The Construction Of Digital Standard Chinese Brain Atlas

Human brain is the unique organ in human body with the most complicated structures and functions. Ever since a long time ago, much work has been done to explore the structures and functions of the human brain. With the development of "Human Brain Project" which was initiated in the United States of America in 1997, the research of exploration to the human brain entered into a new stage. To construct comprehensive brain atlas with the data originated from the integration of neuroscience and informatics science is one important part of this project.Atlases of human neuroanatomy play important roles in the exploration of human brain e.g. in the interpretation of results, in the visualization of information and in the processing of data. Beginning with the detailed drawing of brain structures produced during the Renaissance by Vesalius, numerous paper atlas comprising collections of neuroanatomical illustrations, photographs, and other images have been constructed. As technology advanced, digital atlases extended these efforts by providing interactive collections of brain data. Most of these brain atlases were based on single subjects or on very limited numbers of individuals. These included the Voxel-Man atlas, the Roland Human Brain Atlas, the Digital Anatomist project, the Harvard Brain Atlas etc. In these days, the most popularly used brain atlas around the world is the Talairach and Tournoux Brain Atlas, which has the mark of Brodmann area. Many researchers have developed computerized brain atlas system for clinic applications based on this atlas; moreover, the coordinate system of Talairach brain is always be used for the normalization of cerebral cortex. One of the early descriptions of a multi-subject atlas was presented by Mazziotta et al (1995), who proposed the development of a comprehensive probabilistic brain atlas under the banner of the International Consortium for Brain Mapping (ICBM). This project has collected data from more than 7000 subjects, including images of the brain using various magnetic resonance imaging (MRI) modalities, genetic materials, and demographic information. Multi-subject studies such as ICBM project require methods that can bring the image data from different subjects into a common coordinate frame, numerous research efforts have been made to meet these demands. The first average intensity template termed MNI-305 was produced by co-registering the MRI volumes using a nine-parameter linear transformation and then being averaged at each voxel, a second template was produced by registering a subset of 152 brains to the MNI-305 tempalte, again using a 9-parameter linear transformation, to generate the ICBM152 template. ICBM152 is the average brain atlas originated from 152 human brains therefor it can mostly represent the character of the human brain. Various analysis tools such as SPM and FLS use version of ICBM152 template as an anatomical reference because it provides a registration target. The Federation of American Scientists (FAS) proposed the Digital Human Project in May, 2001, and Human Brain Project became a very important ingredient of it. It dedicated to collect various brain data so as to create visible human brain atlases. This kind of atlases have well-defined location and are mainly used for the identification of anatomical structures, they can also be identified by many methods as well as be analyzed the structures and functions of the cerebral cortex by using surface reconstruction. The concept of four-dimensional brain atlas was proposed in 2001 by Mazziotta et al., it will create new data and insights into the organization of the human nervous system in health and disease, its developments, and its evolution. When successful, the atlas will provide previously unprecedented tools for organizing, storing, and communicating information about the human brain throughout development, maturation, adult life, and old age. Some other researchers used histological methods to delineate the local brain structures e.g. hippocampus and subcortical structures, and to construct some special brain atlases with detailed local structure information. In a certain degree, the existed brain atlases have done a lot for people's recognization and understanding of human brain, and they become more and more important in neuroscience research. But they still have some disadvantages and need to be improved, the most important reason is that most of the brain atlases were constructed with the data originated from Caucasians, which is different from Chinese. A lot of work indicated that there would be some obvious difference between the Chinese human brain and Caucasian human brain because of the race and the different living styles. There will be some errors if we straightly take the above Caucasian brain atlases as the standard brain template in the neuroscience research of Chinese human brain. So it's very necessary to construct a digital standard Chinese brain atlas with the character of Chinese, perfect and precious marks of different structures and fine group representation.In this project, the differences between Chinese brain and Caucasian brain were compared firstly. 35 healthy right-handed Chinese young male (aged 20-30) volunteers were selected and scanned with a 3.0T GE scanner to acquire high resolution 3D T1 structure MRI data, 35 healthy right-handed Caucasian subjects with the same age and gender were drawn from the ICBM(International Consortium for Brain Mapping) datasets and high resolution 3D structure brain MRI data were acquired. After comparing the brain global shape and size and 56 different brain structures of the human brain in these two groups as well as the local structure information difference, we found conspicuous differences on the brain shape and structure information between the two kinds of human brain, which also can illustrate that there will be some differences in the human brain functions. All of these findings provide the theory base of our further research. The construction of digital standard Chinese brain atlas was divided into two parts: 1. 56 healthy right-handed Chinese young male (aged 20-30) volunteers were selected and scanned with a 3.0T GE scanner to acquire high resolution 3D T1 structure MRI data, after some steps of data preprocessing, the digital standard Chinese brain template based on MRI data were constructed with the "AIR Make Atlas" Pipeline in LONI. 2. High quality 0.1mm sectional image data of human brain specimens were obtained using computerized freezing milling technique, after some steps of image processing, the human brain was 3D reconstructed with real color. Subsequently, the 3D reconstructed human brain was transfered into gray scale volume and geometric brain model using some softwares, then the gray scale brain volume was linearly aligned to the digital standard Chinese brain template and get a more precious digital human brain atlas, this kind of brain atlas not only can be used widely like the 3D MRI brain template, but also has a higher spatial resolution and more detailed structure information. Our research has three parts and the abstract was as followed:Part 1: The Morphological Brain Differences between Chinese and CaucasianSection 1: The morphological brain differences between Chinese and Caucasianbased on the structure analysisPurpose: To compare and analyze the morphological differences of global brain and brain structures between Chinese and Caucasian using high resolution 3D structure MRI image data.Materials and methods: 35 healthy right-handed Chinese young male (aged 20-30) volunteers were selected and scanned with a 3.0T GE scanner to acquire high resolution 3D T1 structure MRI data, 35 healthy right-handed Caucasian subjects with the same age and gender were drawn from the ICBM (International Consortium for Brain Mapping) datasets and high resolution 3D structure brain MRI data were acquired. The general features of human brains e.g. Length, width, height of the whole brains and AC-PC line length were measured using the BrainSuites software package, as it can provide a rigorous value of every voxel and the ability to display stimultaneous views of three orthogonal planes through the MRI volumes which will help the users to determine the boundary of every structure. For each subject MRI volume, a total of 50 cortical structures, 4 subcortical areas, the brainstem and the cerebellum were delineated with the LONI Brain Parsering pipeline by using a learning-based approach and a pre-trained model target at common structures of interest, all the structure volumes were measured automatically and preciously, after comparing the acquired data of the two groups we found the differences.Results:1. There are some differences in the brain shape and size between Chinese and Caucasian, the mean values of length,width,height and AC-PC line distance of Chinese human brain are 160.99mm,142.64mm,110.72mm and 26.28mm; while the mean values of Caucasian human brain are 171.68mm,127.48mm,106.31mm and 28.13mm. The ratios of width/length,height/length and height/width of Chinese human brain are 0.89,0.69 and 0.78; while the ratios of Caucasian human brain are 0.74,0.62 and 0.83. So the Caucasian human brain is a bit longer but the Chinese human brain is a bit more round. After statistic the analysis of these data we found the differences of shape and size of human brain between Chinese and Caucasian were significant, P<0.01.2. After analyzing the volumes of all the 56 structure in two different group, we found that some brain structures were significantly different (p<0.01) between Chinese and Caucasian: left middle orbitofrontal gyrus, left gyrus rectus, left precuneus, left middle temporal gyrus, left parahippocampal gyrus, left cingulated gyrus, left lateral orbitofrontal gyrus, left superior parietal gyrus, left middle occipital gyrus, left inferior temporal gyrus, left insular cortex, left insular cortex, left putamen, right superior frontal gyrus, right precentral gyrus, right lateral orbitofrontal gyrus, right gyrus rectus, right postcentral gyrus, right precuneus, right superior occipital gyrus, right middle occipital gyrus, right superior temporal gyrus, right middle temporal gyrus,right inferior temporal gyrus, right parahippocampal gyrus, right insular cortex, right caudate and right putamen.Conclusions: There are some significant differences in the brain general features and local structures between Chinese and Caucasian, which provide a solid base for us to construct the digital standard Chinese brain atlas.Section 2: The differences of brain structure shape between Chinese and Caucasian: a study of Tensor-based Morphology (TBM)Purpose: To explore the differences of local brain structures between Chinese and Caucasian using Tensor-based Morphology (TBM).Materials and methods: 35 healthy right-handed Chinese young male (aged 20-30) volunteers were selected and scanned with a 3.0T GE scanner to acquire high resolution 3D T1 structure MRI data, 35 healthy right-handed Caucasian subjects with the same age and gender were drawn from the ICBM (International Consortium for Brain Mapping) datasets and high resolution 3D structure brain MRI data were acquired. After Skull stripping and some other preprocessing steps, all individual brains in the two groups were linearly aligned to the lpba40.air.icbm452w5.brain.avg brain template using 12 parameters transformation and resampled. We then constructed a minimal deformation target (MDT) which was based on the initial scans of every subject, and a LONI pipeline module was used to construct Jacobian map for every individual subject. And the Jacobian maps were aligned to the standard space defined by the MDT template, thus the regional comparison and group analysis of the subjects were able to be performed, permutation testing was used to assess the overall significance of group differences, corrected for multiple comparisons.Results: After comparing the two groups and calculating the mean Jacobian within each region of interest (ROI) to show the computed overall volume differences for each lobe, we found there were some significant differences in the frontal lobe, occipital lobe, temporal lobe and parietal lobe between the two groups (p<0.01) .Conclusions: There are some significant differences in the local brain structures between Chinese and Caucasian, which provide a solid base for us to construct the digital standard Chinese brain atlas.Part 2: The Construction of Digital Standard Chinese Brain Template Based on Purpose: To construct the digital standard Chinese brain template using high resolution 3D structure MRI volume data.Materials and methods: 56 healthy right-handed Chinese young male (aged 20-30) volunteers were selected and scanned with a 3.0T GE scanner to acquire high resolution 3D T1 structure MRI data. After some preprocessing steps, one of the brain volumes was selected as the target brain and all the 56 brains were linearly aligned to the target brain using 12-parameter transformation, then steps of Define Common and Soft Mean were used to get a intensity average brain template with a common standard position. Taking the intensity average brain template as target brain and repeated the above step we got a spatial standardized brain template with average intensity, which called linear aligned brain template. All the 56 brains were rigid registered to the first target brain using 6-parameter transformation to get 56 new brains with the same spatial coordinate and scale to the average brain template, then all these 56 new brains were nonlinear aligned to the linear average brain template using "align wrap" to get a nonlinear brain template with more structure information. Non-brain tissues were removed by automatic BET and manual corrections to get 56 skull-stripped brain volumes. Repeated the above procedure and adjusted some parameters in some steps we got both skull-stripped linear brain template and skull -stripped nonlinear brain template.Results: We got two groups of digital brain templates: the brain templates before skull stripping and the brain templates after skull stripping. Every group includes two kinds of brain templates: linear aligned average brain template and nonlinear aligned brain template. Although the linear aligned brain templates were lack of precious structure information, they had standardized spatial coordinate, especially the template before skull stripping, so it was called average brain template and always used for spatial normalization in neuroimaging research. The nonlinear aligned average brain templates had more detailed structure information so they were always used for the reference of individual brain volume and the comparison of local structures between different groups.Conclusions: Digital standard Chinese brain templates based on MRI were constructed, which will be a reference for the neuroimaging research based on Chinese brain data.Part 3: The Construction of Digital Standard Chinese Brain Atlas Based on theSerial Thin Sectional DataPurpose: To 3D reconstruct Chinese human brain using serial thin sectional image data and construct digital standard Chinese brain atlas based on serial thin sectional data by registering the 3D brain volume to the digital standard Chinese MRI brain template.Materials and methods: One human brain specimen was selected from four subjects and 0.1mm continous sectional image data were acquired using computerized freezing milling technique. After the format conversion from raw files to JPEG files, Photoshop was used to crop and segment the files into 1506 2D images with a resolution of 512x512, and the files were saved as TIFF format. SHIVA was used to convert all the 1506 TIFF files to ANALYZE files, on the UNIX system workstation, the 1506 serial 2D images were reconstructed into a 3D brain volume, then the brain volume was transformed into geometric 3D model and gray-scale brain template, subsequently, the gray-scale brain template was linear registered to the Chinese MRI brain template using 12-parameter transformation to get a brain atlas based on the serial thin sectional data, semi-automatic method was used to remove the skull and other non-brain tissue and get a skull-stripped brain atlas.Results: A new brain model was established after the 3D reconstruction. We also got the digital standard Chinese brain atlas based on the serial thin sectional image data, which included the whole brain atlas and the skull-stripped brain atlas, these kind of brain atlas not only have detailed anatomical structure information and histological information, but also have the spatial character of MRI brain template, so they can be used more widely.Conclusions: The digital standard Chinese brain atlas based on the serial thin sectional data was constructed, and it can not only be used as a reference for the delineation of anatomic structures but also be used as another brain template in the research of neuroimaging.Conclusions and Significances1. A big sample of in vivo 3D structure MRI data was firstly used to explore the brain structure differences between Chinese and Caucasian. Using many computered measuring and analysis methods, some significant differences in the brain structures between the two groups were founed, which is the theory base of the construction of digital standard Chinese brain atlas, and it will provide detailed and practical morphologic basis for the exploration of Chinese brain structures and functions, the imaging diagnosis and clinic treatments of nervous system diseases of Chinese people as well as the diagnosis and treatments of psychological and psychiatric diseases.1.1 Some advanced image analysis methods were used to measure the brain length,width,height and AC-PC distance for every individual brain subject, after comparing the acquired data in the two groups, some significant differences of the brain shape and size between Chinese and Caucasian were founded, Chinese brain was more round than Caucasian's, which maybe lead to the differences of brain structures between the two human populations.1.2 56 brain structures of every individual brain subject were segmented automatically by using LONI Brain Parser Pipeline, annual method was used to correct the minor errors. Comparing the volumes of 56 structures between the two groups, we found some brain structures are significantly different between Chinese and Caucasian, which further approved the previous research results of the brain function differences between Chinese and Caucasian.1.3 Tensor-based Morphology (TBM) was firstly used to delineate the local brain structure differences between Chinese and Caucasian, by analyzing and computing every voxel of the individual brain MRI images, we found there were some significant differences in the frontal lobe,parietal lobe,temporal lobe and occipital lobe between Chinese and Caucasian. Which will provide scientific theoretical basis of the exploration to the Chinese human brain structures and functions, it can also stimulate the researchers to find the brain structure and function differences between different populations.2. Some advanced methods throughout the world were firstly used to construct the digital standard brain template with the character of Chinese human population based on a big sample of Chinese in vivo 3D high resolutional brain structure MRI data. Comparing to the existed brain template e.g. ICBM152, our brain template has higher resolution and more detailed structure information, and it is more suitable for the brain research of Chinese people. Furthermore, the construction of Chinese brain template will be a good supplement for the ICBM.3. High quality serial thin sectional images of brain specimen were acquired by using advanced computerized freezing milling technique, after the preprocess of the data with advanced image processing methods, we 3D reconstructed the human brain and got the 3D brain template. Subsequently, series of transformations to the 3D brain template using some computer and mathematics techniques were made, and a geometric brain template and a digital standard Chinese brain atlas based on the serial thin sectional data were constructed. This kind of brain atlas not only has more detailed anatomic structure information and histological information, but also has the spatial character of MRI brain template, so it has a wider application value and will provide precious anatomic basis and reference for the exploration of the brain structures and functions in the future.