WO2024232083A1 - Calcification model, blood vessel model, and test system - Google Patents

Abstract

A blood vessel model (200) comprises a simulated blood vessel (210) and a calcification model (100). The simulated blood vessel (210) is provided with: a simulated non-lesion part (212) that simulates a non-lesion portion of a blood vessel; and a simulated narrow part (214) that simulates a narrowed bent part having an inside diameter less than that of the non-lesion portion. The calcification model (100) is provided with: a lesion part (102) that is attached to a simulated constriction part (214), the lesion part (102) containing at least gypsum and simulating an eccentric calcified lesion protruding into a blood vessel; and a support part (104) that protrudes toward the opposite side from the lesion part (102) and supports the lesion part (102).

Description

Calcification model, blood vessel model, and test system

The present invention relates to a calcification model that mimics a lesion, a blood vessel model incorporating the calcification model, and a test system for evaluating the performance of a treatment device that removes the lesion.

　Treatment methods for calcified lesions in the coronary artery include balloon dilation and atherectomy, which removes or crushes the calcified lesions. However, because the lesion morphology (location, thickness, shape, etc.) differs from patient to patient, it is necessary to select an appropriate treatment device. To do this, it is effective to quantitatively evaluate the performance of treatment devices for various lesion morphologies ex vivo. For example, Patent Document 1 discloses a technology for creating a circumferential (cylindrical) calcification model in which calcified lesions are distributed around the entire circumference of the blood vessel, and evaluating the balloon dilation performance for this calcification model.

JP 2020-190583 A

However, unlike circumferential lesions, eccentric lesions that are concentrated in one part of the blood vessel inner wall are difficult to expand with a balloon. In addition, when treating lesions that exist in bent parts of blood vessels, various issues arise, such as poor passability of the treatment device and an increased risk of blood vessel perforation. For this reason, it is becoming increasingly important to evaluate the performance of treatment devices and select the appropriate treatment device.

The present invention was made in consideration of the above problems, and aims to provide a calcification model, a blood vessel model, and a test system that are more useful for evaluating the performance of a treatment device for intravascular lesions outside of a body.

The calcification model of the present invention comprises at least gypsum and has a lesion that mimics an eccentric calcification lesion protruding into a blood vessel.

The blood vessel model according to the present invention comprises a simulated blood vessel having a simulated non-lesioned portion simulating a non-lesioned portion of a blood vessel and a simulated stenosis portion simulating a stenosis portion having an inner diameter smaller than that of the non-lesioned portion, and the above-mentioned calcification model attached to the simulated stenosis portion.

The test system according to the present invention is a test system for evaluating the performance of a treatment device for removing or crushing calcified lesions in blood vessels, and includes a simulated blood vessel having a simulated non-lesioned portion simulating a non-lesioned portion of the blood vessel and a simulated stenosis portion simulating a stenosis portion having a smaller inner diameter than the non-lesioned portion, a calcification model that is attached to the simulated stenosis portion and contains at least gypsum, simulating an eccentric calcified lesion protruding into the blood vessel, and a path for the treatment device to access the calcification model.

The present invention makes it possible to evaluate the lesion removal or lesion crushing ability of a treatment device in vitro using a calcification model that mimics an eccentric calcified lesion.

FIG. 1 is a schematic diagram of a calcification model according to an embodiment of the present invention, which mimics an eccentric calcified lesion. FIG. 1 is a schematic diagram showing a base used when preparing a silicone mold of a calcification model. This is an example of a silicone mold that was actually produced. This is an example of an actual calcification model. FIG. 1 is a schematic diagram of a vascular cast in the shape of a coronary artery. FIG. 2 is a schematic diagram of a coronary artery model incorporating the calcification model shown in FIG. 1 . FIG. 1 is a schematic diagram of an aortic model. FIG. 1 is a schematic diagram of a test system combining a coronary artery model and an aorta model. FIG. 1 is a schematic diagram showing an example of application of a treatment device to a test system. FIG. 13 is a schematic diagram showing the behavior of the treatment device in removing a lesion in a calcification model. FIG. 13 is a schematic diagram of a calcification model in which a calcified lesion is present on the outer diameter side of a bent part of a blood vessel. FIG. 4 is a schematic diagram for explaining a bending angle of a bending portion. FIG. 4 is a schematic diagram for explaining the radius of curvature of a bent portion.

Below, an embodiment of the present invention will be described with reference to the drawings. In the following embodiments, the same or similar components are given the same reference numerals throughout the drawings. The drawings are schematic, and the relationship between planar dimensions and thickness, and the thickness ratio of each component differ from the actual ones. In addition, it goes without saying that the drawings also include parts in which the dimensional relationships and ratios differ from one another.

FIG. 1 shows a schematic diagram of a calcification model 100 of this embodiment. The calcification model 100 is made of at least gypsum and includes a lesion 102 simulating an eccentric calcification lesion protruding into the blood vessel 12, and a support part 104 protruding on the opposite side of the lesion 102 and supporting the lesion 102. In the following embodiment, as shown in FIG. 1, attention is focused on an eccentric calcification lesion present in a bent part of the blood vessel 12, but an eccentric calcification lesion present in a straight part of the blood vessel 12 may also be targeted.

Next, the method (i) to (iii) of producing the calcification model 100 will be described with reference to Figures 2 to 4.

(i) Preparation of a mold for a calcification model First, a plurality of resin molds (hereinafter referred to as lesion molds) are prepared, which are printed in the shape of the calcification model 100 using a 3D stereolithography printer. Next, as shown in FIG. 2, a base 20 having a plurality of depressions 22 on its surface is prepared, and the base 20 is placed in a plastic case. FIG. 2 shows a base 20 having ten depressions 22 as an example. Then, a part of the support portion of each lesion mold (a portion corresponding to the support portion 104 of the calcification model 100) is fitted into each depression 22. In this way, a plurality of lesion molds are fixedly arranged on the base 20.

(ii) Preparation of Silicone Mold Next, liquid silicone is poured into a plastic case in which multiple lesion molds are placed on base 20, to cover each of the lesion molds. As described above, each lesion mold is fixed in a recess 22 in base 20, so that each lesion mold will not flow away even when liquid silicone is poured into the plastic case. Here, as the silicone, for example, a mixture of the same masses of KE-1603-A (agent A) and KE-1603-B (agent B) manufactured by Shin-Etsu Chemical Co., Ltd. is used.

After removing any air bubbles from the liquid silicone inside the plastic case, the liquid silicone is hardened by heating. The hardened silicone is then removed from the plastic case, and the base 20 and each of the lesion molds that are fitted into the silicone are removed, yielding a silicone mold of the calcification model 100. Figure 3 shows an example of an actual silicone mold that was made.

(iii) Creation of the calcified model Next, the calcified model 100 is created using a silicone mold. First, a container (A cup) containing polyurethane (base) and gypsum mixed in a certain ratio, and a container (B cup) containing polyurethane (hardener) and gypsum mixed in another certain ratio are prepared. Then, the A cup, B cup, and silicone mold are placed in a vacuum degassing machine.

Then, the mixture of polyurethane and gypsum is stirred in a vacuum degassing machine and vacuum degassed. After that, the silicone mold is removed from the vacuum degassing machine and heated in an oven at a predetermined temperature (e.g., 70°C) for a predetermined time (e.g., 20 minutes). The silicone mold is then removed from the oven and left at room temperature for a predetermined time (e.g., 1 hour) or more. After that, the hardened model, i.e., the calcified model, is removed from the silicone mold.

Figure 4 shows an example of a calcification model that was actually created. The calcification model shown in Figure 4 mimics an eccentric calcified lesion that exists in a bent part of a coronary artery, and is designed so that the maximum stenosis rate is 80%. By changing parameters related to the stenosis rate and shape, it is possible to create calcification models that correspond to various lesion forms.

Next, with reference to Figures 5 and 6, a method for producing a coronary artery model that mimics a coronary artery with a calcified lesion will be described as an example of a vascular model.

First, as shown in FIG. 5, a resin vascular cast 110 is prepared, which is printed in the shape of a coronary artery using a 3D stereolithography printer. The vascular cast 110 has a non-lesioned portion 112 having the shape of a non-lesioned portion of a coronary artery, a bent stenosis portion 114 with a smaller diameter than the non-lesioned portion 112, and a connection portion 116 for connecting to an aorta model (FIG. 7) described below. The connection portion 116 has a larger diameter than the non-lesioned portion 112. Next, a thin layer of liquid glue is applied to the stenosis portion 114 of the vascular cast 110, and the calcification model 100 is attached so that the diseased portion 102 of the calcification model 100 fits into the stenosis portion 114.

Next, pour the same liquid silicone as described above into the acrylic box until it reaches the specified thickness. After removing any air bubbles from the liquid silicone inside the acrylic box, the liquid silicone is hardened by heating. Next, place the vascular mold 110 with the calcification model 100 on top of the hardened silicone. At this time, place the vascular mold 110 so that both ends are in contact with the sides of the acrylic box.

Next, the liquid silicone is further poured into the acrylic box so that the vascular cast 110 with the calcification model 100 is embedded in the liquid silicone. After removing any air bubbles from the liquid silicone, the liquid silicone is hardened by heating.

Then, the hardened silicone block is removed from the acrylic box. The vascular cast 110 embedded in the silicone block is divided by pulling both ends of the vascular cast 110 with a tool such as pliers, and the divided vascular cast 110 is pulled out from both ends, leaving the calcification model 100 inside. The inside of the silicone block after the vascular cast 110 has been pulled out is then washed with water and dried. In this way, a coronary artery model 200 incorporating the calcification model 100 can be obtained, as shown in Figure 6.

The coronary artery model 200 includes a simulated blood vessel 210, which is a cavity in the shape of a coronary artery, in a silicone block. The simulated blood vessel 210 includes a simulated non-lesioned portion 212 that simulates a non-lesioned portion of the coronary artery, and a simulated stenosis portion 214 that simulates a narrowed, bent portion with a smaller inner diameter than the non-lesioned portion. The calcification model 100 is provided in the simulated stenosis portion 214, and a first connector portion 216 is provided at one end of the simulated blood vessel 210 for connecting to an aortic model (FIG. 7) described below. The first connector portion 216 has a larger inner diameter than the simulated non-lesioned portion 212. The simulated blood vessel 210 is provided in a transparent material such as silicone, so that the behavior of the treatment device within the simulated blood vessel 210 can be visualized, as described below.

The design of the coronary artery model 200 and the calcification model 100 must be carried out in parallel so that the simulated stenosis 214 of the simulated blood vessel 210 and the lesion 102 of the calcification model 100 fit together.

Next, we will explain the test system for evaluating the performance of the treatment device with reference to Figures 7 to 10.

First, as shown in FIG. 7, an aortic model 310 that imitates the aorta is created using a three-dimensional photolithography printer. The aortic model 310 includes a descending aortic section 312, an aortic arch section 314, an ascending aortic section 316, a brachiocephalic artery section 318, and a second connection section 320 for connecting to the coronary artery model 200. The outer diameter of the second connection section 320 is approximately equal to the inner diameter of the first connection section 216 of the coronary artery model 200. While an actual blood vessel has a roughly circular cross section, the aortic model 310 has a semicircular cross section and a flat surface. This flat surface makes it easier to place the aortic model 310 on a flat surface.

As shown in FIG. 8, the test system 300 can be constructed by inserting the second connection part 320 of the aorta model 310 into the first connection part 216 of the coronary artery model 200 and combining the coronary artery model 200 and the aorta model 310.

To make the actual test system 300, first, as shown in FIG. 9, an opening 422 for inserting the catheter 412 of the treatment device 410 is formed on the side of the container 420, and the aorta model 310 is fixed to the bottom of the container 420 with adhesive. Then, liquid 424 is poured into the container 420 so that the entire aorta model 310 is immersed. For example, a glycerin solution can be used as the liquid 424. Then, the coronary artery model 200 is connected to the aorta model 310 in the container 420 to construct the test system 300, the inside of the coronary artery model 200 is filled with the liquid 424, and air bubbles are removed. A camera 430 is installed above the test system 300. The reason why a glycerin solution is used here is that it can match the refractive index with the silicone of the coronary artery model 200, and since it is transparent, the behavior of the treatment device 410 in the coronary artery model 200 can be visualized.

The aortic model 310 shown in Figures 7 and 8 constitutes a path for the treatment device 410 to access the calcification model 100 of the coronary artery model 200. The catheter 412 of the treatment device 410 is inserted from the descending aorta section 312 or the brachiocephalic artery section 318 of the aortic model 310, and moves to the lesion 102 of the calcification model 100 via the second connection section 320 and the first connection section 216. Then, as shown in Figure 10, the treatment device 410 is driven at the position of the lesion 102 present in the simulated stenosis section 214, whereby the lesion 102 can be removed or crushed.

For example, in the Orbital Atherectomy System (OAS), the lesion 102 of the calcification model 100 can be scraped away by centrifugal force by rotating an eccentric diamond-coated crown at the tip of the catheter 412.

As shown in Figures 6 and 10, the calcification model 100 attached to the bent simulated stenosis section 214 has a support section 104 that protrudes on the side opposite the lesion section 102, which prevents the calcification model 100 from shifting in position due to the operation of the treatment device 410.

As described above, the simulated blood vessel 210 is provided in a transparent member, and the glycerin aqueous solution in the container 420 is also transparent, so that a video of the behavior of the treatment device 410 during the evaluation test can be captured by the camera 430. By measuring the cutting depth, cutting cross-sectional area, cutting width, cutting volume, etc. of the lesion 102 from the captured data obtained by the camera 430, the lesion removal ability of the treatment device 410 can be quantitatively evaluated ex vivo, and the relationship between the lesion morphology and the lesion removal ability or lesion crushing ability can be understood.

Note that the above-mentioned calcification model 100 is a representation of a calcified lesion present on the inner diameter side of a bent portion of a blood vessel 12, but the position of the calcified lesion is not limited in this embodiment. As shown in FIG. 11, a calcification model 100B may be used that represents a calcified lesion present on the outer diameter side of a bent portion of a blood vessel 12. The calcification model 100B includes a lesion portion 102B that represents an eccentric calcified lesion protruding from the outer diameter side of the bent portion of a blood vessel 12, and a support portion 104B that protrudes on the opposite side of the lesion portion 102B and supports the lesion portion 102B.

Also, as shown in Figures 12 and 13, by arbitrarily changing the bending angle (Figure 12) and the radius of curvature (Figure 13) of the bent portion of the blood vessel 12, or by arbitrarily changing the stenosis rate of the lesion, it is possible to create various calcification models and coronary artery models (blood vessel models) according to the lesion morphology.

Furthermore, in the test system 300 of FIG. 8, the coronary artery model 200 is detachable from the aortic model 310. Therefore, by preparing various coronary artery models 200 according to the lesion morphology and making them detachable from the aortic model 310, it is possible to perform a performance evaluation of the treatment device 410 for various lesion morphologies at low cost.

The calcification model, blood vessel model, and test system of this embodiment are not only capable of quantitatively evaluating the effectiveness of existing treatment devices for removing or crushing calcified lesions, but are also useful for training on new treatment devices.

The present invention is not limited to the above-described embodiment, and various modifications are possible without departing from the spirit of the present invention.

12 Blood vessel 100, 100B Calcification model 102, 102B Lesion part 104, 104B Support part 110 Blood vessel cast 112 Non-lesion part 114 Stenosis part 200 Coronary artery model (blood vessel model)
210 Simulated blood vessel 212 Simulated non-lesioned portion 214 Simulated stenosis portion 300 Test system 310 Aorta model 410 Treatment device 412 Catheter 430 Camera

Claims (13)

A calcification model comprising at least gypsum and having a lesion simulating an eccentric calcified lesion protruding into a blood vessel. The calcification model according to claim 1, wherein the lesion comprises polyurethane and the gypsum. The calcification model according to claim 1, wherein the lesion is a replica of the calcified lesion present in a bent portion of the blood vessel. The calcification model according to claim 1, comprising a support part that protrudes on the opposite side to the lesion and supports the lesion. A simulated blood vessel having a simulated non-lesioned portion simulating a non-lesioned portion of a blood vessel and a simulated stenosis portion simulating a stenosis portion having an inner diameter smaller than that of the non-lesioned portion;
The calcification model according to any one of claims 1 to 4, which is attached to the simulated stenosis portion;
A blood vessel model comprising: The blood vessel model according to claim 5, wherein the simulated narrowed portion is a representation of a narrowed, bent portion of the blood vessel. The blood vessel model according to claim 5, wherein the simulated blood vessel is a blood vessel-shaped cavity provided in a transparent member. 1. A test system for evaluating the performance of a therapeutic device for removing or disrupting calcified lesions in a blood vessel, comprising:
a simulated blood vessel having a simulated non-lesioned portion simulating a non-lesioned portion of the blood vessel and a simulated stenosis portion simulating a stenosis portion having an inner diameter smaller than that of the non-lesioned portion;
a calcification model that is attached to the simulated stenosis portion, comprises at least gypsum, and simulates an eccentric calcified lesion protruding into the blood vessel;
a pathway for the treatment device to access the calcification model;
A test system comprising: The test system of claim 8, wherein the calcification model comprises polyurethane and the gypsum. A blood vessel model is constructed by the simulated blood vessel and the calcification model,
The pathway constitutes an aortic model that mimics the aorta,
a first connection part for connecting to the aorta model is provided at one end of the simulated blood vessel of the blood vessel model;
the aorta model is provided with a second connection portion for connection to the blood vessel model;
The test system of claim 8 , wherein the blood vessel model and the aorta model are coupled together via the first connection portion and the second connection portion. The test system according to claim 10, wherein the blood vessel model is detachable from the aortic model. The test system according to claim 10, wherein the aortic model has a descending aortic section and a brachiocephalic artery section, and the pathway for the treatment device to access the calcification model from the descending aortic section or the brachiocephalic artery section constitutes the pathway. The testing system of claim 10 , wherein the pathways constituting the aorta model are semicircular in cross section and have flat surfaces.

Images