作者想感谢他们与该项目的帮助下，在不同的阶段，杰夫秋季亚历山大基伦，查尔斯井，凯西皮尔逊，Vaibhav Paneri。这项工作是由UAB的心理学系的启动资金，麦克纳尔蒂- Civitan科学家奖CCTS试点研究资助（5UL1RR025777）RK部支持。

1。扫描个人有发展障碍的的特殊技巧: 虽然神经影像学本身是一个复杂的的技术，用核磁共振成像扫描儿科人口和发育障碍的人可以非常challenging.The的主要问题是:1）头部运动失调，特别是儿童的人，可能很难保持静止整个功能磁共振成像扫描仪扫描会话。这可能会导致头部运动，这反过来可能会影响数据的质量; 2）孤独症儿童有极端的感官的敏感性和可能，在封闭的空间，温度等因素，如扫描仪噪音困扰;和3 ）焦虑和调整到一个新的环境可以有自闭症的人很难。在日常的变化可能会造成问题，如果没有准备好。因此，需要精心准备的创新程序，以取得良好的收益，并提高收集数据的质量。我们从理论和实践中取得的宝贵经验，准备了核磁共振扫描参与者整合，使实验和扫描过程中其乐融融的参与者，以及过程中收集的数据，其中有些是: <ol><li> 社会故事社会故事很短，直接解释与autism8儿童小说和混乱的情况下经常使用的故事。我们用社会的故事，从个人与自闭症的角度写的，说明和口头说明我们的研究过程中的每一步。在每个项目中的故事，无论是口头和图案descriptionsare提供。题为"我的MRI会议"，我们提供的故事提前扫描一天的参与者，使他们能够成​​为熟悉扫描过程。这个故事的目的是增加个人的理解的过程，并且使他/她在新形势下更舒适。 </li><li> 光盘刻录，扫描仪的声音扫描会话期间，核磁共振成像扫描仪产生巨大声响不断，这可能是厌恶与孤独症的一些个人。为了适应环境的participantsto扫描仪的噪音，我们发送的参与者（扫描一天前）由扫描仪的声音的录音。 </li><li> 模拟磁共振成像扫描仪，我们模拟使用一个模拟扫描仪，建造了一个废弃的菲利普斯核磁共振成像扫描仪的参与者与MRI扫描会话。这提供了一个现实的近似实际扫描会话。位于州立大学眼科视光学系，这个模拟扫描仪的使用使参与者成为习惯扫描器环境。 </li><li> 核磁共振成像扫描仪在此之前的巡回扫描开始前的核磁共振成像扫描，参与者提供了一个机会，看到扫描仪和扫描仪的病床上，得到简要。通常，这有助于减轻恐惧和焦虑，以及研究人员提供与行为有关参与者的反应扫描仪的信息。这种反应往往提供有价值的，虽然直观和定性，参与者是否可能完成整个scan.Before参与者到扫描仪的信息，他/她留在更衣室他所有的家当，还采用了金属检查金属探测器。 </li><li> 使核磁共振成像扫描仪对儿童友好的 ，对于我们所有的扫描，我们使用西门子3.0特斯拉Allegra的核磁共振成像扫描仪位于UAB的Civitan国际研究中心。这是一个头只扫描仪，使参与者恐吓。为了使尽可能儿童友好（儿科）的扫描仪环境，扫描仪，可轻松卸除贴纸除了动物，卡通人物等装饰，我们向与会者提供了五颜六色的毯子，让他们在扫描仪的温暖。对于儿童孤独症往往有特殊的利益（如火车），这种利益可以考虑，而装饰的扫描仪。 </li><li> 使用电影或漫画:解剖和DTI图像采集不要求参与者在扫描仪执行的任务。这些扫描期间，参与者都选择观看自己喜欢的电影或卡通系列几分钟。除了提供一个欢迎突破的任务，这有​​助于使扫描过程更愉快的参与者。 </li></ol> 2。刺激的演示软件和按钮响应设备，用于交流与扫描器: <ol><li>实验的任务是用 E -首相（心理学的软件工具，匹兹堡，PA）的刺激演示软件编程。扫描会话之前，参与者的做法在笔记本电脑上的较短版本的任务，使他们熟悉的是什么，他们会看到扫描仪，他们将被要求按什么按钮。 </li><li>的t要求装上集成的功能成像系统（国际金融机构，Invivo公司，佛罗里达州奥兰多市），和同步扫描范式。国际金融机构体系有助于投射屏幕背后的参与者的视觉刺激，而在扫描仪，它通过连接头线圈镜子的参与者意见。 </li><li>中控室的双显示器允许研究人员选择的实验任务，或在扫描期间的电影，和监察参与者的反应（包括响应时间和性能的精确性）。 </li><li>与会者穿着MRI检查，使他们能够听到声音的兼容耳机，听取了研究人员的指示，以及减少扫描仪的突兀噪音。除了耳机，耳塞，以进一步减少扫描仪的噪音。 </li><li>一个光纤按钮响应的设备连接到每手允许参与者以应对任务的问题。国际金融机构的系统记录这些反应，以及结合扫描定时在每个响应时间。 </li><li>紧急"挤球"是考虑到参与的情况下，他/她不希望继续扫描。按这个球将促使研究人员去参与者立即掀起了中控室报警。 </li></ol> 3。使用静态和动态的视觉刺激，引起自闭症的参与者的大脑反应: 虽然一个很好的实验设计是至关重要的任何科学的研究，取得同与会者的共鸣，可以上获得的数据，尤其是在神经影像学，有显著的影响。刺激应在参与者的理解水平，实验应该是短期的，精确和愉快。如果不给予足够的重视这些元素，数据的质量产生负面影响。采取特别护理是设法使实验任务具有挑战性和愉快的创造创新的刺激。 <ol><li>使用动态的视觉刺激，如视频，描绘社会交往，引起参与者的精神状态归属反应。除了短期和愉快的，这些刺激是真实的社会世界的切片，和提供一个与社会认知的相关调查的大脑反应的适当的舞台。 </li><li>静态的视觉刺激，如简笔画字符显示不同的身体姿势，也可以用来研究社会认知。这些刺激，有助于学习情绪，鼓励与会者从身体语言推断感情。 </li><li>也可用于静态的视觉刺激，如涉及多个字符，描绘了社交场合的漫画插图。这些刺激包括根据民间物理学和民间心理的归属。 </li><li>对于研究语言处理的研究中，我们主要使用的任务，涉及句子理解，词汇决策和话语加工。 </li><li>虽然每次实验的长度从另一个不同的，我们尽量保持每一个实验，不到10分钟。此外，我们还尝试夹心贸工部扫描和解剖扫描之间的实验给参与者一些自由/休息时间。我们发现这一战略的合理的成功。我们尝试在一个扫描会话，包括在磁铁花费的总时间约30-40分钟服用2-3任务。为描绘了研究协议的流程图，请参阅图1。 </li></ol> 4。数据采集​​，存储，分析，质量控制: 数据采集​​: <ol><li>功能磁共振成像和DTI数据收集在每个参与者的单一使用西门子3.0特斯拉Allegra的头只扫描仪（西门子医疗系统公司，德国埃尔兰根）设在Civitan国际研究中心，美国阿拉巴马大学伯明翰会议。 </li><li>高分辨率扫描T1加权构造成像扫描会话启动。这些都是后天的使用TR（重复时间）= 200毫秒，TE（回波时间）= 3.34毫秒，翻转角= 12度，视场（视场）160片的三维MPRAGE（磁化编写的快速梯度回波）容积扫描= 25.6厘米，256 × 256矩阵的大小，1毫米层厚。此次收购将持续约8分钟，所获得的数据提供有关每个参与者的大脑解剖信息。 </li><li>其次解剖扫描功能扫描。要获得功能图像，我们使用与TR = 1000毫秒，TE = 30毫秒，翻转角单次召回梯度平面回波脉冲序列= 60度，FOV = 24厘米，和矩阵= 64 × 64。我们收购交错序列中的17个相邻的斜轴位片，切片厚度为5毫米，1毫米的切片差距，一个24厘米的视野，和一个64 × 64的矩阵，导致在一个平面分辨率为3.75 × 3.75 × 5毫米。 </li><li>根据功能磁共振成像实验的长度在60-75分钟，两个或三个实验犹特扫描会话。 </li><li>贸工部图像采集使用单次，自旋回波，长盈集团（Echoplanar成像）与46个正交方向序列。一个弥散加权，单拍，自旋回波，回波平面成像序列TR = 7000毫秒，TE = 90毫秒，带宽= 2790赫兹/体素，FOV =220毫米和矩阵大小= 128X 128。二十七名3毫米厚的片，都没有扩散加权成像（没有片差距）（B = 0s/mm2）和扩散加权（B = 1000s/mm2）适用于46个正交方向上的梯度。 </li></ol>数据存储和数据分析: <ol><li>从MRI会议获得的神经影像数据被转移到了一通墙保护与健康保险流通和责任法案（HIPAA）的大学医院的计算机网络。 </li><li>从该服务器MRI和DTI数据传送到中央电脑实验室的服务器（ 神经元 ），匿名的，之前，它是由可用于数据分析。神经元的服务器房屋所有图像分析程序，以及在内部脚本做了计算，具体到我们的实验。 </li><li>计算机集群采用3个节点，每一个四核处理器，使多个数据集的处理速度更快，并行。此外，由于来自不同的研究数据驻留在一个共同的位置，它可以更容易地组织荟萃分析的数据，并作出总体的推论。 </li><li> fMRI数据前和后处理，并进行统计分析使用SPM8（统计参数图;惠康认知神经部，伦敦，英国）。此外，分析功能NeuroImages（AFNI），其他软件程序，如，fMRIB软件库（FSL）和MRICron也用于其他的分析。 </li><li> DTI图像前和后处理，并进行统计分析使用FSL的。 </li></ol>质量控制: <ol><li>使用功能磁共振成像数据的预处理步骤，如片定时校正，运动校正，调整，空间正常化，空间平滑，完成时间和空间上的调整。 </li><li>信号噪音比（SNR）之间的任务相关的变异性和非任务相关的变异的比例计算。噪音（非任务相关的变异），可以包括热噪声任何头部运动的影响。通过计算SNR获得相对较高的比例（&gt; 0.8）和文物控制，我们可以确保图像满足严格的质量标准。 </li><li>时序信号信噪比（TSNR）是在整个实验过程中的SNR和数学的平均信号强度信号随时间变化的比率定义。在每个体素的平均值和标准差，如果在大脑中的比例是在一个可接受的阈值，图像可以被用于进一步分析。 </li><li>它始终是一个好主意，检查工件在每一步预处理和分析的数据。例如，研究无线电频率（RF）文物原始图像预处理的数据或评估运动伪影。控制为文物的预防性措施之一是屏幕金属或头部周围的科目，如括号或永久固定，以限制信号下降量。 </li><li>如果数据集有太多的噪音甚至运动后的修正程序，并不能满足我们的数据质量标准，该数据集通常是排除进一步分析。 </li></ol> 5。研究在网络级别的孤独症脑为基础的功能磁共振成像解剖连接功能连接和贸工部基于考试调查: 功能连接: 功能连接是指在大脑中的不同地区之间的大脑活动的同步。不同脑区的激活时间进程的相关证据证明这些地区之间的通信或的连接。在这种分析中所涉及的步骤如下: <ol><li>利益（投资回报）​​的地区被确定，无论是功能（激活的反应，以任务为基础）或解剖学（基于标准化的脑地图集）。这些定义的ROI是球半径，这将包括激活，或他们在原来的形状定义。 </li><li>指定半径或实际形状与MNI坐标，纳入创建一个为所有使用内部script.The这些投资回报的地点之间的重叠的存在是调查和纠正的投资回报率的投资回报率（ROI）文件。 </li><li>对于每一个投资回报率，信号是从每个参与者的个人数据的实验时间过程中提取。 </li><li>对于每一个参与者，平均每个投资回报率的信号的时间当然是与所有其他导致相关矩阵的投资回报。的相关性值转换为费舍尔的Z的得分，然后作进一步的统计分析，使个人，团体，和组之间水平的推论。 </li></ol>解剖连接（DTI）的: 为了考察整个大脑的白质完整性，扩散张量图像分析使用fMRIB软件库（FSL）9。以下是所涉及的主要步骤: <ol><li>在此分析的第一步是预处理，包括颅骨剥离和涡流校正。头骨剥离脑提取工具（BET）的使用，以消除任何非实质的组织。当高强度的扩散梯度正在迅速切换，剪切和拉伸工件生产，这是每个梯度方向不同。纠正这些扭曲是使用固定利差贷款的涡流校正寄存器没有应用扩散梯度扩散的图像参考图像。 </li><li>扩散张量和分数各向异性（FA）值，水沿神经轴突扩散指数，然后计算在体素的水平，所使用的固定利差贷款的扩散工具箱。 </li><li>集团由一个体素体素的水平差异研究使用尿路基于空间统计（TBSS）10 。在这种技术中，所有的扩散图像对齐到一个共同的空间使用非线性登记。 </li><li>创建的所有主要从所有参与者的脑白质大片FA骨架。所有参加者的个人扩散的图像，然后注册这个法道骨架。 </li><li>沿着这条从与会者的图像与孤独症骨架地区相比，体素的体素从控制参与者使用t -检验同一地区。不同的FA值体素分离作为一个大的投资回报率和平均FA值计算。 </li></ol> 6。代表性的成果: 削弱神经反应与自闭症的参与者涉及到我们的研究中出现的主要结果（激活，信号强度变化，在功能连接）和皮质路线改变，在完成认知和社会任务可能使用。举例来说，核心区域发现调解功能（如在推断他人意图的颞交界处后上颞沟;见图2），似乎回应自闭症，相对典型的控制参与者。此外，核心区域似乎underconnected功能与其他节点，特别是空间遥远的（图3）。与DTI，我们也发现一些这些研究结果的解剖学基础（见图4），提供一个全面的网络级图片自闭症的脑组织。 <img src="/files/ftp_upload/3178/3178fig1.jpg" alt="图1"/> 图1。流程图描绘的方法和程序。 <img src="/files/ftp_upload/3178/3178fig2.jpg" alt="图2"/> 图2:a）增加激活在一个典型的语言任务，如句子理解（左额下回，和左后颞上沟），B）增加在心理状态的归属双边的后颞上沟激活他人neurotypical参与者（FWE纠正门槛P &lt;0.05）。 <img src="/files/ftp_upload/3178/3178fig3.jpg" alt="图3"/> 图3。显着减少功能连接（脑激活的同步）与孤独症的参与者之间在社会认知任务的额叶和颞地区（P &lt;0.05）。 LSTG:左颞上回，RSTG:右颞上回，RIFG:右额下回，投资回报率:感兴​​趣区域，边境禁区:功能连接。 <img src="/files/ftp_upload/3178/3178fig4.jpg" alt="图4"/> 图4。贸工部跟踪技术的结果呈现出白质纤维束从颞叶颞交界处出发。最初的出发点跟踪技术是TBSS确定投资回报率相比，年龄匹配的典型控制参与者有一个年轻的成年人患有自闭症的FA值明显变小。

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J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functional+and+Anatomical+Cortical+Underconnectivity+in+Autism:+Evidence+from+an+fMRI+Study+of+an+Executive+Function+Task+and+Corpus+Callosum+Morphometry.">Functional and Anatomical Cortical Underconnectivity in Autism: Evidence from an fMRI Study of an Executive Function Task and Corpus Callosum Morphometry.</a> Cerebral Cortex. 17, 951-961 (2007).</li><li>Castelli, F., Frith, C., Happe, F., Frith, U. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Autism,+Asperger+syndrome+and+brain+mechanisms+for+the+attribution+of+mental+states+to+animated+shapes.">Autism, Asperger syndrome and brain mechanisms for the attribution of mental states to animated shapes.</a> Brain. 125, 1839-1849 (2002).</li><li>Gray, C. A., Garand, J. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Social+stories:+Improving+responses+of+students+with+autism+with+accurate+social+information.">Social stories: Improving responses of students with autism with accurate social information.</a> Focus on Autistic Behavior. 8, 1-10 (1993).</li><li>Smith, S. M., Jenkinson, M., Woolrich, M. W., Beckmann, C. F., Behrens, T. E. J., Johansen-Berg, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Advances+in+functional+and+structural+MR+image+analysis+and+implementation+as+FSL.">Advances in functional and structural MR image analysis and implementation as FSL.</a> NeuroImage. 23, 208-219 (2004).</li><li>Smith, S. M., Jenkinson, M., Johansen-Berg, H., Rueckert, D., Nichols, T. E., Mackay, C. E., Watkins, K. E., Ciccarelli, O., Cader, M. Z., Matthews, P. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tract-based+spatial+statistics:+Voxelwise+analysis+of+multi-subject+diffusion+data.">Tract-based spatial statistics: Voxelwise analysis of multi-subject diffusion data.</a> NeuroImage. 31, 1487-1505 (2006).</li><li>Li, Q., Sun, J., Guo, L., Zang, Y., Feng, Z., Huang, X., Yang, H., Lv, Y., Huang, M., Gong, Q. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Increased+fractional+anisotropy+in+white+matter+of+the+right+frontal+region+in+children+with+attention-deficit/hyperactivity+disorder:+a+diffusion+tensor+imaging+study.">Increased fractional anisotropy in white matter of the right frontal region in children with attention-deficit/hyperactivity disorder: a diffusion tensor imaging study.</a> Neuro Endocrinol Lett. 31, 747-753 (2010).</li><li>Jeong, J. W., Sundaram, S. K., Kumar, A., Chugani, D. C., Chugani, H. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Aberrant+diffusion+and+geometric+properties+in+the+left+arcuate+fasciculus+of+developmentally+delayed+children:+a+diffusion+tensor+imaging+study.">Aberrant diffusion and geometric properties in the left arcuate fasciculus of developmentally delayed children: a diffusion tensor imaging study.</a> AJNR Am J Neuroradiol. 32, 323-330 (2011).</li><li>Mulder, M. J., van Belle, J., van Engeland, H., Durston, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functional+connectivity+between+cognitive+control+regions+is+sensitive+to+familial+risk+for+ADHD.">Functional connectivity between cognitive control regions is sensitive to familial risk for ADHD.</a> Human Brain Mapping. , (2010).</li><li>Vourkas, M., Micheloyanni, S., Simos, P. G., Rezaie, R., Fletcher, J. M., Cirino, P. T., Papanicolaou, A. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dynamic+task-specific+brain+network+connectivity+in+children+with+severe+reading+difficulties.">Dynamic task-specific brain network connectivity in children with severe reading difficulties.</a> Neurosci Lett. 488, 123-128 (2011).</li></ol>

没有利益冲突的声明。

本文中所描述的方法和程序，在认知神经科学和神经影像学的基本原则为基础。两者合计，这些方法提供了一个令人信服的评估系统级的儿童，成人，并在与疾病的人的大脑功能框架。在这些方法的基础上的研究已与孤独症个体特征不和谐的大脑功能，尤其是有影响力的。 虽然这里介绍的技术移植到其他人群，以解决有关的理论问题，11,12,13,14，是需要认真注意小儿神经影像学检查，以及在发育障碍的人神经影像学检查:1）尽管防范和我们扫描所采取的准备措施，头部运动仍是一个在神经影像学的主要关注。该扫描仪是极其敏感的头部运动，与造成显著的运动伪影仅0.5毫米的旋转运动。虽然我们提出了一些技巧，以帮助减轻焦虑，从而减少运动，如模拟扫描仪和扫描仪室装潢，在这些线路的任何努力可能是值得的。目前，我们正在努力适应反馈范式，使用培训，以保持头部运动，以最小的电影; 2）另一个问题涉及到的参与者尤其是在儿童，辍学。许多孩子拒绝进入扫描仪或恐慌，扫描开始后，3）还有一个问题是固有的异质性发育障碍的一种表现。发育障碍的研究人员必须要小心处理，否则可能会经常报道组级别的推论下埋在他们的样本的变异，以及4）即使是轻微的设备问题，可以有显著影响的研究协议和研究者使用。例如，刺激演示程序电子总理没有播放视频刺激的能力。虽然该软件的最新版本的播放视频，该版本是与国际金融机构系统的不兼容。在这样的实例中，我们使用 Inquisit的软件，发挥我们的动画和视频，但与手动同步视频与扫描仪的计算机的额外的步骤。尽管上述的一些限制，功能性磁共振成像使它成为最好的神经影像学技术来研究大脑的功能之一以下几个优点:1，不同技术，如正电子发射断层扫描（PET）），磁共振成像不需要注入人体的放射性同位素; 2）功能磁共振成像的空间分辨率优于脑电图（EEG）等技术; 3）采集时间可短取决于范式，这可能是像自闭症障碍的人的工作很有帮助。 为了表征复杂的，多维像自闭症障碍的神经生物学，综合神经科学的方法，即包括新颖，多样的方法和技巧，是自闭症断定needed.Current理论underconnectivity的大脑区域，尤其是额叶皮层和更后的地区之间，可能是在解释孤独症的关键赤字至关重要。在这个方向下一个可能的合乎逻辑的步骤是通过同一个目标的翻译方法来解决这样的问题，以改善自闭症患者的大脑中的改变连接。一个纵向研究，针对大脑的可塑性，以评估大脑反应前后密集的认知干预可以显示可能产生的影响干预可以有自闭症的个人行为，认知和神经反应。通过继续发展和微调我们的技术，如连接功能，有效和解剖，我们可以得到一个更好的理解这种广泛性发育障碍和翻译的知识获得的干预。

probing the brain in autism using fmri and diffusion tensor imaging

新兴的理论认为，大脑功能不作为一个自闭症的凝聚力单位，这种不一致是反映在个人与孤独症显示行为症状。虽然结构神经影像学检查结果到自闭症的大脑异常提供了一些见解，这些研究结果的一致性是值得商榷的。脑功能成像，另一方面，已经在这方面进行了富有成果的，因为自闭症是一种动态处理的障碍，并允许检查皮质的网络，这似乎是潜在的问题发生在自闭症之间的沟通。被定义为时间相关的空​​间独立的神经events1功能连接。从最近的fMRI研究结果都支持的想法，是大脑的不同部位，应共同努力，完成复杂的社会或语言问题2,3,4,5,6弱之间的协调。孤独症的奥秘之一，是伴随着相对完整的，有时会增强，能力，在若干领域的赤字共存。这种复杂的孤独症的表现要求在神经层面，为全球和全面的无序的检查。最近在自闭症大脑功能的一个引人注目的帐户，2,7皮质underconnectivity理论，提供了一个孤独症的神经生物学基础的综合性框架。皮质underconnectivity自闭症的理论表明，任何一种语言，社会，心理功能是依赖于多个大脑区域一体化是容易中断处理需求的增加。自闭症，在大脑中的一体化电路underfunctioning，可能会导致广泛underconnectivity。换句话说，有自闭症的人可能在一个头痛医头，脚痛医脚的方式解释整个费用的信息。由于皮质underconnectivity的大脑区域之间，尤其是额叶皮层和更多的3,6后地区，现在已经比较完善，我们就可以开始进一步了解大脑连接的自闭症症状的重要组成部分。 逻辑在这个方向的下一个步骤是检查的解剖连接可能调解上述功能连接。弥散张量成像（DTI）是一个相对较新的神经影像学技术，帮助探针在大脑中扩散的水来推断脑白质纤维的完整性。在这种技术中，在大脑中的水扩散研究在几个方向扩散梯度。虽然功能连接提供有关的大脑在不同的脑区的激活在一个任务或在休息的同步信息，贸工部有助于理解底层的轴突组织可能有助于脑区之间的串扰。本文将介绍作为有价值的工具在了解自闭症，并在这方面的研究行所面临的挑战大脑的这些技术。

Watch this Scientific Journal Video about Probing the Brain in Autism Using fMRI and Diffusion Tensor Imaging at JoVE.com

Probing the Brain in Autism Using fMRI and Diffusion Tensor Imaging

影像学技术，如功能磁共振成像和弥散张量成像，已成为越来越有用的刻画在自闭症的认知和神经赤字。在自闭症患者的大脑连接在沿扫描与发育残疾的儿童改编的网络水平考试。

探讨孤独症的脑功能磁共振成像和弥散张量成像

Newly emerging theories suggest that the brain does not function as a cohesive unit in autism, and this discordance is reflected in the behavioral ...

probing-the-brain-in-autism-using-fmri-and-diffusion-tensor-imaging

Nanyang Technological University

Research

JoVE Journal

Medicine

25.0K 次观看.  University of Alabama at Birmingham. 影像学技术，如功能磁共振成像和弥散张量成像，已成为越来越有用的刻画在自闭症的认知和神经赤字。在自闭症患者的大脑连接在沿扫描与发育残疾的儿童改编的网络水平考试。

视频: Probing the Brain in Autism Using fMRI and Diffusion Tensor Imaging

Magnetic Resonance Derived Myocardial Strain Assessment Using Feature Tracking

Purpose: An accurate and practical method to measure parameters like strain in myocardial tissue is of great clinical value, since it has been shown, that strain is a more sensitive and earlier marker for contractile dysfunction than the frequently used parameter EF. Current technologies for CMR are time consuming and difficult to implement in clinical practice. Feature tracking is a technology that can lead to more automization and robustness of quantitative analysis of medical images with less time consumption than comparable methods.
Methods: An automatic or manual input in a single phase serves as an initialization from which the system starts to track the displacement of individual patterns representing anatomical structures over time. The specialty of this method is that the images do not need to be manipulated in any way beforehand like e.g. tagging of CMR images.
Results: The method is very well suited for tracking muscular tissue and with this allowing quantitative elaboration of myocardium and also blood flow.
Conclusions: This new method offers a robust and time saving procedure to quantify myocardial tissue and blood with displacement, velocity and deformation parameters on regular sequences of CMR imaging. It therefore can be implemented in clinical practice.

An accurate and practical method to measure parameters like strain in myocardial tissue is of great clinical value, since it has been shown, that strain is a more sensitive and earlier marker for contractile dysfunction than the frequently used parameter EF.

磁共振衍生的心肌劳损评估使用特征跟踪

Purpose: An accurate and practical method to measure parameters like strain in myocardial tissue is of great clinical value, since it has been shown, that ...

科研

医学

A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia

There are several lines of evidence supporting the role of de novo mutations as a mechanism for common disorders, such as autism and schizophrenia. First, the de novo mutation rate in humans is relatively high, so new mutations are generated at a high frequency in the population. However, de novo mutations have not been reported in most common diseases. Mutations in genes leading to severe diseases where there is a strong negative selection against the phenotype, such as lethality in embryonic stages or reduced reproductive fitness, will not be transmitted to multiple family members, and therefore will not be detected by linkage gene mapping or association studies. The observation of very high concordance in monozygotic twins and very low concordance in dizygotic twins also strongly supports the hypothesis that a significant fraction of cases may result from new mutations. Such is the case for diseases such as autism and schizophrenia. Second, despite reduced reproductive fitness1 and extremely variable environmental factors, the incidence of some diseases is maintained worldwide at a relatively high and constant rate. This is the case for autism and schizophrenia, with an incidence of approximately 1% worldwide. Mutational load can be thought of as a balance between selection for or against a deleterious mutation and its production by de novo mutation. Lower rates of reproduction constitute a negative selection factor that should reduce the number of mutant alleles in the population, ultimately leading to decreased disease prevalence. These selective pressures tend to be of different intensity in different environments. Nonetheless, these severe mental disorders have been maintained at a constant relatively high prevalence in the worldwide population across a wide range of cultures and countries despite a strong negative selection against them2. This is not what one would predict in diseases with reduced reproductive fitness, unless there was a high new mutation rate. Finally, the effects of paternal age: there is a significantly increased risk of the disease with increasing paternal age, which could result from the age related increase in paternal de novo mutations. This is the case for autism and schizophrenia3. The male-to-female ratio of mutation rate is estimated at about 4&#x2013;6:1, presumably due to a higher number of germ-cell divisions with age in males. Therefore, one would predict that de novo mutations would more frequently come from males, particularly older males4. A high rate of new mutations may in part explain why genetic studies have so far failed to identify many genes predisposing to complexes diseases genes, such as autism and schizophrenia, and why diseases have been identified for a mere 3% of genes in the human genome. Identification for de novo mutations as a cause of a disease requires a targeted molecular approach, which includes studying parents and affected subjects. The process for determining if the genetic basis of a disease may result in part from de novo mutations and the molecular approach to establish this link will be illustrated, using autism and schizophrenia as examples.

Molecular genetic strategy for finding de novo mutations causing common disorders such as autism and schizophrenia.

一项战略，以确定在常见的疾病，如自闭症和精神分裂症的新突变

There are several lines of evidence supporting the role of de novo mutations as a mechanism for common disorders, such as autism and schizophrenia. First, ...

MRI-guided Disruption of the Blood-brain Barrier using Transcranial Focused Ultrasound in a Rat Model

Focused ultrasound (FUS) disruption of the blood-brain barrier (BBB) is an increasingly investigated technique for circumventing the BBB1-5. The BBB is a significant obstacle to pharmaceutical treatments of brain disorders as it limits the passage of molecules from the vasculature into the brain tissue to molecules less than approximately 500 Da in size6. FUS induced BBB disruption (BBBD) is temporary and reversible4 and has an advantage over chemical means of inducing BBBD by being highly localized. FUS induced BBBD provides a means for investigating the effects of a wide range of therapeutic agents on the brain, which would not otherwise be deliverable to the tissue in sufficient concentration. While a wide range of ultrasound parameters have proven successful at disrupting the BBB2,5,7, there are several critical steps in the experimental procedure to ensure successful disruption with accurate targeting. This protocol outlines how to achieve MRI-guided FUS induced BBBD in a rat model, with a focus on the critical animal preparation and microbubble handling steps of the experiment.

Microbubble-mediated focused ultrasound disruption of the blood-brain barrier (BBB) is a promising technique for non-invasive targeted drug delivery in the brain1-3. This protocol outlines the experimental procedure for MRI-guided transcranial BBB disruption in a rat model.

MRI引导下的破坏血脑屏障在大鼠模型经颅聚焦超声

Focused ultrasound (FUS) disruption of the blood-brain barrier (BBB) is an increasingly investigated technique for circumventing the BBB1-5. The BBB is a ...

Eye Tracking Young Children with Autism

The rise of accessible commercial eye-tracking systems has fueled a rapid increase in their use in psychological and psychiatric research. By providing a direct, detailed and objective measure of gaze behavior, eye-tracking has become a valuable tool for examining abnormal perceptual strategies in clinical populations and has been used to identify disorder-specific characteristics1, promote early identification2, and inform treatment3. In particular, investigators of autism spectrum disorders (ASD) have benefited from integrating eye-tracking into their research paradigms4-7. Eye-tracking has largely been used in these studies to reveal mechanisms underlying impaired task performance8 and abnormal brain functioning9, particularly during the processing of social information1,10-11. While older children and adults with ASD comprise the preponderance of research in this area, eye-tracking may be especially useful for studying young children with the disorder as it offers a non-invasive tool for assessing and quantifying early-emerging developmental abnormalities2,12-13. Implementing eye-tracking with young children with ASD, however, is associated with a number of unique challenges, including issues with compliant behavior resulting from specific task demands and disorder-related psychosocial considerations. In this protocol, we detail methodological considerations for optimizing research design, data acquisition and psychometric analysis while eye-tracking young children with ASD. The provided recommendations are also designed to be more broadly applicable for eye-tracking children with other developmental disabilities. By offering guidelines for best practices in these areas based upon lessons derived from our own work, we hope to help other investigators make sound research design and analysis choices while avoiding common pitfalls that can compromise data acquisition while eye-tracking young children with ASD or other developmental difficulties.

Eye tracking has long been used to study gaze patterns in typically-developing individuals, but recent technological advancements have made its use with clinical populations, including autism, more feasible. While eye-tracking young children with autism can offer insight into early symptom manifestations, it involves methodological challenges. Suggestions for best practices are provided.

自闭症幼儿的眼动追踪

The rise of accessible commercial eye-tracking systems has fueled a rapid increase in their use in psychological and psychiatric research. By providing a ...

The Use of Pharmacological-challenge fMRI in Pre-clinical Research: Application to the 5-HT System

Pharmacological MRI (phMRI) is a new and promising method to study the effects of substances on brain function that can ultimately be used to unravel underlying neurobiological mechanisms behind drug action and neurotransmitter-related disorders, such as depression and ADHD. Like most of the imaging methods (PET, SPECT, CT) it represents a progress in the investigation of brain disorders and the related function of neurotransmitter pathways in a non-invasive way with respect of the overall neuronal connectivity. Moreover it also provides the ideal tool for translation to clinical investigations. MRI, while still behind in molecular imaging strategies compared to PET and SPECT, has the great advantage to have a high spatial resolution and no need for the injection of a contrast-agent or radio-labeled molecules, thereby avoiding the repetitive exposure to ionizing radiations. Functional MRI (fMRI) is extensively used in research and clinical setting, where it is generally combined with a psycho-motor task. phMRI is an adaptation of fMRI enabling the investigation of a specific neurotransmitter system, such as serotonin (5-HT), under physiological or pathological conditions following activation via administration of a specific challenging drug.
The aim of the method described here is to assess brain 5-HT function in free-breathing animals. By challenging the 5-HT system while simultaneously acquiring functional MR images over time, the response of the brain to this challenge can be visualized. Several studies in animals have already demonstrated that drug-induced increases in extracellular levels of e.g. 5-HT (releasing agents, selective re-uptake blockers, etc) evoke region-specific changes in blood oxygenation level dependent (BOLD) MRI signals (signal due to a change of the oxygenated/deoxygenated hemoglobin levels occurring during brain activation through an increase of the blood supply to supply the oxygen and glucose to the demanding neurons) providing an index of neurotransmitter function. It has also been shown that these effects can be reversed by treatments that decrease 5-HT availability16,13,18,7. In adult rats, BOLD signal changes following acute SSRI administration have been described in several 5-HT related brain regions, i.e. cortical areas, hippocampus, hypothalamus and thalamus9,16,15. Stimulation of the 5-HT system and its response to this challenge can be thus used as a measure of its function in both animals and humans2,11.

The goal of this technique is to assess serotonin (5-HT) neurotransmitter function in the live and free-breathing animal with pharmacological magnetic resonance imaging (phMRI) and an intravenous challenge with a selective serotonin reuptake inhibitor (SSRI), fluoxetine.

挑战的药理功能磁共振成像:在临床前研究使用的5  - 羟色胺系统中的应用

Pharmacological MRI (phMRI) is a new and promising method to study the effects of substances on brain function that can ultimately be used to unravel ...

Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases

Diffusion tensor imaging (DTI) techniques provide information on the microstructural processes of the cerebral white matter (WM) in vivo. The present applications are designed to investigate differences of WM involvement patterns in different brain diseases, especially neurodegenerative disorders, by use of different DTI analyses in comparison with matched controls. 	
DTI data analysis is performed in a variate fashion, i.e. voxelwise comparison of regional diffusion direction-based metrics such as fractional anisotropy (FA), together with fiber tracking (FT) accompanied by tractwise fractional anisotropy statistics (TFAS) at the group level in order to identify differences in FA along WM structures, aiming at the definition of regional patterns of WM alterations at the group level. Transformation into a stereotaxic standard space is a prerequisite for group studies and requires thorough data processing to preserve directional inter-dependencies. The present applications show optimized technical approaches for this preservation of quantitative and directional information during spatial normalization in data analyses at the group level. On this basis, FT techniques can be applied to group averaged data in order to quantify metrics information as defined by FT. Additionally, application of DTI methods, i.e. differences in FA-maps after stereotaxic alignment, in a longitudinal analysis at an individual subject basis reveal information about the progression of neurological disorders. Further quality improvement of DTI based results can be obtained during preprocessing by application of a controlled elimination of gradient directions with high noise levels.	
In summary, DTI is used to define a distinct WM pathoanatomy of different brain diseases by the combination of whole brain-based and tract-based DTI analysis.

Diffusion tensor imaging (DTI) basically serves as an MRI-based tool to identify in vivo the microstructure of the brain and pathological processes due to neurological disorders within the cerebral white matter. DTI-based analyses allow for application to brain diseases both at the group level and in single subject data.

磁共振扩散张量成像在神经退行性疾病的分析

Diffusion tensor imaging (DTI) techniques provide information on the microstructural processes of the cerebral white matter (WM) in vivo. The present ...

MRI and PET in Mouse Models of Myocardial Infarction

Myocardial infarction is one of the leading causes of death in the Western world. The similarity of the mouse heart to the human heart has made it an ideal model for testing novel therapeutic strategies.
In vivo magnetic resonance imaging (MRI) gives excellent views of the heart noninvasively with clear anatomical detail, which can be used for accurate functional assessment. Contrast agents can provide basic measures of tissue viability but these are nonspecific. Positron emission tomography (PET) is a complementary technique that is highly specific for molecular imaging, but lacks the anatomical detail of MRI. Used together, these techniques offer a sensitive, specific and quantitative tool for the assessment of the heart in disease and recovery following treatment.
In this paper we explain how these methods are carried out in mouse models of acute myocardial infarction. The procedures described here were designed for the assessment of putative protective drug treatments. We used MRI to measure systolic function and infarct size with late gadolinium enhancement, and PET with fluorodeoxyglucose (FDG) to assess metabolic function in the infarcted region. The paper focuses on practical aspects such as slice planning, accurate gating, drug delivery, segmentation of images, and multimodal coregistration. The methods presented here achieve good repeatability and accuracy maintaining a high throughput.

We describe how to perform MRI and PET imaging of the mouse heart. The protocol is tailored to assess treatment efficacy in models of myocardial infarction and heart failure.

MRI和PET心肌梗死小鼠模型

Myocardial infarction is one of the leading causes of death in the Western world. The similarity of the mouse heart to the human heart has made it an ...

In Vivo Optical Imaging of Brain Tumors and Arthritis Using Fluorescent SapC-DOPS Nanovesicles

We describe a multi-angle rotational optical imaging (MAROI) system for in vivo monitoring of physiopathological processes labeled with a fluorescent marker. Mouse models (brain tumor and arthritis) were used to evaluate the usefulness of this method. Saposin C (SapC)-dioleoylphosphatidylserine (DOPS) nanovesicles tagged with CellVue Maroon (CVM) fluorophore were administered intravenously. Animals were then placed in the rotational holder (MARS) of the in vivo imaging system. Images were acquired in 10&#176; steps over 380&#176;. A rectangular&#160;region of interest (ROI) was placed across the full image width at the model disease site. Within the ROI, and for every image, mean fluorescence intensity was computed after background subtraction. In the mouse models studied, the labeled nanovesicles were taken up in both the orthotopic and transgenic brain tumors, and in the arthritic sites (toes and ankles). Curve analysis of the multi angle image ROIs determined the angle with the highest signal. Thus, the optimal angle for imaging each disease site was characterized. The MAROI method applied to imaging of fluorescent compounds is a noninvasive, economical, and precise tool for in vivo quantitative analysis of the disease states in the described mouse models.

In Vivo Optical Imaging of Brain Tumors and Arthritis Using Fluorescent SapC-DOPS Nanovesicles

We describe a multi-angle rotational optical imaging (MAROI) system for in vivo quantitation of a fluorescent marker delivered by saposin C (SapC)-dioleoylphosphatidylserine (DOPS) nanovesicles. Employing mouse models of cancer and arthritis, we demonstrate how the MAROI signal curve analysis can be used for the precise mapping and biological characterization of disease processes.

在脑肿瘤和关节炎的用荧光SAPC-DOPS纳米囊泡体光学成像

We describe a multi-angle rotational optical imaging (MAROI) system for in vivo monitoring of physiopathological processes labeled with a fluorescent ...

Tracking the Mammary Architectural Features and Detecting Breast Cancer with Magnetic Resonance Diffusion Tensor Imaging

Breast cancer is the most common cause of cancer among women worldwide. Early detection of breast cancer has a critical role in improving the quality of life and survival of breast cancer patients. In this paper a new approach for the detection of breast cancer is described, based on tracking the mammary architectural elements using diffusion tensor imaging (DTI). 
The paper focuses on the scanning protocols and image processing algorithms and software that were designed to fit the diffusion properties of the mammary fibroglandular tissue and its changes during malignant transformation. The final output yields pixel by pixel vector maps that track the architecture of the entire mammary ductal glandular trees and parametric maps of the diffusion tensor coefficients and anisotropy indices. 
The efficiency of the method to detect breast cancer was tested by scanning women volunteers including 68 patients with breast cancer confirmed by histopathology findings. Regions with cancer cells exhibited a marked reduction in the diffusion coefficients and in the maximal anisotropy index as compared to the normal breast tissue, providing an intrinsic contrast for delineating the boundaries of malignant growth. Overall, the sensitivity of the DTI parameters to detect breast cancer was found to be high, particularly in dense breasts, and comparable to the current standard breast MRI method that requires injection of a contrast agent. Thus, this method offers a completely non-invasive, safe and sensitive tool for breast cancer detection.

We describe how to obtain parametric and vector maps of the diffusion tensor of the breast using magnetic resonance imaging. The protocol and final output following imaging processing are tailored for tracking breast architectural features and detecting breast malignancy.

跟踪乳腺建筑特色与检测乳腺癌的磁共振扩散张量成像

Breast cancer is the most common cause of cancer among women worldwide. Early detection of breast cancer has a critical role in improving the quality of ...

Using Saccadometry with Deep Brain Stimulation to Study Normal and Pathological Brain Function

The oculomotor system involves a large number of brain areas including parts of the basal ganglia, and various neurodegenerative diseases including Parkinson's and Huntington's can disrupt it. People with Parkinson's disease, for example, tend to have increased saccadic latencies. Consequently, the quantitative measurement of saccadic eye movements has received considerable attention as a potential biomarker for neurodegenerative conditions. A lot more can be learned about the brain in both health and disease by observing what happens to eye movements when the function of specific brain areas is perturbed. Deep brain stimulation is a surgical intervention used for the management of a range of neurological conditions including Parkinson's disease, in which stimulating electrodes are placed in specific brain areas including several sites in the basal ganglia. Eye movement measurements can then be made with the stimulator systems both off and on and the results compared. With suitable experimental design, this approach can be used to study the pathophysiology of the disease being treated, the mechanism by which DBS exerts it beneficial effects, and even aspects of normal neurophysiology.

This paper describes the use of quantitative measurement of eye movements in conjunction with stimulation of focal areas of the deep brain in order to study physiology, pathophysiology, and the mechanisms of deep brain stimulation.

使用Saccadometry与深部脑刺激来研究正常和病理脑功能

The oculomotor system involves a large number of brain areas including parts of the basal ganglia, and various neurodegenerative diseases including ...