Vascular phantoms and method of making same

Abstract

A method of making a vascular phantom based on imaging data of vasculature of a subject. A mold having a core and a shell is constructed based on the imaging data. A liquid precursor is introduced into the mold and is cured. The mold is removed, leaving a model of the vasculature of the subject. A plaque component is fabricated by making a plaque mold and introducing liquid precursors containing T1 and T2 modifiers to mimic the T1 and T2 of portions of the plaque. The plaque components are attached to the vasculature using adhesive.

Claims

1. A method of fabricating a vascular phantom from imaging data of vasculature of a subject, comprising the steps of: forming a core-shell mold having a core and an outer shell with dimensions based on the imaging data of the vasculature of the subject; infusing the core-shell mold with a liquid precursor; curing the liquid precursor; dissolving the core-shell mold to recover a vascular phantom that represents the vasculature of the subject; forming a plaque mold representing a plaque having dimensions based on the imaging data of the vasculature of the subject; infusing the plaque mold with a plaque component; freezing the plaque component; removing the plaque component from the plaque mold; and attaching the plaque component to the vascular phantom that represents the vasculature of the subject.

2. The method of fabricating a vascular phantom of claim 1, wherein said plaque represents one or more of a hemorrhage, a lipid core, and a fibrous cap.

3. The method of fabricating a vascular phantom of claim 2, wherein said one or more of the hemorrhage, the lipid core, and the fibrous cap comprises respective amounts of a T1 modifier and a T2 modifier.

4. The method of fabricating a vascular phantom of claim 1, wherein said step of attaching the plaque to the vascular phantom includes by coating a layer of adhesive on one or both of the shaped plaque and the vascular replica and performing a curing process.

5. The method of fabricating a vascular phantom of claim 1, wherein plaque component can comprise T1 and T2 modifiers, water, agarose, and carrageenan.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) The objects and features of the invention can be better understood with reference to the drawings described below, and the claims. The drawings are not necessarily to scale, emphasis instead generally being placed upon illustrating the principles of the invention. In the drawings, like numerals are used to indicate like parts throughout the various views.

(2) FIG. 1A is an image of the fibrous cap component of a stenosed vessel.

(3) FIG. 1B is an image of the lipid component of a stenosed vessel.

(4) FIG. 1C is an image of the vessel component of a stenosed vessel.

(5) FIG. 1D is an image of the reconstructed stenosed vessel.

(6) FIG. 2A is an image of a core in a core-shell model of a stenosed vessel.

(7) FIG. 2B is an image of a shell with a core situated therein in a core-shell model of a stenosed vessel.

(8) FIG. 2C is an image of a hydrogel vascular replica of a stenosed vessel.

(9) FIG. 3A is an image of a lipid core component constructed using a mixture of gadolinium chloride and agarose.

(10) FIG. 3B is an image of a mold used to form the lipid core of FIG. 3A.

(11) FIG. 4 shows a lateral view of an atherosclerotic plaque model.

(12) FIG. 5 shows a lateral view of a core-shell mold for PVA infusion.

(13) FIG. 6 shows a cross-section view of the core-shell model.

DETAILED DESCRIPTION

(14) Currently, there is no standard protocol for MR-imaging of ICAD, nor a gold standard phantom to compare MR-sequences. In addition, MRI scanners produced by different vendors will have different sequences for ICAD imaging. The present invention provides a platform for establishing a uniform imaging method for diagnosis of ICAD.

(15) In a first embodiment, one can prepare a vascular replica of atherosclerotic plaque which comprises a stenosed vessel lumen and intracranial atherosclerotic plaque components, including a lipid core, a hemorrhage, and a fibrous cap constructed for MR imaging.

(16) In order to overcome the aforesaid limitations, a small batch manufacturing process has been employed to construct the stenosed vessel lumen. Clinical imaging data such as CT or MRI of patients with atherosclerotic plaques can be used for 3D reconstruction of cerebrovasculatures and each plaque component.

(17) FIG. 1A is an image of the fibrous cap component of a stenosed vessel. In FIG. 1A width dimensions are shown as W1 and W2 and a length dimension is shown as L1.

(18) FIG. 1B is an image of the lipid component of a stenosed vessel. In FIG. 1B width dimensions are shown as W3 and W4 and a length dimension is shown as L2.

(19) FIG. 1C is an image of the vessel component of a stenosed vessel. In FIG. 1C width dimensions are shown as W5 and W6 and a length dimension is shown as L3.

(20) The dimensions for one example are listed in Table 1.

(21) TABLE-US-00001 TABLE 1 Parameter Value in millimeters W1 2.960 W2 3.395 L1 8.814 W3 4.345 W4 4.489 L2 7.116 W5 6.120 W6 7.045 L3 20.042

(22) FIG. 1D is an image of the reconstructed stenosed vessel.

(23) With the knowledge of the geometric parameters such as vessel diameter and length, a computer core-shell model can be designed, as illustrated in FIG. 2A and FIG. 2B. FIG. 2A is an image of a core in a core-shell model of a stenosed vessel. FIG. 2B is an image of a shell with a core situated therein in a core-shell model of a stenosed vessel.

(24) The distance between the core and shell in FIG. 2B represents the thickness of the vascular replica, and can be precisely adjusted. A 3D printer converts the virtual design into a physical model by using the fused deposit manufacturing technique. Hydrogel is infused into the core-shell model by liquid injection molding and undergoes several freeze-thaw cycles for coagulation. The whole model is then immersed in xylene for complete mold dissolution, resulting in a hydrogel vascular replica as shown in FIG. 2C.

(25) Three plaque models can be created including a hemorrhage, a lipid core, and a fibrous cap. Each component has different T1 and T2 values. Altering amounts of the T1 and T2 modifiers, gadolinium chloride and agarose, respectively, the plaque phantoms exhibit T1 and T2 times similar to the clinical values. In addition to the T1 and T2 modifiers, the plaque phantoms are comprised of carrageenan, sodium azide, water, and sodium chloride. To precisely control the volume of each plaque component, a plaque mold made of silicone with known shape and dimension can be built.

(26) FIG. 3A is an image of a lipid core component constructed using a mixture of gadolinium chloride, agarose carrageenan, sodium azide, water, and sodium chloride.

(27) FIG. 3B is an image of a plaque mold used to form the lipid core of FIG. 3A.

(28) In FIG. 3B an outside dimension is shown as OD, a wall thickness dimension is shown as WT, and a length dimension is shown as L.

(29) The dimensions for one example are listed in Table 2.

(30) TABLE-US-00002 TABLE 2 Parameter Value in millimeters OD 5.861 WT 0.996 L 6.523

(31) Each plaque component can be attached or glued to the vascular replica by using an adhesive such as polyvinyl alcohol. As a result, the replica can be used as a gold standard phantom for imaging of intracranial atherosclerotic disease on which MRI sequences, specifically developed to visualize intracranial plaque, can be evaluated by quantifiable metrics, such as volume and length measurements. The replica can be attached to a flow-loop filled with a blood mimicking fluid driven by a cardiac duplicator in order to optimize the signal suppression from blood flow.

(32) In a second embodiment, one can construct a vascular model with complex and detailed structure for medical simulation and imaging by using a multi-step manufacturing process.

(33) In this embodiment, a small batch manufacturing technique is provided to create cerebrovascular replicas that offer detailed geometry from clinical imaging data. The vascular replica also provides versatile applications such as surgical simulation, interventional practice, and hemodynamic research in vitro. To facilitate optical observation and simulate physiological environment, the replica is designed to be transparent and elastic with low friction, uniform thickness and good compatibility with imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI) and three-dimensional rotational angiography. The multi-step manufacturing process is described below.

(34) Step 1Preparation of a Core-Shell Mold

(35) In the method of the present invention, different clinical imaging data such as CT or MRI of patients with or without pathologic findings can be used for 3D reconstruction of cerebrovasculatures. To prepare a diseased phantom such as the plaque model presented in FIG. 4, a stenosed vessel wall (401 in FIG. 4 and 501 FIG. 5) is used as the core to design and construct a layer of outer shell (502 in FIG. 5).

(36) FIG. 4 shows a lateral view of an atherosclerotic plaque model. In FIG. 4, 401 is a stenosed vessel lumen, 402 is a fibrous cap plaque component, and 403 is a lipid plaque component.

(37) FIG. 5 shows a lateral view of a core-shell mold for PVA infusion. In FIG. 5, 501 is a core of a stenosed vessel wall, and 502 is an outer shell.

(38) FIG. 6 shows a cross-section view of the core-shell model. In FIG. 6, 601 is a core of a stenosed vessel wall, 602 is an outer shell, 603 is support material, and 604 is empty space between core and shell for PVA infusion. Support material 603 is added between the core and the outer shell to prevent the outer shell from collapsing. The distance of empty space 604 between the core 601 and shell 602 represents the thickness of the vascular replica, which can be precisely controlled. The virtual design is converted into a physical model by using the fused deposit manufacturing technique or other 3D printing technologies as is convenient.

(39) Step 2Infusion of a Precursor

(40) A precursor, for example a hydrogel such as polyvinyl alcohol (PVA) or a thermoplastic material, is infused into the core-shell model for example by liquid injection molding.

(41) Step 3Curing the Precursor to Form a Model Part

(42) The infused core-shell model is subjected to one or more freeze-thaw cycles for curing. Preferably, more than one freeze-thaw cycle is performed. This forms the model part within the core-shell model.

(43) Step 4Dissolution or Removal of the Core-Shell Mold

(44) In one embodiment, the whole model including the core-shell mold is immersed in a solvent, for example xylene, for mold dissolution.

(45) One improvement provided by the second embodiment (the PVA model) is that it doesn't swell in xylene after removal of the outer shell as does the first embodiment (the silicone model).

(46) In the second embodiment, it is also possible to modify the inner core 401, 501, 601. In a prior design the inner core was a solid piece. In the second embodiment, the inner core can be designed to have a hollow structure which allows xylene to flow into the mold and to quickly dissolve the tortuous inner core, such as 601. After removing the inner core, a transparent PVA vascular replica of a stenosed vessel wall is obtained.

(47) The second embodiment is used to build a core-shell mold for each plaque component (402, 403 in FIG. 4). The core-shell molds for plaque components are filled with silicone (not PVA), and dissolved in xylene to yield silicone containers for lesion creation. Plaque component made of gelatin/gadolinium-based MRI contrast agent mixture is infused into the silicone container and set at 80 C. for 1 hour. The silicone container is carefully cut open to release the shaped plaque component. The shaped plaque component is then attached to the PVA vascular replica of a stenosed vessel wall by coating a layer of adhesive such as liquid PVA solution on one or both of the shaped plaque and the PVA vascular replica and performing a curing process.

(48) The replica is useful for workers who wish to evaluate their MR-imaging setup/sequence for imaging of ICAD. The technique has larger implications for also medical device testing in realistic models of the human vasculature.

(49) The present model is built from medical imaging data. The data can be data recorded from test subjects, or from medical subjects whose vasculature is the subject of interest. It is also possible to use synthetic data if one wants to generate a phantom for study under assumptions of some general medical condition of interest that is not specific to any one individual (e.g., how different amounts of plaque, or different locations where plaque is found might affect a specific situation).

(50) The vascular phantoms of the invention can be used to perform a medical procedure on the vascular phantom as a trial procedure prior to performing the medical procedure on the living subject. This can allow a medical professional to gain a better understanding of how to carry out the proposed procedure on a specific living subject without subjecting that living subject to the hazards of an actual procedure, and then performing the procedure on the living subject after a determination is made that the proposed procedure is suitable for that living subject.

(51) Theoretical Discussion

(52) Although the theoretical description given herein is thought to be correct, the operation of the devices described and claimed herein does not depend upon the accuracy or validity of the theoretical description. That is, later theoretical developments that may explain the observed results on a basis different from the theory presented herein will not detract from the inventions described herein.

(53) Any patent, patent application, patent application publication, journal article, book, published paper, or other publicly available material identified in the specification is hereby incorporated by reference herein in its entirety. Any material, or portion thereof, that is said to be incorporated by reference herein, but which conflicts with existing definitions, statements, or other disclosure material explicitly set forth herein is only incorporated to the extent that no conflict arises between that incorporated material and the present disclosure material. In the event of a conflict, the conflict is to be resolved in favor of the present disclosure as the preferred disclosure.

(54) While the present invention has been particularly shown and described with reference to the preferred mode as illustrated in the drawing, it will be understood by one skilled in the art that various changes in detail may be affected therein without departing from the spirit and scope of the invention as defined by the claims.