CN115445097A - System for regulating and controlling dynamic change of blood flow and blood volume function in blood vessel - Google Patents
System for regulating and controlling dynamic change of blood flow and blood volume function in blood vessel Download PDFInfo
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- CN115445097A CN115445097A CN202211046775.3A CN202211046775A CN115445097A CN 115445097 A CN115445097 A CN 115445097A CN 202211046775 A CN202211046775 A CN 202211046775A CN 115445097 A CN115445097 A CN 115445097A
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- 210000004204 blood vessel Anatomy 0.000 title claims abstract description 70
- 230000017531 blood circulation Effects 0.000 title claims abstract description 38
- 230000008859 change Effects 0.000 title claims abstract description 35
- 239000008280 blood Substances 0.000 title claims abstract description 19
- 210000004369 blood Anatomy 0.000 title claims abstract description 19
- 230000001276 controlling effect Effects 0.000 title claims abstract description 10
- 230000001105 regulatory effect Effects 0.000 title claims abstract description 10
- 230000000638 stimulation Effects 0.000 claims abstract description 54
- 238000003384 imaging method Methods 0.000 claims abstract description 50
- 239000013307 optical fiber Substances 0.000 claims abstract description 34
- 210000003710 cerebral cortex Anatomy 0.000 claims abstract description 22
- 230000033228 biological regulation Effects 0.000 claims abstract description 9
- 238000001208 nuclear magnetic resonance pulse sequence Methods 0.000 claims description 4
- 239000010453 quartz Substances 0.000 claims description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 4
- 210000001367 artery Anatomy 0.000 abstract 1
- 230000000694 effects Effects 0.000 description 5
- 230000002792 vascular Effects 0.000 description 5
- 230000004913 activation Effects 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 102000034287 fluorescent proteins Human genes 0.000 description 2
- 108091006047 fluorescent proteins Proteins 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 210000005257 cortical tissue Anatomy 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000003014 reinforcing effect Effects 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 229940043263 traditional drug Drugs 0.000 description 1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N5/0613—Apparatus adapted for a specific treatment
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N5/0601—Apparatus for use inside the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N5/067—Radiation therapy using light using laser light
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N5/0601—Apparatus for use inside the body
- A61N2005/0602—Apparatus for use inside the body for treatment of blood vessels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N2005/0626—Monitoring, verifying, controlling systems and methods
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N2005/063—Radiation therapy using light comprising light transmitting means, e.g. optical fibres
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N2005/0658—Radiation therapy using light characterised by the wavelength of light used
- A61N2005/0659—Radiation therapy using light characterised by the wavelength of light used infrared
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- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pathology (AREA)
- Radiology & Medical Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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Abstract
The invention discloses a system for regulating and controlling dynamic changes of blood flow and blood volume functions in blood vessels. The output end of the infrared laser stimulation instrument is connected with the optical fiber; the optical fiber is arranged in a target blood vessel of an experimental object, and the output end of the infrared laser stimulation instrument emits infrared laser which is conducted to the target blood vessel through the optical fiber for stimulation; the imaging instrument generates light beams to enter the multi-photon microscope, and the multi-photon microscope focuses the imaging light beams generated by the imaging instrument and then images the cerebral cortex blood vessels; the modulator generates a modulation signal and sends the modulation signal to the infrared laser stimulation instrument, and the infrared laser stimulation instrument is controlled to send out specific infrared laser; the controller generates control signals to the imaging instrument and the infrared laser stimulation instrument respectively, and the work of the imaging instrument and the work of the infrared laser stimulation instrument are switched. The invention combines the infrared laser stimulation with the multiphoton microscope technology to realize the regulation and control of the blood flow and the blood volume change of a specific blood vessel, and regulates and controls the dynamic change of the blood vessel through the infrared laser stimulation of the specific artery blood vessel part.
Description
Technical Field
The invention relates to a regulation and control system for activating blood vessel change, in particular to a regulation and control system for inducing blood flow in blood vessels in cerebral cortex and dynamic change of blood volume function by infrared laser stimulation.
Background
The study of vascular changes in the cerebral cortex is crucial to understanding vascular network changes in the brain and their relationship to disease. In previous studies, there have been many systems that produce dynamic blood flow changes in arterial vessels in the cortex, but none have activated arterial vessel activity alone without the use of drugs or fluorescent proteins. The use of drugs can induce vascular flux changes, but often accompanied by drug toxicity effects, while drugs can regulate blood flow rate and blood volume throughout the blood vessel, but cannot regulate local vascular changes. The fluorescent protein is used for transfecting blood vessel cells, and the dynamic change regulation and control of the blood vessel can be carried out after 2-3 weeks.
Disclosure of Invention
In order to solve the problems in the background technology, the invention provides a system for regulating and controlling the blood flow and blood volume function dynamic change in blood vessels by combining near-infrared laser stimulation induced blood vessel change and a two-photon imaging technology, which can regulate and control the flow and speed change of local blood vessels, and a high-resolution regulation and control technology for researching the flow of local blood vessels by using infrared laser stimulation in multi-photon imaging.
The technical scheme adopted by the invention for solving the technical problem comprises the following steps:
the device comprises an infrared laser stimulation instrument, wherein the output end of the infrared laser stimulation instrument is connected with one end of an optical fiber;
the device comprises an optical fiber, wherein the other end of the optical fiber is arranged in a target blood vessel of an experimental object, and an output end of an infrared laser stimulation instrument emits infrared laser which is conducted to the target blood vessel of the experimental object through the optical fiber for infrared laser stimulation;
comprises an imaging instrument, wherein the imaging instrument generates a light beam to be incident to a multi-photon microscope;
the system comprises a multi-photon microscope, a light source control module and a control module, wherein the multi-photon microscope is used for focusing an imaging light beam generated by an imaging instrument and then inputting the focused imaging light beam into a target blood vessel of an experimental object for imaging;
the infrared laser stimulation device comprises a modulator, a laser processing unit and a control unit, wherein the modulator is used for generating a modulation signal and sending the modulation signal to the infrared laser stimulation device and controlling the infrared laser stimulation device to send specific infrared laser;
the infrared laser stimulation device comprises a controller, wherein the controller is used for generating control signals to the imaging instrument and the infrared laser stimulation instrument respectively and switching the work of the imaging instrument and the work of the infrared laser stimulation instrument.
The imaging apparatus comprises:
the laser comprises a femtosecond laser, wherein laser generated as an imaging beam is incident to a vibration mirror group;
the laser imaging device comprises a vibrating mirror group, and controls laser to focus on a target blood vessel for scanning imaging after being modulated by the vibrating mirror group.
The modulator generates modulation signals to control the infrared laser stimulation instrument to emit specific infrared laser, and the infrared laser consists of a pulse sequence with single pulse duration of 0.25 millisecond, frequency of 200 Hz and total duration of 0.5s-1s, and has laser wavelength of 1500nm-2000nm and laser energy range of 0.4-1.2J/cm 2 。
Preferably, the laser wavelength is 1875nm.
The system can regulate and control the blood flow speed and the blood flow capacity of a target blood vessel section under the stimulation of outputting specific infrared laser.
The blood vessels are non-capillary vessels and the system of the invention is effective only on non-capillary vessels.
The experimental object is specifically rat, mouse, cat, experimental monkey and human, but not limited thereto.
The target blood vessel section of the experimental object is the surface of cerebral cortex or a part with blood vessels on the cerebral cortex.
The other end of the optical fiber is tightly attached to the surface of the cerebral cortex or inserted into the cerebral cortex.
When the other end of the optical fiber is tightly inserted into the cerebral cortex, the optical fiber is fixed by the quartz capillary.
The change of the blood flow velocity is determined by the line scanning of the imaging instrument and the observation of a multi-photon microscope, the change of the blood vessel diameter is determined by the galvanometer scanning of the imaging instrument and the observation of the multi-photon microscope, the total blood vessel flow is determined according to the change of the blood flow velocity and the blood vessel diameter, and the change of the blood flow velocity and the blood volume is adjusted by controlling the change of the blood vessel diameter.
The system of the invention combines infrared laser stimulation with a multiphoton microscope to realize regulation and observation of blood flow change of specific blood vessels, and regulates and controls blood flow dynamic change of the blood vessels by infrared stimulation of blood vessel parts.
The invention uses infrared laser stimulation in a multi-photon microscope to study the blood flow dynamic change of local blood vessels, and obtains the blood flow regulation and control effect of high resolution and pertinence blood vessels.
The beneficial effects of the invention are:
compared with the traditional drug induction, the invention utilizes the thermal effect stimulated by the infrared laser conducted by the optical fiber to activate the local blood vessel of the cortex, has high targeting property, and can independently activate a single blood vessel or activate the local blood vessel; compared with the optogenetic technology, the experiment does not need to inject viruses and is performed after 1-2 weeks.
The laser activation effect of the invention is safe and reliable for cortical tissues and has high repeatability, and the change of the blood vessel activation and the laser intensity are linearly related within a certain laser intensity range.
Drawings
FIG. 1 is a logical connection diagram of the system of the present invention.
FIG. 2 is a diagram illustrating an embodiment of the present invention.
Fig. 3 is a diagram of blood flow regulation imaging and effect.
Detailed Description
The invention is further described with reference to the accompanying drawings and the detailed description.
As shown in fig. 1, the system of the present invention comprises:
the device comprises an infrared laser stimulation instrument, wherein the output end of the infrared laser stimulation instrument is connected with one end of an optical fiber;
the device comprises an optical fiber, wherein the other end of the optical fiber is arranged at a target blood vessel section of an experimental object, and infrared laser emitted by the output end of an infrared laser stimulation instrument is conducted to the target blood vessel section of the experimental object through the optical fiber for stimulation;
the multi-photon microscope imaging device comprises an imaging instrument, wherein the imaging instrument generates light beams to enter the multi-photon microscope, and comprises a femtosecond laser and a galvanometer group:
the laser comprises a femtosecond laser, wherein laser generated as an imaging beam is incident to a vibration mirror group;
comprises a vibrating mirror group, and controls laser to focus on a target blood vessel section and scan after reflection or transmission modulation of the vibrating mirror group.
The multi-photon microscope is used for focusing an imaging light beam generated by an imaging instrument and then inputting the imaging light beam into a target blood vessel section of an experimental object;
the infrared laser stimulation device comprises a modulator, a laser processing unit and a control unit, wherein the modulator is used for generating a modulation signal and sending the modulation signal to the infrared laser stimulation device and controlling the infrared laser stimulation device to send specific infrared laser;
the infrared laser stimulation instrument comprises a controller, wherein the controller is used for generating control signals to the imaging instrument and the infrared laser stimulation instrument respectively and switching the work of the imaging instrument and the work of the infrared laser stimulation instrument.
The modulator generates a modulation signal to control the infrared laser stimulation instrument to emit specific infrared laser, and the specific infrared laser consists of a pulse sequence with the single-pulse duration of 0.25 millisecond, the frequency of 200 Hz and the total duration of 0.5s-2s, the laser wavelength is 1500nm-2000nm, and the laser energy range is 0.4-1.2J/cm 2 。
The other end of the optical fiber is tightly attached to the surface of the cerebral cortex or is implanted into the cerebral cortex. When the other end of the optical fiber is implanted into the cerebral cortex, the optical fiber is fixed in a mode of fixing the optical fiber through the quartz capillary tube, 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 reinforcing a fixed quartz capillary tube through a skull drill hole as an optical fiber guide tube, so that an optical fiber head is arranged on the surface of a cortex layer.
The optical fiber has three diameters of 100, 200 and 400um, the numerical aperture is 0.22, the infrared laser stimulates cerebral cortex blood vessels, and the activation range generated on the cerebral cortex is the range of 50-500um in diameter.
In the specific implementation, the change of the blood flow velocity is determined by the line scanning of the imaging instrument and the observation of the multiphoton microscope, the change of the blood vessel diameter is determined by the galvanometer scanning of the imaging instrument and the observation of the multiphoton microscope, the total blood flow rate is determined according to the change of the blood flow velocity and the blood vessel diameter, and the change of the blood flow velocity and the blood volume is adjusted by controlling the change of the blood vessel diameter.
As shown in fig. 2, the implementation process of the present invention is as follows:
the experimental subject was placed under a two-photon microscope, and the cerebral cortex vascular structure was imaged by the cooperation of the imaging laser and the two-photon microscope, as shown in fig. 3A, with the optical fiber placed at a specific vessel segment. A time series image of the blood flow and blood volume of a particular vessel in the cortex may then be made as shown in fig. 3B. And analyzing and processing image data according to the blood flow and the time series imaging result of the blood volume to obtain a blood vessel dynamic change result stimulated by the infrared laser.
Then the tip of the optical fiber is fixed on the surface blood vessel of the cerebral cortex, the infrared laser stimulation is conducted to the cerebral cortex through the optical fiber, and the modulator is used for generating a modulation signal in real time to control the infrared laser stimulation instrument to emit specific infrared laser for stimulation. The specific infrared laser consists of a pulse sequence with the single pulse duration of 0.25 millisecond, the frequency of 200 Hz and the total duration of 0.5s-2s, the laser wavelength is 1500nm-2000nm, and the laser energy range is 0.4-1.2J/cm 2 。
During the stimulation, the dynamic changes of the blood vessels are obtained and observed in real time through the cooperation of an imaging instrument and a multi-photon microscope, and the diameters of the blood vessels and the changes of blood flow are analyzed and shown in fig. 3C (the diameters of the left images and the blood flow of the right images).
From the results, the diameter of the cortical blood vessel can be changed to regulate and control the blood flow through the infrared laser stimulation, so that the local blood vessel blood flow is changed. The method is simple and easy to implement and has high repeatability. Has strong practical value.
Claims (7)
1. A blood flow and blood volume function dynamic change regulation and control system in blood vessels is characterized in that:
the device comprises an infrared laser stimulation instrument, wherein the output end of the infrared laser stimulation instrument is connected with one end of an optical fiber;
the device comprises an optical fiber, wherein the other end of the optical fiber is arranged in a target blood vessel of an experimental object, and an output end of an infrared laser stimulation instrument emits infrared laser which is conducted to the target blood vessel of the experimental object through the optical fiber for infrared laser stimulation;
comprises an imaging instrument, wherein the imaging instrument generates a light beam to be incident to a multi-photon microscope;
the system comprises a multi-photon microscope, a light source control module and a control module, wherein the multi-photon microscope is used for focusing an imaging light beam generated by an imaging instrument and then inputting the focused imaging light beam into a target blood vessel of an experimental object for imaging;
the infrared laser stimulation device comprises a modulator, a laser processing unit and a control unit, wherein the modulator is used for generating a modulation signal and sending the modulation signal to the infrared laser stimulation device and controlling the infrared laser stimulation device to send specific infrared laser;
the infrared laser stimulation instrument comprises a controller, wherein the controller is used for generating control signals to the imaging instrument and the infrared laser stimulation instrument respectively and switching the work of the imaging instrument and the work of the infrared laser stimulation instrument.
2. The system for regulating the dynamic change of blood flow and blood volume function in a blood vessel according to claim 1, wherein: the imaging apparatus comprises:
the device comprises a femtosecond laser, a laser source and a laser processing unit, wherein the femtosecond laser is used for generating laser as an imaging beam to enter a vibrating mirror group;
the laser imaging device comprises a vibrating mirror group, and controls laser to focus on a target blood vessel for scanning imaging after being modulated by the vibrating mirror group.
3. The system for regulating the dynamic changes of blood flow and blood volume functions in blood vessels according to claim 1, wherein: the modulator generates a modulation signal to control the infrared laser stimulation instrument to emit specific infrared laser, and the specific infrared laser consists of a pulse sequence with the single-pulse duration of 0.25 millisecond, the frequency of 200 Hz and the total duration of 0.5s-1s, the laser wavelength is 1500nm-2000nm, and the laser energy range is 0.4-1.2J/cm 2 。
4. The system for regulating the dynamic change of blood flow and blood volume function in a blood vessel according to claim 1, wherein: the target blood vessel section of the experimental object is the surface of cerebral cortex or a part with blood vessels on the cerebral cortex.
5. The system for regulating the dynamic change of blood flow and blood volume function in a blood vessel according to claim 1, wherein: the other end of the optical fiber is tightly attached to the surface of the cerebral cortex or inserted into the cerebral cortex.
6. The system for regulating the dynamic change of blood flow and blood volume function in a blood vessel according to claim 1, wherein: when the other end of the optical fiber is tightly inserted into the cerebral cortex, the optical fiber is fixed by the quartz capillary.
7. The system for regulating the dynamic changes of blood flow and blood volume functions in blood vessels according to claim 1, wherein: the change of the blood flow velocity is determined by the line scanning of the imaging instrument and the observation of a multi-photon microscope, the change of the blood vessel diameter is determined by the galvanometer scanning of the imaging instrument and the observation of the multi-photon microscope, the total blood vessel flow is determined according to the change of the blood flow velocity and the blood vessel diameter, and the change of the blood flow velocity and the blood volume is adjusted by controlling the change of the blood vessel diameter.
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| CN202211046775.3A CN115445097A (en) | 2022-08-30 | 2022-08-30 | System for regulating and controlling dynamic change of blood flow and blood volume function in blood vessel |
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| CN202211046775.3A CN115445097A (en) | 2022-08-30 | 2022-08-30 | System for regulating and controlling dynamic change of blood flow and blood volume function in blood vessel |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040004194A1 (en) * | 2000-11-20 | 2004-01-08 | Francois Amblard | Multi-photon imaging installation |
| US20060142746A1 (en) * | 2002-12-11 | 2006-06-29 | Beth Friedman | Device and method for inducing vascular injury and/or blockage in an animal model |
| US20180106729A1 (en) * | 2016-10-19 | 2018-04-19 | The Regents Of The University Of California | Imaging platform based on nonlinear optical microscopy for rapid scanning large areas of tissue |
| CN110292359A (en) * | 2019-07-09 | 2019-10-01 | 浙江大学 | A kind of method and apparatus of unmarked full optical neuron regulation and imaging |
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- 2022-08-30 CN CN202211046775.3A patent/CN115445097A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040004194A1 (en) * | 2000-11-20 | 2004-01-08 | Francois Amblard | Multi-photon imaging installation |
| US20060142746A1 (en) * | 2002-12-11 | 2006-06-29 | Beth Friedman | Device and method for inducing vascular injury and/or blockage in an animal model |
| US20180106729A1 (en) * | 2016-10-19 | 2018-04-19 | The Regents Of The University Of California | Imaging platform based on nonlinear optical microscopy for rapid scanning large areas of tissue |
| CN110292359A (en) * | 2019-07-09 | 2019-10-01 | 浙江大学 | A kind of method and apparatus of unmarked full optical neuron regulation and imaging |
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