Name: measuring connectivity in the primary visual pathway in human albinism using diffusion tensor imaging and tractography
Uploaded: 2016-08-11T13:00:00.000+00:00
Duration: 13 min 26 s
Description: Watch this Scientific Journal Video about Measuring Connectivity in the Primary Visual Pathway in Human Albinism Using Diffusion Tensor Imaging and Tractography at JoVE.com

这项工作是由加拿大自然科学和工程研究理事会（NSERC）的部分支持。作者感谢与会者，里克·汤普森博士，他在招募白化病的患者提供援助，丹尼斯Romanovsky运行一些分析和修改的身影他的帮助，莫妮卡希拉尔奇卡她与示踪她的帮助的知识和建议，乔伊·威廉姆斯在MRI采集和阿曼戈亚尔他的MRI分析的专业知识。

<html>伦理声明:目前的研究研究已获得约克大学，多伦多人参加审查委员会（HPRC）。所有参加了知情同意书。 1.除准备注:11学员OCA，年龄36±4岁（女6）进行比较十个年龄匹配的对照，年龄32±4年（6女）。参与者历史被记录在表1中 。 <ol><li>要求每名参加者填写并签署一份同意书，列出MRI安全准则和成像协议。 </li><li>对于每一个参与者，为耳耳塞。位置参与者仰卧和头部先在磁铁，具有里程碑意义的眼睛上方的眉毛水平。安全参与者的头垫，以减少头部运动。使参加培训的病人警报挤压球。 </li></ol> 2.结构MRI参数e_content"&gt;注意:所有成像获取使用一个32通道头线圈的3T核磁共振成像扫描仪在每个主题一个会话: <ol><li>使用覆盖整个大脑具有以下参数的3D-MPRAGE序列获得高分辨率T1加权解剖:采集时间4分钟26秒，视256毫米字段，256矩阵，192片，用1毫米的切片厚度，以1.0mm的3，TR = 1900毫秒，TE（回波时间）= 2.52毫秒，900毫秒反转时间和9°，1平均翻转角度造成的各向同性体素的大小，并行成像（IPAT格拉巴，2加速因子） 。 </li><li>获得覆盖皮质一个DTI序列，继前连合/后连合（AC-PC）的线在横向取向片，使用下列参数:采集时间8分5秒，视192毫米字段，128矩阵，体素1.5 1.5mm的平面，连续的56个（无间隙）切片用2毫米的厚度，TR = 6900毫秒，TE = 86毫秒，64路线，100 b值0秒/毫米，平均1，并行成像（IPAT格拉巴）为3的加速因子2（0秒/毫米2的低b值参考图像）。 </li><li>获得30-40的PD-加权图像在冠状方向，平行于脑干，从脑桥至下丘的后部的前程度覆盖。 <ol><li>使用Turbo自旋回波（快速自旋回波）脉冲序列和以下参数:采集时间1分钟每次扫描29秒，视192毫米字段，256矩阵，30-40切片以1毫米的厚度，得到的体素尺寸0.75 0.75 1 立方毫米，TR = 3000毫秒，TE = 22毫秒，5涡轮因素，重新调整的120°翻转角，1平均值，并行成像（IPAT格拉巴）为2的加速因子。 注意:使用下列参数S12被扫描:视180毫米字段，512矩阵，30片，用1mm厚的切片，所得体素尺寸0.4×0.4×1.0 立方毫米。所有其他参数保持不变。 Acquisit离子时间2分47秒。 </li></ol></li><li>前处理所有扫描使用程​​序dcm2nii原始DICOM转换为NIfTI格式。 </li></ol> 3. LGN划定注意:LGN是一个小的皮质下结构位于深处的脑，因此，高分辨率的PD图像被需要，以确定其解剖边界。在这些扫描中，LGN显示为强度相对于周围的WM大片高信号的区域，促进其检测21。然后所识别的解剖LGN用作示踪种子区域。 <ol><li>虽然盲人组成员，手动跟踪左右LGN口罩三次，每次上插值到两倍的分辨率均PD图像和三维像素大小的一半（原来的256×256矩阵，0.75×0.75×1毫米3像素的大小）。 <ol><li>为了获得高分辨率图像PD使用免费提供的FLIRT功能和其他软件工具FMRIB的软件中加入库（FSL，http://www.fmrib.ox.ac.uk/fsl/）。上采样，如以前在其他地方22所描述串联，动作正确，平均PD图像每个参与者。 </li><li>装载高分辨率PD形象FSLView，然后单击工具选项卡上选择单选项（或按<img alt="图1" src="/files/ftp_upload/53759/53759symbol1.jpg" /> ），以放大图像。 </li><li>点击文件选项卡，选择创建模板选项，然后使用工具栏上的屏幕左上方追查LGN在每个片。如果需要的话，通过在工具栏沿着最小/最大拖动便于LGN检测改变图像的对比度。 </li></ol></li><li>合并的利益（投资回报）​​，这些地区到使用fslmerge命令中位掩码。 </li><li>结合所有评估者的平均面具到使用相同的命令单位掩码。 </li></ol> 4. V1分割<ol><li>在脑FreeSurfer23（V5.3.0）运行"侦察-all"命令S IN用于自动处理本地解剖空间（T1加权像）。 </li><li>在转换新创建的文件夹MRI（orig.mgz，brain.mgz，rawavg.mgz，T1.mgz），以NIfTI使用"mri_convert"适当的输出。 </li><li>使用在FSL GUI BET大脑提取必要时更正在FreeSurfer空间头骨剥离脑输出（brain.nii.gz）。选择使用BET2选项（默认）运行标准大脑提取。降低门槛，如果图像是缺失的脑组织，或无脑组织被捕获（默认的阈值0.5）增加。选择在高级选项输出脑提取的图像和输出二进制脑掩模图像（后者可用于手动校正）。 </li><li>转换输出V1到地块划分用"label2surf"和"surf2volume"命令体积面具。 </li></ol> 5.预注册的跟踪注意:在接下来的步骤中，调用FSL GUI打开每个跟随着的摹工具。 <ol><li>使用BET大脑提取和选择偏场和颈部的清理选项头骨条rawavg.nii.gz，位于由"侦察所有"创建的文件夹MRI。调整阈值作为必要的。 </li><li>运行FLIRT线性登记，使大脑在FreeSurfer和本地解剖空间扩散的空间。 <ol><li>选择brain.nii.gz的侦察-所有（FreeSurfer空间）输出，或提取的T1（天然解剖空间）作为输入图像的受试者的脑，和一个涡流校正和脑提取扩散加权图像（DWI）作为参考图片。然后单击"转到"。 注意:此步骤创建两个输出，注册到参考图像（.nii.gz）和转换矩阵（.MAT）输入大脑。除了注册，需要示踪后者的文件时，种子空间不是扩散。在7.4.2上使用手机在这一步示踪创建的输出变换矩阵（.MAT）。 </li></ol></li><li>类似5.2，运行FLIRT线性登记带给参与者的PD大脑FreeSurfer空间和本地解剖空间。 </li><li>准备种子口罩示踪: <ol><li>从utils的在调情线性登记工具箱应用FLIRT转型。使用.MAT输出作为变换矩阵，原LGN掩模作为输入和brain.nii.gz（FreeSurfer空间）或T1_brain.nii.gz（天然解剖空间）（见5.2）作为基准容积。选择高级选项的近邻插值方法。 </li></ol></li><li>仅使用brain.nii.gz文件，准备示踪目标罩: <ol><li>注册FreeSurfer大脑解剖本土的空间和应用转型V1口罩创建目标罩（见5.2，5.4.1），使用三线性插值。点击"GO"。 </li></ol></li></ol> 6. LGN规范化<ol><li>使用如先前在http描述FNIRT非线性登记://fsl.fmrib.ox.ac.uk / FSL / fslwiki / FNIRT带给参与者的非大脑中提取原生解剖空间MNI空间，利用蒙特利尔神经学研究所的全脑模板（MNI152）。 注意:被推荐用于此步骤原始解剖图像的非线性登记，因为当FNIRT施加到非萃取个T1相比调情上提取大脑登记更准确。 </li><li>应用转型到解剖空间LGN口罩使用近邻插值5.4.1描述把口罩MNI空间（原LGN以前转化为本地解剖空间5.4）。 </li><li>平均LGN所有口罩跨两组MNI空间使用AFNI的"3dMean"命令。 </li><li>用"fslmaths -Thr"到阈值应用到MNI空间平均掩模。 </li><li>计算在用V MNI空间平均掩模的半径= 4/3πR3（假设球体）。 </li><li>记录质量coordi中心使用命令在本地解剖空间每个LGN面具纳茨"fslstats -C"。 </li><li>创建跨参与者相同体积的球的ROI: <ol><li>使用"fslmaths"创建与本地解剖空间适当的个人LGN面具的坐标的ROI点记录在6.6 </li><li>使用"fslmaths"，适用于MNI空间平均掩模的半径，以创建围绕在天然解剖空间在ROI点的球体。 </li></ol></li><li>使用这些标准化的面具作为种子跟踪技术。 </li></ol> 7.概率束成像（FSL 5.0.4） 注意:在接下来的步骤中，调用Fdt_gui访问每个以下工具。 <ol><li>纠正与涡流校正DWIs扭曲。在扩散工具箱窗口顶部从菜单中选择涡流校正选项，并上传DWI作为输入，留下defaulT参考量（0）。 </li><li>大脑在4.3​​描述的BET提取图像。 </li><li>从菜单中选择的DTIFIT重建扩散张量选项。指定包含以下文件的输入目录:弥散加权数据，nodif_brain_mask（BET的输出），bvec和BVAL（一定要重命名为bvecs和bvals;约含扩散图像采集参数，DICOM的输出扩散NIfTI转换信息的文本文件数据）。点击"开始"运行dtifit，这符合扩散张量模型的每个像素，开创了后处理文件。 </li><li>接下来，选择BedpostX（扩散参数估计），从菜单中选择。使用相同的输入目录作为DTIFIT。点击"开始"，生成的跟踪技术所需的所有文件。 </li><li>从相同的菜单中，选择ProbtrackX的概率跟踪并单独运行每个半球。保持默认的基本选项（000个样本，0.2曲率和loopcheck applied）和选择修改欧拉计算从提高准确度的高级选项的概率流线。 <ol><li>选择BedpostX含有.merged文件作为BEDPOSTX目录的输出。 </li><li>选择单一的面具作为种子的空间和装载转化LGN面具（原生解剖空间）作为种子形象，T1（在本地解剖空间大脑）扩散变换矩阵作为种子扩散转换和V1（原生解剖空间）在"可选指标"（所有，但排除口罩）作为目标。 </li><li>使用默认的网格约定（尖）和原生解剖空间（T1图像）作为表面参考图像加载大脑。 </li></ol></li><li>使用标准的球形的ROI（在第6步创建）作为示踪种子区域如7.5.2所述重复ProbtrackX的概率跟踪。在转化LGN（解剖空间）以同样的方式上传的ROI在7.5.2上载。 </li><li>重新运行示踪（7.5），此时种子（非标准化）和目标口罩与另外FreeSurfer的对侧白质边界掩码排除面具FreeSurfer空间，在避免任何交叉，确保直接连接同侧。检查从ProbtrackX工具箱表面选项并选择FreeSurfer网状约定。 注意:重​​要的是要强调的是，束成像总是从扩散空间运行，但Probtrackx用于概率跟踪允许种子和目标掩模的输入在不同的空间，用变换矩阵到扩散空间沿。在这项研究中，概率示踪用两种天然解剖和FreeSurfer空间（ 图2）口罩运行。 </li></ol> 8.确定性束成像（DSI工作室） <ol><li>开源图片:打开艾迪单击步骤1中得到纠正DSI工作室24弥散加权图像。负载bvec和BVAL文件到自动为B表格窗口OPE斯内德创建源（.SRC）文件。 </li><li>加载生成的源文件到重建窗口修改默认重建大脑口罩是必要的。 </li><li>然后，选择DTI作为重建方法25和源文件运行它生产纤维信息文件（.fib）。 </li><li>使用带线性FLIRT报名参加"PD大脑扩散的空间。 </li><li>申请转变为使用最邻近插值5.4.1描述LGN口罩。 </li><li>在程序的跟踪窗口中打开.fib文件。 </li><li>请针对每个半球跟踪分别在扩散空间距离可以从DSI工作室布罗德曼图谱作为终结区种子和地区17（V1）使用LGN。通过点击标签区域开放区域加载LGN面具。选择类型下的地区清单上屏幕左侧的种子选项。要加载从地图集V1面具，点击阿特拉斯从工具栏中的地区列表和选择适当的地图集。 </li><li>在每次运行中，将对侧WM（名为左/右脑 - 白质）从FreeSurfer分割图谱（见跟踪窗口区域列表框）为避免（ROA）的区域的面具。 </li><li>重复跟踪（8.7-8.8），使用球形的投资回报扩散空间，而不是个人的LGN作为种子区域的跟踪技术。 注意:球形的感兴趣区具有在所有受试者的相同的体积和每个LGN的质心为中心。 </li><li>重复LGN正常化，第6节，只是这一次登记扩散空间，以标准的MNI空间的大脑，并在扩散空间应用转换到LGN（原LGN以前转化为8.4-8.5中的扩散空间），使口罩标准MNI空间。计算投资回报率球形横​​跨科目MNI空间的所有LGN的平均体积的体积。 注:跟踪参数可以由用户进行修改。对于大多数运行，被应用默认跟踪参数。对于一些人（A5，A7，S12），各向异性阈值（默认值0.14-0.15）降低（0.10-0.12）和角度阈值（默认为60）增加（65-85），用于更好的可视化。该技术的示意图示于图3。 </li></ol> 9.统计分析 - TBSS（FSL） 注:基于道空间统计是参与者的FA的voxelwise统计分析dtifit26 maps16获得。它被广泛用于上扩散数据的统计信息。这voxelwise方法克服了VBM风格的FA分析看出潜在的对齐和平滑问题，并提供全脑调查，高不可攀通过基于示踪-approaches16。 <ol><li>运行"tbss_1_preproc"在位于新创建的目录TBSS英足总的数据。 </li><li>运行"tbss_2_reg" - T的应用非线性登记，使每个参与者的FA数据转换成公共空间（FMRIB58_FA，在TBSS目标图像）。 </li><li>创建一个平均FA骨架与所有普通大片的使用"tbss_3_postreg -S"参与者之间的中心。 </li><li>跑 "tbss_4_prestats 0.2"到每个参与者的一致FA图投射到所有排列FA图的平均骨架。 </li><li>创建design.con和design.mat文件，确保矩阵的顺序是与其中TBSS预加工在FA数据的顺序是一致的。 </li><li>运行"随机化"，利用T2选项，这建议用于TBSS，因为它作用于骨架（3D数据的一个缩小的子集），以及5000预突变，从而使更精确的p值。 </li></ol> 10.统计分析 - SPSS <ol><li>从确定的数据提取FA值 注:基于确定性-FA值从DSI工作室产量统计文本文件的。这些值表示所产生的束内的平均FA，WHICH在这种情况下，对应于或地区。 <ol><li>在DSI Studio中运行纤维跟踪。 </li><li>节省DSI Studio中创建的"统计信息"的文本文件的每个生成的一组大片，并从他们记录"FA意味着&#39;值。 </li></ol></li><li>从概率数据提取FA值 注意:概率基于-FA值从ProbtrackX2输出fdt_paths文件而得。这些是在本研究中包括对应于或面积3D道密度的图像。 <ol><li>使用FLIRT线性登记，使每个参与者的fdt_paths文件扩散的空间。 </li><li>二值化利用"fslmaths - 宾"输出口罩。 </li><li>对于每一个参与者，由dtifit使用"fslmaths -mul"他们的FA图乘以面具。 </li><li>运行"fslmeants"命令从各道面具发现平均FA。 </li></ol></li><li>跑步用SPSS（使用确定性和概率分析 数据） ñOTE:采用SPSS 20 for Mac是进行统计分析。因为半球是受试者内可变，与大脑中的每一侧的效果可以在分别被看作一个广义线性模型（根林），被应用。具体地，广义估计方程（GEE）被使用。 <ol><li>在单独测试中，设置每个均值足总杯和简化计数（waytotal或百分比生成的流线，PGSL）作为因变量。 注:在本研究中，简化计数是基于这样计值。 Waytotal描述尚未被拒绝通过纳入/排除标准27产生流线的总数。产生的流线（NGSL）的数量，这是指发送流线的总数，等于在种子掩膜乘以从每个体素（5000在这种情况下）得出的样本数量的体素的数目。百分比产生流线（PGSL），waytotal通过NGSL次100分，成功连接到的措施种子和目标之间ctivity。 </li><li>将其设定在所有测试中作为独立变量研究组和性别对LGN与V1连接的影响。 注:主要效果以及二，三路的相互作用进行了研究。要注意，这些个别测试不习惯于彼此是很重要的，因此，其中一个主要作用或相互作用的意义是彼此独立的。 </li><li>使用年龄作为所有测试协变量。此外，使用的LGN体积作为与平均FA测试和waytotal作为应变量协变量，而是从与PGSL作为因变量测试省略。 注意:总脑体积被认为是微不足道的协变量，因此，从统计被删去。 </li><li>选择Bonferroni校正方法来调整多重比较图28（显着差异p &lt;0.05的水平）。 </li></ol></li></ol>

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The authors declare no conflict of interest.

改变WM和，更具体地，与对照组相比，预计在白化病的连通减小。因此，在白化病的右半球减小的FA与对照相比，以及在男性患者白化病这里报告的减少连接在与我们的预测一致。性别与半球效果并不完全清楚，虽然健康的大脑研究表明男性的左半球女性相比下降WM复杂30-31可以解释一些在这项研究中观察到的性别和半球相关的差异。雄性白化病减少连接相比雌性白化病可能部分是由于在这...

白化病是一种遗传性疾病，主要特点是在受影响的个人观察到明显的色素减退。它是由遗传突变引起向参与黑色素的合成1的基因。白化病出现在两种主要形式:眼 - 皮肤白化病（OCA），为常染色体隐性性状都呈现眼部和皮肤的功能;和眼白化病（OA），X连锁的性状在男性更普遍，由眼部症状2特征主要。黑色素在视网膜色素上皮细胞（RPE）是中央视觉通路的适当发展是至关重要的。因此，其在没有白化病导致视力障碍，包括怕光，眼球震颤，视力下降及双眼视2-3损失。视力已链接到中心凹的形态，这是在白化病4改变。在人类中，十字交叉的视网膜线沿在于通过凹的nasotemporal边框，从鼻侧视网膜的纤维穿越到另一个半球和从颞侧视网膜同侧延伸。减少视觉功能在白化病的程度已被链接到色素减退的水平。具体地说，色素沉着成反比移位成十字交叉5的线的颞视网膜。如线十字交叉成颞视网膜的移位的结果，视神经纤维的交叉增大-一个共同特点在所有物种3。 对人类的结构的MRI研究已经表明在白化病较窄视神经chiasms与对照组相比，这很可能增加在白化病6-8观察视网膜神经节细胞的交叉的结果。视网膜和视交叉表达轴突指导线索如Eph家族受体和它们的配体9，因此对于错打10个候选点。 与诱发青光眼猴子的一项研究揭示了显著月rease在LGN小清蛋白免疫阳性中继神经元和LGN卷11的数量。这表明LGN大小和脑白质（WM）的轨迹通过或行驶到V1的数量之间的相关性。人类白化病验尸研究还揭示与融合M和P层12小LGN。高分辨率的结构MRI证实在白化病8 LGN量显著减少。两者合计，这些研究结果表明，降低LGN体积可以导致在LGN神经元数量的减少，并依次在LGN和V1之间减少连接。 在人类解剖连通的检查模式已被限制。夹层，示踪剂注入和病变感应是只能用验尸，并通常涉及一个非常小数量的患者侵入性技术。使用碳菁染料的DiI注射以往的研究表明V1和V2（次要的Visual C之间的神经连接ortex）13，以及内醛固定验尸人类大脑14海马复杂。以这种方式标记的纤维被限制为只有几十从注射14的点毫米的距离。弥散张量成像，DTI，是20世纪90年代初，中期开发，以确定纤维束的方向和组织核磁共振检查方式。它是一种非侵入性的方法，允许在活脑大WM通路映射。 DTI是水分子的生物组织15中的扩散敏感。在大脑中，水的扩散是各向异性（不均匀的），由于例如膜和髓鞘的障碍。 WM具有高的扩散各向异性，这意味着扩散大于平行于比垂直于纤维16的方向。 分数各向异性（FA）是描述分子的偏好在各向异性地扩散一个标量。 FA值的范围从0-1，由低到高anisot粘稠（脑脊髓液（CSF）&lt;灰质（GM）的&lt;WM）16。 简化（确定性）和概率纤维跟踪是三维重构路径两种不同的算法。确定性示踪使用线传播的方法，在一个限定的种子区域连接相邻体素。在这种算法中使用两个停止标准是转弯角度和F​​A值。因此，道相邻像素之间的跟踪是不可能在大转弯角度。该算法将因此也前进仅当在FA中的体素超过特定阈值时，限制在邻近灰质，其中各向异性滴准确限定通路的有效性。概率示踪，另一方面，产生描述的体素的概率连接映射到感兴趣（投资回报）的两个区域之间的管道的一部分，因此前进到灰质如V1 17。使用这个应用MRI，重点WM结构像或可被划定，如图以往的研究18-20。 因此，本研究采用扩散数据和跟踪技术，探索性轴索误传对眼膜 - geniculo皮质的连接效果。基于在LGN卷先前报道的降低在人类白化病8，我们预测从LGN纤维凸起为V1也减少（ 图1）。

<table><tbody><tr><td>Magnetom Tim Trio 3T MRI</td><td>Siemens (Erlangen, Germany)</td><td></td><td></td></tr><tr><td>FMRIB&amp;rsquo;s Software Library (FSL)</td><td></td><td></td><td>http://www.fmrib.ox.ac.uk/fsl/</td></tr><tr><td>FreeSurfer</td><td></td><td></td><td>http://surfer.nmr.mgh.harvard.edu</td></tr><tr><td>DSI Studio</td><td></td><td></td><td>http://dsi-studio.labsolver.org</td></tr><tr><td>SPSS</td><td></td><td></td><td></td></tr></tbody></table>

measuring connectivity in the primary visual pathway in human albinism using diffusion tensor imaging and tractography

在白化病，同侧突出视网膜神经节细胞（RGC）的数目显著减少。视网膜和视交叉已被提议作为候选场址为错打。因为外侧膝状体（LGN）的数量之间的相关性中继神经元和LGN尺寸已经示出，并且基于在人类白化病LGN卷先前报道的减少，我们建议从LGN纤维凸出到初级视觉皮层（V1）也减少。研究在白化病的视觉系统的结构差异可以提高错误路由和随后的临床应用的机制的理解。扩散的数据和跟踪技术是用于映射或（视辐射）是有用的。这份手稿介绍两种算法或重建，以便在白化病和controls.An MRI扫描仪具有32通道头线圈用于获取结构性扫描大脑比较连通。用1mm的T1加权3D-MPRAGE序列3各向同性体素尺寸是用来产生为V1分割高分辨率图像。多质子密度（PD）加权图像冠收购了左，右LGN定位。弥散张量成像（DTI）扫描，以64扩散方向收购。无论确定性和概率跟踪方法已经运行和相比，具有LGN作为籽面膜和V1作为目标罩。虽然DTI提供空间分辨率相对较差，和OR的精确划定可能是具有挑战性的，由于其纤维密度低，束成像已被证明是有利的无论是在研究和临床。根据道空间统计（TBSS）比对照组患者的白化病透露或在显著降低白质完整性方面。两两比较揭示LGN到V1连接在一个白化病减少显著与对照组相比。比较两个跟踪算法透露常见的结果，加强可靠性的技术。

本节中提供了使用示踪，确定性和概率的两个不同的算法得到的结果的总结。在PD空间LGN卷，其中掩模最初拉伸，以及在该研究中使用的所有其它空间，记录在表2中 ，并LGN跟踪在图 4中示出。这里报告的结果是基于所使用的标准球作为LGN ROI运行。标准LGN量是左，右半球461毫米3在解剖空间（概率运行）两个半球，和292.5毫米<sup...

Watch this Scientific Journal Video about Measuring Connectivity in the Primary Visual Pathway in Human Albinism Using Diffusion Tensor Imaging and Tractography at JoVE.com

Measuring Connectivity in the Primary Visual Pathway in Human Albinism Using Diffusion Tensor Imaging and Tractography

这份手稿描述了白质（WM）重建，用于检查白化病和对照组之间视辐射（OR）连接差异确定性和概率算法。虽然概率示踪如下神经纤维的真实过程更加紧密的，确定性的示踪已运行以比较两种技术的可靠性和可重复性。

在人类白化病的初级视途径弥散张量成像和测量束成像连通

In albinism, the number of ipsilaterally projecting retinal ganglion cells (RGCs) is significantly reduced. The retina and optic chiasm have been proposed ...

measuring-connectivity-primary-visual-pathway-human-albinism-using

Research

JoVE Journal

Neuroscience

12.2K 次观看.  York University. 这份手稿描述了白质（WM）重建，用于检查白化病和对照组之间视辐射（OR）连接差异确定性和概率算法。虽然概率示踪如下神经纤维的真实过程更加紧密的，确定性的示踪已运行以比较两种技术的可靠性和可重复性。 

视频: Measuring Connectivity in the Primary Visual Pathway in Human Albinism Using Diffusion Tensor Imaging and Tractography

Probing the Brain in Autism Using fMRI and Diffusion Tensor Imaging

Newly emerging theories suggest that the brain does not function as a cohesive unit in autism, and this discordance is reflected in the behavioral symptoms displayed by individuals with autism. While structural neuroimaging findings have provided some insights into brain abnormalities in autism, the consistency of such findings is questionable. Functional neuroimaging, on the other hand, has been more fruitful in this regard because autism is a disorder of dynamic processing and allows examination of communication between cortical networks, which appears to be where the underlying problem occurs in autism. Functional connectivity is defined as the temporal correlation of spatially separate neurological events1. Findings from a number of recent fMRI studies have supported the idea that there is weaker coordination between different parts of the brain that should be working together to accomplish complex social or language problems2,3,4,5,6. One of the mysteries of autism is the coexistence of deficits in several domains along with relatively intact, sometimes enhanced, abilities. Such complex manifestation of autism calls for a global and comprehensive examination of the disorder at the neural level. A compelling recent account of the brain functioning in autism, the cortical underconnectivity theory,2,7 provides an integrating framework for the neurobiological bases of autism. The cortical underconnectivity theory of autism suggests that any language, social, or psychological function that is dependent on the integration of multiple brain regions is susceptible to disruption as the processing demand increases. In autism, the underfunctioning of integrative circuitry in the brain may cause widespread underconnectivity. In other words, people with autism may interpret information in a piecemeal fashion at the expense of the whole. Since cortical underconnectivity among brain regions, especially the frontal cortex and more posterior areas 3,6, has now been relatively well established, we can begin to further understand brain connectivity as a critical component of autism symptomatology.
A logical next step in this direction is to examine the anatomical connections that may mediate the functional connections mentioned above. Diffusion Tensor Imaging (DTI) is a relatively novel neuroimaging technique that helps probe the diffusion of water in the brain to infer the integrity of white matter fibers. In this technique, water diffusion in the brain is examined in several directions using diffusion gradients. While functional connectivity provides information about the synchronization of brain activation across different brain areas during a task or during rest, DTI helps in understanding the underlying axonal organization which may facilitate the cross-talk among brain areas. This paper will describe these techniques as valuable tools in understanding the brain in autism and the challenges involved in this line of research.

Neuroimaging techniques, such as functional MRI and Diffusion Tensor Imaging have become increasingly useful in characterizing the cognitive and neural deficits in autism. An examination of brain connectivity in autism at a network level along with adaptations for scanning children with developmental disabilities is presented.

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 ...

科研

医学

Time-lapse Live Imaging of Clonally Related Neural Progenitor Cells in the Developing Zebrafish Forebrain

Precise patterns of division, migration and differentiation of neural progenitor cells are crucial for proper brain development and function1,2. To understand the behavior of neural progenitor cells in the complex in vivo environment, time-lapse live imaging of neural progenitor cells in an intact brain is critically required. In this video, we exploit the unique features of zebrafish embryos to visualize the development of forebrain neural progenitor cells in vivo. We use electroporation to genetically and sparsely label individual neural progenitor cells. Briefly, DNA constructs coding for fluorescent markers were injected into the forebrain ventricle of 22 hours post fertilization (hpf) zebrafish embryos and electric pulses were delivered immediately. Six hours later, the electroporated zebrafish embryos were mounted with low melting point agarose in glass bottom culture dishes. Fluorescently labeled neural progenitor cells were then imaged for 36hours with fixed intervals under a confocal microscope using water dipping objective lens. The present method provides a way to gain insights into the in vivo development of forebrain neural progenitor cells and can be applied to other parts of the central nervous system of the zebrafish embryo.

The present video demonstrates a method which takes advantage of the combination of electroporation and confocal microscopy to perform live imaging on individual neural progenitor cells in the developing zebrafish forebrain. In vivo analysis of the development of forebrain neural progenitor cells at a clonal level can be achieved in this way.

在发展中国家斑马鱼的前脑的神经祖细胞克隆相关的定时实时成像

Precise patterns of division, migration and differentiation of neural progenitor cells are crucial for proper brain development and function1,2. To ...

神经科学

Co-analysis of Brain Structure and Function using fMRI and Diffusion-weighted Imaging

The study of complex computational systems is facilitated by network maps, such as circuit diagrams. Such mapping is particularly informative when studying the brain, as the functional role that a brain area fulfills may be largely defined by its connections to other brain areas. In this report, we describe a novel, non-invasive approach for relating brain structure and function using magnetic resonance imaging (MRI). This approach, a combination of structural imaging of long-range fiber connections and functional imaging data, is illustrated in two distinct cognitive domains, visual attention and face perception. Structural imaging is performed with diffusion-weighted imaging (DWI) and fiber tractography, which track the diffusion of water molecules along white-matter fiber tracts in the brain (Figure 1). By visualizing these fiber tracts, we are able to investigate the long-range connective architecture of the brain. The results compare favorably with one of the most widely-used techniques in DWI, diffusion tensor imaging (DTI). DTI is unable to resolve complex configurations of fiber tracts, limiting its utility for constructing detailed, anatomically-informed models of brain function. In contrast, our analyses reproduce known neuroanatomy with precision and accuracy. This advantage is partly due to data acquisition procedures: while many DTI protocols measure diffusion in a small number of directions (e.g., 6 or 12), we employ a diffusion spectrum imaging (DSI)1, 2 protocol which assesses diffusion in 257 directions and at a range of magnetic gradient strengths. Moreover, DSI data allow us to use more sophisticated methods for reconstructing acquired data. In two experiments (visual attention and face perception), tractography reveals that co-active areas of the human brain are anatomically connected, supporting extant hypotheses that they form functional networks. DWI allows us to create a "circuit diagram" and reproduce it on an individual-subject basis, for the purpose of monitoring task-relevant brain activity in networks of interest.

We describe a novel approach for simultaneous analysis of brain function and structure using magnetic resonance imaging (MRI). We assess brain structure with high-resolution diffusion-weighted imaging and white-matter fiber tractography. Unlike standard structural MRI, these techniques allow us to directly relate anatomical connectivity to functional properties of brain networks.

使用功能磁共振成像和弥散加权成像脑结构与功能分析

The study of complex computational systems is facilitated by network maps, such as circuit diagrams. Such mapping is particularly informative when ...

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 ...

DTI of the Visual Pathway - White Matter Tracts and Cerebral Lesions

DTI is a technique that identifies white matter tracts (WMT) non-invasively in healthy and non-healthy patients using diffusion measurements. Similar to visual pathways (VP), WMT are not visible with classical MRI or intra-operatively with microscope. DTI will help neurosurgeons to prevent destruction of the VP while removing lesions adjacent to this WMT. We have performed DTI on fifty patients before and after surgery between March 2012 to January 2014. To navigate we used a 3DT1-weighted sequence. Additionally, we performed a T2-weighted and DTI-sequences. The parameters used were, FOV: 200 x 200 mm, slice thickness: 2 mm, and acquisition matrix: 96 x 96 yielding nearly isotropic voxels of 2 x 2 x 2 mm. Axial MRI was carried out using a 32 gradient direction and one b0-image. We used Echo-Planar-Imaging (EPI) and ASSET parallel imaging with an acceleration factor of 2 and b-value of 800 s/mm&#178;. The scanning time was less than 9 min.
The DTI-data obtained were processed using a FDA approved surgical navigation system program which uses a straightforward fiber-tracking approach known as fiber assignment by continuous tracking (FACT). This is based on the propagation of lines between regions of interest (ROI) which is defined by a physician. A maximum angle of 50, FA start value of 0.10 and ADC stop value of 0.20 mm&#178;/s were the parameters used for tractography.
There are some limitations to this technique. The limited acquisition time frame enforces trade-offs in the image quality. Another important point not to be neglected is the brain shift during surgery. As for the latter intra-operative MRI might be helpful. Furthermore the risk of false positive or false negative tracts needs to be taken into account which might compromise the final results.

Diffusion tensor imaging (DTI) was performed to try to depict the major parts of the visual pathway. The goal was to use an FDA approved standard commercial workstation which could be used for everyday routine in order to try to reduce postoperative damage of the visual pathway in the patients.

贸工部视觉通路的 - 白质及脑病变

DTI is a technique that identifies white matter tracts (WMT) non-invasively in healthy and non-healthy patients using diffusion measurements. Similar to ...

Diffusion Imaging in the Rat Cervical Spinal Cord

Magnetic resonance imaging (MRI) is the state of the art approach for assessing the status of the spinal cord noninvasively, and can be used as a diagnostic and prognostic tool in cases of disease or injury. Diffusion weighted imaging (DWI), is sensitive to the thermal motion of water molecules and allows for inferences of tissue microstructure. This report describes a protocol to acquire and analyze DWI of the rat cervical spinal cord on a small-bore animal system. It demonstrates an imaging setup for the live anesthetized animal and recommends a DWI acquisition protocol for high-quality imaging, which includes stabilization of the cord and control of respiratory motion. Measurements with diffusion weighting along different directions and magnitudes (b-values) are used. Finally, several mathematical models of the resulting signal are used to derive maps of the diffusion processes within the spinal cord tissue that provide insight into the normal cord and can be used to monitor injury or disease processes noninvasively.

The goal of this protocol is to obtain high-quality diffusion weighted magnetic resonance imaging (DWI) of the rat spinal cord for noninvasive characterization of tissue microstructure. This protocol describes optimizations of the MRI sequence, radiofrequency coil, and analysis methods to enable DWI images free from artifacts.

在大鼠颈脊髓弥散成像

Magnetic resonance imaging (MRI) is the state of the art approach for assessing the status of the spinal cord noninvasively, and can be used as a ...

Fiber Connections of the Supplementary Motor Area Revisited: Methodology of Fiber Dissection, DTI, and Three Dimensional Documentation

The purpose of this study is to show the methodology for the examination of the white matter connections of the supplementary motor area (SMA) complex (pre-SMA and SMA proper) using a combination of fiber dissection techniques on cadaveric specimens and magnetic resonance (MR) tractography. The protocol will also describe the procedure for a white matter dissection of a human brain, diffusion tensor tractography imaging, and three-dimensional documentation. The fiber dissections on human brains and the 3D documentation were performed at the University of Minnesota, Microsurgery and Neuroanatomy Laboratory, Department of Neurosurgery. Five postmortem human brain specimens and two whole heads were prepared in accordance with Klingler's method. Brain hemispheres were dissected step by step from lateral to medial and medial to lateral under an operating microscope, and 3D images were captured at every stage. All dissection results were supported by diffusion tensor imaging. Investigations on the connections in line with Meynert's fiber tract classification, including association fibers (short, superior longitudinal fasciculus I and frontal aslant tracts), projection fibers (corticospinal, claustrocortical, cingulum, and frontostriatal tracts), and commissural fibers (callosal fibers) were also conducted.

The purpose of this study is to show each step of the fiber dissection technique on human cadaveric brains, the 3D documentation of these dissections, and the diffusion tensor imaging of the anatomically dissected fiber pathways.

补充电机区的光纤连接重新审视:光纤解剖，DTI和三维文档的方法

The purpose of this study is to show the methodology for the examination of the white matter connections of the supplementary motor area (SMA) complex ...

Mapping Regional Homogeneity and Functional Connectivity of the Visual Cortex in Resting-State fMRI

A combined regional homogeneity (ReHo) and functional connectivity (FC) method, a type of noninvasive functional magnetic resonance imaging (fMRI) method, has been used to evaluate synchronous neuronal activity changes in retinitis pigmentosa (RP). The purpose of this study is to describe our method for analysis of intra- and interregional synchronizations of changes in neuronal activity in RP patients. The advantages of the combined ReHo and FC method are that it is both noninvasive and sufficiently sensitive to investigate changes in cerebral synchronous neuronal activity changes in vivo. Here, 16 RP patients and 14 healthy controls closely matched in age, sex, and education underwent resting-state fMRI scans. Two sample t-tests were conducted to compare ReHo and FC across groups. Our results showed that visual network disconnection and reorganization of the retino-thalamocortical pathway and dorsal visual stream occurred in the RP patients. Here, we describe the details of this method, its use, and the impact of its key parameters in a step-by-step manner.

We present a protocol for analyzing functional magnetic resonance imaging data to investigate spontaneous neural activity alterations in retinitis pigmentosa patient using a combined regional homogeneity and functional connectivity method.

A combined regional homogeneity (ReHo) and functional connectivity (FC) method, a type of noninvasive functional magnetic resonance imaging (fMRI) method, ...

Role of Diffusion MRI Tractography in Endoscopic Endonasal Skull Base Surgery

Endoscopic endonasal surgery has gained a prominent role in the management of complex skull base tumors. It allows the resection of a large group of benign and malignant lesions through a natural anatomical extra-cranial pathway, represented by the nasal cavities, avoiding brain retraction and neurovascular manipulation. This is reflected by the patients' prompt clinical recovery and the low risk of permanent neurological sequelae, representing the main caveat of conventional skull base surgery. This surgery must be tailored to each specific case, considering its features and relationship with surrounding neural structures, mostly based on preoperative neuroimaging. Advanced MRI techniques, such as tractography, have been rarely adopted in skull base surgery due to technical issues: lengthy and complicated processes to generate reliable reconstructions for inclusion in the neuronavigation system. 
This paper aims to present the protocol implemented in the institution and highlights the synergistic collaboration and teamwork between neurosurgeons and the neuroimaging team (neurologists, neuroradiologists, neuropsychologists, physicists, and bioengineers) with the final goal of selecting the optimal treatment for each patient, improving the surgical results and pursuing the advancement of personalized medicine in this field.

We present a protocol to integrate diffusion MRI tractography in patient work-up to endoscopic endonasal surgery for a skull base tumor. The methods for adopting these neuroimaging studies in the pre- and intra-operative phases are described.

扩散MRI造影术在内窥镜内窥镜颅骨基础外科中的作用

Endoscopic endonasal surgery has gained a prominent role in the management of complex skull base tumors. It allows the resection of a large group of ...

Using Diffusion Tensor Imaging in Traumatic Brain Injury

Source: Laboratories of Jonas T. Kaplan and Sarah I. Gimbel&#8212;University of Southern California
Traditional brain imaging techniques using MRI are very good at visualizing the gross structures of the brain. A structural brain image made with MRI provides high contrast of the borders between gray and white matter, and information about the size and shape of brain structures. However, these images do not detail the underlying structure and integrity of white matter networks in the brain, which consist of axon bundles that interconnect local and distant brain regions.
Diffusion MRI uses pulse sequences that are sensitive to the diffusion of water molecules. By measuring the direction of diffusion, it is possible to make inferences about the structure of white matter networks in the brain. Water molecules within an axon are constrained in their movements by the cell membrane; instead of randomly moving in every direction with equal probability (isotropic movement), they are more likely to move in certain directions, in parallel with the axon (anisotropic movement; Figure 1). Therefore, measures of diffusion anisotropy are thought to reflect properties of the white matter such as fiber density, axon thickness, and degree of myelination. One common measure is fractional anisotropy (FA). FA values range from 0, which represents completely isotropic movement, to 1, reflecting maximum anisotropy.
<img alt="Figure 1" src="/files/ftp_upload/10276/10276fig1.jpg" /> 
Figure 1: Diffusion anisotropy. When the direction of diffusion is unconstrained and random, movement is measured in all directions equally. This is isotropic diffusion (A). When water molecules are contained within the axon of a neuron, diffusion is anisotropic, tending to occur more frequently along the direction of the axon (B). <a href="http://www.jove.com/files/ftp_upload/10276/10276fig1large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
In this experiment we will use diffusion tensor imaging (DTI) to measure white matter integrity in traumatic brain injury (TBI). TBI occurs when an external force injures the brain, such as a blow to the head or a sudden movement like the kind that might occur in a car accident. This type of brain injury from mechanical forces is associated with diffuse axonal injury-damage to white matter throughout the brain. Because it is an injury affecting white matter integrity, standard neuroimaging techniques may not reveal the damage. However, measures of diffusion are especially sensitive to these anatomical changes. Following a study by Kraus et al.1, we compare a group of healthy controls to a group of people with TBI and use diffusion imaging to measure the effect of TBI on cerebral white matter. Furthermore, we will test the relationship between white matter integrity and cognitive function using an attention task.2 This study uses a region of interest (ROI) approach focusing on three white matter tracts: the splenium of the corpus callosum, the anterior corona radiata, and the superior longitudinal fasciculus (Figure 2).
<img alt="Figure 2" src="/files/ftp_upload/10276/10276fig2.jpg" /> 
Figure 2: Regions of interest. The three ROIs, defined from the ICBM DTI-81 atlas, are shown here in horizontal slices through the brain. In green is the splenium of the corpus callosum. The splenium is the most posterior part of the corpus callosum. In blue is the anterior corona radiata. The superior longitudinal fasciculus is shown in red. <a href="http://www.jove.com/files/ftp_upload/10276/10276fig2large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>

Diffusion Tensor Imaging in Traumatic Brain Injury

弥散张量成像在创伤性脑损伤

Source: Laboratories of Jonas T. Kaplan and Sarah I. Gimbel&#8212;University of Southern California
Traditional brain imaging techniques using MRI are ...