Cerebral cortex nerve and immune activity monitoring system based on temperature regulation and control

Abstract

The invention relates to the technical field of medical monitoring, and provides a cerebral cortical nerve and immune activity monitoring system based on temperature regulation, a temperature regulation device comprises a temperature regulation assembly and a temperature regulation carrier containing a fluid, and the temperature regulation assembly is used for regulating the temperature of the fluid; the light-transmitting carrier is provided with an accommodating cavity for directly accommodating a target brain region; the conveying assembly communicates with the containing cavities of the temperature regulation and control carrier and the light-transmitting carrier and is used for fluid conveying between the containing cavities of the temperature regulation and control carrier and the light-transmitting carrier. The brain temperature monitoring assembly is used for monitoring temperature information of a target brain region in real time and feeding back the temperature information to the temperature regulation and control assembly; the cortex imaging device is used for collecting cerebral cortex nerve and immune activity images of the target brain area through the light-transmitting carrier. The light-transmitting carrier is adopted to replace the skull corresponding to the position of the target brain region, and the wide-field imaging technology and the temperature regulation and control device are combined, so that cerebral cortex nerve and immune activity monitoring based on temperature regulation and control can be realized.

Description

Technical Field

[0001] The present invention relates to the technical field of medical monitoring, and in particular to a monitoring system for cerebral cortex nerve and immune activities based on temperature regulation. Background Art

[0002] Due to characteristics such as high resolution, large field of view, and fast imaging, wide-field imaging technology has become an important means for studying the mechanism of in vivo neuro-immunity.

[0003] However, since the nerve and immune responses in the in vivo environment (such as brain tissue) are closely related to temperature, it is difficult for the existing technology to synchronously adjust the temperature of the in vivo environment (such as brain tissue) during wide-field imaging, which hinders the in-depth exploration of related mechanisms. Summary of the Invention

[0004] The present invention provides a monitoring system for cerebral cortex nerve and immune activities based on temperature regulation to solve the above technical defects in the existing technology. By using a light-transmitting carrier to replace the skull corresponding to the position of the target brain region, combining wide-field imaging technology with a temperature regulation device, high-resolution monitoring of the activities of neurons and glial cells in the whole cerebral cortex of live animals is achieved under temperature regulation, providing a new technical tool for neuro-immune research.

[0005] The present invention provides a monitoring system for cerebral cortex nerve and immune activities based on temperature regulation, including: A temperature regulation device, including: A temperature regulation carrier, which internally accommodates a fluid; A temperature regulation component, used for adjusting the temperature of the fluid; A light-transmitting carrier, provided with a cavity directly accommodating the target brain region; A conveying component, respectively communicating with the temperature regulation carrier and the cavity of the light-transmitting carrier, used for conveying the fluid between the temperature regulation carrier and the cavity of the light-transmitting carrier; A brain temperature monitoring component, electrically connected to the temperature regulation component, used for real-time monitoring of the temperature information of the target brain region and feeding back the temperature information to the temperature regulation component; A cortical imaging device, used for collecting images of cerebral cortex nerve and immune activities of the target brain region through the light-transmitting carrier.

[0006] According to the monitoring system for cerebral cortex nerve and immune activities based on temperature regulation provided by the present invention, the light-transmitting range of the light-transmitting carrier is 185 - 2500 nm.

[0007] According to the monitoring system for cerebral cortex nerve and immune activities based on temperature regulation provided by the present invention, the light-transmitting carrier includes: A quartz carrier, the size of the quartz carrier being adapted to the size of the target brain region, and the height of the quartz carrier being less than or equal to the working distance of the cortical imaging device.

[0008] According to the monitoring system for cerebral cortex nerve and immune activities based on temperature regulation provided by the present invention, the temperature regulation component includes: A temperature regulation module; A medium inflow catheter, connected between the temperature regulation carrier and the temperature regulation module, for sending the fluid of the temperature regulation carrier into the temperature regulation module; A medium outflow catheter, connected between the temperature regulation module and the temperature regulation carrier, for sending the fluid that has been temperature-regulated by the temperature regulation module into the temperature regulation carrier; A temperature regulation pump body, provided on at least one of the medium inflow catheter and the medium outflow catheter, for pumping the fluid.

[0009] According to the monitoring system for cerebral cortex nerve and immune activities based on temperature regulation provided by the present invention, the temperature regulation component further includes: A temperature monitoring probe, electrically connected to the temperature regulation module, for monitoring the temperature information of the fluid in the temperature regulation carrier and transmitting the temperature information to the temperature regulation module.

[0010] According to the monitoring system for cerebral cortex nerve and immune activities based on temperature regulation provided by the present invention, the delivery component includes: A medium input pipe, connected between the temperature regulation carrier and the accommodation cavity of the light-transmitting carrier, for delivering the fluid in the temperature regulation carrier to the accommodation cavity; A medium output pipe, connected between the temperature regulation carrier and the accommodation cavity of the light-transmitting carrier, for returning the fluid in the accommodation cavity to the temperature regulation carrier.

[0011] According to the monitoring system for cerebral cortex nerve and immune activities based on temperature regulation provided by the present invention, the temperature regulation device further includes: An incubator, covering the outside of the temperature regulation carrier, for keeping the temperature regulation carrier warm.

[0012] According to the monitoring system for cerebral cortex nerve and immune activities based on temperature regulation provided by the present invention, it further includes: A fixing component, for fixing the light-transmitting carrier to a preset position.

[0013] According to the monitoring system for cerebral cortex nerve and immune activities based on temperature regulation provided by the present invention, the fixing component includes: Clamps, respectively clamped to the inlet end and the outlet end of the light-transmitting carrier; Fixing clips, used to be clamped to the preset position; A length adjusting component, one end of which is connected to the clamp, and the other end is connected to the fixing clip.

[0014] According to the brain cortex nerve and immune activity monitoring system based on temperature regulation provided by the present invention, the cortex imaging device includes: a light intensity modulation element, a dispersion device, a collimating lens, an objective lens, a dichroic mirror, a tube lens and a camera; Among them, after the light source passes through the light intensity modulation element, it is incident into the dispersion device for dispersion, passes through the collimating lens and the objective lens and then converges again on the sample, transmits through the dichroic mirror, the fluorescence of the sample is collected by the objective lens and then reflected by the dichroic mirror, and then passes through the tube lens After converging, it is collected by the camera. The camera respectively collects low-light-intensity images and high-light-intensity images, and performs a linear transformation on the low-light-intensity images and the high-light-intensity images according to the illumination relationship in the collection of the low-light-intensity images and the high-light-intensity images to obtain a wide-field high-resolution image.

[0015] The brain cortex nerve and immune activity monitoring system based on temperature regulation provided by the present invention uses a light-transmitting carrier to replace the skull corresponding to the location of the target brain region, combines wide-field imaging technology with a temperature regulation device, and realizes high-resolution monitoring of the activities of neurons and glial cells in the whole brain cortex of live animals under temperature regulation, providing a powerful tool for neuroscience, immunology and clinical medical research, and having important scientific research and clinical application values.

[0016] Compared with the prior art, the embodiment of the present invention replaces the skull with a light-transmitting carrier, eliminates skull scattering, can optimize the quality of wide-field imaging, ensures that the wide-field imaging is not interfered by skull scattered light, reduces optical path distortion, improves imaging clarity and signal-to-noise ratio, ensures the imaging quality of wide-field imaging in deep brain regions, realizes high-resolution dynamic observation of the whole brain range, simultaneously records neuron discharge and glial cell calcium activity, can break through the optical limitations of traditional wide-field imaging, and improves the reliability of the experiment.

[0017] Meanwhile, by providing temperature-regulated fluid to the light-transmitting carrier through the temperature regulation system and the conveying component, uniform and stable temperature regulation of each sub-region of the whole cerebral cortex can be achieved, meeting the stringent requirements of neuroimmune research. It provides a new experimental paradigm for the study of neuro-immune interaction, supports real-time observation of the effects of hypothermia (such as mild hypothermia treatment) on neuroimmune responses in live animals, and reveals the differences in temperature sensitivity among different brain regions. It can dynamically analyze the interaction mechanisms among microglia, astrocytes and neurons under hypothermic conditions, providing new targets for the treatment of diseases such as neuroinflammation and ischemic brain injury. It can promote the optimization of clinical hypothermic treatment strategies for acute brain injury. Through high-precision temperature regulation at the whole-brain scale, it simulates the brain protection effect of clinical hypothermic treatment and verifies the neuroprotective effects of different cooling rates and temperature maintenance times. It provides an experimental basis for rapid hypothermic intervention in acute brain injury (such as stroke and traumatic brain injury), and provides the possibility to optimize the treatment plan and improve the success rate of treatment.

[0018] Moreover, the temperature regulation device realizes a closed-loop feedback mechanism through the brain temperature monitoring component, which can ensure the temperature stability of long-term experiments and is used for chronic neuroimmune research. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] In order to more clearly illustrate the technical solutions in the present invention or the prior art, the following will briefly introduce the drawings required for the description of the embodiments or the prior art. Obviously, the drawings in the following description are some embodiments of the present invention. For those of ordinary skill in the art, other drawings can be obtained based on these drawings without creative efforts.

[0020] Figure 1 is a schematic diagram of a monitoring system for cerebral cortex nerve and immune activities based on temperature regulation provided by an embodiment of the present invention.

[0021] Figure 2 is Figure 1 a schematic diagram of the temperature regulation device in the monitoring system for cerebral cortex nerve and immune activities based on temperature regulation shown.

[0022] Figure 3 is a schematic diagram of the fixing component in the monitoring system for cerebral cortex nerve and immune activities based on temperature regulation provided by an embodiment of the present invention.

[0023] Figure 4 is a partial structural schematic diagram of the fixing component in the monitoring system for cerebral cortex nerve and immune activities based on temperature regulation provided by an embodiment of the present invention.

[0024] Figure 5 is a schematic diagram of the cortical imaging device in the monitoring system for cerebral cortex nerve and immune activities based on temperature regulation provided by an embodiment of the present invention.

[0025] Figure 6 It is the shooting effect diagram of the cortical imaging device in the brain cortex nerve and immune activity monitoring system based on temperature regulation provided by the embodiment of the present invention through the light-transmitting carrier.

[0026] Reference numerals: 10. Temperature regulation device; 11. Temperature regulation carrier; 12. Temperature regulation component; 121. Temperature regulation module; 122. Medium inflow conduit; 123. Medium outflow conduit; 124. Temperature regulation pump body; 125. Temperature monitoring probe; 13. Incubator; 20. Light-transmitting carrier; 30. Brain temperature monitoring component; 40. Cortical imaging device; 41. Light source; 42. Light intensity modulation element; 43. Dispersion device; 44. Collimating lens; 45. Dichroic mirror; 46. Objective lens; 47. Sample; 48. Tube lens; 49. Camera; 410. Controller; 50. Delivery component; 51. Medium input pipe; 52. Medium output pipe; 53. Delivery pump body; 60. Fixing component; 61. Clamp; 62. Fixing clip; 63. Length adjusting part. Detailed implementation manners

[0027] To make the objectives, technical solutions and advantages of the present invention clearer, the technical solutions in the present invention will be clearly and completely described below with reference to the accompanying drawings in the present invention. Obviously, the described embodiments are some but not all of the embodiments of the present invention. All other embodiments obtained by those of ordinary skill in the art based on the embodiments in the present invention without creative efforts shall fall within the protection scope of the present invention.

[0028] In the description of the embodiments of the present application, it should be noted that unless otherwise clearly defined and limited, the terms "connected" and "connection" should be understood in a broad sense. For example, it may be a fixed connection, a detachable connection, or an integral connection; it may be a mechanical connection or an electrical connection; it may be directly connected or indirectly connected through an intermediate medium. For those of ordinary skill in the art, the specific meanings of the above terms in the embodiments of the present application can be understood according to specific situations.

[0029] In the embodiments of the present application, unless otherwise expressly specified or limited, a first feature being "above" or "below" a second feature may mean that the first and second features are in direct contact, or that the first and second features are in indirect contact through an intermediate medium. Furthermore, a first feature being "above," "above," and "above" a second feature may mean that the first feature is directly above or obliquely above the second feature, or simply means that the first feature is higher in horizontal height than the second feature. A first feature being "below," "below," and "below" a second feature may mean that the first feature is directly below or obliquely below the second feature, or simply means that the first feature is lower in horizontal height than the second feature.

[0030] In the description of this specification, the description with reference to the terms "one embodiment", "some embodiments", "example", "specific example", or "some examples" means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the embodiments of the present application. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art can combine and combine different embodiments or examples described in this specification and the features of different embodiments or examples, unless they are contradictory.

[0031] Acute brain injuries (such as stroke and traumatic brain injury) carry high mortality and disability rates. The key to clinical treatment lies in maximizing time and delaying secondary damage. Studies have shown that localized brain hypothermia can effectively reduce brain metabolic rate and inhibit neuroinflammation, thereby extending the therapeutic window.

[0032] However, traditional whole-body cooling can suppress immune function, while simple physical cooling (e.g., ice caps) is difficult to accurately control brain temperature and is easily affected by the external environment and the body's thermoregulatory system, resulting in unstable temperature control and the inability to avoid the antagonistic effects of the body's thermoregulatory system. Therefore, an embodiment of the present invention provides a schematic diagram of a system for monitoring cerebral cortical neural and immune activity based on temperature regulation.

[0033] Figure 1 Schematic diagram of a cerebral cortex neural and immune activity monitoring system based on temperature regulation provided by an embodiment of the present invention. Figure 2 yes Figure 1 Schematic diagram of the temperature control device in the temperature control-based cerebral cortex neural and immune activity monitoring system.

[0034] See Figure 1 and Figure 2, the embodiments of the present invention provide a monitoring system for cerebral cortex nerve and immune activities based on temperature regulation, which provides innovative ideas for the hypothermic treatment of acute brain injury, promotes the research on neuroimmune mechanisms, and has important clinical transformation value and scientific research application prospects.

[0035] The monitoring system for cerebral cortex nerve and immune activities based on temperature regulation includes a temperature regulation device 10, a light-transmitting carrier 20, a conveying component 50, a brain temperature monitoring component 30, and a cortical imaging device 40.

[0036] The temperature regulation device 10 includes a temperature regulation carrier 11 and a temperature regulation component 12. The shape of the temperature regulation carrier 11 can be a cuboid or a cylinder. The temperature regulation carrier 11 can be a sealed container with good heat insulation performance. For example, the temperature regulation carrier 11 is made of single-layer or double-layer stainless steel. When the temperature regulation carrier 11 is made of double-layer stainless steel, heat insulation materials (such as a vacuum insulation layer or high-performance heat insulation foam) can be filled in the middle of the double-layer stainless steel.

[0037] Among them, the volume of the temperature regulation carrier 11 is designed according to actual needs, for example, ranging from 1 liter to 10 liters, to accommodate enough fluid (such as water) to provide sufficient temperature control medium for the light-transmitting carrier 20. The temperature regulation carrier 11 can be installed near experimental equipment or clinical monitoring equipment. For example, in animal experiments, it is installed on a bracket near the animal breeding cage, or in a clinical scenario, it is installed on a trolley beside the hospital bed. The temperature regulation carrier 11 needs to be kept stable to avoid abnormal fluid flow caused by shaking.

[0038] The temperature regulation component 12 is used to adjust the temperature of the fluid. The temperature regulation component 12 can adopt a thermoelectric cooler based on the Peltier effect. The thermoelectric cooler can realize the refrigeration or heating function according to the direction of the current. By precisely controlling the magnitude of the current input to the thermoelectric cooler, the temperature of the fluid can be accurately adjusted, and the adjustment accuracy can reach ±0.1°C. The temperature regulation component 12 can also adopt a traditional heating-cooling cycle system, such as a system composed of a heating wire and a refrigeration compressor. The heating wire is used to increase the temperature of the fluid, and the refrigeration compressor is used to lower the temperature. In this system, based on the information fed back by the brain temperature monitoring component 30, the temperature regulation device 10 can selectively start the heating wire or the refrigeration compressor to work to adjust the temperature.

[0039] It should be noted that according to different experimental or clinical requirements, the temperature regulation component 12 can adjust the temperature range of the fluid differently. For example, when studying the effects of hypothermia on cerebral cortex nerve and immune activities, the temperature range can be set to 10°C - 30°C; while when simulating the normal physiological state or conducting certain special studies, the temperature range can be extended to 30°C - 40°C.

[0040] The shape of the light-transmitting carrier 20 is designed to conform to the shape of the target brain region. For example, for the cerebral cortex of a mouse, it can be a thin sheet-like structure with a certain curvature. The material of the light-transmitting carrier 20 can be selected from transparent and biocompatible materials such as quartz, polycarbonate, or polymethyl methacrylate (PMMA). The light-transmitting carrier 20 is provided with a receiving cavity directly accommodating the target brain region.

[0041] The light-transmitting carrier 20 can be fixed to the target brain region through a bioadhesive fluid or the like to replace the skull corresponding to the position where the target brain region is located. The bioadhesive fluid is made of a material that is non-irritating to brain tissue and can maintain viscosity in a physiological environment, such as fibrin glue.

[0042] In related technologies, due to the high scattering of the skull affecting the imaging quality, and wide-field imaging being sensitive to the refractive index and working distance of the sample 47, it is difficult to maintain high resolution in deep brain regions. However, in the embodiments of the present invention, by replacing the skull with the light-transmitting carrier 20, the skull scattering can be eliminated, the wide-field imaging quality can be optimized, and at the same time, as an efficient heat exchange interface, it is convenient for local temperature control of brain tissue.

[0043] The delivery component 50 is respectively communicated with the temperature regulation carrier 11 and the receiving cavity of the light-transmitting carrier 20, and is used for fluid delivery between the temperature regulation carrier 11 and the receiving cavity of the light-transmitting carrier 20.

[0044] The brain temperature monitoring component 30 is electrically connected to the temperature regulation component 12, and is used for real-time monitoring of the temperature information of the target brain region and feeding back the temperature information to the temperature regulation component 12. The brain temperature monitoring component 30 can include a temperature sensor and corresponding connecting wires. The temperature sensor in the brain temperature monitoring component 30 can adopt a micro-thermocouple probe or a thermistor probe. The micro-thermocouple probe has the characteristics of fast response speed and high measurement accuracy, and can accurately sense the temperature change of the target brain region in a short time. The thermistor probe has high sensitivity, especially in the case of a narrow temperature change range, and can accurately measure tiny temperature fluctuations. Among them, the diameter of the probe is less than 200μm.

[0045] It should be noted that multiple temperature sensors can be evenly distributed around the target brain region or on the surface where the light-transmitting carrier 20 contacts the brain tissue. For example, for the monitoring of the mouse cerebral cortex, 3 to 5 temperature sensors can be arranged. The sensors are accurately placed at positions that can represent the average temperature of the target brain region to ensure that the collected temperature information can accurately reflect the actual temperature state of the target brain region.

[0046] The cortical imaging device 40 is used to collect images of the cerebral cortex nerves and immune activities of the target brain region through the light-transmitting carrier 20.

[0047] Among them, the cortical imaging device 40 can adopt two-photon microscopy imaging technology. The two-photon microscope can penetrate a certain depth of brain tissue and perform high-resolution imaging on the neural and immune activities of the target brain region. The two-photon microscope uses two low-energy photons to simultaneously excite fluorescently labeled cells or molecules, reducing light scattering and damage to surrounding tissues, thereby obtaining clear images of cell structures and activities.

[0048] In addition, the cortical imaging device 40 can also adopt the miniaturized functional magnetic resonance imaging (fMRI) technology for monitoring small animals or local brain regions in clinical settings. It can indirectly reflect the neural and immune activity conditions by detecting blood flow changes in the cerebral cortex.

[0049] It should be noted that during the image acquisition process, continuous image acquisition can be performed according to a preset time interval. For example, for monitoring rapidly changing neural activities, images can be acquired every 1 - 5 seconds; for the relatively slow process of immune activities, images can be acquired every 5 - 30 seconds. The acquired images are analyzed by specialized image processing software. The software can quantitatively analyze features such as cell morphology, fluorescence intensity changes, and blood flow signal changes in the images, thereby obtaining relevant parameters of neural and immune activities in the target brain region, such as the firing frequency of neurons and the migration speed of immune cells.

[0050] It can be understood that the monitoring system for neural and immune activities in the cerebral cortex based on temperature regulation provided by the embodiments of the present invention uses the light-transmitting carrier 20 to replace the skull corresponding to the location of the target brain region, combines wide-field imaging technology with the temperature regulation device 10, and realizes high-resolution monitoring of the activities of neurons and glial cells in the whole cerebral cortex of live animals under temperature regulation, providing a powerful tool for neuroscience, immunology, and clinical medical research, and having important scientific research and clinical application values.

[0051] Compared with the prior art, the embodiments of the present invention use the light-transmitting carrier 20 to replace the skull, eliminating skull scattering, which can optimize the wide-field imaging quality, ensure that the wide-field imaging is not interfered by skull scattered light, reduce optical path distortion, improve imaging clarity and signal-to-noise ratio, ensure the imaging quality of the wide-field imaging in deep brain regions, realize high-resolution dynamic observation of the whole brain range, record neuron firing and glial cell calcium activities simultaneously, and can break through the optical limitations of traditional wide-field imaging, improving the reliability of the experiment.

[0052] Meanwhile, by means of the temperature regulation system and the conveying component 50, a temperature-regulated fluid is provided for the light-transmitting carrier 20, enabling uniform and stable temperature regulation of each sub-region of the whole cerebral cortex, meeting the stringent requirements of neuro-immunological research. It provides a new experimental paradigm for the study of neuro-immune interaction, supports real-time observation of the effects of hypothermia (such as mild hypothermia treatment) on neuro-immune responses in live animals, and reveals differences in temperature sensitivity among different brain regions. It can dynamically analyze the interaction mechanisms among microglia, astrocytes, and neurons under hypothermic conditions, providing new targets for the treatment of diseases such as neuroinflammation and ischemic brain injury. It can promote the optimization of clinical hypothermia treatment strategies for acute brain injury. Through high-precision temperature regulation at the whole-brain scale, it simulates the brain-protective effect of clinical hypothermia treatment and verifies the neuroprotective effects of different cooling rates and temperature maintenance times. It provides an experimental basis for rapid hypothermic intervention in acute brain injury (such as stroke and traumatic brain injury), and offers the possibility of optimizing treatment plans and improving the success rate of treatment.

[0053] Moreover, the temperature regulation device 10 achieves a closed-loop feedback mechanism through the brain temperature monitoring component 30, which can ensure the temperature stability during long-term experiments and is used for chronic neuro-immunological research.

[0054] In some embodiments of the present invention, the light-transmitting range of the light-transmitting carrier 20 is from 185 nm to 2500 nm, which can adapt to various laser excitation conditions.

[0055] A material with good optical properties and biocompatibility is selected as the light-transmitting carrier 20, such as fused silica JGS1. Fused silica has a high transmittance in the ultraviolet to near-infrared band, which can meet the light-transmitting requirements from 185 nm to 2500 nm.

[0056] The shape of the light-transmitting carrier 20 is set according to the shape and size of the target brain region. For example, the light-transmitting carrier 20 is set as a thin sheet shape, an arc shape, etc., to better fit the surface of the brain region and achieve uniform temperature regulation and light transmission. Additionally, a reasonable temperature control channel and a medium circulation system are designed inside the light-transmitting carrier 20 to form a containing cavity, ensuring that the fluid can be evenly distributed and achieving precise temperature regulation of the brain region.

[0057] In the experiment of monitoring the neural and immune activities in the cerebral cortex of animals, the light-transmitting carrier 20 is fixed on the surface of the animal brain region. The temperature of the carrier is regulated by the temperature regulation device 10, and at the same time, the cortical imaging device 40 is used to collect images of neural and immune activities through the light-transmitting carrier 20, realizing real-time monitoring and temperature regulation of the cerebral cortex activities.

[0058] In the research on the treatment of clinical brain injury, when the light-transmitting carrier 20 is applied to the brain region of a patient, new means and methods for the treatment and monitoring of brain injury can be provided through precise temperature regulation and light-transmitting performance.

[0059] It should be noted that the shape of the light-transmitting carrier 20 can be a cylinder or a cuboid. The light-transmitting carrier 20 is provided with an inlet end and an outlet end, both of which are tubular parts. The inner diameter of the tube openings at the inlet end and the outlet end is 2 mm, and the outer diameter is 4 mm. The inlet end is used for the fluid after temperature adjustment to enter the light-transmitting carrier 20, and the outlet end is used for the fluid after temperature control to return to the temperature control carrier 11. The diameter of the light-transmitting carrier 20 is adapted to the headpiece of the experimental animal and can be designed to be 6, 7, 9 to 100 mm, etc. The specific size depends on the area of the brain region of the experimental animal that needs to be cooled.

[0060] In some embodiments of the present invention, the light-transmitting carrier 20 includes a quartz carrier. The size of the quartz carrier is adapted to the size of the target brain region, and the height of the quartz carrier is less than or equal to the working distance of the cortical imaging device 40.

[0061] When the light-transmitting carrier 20 is applied to the laboratory for the brain of experimental mice, the light-transmitting carrier 20 is designed to fit the shape of the cerebral cortex of the mouse. Its length can be 1.2 - 1.8 cm, and the width is 1 - 1.4 cm to completely cover the cerebral cortex of the mouse. The thickness (height) of the light-transmitting carrier 20 is designed to be 1 - 2 mm, which can effectively accommodate the fluid for temperature control and will not cause excessive pressure on the mouse brain.

[0062] For imaging of the mouse cerebral cortex, the working distance of the cortical imaging device 40 (such as a small two-photon microscope) used is usually in the range of 3 mm to 5 mm. This distance is to avoid damaging the mouse brain tissue while ensuring sufficient resolution and field of view. Since the height of the light-transmitting carrier 20 is 1 - 2 mm, which is significantly less than the working distance (3 - 5 mm) of the cortical imaging device 40, it meets the requirement that the height of the light-transmitting carrier 20 is less than or equal to the working distance of the cortical imaging device 40. This enables the imaging system to clearly collect images of the nerve and immune activities at the preset temperature of the mouse cerebral cortex through the light-transmitting carrier 20.

[0063] When the light-transmitting carrier 20 is applied clinically, assuming a local brain region in the frontal lobe of the human brain is studied, its length may be 3 - 5 cm, and the width is 2 - 4 cm. The thickness of the brain region is approximately 1 - 2 cm, depending on its position in the frontal lobe. The light-transmitting carrier 20 is customized according to the shape of this local brain region. Its length is designed to be 3.5 - 5.5 cm, and the width is 2.5 - 4.5 cm, which can completely cover the target brain region. The height (thickness) of the carrier is 0.8 - 1.5 cm to ensure good adaptation to the surrounding brain tissue while effectively regulating the temperature.

[0064] When imaging the human cerebral cortex, the working distance of the cortical imaging device 40 used (such as a locally adapted version of functional magnetic resonance imaging - fMRI for clinical research or a high - resolution optical imaging device) may be in the range of 2 - 5 cm. Since the height of the light - transmitting carrier 20 is 0.8 - 1.5 cm, which is less than the working distance of the cortical imaging device 40 (2 - 5 cm), the requirements are met. In this way, the cortical imaging device 40 can be used to collect images of neural and immune activities at a preset temperature in this local brain area of the human frontal lobe through the light - transmitting carrier 20, providing effective data support for the research and treatment of related diseases.

[0065] In some embodiments of the present invention, the temperature control component 12 includes a temperature control module 121, a medium inflow conduit 122, a medium outflow conduit 123, and a temperature control pump body 124.

[0066] The temperature control module 121 can use a controller 410 and a thermoelectric cooler as core components. When an electric current passes through a loop composed of two different conductors, heat absorption or heat release occurs at the two connection points, which is used to pump a fluid into it for cooling or heating. For example, in a scenario where precise low - temperature control of the cerebral cortex temperature is required for research, by adjusting the direction and magnitude of the electric current, the thermoelectric cooler can quickly reduce the temperature of the fluid to the required range. For example, it can be reduced from room temperature of 25°C to 10°C within 10 minutes, and the adjustment accuracy can reach ±0.1°C.

[0067] The temperature control module 121 can also combine a compression refrigeration system with heating wires. The compression refrigeration system consists of a compressor, a condenser, an evaporator, and a throttling device. When the fluid temperature needs to be reduced, the compressor works, causing the refrigerant to circulate in the system, and the evaporator absorbs heat, thereby reducing the temperature of the fluid. When the fluid needs to be heated, the heating wires start to work. The heating wires can be evenly distributed at the part where the temperature control module 121 is connected to the medium inflow conduit 122 to ensure uniform heat transfer to the fluid.

[0068] The medium inflow conduit 122 is connected between the temperature control carrier 11 and the temperature control module 121, and is used to send the fluid of the temperature control carrier 11 into the temperature control module 121. The medium outflow conduit 123 is connected between the temperature control module 121 and the temperature control carrier 11, and is used to send the temperature - regulated fluid into the temperature control carrier 11. The temperature control pump body 124 is provided on at least one of the medium inflow conduit 122 and the medium outflow conduit 123 for pumping the fluid. In the embodiments of the present invention, the case where the temperature control pump body 124 is provided on the medium inflow conduit 122 is taken as an example for illustration.

[0069] Among them, both the medium inflow conduit 122 and the medium outflow conduit 123 can be made of medical-grade silicone tubing. This material has good flexibility, biocompatibility, and chemical stability. The inner diameter of the silicone tubing can be 3 - 5 millimeters. For example, a silicone tubing with an inner diameter of 4 millimeters can be selected to ensure that the fluid can flow between the conduit and the receiving cavity at an appropriate flow rate. The wall thickness of the conduit is 1 - 2 millimeters to ensure that it has sufficient strength to withstand the pressure of the temperature control pump body 124, while not being too thick to affect heat transfer.

[0070] The connection between the medium inflow conduit 122 and the medium outflow conduit 123 and the temperature control module 121 uses a sealed threaded connection. External threads are machined at one end of the conduit, and internal threads are provided at the corresponding interface on the temperature control module 121. Threaded connection can ensure the tightness of the connection and prevent fluid leakage.

[0071] The outside of the medium inflow conduit 122 and the medium outflow conduit 123 can be wrapped with a layer of heat insulation material, such as polyurethane foam, to reduce heat loss during transportation.

[0072] Among them, the temperature control pump body 124 can be a peristaltic pump or a centrifugal pump. The peristaltic pump pushes the fluid in the tube by rolling wheels squeezing the silicone tubing. The rolling wheels squeeze the silicone tubing in sequence to form a forward driving force. For example, when precise control of the fluid flow rate is required, the peristaltic pump can achieve this by adjusting the rotation speed of the rolling wheels. The impeller inside the centrifugal pump body rotates at high speed driven by an electric motor, generating centrifugal force, thereby sucking the fluid from the inlet and discharging it from the outlet. The centrifugal pump body is more suitable in cases where a large flow rate is required.

[0073] In some embodiments of the present invention, the temperature control assembly 12 further includes a temperature monitoring probe 125. The temperature monitoring probe 125 is electrically connected to the temperature control module 121 and is used to monitor the temperature information of the fluid in the temperature control carrier 11 and transmit the temperature information to the temperature control module 121 to keep the temperature of the fluid in the temperature control carrier 11 stable.

[0074] Among them, the temperature monitoring probe 125 can be a thermocouple probe. The thermocouple probe works based on the Seebeck effect and consists of two different metal wires. When there is a temperature difference at both ends, a thermoelectric potential is generated, and the temperature value can be accurately obtained by measuring the thermoelectric potential. The temperature monitoring probe 125 can also be a thermistor probe. The resistance value of the thermistor probe changes with temperature, and the temperature value can be obtained by measuring the change in the resistance value.

[0075] Continue to refer to Figure 2 , in some embodiments of the present invention, the conveying assembly 50 includes a conveying pump body 53, a medium input pipe 51, and a medium output pipe 52.

[0076] The transfer pump body 53 is similar to the above-mentioned temperature control pump body 124, and a peristaltic pump or a centrifugal pump can be used. The medium input pipe 51 is connected between the accommodating cavity of the temperature control carrier 11 and the light-transmitting carrier 20, and is used to transport the fluid in the temperature control carrier 11 to the accommodating cavity. The medium output pipe 52 is connected between the accommodating cavity of the temperature control carrier 11 and the light-transmitting carrier 20, and is used to return the fluid in the accommodating cavity to the temperature control carrier 11; the transfer pump body 53 is arranged on at least one of the medium input pipe 51 and the medium output pipe 52 for pumping the fluid.

[0077] Both the medium input pipe 51 and the medium output pipe 52 are made of medical silicone tubes. The medical silicone tubes have good biocompatibility and will not have an adverse effect on the human body or experimental animals. The inner diameter of the silicone tube is 3.5 mm. The medium input pipe 51 is connected to the pipe body at the inlet end of the light-transmitting carrier 20 for transferring the fluid (such as water) in the temperature control carrier 11 to the light-transmitting carrier 20. The medium output pipe 52 is connected to the pipe body at the outlet end of the light-transmitting carrier 20 for discharging the fluid (such as water) in the light-transmitting carrier 20.

[0078] Among them, when the medium input pipe 51 is connected to the transfer pump body 53 and the medium output pipe 52 is connected to the transfer pump body 53, quick-release connectors can be used. The quick-release connector consists of a male head and a female head. The male head and the female head are sealed through a sealing structure (such as an O-ring), which is convenient for installation, disassembly and maintenance.

[0079] Continue to refer to Figure 2 In some embodiments of the present invention, the temperature control device 10 further includes a heat preservation box 13. The heat preservation box 13 covers the outside of the temperature control carrier 11 for heat preservation of the temperature control carrier 11.

[0080] The heat preservation box 13 can effectively reduce the heat exchange between the temperature control carrier 11 and the external environment, making the temperature inside the temperature control carrier more stable. This is crucial for experiments or application scenarios that require precise temperature control (such as cerebral cortex temperature control research), and helps to improve the accuracy and reliability of experimental results. In addition, the heat preservation box 13 can reduce the energy consumption of the temperature control system by reducing heat dissipation. In long-term experiments or clinical applications, this can not only save energy, but also reduce the operating cost.

[0081] Among them, the length, width and height of the heat preservation box 13 should be greater than or equal to 1.2 times the length, width and height of the temperature control carrier 11, so that the temperature control carrier 11 can be completely located inside the heat preservation box 13.

[0082] Figure 3 It is a schematic structural diagram of the fixing component 60 in the monitoring system for cerebral cortex nerve and immune activities based on temperature control provided by the embodiment of the present invention. Figure 4It is a partial structural schematic diagram of the fixing component 60 in the monitoring system for cerebral cortex nerve and immune activities based on temperature regulation provided by an embodiment of the present invention.

[0083] Refer to Figure 3 and Figure 4 The monitoring system for cerebral cortex nerve and immune activities based on temperature regulation further includes a fixing component 60, and the fixing component 60 is used to fix the light-transmitting carrier 20 to a preset position to prevent the light-transmitting carrier 20 from shaking to change the imaging surface focal length.

[0084] The fixing component 60 includes a clamp 61, a "U"-shaped fixing clip 62, and a length adjusting component 63. The clamp 61 is clamped to the inlet end and the outlet end of the light-transmitting carrier 20; the fixing clip 62 is used to be clamped to a preset position, and this preset position can be a specific position on the cranial vertex. One end of the length adjusting component 63 is connected to the clamp 61, and the other end is connected to the fixing clip 62, and it is used to adjust the distance between the clamp 61 and the fixing clip 62, so as to play a role in supporting and adjusting the height of the light-transmitting carrier 20.

[0085] Figure 5 It is a schematic diagram of the cortical imaging device 40 in the monitoring system for cerebral cortex nerve and immune activities based on temperature regulation provided by an embodiment of the present invention.

[0086] Refer to Figure 5 The cortical imaging device 40 includes a light source 41, a light intensity modulation element 42, a dispersion device 43, a collimating lens 44, an objective lens 46, a sample 47, a dichroic mirror 45, a tube lens 48, a camera 49, and a controller 410.

[0087] Among them, after the light source 41 passes through the light intensity modulation element 42, it is incident into the dispersion device 43 for dispersion, and after passing through the collimating lens 44 and the objective lens 46, it converges again on the sample 47, and then passes through the dichroic mirror 45. The fluorescence of the sample 47 is collected by the objective lens 46 and then reflected by the dichroic mirror 45, and then converges through the tube lens 48 and is collected by the camera 49. The camera 49 respectively collects low-light intensity images and high-light intensity images, and according to the illumination relationship in the collection of the low-light intensity images and the high-light intensity images, linearly transforms the low-light intensity images and the high-light intensity images to obtain wide-field high-resolution images.

[0088] That is, after passing through the light intensity modulation component 42, the light source 41 enters the dispersion device 43 for dispersion, and after passing through the collimating lens 44 and the objective lens 46, it converges again on the sample 47, where it passes through the dichroic mirror 45. The fluorescence of the sample 47 is collected by the objective lens 46 and then reflected by the dichroic mirror 45. After that, it is converged by the tube lens 48 and collected by the camera 49. The camera 49 respectively collects low-light intensity images and high-light intensity images, and performs a linear transformation on the low-light intensity images and the high-light intensity images according to the illumination relationship in the collection of the low-light intensity images and the high-light intensity images to obtain a wide-field high-resolution image. The controller 410 is used to control the synchronous operation of the light modulation component and the camera 49, and the controller 410 selects a PC and an NI board-level controller 410.

[0089] In the embodiment of the present invention, the light intensity modulation component 42 selects an electro-optic modulator, and the dispersion device 43 selects a grating. The light source 41 includes low illumination and high illumination. Among them, in the case of low illumination, when the fluorescence of the sample 47 does not saturate, low-light intensity images are collected. In the case of high illumination, when the fluorescence of the sample 47 saturates, high-light intensity images are collected.

[0090] Figure 6 It is the shooting effect diagram of the cortical imaging device 40 in the brain cortex nerve and immune activity monitoring system based on temperature regulation provided by the embodiment of the present invention through the light-transmitting carrier 20.

[0091] Refer to Figure 6 , the red part is the edge of the light-transmitting carrier 20. It can be seen from the figure that the scheme is indeed feasible. By covering the light-transmitting carrier 20 that covers the entire cerebral cortex, that is, replacing the animal skull with the light-transmitting carrier 20 and fixing it on the animal's head, and using a fluid at a specific temperature (such as water) to conduct at high speed in the light-transmitting carrier 20 to achieve real-time and accurate regulation of the brain temperature, it is possible to simultaneously observe and regulate the activities of neurons and glial cells in each sub-region of the entire cerebral cortex, and accurately analyze the biological basis of the nerve and immune responses under hypothermia regulation from the whole-brain range. Furthermore, it provides an effective rapid hypothermia treatment strategy for acute brain injury diseases. It helps to provide a closed-loop research strategy for brain temperature regulation and biological basic information detection in the field of brain science, provides feasibility technical support and biological mechanism support for further analyzing the nerve-immune interaction mechanism under hypothermia regulation, and promoting the hypothermia medical treatment plan for clinical acute trauma.

[0092] In addition, the brain cortex nerve and immune activity monitoring system based on temperature regulation provided by the embodiment of the present invention can also realize synchronous detection of single-cell fluorescence calcium activity in the entire cerebral cortex and closed-loop brain temperature regulation, providing a new regulation means for the temperature regulation and mechanism research of clinical acute brain injury diseases, and having important value in extending the treatment time window for critically injured patients.

[0093] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that they can still modify the technical solutions described in the foregoing embodiments, or perform equivalent replacements for some of the technical features; and these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the various embodiments of the present invention.

Claims

1. A monitoring system for cerebral cortical nerve and immune activities based on temperature regulation, characterized in that, Comprising: A temperature control device, comprising: A temperature control carrier, internally accommodating a fluid; A temperature control component for adjusting the temperature of the fluid; A light-transmitting carrier provided with a receiving cavity directly accommodating the target brain region; A conveying component respectively communicating with the temperature control carrier and the receiving cavity of the light-transmitting carrier for conveying the fluid between the temperature control carrier and the receiving cavity of the light-transmitting carrier; A brain temperature monitoring component electrically connected to the temperature control component for real-time monitoring of the temperature information of the target brain region and feedback of the temperature information to the temperature control component; A cortical imaging device for collecting images of the cerebral cortex nerves and immune activities of the target brain region through the light-transmitting carrier.

2. The monitoring system for cerebral cortex nerve and immune activities based on temperature regulation according to claim 1, wherein The light-transmitting range of the light-transmitting carrier is 185 - 2500 nm.

3. The monitoring system for cerebral cortex nerve and immune activities based on temperature regulation according to claim 2, characterized in that, The light-transmitting carrier comprises: A quartz carrier, the size of the quartz carrier being adapted to the size of the target brain region, and the height of the quartz carrier being less than or equal to the working distance of the cortical imaging device.

4. The monitoring system for cerebral cortex nerve and immune activities based on temperature regulation according to claim 1, characterized in that, The temperature control component comprises: A temperature control module; A medium inflow conduit connected between the temperature control carrier and the temperature control module for feeding the fluid in the temperature control carrier into the temperature control module; A medium outflow conduit connected between the temperature control module and the temperature control carrier for feeding the fluid that has been temperature-adjusted by the temperature control module into the temperature control carrier; A temperature control pump body provided on at least one of the medium inflow conduit and the medium outflow conduit for pumping the fluid.

5. The monitoring system for cerebral cortex nerve and immune activities based on temperature regulation according to claim 4, wherein The temperature control component further comprises: A temperature monitoring probe electrically connected to the temperature control module for monitoring the temperature information of the fluid in the temperature control carrier and transmitting the temperature information to the temperature control module.

6. The monitoring system for cerebral cortex nerve and immune activities based on temperature regulation according to claim 4, characterized in that, The conveying component comprises: A medium input pipe connected between the temperature control carrier and the receiving cavity of the light-transmitting carrier for conveying the fluid in the temperature control carrier to the receiving cavity; A medium output pipe connected between the temperature control carrier and the receiving cavity of the light-transmitting carrier for returning the fluid in the receiving cavity to the temperature control carrier; A conveying pump body provided on at least one of the medium input pipe and the medium output pipe for pumping the fluid.

7. The monitoring system for cerebral cortex nerve and immune activities based on temperature regulation according to claim 1, wherein The temperature control device further comprises: A heat preservation box covering the outside of the temperature control carrier for heat-preserving the temperature control carrier.

8. The monitoring system for cerebral cortex nerve and immune activities based on temperature regulation according to claim 1, wherein Also comprising: A fixing component for fixing the light-transmitting carrier to a preset position.

9. The monitoring system for cerebral cortex nerve and immune activities based on temperature regulation according to claim 8, wherein The fixing component comprises: A clamp respectively clamped to the inlet end and the outlet end of the light-transmitting carrier; A fixing clip for clamping to the preset position; A length adjusting component, one end of which is connected to the clamp and the other end of which is connected to the fixing clip.

10. The monitoring system for cerebral cortex nerve and immune activities based on temperature regulation according to any one of claims 1 to 9, characterized in that, The cortical imaging device comprises: a light intensity modulation element, a dispersion device, a collimating lens, an objective lens, a dichroic mirror, a tube lens and a camera; Among them, after the light source passes through the light intensity modulation element, it enters the dispersion device for dispersion, and after passing through the collimating lens and the objective lens, it is re-converged on the sample. It passes through the dichroic mirror, and the fluorescence of the sample is collected by the objective lens and then reflected by the dichroic mirror. After that, it is converged by the tube lens and then collected by the camera. The camera respectively collects low-light intensity images and high-light intensity images, and performs a linear transformation on the low-light intensity images and the high-light intensity images according to the illumination relationship in the collection of the low-light intensity images and the high-light intensity images to obtain a wide-field high-resolution image.

Images