Atlas making and registering method and system for mouse brain in special development period
By combining iterative registration methods with VISoR imaging technology, the problems of lack and poor adaptability of mouse brain maps during special developmental periods were solved, more accurate map production and registration were achieved, and neuroscience research was promoted.
Patent Information
- Application Number
- CN202510544700.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-04-28
- Publication Date
- 2025-09-23
AI Technical Summary
Existing mouse brain maps lack maps of specific developmental periods, the production process is complex, and the VISoR imaging technology is poorly compatible with traditional imaging technology, resulting in large registration errors and unable to meet the needs of neuroscience research.
An iterative registration method was used to average the reconstructed mouse brains to create an average template and annotate the brain region templates to generate a structural information file. VISoR imaging technology was used for atlas creation and registration, and the characteristics of VISoR imaging technology were combined to improve the accuracy of registration.
In the absence of existing maps, a suitable map of the mouse brain at a specific developmental period was drawn to achieve good adaptation with VISoR imaging technology, improve the accuracy of image registration, and provide a more precise tool for neuroscience research.
Smart Images
Figure CN120678383A_ABST
Abstract
Description
Technical Field
[0001] The present application relates to the field of biomedical engineering technology, and in particular to a method and system for producing and registering a mouse brain map during a special developmental period. Background Art
[0002] In neuroscience research, mouse brain atlases are an important tool for studying mouse brain structure and function. By imaging the mouse brain and then registering it with the atlas, researchers can accurately locate and analyze different regions of the mouse brain, understanding neural development processes, neural circuit mechanisms, and more. Currently, relatively mature atlases exist for the adult mouse brain, such as the CCFv3 (Common Coordinate Framework, third edition of the mouse standard brain atlas) template, which has been widely used in adult mouse brain research. However, for the mouse brain at specific developmental stages, existing developmental atlases do not cover all developmental stages. Furthermore, due to the significant differences in the structure and developmental characteristics of the mouse brain at different developmental stages, existing atlases cannot meet some research needs, resulting in the lack of a reference atlas. At the same time, with the development of imaging technology, different imaging technologies are constantly emerging. The VISoR imaging technology used in our laboratory differs from traditional imaging technologies in terms of imaging principles and image features, which also brings new challenges to registration.
[0003] Among them, the atlas usually includes two parts: the average template and the brain region template. The average template is a representative, averaged brain image model obtained by processing and analyzing a large number of brain image data of the same species. It is based on the statistical average of many individual brain images and can reflect the general morphology and characteristics of the brain structure of the species. The brain region template is a template formed by accurately dividing and labeling the different anatomical regions in the brain on the basis of the average template. It clarifies the boundaries, range and position of each brain region, and divides the brain into different functional and anatomical units. This application usually uses different grayscale values to distinguish different brain regions, so standardized files will also be used as descriptions of information on different brain regions.
[0004] Currently, many research institutions have released numerous atlases covering various developmental stages, which contain a wealth of biological information and are relatively easy to use. The most commonly used is the registration of the adult mouse brain based on the CCFv3 template. These published atlases are time-consuming to produce, as they require not only structural information but also a range of visualization tools and even genetic data to enrich them. However, if you simply want to perform registration, you only need to create an average template and map the brain region of interest, allowing for rapid registration.
[0005] The following problems exist in the production of existing mouse brain atlases: (1) Lack of maps for special developmental periods: The existing mouse brain atlas does not include all developmental periods, and there is no atlas suitable for the mouse brain in a special developmental period (such as P7), which cannot provide an accurate registration basis for the study of the mouse brain in this period. (2) The production process is complicated: There is no simple process. The existing atlas production process is mostly aimed at producing detailed atlases, rather than using atlas registration and analysis. (3) Poor adaptability of imaging technology: Most of the existing registrations are based on templates obtained by traditional imaging technology. The VISoR imaging technology used in this laboratory has differences in deformation, resolution, etc. with other imaging methods, resulting in different feature points. The application of existing templates to the mouse brain images obtained by VISoR imaging technology will produce certain errors. Summary of the Invention
[0006] The embodiments of the present application provide a method and system for producing and registering a mouse brain map during a special developmental period. This method can draw a suitable map and perform registration specifically for the mouse brain during a special developmental period in the absence of an existing map. It also fully considers the characteristics of VISoR imaging technology, achieves good adaptation to the imaging technology, improves the accuracy of registration of mouse brain images during a special developmental period, provides more precise tools for neuroscience research, and promotes in-depth research on the structure and function of the mouse brain during a special developmental period.
[0007] To solve the above technical problems, an embodiment of the present application provides a method for producing and aligning a mouse brain map for a special developmental period, comprising the following steps: first, performing data preprocessing on the mouse brain image to obtain a reconstructed image; then, averaging the reconstructed multiple mouse brains using an iterative alignment method to produce an average template, and then annotating the average template to produce a brain region template, and then generating a structural information file of the mouse brain map; finally, aligning the individual mouse brain image with the mouse brain map to achieve accurate alignment of the brain regions.
[0008] In some exemplary embodiments, data preprocessing is performed on mouse brain images to obtain reconstructed images, including: using VISoR imaging technology to image the brains of experimental mice at a specific developmental period; and splicing the captured mouse brain images within and between slices to obtain reconstructed images.
[0009] In some exemplary embodiments, an iterative registration method is used to average the reconstructed brains of multiple rats to produce an average template, including: selecting the reconstruction results of multiple rat brains from the reconstructed images as samples, using multiple iterations, data diversification processing, and average transformation calculation, through continuous iterative registration and updating of the template, using different forms of the image to increase data information, combining all registration results with the average transformation, and optimizing the template image to obtain an average brain that eliminates individual differences. The average brain is an average template of the rat brain, which is resampled to a resolution of 25 μm; the data diversification processing includes image flipping processing, image sharpening processing, and image smoothing processing.
[0010] In some exemplary embodiments, in the process of making the brain region template, brain region drawing software is used to draw the hypothalamus and part of the nucleus structure of P7 on the template to generate the brain region template.
[0011] In some exemplary embodiments, after generating a brain region template, the different brain region information contained in the brain region template is sorted out to generate a structural information file of a mouse brain atlas, including: sorting out the structural information of each brain region in the drawn brain region template, writing it into a json file, and generating a structural information file of a mouse brain atlas; the structural information includes the brain region name, abbreviation, number, color and structural path.
[0012] In some exemplary embodiments, registering the individual mouse brain image with the mouse brain atlas includes: automatically registering the individual mouse brain image with the mouse brain atlas using a registration tool adapted to the VISoR imaging technology and analysis process to generate a registered image and deformation field information.
[0013] In some exemplary embodiments, the registration tool includes one of visor_reconstruction, mBrainAligner, and brainreg.
[0014] In the second aspect, the present application also provides a system for producing and registering a mouse brain map for a special developmental period, which uses the method for producing and registering a mouse brain map for a special developmental period described in the above embodiment to perform map production and registration, including: an imaging and reconstruction module, a map production module, and a registration module connected in sequence; the imaging and reconstruction module is used to perform data preprocessing on the mouse brain image to obtain a reconstructed image; an iterative registration method is used to average the reconstructed multiple mouse brains to produce an average template, and then the average template is annotated to produce a brain area template, and then a structural information file of the mouse brain map is generated; the registration module is used to align individual mouse brain images with the mouse brain map to achieve accurate alignment of brain areas.
[0015] In some exemplary embodiments, the imaging and reconstruction module includes an imaging unit and a reconstruction unit; wherein the imaging unit is used to use VISoR imaging technology to image the brain of an experimental mouse at a special developmental period; the reconstruction unit is used to splice the captured mouse brain images within and between slices to obtain a reconstructed image.
[0016] In some exemplary embodiments, the atlas production module includes an average template production unit, a brain region template production unit, and a structural information file generation unit; wherein, the average template production unit is used to select the reconstruction results of multiple mouse brains from the reconstructed image as samples, use multiple iterations, data diversification processing, and average transformation calculation, through continuous iterative registration and updating of templates, use different forms of images to increase data information, combine all registration results with average transformation, optimize the template image, and obtain the average template; the brain region template production unit is used to use brain region drawing software to draw the hypothalamus and part of the nucleus structure of P7 on the template to generate a brain region template; the structural information file generation unit is used to organize the different brain region information contained in the brain region template to generate a structural information file of the mouse brain atlas.
[0017] The technical solution provided by the embodiments of the present application has at least the following advantages:
[0018] An embodiment of the present application provides a method and system for producing and aligning a mouse brain map for a special developmental period. The method includes the following steps: first, performing data preprocessing on a mouse brain image to obtain a reconstructed image; then, averaging multiple reconstructed mouse brains using an iterative alignment method to produce an average template, and then annotating the average template to produce a brain region template, and then generating a structural information file of the mouse brain map; finally, aligning the individual mouse brain images with the mouse brain map to achieve accurate alignment of brain regions.
[0019] The purpose of this application is to provide a method for mapping and registering the mouse brain at a specific developmental period (such as P7). This method can map and register a suitable map specifically for the mouse brain at a specific developmental period in the absence of an existing map. It also fully considers the characteristics of VISoR imaging technology, achieves good adaptation to the imaging technology, improves the accuracy of registration of mouse brain images at a specific developmental period, provides more accurate tools for neuroscience research, and promotes in-depth research on the structure and function of the mouse brain at a specific developmental period. BRIEF DESCRIPTION OF THE DRAWINGS
[0020] One or more embodiments are exemplarily described by the pictures in the corresponding drawings. These exemplifications do not constitute limitations on the embodiments. Unless otherwise stated, the pictures in the drawings do not constitute proportional limitations.
[0021] Figure 1A flowchart of a method for producing and registering a mouse brain map for a specific developmental period is provided in one embodiment of the present application.
[0022] Figure 2 A schematic diagram of the framework flow of a method for producing and registering a mouse brain map during a specific developmental period, provided in one embodiment of the present application.
[0023] Figure 3 A schematic diagram of the average template generation principle provided in one embodiment of the present application.
[0024] Figure 4 This is the average VISoR template for the P7 developmental period provided in one embodiment of the present application.
[0025] Figure 5 A schematic diagram of a brain region template generation strategy provided in one embodiment of the present application.
[0026] Figure 6 This is a hypothalamus brain region template for the P7 developmental period provided in one embodiment of the present application.
[0027] Figure 7 This is the registration result of the P7 developmental period provided in one embodiment of the present application.
[0028] Figure 8 This is a schematic diagram of the structure of a mouse brain atlas production and registration system for a special developmental period provided in one embodiment of the present application. DETAILED DESCRIPTION
[0029] As can be seen from the background technology, the existing mouse brain atlas production has problems such as lack of atlases for specific developmental periods, complex production process and poor adaptability of imaging technology.
[0030] Currently, the most commonly used atlas for different developmental stages is the registration of the adult mouse brain based on the CCFv3 template. These published atlases are time-consuming to produce, as they require not only structural information but also a series of visualization tools and even genetic data to enrich them. However, if registration is simply desired, one only needs to create an average template and map the brain region of interest, allowing for rapid registration. Furthermore, these published atlases do not cover all stages of mouse development, and there is currently a lack of available atlases for registration of the mouse brain at specific developmental stages. Furthermore, the VISoR (high-throughput three-dimensional fluorescence microscopy) technology used in our laboratory differs from other imaging modalities in terms of deformation and resolution, resulting in different feature points. Existing registration methods, most of which are based on templates from other imaging techniques, are not well-suited to mouse brain images obtained using VISoR imaging, making accurate registration difficult and hindering precise study of mouse brain structure and function at specific developmental stages.
[0031] Therefore, the existing mouse brain atlas production does not include all developmental periods, and there is no atlas suitable for the mouse brain in a specific developmental period (such as P7). As a result, it is impossible to provide an accurate registration basis for the study of the mouse brain in this period. Moreover, the production process is often relatively complicated. In addition, the existing registration is mostly based on templates obtained by traditional imaging technology. When the existing templates are applied to the mouse brain images obtained by VISoR imaging technology, there will be certain errors, resulting in the technical problem of poor adaptability of imaging technology.
[0032] In order to solve the above technical problems, the embodiment of the present application provides a method for producing and registering a mouse brain map for a special developmental period, the method comprising the following steps: first, performing data preprocessing on the mouse brain image to obtain a reconstructed image; then, averaging the reconstructed multiple mouse brains using an iterative registration method to produce an average template, annotating the average template to produce a brain region template, and then generating a structural information file of the mouse brain map; finally, registering the individual mouse brain image with the mouse brain map to achieve accurate alignment of the brain regions. The purpose of this application is to provide a method for drawing and registering a mouse brain map for a special developmental period (such as P7), which can draw a suitable map and perform registration specifically for the mouse brain in a special developmental period in the absence of an existing map, and fully consider the characteristics of the VISoR imaging technology to achieve good adaptation to the imaging technology, improve the accuracy of the registration of mouse brain images in a special developmental period, provide a more accurate tool for neuroscience research, and promote in-depth research on the structure and function of the mouse brain in a special developmental period.
[0033] The following detailed description of the various embodiments of the present application is provided in conjunction with the accompanying drawings. However, those skilled in the art will appreciate that many technical details are provided in the various embodiments of the present application to facilitate a better understanding of the present application. However, even without these technical details and the various variations and modifications based on the following embodiments, the technical solutions claimed in the present application can still be implemented.
[0034] See Figure 1 The present invention provides a method for producing and registering a mouse brain map at a specific developmental stage, including the following steps:
[0035] Step S1: performing data preprocessing on the mouse brain image to obtain a reconstructed image.
[0036] Step S2: using an iterative registration method to average the reconstructed multiple mouse brains to create an average template, then annotating the average template to create a brain region template, and then generating a structural information file of the mouse brain atlas.
[0037] Step S3: registering the individual mouse brain image with the mouse brain atlas to achieve accurate alignment of brain regions.
[0038] The embodiment of the present application provides a method for making and registering a mouse brain map for a special developmental period. First, a map is made. An average template is made for multiple mouse brains that have undergone data preprocessing (imaging using VISoR imaging technology, splicing the captured mouse brain images within and between slices, and reconstructing them into complete 4μm resolution mouse brain images), and the mouse brains are averaged using an iterative registration method. Then a brain area template is made, and professional brain area drawing software is used to mark the template with reference to existing anatomical knowledge. Finally, a relevant information file is generated. Registration is then performed, and the individual mouse brain images are registered with the above-mentioned template to achieve accurate alignment of the brain areas. The method provided in the present application can draw a suitable map and perform registration specifically for the mouse brain in a special developmental period in the absence of an existing map, and fully considers the characteristics of the VISoR imaging technology to achieve good adaptation to the imaging technology, improve the accuracy of registration of mouse brain images in a special developmental period, provide more accurate tools for neuroscience research, and promote in-depth research on the structure and function of the mouse brain in a special developmental period.
[0039] The technical solution process of this application is as follows Figure 2 As shown in the figure, it mainly includes three main steps: data preprocessing, atlas production and registration. Among them, the data preprocessing step includes imaging and reconstruction, aiming to obtain complete mouse brain image data. After that, an appropriate number of mouse brains are selected to make an average template. On this basis, the brain area template is drawn and the structural information file is sorted to complete the atlas production. Finally, the complete mouse brain image is registered with the atlas to achieve the transformation of the individual brain to the standard space.
[0040] In some embodiments, step S1 performs data preprocessing on the mouse brain image to obtain a reconstructed image, including:
[0041] Step S101: Using VISoR imaging technology to image the brain of an experimental mouse at a specific developmental period.
[0042] Step S102 : splicing the captured mouse brain images within and between slices to obtain a reconstructed image.
[0043] Specifically, in data preprocessing, the present application uses the VISoR imaging technology developed by this laboratory to image the brains of experimental mice at a special developmental period (such as P7).
[0044] In some embodiments, in step S2, an iterative registration method is used to average the reconstructed multiple mouse brains to produce an average template, including: selecting the reconstruction results of multiple mouse brains from the reconstructed images as samples, using multiple iterations, data diversification processing and average transformation calculation, through continuous iterative registration and updating of the template, using different forms of the image to increase data information, combining all registration results with the average transformation, optimizing the template image, and obtaining an average brain with individual differences eliminated, wherein the average brain is an average mouse brain template, resampled to a resolution of 25 μm; the data diversification processing includes image flipping processing, image sharpening processing and image smoothing processing.
[0045] In some embodiments, during the process of making the brain region template, brain region drawing software is used to draw the hypothalamus and part of the nucleus structure of P7 on the template to generate the brain region template.
[0046] It should be noted that, as an example, this application proposes drawing the hypothalamus and some nucleus structures of P7 on the template. Other brain region structures can also be drawn on the template to generate a brain region template according to the actual required brain region.
[0047] In some embodiments, after generating a brain region template, the different brain region information contained in the brain region template is sorted out to generate a structural information file of a mouse brain atlas, including: sorting out the structural information of each brain region in the drawn brain region template, writing it into a json file, and generating a structural information file of a mouse brain atlas; the structural information includes the brain region name, abbreviation, number, color and structural path.
[0048] During the atlas drawing process (taking P7 as an example), for different developmental periods, this application requires different atlases as the basis for registration. The atlas of the adult mouse brain often uses the Allen CCFv3 25μm template. For other existing developmental period atlases, appropriate rigid transformations can also be used as atlases for registration. For developmental periods for which there are no available atlases, the lack of information can still be compensated by constructing an atlas for that developmental period, and the VISoR mouse brain imaging and data analysis process can be used to perform subsequent processing and analysis on the sample individual brains of that developmental period.
[0049] Therefore, this application proposes the principles and steps for constructing a mouse brain atlas at a specific developmental period. Using the Allen CCFv3 25μm template of the adult mouse brain as a reference, the appropriate resolution is selected as the atlas standard to construct a mouse brain average template, brain region template, and structural information file to meet the needs of mouse brain registration at different developmental periods.
[0050] Generating an average template is a crucial foundation for atlas construction. This application proposes a method for generating a standard template based on the registration and iterative averaging of multiple mouse brain images. First, a certain number of mouse brain images are selected, maximizing the diversity of individuals from the same period to ensure that the generated template is broadly representative. These images are preprocessed, including downsampling and format conversion, to meet the requirements of the registration algorithm. Next, one image is selected as a fixed reference image, and the remaining images are used as moving images to be aligned. Using a non-rigid registration algorithm, the moving image is precisely aligned with the fixed image. The aligned images are then accumulated and the intermediate results are stored. To fully account for various possible image flipping scenarios during the registration process and achieve a more comprehensive alignment effect from different perspectives, the moving images in each dataset are further flipped. The alignment transformation is then recalculated and added to the previous result. This process generates a new average image, which serves as the fixed image for the next iteration. This process iterates through all images, continuously updating the fixed image and accumulating the alignment results, ultimately completing the image averaging operation. This step creates a high-quality unified template by repeatedly aligning and averaging a group of images, ensuring that the template can accurately represent the data features of all images. The principle of generating the average template is as follows: Figure 3 It should be noted that Figure 3 The figure below is an illustration of an alignment process. The Average graph needs to be used as a template for a new round of iterations.
[0051] Specifically, when drawing the atlas (taking P7 as an example), first make an average template of the mouse brain. Among them, sample selection: select the reconstruction results of 15 mouse brains from the reconstructed mouse brain images as samples. Selecting an appropriate number of samples can ensure the representativeness of the template while eliminating individual differences. Then perform iterative registration and averaging processing: use multiple iterations, data diversification processing (image flipping) and average transformation calculation, through continuous iterative registration and updating of templates, use different forms of images to increase data information, combine all registration results with average transformation, and gradually optimize the template image to obtain an average brain that eliminates individual differences. The average brain is used as the average template of the mouse brain and is resampled to 25um resolution for subsequent comparison and analysis. The VISoR average template of the P7 developmental period is as follows: Figure 4 shown.
[0052] Then, a brain region template is made. Software selection: Use commonly used brain region drawing software, such as ITK Snap, which has a friendly user interface and rich drawing tools, and can easily draw brain regions on the template. Brain region drawing: Based on neuroanatomy knowledge, carefully draw the hypothalamus and some nucleus structures of P7 on the template to generate a brain region template. During the brain region drawing process, it is necessary to refer to relevant anatomical literature and atlases to ensure the accuracy of brain region labeling. Finally, generate a structural information file: organize the detailed information of each brain region in the drawn brain region template, including brain region name, abbreviation, number, color, structural path, etc., and write it into a json file.
[0053] In the process of brain region annotation, the brain region template is a key step in atlas construction, which is directly related to the accuracy of brain region positioning and functional analysis in subsequent studies. Considering the complexity of brain region structure, this application combines anatomical prior knowledge and uses common annotation tools such as ITK-Snap to adopt a hierarchical definition of parent-child brain region structure to perform brain region annotation on the prepared average template. Due to the symmetry of the average template, this application can only annotate one half of the brain, and a symmetrical complete template can be obtained by using a flip operation.
[0054] For brain region annotation with a relatively simple structure and a relatively simple parent-child structure, the method of hierarchical definition of the parent-child brain region structure is to first mark the entire range of the parent brain region as the parent brain region template, and then use different marking values to re-mark the child brain region as the child brain region template. Different marking values represent different brain regions. Each level of brain region is saved separately, and finally the child brain region template is superimposed on the parent brain region template to show the minimum brain region structure of each area. This method can effectively save annotation time. For the range of the parent brain region without child brain regions, the strategy of overall minus local is adopted to avoid the boundary error and annotation difficulty caused by irregular boundary annotation, and it also has a good corresponding effect logically. On the other hand, if it is necessary to draw a fine and complex brain region template, the complexity of the parent-child structure and the diversity of brain regions make the number of levels large and complex. At this time, the best hierarchical definition strategy will be modified to start from the smallest brain region for annotation, and define the parent-child relationship by redefining the child brain regions as the parent brain region. In the process of integrating brain region templates at different levels, there are still some practices that can be modified in a targeted manner by different researchers, such as reassigning brain region labeling values, assigning different labeling values to the corresponding brain regions of the left and right hemispheres, etc., so that different researchers can flexibly create their own brain region templates.
[0055] This hierarchical annotation strategy helps to better understand the interrelationships and functional integration between brain regions, and provides an accurate anatomical basis for in-depth research on the structure and function of the brain. Figure 5As shown in Figure 1. Different values represent different brain regions, i.e., the selected annotation values. The hypothalamus brain region template during the P7 development period is shown in Figure 1. Figure 6 As shown, different gray values represent different brain regions.
[0056] After obtaining the brain region template, the brain region information is defined. This process requires defining different brain regions based on different annotation values, which are referred to as brain region IDs. Subsequently, this application organizes various information, such as brain region IDs and parent-child structures, by referring to the corresponding CCFv3 structural information file and saving it in JSON format. This serves as a reference for the correspondence between brain region templates and brain region information, making the brain atlas more meaningful.
[0057] In some embodiments, the individual mouse brain image is registered with the mouse brain atlas in step S3, including: using a registration tool adapted to the VISoR imaging technology and analysis process to automatically register the individual mouse brain image with the mouse brain atlas, and generate a registered image and deformation field information.
[0058] In some embodiments, the registration tool includes one of visor_reconstruction, mBrainAligner, and brainreg.
[0059] It should be noted that this application uses the visor_reconstruction tool that has been developed by the laboratory. This tool is specially designed to adapt to VISoR imaging technology and analysis processes. It can automatically perform registration and generate information such as registered images and deformation fields. The registration results of the P7 developmental period are as follows Figure 7 As shown, the original image is superimposed on the brain region template and the result is registered to the individual brain.
[0060] In summary, on the one hand, this application maps the mouse brain at a special developmental period (such as P7), which solves the problem of the lack of mouse brain maps at special developmental periods in the prior art, and is more convenient. On the other hand, this application takes into account the characteristics of VISoR imaging technology, and uses the template obtained by VISoR imaging for registration, thereby improving the adaptability of the registration method and imaging technology. In addition, this application uses an iterative registration averaging method to draw an average template of the mouse brain, eliminating individual differences, while continuing to use a resolution of 25 μm to facilitate comparison with adult mouse brain studies.
[0061] Compared with the prior art, the method for producing and registering a mouse brain map for a specific developmental period provided in the embodiments of the present application has the following advantages:
[0062] (1) This application aims to produce a mouse brain atlas at a specific developmental period (such as P7) based on specific research needs. Researchers can choose the number and range of brain regions in the brain region template according to specific needs, and solve the registration problem in different studies in a more personalized way.
[0063] (2) The registration method provided by this application has better adaptability. Most existing registration methods are based on templates of traditional imaging technology, which are not compatible with the VISoR imaging technology of this laboratory. This application uses the template obtained by the VISoR imaging method for registration, which improves the accuracy and reliability of the registration and can better adapt to the image features generated by the VISoR imaging technology. Similarly, different studies can use their own imaging methods to adapt to their own data.
[0064] (3) The method of obtaining the template in this application is different, which will be more convenient and time-saving.
[0065] See Figure 8 The present application also provides a system for producing and registering a mouse brain map for a special developmental period, which uses the method for producing and registering a mouse brain map for a special developmental period described in the above embodiment to perform map production and registration, including: an imaging and reconstruction module 101, a map production module 102, and a registration module 103 connected in sequence; the imaging and reconstruction module 101 is used to perform data preprocessing on the mouse brain image to obtain a reconstructed image; the map production module 102 is used to average the reconstructed multiple mouse brains in an iterative registration manner to produce an average template, and then annotate the average template to produce a brain region template, and then generate a structural information file of the mouse brain map; the registration module 103 is used to register individual mouse brain images with the mouse brain map to achieve accurate alignment of brain regions.
[0066] In some embodiments, the imaging and reconstruction module 101 includes an imaging unit and a reconstruction unit; wherein the imaging unit is used to use VISoR imaging technology to image the brain of an experimental mouse at a special developmental period; and the reconstruction unit is used to splice the captured mouse brain images within and between slices to obtain a reconstructed image.
[0067] In some embodiments, the atlas production module 102 includes an average template production unit, a brain region template production unit, and a structural information file generation unit; wherein, the average template production unit is used to select the reconstruction results of multiple mouse brains from the reconstructed image as samples, use multiple iterations, data diversification processing, and average transformation calculation, through continuous iterative registration and updating of templates, use different forms of images to increase data information, combine all registration results with average transformation, optimize the template image, and obtain the average template; the brain region template production unit is used to use brain region drawing software to draw the hypothalamus and part of the nucleus structure of P7 on the template to generate a brain region template; the structural information file generation unit is used to organize the different brain region information contained in the brain region template to generate a structural information file of the mouse brain atlas.
[0068] This application has been experimentally validated. In the experiment, the method described in this application was used to map and align the brain of a mouse at a specific developmental stage (P7). An average template for the P7 mouse brain, as well as a brain region template containing information about a portion of the hypothalamus, was obtained. The P7 mouse brain was successfully aligned and analyzed.
[0069] It should be noted that the sample size in this application can be adjusted based on actual circumstances. When creating the average mouse brain template, the sample size can be adjusted based on actual circumstances. Increasing the sample size can further improve the representativeness of the template, but at the expense of increased processing time and computational cost; decreasing the sample size may affect the accuracy of the template.
[0070] In terms of resolution selection, although this application uses a 25μm resolution, in some cases, templates with other resolutions, such as 10μm or 50μm, can be selected according to research needs to meet research requirements of different precision.
[0071] In terms of brain region selection, when drawing brain region templates, different brain regions can be selected for drawing according to the research focus. It is not limited to the hypothalamus and some nucleus structures of P7, but can also include other brain regions such as the hippocampus and cerebral cortex.
[0072] In addition, there are many imaging methods for mouse brain research, not limited to the VISoR imaging method shown in this application. Other imaging methods can also produce their own maps to suit their respective research.
[0073] The method of this application can be applied not only to neuroscience research on the mouse brain during specific developmental periods, but can also be extended to brain mapping and registration of other animal models, such as rats and tree shrews. Furthermore, the template drawing and registration techniques involved in this method can also be applied to image analysis and processing in other fields, such as medical image analysis and computer vision.
[0074] Based on the above technical solution, the embodiment of the present application provides a method and system for producing and aligning a mouse brain map for a special developmental period. The method includes the following steps: first, performing data preprocessing on the mouse brain image to obtain a reconstructed image; then, using an iterative alignment method to average the reconstructed multiple mouse brains to produce an average template, and then annotating the average template to produce a brain region template to generate a structural information file of the mouse brain map; finally, aligning the individual mouse brain image with the mouse brain map to achieve accurate alignment of the brain regions.
[0075] The purpose of this application is to provide a method for mapping and registering the mouse brain at a specific developmental period (such as P7). This method can map and register a suitable map specifically for the mouse brain at a specific developmental period in the absence of an existing map. It also fully considers the characteristics of VISoR imaging technology, achieves good adaptation to the imaging technology, improves the accuracy of registration of mouse brain images at a specific developmental period, provides more accurate tools for neuroscience research, and promotes in-depth research on the structure and function of the mouse brain at a specific developmental period.
[0076] Those skilled in the art will appreciate that the above-described embodiments are specific examples for implementing the present application, and that in actual applications, various changes in form and detail may be made thereto without departing from the spirit and scope of the present application. Any person skilled in the art may make changes and modifications without departing from the spirit and scope of the present application. Therefore, the scope of protection of the present application shall be subject to the scope defined in the claims.
Claims
1. A method for producing and registering a mouse brain atlas for a specific developmental period, characterized in that: The following steps are involved: Data preprocessing is performed on the mouse brain image to obtain a reconstructed image; The reconstructed brains of multiple rats were averaged using iterative registration to create an average template, which was then annotated to create a brain region template, and then a structural information file of the rat brain atlas was generated. Individual mouse brain images were registered with the mouse brain atlas to achieve accurate alignment of brain regions.
2. The method for producing and registering a mouse brain atlas for a specific developmental period according to claim 1, characterized in that: Data preprocessing is performed on the mouse brain image to obtain the reconstructed image, including; Using VISoR imaging technology to image the brains of experimental mice at specific developmental stages; The captured mouse brain images are spliced within and between slices to obtain a reconstructed image.
3. The method for producing and registering a mouse brain map at a specific developmental stage according to claim 1, wherein: The reconstructed brains of multiple rats were averaged using iterative registration to create an average template, including: Selecting reconstruction results of multiple mouse brains from the reconstructed images as samples, using multiple iterations, data diversification processing, and average transformation calculation, through continuous iterative registration and template updating, using different image morphologies to increase data information, combining all registration results with average transformation, and optimizing the template image to obtain an average brain that eliminates individual differences, wherein the average brain is an average mouse brain template and is resampled to a resolution of 25 μm; The data diversification processing includes image flipping processing, image sharpening processing and image smoothing processing.
4. The method for producing and registering a mouse brain map at a specific developmental stage according to claim 1, wherein: In the process of making the brain region template, brain region drawing software was used to draw the hypothalamus and some nucleus structures of P7 on the template to generate the brain region template.
5. The method for producing and registering a mouse brain atlas for a specific developmental period according to claim 1, wherein: After generating the brain region template, the different brain region information contained in the template is sorted out to generate the structural information file of the mouse brain atlas, including: The structural information of each brain region in the drawn brain region template is sorted and written into a json file to generate a structural information file of the mouse brain atlas; the structural information includes the brain region name, abbreviation, number, color and structural path.
6. The method for producing and registering a mouse brain map at a specific developmental stage according to claim 1, wherein: Registering the individual mouse brain image with the mouse brain atlas includes: An alignment tool adapted to the VISoR imaging technology and analysis process is used to automatically align individual mouse brain images with the mouse brain atlas, generating a registered image and deformation field information.
7. The method for producing and registering a mouse brain atlas for a specific developmental period according to claim 1, wherein: The registration tool includes one of visor_reconstruction, mBrainAligner, and brainreg.
8. A system for producing and registering a mouse brain map at a specific developmental period, which uses the method for producing and registering a mouse brain map at a specific developmental period as claimed in any one of claims 1 to 7 to produce and register the map, characterized in that: include: An imaging and reconstruction module, an atlas production module, and a registration module are connected in sequence; The imaging and reconstruction module is used to perform data preprocessing on the mouse brain image to obtain a reconstructed image; The atlas production module is used to average the reconstructed multiple mouse brains using an iterative registration method to produce an average template, then annotate the average template to produce a brain region template, and then generate a structural information file of the mouse brain atlas; The registration module is used to register individual mouse brain images with the mouse brain atlas to achieve accurate alignment of brain regions.
9. The system for producing and registering mouse brain maps at specific developmental stages according to claim 8, characterized in that: The imaging and reconstruction module includes an imaging unit and a reconstruction unit; wherein, The imaging unit is used to use VISoR imaging technology to image the brain of an experimental mouse at a specific developmental period; The reconstruction unit is used to perform intra-slice and inter-slice splicing on the captured mouse brain images to obtain a reconstructed image.
10. The system for producing and registering mouse brain maps at specific developmental stages according to claim 8, characterized in that: The atlas production module includes an average template production unit, a brain region template production unit and a structure information file generation unit; wherein, The average template making unit is used to select the reconstruction results of multiple mouse brains from the reconstructed images as samples, use multiple iterations, data diversification processing and average transformation calculation, continuously iterate the registration and update the template, use different forms of the image to increase data information, combine all the registration results with the average transformation, optimize the template image, and obtain the average template; The brain region template making unit is used to use brain region drawing software to draw the hypothalamus and part of the nucleus structure of P7 on the template to generate a brain region template; The structure information file generating unit is used to organize the different brain region information contained in the brain region template and generate the structure information file of the mouse brain atlas.
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Section image registration and labeling method
CN121353359A