A system for regulating dynamic changes of blood flow and blood volume function in blood vessels

Abstract

The present invention discloses a system for regulating the dynamic changes of blood flow and blood volume function in blood vessels. The output end of an infrared laser stimulation instrument is connected to an optical fiber; the optical fiber is placed in the target blood vessel of an experimental subject, and the output end of the infrared laser stimulation instrument emits an infrared laser which is transmitted to the target blood vessel through the optical fiber for stimulation; the imaging instrument generates a light beam which is incident on a multiphoton microscope, and the multiphoton microscope focuses the imaging light beam generated by the imaging instrument to image the cerebral cortex blood vessels; the modulator generates a modulation signal which is sent to the infrared laser stimulation instrument to control the infrared laser stimulation instrument to emit a specific infrared laser; the controller generates a control signal to the imaging instrument and the infrared laser stimulation instrument respectively to switch the operation of the imaging instrument and the infrared laser stimulation instrument. The present invention combines infrared laser stimulation with multiphoton microscopy technology to achieve regulation of changes in blood flow and blood volume in specific blood vessels, and regulates the dynamic changes of blood vessels by infrared laser stimulation of specific arterial blood vessels.

Description

Technical Field

[0001] The invention relates to a control system for activating blood vessel changes, in particular to a control system for dynamic changes of blood flow and blood volume function in blood vessels in cerebral cortex induced by infrared laser stimulation. Background Art

[0002] Studying vascular changes in the cerebral cortex is crucial to understanding changes in the vascular network in the brain and its relationship to disease. In previous studies, there are many systems that can produce dynamic blood flow changes in the arteries in the cortex, but there is no system that can activate arterial vascular activity alone without the use of drugs or fluorescent proteins. The use of drugs can induce changes in vascular flow, but it is often accompanied by drug toxicity. At the same time, drugs will regulate the blood flow rate and blood volume of the entire blood vessel, but cannot regulate local vascular changes. Using fluorescent proteins to transfect vascular cells requires 2-3 weeks to regulate the dynamic changes of blood vessels. Summary of the invention

[0003] In order to solve the problems existing in the background technology, the present invention provides a system for regulating the dynamic changes of blood flow and blood volume function in blood vessels by combining near-infrared laser stimulation to induce vascular changes with two-photon imaging technology. The system is capable of regulating changes in local vascular flow and velocity, and uses infrared laser stimulation in multi-photon imaging to study high-resolution regulation technology of local vascular flow.

[0004] The technical solution adopted by the present invention to solve the technical problem includes the following steps:

[0005] It includes an infrared laser stimulation instrument, wherein the output end of the infrared laser stimulation instrument is connected to one end of the optical fiber;

[0006] It includes an optical fiber, the other end of which is placed on a target blood vessel of an experimental subject, and an infrared laser is emitted from an output end of the infrared laser stimulation instrument and transmitted to the target blood vessel of the experimental subject through the optical fiber for infrared laser stimulation;

[0007] An imaging instrument is included, wherein the imaging instrument generates a light beam incident on a multiphoton microscope;

[0008] It includes a multiphoton microscope, which focuses the imaging beam generated by the imaging instrument and then injects it into the target blood vessel of the experimental subject for imaging;

[0009] It includes a modulator, which generates a modulation signal and sends it to the infrared laser stimulation instrument to control the infrared laser stimulation instrument to emit a specific infrared laser;

[0010] The invention comprises a controller, which generates control signals to the imaging instrument and the infrared laser stimulation instrument respectively, and switches the operation of the imaging instrument and the infrared laser stimulation instrument.

[0011] The imaging device comprises:

[0012] It includes a femtosecond laser, which generates laser light as an imaging beam and is incident on a galvanometer group;

[0013] It includes a galvanometer group, which controls the laser to focus on the target blood vessel for scanning imaging after being modulated by the galvanometer group.

[0014] The modulator generates a modulation signal to control the infrared laser stimulation instrument to emit a specific infrared laser, which is composed of a pulse sequence with a single pulse duration of 0.25 milliseconds, a frequency of 200 Hz, and a total duration of 0.5s-1s. The laser wavelength is 1500nm-2000nm and the laser energy range is 0.4-1.2J / cm 2 .

[0015] Preferably, the laser wavelength is 1875 nm.

[0016] The system of the present invention can regulate the blood flow velocity and blood flow volume of the target blood vessel segment under the output of specific infrared laser stimulation.

[0017] The blood vessels described are non-capillaries, and the system of the present invention is only effective for non-capillaries.

[0018] The experimental subjects are specifically rats, mice, cats, experimental monkeys and humans, but are not limited thereto.

[0019] The target blood vessel segment of the experimental subject is the surface of the cerebral cortex or a blood vessel site on the cerebral cortex.

[0020] The other end of the optical fiber is closely attached to the surface of the cerebral cortex or inserted into the cerebral cortex.

[0021] When the other end of the optical fiber is tightly inserted into the cerebral cortex, the optical fiber is fixed by a quartz capillary.

[0022] The changes in blood flow velocity are determined by line scanning of the imaging instrument and observation with a multiphoton microscope. The changes in blood vessel diameter are determined by galvanometer scanning of the imaging instrument and observation with a multiphoton microscope. The total blood vessel flow is determined based on the changes in blood flow velocity and blood vessel diameter, and the changes in blood flow velocity and blood volume are adjusted by controlling the changes in blood vessel diameter.

[0023] The system of the present invention combines infrared laser stimulation with a multiphoton microscope to achieve the regulation and observation of blood flow changes in specific blood vessels, and regulates the dynamic changes of blood flow in blood vessels by infrared stimulation of blood vessel parts.

[0024] The present invention uses infrared laser stimulation in a multiphoton microscope to study the dynamic changes of blood flow in local blood vessels, thereby achieving high-resolution and targeted blood vessel blood flow regulation effects.

[0025] The beneficial effects of the present invention are:

[0026] Compared with traditional drug induction, the present invention uses the thermal effect of infrared laser stimulation transmitted by optical fiber to activate local blood vessels in the cortex. It has high targeting and can activate a single blood vessel or local blood vessels alone. Compared with optogenetics, this experiment does not require virus injection and the experiment can be conducted after waiting for 1-2 weeks.

[0027] The laser activation effect of the present invention is safe and reliable for cortical tissue and has high repeatability. Moreover, within a certain laser intensity range, the change in blood vessel activation is also linearly related to the laser intensity. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 It is a logical connection diagram of the system of the present invention.

[0029] Figure 2 It is a specific implementation step diagram of the present invention.

[0030] Figure 3 This is the blood flow regulation imaging and effect diagram. DETAILED DESCRIPTION

[0031] The present invention will be further described below in conjunction with the accompanying drawings and specific implementations.

[0032] like Figure 1 As shown, the system of the present invention includes:

[0033] It includes an infrared laser stimulation instrument, wherein the output end of the infrared laser stimulation instrument is connected to one end of the optical fiber;

[0034] It includes an optical fiber, the other end of which is placed on a target blood vessel segment of an experimental subject, and an infrared laser is emitted from an output end of the infrared laser stimulation instrument and transmitted to the target blood vessel segment of the experimental subject through the optical fiber for stimulation;

[0035] The imaging instrument includes an imaging instrument, which generates a light beam incident on a multiphoton microscope, and the imaging instrument includes a femtosecond laser and a galvanometer group:

[0036] It includes a femtosecond laser, which generates laser light as an imaging beam and is incident on a galvanometer group;

[0037] It includes a galvanometer group, which controls the laser to focus on the target blood vessel segment and scan it after reflection or transmission modulation by the galvanometer group.

[0038] It includes a multiphoton microscope, which focuses an imaging beam generated by an imaging instrument and then directs it onto a target blood vessel segment of an experimental subject;

[0039] It includes a modulator, which generates a modulation signal and sends it to the infrared laser stimulation instrument to control the infrared laser stimulation instrument to emit a specific infrared laser;

[0040] The invention comprises a controller, which generates control signals to the imaging instrument and the infrared laser stimulation instrument respectively, and switches the operation of the imaging instrument and the infrared laser stimulation instrument.

[0041] The modulator generates a modulation signal to control the infrared laser stimulation instrument to emit a specific infrared laser, which is composed of a pulse sequence with a single pulse duration of 0.25 milliseconds, a frequency of 200 Hz, and a total duration of 0.5s-2s. The laser wavelength is 1500nm-2000nm and the laser energy range is 0.4-1.2J / cm 2 .

[0042] The other end of the optical fiber is closely attached to the surface of the cerebral cortex or implanted in the cerebral cortex. When the other end of the optical fiber is implanted in the cerebral cortex, the optical fiber is fixed by a quartz capillary as an optical fiber fixing method, so that the optical fiber is placed on the surface of the cerebral cortex or other parts with blood vessels. Specifically, the optical fiber is fixed by a quartz capillary as an optical fiber catheter through a skull drilling hole, so that the optical fiber head is placed on the surface of the cortex.

[0043] The optical fiber has three diameters of 100, 200 and 400um, and a numerical aperture of 0.22. The infrared laser stimulates the blood vessels of the cerebral cortex, and the activation range on the cerebral cortex is 50-500um in diameter.

[0044] In a specific implementation, the change in blood flow velocity is determined by line scanning of an imaging instrument and observation with a multiphoton microscope, the change in blood vessel diameter is determined by galvanometer scanning of an imaging instrument and observation with a multiphoton microscope, the total blood vessel flow is determined based on the change in blood flow velocity and blood vessel diameter, and the change in blood flow velocity and blood volume is adjusted by controlling the change in blood vessel diameter.

[0045] like Figure 2 As shown, the implementation process of the present invention is as follows:

[0046] The experimental subjects were placed under a two-photon microscope, and the vascular structure of the cerebral cortex was imaged by combining an imaging laser with a two-photon microscope. Figure 3 As shown in A, optical fibers are placed in specific blood vessel segments. Time series imaging of blood flow and blood volume in specific blood vessels in the cortex can then be performed. Figure 3 B. Image data analysis and processing are performed based on the time series imaging results of blood flow and blood volume to obtain the dynamic changes of blood vessels stimulated by infrared laser.

[0047] Then the tip of the optical fiber is fixed to the surface blood vessels of the cerebral cortex, and the infrared laser stimulation is transmitted to the cerebral cortex through the optical fiber. In real time, the modulator is used to generate a modulation signal to control the infrared laser stimulation instrument to emit a specific infrared laser for stimulation. The specific infrared laser is composed of a pulse sequence with a single pulse duration of 0.25 milliseconds, a frequency of 200 Hz, and a total duration of 0.5s-2s. The laser wavelength is 1500nm-2000nm, and the laser energy range is 0.4-1.2J / cm 2 .

[0048] During the stimulation process, the dynamic changes of blood vessels are obtained and observed in real time through the cooperation of imaging instruments and multiphoton microscopes, and the changes in blood vessel diameter and blood flow are analyzed. Figure 3 C (diameter on the left, blood flow on the right).

[0049] The results show that through infrared laser stimulation, the diameter of cortical blood vessels can change to regulate blood flow, causing changes in local blood vessel blood flow. This method is simple and easy to use, with high repeatability and strong practical value.

Claims

1. A system for regulating dynamic changes of blood flow and blood volume function in blood vessels, characterized by: It includes an infrared laser stimulation instrument, wherein the output end of the infrared laser stimulation instrument is connected to one end of the optical fiber; It includes an optical fiber, the other end of which is placed on a target blood vessel of an experimental subject, and an infrared laser is emitted from an output end of the infrared laser stimulation instrument and transmitted to the target blood vessel of the experimental subject through the optical fiber for infrared laser stimulation; An imaging instrument is included, wherein the imaging instrument generates a light beam incident on a multiphoton microscope; It includes a multiphoton microscope, which focuses the imaging light beam generated by the imaging instrument and then injects it into the target blood vessel of the experimental subject for imaging; determines the change of blood flow velocity by line scanning of the imaging instrument and observation with the multiphoton microscope, determines the change of blood vessel diameter by galvanometer scanning of the imaging instrument and observation with the multiphoton microscope, determines the total blood vessel flow according to the change of blood flow velocity and blood vessel diameter, and then adjusts the change of blood flow velocity and blood volume by controlling the change of blood vessel diameter; It includes a modulator, which generates a modulation signal and sends it to the infrared laser stimulation instrument to control the infrared laser stimulation instrument to emit a specific infrared laser; It includes a controller, which generates control signals to the imaging instrument and the infrared laser stimulation instrument respectively, and switches the operation of the imaging instrument and the infrared laser stimulation instrument; The modulator generates a modulation signal to control the infrared laser stimulation instrument to emit a specific infrared laser, which is composed of a pulse sequence with a single pulse duration of 0.25 milliseconds, a frequency of 200 Hz, and a total duration of 0.5s-1s. The laser wavelength is 1500nm-2000nm and the laser energy range is 0.4-1.2J / cm 2 ; The target blood vessel segment of the experimental subject is the surface of the cerebral cortex or a blood vessel site on the cerebral cortex.

2. A blood vessel blood flow and blood volume function dynamic change control system according to claim 1, characterized in that: The imaging device comprises: It includes a femtosecond laser, which generates laser light as an imaging beam and is incident on a galvanometer group; It includes a galvanometer group, which controls the laser to focus on the target blood vessel for scanning imaging after being modulated by the galvanometer group.

3. A blood flow and blood volume function dynamic change control system in a blood vessel according to claim 1, characterized in that: The other end of the optical fiber is closely attached to the surface of the cerebral cortex or inserted into the cerebral cortex.

4. A blood flow and blood volume function dynamic change control system in a blood vessel according to claim 1, characterized in that: When the other end of the optical fiber is tightly inserted into the cerebral cortex, the optical fiber is fixed by a quartz capillary.

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