技术领域technical field
本发明涉及生物医学技术领域，特别是涉及一种用于经颅超声刺激影响下的多参数动物脑皮层血流监测装置和方法。The invention relates to the technical field of biomedicine, in particular to a multi-parameter animal cerebral cortex blood flow monitoring device and method under the influence of transcranial ultrasonic stimulation.
背景技术Background technique
脉冲式经颅超声刺激(pulsed Transcranial Ultrasound Stimulation,pTUS)是近年来发展迅速，得到广泛关注的一种大脑神经调控技术。它通过超声穿过完整的颅骨作用于大脑皮层的神经元细胞，从而改变大脑的神经活动。相比于其他神经调控技术，比如深部脑刺激(DBS)、经颅磁刺激(TMS)、经颅直流电刺激(tDCS)，pTUS具有安全无创、精准刺激等优点。Pulsed Transcranial Ultrasound Stimulation (pTUS) is a brain neuromodulation technology that has developed rapidly in recent years and has attracted widespread attention. It acts on neurons in the cerebral cortex by passing ultrasound through the intact skull, thereby altering the neural activity of the brain. Compared with other neuromodulation techniques, such as deep brain stimulation (DBS), transcranial magnetic stimulation (TMS), and transcranial direct current stimulation (tDCS), pTUS has the advantages of safe, non-invasive and precise stimulation.
通过其神经调控效应，pTUS在神经系统疾病治疗、大脑功能研究等方面具有独特的潜力。例如，脑卒中是一种影响脑中动脉系统的疾病。脑卒中发生时，脑中动脉被堵塞或者破裂，血液无法及时向脑组织供应充足的氧气与养料，继而致使脑细胞死亡。脑卒中一直呈高发态势，是导致病人死亡或残疾的主要原因之一。有动物研究表明pTUS对于治疗脑卒中很可能具有一定效果，而pTUS对血流动力学的影响可能是其作用的机制之一。因此实时监测pTUS刺激下脑血流的变化具有重要意义。更进一步，在脑卒中的病理条件下监测pTUS引起的脑血流变化更能直接反映pTUS治疗脑卒中的可能机制。Through its neuromodulatory effect, pTUS has unique potential in the treatment of neurological diseases and the study of brain function. For example, stroke is a disease that affects the arterial system in the middle brain. When a stroke occurs, the middle cerebral artery is blocked or ruptured, and the blood cannot supply sufficient oxygen and nutrients to the brain tissue in time, resulting in the death of brain cells. Stroke has always been a high incidence and is one of the main causes of death or disability of patients. Animal studies have shown that pTUS may have a certain effect on the treatment of stroke, and the effect of pTUS on hemodynamics may be one of its mechanisms. Therefore, real-time monitoring of changes in cerebral blood flow under pTUS stimulation is of great significance. Furthermore, monitoring the cerebral blood flow changes induced by pTUS under the pathological conditions of stroke can more directly reflect the possible mechanism of pTUS treatment of stroke.
而在脑卒中的研究中，动物实验具有重要意义，在动物体内诱导脑卒中是进行动物实验的前提。光化学法是一种具有代表性的微创、快速、精确的脑卒中诱导技术。研究表明，某些光敏物质在特定波长光照的激发下会发生化学变化，变化产物可以进一步与血管壁发生反应从而堵塞血管。光化学法诱导的脑卒中由于光照的位置、范围、能量可控，相比于其他方法，具有精确、稳定的优势。因此光化学法具有广泛的应用。In the study of stroke, animal experiments are of great significance, and inducing stroke in animals is a prerequisite for animal experiments. Photochemical method is a representative technique for minimally invasive, rapid and precise stroke induction. Studies have shown that some photosensitive substances will undergo chemical changes under the excitation of specific wavelengths of light, and the changed products can further react with blood vessel walls to block blood vessels. Compared with other methods, the stroke induced by photochemical method has the advantages of accuracy and stability due to the controllable position, range and energy of light. Therefore, the photochemical method has a wide range of applications.
另外，由于存在神经血管耦合，对多个脑皮层血流动力学参数，例如血液流速、脑血容量等的监测可以反映神经活动的变化，因此可以作为反映大脑神经活动的指标，进而可以用来研究pTUS对脑皮层的神经调控效应。光学成像技术具有高时空分辨率特性，作为一种重要的脑成像手段被广泛应用于脑科学的研究中。其中的激光散斑衬比成像(laserspeckle contrast imaging,LSCI)、内源光成像(optical imaging of intrinsicsignals,OIS)，可以分别得到血液流速和脑血容量的信息。In addition, due to the existence of neurovascular coupling, the monitoring of multiple cerebral cortex hemodynamic parameters, such as blood flow rate and cerebral blood volume, can reflect changes in neural activity, so it can be used as an indicator to reflect brain neural activity, which in turn can be used to To study the neuromodulatory effect of pTUS on the cerebral cortex. Optical imaging technology has high spatio-temporal resolution and is widely used in brain science research as an important brain imaging method. Among them, laser speckle contrast imaging (laser speckle contrast imaging, LSCI) and optical imaging of intrinsic signals (OIS), can respectively obtain the information of blood flow velocity and cerebral blood volume.
而在脑卒中病理的研究过程中，病理过程早期的治疗和监测对寻找最佳治疗窗口具有重要意义。然而，由于传统的超声换能器，光学成像技术以及光化学法的工作方式，现阶段的实验条件无法完成pTUS刺激过程中的血流动力学参数的实时监测，更无法实现光化学法诱导过程中的全程pTUS刺激和实时监测。因此本发明将pTUS系统、光学成像系统和脑卒中诱导系统相互结合，提出一种实现生理和病理条件下pTUS刺激和监测系统具有重要意义。In the research process of stroke pathology, the early treatment and monitoring of the pathological process is of great significance to find the optimal treatment window. However, due to the working methods of traditional ultrasonic transducers, optical imaging technology and photochemical methods, the current experimental conditions cannot complete the real-time monitoring of hemodynamic parameters during pTUS stimulation, let alone realize the real-time monitoring of hemodynamic parameters during photochemical induction. Full pTUS stimulation and real-time monitoring. Therefore, the present invention combines the pTUS system, the optical imaging system and the stroke induction system to propose a pTUS stimulation and monitoring system under physiological and pathological conditions, which is of great significance.
发明内容Contents of the invention
为克服上述现有技术存在的不足，本发明之目的在于提供一种多参数动物脑皮层血流监测装置和方法，以通过将pTUS系统、光学成像系统和脑卒中诱导系统相互结合，实现实时监测生理和脑卒中病理条件下脉冲式经颅超声刺激(pTUS)引起的脑血流的变化，并且用多参数的血流动力学变化实现对pTUS神经调控效应的评估。In order to overcome the deficiencies in the above-mentioned prior art, the object of the present invention is to provide a multi-parameter animal cerebral cortex blood flow monitoring device and method to realize real-time monitoring by combining pTUS system, optical imaging system and stroke induction system The changes of cerebral blood flow induced by pulsed transcranial ultrasound stimulation (pTUS) under physiological and pathological conditions of stroke, and the evaluation of the neuromodulatory effect of pTUS by multi-parameter hemodynamic changes.
为达上述及其它目的，本发明提出一种多参数动物脑皮层血流监测装置，包括：In order to achieve the above and other purposes, the present invention proposes a multi-parameter animal cerebral cortex blood flow monitoring device, comprising:
聚焦超声换能器，具有中间的成像孔，连接成像系统和病理诱导系统；The focused ultrasound transducer has an imaging hole in the middle, connecting the imaging system and the pathological induction system;
成像系统，用于利用光源通过所述聚焦超声换能器的成像孔对动物的大脑皮层表面的成像范围照明，捕捉并生成所述光源照射所述动物大脑皮层表面特定位置时的图像；The imaging system is used to use a light source to illuminate the imaging range of the surface of the cerebral cortex of the animal through the imaging hole of the focused ultrasound transducer, and capture and generate an image when the light source illuminates a specific position on the surface of the animal's cerebral cortex;
病理诱导系统，用于利用激发光源照射所述动物大脑皮层表面的特定位置，诱导该位置的病理变化。The pathological induction system is used for irradiating a specific position on the surface of the cerebral cortex of the animal with an exciting light source to induce pathological changes at the position.
进一步地，所述聚焦超声换能器、成像系统、病理诱导系统保持同一轴心。Further, the focused ultrasound transducer, the imaging system, and the pathology induction system maintain the same axis.
进一步地，所述聚焦超声换能器前端与一超声耦合模块相连，并于其中注入除气去离子水用于超声和被刺激部位之间的耦合。Further, the front end of the focused ultrasound transducer is connected to an ultrasound coupling module, and degassed deionized water is injected into it for coupling between the ultrasound and the stimulated part.
进一步地，所述超声耦合模块包括：Further, the ultrasonic coupling module includes:
水密性薄膜，用于通过其中的除气去离子水实现所述聚焦超声换能器与被刺激部位之间的紧密耦合；a water-tight film for achieving tight coupling between the focused ultrasound transducer and the stimulated site through degassed deionized water therein;
进水口以及出水口，分别用于向所述超声耦合模块内注水，以及挤压所述水密性薄膜使之与被刺激部位紧密贴合过程中部分水的排出。The water inlet and the water outlet are respectively used to inject water into the ultrasonic coupling module, and to discharge part of the water during the process of squeezing the water-tight film to closely adhere to the stimulated part.
进一步地，所述成像系统包括：Further, the imaging system includes:
光源，通过所述聚焦超声换能器的成像孔对动物的大脑皮层表面的成像范围照明；A light source illuminates the imaging range of the surface of the cerebral cortex of the animal through the imaging hole of the focused ultrasound transducer;
镜头及相机，用于通过所述聚焦超声换能器的成像孔捕捉所述光源照射所述动物的大脑皮层表面特定位置时的图像；A lens and a camera are used to capture the image when the light source illuminates a specific position on the surface of the cerebral cortex of the animal through the imaging hole of the focused ultrasound transducer;
滤光片，用于滤除成像光源波长之外的其他波长的光。Filters for filtering out light of wavelengths other than the wavelength of the imaging light source.
进一步地，所述光源包括第一光源与第二光源，所述第一光源采用用于激光散斑衬比成像的波长范围在630-800nm激光二极管，所述第二光源采用用于内源光成像的580-600nm的发光二极管。Further, the light source includes a first light source and a second light source, the first light source uses a laser diode with a wavelength range of 630-800nm for laser speckle contrast imaging, and the second light source uses a laser diode for internal light Imaging with 580-600nm LEDs.
进一步地，所述聚焦超声换能器的成像孔中间具有水密性的透明刚性部件，用于将所述成像系统的光电元件与超声耦合模块的除气去离子水相隔离。Further, there is a watertight transparent rigid part in the middle of the imaging hole of the focused ultrasound transducer, which is used to isolate the photoelectric element of the imaging system from the degassed deionized water of the ultrasonic coupling module.
进一步地，所述病理诱导系统利用光化学法造模激发光源照射所述动物大脑皮层表面的特定位置，诱导该位置的病理变化。Further, the pathological induction system utilizes a photochemical method to model an excitation light source to irradiate a specific position on the surface of the cerebral cortex of the animal to induce pathological changes at the position.
为达到上述目的，本发明还提供一种多参数动物脑皮层血流监测方法，包括如下步骤：In order to achieve the above object, the present invention also provides a multi-parameter animal cerebral cortex blood flow monitoring method, comprising the following steps:
步骤一，对聚焦超声换能器输入脉冲式驱动电压；Step 1, inputting a pulsed driving voltage to the focused ultrasound transducer;
步骤二，利用第一光源或第二光源通过所述聚焦超声换能器的成像孔对动物的大脑皮层表面的成像范围照明；Step 2, using the first light source or the second light source to illuminate the imaging range of the surface of the cerebral cortex of the animal through the imaging hole of the focused ultrasound transducer;
步骤三，利用成像系统通过所述聚焦超声换能器的成像孔捕捉并生成所述第一或第二光源照射的动物大脑皮层表面特定位置的图像。Step 3, using an imaging system to capture and generate an image of a specific position on the surface of the animal's cerebral cortex irradiated by the first or second light source through the imaging hole of the focused ultrasound transducer.
进一步地，所述方法还包括：Further, the method also includes:
利用病理诱导系统的光化学法造模激发光源照射动物大脑皮层表面特定位置，诱导该位置的病理变化。The photochemical method of the pathological induction system is used to model the excitation light source to irradiate a specific position on the surface of the cerebral cortex of the animal to induce pathological changes in the position.
与现有技术相比，本发明一种多参数动物脑皮层血流监测装置及方法通过在聚焦超声换能器中间设置成像孔与成像系统和病理诱导系统相连接，避免了超声刺激过程中对成像和病理诱导光路的遮挡，从而可以实现经颅超声刺激的同时对被刺激部位脑血流进行成像或者进行病理诱导，可实现实时监测生理和脑卒中病理条件下脉冲式经颅超声刺激(pTUS)刺激引起的脑血流的变化，并且用多参数的血流动力学变化实现对pTUS神经调控效应的评估的目的。Compared with the prior art, a multi-parameter animal cerebral cortex blood flow monitoring device and method of the present invention is connected with the imaging system and the pathological induction system by setting an imaging hole in the middle of the focused ultrasonic transducer, avoiding damage to the blood flow during the ultrasonic stimulation process. Imaging and pathologically induced optical path occlusion, so that the cerebral blood flow of the stimulated part can be imaged or pathologically induced during transcranial ultrasound stimulation, and real-time monitoring of pulsed transcranial ultrasound stimulation (pTUS) under physiological and pathological conditions of stroke can be realized. ) stimulation-induced changes in cerebral blood flow, and use multi-parameter hemodynamic changes to achieve the purpose of evaluating the neuromodulatory effect of pTUS.
附图说明Description of drawings
图1为本发明一种多参数动物脑皮层血流监测装置的系统结构图；Fig. 1 is a system structure diagram of a multi-parameter animal cerebral cortex blood flow monitoring device of the present invention;
图2为本发明一种多参数动物脑皮层血流监测方法的步骤流程图。Fig. 2 is a flow chart of steps of a multi-parameter animal cerebral cortex blood flow monitoring method according to the present invention.
具体实施方式detailed description
以下通过特定的具体实例并结合附图说明本发明的实施方式，本领域技术人员可由本说明书所揭示的内容轻易地了解本发明的其它优点与功效。本发明亦可通过其它不同的具体实例加以施行或应用，本说明书中的各项细节亦可基于不同观点与应用，在不背离本发明的精神下进行各种修饰与变更。The implementation of the present invention is described below through specific examples and in conjunction with the accompanying drawings, and those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. The present invention can also be implemented or applied through other different specific examples, and various modifications and changes can be made to the details in this specification based on different viewpoints and applications without departing from the spirit of the present invention.
图1为本发明一种多参数动物脑皮层血流监测装置的系统结构图。如图1所示，本发明一种多参数动物脑皮层血流监测装置，应用于动物的大脑皮层表面，用于多参数地监测动物在生理和病理条件下经颅超声刺激引起的脑血流的变化，其包括：Fig. 1 is a system structure diagram of a multi-parameter animal cerebral cortex blood flow monitoring device of the present invention. As shown in Figure 1, a multi-parameter animal cerebral cortex blood flow monitoring device of the present invention is applied to the surface of the cerebral cortex of animals for multi-parameter monitoring of cerebral blood flow caused by transcranial ultrasound stimulation of animals under physiological and pathological conditions changes, which include:
聚焦超声换能器110，具有中间的成像孔111，成像孔111处有螺纹112用于连接成像系统和病理诱导系统；The focused ultrasound transducer 110 has an imaging hole 111 in the middle, and the imaging hole 111 has a thread 112 for connecting the imaging system and the pathological induction system;
成像系统，用于利用光源通过所述聚焦超声换能器110的成像孔111对所述动物的大脑皮层表面121的成像范围照明，捕捉并生成所述光源照射动物大脑皮层表面121特定位置时的图像；The imaging system is used to illuminate the imaging range of the cerebral cortex surface 121 of the animal through the imaging hole 111 of the focused ultrasound transducer 110 with a light source, and capture and generate an image of the animal's cerebral cortex surface 121 when the light source illuminates a specific position. image;
病理诱导系统，包括光化学法造模激发光源131，用于照射动物大脑皮层表面121特定位置132，诱导该位置的病理变化，其中所述动物被注射过特定的药物，在本发明中，光化学法造模光源131具有调节光照射在所述动物的大脑皮层表面的角度和位置132的功能。The pathological induction system includes a photochemical method modeling excitation light source 131, which is used to irradiate a specific position 132 on the surface of the cerebral cortex 121 of an animal to induce pathological changes at this position, wherein the animal has been injected with a specific drug. In the present invention, the photochemical method The modeling light source 131 has the function of adjusting the angle and position 132 of light irradiated on the surface of the cerebral cortex of the animal.
在本发明具体实施例中，所述聚焦超声换能器110、成像系统、病理诱导系统应保持同一轴心。In a specific embodiment of the present invention, the focused ultrasound transducer 110, the imaging system, and the pathology induction system should maintain the same axis.
优选地，在所述多参数动物脑皮层血流监测装置中，所述聚焦超声换能器110前端与一超声耦合模块相连，并于其中注入除气去离子水用于超声和被刺激部位之间的耦合。具体地，所述超声耦合模块包括：Preferably, in the multi-parameter animal cerebral cortex blood flow monitoring device, the front end of the focused ultrasound transducer 110 is connected to an ultrasound coupling module, and degassed deionized water is injected into it for use between the ultrasound and the stimulated part. Coupling between. Specifically, the ultrasonic coupling module includes:
水密性薄膜113，用于通过其中的除气去离子水114实现聚焦超声换能器110与被刺激部位之间的紧密耦合。The water-tight film 113 is used to achieve close coupling between the focused ultrasound transducer 110 and the stimulated part through the degassed deionized water 114 therein.
进水口115以及出水口116，分别用于向超声耦合模块内注水，以及挤压水密性薄膜113使之与被刺激部位118紧密贴合过程中部分水的排出。The water inlet 115 and the water outlet 116 are respectively used to inject water into the ultrasonic coupling module, and to discharge part of the water during the process of squeezing the water-tight film 113 to closely adhere to the stimulated part 118 .
优选地，在所述多参数动物脑皮层血流监测装置中，所述聚焦超声换能器110的成像孔111中间具有水密性的透明刚性部件117，在本实施例中采用厚度为0.5mm的光学玻璃材料，用于将成像系统的光电元件与超声耦合模块的除气去离子水相隔离。Preferably, in the multi-parameter animal cerebral cortex blood flow monitoring device, there is a watertight transparent rigid member 117 in the middle of the imaging hole 111 of the focused ultrasound transducer 110. In this embodiment, a transparent rigid member 117 with a thickness of 0.5 mm is used. Optical glass material used to isolate the optoelectronic components of the imaging system from the degassed deionized water of the ultrasound coupling module.
具体地，在所述多参数动物脑皮层血流监测装置中，所述的成像系统具体包括：Specifically, in the multi-parameter animal cerebral cortex blood flow monitoring device, the imaging system specifically includes:
光源，为成像提供照明，在本发明具体实施例中，光源包括第一光源125与第二光源126，第一光源125用于激光散斑衬比成像的波长范围在630-800nm激光二极管(LD)，本实施例采用激光波长为780nm；第二光源126用于内源光成像的580-600nm发光二极管(LED)，本实施例采用的波长为590nm；The light source provides illumination for imaging. In a specific embodiment of the present invention, the light source includes a first light source 125 and a second light source 126. The wavelength range of the first light source 125 for laser speckle contrast imaging is 630-800nm laser diode (LD ), the laser wavelength used in this embodiment is 780nm; the second light source 126 is used for 580-600nm light-emitting diodes (LEDs) for internal light imaging, and the wavelength used in this embodiment is 590nm;
镜头122及相机123，用于捕捉光源照射所述动物的大脑皮层表面121特定位置时的图像；The lens 122 and the camera 123 are used to capture the image when the light source illuminates the specific position of the cerebral cortex surface 121 of the animal;
滤光片124，用于滤除成像光源波长之外的其他波长的光。The filter 124 is used to filter out light of other wavelengths than the wavelength of the imaging light source.
图2为本发明一种多参数动物脑皮层血流监测方法的步骤流程图。如图2所示，本发明一种多参数动物脑皮层血流监测方法，应用于动物的大脑皮层表面，用于多参数地监测动物在生理和病理条件下经颅超声刺激引起的脑血流的变化，包括如下步骤：Fig. 2 is a flow chart of steps of a multi-parameter animal cerebral cortex blood flow monitoring method according to the present invention. As shown in Figure 2, a multi-parameter animal cerebral cortex blood flow monitoring method of the present invention is applied to the surface of the cerebral cortex of animals, and is used for multi-parameter monitoring of cerebral blood flow caused by transcranial ultrasound stimulation of animals under physiological and pathological conditions changes, including the following steps:
步骤201，对聚焦超声换能器输入脉冲式驱动电压；Step 201, inputting a pulsed driving voltage to the focused ultrasound transducer;
步骤202，利用光源通过所述聚焦超声换能器的成像孔对所述动物的大脑皮层表面的成像范围照明；在本发明具体实施例中，利用第一光源或第二光源通过所述聚焦超声换能器的成像孔对所述动物的大脑皮层表面的成像范围照明；Step 202, using a light source to illuminate the imaging range of the surface of the cerebral cortex of the animal through the imaging hole of the focused ultrasound transducer; the imaging aperture of the transducer illuminates the imaging range of the surface of the cerebral cortex of the animal;
步骤203，利用成像系统通过所述聚焦超声换能器的成像孔捕捉并生成所述光源(第一或第二光源)照射的动物大脑皮层表面特定位置的图像。Step 203, using the imaging system to capture and generate an image of a specific position on the surface of the animal's cerebral cortex irradiated by the light source (first or second light source) through the imaging hole of the focused ultrasound transducer.
优选地，本发明之多参数动物脑皮层血流监测方法，还包括如下步骤：Preferably, the multi-parameter animal cerebral cortex blood flow monitoring method of the present invention also includes the following steps:
利用病理诱导系统的光化学法造模激发光源照射动物大脑皮层表面特定位置，诱导该位置的病理变化，其中所述动物被注射过特定的药物。The photochemical method of the pathological induction system is used to model the exciting light source to irradiate a specific position on the surface of the cerebral cortex of the animal to induce pathological changes at the position, wherein the animal has been injected with a specific drug.
综上所述，本发明一种多参数动物脑皮层血流监测装置及方法通过在聚焦超声换能器中间设置成像孔与成像系统和病理诱导系统相连接，避免了超声刺激过程中对成像和病理诱导光路的遮挡，从而可以实现经颅超声刺激的同时对被刺激部位脑血流进行成像或者进行病理诱导，可实现实时监测生理和脑卒中病理条件下pTUS刺激引起的脑血流的变化，并且用多参数的血流动力学变化实现对pTUS神经调控效应的评估的目的。In summary, a multi-parameter animal cerebral cortex blood flow monitoring device and method of the present invention connects the imaging system and the pathological induction system by setting an imaging hole in the middle of the focused ultrasound transducer, avoiding the need for imaging and pathology during the ultrasonic stimulation process. The occlusion of the pathologically induced light path can realize the imaging of the stimulated cerebral blood flow or the pathological induction at the same time as the transcranial ultrasound stimulation, and can realize the real-time monitoring of the cerebral blood flow changes caused by pTUS stimulation under the physiological and pathological conditions of stroke. And use the hemodynamic changes of multiple parameters to realize the purpose of evaluating the neuromodulation effect of pTUS.
上述实施例仅例示性说明本发明的原理及其功效，而非用于限制本发明。任何本领域技术人员均可在不违背本发明的精神及范畴下，对上述实施例进行修饰与改变。因此，本发明的权利保护范围，应如权利要求书所列。The above-mentioned embodiments only illustrate the principles and effects of the present invention, but are not intended to limit the present invention. Any person skilled in the art can modify and change the above-mentioned embodiments without departing from the spirit and scope of the present invention. Therefore, the protection scope of the present invention should be listed in the claims.
| Application Number | Priority Date | Filing Date | Title |
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| CN201711009197.5ACN107692974A (en) | 2017-10-25 | 2017-10-25 | A kind of multi-parameter animal cortex blood flow monitoring device and method |
| Application Number | Priority Date | Filing Date | Title |
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| CN201711009197.5ACN107692974A (en) | 2017-10-25 | 2017-10-25 | A kind of multi-parameter animal cortex blood flow monitoring device and method |
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| CN201711009197.5APendingCN107692974A (en) | 2017-10-25 | 2017-10-25 | A kind of multi-parameter animal cortex blood flow monitoring device and method |
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