摘要
人脑是人体内结构和功能最为复杂的器官。长期以来,人类对脑的结构和功能进行了大量的研究工作;随着1997年“人类脑计划”在美国的正式启动,人们对大脑的探索进入了一个新的高度。将脑科学与信息学结合起来,建立数据库,绘制相应的脑图谱是该计划的一项重要内容。
脑图谱是对人脑进行探索的一项重要的工具。从文艺复兴时期的著名解剖学家Vesalius对大脑结构进行详细的描述开始,大量的神经解剖描述,图片和图像陆续出现。随着技术的进步,数字化脑图谱层出不穷,其中绝大部分脑图谱是建立在一个或者是数量极其有限的个体标本上,这些包括Vox-man脑图谱,Roland脑图谱,数字解剖学家计划脑图谱,哈佛脑图谱等等,其中当前世界上应用比较广泛的是Talairach and Tournoux脑图谱,此图谱标注Brodmann分区,许多学者依据该图谱开发出了计算机脑图谱系统用于临床;另外,Talairach坐标系统也经常被用于脑皮质的标准化。ICBM计划首次提出了概率性脑图谱的概念,概率性脑图谱的研究主要是通过将大量的个体影像数据置于一个共用的标准空间来建立可以代表人群共性的大标本脑图谱,很多学者都在致力于这方面的研究。当前常用的标准脑模板是ICBM152,其数据来自152名23岁左右健康成年人的MR扫描,因此,ICBM152是152名健康成年人脑的平均脑,更能代表大多数人脑的特征,它为个体人脑MRI图像的研究提供了一个标准的空间,便于不同研究对象之间的比较。2001年5月美国科学家联盟(FAS)提出了数字人计划,并且把人类脑计划作为其重要的组成部分,获得人脑数据以后建立了人类可视化脑图谱,这类脑图谱有明确的定位,也可通过多种方式识别,可以通过表面重建的方式来分析人脑皮质的结构和功能,主要用于解剖结构的标识。还有学者在三维的脑图谱研究中加上时间的因素,建立四维脑图谱,用来研究人脑的发展变化。也有学者利用组织学的方法来研究一些局部的大脑结构,例如海马、皮质下结构等,建立特定区域的脑图谱。现有的数字化标准脑图谱在一定程度上增加了人们对大脑的认识和研究,但是都有相应的不足之处并有待于进一步改善,并且这些脑图谱基本上是来源于西方人的数据,不具备东方人的特征。大量的研究表明,由于人种和生长环境的影响,东西方人脑会有比较显著的差别,在神经科学的研究中,假如我们直接把上述的脑图谱作为标准脑模板的话,可能会出现一些误差。因此,建立具有东方人特征且具有人群代表性的数字化标准脑图谱有其必要性。
本研究中,首先利用3.0 T磁共振扫描仪获取35例中国人高分辨率三维脑结构数据,并从ICBM数据库中选择年龄和性别完全匹配的35例Caucasian高分辨率三维脑结构数据,运用整体比较、大脑结构比较、局部大脑结构信息比较等多种方法对这两组的东西方人脑数据进行对比分析研究,发现东西方人脑在形状和结构上都有有明显的差异,这为我们下一步的研究奠定了坚实的理论依据。脑图谱的研究分为两步:1.利用3.0T磁共振扫描仪对56名健康成年男性进行扫描,获得高分辨率三维结构数据,对原始数据进行预处理,借鉴ICBM152的建立模式建立基于MRI图像的中国人数字化标准脑模板。2.利用数控冷冻铣切技术获得高质量的连续薄层脑断面数据,通过图像处理以后进行三维重建,获得真彩色的三维重建人脑,接着利用一系列的转换获得灰度几何人脑数据,最后把三维人脑数据配准到基于MRI的中国人数字化标准脑模板中,获得既有很高的空间分辨率,又有详细的结构信息的数字化标准脑图谱。
本研究分为三个部分,摘要如下:
第一部分中国人和Caucasian大脑结构的差别研究
第一章:基于结构分析的中国人和Caucasian大脑形态差异研究
目的:利用高分辨率结构MRI数据研究中国人和Caucasian大脑整体和大脑结构的差异。
材料和方法:选择年龄和性别完全匹配的健康右利中国和Caucasian年轻志愿者各35人,利用高分辨率结构MRI扫描仪进行扫描,获得高分辨率三维结构MRI数据。首先在BrainSuite软件中对大脑的整体特征进行评价,具体测量大脑的连合间线(AC-PC)长度,整个大脑的长、宽、高。利用LONI Brain Parser软件对大脑的56个结构进行分割,计算每一个结构的体积,获得精确的测量数据,利用统计学方法对两组不同的数据进行比较,找出两者的差别。
结果:
1.中国人和Caucasian在大脑的形状和尺寸上有一定的区别,中国人大脑的长、宽、高以及AC-PC线长度平均值分别是160.99mm、142.64mm、110.72mm和26.28mm,Caucasian大脑的长、宽、高以及AC-PC线长度平均值分别为171.68mm、127.48mm、106.31mm和28.13mm。中国人大脑的宽/长、高/长以及高/宽平均值分别为0.89、0.69、0.78;Caucasian则为0.74、0.62、0.83,因此可以看出中国人和Caucasian的大脑形状有差异,中国人大脑更圆一些,这一结果可能是因为大脑结构的不同造成,对上述数据进行统计分析发现中国人大脑的长、宽、高以及AC-PC线长度与Caucasian有明显差异,p＜0.01。
2.通过对两组大脑56个结构的体积测量结果分析,中国人和Caucasian在大脑结构上有一定的区别。左侧半球有明显区别(p＜0.01)的结构为:眶额回,直回,顶上回,枕中回,颞下回,颞中回,楔前叶,海马旁回,扣带回,岛叶皮质,壳和尾状核;右侧半球有明显区别(p＜0.01)的结构为:额上回,眶额回,中央后回,枕上回,枕中回,颞上回,颞中回,颞下回,中央前回,直回,楔前叶,海马旁回,岛叶皮质,壳和尾状核。
结论:中国人和Caucasian在大脑形态大小以及结构上有一定的差异性,这为我们建立中国人数字化标准脑图谱提供了坚实的理论基础。
第二章:中国人和Caucasian大脑局部结构差异:基于张量的形态测定研究
目的:利用基于张量的形态测定法(TBM)研究中国人和Caucasian在大脑局部结构上的差异。
材料和方法:选择年龄和性别完全匹配的健康右利中国和Caucasian年轻志愿者各35人,利用高分辨率结构MRI扫描仪进行扫描,获得高分辨率三维结构MRI数据。首先对原始数据进行预处理,利用BET软件自动去除颅骨和其他非脑组织,对自动处理结果进行手工矫正后获得去颅骨后大脑;将两组数据分别采取12参数线性转换仿射到lpba40.air.icbm452w5.brain.avg标准空间以调整个体大脑之间的位置和刻度差异,对两组数据分别建立最小变形目标脑模板(MDT),将每一个大脑数据分别仿射到MDT中,经过一系列的步骤建立每一个个体大脑的Jacobian脑图谱用以分析个体局部容积的差别;分别利用每组35个个体Jacobian图谱建立平均脑图谱,最后通过叠加表达以后对每一个体素的量值以及有效度进行评价,对感兴趣区域(ROI)进行分析,得到通过颜色标注两个个体大脑之间或者两个平均脑图谱之间的差异的脑图谱,分析说明中国人和Caucasian在相应大脑局部结构上的差异。
结果:通过对两组Jacobian平均脑图谱的对照研究以及对感兴趣大脑区域的分析,发现中国人和Caucasian在大脑额叶,大脑顶叶,大脑颞叶和大脑枕叶都有明显的差别(p＜0.01)。
结论:中国人和Caucasian在大脑的局部结构上都有明显的区别,这为我们建立中国人数字化标准脑图谱提供了理论基础。
第二部分:基于MRI数据的中国人数字化标准脑模板的建立
目的:利用高分辨率三维结构MRI数据建立中国人数字化标准脑模板。
材料和方法:利用3.0T磁共振扫描仪对56个年龄在20到30岁之间(平均年龄=24.03±2.06)的健康右利中国志愿者进行扫描,获取高分辨率三维结构MRI数据,对数据进行预处理。选择其中一个人脑作为目标脑,将所有的56个大脑利用12参数转换模式空间标准化到目标脑中并进行平均化处理后获得密度平均脑模型,然后再一次将所有的56个大脑仿射到该密度平均脑中,进行平均化后获得密度和空间都平均化的线性转换脑模板。将56个原始脑MRI数据线性(6参数)转换到起初的目标脑中获得56个与平均脑模板具有相同空间坐标的脑体积数据,以上述线性转换脑模板为目标脑,利用“align warp”的方法将此56个大脑非线性转换配准到目标脑中获得结构细节更加清楚的非线性转换脑模板。利用BET软件自动去除56个大脑的颅骨和非脑组织,对于自动处理结果进行手工矫正,获得56个去除颅骨以后的大脑体积数据,重复上述步骤,只是在相应的步骤做一下参数调整,最后获得去除颅骨的线性转换和非线性转换平均脑模板。
结果:通过对上述步骤的重复运行,调整好相应步骤中的关键性参数,获得基于MRI数据的两组数字化标准脑模板,分别为整个大脑脑模板和去颅骨后脑模板。其中每一组又有两个部分:线性转换平均脑模板和非线性转换平均脑模板。相对于非线性转换平均脑模板而言,线性转换平均脑模板缺少详细的结构信息,但是具有标准的空间坐标信息,尤其是整脑线性转换平均脑模板,因此也被称为平均脑模型;非线性转换平均脑模板具有比较清楚的大脑结构细节,因此可以用来更深一步的脑图谱研究,并且可以作为参考图谱来对一些具体的大脑结构进行对比分析。
结论:建立基于MRI数据的中国人数字化标准脑模板,为基于中国人数据的神经影像学研究提供基本的参考。
第三部分:基于标本断面数据的中国人数字化标准脑图谱的建立
目的:利用连续薄层断面数据对人脑进行三维重建,并将三维脑体积通过空间标准化配准到基于MRI数据的中国人数字化脑模板中建立基于连续薄层断面数据的中国人数字化标准脑图谱。
材料和方法:从4例尸体标本中选择1例作为研究对象,利用数字化冷冻铣切技术获取层厚为0.1毫米的连续薄层脑断面数据,将原始数据转换成JPEG格式,在Photoshop软件中进行数据裁减、分割,获得分辨率为512×512的二维图像共1506张,保存为TIFF格式。利用SHIVA软件将TIFF格式文件转换为ANALYZE格式文件,在UNIX系统服务器上用“cat”命令将1506个文件重建成为3D脑体积文件,将3D脑体积转换成几何三维模型和灰度三维脑模型,然后将灰度三维脑模型利用12参数转换模式空间标准化到已经建立的中国人数字化标准MRI脑模板中获得基于连续薄层断面数据的数字化标准脑图谱,去除颅骨和其他非脑组织后获得具有更加详细结构信息的数字化脑图谱。
结果:获得三维重建以后的三维脑模型,建立基于标本断面数据的中国人数字化脑图谱,包括全脑图谱和去除颅骨后的脑图谱,该脑图谱不仅具有详细的解剖结构信息和组织学信息,而且具有MRI脑模板的空间特征。
结论:建立基于标本断面数据的中国人数字化标准脑图谱,该脑图谱不仅可以作为解剖结构信息描述的参考,而且可以用来作为神经影像学研究中的脑模板。
结论和意义
一、首次利用较大样本的活体脑MRI数据,采用多种计算机图像分析方法对中国人和Caucasian大脑进行差异性研究,发现中国人和Caucasian在大脑结构上具有明显的差异,这为建立中国人数字化标准脑图谱提供了理论依据,为深入探讨东西方人脑的结构和功能差异提供了解剖学基础。
1.获取两组较大样本(年龄和性别完全匹配的中国男性右利青年和Caucasian男性右利青年各35例)的3D结构MRI数据,采用当前常用的图像分析方法直观地测量每个个体大脑的长、宽、高以及AC-PC线长度,对数据进行比较分析以后发现中国人和Caucasian的大脑形态和大小具有明显的区别,中国人大脑比Caucasian大脑更圆,因此大脑结构会有一定的区别。
2.利用LONI Brain Parser Pipeline对大脑的56个结构进行分割,手动校正,测量每个结构的体积,对比分析以后发现中国人和Caucasian在一些大脑结构上有明显的不同,进一步证实了以前关于中国人和Caucasian大脑功能存在显著差异的研究结果。
3.利用基于张量的形态测定法(TBM)研究中国人和Caucasian在大脑局部结构上的差异,对个体大脑MRI图像的每一个体素进行分析运算,发现中国人和Caucasian在大脑额叶、顶叶、颞叶、枕叶都有一定的区别。为将来进行中国人大脑结构和功能的研究提供科学的理论依据,激励研究人员进一步探索不同种群人脑之间的结构和功能差异。
二、首次获取较大样本(56例)的中国人活体大脑3.0 T MRI三维结构数据,并利用国际上最先进的脑图像计算机处理方法和脑图谱建立方法建立具有中国人群特征的数字化标准脑模板。相比较ICBM152等已存在的脑模板来说,本模板具有更高的分辨率和更详细结构信息,而且更加适合中国人大脑研究;同时为全球性的ICBM的研究添加了中国人的数据。
三、利用先进的数控冷冻铣切技术获取成人大脑标本的高质量的连续薄层断面数据,采用当前世界上常用的图像处理方法对数据进行预处理,并进行三维重建,获得大脑的三维重建模型,利用计算机和数学技术对三维脑模型进行一系列转换和空间标准化,首次建立了基于标本断面数据的中国人数字化标准脑图谱。该脑图谱不仅具有详细的解剖结构信息,而且具有MRI脑模板的空间特征,具有更加广泛的应用价值,为将来大脑结构和功能的探索提供详细的解剖学基础和值得借鉴的方法。
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 Caucasian
Section 1: The morphological brain differences between Chinese and Caucasian
based on the structure analysis
Purpose: 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 the
Serial Thin Sectional Data
Purpose: 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 Significances
1. 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.
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2.Ventegodt,S.,et al.,Human development Ⅻ:a theory for the structure and function of the human brain.ScientificWorldJournal,2008.8:p.621-42.
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4.Toga,A.W.,et al.,Towards multimodal atlases of the human brain.Nat Rev Neurosci,2006.7(12):p.952-66.
5.Gore,J.C.,et al.,Integration of fMRI,NIROT and ERP for studies of human brain function.Magn Reson Imaging,2006.24(4):p.507-13.
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