprehensively evaluates the embolization effect from macro to micro through three dimensions, three levels, from general appearance to angiography to pathological evaluation, so that the evaluation standard is more perfect.

Description

Technical Field

[0001] This invention belongs to the field of interventional medicine and peripheral vascular disease, and relates to a method, system and application for evaluating the efficacy of peripheral vascular embolization. Background Technology

[0002] Interventional endovascular embolization, also known as superselective intra-arterial embolization, is an important technique in interventional endovascular therapy. This technique evolved from catheter technology developed in the 1950s. With the advancement of X-ray imaging technology, especially the emergence of digital subtraction angiography (DSA) in the 1970s, doctors can insert specialized catheters into small arteries in almost any lesion area under fluorescent guidance. This results in clearer imaging of the angiographic area, less trauma, more targeted and effective treatment, and the catheters can be reused without leaving severe soft or hard tissue deformities, demonstrating broad development prospects. Because interventional endovascular embolization is performed entirely within the blood vessel, the procedure is highly targeted. The objectives of the procedure are divided into three categories: bleeding control, preoperative adjuvant embolization, and therapeutic embolization. Based on the methods and embolization materials used in treatment, surgical indications can be divided into three categories: some difficult-to-control acute bleeding, diseases where bleeding is difficult to control surgically, and benign and malignant lesions unsuitable for resection: 1. Various difficult-to-control non-hematologic bleeding, such as gingival bleeding from jaw arteriovenous malformations, massive bleeding in late-stage malignant tumors, and epistaxis. 2. High-flow-rate vascular malformations, such as arteriovenous malformations, congenital or traumatic arteriovenous fistulas. 3. Benign tumors with rich blood supply, such as giant hemangiomas, neurofibromas, carotid body tumors, nasopharyngeal angiofibromas, and glomus jugulare tumors. 4. Malignant tumors that surround or erode important blood vessels; embolization combined with drug treatment can control and slow the growth rate of the tumor and prevent bleeding.

[0003] Drugs or devices that exert an embolic effect during embolization are called embolic materials. Common embolic materials can be divided into solid embolic materials and liquid embolic materials, each with different properties. Solid embolic materials include polyvinyl alcohol (PVA) particles, gelatin sponge particles, and coils, while liquid embolic materials include ethanol, iodized oil, n-butyl-2-cyanoacrylate (NBCA), and Onyx glue. Although many embolic materials have been used clinically, they often have some drawbacks during use. Therefore, the research and improvement of embolic materials is an area that urgently needs in-depth development. In the research of embolic materials, the construction of animal models of peripheral vascular embolization and the evaluation criteria for embolic efficacy have not yet been standardized, which has limited the development of embolic materials to some extent. Summary of the Invention

[0004] This invention represents an innovative attempt to construct an animal model of peripheral vascular embolization using ethanol injection, and for the first time systematically evaluates the degree of embolization in the central auricular artery of rabbits from multiple perspectives. Because ethanol is rapidly metabolized in vivo, it does not remain in the blood vessels and thus does not affect the assessment of the embolization effect. This invention uses different concentrations and doses of ethanol as the ethanol injection solution for embolization in the rabbit auricular artery. In a single operation, experimental rabbits are selected, and a controlled administration rate is maintained during a single injection into the central auricular artery. Post-operatively, the experimental animals are resuscitated and their long-term survival is observed. The embolization effect of each group is comprehensively evaluated from three aspects: gross appearance, angiography, and pathological examination.

[0005] The purpose of this invention is to provide a novel method for evaluating the efficacy of peripheral vascular embolization. Firstly, changes in the gross appearance of the ear can reflect the blood supply to the ear tissues. Secondly, ear angiography allows for direct observation of the degree of vascular occlusion in the ear. Finally, pathological examination of the embolization site can more effectively verify the embolization effect on the blood vessels and surrounding tissues. Evaluating ear embolization in experimental animals from these three levels enables quantitative analysis of the peripheral vascular embolization efficacy of ethanol injection, making the evaluation process more accurate and standardized.

[0006] This invention proposes a method for constructing an animal model of peripheral vascular embolism, the method comprising the following steps:

[0007] (1) Animals were given an intramuscular injection of a mixture of Shutai 50 and Lumian Ning injection, followed by tracheal intubation.

[0008] (2) Insert an indwelling needle into the central auricular artery of one ear of the animal after the intramuscular injection in step (1) and fix it in place;

[0009] (3) Perform basic preoperative angiography;

[0010] (4) Inject the embolic agent through the indwelling needle;

[0011] (5) After the injection, another angiography of the embolized ear was performed to obtain an animal model of embolized peripheral blood vessels.

[0012] In step (1), the animal is a male New Zealand white rabbit: approximately 100 days old and weighing approximately 3.5-4.0 kg.

[0013] In step (1), the dosage of Shutai 50 is 0.3-0.4 ml; preferably, it is 0.36 ml.

[0014] In step (1), the dosage of Lu Mian Ning injection is 0.1-0.2 ml; preferably, it is 0.14 ml.

[0015] In step (1), the diameter of the cannula is 2.5 mm.

[0016] In step (2), the indwelling needle is a 22G or 24G indwelling needle.

[0017] In step (3), the application 300 lines of basic preoperative angiography.

[0018] In step (4), the embolic agent is 0.5-1.5 mL of 80% ethanol; preferably, it is 0.5 mL of 80% ethanol, 1 mL of 80% ethanol, or 1.5 mL of 80% ethanol.

[0019] In step (4), the injection rate is 15-25 mL / h; preferably, it is 20 mL / h.

[0020] In one specific embodiment, the method for constructing the animal model of peripheral embolism includes the following steps:

[0021] (1) Select 12 male New Zealand white rabbits: approximately 100 days old and weighing approximately 3.5-4.0 kg.

[0022] (2) Animals were given a total of 0.5 ml of a mixture of Shutai 50 (0.36 ml) and Lumian Ning injection (0.14 ml) intramuscularly, followed by tracheal intubation (2.5 mm diameter); isoflurane or sevoflurane was used for continuous inhalation anesthesia during the operation.

[0023] (3) Insert a 22G or 24G indwelling needle into the central auricular artery on one side and fix it in place. Use a II-lead electrocardiogram to continuously monitor heart rhythm and heart rate. Place a blood oxygen probe on the rabbit's tail to monitor blood oxygen changes throughout the process.

[0024] (4) Application 300 lines of basic preoperative angiography.

[0025] (5) The experimental animals were divided into 4 groups of 3 animals each: 1. Anhydrous ethanol positive control group (1 mL anhydrous ethanol was injected); 2. 80% ethanol low-dose group (0.5 mL 80% ethanol was injected); 3. 80% ethanol medium-dose group (1 mL 80% ethanol was injected); 4. 80% ethanol high-dose group (1.5 mL 80% ethanol was injected).

[0026] (6) Administer the above dose of ethanol injection solution through an indwelling needle at a rate of 20 mL / h.

[0027] (7) Two hours after the injection, angiography was performed again on the embolized side of the ear. The experimental rabbits were then resuscitated and returned to their cages for survival observation.

[0028] (8) Ibuprofen and cefoxitin sodium are used for postoperative analgesia and anti-inflammation, respectively.

[0029] This invention proposes an animal model of embolized peripheral blood vessels constructed using the above method.

[0030] This invention proposes the application of the aforementioned animal model of peripheral vascular embolization in the evaluation of peripheral vascular embolization efficacy.

[0031] This invention also proposes a method for evaluating the efficacy of peripheral vascular embolization, comprising the following steps:

[0032] Step (1) General appearance of the ear

[0033] Before the operation, and at 3, 7, and 14 days after the operation, photographs of the front and back of the normal and embolized sides of the ears of the experimental rabbits were taken to record the dynamic changes in the appearance of the ears after the embolization of the ear artery.

[0034] The specific procedure for the surgery was as follows: Twelve male New Zealand white rabbits, approximately 100 days old and weighing approximately 3.5-4.0 kg, were selected. The animals were administered a 0.5 ml intramuscular injection of a mixture of 0.36 ml of chlorpheniramine maleate and 0.14 ml of chlorpheniramine maleate injection, followed by endotracheal intubation (2.5 mm diameter). Continuous inhalation anesthesia with isoflurane or sevoflurane was used. A 22G or 24G indwelling needle was inserted into the central auricular artery of one ear and secured. Heart rhythm and rate were continuously monitored using a lead II electrocardiogram. A pulse oximeter was placed in the rabbit's tail to monitor blood oxygenation changes throughout the procedure. 300 basic preoperative angiography lines were performed. The experimental animals were divided into four groups of three: 1. Anhydrous ethanol positive control group (1 mL anhydrous ethanol injected); 2. Low-dose 80% ethanol group (0.5 mL 80% ethanol injected); 3. Medium-dose 80% ethanol group (1 mL 80% ethanol injected); 4. High-dose 80% ethanol group (1.5 mL 80% ethanol injected). The ethanol was injected at a rate of 20 mL / h through an indwelling needle. Two hours after injection, a second angiography of the embolized side of the ear was performed. The rabbits were then resuscitated and returned to their cages for survival observation. Ibuprofen and cefoxitin sodium were used for postoperative analgesia and anti-inflammation, respectively.

[0035] Step (2) Ear angiography

[0036] Long-term embolization effect: After surgery, the experimental animals were revived and continued to be fed. Angiography was performed again on day 14. The angiography was compared with the preoperative angiography to calculate the extent of vascular occlusion.

[0037] The calculation method involves using ImageJ software to process the grayscale image of the ear angiography, and the vascular occlusion rate is calculated as: preoperative angiography vessel area / postoperative angiography vessel area 14 days after surgery × 100%.

[0038] Step (3) Pathological staining

[0039] The central auricular artery, ear tissue, and marginal auricular vein at the site of embolism were excised, with normal central auricular artery, ear tissue, and marginal auricular vein from the contralateral side serving as controls. Paraffin sections were prepared and stained with hematoxylin and eosin (HE) and Masson staining. The extent of thrombus formation within the vessel lumen and the degree of pervascular tissue damage were analyzed using ImageJ software.

[0040] Step (4) Rabbit ear artery embolization efficacy scoring table

[0041] After obtaining the gross appearance of rabbit ears, angiography and pathological examination results, the arterial embolization efficacy of the reagent was evaluated from three dimensions. Table 1 below is used as the standard to score each experimental rabbit, and finally statistical analysis is performed.

[0042] Table 1 Arterial Embolism Scoring Criteria (Total 30 points) Table 1-1 Ear Appearance Scoring Criteria

[0043]

[0044]

[0045] Table 1-2 Angiography Scoring Table

[0046]

[0047] Table 1-3 Pathological Examination Scoring Table

[0048]

[0049] Based on the above methods for evaluating the efficacy of peripheral vascular embolization, this invention also proposes a system for evaluating the efficacy of peripheral vascular embolization, the system comprising:

[0050] The imaging and recording module is used to take pictures of the normal side and the embolized side of the ear and record the dynamic changes in the appearance of the ear after the ear artery embolism;

[0051] The angiography calculation module is used for angiography, comparing it with preoperative angiography to calculate the extent of vascular occlusion.

[0052] The staining analysis module is used to stain paraffin sections to analyze the extent of thrombus formation in the blood vessel lumen and the extent of damage to the perivascular tissue.

[0053] The efficacy scoring module is used to evaluate the arterial embolization efficacy of the reagent from three dimensions, score each animal, and finally perform statistical analysis.

[0054] The present invention also proposes the application of the peripheral vascular embolization efficacy evaluation system in the evaluation of embolization efficacy in solid organs.

[0055] The beneficial effects of this invention include:

[0056] The rabbit ear has a relatively simple anatomical and vascular structure, making its embolization effect readily apparent. Rabbits are an ideal animal for constructing a peripheral embolization efficacy evaluation system; the central auricular artery is an ideal drug administration site; and ear tissue is an ideal observation site. Therefore, this invention provides a reliable animal model for peripheral vascular embolization. Previous reports have shown inconsistent methods for quantitative analysis after embolization to assess the embolic efficacy of embolic agents. This invention provides a quantitative index for evaluating embolization efficacy, comprehensively assessing the embolization effect from three dimensions and three levels—from gross appearance to angiography to pathological evaluation—from macroscopic to microscopic perspectives, thus improving the evaluation criteria. Attached Figure Description

[0057] Figure 1 A schematic diagram of cannulation of the central artery in a rabbit ear and administration of ethanol injection.

[0058] Figure 2 Figure 1 shows an experiment involving catheterization of the central artery in a rabbit ear and administration of ethanol injection.

[0059] Figure 3 Photos of the front and back of the rabbit's embolized ear.

[0060] Figure 4 A statistical chart showing the gross appearance score of the embolized side ear of a rabbit.

[0061] Figure 5 Image of blood vessels in the embolized side of a rabbit's ear.

[0062] Figure 6 Statistical chart of angiography scores for the embolized side ear vessels of a rabbit.

[0063] Figure 7 The pathological staining images of the tissue and vein of the embolized lateral auricular artery in a rabbit were obtained.

[0064] Figure 8 A statistical chart of pathological scores for the embolized side of the ear in rabbits.

[0065] Figure 9 A statistical chart showing the overall score of embolization efficacy in rabbits with lateral ear embolization. Detailed Implementation

[0066] The present invention is further illustrated below with reference to embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention.

[0067] Experimental materials:

[0068] Twelve male New Zealand white rabbits, approximately 100 days old and weighing 3.5-4.0 kg, were selected. The animals were fasted from food and water the night before surgery. They were administered a 0.5 ml intramuscular injection of a mixture of 0.36 ml of chlorpheniramine maleate and 0.14 ml of chlorpheniramine maleate injection, followed by endotracheal intubation (2.5 mm diameter). Continuous inhalation anesthesia with isoflurane or sevoflurane was used during the procedure. A 22G or 24G indwelling needle was inserted into the central auricular artery of one ear and secured. Heart rhythm and rate were continuously monitored using a lead II electrocardiogram. A pulse oximeter was placed in the rabbit's tail to monitor blood oxygenation changes throughout the procedure. 300 basic preoperative angiography procedures were performed. The experimental animals were divided into four groups of three: 1. Anhydrous ethanol positive control group (1 mL anhydrous ethanol injected); 2. Low-dose 80% ethanol group (0.5 mL 80% ethanol injected); 3. Medium-dose 80% ethanol group (1 mL 80% ethanol injected); 4. High-dose 80% ethanol group (1.5 mL 80% ethanol injected). The above doses of ethanol were then injected via an indwelling needle at a rate of 20 mL / h. Two hours after injection, a second angiography of the embolized side of the ear was performed. The rabbits were then resuscitated and returned to their cages for survival observation. Ibuprofen and cefoxitin sodium were used for postoperative analgesia and anti-inflammation, respectively. Angiography was performed again 14 days postoperatively to compare the pre- and post-injection images and assess the degree of vascular occlusion. After angiography, the animals were euthanized, and tissue samples were collected for pathological sectioning and staining.

[0069] Example 1

[0070] Step 1: Rabbit ear artery catheterization and injection method

[0071] The diagram shows the procedure for placing a central artery cannula in a rabbit ear and administering ethanol injection. Figure 1 As shown, the experimental diagram is as follows. Figure 2 As shown.

[0072] Step 2: Dynamic changes and scoring of rabbit ear appearance

[0073] Before ethanol injection (Pre): The rabbit ears are white or light pink in color, and the blood vessels in the rabbit ears are evenly distributed;

[0074] On the third day after ethanol injection (3D): In the anhydrous ethanol group (EtOH), the plugged area in the rabbit's ear was purple, accounting for 25-50% of the total area of ​​the rabbit's ear; in the low-dose 80% ethanol group (LD sample), the plugged area in the rabbit's ear was purple, accounting for 25-50% of the total area of ​​the rabbit's ear; in the medium-dose 80% ethanol group (MD sample), the plugged area in the rabbit's ear was purple, accounting for 25-50% of the total area of ​​the rabbit's ear; and in the high-dose 80% ethanol group (HD sample), the plugged area in the rabbit's ear was dark brown, accounting for 50-75% of the total area of ​​the rabbit's ear.

[0075] On the seventh day after ethanol injection (7D): In the anhydrous ethanol group (EtOH), the rabbit ear plugging area was dark brown, accounting for 25-50% of the total rabbit ear area; in the low-dose 80% ethanol group (LD sample), the rabbit ear plugging area was purple, accounting for 25-50% of the total rabbit ear area; in the medium-dose 80% ethanol group (MD sample), the rabbit ear plugging area was light brown, accounting for 25-50% of the total rabbit ear area; and in the high-dose 80% ethanol group (HD sample), the rabbit ear plugging area was dark brown, accounting for 50-75% of the total rabbit ear area.

[0076] On day 14 (14D) after ethanol injection: In the anhydrous ethanol group (EtOH), the ear plugging area was blackish-brown, covering 25-50% of the total ear area; in the low-dose 80% ethanol group (LD sample), the ear plugging area was purple, covering 25-50% of the total ear area; in the medium-dose 80% ethanol group (MD sample), the ear plugging area was dark brown, covering 25-50% of the total ear area; and in the high-dose 80% ethanol group (HD sample), the ear plugging area was blackish-brown, covering 50-75% of the total ear area. Figure 3 )

[0077] like Figure 4 As shown, the scores for the overall appearance of the rabbit ears in each group exhibit a gradient change.

[0078] Step 3: Rabbit ear angiography and scoring

[0079] On day 14 (14D) after ethanol injection: In the anhydrous ethanol group (EtOH), the vascular occlusion area of ​​rabbit ears accounted for 25-50% of the total area; in the low-dose 80% ethanol group (LD sample), the embolized area of ​​rabbit ears was purple, accounting for 1-25% of the total ear area; in the medium-dose 80% ethanol group (MD sample), the embolized area of ​​rabbit ears was dark brown, accounting for 25-50% of the total ear area; and in the high-dose 80% ethanol group (HD sample), the embolized area of ​​rabbit ears was blackish-brown, accounting for 50-75% of the total ear area. Figure 5 )

[0080] like Figure 6 As shown, the angiography scores of rabbit ears in each group showed a gradient change.

[0081] Step 4: Pathological examination and scoring of rabbit ear arteries, tissues, and veins.

[0082] On day 14 (14D) after ethanol injection: In the anhydrous ethanol group (EtOH), the central auricular artery of rabbits was completely occluded, and dry gangrene occurred in the periarterial tissue and the peripheral ear tissue; in the low-dose 80% ethanol group (LD sample), the central auricular artery of rabbits was not completely occluded, and dry gangrene did not occur in the periarterial tissue or the peripheral ear tissue; in the medium-dose 80% ethanol group (MD sample), the central auricular artery of rabbits was completely occluded, and dry gangrene occurred in the periarterial tissue but not in the peripheral ear tissue; in the high-dose 80% ethanol group (HD sample), the central auricular artery of rabbits was completely occluded, and dry gangrene occurred in the periarterial tissue and the peripheral ear tissue. Figure 7 )

[0083] like Figure 8 As shown, the pathological scores of rabbit ears in each group showed a gradient change.

[0084] Step 5: Total score of rabbit ear artery embolization efficacy

[0085] like Figure 9 As shown, the total score of rabbit ear artery embolization efficacy at the observation endpoint (14D) exhibited a gradient change. The high-dose 80% ethanol group (HD sample) showed statistically significant differences in total score compared to all other experimental groups (P<0.05). These results indicate that the peripheral vascular embolization efficacy score in this invention can differentiate the embolization capacity of ethanol samples with different doses and concentrations.

[0086] The scope of protection of this invention is not limited to the above embodiments. Any variations and advantages that can be conceived by those skilled in the art without departing from the spirit and scope of the inventive concept are included in this invention and are protected by the appended claims.

Claims

1. A system for evaluating the efficacy of peripheral vascular embolization, characterized in that, The system employs a method for evaluating the efficacy of peripheral vascular embolization; the embolic agent used in peripheral vascular embolization is 80% ethanol; the dosage of the embolic agent is 0.5-1.5 mL; the injection rate of the embolic agent is 15-25 mL / h; the method includes the following steps: Step (1) General appearance of the ear Before the operation, and at 3, 7 and 14 days after the operation, photographs of the front and back of the normal and embolized sides of the ears of the experimental rabbits were taken to record the dynamic changes in the appearance of the ears after the embolization of the ear artery. Step (2) Ear angiography The experimental animals were revived after surgery and continued to be fed. Angiography was performed again on day 14. The angiography was compared with the preoperative angiography to calculate the extent of vascular occlusion. In step (2), the calculation method is as follows: vascular occlusion rate = preoperative angiographic vascular area / postoperative angiographic vascular area 14 days after surgery × 100%; Step (3) Pathological staining The central auricular artery, ear tissue, and marginal auricular vein of the embolized portion were excised, with the normal central auricular artery, ear tissue, and marginal auricular vein of the contralateral side serving as controls; paraffin sections were prepared and subjected to HE and Masson staining; the extent of thrombus formation in the vascular lumen and the extent of perivascular tissue damage were analyzed using ImageJ software; Step (4) Rabbit ear artery embolization efficacy scoring table After obtaining the gross appearance of rabbit ears, angiography and pathological examination results, the arterial embolization efficacy of the reagent was evaluated from three dimensions, and finally statistical analysis was performed. The evaluation criteria are shown in the table below. Table 1-1 Ear Appearance Scoring Table Table 1-2 Angiography Scoring Table Table 1-3 Pathological Examination Scoring Table 。 2. The system as described in claim 1, characterized in that, The experimental rabbits were male New Zealand White rabbits, 100 days old, weighing 3.5-4.0 kg.

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