CN109999348A - A method of transcranial magnetic stimulation deep brain area is realized based on diffusion tensor - Google Patents
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Abstract
本发明公开了一种基于弥散张量成像实现经颅磁刺激深部脑区的方法，其包括以下步骤：获取待接受经颅磁刺激被试的大脑结构像信息和弥散张量成像信息；基于弥散张量成像技术确定待接受经颅磁刺激被试的深部脑区坐标；基于弥散张量成像信息构建待接受经颅磁刺激被试的深部脑区和全脑的白质结构连接特征，提取与深部脑区存在白质结构连接的皮层脑区；基于与深部脑区存在白质结构连接的皮层脑区确定待接受经颅磁刺激被试的最佳皮层位置坐标；借助导航定位系统，以最佳皮层位置坐标作为常规刺激线圈的直接干预位点，以白质结构连接特征中的白质纤维连接走向引导刺激线圈的摆放方向，实现经颅磁刺激线圈对深部脑区的精准、个体化干预。
The invention discloses a method for realizing transcranial magnetic stimulation of deep brain regions based on diffusion tensor imaging. The tensor imaging technology determines the coordinates of the deep brain region of the subject to be subjected to transcranial magnetic stimulation; based on the information of diffusion tensor imaging, the structural connectivity features of the deep brain region and the whole brain of the subject to be subjected to transcranial magnetic stimulation are constructed to extract Cortical brain regions with white matter structural connections in the brain regions; based on the cortical brain regions with white matter structural connections with deep brain regions to determine the optimal cortical position coordinates of the subjects to be subjected to transcranial magnetic stimulation; The coordinates are used as the direct intervention site of the conventional stimulation coil, and the direction of the placement of the stimulation coil is guided by the white matter fiber connection in the white matter structural connection feature, so as to realize the precise and individualized intervention of the deep brain region by the transcranial magnetic stimulation coil.
Description
技术领域technical field
本发明涉及一种对深部脑区实现经颅磁刺激的方法，尤其是基于弥散张量成像对深部脑区实施个体化、精准经颅磁刺激的方法。The invention relates to a method for implementing transcranial magnetic stimulation to deep brain regions, in particular to a method for implementing individualized and precise transcranial magnetic stimulation to deep brain regions based on diffusion tensor imaging.
背景技术Background technique
经颅磁刺激是一种颅外无创神经调控技术，通过在颅外施加电磁场，磁场穿透颅骨在大脑皮层产生感应电场，可以促使神经元去极化，起到兴奋或抑制效果，改变局部大脑的可塑性。1985年，Barker及其合作者在英国谢菲尔德研发了第一台现代经颅磁刺激仪器，之后经颅磁刺激技术首先被应用于脑功能定位的基础研究和认知研究。随后发现，特定模式的经颅磁刺激对大脑活动的影响在刺激结束后的一定时间内仍然存在，经颅磁刺激的治疗作用受到大众关注，目前已被批准应用于抑郁障碍的临床治疗，也有大量在精神分裂症、帕金森、疼痛等精神和神经性疾病中的临床研究证据。经颅磁刺激技术具有无创、安全性好、副作用小的有点，具有重要的临床价值和需求。Transcranial magnetic stimulation is an extracranial non-invasive neuromodulation technology. By applying an electromagnetic field outside the skull, the magnetic field penetrates the skull to generate an induced electric field in the cerebral cortex, which can promote the depolarization of neurons, play an excitatory or inhibitory effect, and change the local brain. of plasticity. In 1985, Barker and his collaborators developed the first modern transcranial magnetic stimulation device in Sheffield, UK, and then transcranial magnetic stimulation technology was first applied to the basic research and cognitive research of brain function localization. Subsequently, it was found that the effect of a specific mode of transcranial magnetic stimulation on brain activity still exists within a certain period of time after the stimulation. The therapeutic effect of transcranial magnetic stimulation has attracted public attention and has been approved for clinical treatment of depression. There are also some A large number of clinical research evidences in schizophrenia, Parkinson's, pain and other mental and neurological diseases. Transcranial magnetic stimulation technology has the advantages of non-invasiveness, good safety and little side effects, and has important clinical value and demand.
经颅磁刺激干预位置，是影响磁刺激效果和临床疗效的关键参数。目前常规磁刺激线圈(以八字形线圈为例)可达线圈下2-3cm，最新H型磁刺激线圈最深可达4-6cm，磁刺激有效作用部位主要还是位于皮层。因此，现有磁刺激线圈存在无法有效作用大脑深部位置的瓶颈。而位于大脑深部的皮层下结构，例如扣带、海马、杏仁核、纹状体等，是情绪和认知神经通路中的关键位置，与多种精神和神经性疾病的发病机制密切相关。现有经颅磁刺激技术无法实现对大脑深部结构的有效干预，限制了大脑可塑性研究的范围，也制约了该技术在临床治疗中的疗效，限制了临床应用和推广。The location of transcranial magnetic stimulation intervention is a key parameter that affects the effect of magnetic stimulation and clinical efficacy. At present, the conventional magnetic stimulation coil (take the figure-of-eight coil as an example) can reach 2-3 cm below the coil, and the latest H-shaped magnetic stimulation coil can reach the maximum depth of 4-6 cm. The effective role of magnetic stimulation is mainly located in the cortex. Therefore, the existing magnetic stimulation coils have the bottleneck that they cannot effectively act on the deep part of the brain. Subcortical structures located deep in the brain, such as the cingulate, hippocampus, amygdala, and striatum, are key locations in emotional and cognitive neural pathways and are closely related to the pathogenesis of a variety of psychiatric and neurological diseases. The existing transcranial magnetic stimulation technology cannot achieve effective intervention on the deep structure of the brain, which limits the scope of brain plasticity research, also restricts the efficacy of this technology in clinical treatment, and limits its clinical application and promotion.
发明内容SUMMARY OF THE INVENTION
本发明针对现有技术存在的问题和不足，提供一种基于弥散张量成像实现经颅磁刺激深部脑区的方法，该方法通过弥散张量成像技术，构建与位于深部的干预靶点存在最强白质结构连接的皮层位置，作为常规磁刺激线圈的干预位置；基于白质纤维束走向引导刺激线圈的摆放方向，实现对深部脑区的精准、个体化干预。Aiming at the problems and deficiencies in the prior art, the present invention provides a method for transcranial magnetic stimulation of deep brain regions based on diffusion tensor imaging. The cortical position of the strong white matter structure connection is used as the intervention position of the conventional magnetic stimulation coil; based on the direction of the white matter fiber bundle to guide the placement of the stimulation coil, the precise and individualized intervention of the deep brain area is realized.
本发明是通过下述技术方案来解决上述技术问题的：The present invention solves the above-mentioned technical problems through the following technical solutions:
本发明提供一种基于弥散张量成像实现经颅磁刺激深部脑区的方法，其特点在于，其包括以下步骤：The present invention provides a method for realizing transcranial magnetic stimulation of deep brain regions based on diffusion tensor imaging, which is characterized in that it comprises the following steps:
S1、获取待接受经颅磁刺激被试的大脑结构像信息和弥散张量成像信息；S1. Obtain the brain structure image information and diffusion tensor imaging information of the subject to be subjected to transcranial magnetic stimulation;
S2、基于弥散张量成像技术确定待接受经颅磁刺激被试的深部脑区坐标；S2. Determine the coordinates of the deep brain region of the subject to be subjected to transcranial magnetic stimulation based on diffusion tensor imaging technology;
S3、基于弥散张量成像信息构建待接受经颅磁刺激被试的深部脑区和全脑的白质结构连接特征，提取与深部脑区存在白质结构连接的皮层脑区；S3. Based on the information of diffusion tensor imaging, construct the connection features of the deep brain region and the white matter structure of the whole brain of the subject to be subjected to transcranial magnetic stimulation, and extract the cortical brain regions that have white matter structure connections with the deep brain region;
S4、基于与深部脑区存在白质结构连接的皮层脑区确定待接受经颅磁刺激被试的最佳皮层位置坐标；S4. Determine the optimal cortical position coordinates of the subject to be subjected to transcranial magnetic stimulation based on the cortical brain regions that have white matter structural connections with the deep brain regions;
S5、借助导航定位系统，以最佳皮层位置坐标作为常规刺激线圈的直接干预位点，以白质结构连接特征中的白质纤维连接走向引导刺激线圈的摆放方向，实现经颅磁刺激线圈对深部脑区的精准、个体化干预。S5. With the help of the navigation and positioning system, the optimal cortical position coordinates are used as the direct intervention site of the conventional stimulation coil, and the connection direction of the white matter fibers in the white matter structural connection feature guides the placement direction of the stimulation coil, so as to realize the transcranial magnetic stimulation coil to the deep part. Precise and individualized intervention in brain regions.
较佳地，在步骤S1中，大脑结构像信息包括单体素或多体素，大脑结构像信息来源于待接受经颅磁刺激被试的磁共振结构像或公开的标准结构像图像。Preferably, in step S1, the brain structural image information includes a single voxel or multiple voxels, and the brain structural image information is derived from a magnetic resonance structural image or a public standard structural image image of the subject to be subjected to transcranial magnetic stimulation.
较佳地，步骤S2包括以下步骤：Preferably, step S2 includes the following steps:
S21、建立获取的大脑结构像信息与弥散张量成像信息间的映射和转化关系；S21. Establish the mapping and transformation relationship between the acquired brain structural image information and the diffusion tensor imaging information;
S22、在弥散张量成像图像上确定待接受经颅磁刺激被试的深部脑区坐标。S22, determining the coordinates of the deep brain region of the subject to be subjected to transcranial magnetic stimulation on the diffusion tensor imaging image.
较佳地，步骤S3包括以下步骤：Preferably, step S3 includes the following steps:
S31、根据弥散张量成像图像上确定的深部脑区坐标，采用白质纤维跟踪算法，可但不限于采用确定跟踪算法或概率跟踪算法等，计算深部脑区坐标与全脑所有体素的白质结构连接特征值；S31. According to the coordinates of the deep brain region determined on the diffusion tensor imaging image, use a white matter fiber tracking algorithm, but not limited to using a deterministic tracking algorithm or a probability tracking algorithm, etc., to calculate the coordinates of the deep brain region and the white matter structure of all voxels in the whole brain connecting eigenvalues;
S32、提取与深部脑区存在白质结构连接的皮层脑区，作为经颅磁刺激的候选刺激位置。S32 , extracting a cortical brain region that is connected to a deep brain region with a white matter structure as a candidate stimulation location for transcranial magnetic stimulation.
在符合本领域常识的基础上，上述各优选条件，可任意组合，即得本发明各较佳实例。On the basis of conforming to common knowledge in the art, the above preferred conditions can be combined arbitrarily to obtain preferred examples of the present invention.
本发明的积极进步效果在于：The positive progressive effect of the present invention is:
1)针对现有磁刺激干预无法作用于深部脑区的缺陷，本技术方案基于弥散张量成像可以实现对深部脑区的磁刺激干预，扩大和延伸了磁刺激对大脑的有效干预范围。1) In view of the defect that the existing magnetic stimulation intervention cannot act on the deep brain region, this technical solution can realize the magnetic stimulation intervention on the deep brain region based on diffusion tensor imaging, and expand and extend the effective intervention scope of the magnetic stimulation on the brain.
2)相较于现有神经导航定位方法，本技术方案不仅提供精确的皮层干预位点，而且根据个体白质纤维走向确定经颅磁刺激的干预方向，进一步提高了定位的准确度。2) Compared with the existing neuronavigation positioning methods, the technical solution not only provides precise cortical intervention sites, but also determines the intervention direction of transcranial magnetic stimulation according to the orientation of individual white matter fibers, which further improves the positioning accuracy.
3)本方法借助常规经颅磁刺激线圈就可实现，与现有硬件兼容，将大大提高设备使用效果和应用范围，惠及基础研究和临床应用。3) The method can be realized with the help of conventional transcranial magnetic stimulation coils, and is compatible with existing hardware, which will greatly improve the use effect and application scope of the equipment, and benefit basic research and clinical applications.
附图说明Description of drawings
图1为本发明较佳实施例的基于弥散张量成像实现经颅磁刺激深部脑区的方法的流程图。FIG. 1 is a flowchart of a method for implementing transcranial magnetic stimulation of deep brain regions based on diffusion tensor imaging according to a preferred embodiment of the present invention.
图2为本发明较佳实施例的基于弥散张量成像实现的对深部脑区(海马)实施磁刺激的流程图。FIG. 2 is a flow chart of implementing magnetic stimulation to a deep brain region (hippocampus) based on diffusion tensor imaging according to a preferred embodiment of the present invention.
图3为本发明较佳实施例的基于弥散张量成像实现的对深部脑区(海马)实施磁刺激的效果图。3 is an effect diagram of implementing magnetic stimulation to a deep brain region (hippocampus) based on diffusion tensor imaging according to a preferred embodiment of the present invention.
具体实施方式Detailed ways
为使本发明实施例的目的、技术方案和优点更加清楚，下面将结合本发明实施例中的附图，对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动的前提下所获得的所有其他实施例，都属于本发明保护的范围。In order to make the purposes, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments These are some embodiments of the present invention, but not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative work fall within the protection scope of the present invention.
如图1所示，本实施例提供一种基于弥散张量成像实现经颅磁刺激深部脑区的方法，其包括以下步骤：As shown in FIG. 1 , this embodiment provides a method for implementing transcranial magnetic stimulation of deep brain regions based on diffusion tensor imaging, which includes the following steps:
步骤1：获取待接受经颅磁刺激被试的大脑结构像信息和弥散张量成像信息。Step 1: Obtain the brain structure image information and diffusion tensor imaging information of the subject to be subjected to transcranial magnetic stimulation.
在步骤1中，大脑结构像信息包括单体素或多体素，大脑结构像信息来源于待接受经颅磁刺激被试的磁共振结构像或公开的标准结构像图像。In step 1, the brain structural image information includes single voxel or multiple voxels, and the brain structural image information is derived from the magnetic resonance structural image or the public standard structural image image of the subject to be subjected to transcranial magnetic stimulation.
步骤2：基于弥散张量成像技术确定待接受经颅磁刺激被试的深部脑区坐标。Step 2: Determine the coordinates of the deep brain region of the subject to be subjected to transcranial magnetic stimulation based on diffusion tensor imaging technology.
步骤2.1：建立获取的大脑结构像信息与弥散张量成像信息间的映射和转化关系。Step 2.1: Establish the mapping and transformation relationship between the acquired brain structural image information and the diffusion tensor imaging information.
步骤2.2：在弥散张量成像图像上确定待接受经颅磁刺激被试的深部脑区坐标。Step 2.2: Determine the coordinates of the deep brain region of the subject to be subjected to transcranial magnetic stimulation on the diffusion tensor imaging image.
步骤3：基于弥散张量成像信息构建待接受经颅磁刺激被试的深部脑区和全脑的白质结构连接特征，提取与深部脑区存在白质结构连接的皮层脑区。Step 3: Based on the diffusion tensor imaging information, construct the white matter structural connectivity features of the deep brain region and the whole brain of the subject to be subjected to transcranial magnetic stimulation, and extract the cortical brain regions that have white matter structural connections with the deep brain region.
步骤31：根据弥散张量成像图像上确定的深部脑区坐标，采用白质纤维跟踪算法，可但不限于采用确定跟踪算法或概率跟踪算法等，计算深部脑区坐标与全脑所有体素的白质结构连接特征值。Step 31: According to the coordinates of the deep brain region determined on the diffusion tensor imaging image, use a white matter fiber tracking algorithm, but not limited to using a deterministic tracking algorithm or a probability tracking algorithm, etc., to calculate the coordinates of the deep brain region and the white matter of all voxels in the whole brain. Structural connection eigenvalues.
步骤32：提取与深部脑区存在白质结构连接的皮层脑区，作为经颅磁刺激的候选刺激位置。Step 32: Extract the cortical brain regions that have white matter structural connections with deep brain regions as candidate stimulation locations for transcranial magnetic stimulation.
步骤4：基于与深部脑区存在白质结构连接的皮层脑区确定待接受经颅磁刺激被试的最佳皮层位置坐标。Step 4: Determine the optimal cortical location coordinates of the subject to be subjected to transcranial magnetic stimulation based on the cortical brain regions with white matter structural connections to the deep brain regions.
步骤5：借助导航定位系统，以最佳皮层位置坐标作为常规刺激线圈的直接干预位点，以白质结构连接特征中的白质纤维连接走向引导刺激线圈的摆放方向，实现经颅磁刺激线圈对深部脑区的精准、个体化干预。Step 5: With the help of the navigation and positioning system, the optimal cortical position coordinates are used as the direct intervention site of the conventional stimulation coil, and the white matter fiber connection in the white matter structural connection feature guides the placement direction of the stimulation coil, so as to realize the alignment of the transcranial magnetic stimulation coil. Precise, individualized intervention in deep brain regions.
基于上述的基于弥散张量成像实现经颅磁刺激深部脑区的方法的原理，下面举一具体的例子来说明本发明，以使得本领域的技术人员能够更好地理解本发明的技术方案：Based on the principle of the above-mentioned method for realizing transcranial magnetic stimulation of deep brain regions based on diffusion tensor imaging, a specific example is given below to illustrate the present invention, so that those skilled in the art can better understand the technical scheme of the present invention:
本实施例以深部脑区海马为实施例，具体实现步骤如图2所示，包括：This embodiment takes the hippocampus of the deep brain region as an embodiment, and the specific implementation steps are shown in FIG. 2 , including:
步骤1：采集获取待接受经颅磁刺激被试的磁共振结构像(sMRI)和弥散张量成像(DTI)图像。Step 1: Acquire the structural magnetic resonance image (sMRI) and diffusion tensor imaging (DTI) images of the subject to be subjected to transcranial magnetic stimulation.
步骤2.1：将sMRI和DTI图像进行常规预处理后，进行配准，生成sMRI和DTI空间间的映射、转换信息。Step 2.1: After routine preprocessing of sMRI and DTI images, registration is performed to generate mapping and transformation information between sMRI and DTI spaces.
步骤2.2：基于待接受经颅磁刺激被试的sMRI图像，确定带刺激的深部脑区位置作为感兴趣区(ROI)。ROI选择根据实际需要，可采用单体素或多体素ROI。本实施例中ROI选择位于深部的皮层下结构左侧海马，包含多体素，生成左侧海马模板的方法是从Harvard-Oxford模板提取，如图3中的(a)所示。Step 2.2: Based on the sMRI image of the subject to be subjected to transcranial magnetic stimulation, determine the location of the deep brain region with stimulation as a region of interest (ROI). ROI selection According to actual needs, single voxel or multi-voxel ROI can be used. In this embodiment, the ROI selects the left hippocampus, which is located in the deep subcortical structure, and contains multiple voxels. The method for generating the left hippocampus template is to extract from the Harvard-Oxford template, as shown in (a) of FIG. 3 .
步骤2.3：生成DTI空间的感兴趣区模板。根据感兴趣区模板所处的空间(个体sMRI空间或标准模板空间)实施转换。本实施例中，左侧海马模板取自标准空间，需要完成标准空间至个体DTI空间的转换，生成个体DTI空间的ROI模板，如图3中的(b)所示。Step 2.3: Generate ROI template in DTI space. The transformation is performed according to the space in which the ROI template is located (individual sMRI space or standard template space). In this embodiment, the left hippocampal template is taken from the standard space, and the conversion from the standard space to the individual DTI space needs to be completed to generate the ROI template of the individual DTI space, as shown in (b) of FIG. 3 .
步骤3：以DTI空间的ROI模板，基于白质纤维跟踪算法，获得感兴趣区与全脑的白质结构连接图。本实施例中以被试DTI空间的左侧海马模板作为种子点，获得左侧海马与全脑的白质结构连接图，如图3中的(c)所示。Step 3: Using the ROI template in the DTI space, based on the white matter fiber tracking algorithm, obtain the white matter structure connection map between the region of interest and the whole brain. In this example, the left hippocampal template in the subject's DTI space was used as a seed point to obtain a connection map of the white matter structure between the left hippocampus and the whole brain, as shown in (c) of FIG. 3 .
步骤4：根据位置以及与ROI的功能连接强度确定作为常规磁刺激线圈直接干预的最佳位点。本实施例中，在步骤3获得的左侧海马与全脑的白质功能连接图中，最佳干预位点为左侧顶叶，如图3中的(d)十字坐标所示。Step 4: Determine the optimal site for direct intervention with conventional magnetic stimulation coils based on location and strength of functional connectivity to the ROI. In this embodiment, in the white matter functional connection diagram of the left hippocampus and the whole brain obtained in step 3, the optimal intervention site is the left parietal lobe, as shown by the cross coordinate in (d) in FIG. 3 .
步骤5：借助导航定位系统，以皮层位点作为常规刺激线圈的直接干预位点，白质纤维连接走向引导刺激线圈的摆放方向，实现常规磁刺激线圈对深部脑区的精准、个体化干预。Step 5: With the help of the navigation and positioning system, the cortical site is used as the direct intervention site of the conventional stimulation coil, and the white matter fibers are connected to guide the placement direction of the stimulation coil, so as to realize the precise and individualized intervention of the conventional magnetic stimulation coil in the deep brain area.
本发明基于弥散张量成像构建大脑深部结构(>5cm)与浅表皮层(2-3cm)间的白质结构连接图；通过磁刺激线圈直接作用于浅表皮层位点，实现间接作用于深部结构的效果。The invention constructs the white matter structure connection map between the deep brain structure (>5cm) and the superficial epidermis (2-3cm) based on diffusion tensor imaging; the magnetic stimulation coil directly acts on the superficial epidermis to realize indirect action on the deep structure Effect.
本方法中不仅准确定位浅表直接干预位点的位置，且根据白质纤维走向可精准控制磁刺激线圈的摆放方向，实现精准、个体化此磁刺激干预。In this method, not only the position of the superficial direct intervention site is accurately located, but also the placement direction of the magnetic stimulation coil can be precisely controlled according to the direction of the white matter fibers, so as to realize the precise and individualized magnetic stimulation intervention.
虽然以上描述了本发明的具体实施方式，但是本领域的技术人员应当理解，这些仅是举例说明，本发明的保护范围是由所附权利要求书限定的。本领域的技术人员在不背离本发明的原理和实质的前提下，可以对这些实施方式做出多种变更或修改，但这些变更和修改均落入本发明的保护范围。Although specific embodiments of the present invention have been described above, those skilled in the art should understand that these are merely illustrative, and the scope of the present invention is defined by the appended claims. Those skilled in the art can make various changes or modifications to these embodiments without departing from the principle and essence of the present invention, but these changes and modifications all fall within the protection scope of the present invention.
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