Device for monitoring cerebrospinal fluid pressure of animal occipital pond by using optical fiber pressure sensor

Abstract

The invention provides a device for monitoring cerebrospinal fluid pressure of an animal occipital pond by using an optical fiber pressure sensor, and belongs to the technical field of medicine. The invention provides a device for monitoring the pressure of cerebrospinal fluid in an occipital pond of an animal by using an optical fiber pressure sensor. The device comprises a sleeve and the optical fiber pressure sensor, according to the method, the cerebrospinal fluid pressure is monitored in the occipital pool, the hydrodynamic change condition of the cerebrospinal fluid in the craniocervical junction area can be directly reflected, and a new thought is provided for early screening and diagnosis of clinical diseases related to abnormal cerebrospinal fluid dynamics in the craniocervical junction area.

Description

Technical Field

[0001] The invention relates to the field of medical technology, and in particular to a device for monitoring the pressure of cerebrospinal fluid in the cisterna magna of animals by using an optical fiber pressure sensor. Background Art

[0002] Neurodegenerative diseases (such as Alzheimer's disease) are closely related to abnormal clearance of metabolic waste in the brain parenchyma. The tracer drug is injected into the occipital cisterna magna or lateral ventricle. Within a specific period of time after the tracer injection, the circulation pathway and movement of the tracer are observed through two-photon imaging technology, transcranial macroscopic imaging, magnetic resonance imaging and other methods, and then the cerebrospinal fluid clearance pathway of metabolic waste in the brain is evaluated. At this stage, this injection technology has been widely used in animal experiments.

[0003] Traumatic brain injury, hydrocephalus and other diseases often cause intracranial hypertension. Implanting a catheter in the ventricle is the "gold standard" for clinical measurement of human intracranial pressure. The technology of monitoring intracranial pressure in the epidural space, subdural space (subarachnoid space) and brain parenchyma (lateral ventricle) of experimental animals is relatively mature. Among them, monitoring cerebrospinal fluid pressure with the help of fiber optic pressure sensors can obtain high-fidelity pressure signals, sensitively and accurately record pressure values, and thus reflect the real-time changes in cerebrospinal fluid pressure. The main working process of the fiber optic pressure sensor is: ① The light source emits light waves and sends them to the sensor head (modulator) through the transmission optical fiber; ② In the modulator, the light waves interact with the external pressure; ③ The modulated light waves are transmitted to the photodetector through the transmission optical fiber, and the light signals are converted into electrical signals; ④ The electrical signals are processed by the signal processor to restore the measured pressure value.

[0004] Central nervous system diseases with abnormal cerebrospinal fluid dynamics in the craniocervical junction, represented by Chiari I malformation and syringomyelia, have always been a hot topic in clinical research. Among them, the occipital cistern is a hub for regulating cerebrospinal fluid dynamics between the cranial cavity and the spinal canal, and plays a key role in maintaining the balance and stability of cerebrospinal fluid pressure in the craniocervical junction. Abnormal pressure environment in the occipital cistern may be the key pathological mechanism of such diseases. The cerebrospinal fluid pressure changes obtained by lumbar puncture monitoring in the prior art reflect the distal effects of cerebrospinal fluid pressure changes caused by the disease, and cannot directly and accurately reflect the cerebrospinal fluid pressure changes in the lesion site (occipital cistern) of Chiari I malformation and other diseases (the cerebrospinal fluid pressure changes in the lumbar subarachnoid space may be caused by the occipital cistern pressure changes); it is not conducive to the early screening and diagnosis of the disease. In animal experiments, there is no experimental method for monitoring the cerebrospinal fluid pressure in the occipital cistern. According to the previous pressure monitoring method, monitoring the changes in intracranial pressure in the epidural space, subdural space or lateral ventricle cannot accurately reflect the degree of pathology of such diseases (intracranial pressure changes may be caused by changes in the pressure of the occipital cistern). Therefore, it is urgent to invent a new device for monitoring the cerebrospinal fluid pressure in the occipital cistern, which is very important for basic research and clinical application translation research. At the same time, conducting cerebrospinal fluid pressure monitoring experiments on animal models will help to gain a deeper understanding of the pathogenesis of diseases related to abnormal cerebrospinal fluid pressure, and provide new ideas for the diagnosis and treatment of related diseases. Summary of the invention

[0005] The purpose of the present invention is to provide a device that uses an optical fiber pressure sensor to monitor the cerebrospinal fluid pressure in the cisterna magna of animals, which can directly reflect the changes in the cerebrospinal fluid fluid dynamics at the craniocervical junction and provide new ideas for the early screening and diagnosis of clinical diseases related to abnormal cerebrospinal fluid dynamics at the craniocervical junction.

[0006] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0007] The invention discloses a device for monitoring the cerebrospinal fluid pressure of the cisterna magna of an animal by using an optical fiber pressure sensor. The device comprises a sleeve and an optical fiber pressure sensor.

[0008] Preferably, the cannula is inserted into the cerebrospinal fluid of the cisterna magna to establish a fiber optic channel.

[0009] Preferably, the optical fiber pressure sensor comprises a connector, an optical fiber and a probe.

[0010] Preferably, the probe passes through the optical fiber channel to reach the cerebrospinal fluid in the cisterna magna to monitor the cerebrospinal fluid pressure in the cisterna magna of the animal.

[0011] Preferably, before the sensor probe is passed through the optical fiber channel, the optical fiber pressure sensor is first started and zeroed, and after the pressure baseline is stabilized, the probe is inserted through the optical fiber channel into the cisterna magna and fixed.

[0012] Preferably, the animal is a male ICR mouse aged 8-12 weeks.

[0013] Preferably, the cannula is a disposable sterile puncture needle 24G cannula, 2 cm long, and the puncture depth is 1 mm, so as to establish a fiber optic channel.

[0014] Preferably, the zero calibration is to adjust the pressure baseline to a curve fluctuating within the range of 0±0.3 mmHg.

[0015] Preferably, the monitoring requires collecting a cerebrospinal fluid pressure waveform graph of the cistern magna for 30-45 seconds.

[0016] The present invention optimizes the existing experimental methods of "cistern drug injection method" and "monitoring cerebrospinal fluid pressure through optical fiber pressure sensor", and aims at the difficulties in the prior art, such as the anatomical location of the cistern is located in the deepest layer of the craniocervical junction, and the location and size of the cistern vary in different experimental animals; the technical solution of the present invention is to separate the superficial tissue of the back of the neck with minimal damage and accurately expose the location of the cistern; in addition, during the process of implanting the puncture needle cannula into the cistern, the volume of the cistern is small and it is adjacent to important anatomical structures such as the spinal cord, cerebellum, spinal nerves, and blood vessels; in the direction and size of the cannula into the cistern, the puncture needle cannula is inserted into the cistern, and ... The angle should be determined based on an accurate understanding of the anatomical structure of the region and the position of the cistern, rather than being 90° in the vertical direction. The technical solution of the present invention selects a suitable type of puncture needle, accurately controls the puncture depth and angle, and ensures that the cannula is located in the cerebrospinal fluid area surrounded by the cistern rather than other solid tissues; finally, due to the tilt in the direction of cannula insertion in the cistern, the sensor probe is extremely fragile and sensitive; the process of inserting the sensor probe into the cistern requires stability and accuracy, and the sensor probe should be prevented from touching the cannula wall and surrounding tissues as much as possible, and the insertion depth of the optical fiber pressure sensor probe should be accurately controlled.

[0017] The present invention monitors cerebrospinal fluid pressure in the cistern magna, which can directly reflect the changes in cerebrospinal fluid fluid dynamics at the craniocervical junction, and provides a new idea for the early screening and diagnosis of clinical diseases related to abnormal cerebrospinal fluid dynamics at the craniocervical junction, filling the gap in the pressure monitoring method at this site; the operation is simple, flexible, and highly safe, and can minimize cerebrospinal fluid leakage and ensure that the animals can still survive normally after the experiment is completed, so as to meet the needs of subsequent animal experiments. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 This is a product diagram of the optical fiber pressure sensor and its connecting device in Example 1;

[0019] Figure 2 This is a product diagram of the optical fiber pressure sensor of Example 1;

[0020] Figure 3 This is a schematic diagram of a method for monitoring the cerebrospinal fluid pressure of the cisterna magna of small animals using an optical fiber pressure sensor in Example 1;

[0021] Figure 4 Figure A: After anesthesia and skin preparation, a sterile scalpel was used to make a longitudinal incision along the midline of the head and neck; Figure B: The superficial fascia and muscles were exposed; Figure C: The superficial fascia and muscles were cut to expose the rectus major muscle (RCDma); Figure D: The rectus major and minor muscles on the left and right sides were separated, and the translucent posterior atlanto-occipital membrane was visible; at the lower edge of the occipital bone, a A pillow pool like this; The black dot in the middle of the inverted triangle is the puncture point of the mouse cistern; Figure E: After the cannula is placed into the mouse cistern, the fiber optic pressure sensor probe is inserted into the cistern through the established fiber optic channel, and the entrance of the fiber optic pressure sensor is sealed with 3M transparent gel quick-drying adhesive to form a closed environment.

[0022] Figure 5 This is a waveform curve of the optical fiber pressure sensor after zero calibration in Example 1;

[0023] Figure 6 This is a cerebrospinal fluid pressure waveform of the occipital cisterna magna that does not meet the standards;

[0024] Figure 7 The standard cerebrospinal fluid pressure waveform with a duration of 30 seconds was obtained by monitoring the cisterna magna of mice in Example 1. DETAILED DESCRIPTION

[0025] The technical solutions provided by the present invention are described in detail below in conjunction with the embodiments, but they should not be construed as limiting the protection scope of the present invention.

[0026] Example 1

[0027] The optical fiber pressure sensor used in the present invention ( Figure 1-Figure 2 ) was purchased from Fogan Optoelectronics Technology (Shenzhen) Co., Ltd.; model: FOSP-MP260; size diameter (mm): 0.26mm; signal demodulator compatibility: FOSP-OEM series; resolution: 0.1mmHg; pressure range: 0mmHg-300mmHg (relative to atmospheric pressure); accuracy: ±1% of full scale; operating humidity range: 0-100%; operating temperature: 10℃-50℃; electromagnetic / RF / microwave sensitivity: completely immune.

[0028] The principle of the method for monitoring the cerebrospinal fluid pressure of the cisterna magna of small animals by using an optical fiber pressure sensor is as follows: Figure 3As shown: after the cannula is punctured and inserted into the cistern to establish the optical fiber channel, the optical fiber pressure sensor is started and zeroed; after the pressure baseline is stabilized, the optical fiber pressure sensor probe is inserted into the cistern and fixed; the light wave emitted by the light source is transmitted to the pressure sensor probe through the transmission optical fiber, and the light wave interacts with the external pressure signal monitored by the probe; the modulated light wave is transmitted to the optical fiber pressure sensor signal demodulator through the transmission optical fiber for photoelectric conversion; the electrical signal is transmitted to the demodulation software supporting the PC through the USB interface; after the corresponding parameters are set in the demodulation software supporting the PC (sampling frequency, pressure display range, pressure unit, etc.), the demodulation software can perform signal processing according to the set parameters; the PC obtains the cerebrospinal fluid pressure monitoring waveform and real-time pressure monitoring value of the cistern; the data is exported and analyzed.

[0029] The specific steps are as follows:

[0030] (1) Anesthesia and skin preparation: After inducing anesthesia on the experimental animals (the animals used in this experiment were 8-week-old male ICR mice), the skin of the neck was prepared and disinfected;

[0031] (2) Use a sterile scalpel to make a longitudinal incision along the midline of the head and neck to expose the superficial fascia and muscles, such as Figure 4 A, as shown in 4B;

[0032] (3) Cut the superficial fascia and muscles, separate the semispinalis capitis muscle, and expose the rectus capitis major muscle (RCDma). Figure 4 As shown in C;

[0033] (4) Move the mouse to the stereotaxic apparatus, fix the head by fixing the zygomatic arch, and then tilt the head slightly downward by about 45°;

[0034] (5) Separate the rectus major and minor muscles on the dorsal side of the head on both sides, and the translucent posterior atlanto-occipital membrane can be seen; at the lower edge of the occipital bone, a The semi-transparent pool is the cistern of mice. Figure 4 D The black dot in the middle of the inverted triangle is the puncture point of the cistern magnum of mice);

[0035] (6) Cut off the disposable sterile 30G injection needle to keep only the metal part of the needle, blunt the needle tip and connect it to a P10 polyethylene tube (filled with mouse artificial cerebrospinal fluid), puncture the needle into the cistern magna at an angle of 45° relative to the mouse head to a depth of about 1 mm, and then remove the needle;

[0036] Note: ① The purpose of this step is to create an entrance for the insertion of the puncture needle cannula, because the cannula is very soft and cannot directly pierce the posterior atlanto-occipital membrane; ② Choose a blunt 30G small needle to reduce tissue damage and reduce cerebrospinal fluid leakage when the needle is withdrawn; ③ This step is only for small experimental animals. If the animal is larger, you can directly use the matching puncture needle and use conventional puncture techniques to insert the cannula into the cisterna magna of the corresponding animal to avoid cerebrospinal fluid leakage.

[0037] (7) Insert the cannula (2 cm long) of a disposable sterile puncture needle (24G) into the cistern (depth of about 1 mm) at an angle of 45° relative to the mouse head to establish a fiber optic channel. Use 3M transparent gel quick-drying adhesive to seal the contact surface between the cannula opening and the posterior atlanto-occipital membrane. Leave it for about 5 minutes to ensure that the cannula is tightly fixed in the cistern. Connect the interfaces of the fiber optic pressure sensor and calibrate it to zero. Before inserting the fiber optic pressure sensor probe (the sensor probe used in this study has a diameter of 0.26 mm; probe size: cistern size <1:2) into the cistern, ensure that the pressure curve fluctuates slightly above and below the baseline or the baseline value is 0 mmHg.

[0038] Principle: The fiber optic pressure sensor probe is very sensitive. After zero calibration, slight vibrations in the environment or breezes will cause slight changes in the pressure of the probe. Therefore, the pressure baseline after zero calibration is not 0 mmHg, but an oscillating curve that fluctuates slightly above and below the baseline (a curve that fluctuates within the range of 0±0.3 mmHg above and below the baseline).

[0039] (8) The fiber optic pressure sensor probe is inserted 2 cm into the cannula through the established fiber optic channel and placed in the cerebrospinal fluid of the cisterna magna;

[0040] (9) Use 3M transparent gel quick-drying adhesive to seal the entrance of the optical fiber pressure sensor to form a closed environment; Figure 4 As shown in E;

[0041] (10) After the pressure reading stabilizes, monitor and record the changes in cerebrospinal fluid pressure in the cisterna magna.

[0042] (11) Judgment criteria for changes in cerebrospinal fluid pressure in the occipital cistern: The waveform curve fluctuates steadily and regularly above and below a certain pressure level. The standard deviation of pressure fluctuation should not be too large, and the standard is set at a standard deviation of <0.5. Figure 5 shown.

[0043] The cerebrospinal fluid pressure waveform of the occipital cistern that does not meet the standard: the pressure waveform is not a curve with stable and regular fluctuations; the pressure waveform curve fluctuates greatly, such as Figure 6 shown.

[0044] Fiber optic pressure sensor probe failure: If the sensor probe fails, the pressure monitoring value will increase or decrease significantly within a certain time range (under static state), and its fluctuation amplitude will be much larger than the specified pressure fluctuation standard deviation <0.5.

[0045] In this experiment, the cerebrospinal fluid pressure waveform obtained by monitoring the occipital cisterna magna of mice for 30 seconds is shown in the figure below. Figure 7 As shown in Figure 1, the cerebrospinal fluid pressure in the occipital cistern is 9.05±0.10 mmHg, which meets the standard. Some XLS worksheet data generated synchronously by the PC demodulation software are shown in Table 1.

[0046] Table 1 Data on changes in cerebrospinal fluid pressure in some cistern magna

[0047]

[0048]

[0049] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A device for monitoring the cerebrospinal fluid pressure of the cisterna magna of an animal using an optical fiber pressure sensor, characterized in that: The device includes a casing and an optical fiber pressure sensor.

2. The device according to claim 1, characterized in that The cannula is placed into the cerebrospinal fluid of the cisterna magna to establish an optical fiber channel.

3. The device according to claim 2, characterized in that The optical fiber pressure sensor comprises a connector, an optical fiber and a probe.

4. The device according to claim 3, characterized in that The probe passes through the optical fiber channel to reach the cerebrospinal fluid in the cisterna magna to monitor the cerebrospinal fluid pressure in the cisterna magna of the animal.

5. The device according to claim 4, characterized in that Before passing the sensor probe through the optical fiber channel, the optical fiber pressure sensor is first started and zeroed, and after the pressure baseline is stabilized, the probe is inserted through the optical fiber channel into the cisterna magna and fixed.

6. The device according to claim 5, characterized in that The animals were 8-12 weeks old male ICR mice.

7. The device according to claim 6, characterized in that The cannula is a disposable sterile 24G puncture needle cannula, 2 cm long, and the puncture depth is 1 mm, so as to establish an optical fiber channel.

8. The device according to claim 5, characterized in that The zero calibration is to adjust the pressure baseline to a curve that fluctuates within the range of 0±0.3 mmHg.

9. The device according to claim 4, characterized in that The monitoring requires collecting a 30-45 second cerebrospinal fluid pressure waveform graph of the cisterna magna.

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