A visual minimally invasive intracranial administration device

Abstract

The present application relates to the technical field of biological experimental apparatus, and particularly relates to a visible minimally invasive intracranial administration device, which comprises an injection base, the bottom of the injection base is provided with a liquid storage cavity, and the bottom of the liquid storage cavity is connected with a ventricular catheter; a plurality of liquid injection adjusting assemblies are arranged on the liquid storage cavity, the liquid injection adjusting assemblies are all connected with hydraulic steering assemblies, and the hydraulic steering assemblies are uniformly arranged along the circumference of the ventricular catheter; the liquid injection adjusting assemblies are used for injecting fluid after microneedle puncture by experimenters, and the fluid is conducted to the inside of the corresponding hydraulic steering assembly to adjust the real-time hydraulic pressure in the corresponding hydraulic steering assembly; based on the fact that the internal hydraulic pressure increments of the hydraulic steering assemblies are different, the distal end of the ventricular catheter is driven to be bent and deformed in a specific direction and amplitude in the ventricular cavity; the present application additionally provides active bending adjustment of the hydraulic drive of the ventricular catheter, reduces the risk that the ventricular catheter in the traditional device is dislocated or drifts due to the fact that the ventricular catheter relies on glue and suture fixation and is easily interfered.

Description

Technical Field

[0001] This invention relates to the field of biological experimental equipment technology, specifically to a visual, minimally invasive intracranial drug delivery device. Background Technology

[0002] Intracranial drug delivery involves directly delivering drugs to the brain parenchyma or ventricular space, achieving targeted delivery by bypassing the blood-brain barrier and reducing systemic side effects. Based on this technology, visualized intracranial drug delivery commonly uses live mice (a classic model in neuroscience research) as experimental subjects in preclinical studies. Image guidance enables real-time monitoring of the needle tip location and drug diffusion process, thus providing an image-guided technical bridge for the clinical translation of central nervous system drug delivery.

[0003] Existing devices for intracranial drug delivery in mice, such as Murine Ommaya, have a basic structure consisting of a stainless steel micro-injection port permanently fixed to the mouse skull and a ventricular catheter connected to it. This port allows for repeated punctures to deliver the drug solution into the ventricle via the catheter. Compared to traditional multiple intrathecal injections or stereotactic injections, this device can effectively reduce drug waste, improve delivery efficiency, and support repeated intracranial micro-dose delivery in mouse models.

[0004] However, in practical applications, the miniaturized device is limited by its structural size, its reliance on a single skull surface fixation method consisting solely of quick-drying adhesive and skin sutures, and the fact that the mechanical restraint around the implant is far less than in larger laboratory animals due to the thin scalp and loose subcutaneous tissue in mice. Even slight interference within the cage during the postoperative recovery period can cause the device to dislocate completely or even detach entirely from the skull surface, leading to uncontrollable spatial drift of the catheter tip within the ventricles or brain parenchyma. Based on these technical limitations, it is necessary to propose a visually-guided, minimally invasive intracranial drug delivery device suitable for mouse intracranial drug delivery models. Summary of the Invention

[0005] To address the aforementioned issues, this invention provides a visually-guided minimally invasive intracranial drug delivery device, which incorporates a hydraulically driven active bending adjustment for the ventricular catheter. This reduces the risk of displacement or drift of the ventricular catheter, which relies on glue and sutures for fixation in traditional devices and is susceptible to interference.

[0006] To achieve the above objectives, the technical solution of the present invention is as follows: a visual minimally invasive intracranial drug delivery device, comprising an injection base for fixing to the skull of a mouse, a reservoir attached to the surface of the skull at the bottom of the injection base, and a ventricular catheter extending into the ventricle of the mouse after puncture at the bottom of the reservoir.

[0007] It also includes a visual system for acquiring images of mouse brains;

[0008] The reservoir is surrounded by several injection adjustment components, each of which is connected to a hydraulic steering component. The hydraulic steering components are fixedly connected to the outer wall of the ventricular duct and are evenly arranged along the circumference of the ventricular duct.

[0009] The fluid injection adjustment component is used by the experimenter to inject fluid after microneedle puncture and conduct the fluid to the corresponding hydraulic steering component to adjust the real-time hydraulic pressure in the corresponding hydraulic steering component;

[0010] Based on the different hydraulic increments inside each hydraulic steering component, each hydraulic steering component applies different radial expansion or contraction forces along the circumference of the ventricular duct. These asymmetrically distributed forces act together on the distal sidewall of the ventricular duct, driving the distal end of the ventricular duct to undergo bending deformation in a specific direction and amplitude within the ventricular cavity.

[0011] The end of the ventricular catheter away from the reservoir is equipped with an enhancement component to improve the positioning and acquisition of the ventricular catheter tip by the visualization system.

[0012] The technical principle of the above scheme is as follows: This scheme establishes an intraventricular drug delivery channel by implanting an injection base into the mouse skull and a ventricular catheter, and sets several independent injection adjustment components on the periphery of the reservoir sac. All injection adjustment components are connected to hydraulic steering components that are evenly arranged along the circumference of the catheter.

[0013] Researchers can use microneedles to puncture and inject saline fluid into the fluid adjustment components to regulate the real-time hydraulic pressure within each hydraulic steering component. When the hydraulic pressure increments of the hydraulic steering components differ, the asymmetric radial expansion or contraction force applied by the hydraulic steering components to the distal sidewall of the ventricular catheter will result in a combined force driving the ventricular catheter tip to undergo bending deformation in a specific direction and amplitude within the ventricular cavity. Simultaneously, a display enhancement component is installed at the distal end of the ventricular catheter, which, in conjunction with a visual system, acquires and displays the catheter tip position in real time, enabling visualized closed-loop adjustment during drug administration.

[0014] The above approach has the following beneficial effects:

[0015] 1. This solution uses hydraulically driven active bending adjustment to dynamically compensate for the three-dimensional position of the catheter tip without the need for a second craniotomy after surgery. This effectively reduces the risk of dislocation or drift caused by the traditional device which relies solely on glue and sutures for fixation and is susceptible to slight interference. It also solves the problem of catheter displacement caused by weak fixation.

[0016] 2. This protocol can reduce the risk of accidental injection of drugs into the brain parenchyma or local tissues due to catheter tip drift, reduce experimental bias, ensure the reproducibility and animal welfare of chronic drug administration studies, and improve the reliability of data from long-term drug administration experiments.

[0017] 3. This solution combines a visual system with an enhanced display component, enabling researchers to monitor the position and orientation of the catheter tip in real time and precisely adjust the bending direction, transforming traditional experience-based operations into quantifiable closed-loop navigation and achieving visualized and precise control.

[0018] Furthermore, all injection adjustment components include an injection adjustment bladder, which is integrally formed with the reservoir body.

[0019] Beneficial effects: The injection adjustment bladder and the reservoir bladder are molded as one piece, ensuring the independence of each hydraulic circuit during repeated puncture and injection and long-term sealing reliability. At the same time, it simplifies the overall structure of the device and reduces the operational complexity of the implantation surgery.

[0020] Furthermore, there are four injection adjustment bladders, and the four injection adjustment bladders are evenly arranged around the circumference of the reservoir body.

[0021] Beneficial effects: The four injection adjustment bladders are evenly arranged around the circumference of the reservoir to form a petal-like structure, which enables the injection adjustment bladders to generate a centripetal clamping force at the bottom when the fluid expands, improving the conformity with the curved surface of the mouse skull; when the mouse shakes its head or rubs in the cage, the symmetrically distributed clamping action effectively counteracts the tangential and vertical external forces, reducing the risk of device loosening or overall displacement.

[0022] Furthermore, the top of the injection adjustment bladder is integrally formed with a silicone thickening layer, and the elastic modulus of the silicone thickening layer is greater than that of the sidewall of the injection adjustment bladder.

[0023] Beneficial effects: The addition of a thickened silicone layer allows the injection regulating capsule to maintain a stable dome shape at the top during injection and pressurization, while the sidewalls preferentially expand radially. This guides the saline fluid into the hydraulic steering component and enhances the capsule's tolerance to repeated microneedle punctures. Simultaneously, the differentiated elastic design allows the bottom of the injection regulating capsule to form a progressive compliant contact with the skull's curved surface, dispersing local pressure and reducing device tilting caused by uneven surface tension of the mouse skull.

[0024] Furthermore, each hydraulic steering component includes a fluid guide tube and a deformable bladder. The fluid guide tube is connected to the corresponding injection adjustment bladder and fixedly connected to the outer wall of the ventricular duct. The deformable bladder is connected to the end of the corresponding fluid guide tube away from the injection adjustment bladder, and the deformable bladder is fixedly connected to the ventricular duct.

[0025] Beneficial effects: The design of this fluid inlet tube and deformable sac structure allows for the seamless transmission of the pressure of the injected saline fluid to the distal end of the ventricular duct. The selective expansion of the deformable sac enables independent and precise control over the bending direction and amplitude of the ventricular duct tip, and can reduce mechanical damage to brain tissue.

[0026] Furthermore, the cross-sectional area of ​​the deformed cyst along the radial direction of the ventricular duct is larger than the cross-sectional area of ​​the fluid inlet tube.

[0027] Beneficial effects: Under this design, the radial expansion deformation generated after the same volume of fluid enters the deformable cyst will be greater than that of the fluid guide tube. This allows the expanded deformable cyst to not only exert a directional bending moment on the sidewall of the catheter, but also to increase its radial dimension to lightly touch the ventricular wall and form an auxiliary anchoring force.

[0028] Furthermore, each injection adjustment capsule has a wing-shaped extension layer fixedly connected to the side away from the reservoir body, and each wing-shaped extension layer has several tissue pores.

[0029] Beneficial effects: The wing-shaped extension layer is embedded between the subcutaneous layer of the scalp and the galea aponeurotica, increasing the contact interface between the device and connective tissue; after implantation, the tissue pores induce fibroblasts and collagen fibers to grow in, forming a biological interlocking anchor, dispersing the detachment stress to multiple tissue columns, thereby transforming passive friction fixation into active tissue integration fixation, reducing the probability of device detachment during cage-house rearing after intracranial drug administration in mice, without increasing the overall height, maintaining a low profile and miniaturization.

[0030] Furthermore, the enhancement component includes an enhancement tube integrally formed on the end of the ventricular duct away from the reservoir, with several imaging rings fixedly connected to both the inner and outer walls of the enhancement tube.

[0031] Beneficial effects: The imaging ring on the inner side of the intensifying tube can provide a spatial trajectory reference for the catheter centerline, while the imaging ring on the outer side of the intensifying tube directly marks the radial boundary of the deformed capsule after expansion. Experimenters can intuitively determine the bending direction and amount of the distal end of the catheter by comparing the changes in the distance between the inner and outer rings, thereby accurately controlling the injection volume of each injection adjustment capsule under visual navigation, and realizing directional fine-tuning and closed-loop calibration of the catheter position.

[0032] Furthermore, the visual system includes an image acquisition module, an image processing module, and a display module;

[0033] The image acquisition module is used to acquire real-time images of the mouse brain region, and the real-time images show the imaging signal of the intensifier tube.

[0034] The image processing module is used to identify the spatial coordinates of the imaging signal of the intensifying tube and to calculate the three-dimensional position, axial direction and curvature parameters of the distal end of the ventricle in the mouse ventricle.

[0035] The display module is used to graphically overlay and display three-dimensional position, axial direction and bending curvature parameters on real-time images;

[0036] Based on the real-time pose information of the distal end of the ventricular duct fed back from the real-time images, the experimenters can inject saline fluid into the corresponding injection adjustment capsule until the actual pose of the distal end of the ventricular duct matches the pose of the preset target point.

[0037] Beneficial effects: Based on the design of the visual system, the experimenters adjust the injection volume of each injection adjustment capsule according to the feedback of real-time pose information until the actual pose of the distal end of the catheter matches the preset target point, thereby realizing the transformation from experience-based operation to visual closed-loop precise navigation.

[0038] Furthermore, the image processing module is also used to establish a spatial coordinate system based on the individual differences in preoperative three-dimensional brain imaging data of different mice before the implantation surgery, and to perform initial calibration of the intensifying tube in the spatial coordinate system.

[0039] Before each subsequent drug administration or adjustment operation, the image acquisition module acquires the imaging signal of the intensifying tube in real time. The image processing module calculates the three-dimensional displacement vector of the distal end of the ventricular duct by comparing the current spatial coordinates of the intensifying tube in the real-time image with the initial calibration coordinates, and determines whether the three-dimensional displacement vector exceeds the preset safety threshold.

[0040] If the safety threshold is exceeded, the display module can issue a visual correction prompt.

[0041] Beneficial effects: This early warning function enables researchers to intervene in the early stages of minor drift in the ventricular duct, reducing the probability of cumulative displacement leading to drug mis-injection or ventricular wall damage, and improving the data reliability and animal welfare level of long-term chronic drug administration experiments.

[0042] Additional aspects and advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. Attached Figure Description

[0043] Figure 1 This is an isometric view of the overall structure of the visual minimally invasive intracranial drug delivery device embodiment of the present invention;

[0044] Figure 2 This is a front view of the overall device in an embodiment of the visual minimally invasive intracranial drug delivery device of the present invention;

[0045] Figure 3 for Figure 2 A sectional view of section AA in the middle;

[0046] Figure 4 for Figure 2 A sectional view of section BB in the middle;

[0047] Figure 5 This is a magnified view of the injection adjustment bladder and wing-shaped extension layer in an embodiment of the visual minimally invasive intracranial drug delivery device of the present invention.

[0048] Figure 6 This is a schematic diagram of the enhancement component structure in an embodiment of the visual minimally invasive intracranial drug delivery device of the present invention.

[0049] The reference numerals in the accompanying drawings include: 1. Injection base; 2. Reservoir; 3. Ventricular catheter; 4. Injection adjustment capsule; 41. Silicone thickened layer; 5. Fluid guide tube; 6. Deformable capsule; 7. Enhancement tube; 71. Contrast ring; 8. Wing-shaped extension layer; 81. Tissue pore. Detailed Implementation

[0050] The technical solution of the present invention will now be clearly and completely described with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0051] In the description of this invention, it should be noted that the terms "center," "upper," "lower," "left," "right," "vertical," "horizontal," "inner," and "outer," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are used only for the convenience of describing the invention and for simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on the invention. Furthermore, the terms "first," "second," and "third" are used for descriptive purposes only and should not be construed as indicating or implying relative importance.

[0052] In the description of this invention, it should be noted that, unless otherwise explicitly specified and limited, the terms "installation," "connection," and "linking" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal connection of two components. Those skilled in the art can understand the specific meaning of the above terms in this invention based on the specific circumstances.

[0053] The following detailed description illustrates the specific implementation method:

[0054] Example 1:

[0055] This embodiment provides a visual, minimally invasive intracranial drug delivery device, specifically as follows: Figure 1 and Figure 2As shown, it includes an injection base 1, with a reservoir 2 attached to the surface of the skull at the bottom of the injection base 1. The bottom of the reservoir 2 is connected to a ventricular catheter 3 that extends into the lateral ventricle of the mouse after stereotactic puncture; referring to the clinical application of the existing Murine Ommaya device, which achieves repeated intraventricular drug delivery by pre-embedding a micro-injection port.

[0056] Specifically, the outer circumference of the reservoir body 2 is integrally formed with four injection adjustment components, combined with... Figure 2 and Figure 3 As shown, each injection adjustment component includes an injection adjustment bladder 4 (preferably made of medical-grade silicone rubber material with biocompatibility, high elasticity and tear resistance); each injection adjustment bladder 4 is connected to a set of hydraulic steering components, each hydraulic steering component includes a guide tube 5 and a deformable bladder 6, the guide tube 5 is attached and fixed to the outer wall of the ventricular catheter 3, and each guide tube 5 is connected to the injection adjustment bladder 4 at the corresponding position, the number and position of the deformable bladder 6 correspond one-to-one with the number and position of the guide tube 5, the deformable bladder 6 is connected to the distal end (the end near the ventricle) of the corresponding guide tube 5, and the deformable bladder 6 is attached and fixed to the outer wall of the distal end of the ventricular catheter 3.

[0057] Existing technologies rely solely on adhesive bonding and skin suturing for fixation. Mice have thin scalps and loose subcutaneous tissue, resulting in weak mechanical restraint. Even slight disturbances during post-operative co-hospital rearing can lead to device dislocation or three-dimensional drift of the catheter tip, potentially causing accidental injection of medication into the brain parenchyma, local tissue damage, and severely compromising the reproducibility of long-term experimental data and animal welfare. In this embodiment, researchers can puncture each injection adjustment sac 4 with a microneedle and inject a predetermined volume of sterile saline fluid. The saline fluid is then transferred via the corresponding drainage tube 5 to the deformable sac 6 attached to the distal end of the ventricular duct 3. Since each deformable sac 6 is uniformly arranged circumferentially along the ventricular duct 3 and its expansion degree can be independently controlled, the asymmetric radial expansion force (i.e., deformable sacs 6 with different internal hydraulic environments) acts together on the distal sidewall of the catheter, driving the catheter tip to actively bend in a specific direction and amplitude within the ventricular cavity. This achieves dynamic compensation and precise repositioning of the three-dimensional position of the catheter tip post-operatively without the need for a second craniotomy, reducing experimental deviations caused by displacement of the ventricular duct 3.

[0058] In addition, combined Figure 2 and Figure 4As shown, in this embodiment, the cross-sectional area of ​​the deformable sac 6 along the radial direction of the ventricular duct 3 is larger than that of the fluid guide tube 5. Based on the principle of hydrostatic pressure, when the same volume of fluid enters the deformable sac 6 with a larger cross-sectional area, the radial expansion deformation of the deformable sac 6 will be greater than that of the fluid guide tube 5. The expanded deformable sac 6 will not only apply a directional bending moment to the sidewall of the ventricular duct 3, but also lightly touch the ventricular wall or brain tissue interface with its locally increased radial size, generating an auxiliary fixing force for the anchoring point in the ventricle. This achieves the effect of integrated directional adjustment and anchoring enhancement, whereby the experimenter actively adjusts the bending direction of the duct to align with the target point, and the expansion of the deformable sac 6 simultaneously enhances the anti-dislodgement stability of the distal end of the ventricular duct 3 in the ventricle.

[0059] like Figure 2 As shown, four injection adjustment sacs 4 are evenly arranged around the circumference of the reservoir sac 2 to form a petal-like structure. Based on the principle that the hydraulic pressure in each injection adjustment sac 4 will selectively change when the experimenter adjusts the direction of the ventricular catheter 3, the bottom of the four evenly arranged injection adjustment sacs 4 will expand radially and bend relative to the reservoir sac 2 during the injection expansion process. This achieves the centripetal clamping force distributed on the arc surface of the mouse skull when the hydraulic pressure in the injection adjustment sac 4 changes, forming a grasping and fitting effect. This improves the compliance of the reservoir sac 2 with the curvature of the skull surface. When the mouse's normal movement (such as head swinging, cage friction or scratching behavior) generates tangential shear force or vertical lifting force, the petal-like structure effectively counteracts the above external forces through symmetrically distributed clamping action, reducing the risk of the device loosening or overall displacement due to local stress concentration.

[0060] Combination Figure 2 and Figure 3 As shown, each injection regulating capsule 4 has an integrally formed silicone thickened layer 41 at its top, which allows the top of the injection regulating capsule 4 to maintain a stable dome shape while the sidewalls preferentially expand radially during injection and pressurization. This facilitates the directional flow of physiological saline fluid to the infusion tube 5, and the thickened layer structure enhances the tolerance of the top of the injection regulating capsule 4 to repeated microneedle punctures, allowing it to withstand dozens of punctures within the experimental period without leakage or loss of elasticity. In addition, the elastic modulus of the silicone thickened layer 41 is greater than that of the sidewall of the injection regulating capsule 4. The design of the differentiated elastic modulus makes the overall deformation of the injection regulating capsule 4 controllable after injection, and the bottom forms a progressive compliant contact with the arc-shaped surface of the mouse skull, effectively dispersing local pressure and reducing the risk of device tilting due to uneven scalp tension.

[0061] In addition, the visual minimally invasive intracranial drug delivery device described in this embodiment also includes a visual system, which is used to acquire real-time images of the mouse brain region and provide spatial location information for intracranial drug delivery in mice. The spatial location information for intracranial drug delivery in mice includes diffusion information of intracranial drug solution and location information of ventricular duct 3.

[0062] Correspondingly, such as Figure 6 As shown, the distal end of the ventricular catheter 3 is also equipped with an intensification component, which includes an intensification tube 7 integrally formed at the distal end of the ventricular catheter 3. Several imaging rings 71 are fixed on the inner and outer walls of the intensification tube 7. Since the four deformable cysts 6 are made of silicone, their attenuation coefficients are similar to those of cerebrospinal fluid and brain tissue under X-rays, making it difficult to identify their boundaries and filling state, inevitably forming a visual blind spot (i.e., a blurred area in image acquisition). The traditional single-layer imaging ring 71 cannot reflect the true outer contour of the balloon after inflation. The inner imaging ring 71 provides the experimenter with a spatial trajectory reference for the catheter centerline during intracranial image acquisition, enabling the operator to clearly identify the catheter. The distal axial direction and overall direction of travel are indicated; the outer imaging ring 71 directly marks the radial boundary of the deformed sac 6 after expansion, and presents the real-time expansion degree of the air sacs in each direction in the image as a visual change in the distance between the two rings; by comparing the local widening position and magnitude of the projection distance between the inner and outer imaging rings 71, the experimenter can intuitively judge the current bending direction and bending amount of the end of the ventricular catheter 3 during the injection adjustment process, thereby accurately controlling the injection volume of each injection adjustment sac 4 under visual navigation, realizing the directional fine adjustment and closed-loop calibration of the three-dimensional pose of the distal end of the catheter in the ventricle, and improving the directionality and success rate of the adjustment operation.

[0063] Example 2:

[0064] As attached Figure 5 As shown, the difference from Embodiment 1 is that in this embodiment, a wing-shaped extension layer 8 is integrally formed on the side of the injection adjustment bladder 4 away from the reservoir bladder 2; specifically:

[0065] Each injection adjustment capsule 4 has an outer edge at the top that extends outward to form a tongue-shaped wing-shaped extension layer 8, and several tissue pores 81 are uniformly opened on the wing-shaped extension layer 8.

[0066] To address the technical shortcomings of traditional glue-suture fixation methods, which utilize thin scalp, loose subcutaneous tissue, and a lack of dense fascia layer in mice, making the device susceptible to dislocation or micro-displacement due to slight disturbances during cage rearing, a wing-shaped extension layer 8 is embedded between the subcutaneous layer of the mouse scalp and the galea aponeurotica. Its large, thin wing structure increases the contact interface between the device and the surrounding connective tissue. Furthermore, after implantation, the tissue pores 81 induce fibroblasts and collagen fibers to grow into them, forming a bio-interlocking structure similar to an anchor. The multiple tissue pores 81 disperse the dislocation stress borne by each individual onto multiple independent tissue columns, increasing the critical dislocation threshold.

[0067] Meanwhile, the micro-rough structure and open-pore design of the wing-shaped extension layer 8 change the passive friction mode between the traditional smooth silicone surface and tissue, transforming it into an active bio-integrated fixation; reducing the probability of device detachment during co-hospital rearing after intracranial drug administration in mice, and the structure does not increase the overall height of the device, making the entire device low-profile and miniaturized.

[0068] Example 3:

[0069] The difference from Embodiment 2 is that the visual system includes an image acquisition module, an image processing module, and a display module.

[0070] The image acquisition module uses intraoperative CT or open MRI equipment to acquire real-time images of the mouse cranial brain region during drug administration or adjustment of the ventricle 3. The real-time images show the imaging signal of the imaging ring 71 on the intensifying tube 7 within the imaging field (image).

[0071] The image processing module is configured to perform the following calibration and processing logic: Before the implantation surgery, a spatial coordinate system containing the lateral ventricle, septum pellucidum and target point of the mouse is established based on the preoperative high-resolution three-dimensional brain imaging data for different mice, and the intensification tube 7 is initially calibrated, and its three-dimensional coordinates, axis and relative distance to the anatomical landmarks of the ventricle are recorded.

[0072] During each subsequent drug administration or bending adjustment operation of the ventricular catheter 3, the image acquisition module will acquire and display an image showing the position of the intensifying tube 7 in real time. The image processing module uses a preset imaging pattern code (including the width, spacing or number of imaging rings 71) to identify the distal end of the ventricular catheter 3, calculates the spatial coordinates of the intensifying tube 7 through edge detection and centroid algorithm, and then calculates the real-time three-dimensional position, axial direction and bending curvature parameters of the distal end of the ventricular catheter 3.

[0073] The image processing module can also compare the current coordinates of several intensifying tubes 7 with the initial calibration coordinates, calculate the three-dimensional displacement vectors in the front-back, left-right and depth directions of the distal end of the catheter, and determine whether the displacement vector exceeds the preset safety threshold.

[0074] The display module overlays the real-time pose parameters of the distal end of the ventricular duct 3 (i.e., the augmentation tube 7) onto the real-time anatomical image in a color graphic manner (e.g., three-dimensional arrows indicate direction and color gradients indicate the degree of curvature), forming an augmented reality navigation interface; if the displacement exceeds the safety threshold, the display module simultaneously issues a visual correction prompt (such as a red alarm box or target reset trajectory).

[0075] Based on the real-time pose information fed back on the interface, the experimenters injected and adjusted the volume of each injection adjustment capsule 4 to adjust the position and curvature of the ventricular duct 3 through each deformable capsule 6 until the virtual model of the distal end of the ventricular duct 3 in the display interface coincides with the preset target point model.

[0076] Based on this, this embodiment transforms the adjustment of catheter curvature from an empirical, open-loop operation to a visualized, quantitative closed-loop navigation; at the same time, the automatic displacement warning function enables researchers to intervene at the early stage of minor catheter drift, avoiding drug mis-injection or ventricular wall damage caused by cumulative displacement, thus improving the data reliability and animal welfare level of long-term chronic intracranial drug administration mouse experiments.

[0077] Obviously, the above embodiments are merely illustrative examples for clear explanation and are not intended to limit the implementation. Those skilled in the art will recognize that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively list all possible implementations here. However, obvious variations or modifications derived therefrom are still within the scope of protection of this invention.

Claims

1. A visually-guided minimally invasive intracranial drug delivery device, comprising an injection base (1) for fixation to the skull of a mouse, wherein a fluid reservoir (2) is provided at the bottom of the injection base (1) and attached to the surface of the skull, and a ventricular catheter (3) is connected at the bottom of the fluid reservoir (2) to extend into the ventricle of the mouse after puncture, characterized in that, It also includes a visual system for acquiring images of mouse brains; The reservoir (2) is provided with several injection adjustment components on its outer periphery. Each injection adjustment component is connected to a hydraulic steering component. The hydraulic steering components are fixedly connected to the outer wall of the ventricular duct (3) and are evenly arranged along the circumference of the ventricular duct (3). The fluid injection adjustment component is used by the experimenter to inject fluid after microneedle puncture and conduct the fluid to the corresponding hydraulic steering component to adjust the real-time hydraulic pressure in the corresponding hydraulic steering component. Based on the different hydraulic increments inside each hydraulic steering component, each hydraulic steering component applies different radial expansion or contraction forces along the circumference of the ventricular duct (3). These asymmetrically distributed forces act together on the distal sidewall of the ventricular duct (3), driving the distal end of the ventricular duct (3) to undergo bending deformation in a specific direction and amplitude within the ventricular cavity. The end of the ventricular catheter (3) away from the reservoir (2) is equipped with an enhancement component for enhancing the positioning and acquisition of the end of the ventricular catheter (3) by the visual system.

2. The visual minimally invasive intracranial drug delivery device according to claim 1, characterized in that, All injection adjustment components include an injection adjustment bladder (4), which is integrally formed with the reservoir body (2).

3. The visual minimally invasive intracranial drug delivery device according to claim 2, characterized in that, The number of injection regulating bladders (4) is four, and the four injection regulating bladders (4) are evenly arranged around the circumference of the reservoir body (2).

4. The visual minimally invasive intracranial drug delivery device according to claim 3, characterized in that, The top of the injection adjustment bladder (4) is integrally formed with a silicone thickening layer (41), and the elastic modulus of the silicone thickening layer (41) is greater than that of the side wall of the injection adjustment bladder (4).

5. The visual minimally invasive intracranial drug delivery device according to claim 4, characterized in that, The hydraulic steering components all include a fluid guide tube (5) and a deformable bladder (6). The fluid guide tube (5) is connected to the corresponding injection adjustment bladder (4) and fixedly connected to the outer wall of the ventricular duct (3). The deformable bladder (6) is connected to the end of the corresponding fluid guide tube (5) away from the injection adjustment bladder (4). The deformable bladder (6) is fixedly connected to the ventricular duct (3).

6. The visual minimally invasive intracranial drug delivery device according to claim 5, characterized in that, The cross-sectional area of ​​the deformable cyst (6) along the radial direction of the ventricular duct (3) is greater than the cross-sectional area of ​​the fluid conduit (5).

7. The visual minimally invasive intracranial drug delivery device according to claim 6, characterized in that, The injection adjustment bladder (4) is fixedly connected to a wing-shaped extension layer (8) on the side away from the reservoir bladder (2), and several tissue pores (81) are opened on the wing-shaped extension layer (8).

8. The visual minimally invasive intracranial drug delivery device according to claim 7, characterized in that, The enhancement component includes an enhancement tube (7) integrally formed on the end of the ventricular duct (3) away from the reservoir (2), and several imaging rings (71) are fixedly connected to the inner and outer walls of the enhancement tube (7).

9. The visual minimally invasive intracranial drug delivery device according to claim 8, characterized in that, The visual system includes an image acquisition module, an image processing module, and a display module; The image acquisition module is used to acquire real-time images of the mouse brain region, and the real-time images show the imaging signal of the intensifier tube (7); The image processing module is used to identify the spatial coordinates of the imaging signal of the intensifying tube (7) and to calculate the three-dimensional position, axial direction and curvature parameters of the distal end of the ventricular duct (3) in the mouse ventricle; The display module is used to graphically overlay and display three-dimensional position, axial direction and bending curvature parameters on real-time images; Based on the real-time pose information of the distal end of the ventricular catheter (3) fed back on the real-time image, the experimenter can inject saline fluid into the corresponding injection adjustment capsule (4) until the actual pose of the distal end of the ventricular catheter (3) matches the pose of the preset target point.

10. The visual minimally invasive intracranial drug delivery device according to claim 9, characterized in that, The image processing module is also used to establish a spatial coordinate system based on the different preoperative three-dimensional brain imaging data of different mice before the implantation surgery, and to perform initial calibration of the intensifying tube (7) in the spatial coordinate system. Before each subsequent administration or adjustment operation, the image acquisition module acquires the imaging signal of the intensifying tube (7) in real time. The image processing module calculates the three-dimensional displacement vector of the distal end of the ventricular duct (3) by comparing the current spatial coordinates of the intensifying tube (7) in the real-time image with the initial calibration coordinates, and determines whether the three-dimensional displacement vector exceeds the preset safety threshold. If the safety threshold is exceeded, the display module can issue a visual correction prompt.

Images