笔者想从CAMH基金会的认可支持，感谢迈克尔和宋佳柯纳的Kimel家庭，和保罗·加芬克尔新研究员催化剂奖。该项目资金由全宗德RECHERCHES桑特魁北克健康研究加拿大学院（CIHR），自然科学和加拿大，韦斯顿脑研究所，加拿大阿尔茨海默氏症协会工程研究理事会，和迈克尔J. Fox基金会帕金森病研究（MMC），以及CIHR，安大略省精神卫生基金会，NARSAD和心理健康国家研究所（R01MH099167）（ANV）。作者还要感谢Anusha Ravichandran寻求帮助获取图像。

研究参与者 （; 29-57岁，平均37。3楼，2M）谁是自由的神经和神经精神障碍和重度​​颅脑外伤的情况下在这个手稿的协议，从健康志愿者采集的五个有代表性的高清晰度图像的开发。所有受试者入组，在该中心的成瘾和精神健康（CAMH）。这项研究是由CAMH研究伦理委员会，并符合赫尔辛基宣言进行。提供书面所有受试者知情同意进行数据采集和共享。有关用于收集这些图像采集序列的详细信息，请参阅温特伯恩等人 ，2013年和公园等，2014年26,34图片全部五科进行了检查质量和保留。海马在这些图像平均118冠状切片跨越。 1.软件设置<ol><li> 打开显示： </str翁&gt;从终端​​使用以下命令：显示image_name.mnc -label label_name.mnc。该程序将打开窗户3：三维可视化窗口，3-取向图像观察窗，和一个导航窗口。该终端也将用于运行程序。放大的冠状面，因为分割将冠进行。放大的海马。在导航窗口中选择F（分段）。选择F（XY半径：0.1）。在终端窗口会提示用户“输入XY画笔大小”。设置为0.1。这将设置你的画笔的大小。用户现在可以开始了海马绘制到MR图像。 </li></ol> 2.整个海马手动分割<ol><li> 设置：使用T1加权像，滚动到海马的最前冠状切片。为了推进切片的前方向，用“+”键;用&#39; - &#39;键在后方向上移动。 </li><li><strong&gt;的切片答：最前片：用鼠标右键单击，画的海马灰质在那里遇到周围颞叶白质最外层的边界，并使用alveus的高强度的白质以协助上缘，其中所述海马满足杏仁核12,22。使用E（标签填充）键在导航窗口中的分段菜单，以填补在边境内侧的标签。继续在整个前海马头应用这些边界。 </li><li> 切片B：海马头1（图1B）： <ol><li>上，下，外侧，内侧边框：继续绘制边框如步骤2.2中所述，使用颞叶和alveus为指导的白质。 </li><li> Supero-内侧缘：对于这一点，使用轴向图，画一条水平线从横向海马29的前部边缘，包括下面这条线作为海马什么。注：supero-内侧缘成为这些片，其中海马的灰​​质融合与杏仁核的灰质比较模糊。 </li></ol></li><li> 切片C：海马头2齿状：根据不同的主题，海马齿状可能是3-4片可见（通常情况下，他们是在T2加权相对于T1加权像更明显）。在这些切片，继续使用alveus和颞叶白质，引导边界分割12,22。有关详细信息，按照步骤2.5.1-2.5.2。 </li><li> 片D：海马头3： <ol><li>上，下，外侧，内侧边框：绘制海马的下缘在颞叶，在侧脑室，上缘的下角外侧缘的白质，继齿状的曲线，在白质的alveus /伞，而内侧缘在低信号区域选择性n个环池12,22的。 </li><li> Supero-内侧和infero-内侧边界：继续定义supero，内侧缘如步骤2.3.2描述。绘制内侧缘所在的海马变薄略，并延伸到内嗅皮层12,22的轻度高信号灰质的下部。 </li></ol></li><li> 片E：海马头4钩回：继续绘制步骤2.5.1-2.5.2描述下，横向和优越的边界。包括钩回（位于游戏币向海马的主体，并且由低强度CSF包围）在海马分割12,2 2。 </li><li> 片F：海马体：继续绘制步骤2.5.1-2.5.2描述下，外侧，内侧，和优越的边界。绘制infero，内侧缘处，其中海马变薄，因为它转换到内嗅皮质/准海马回12,22点。不要在分割的残留海马沟的低强度CSF。 </li><li> 切片G：海马尾1：开始分割海马尾型切片时，穹窿的小腿是第一个可见。通过外推束状回的捏成从更前片12,22海马尾排除在分割的束状回（一灰质结构融合与海马尾部分海马）。此外推是唯一可能为2-3片，之后，两个结构不能准确分辨;在这一点上，对待这地区如海马所有可见灰质。 </li><li> 切片H：海马尾2：段从周边高强度的白质后的海马尾部的低强度的灰质。 </li><li> 切片我：最靠后的切片：段海马灰质从小其余区域周围白质的颞叶。 </li></ol> 3.海马子字段手动分割<ol><li> 设置：使用T2加权图像，滚动到海马的最前冠状切片（如在步骤2.1）。要改变画笔的颜色，选择D（设置在导航窗口中的分割菜单上涂料的Lbl :)。该命令终端将提示：“请输入当前绘制的标签：”。输入一个数字255 1至每个号对应于不同的标签的颜色。 </li><li> 切片答：最前片：由于子部门都在最前片还没有看到，画线分割沿其最长可见轴可见海马灰质（这不一定平行于任何基本轴）成两个相等的部分，以接近真实的解剖12,22。标签上级这两部分的CA1区和下部分为下脚由choosi纳克不同颜色的标签，每个子23,35。 </li><li> 切片B：海马负责人1：海马结构为SR / SL / SM 13,37的中间标签的低烈度区。当沿着海马的下部边缘的弯曲变得清晰，使用这一具有里程碑意义从CA1 12,22分离下托的外侧缘。继续按照海马的最长轴绘制CA1，下托边境上的supero-内侧尖37。 </li><li> 切片C：海马头2齿状： <ol><li> SR / SL / SM，CA4 / DG和下托：标签的SR / SL / SM，CA4 / DG和所描述的片D下脚（步骤3.5.1）。 </li><li> CA2 / CA3和CA1：定义CA1和CA2 / CA3之间的边界为从发SR / SL / SM 12,22的最supero -外侧边缘在supero -横向方向延伸的45度角线。内侧沿上边缘延伸CA2 / CA3到登塔之间的槽系统蒸发散12,22。标签上缘为CA1 12,22的其余部分。 </li></ol></li><li> 片D：海马头3 <ol><li> SR / SL / SM，CA4 / DG和下托：第一个标签黑暗SR / SL / SM频段，这将遵循CA1 37的曲线。标签的SR / SL / SM为CA4 / DG 12,22,23,35,37内部的任何高强度的灰质。这可能不是连续的区域，如图2C所示。继续使用弯曲的劣势海马12,22定义下托-CA1边界。 </li><li> CA2 / CA3和​​CA1：继续定义CA1和CA2 / CA3边界按步骤3.4.2。延长CA2 / CA3内侧中途沿着海马12,22的上边缘和标签上缘的另一半作为CA1 12,22。 </li><li> Supero-内侧的海马头：在这片，垂直划分supero-内侧的海马头的一半。标签内侧一半SR / SL / SM 12。除以横向一半一半，这一次水平。标签上级部分为CA4 / DG和下部分为CA2 / CA3 12。 </li></ol></li><li> 片E：海马头4钩回 <ol><li>外侧海马头（下托）：在这些片的侧部，定义下托-CA1边框，从最内侧缘CA4 / DG 12,22在上下方向延伸的垂直线。 </li><li>横向海马头（CA1，CA2 / CA3，CA4 / DG，SR / SL / SM）：定义以同样的方式在CA1-CA2 / CA3边界的步骤3.4.2。继续按照CA区域的曲线SR / SL / SM标注为低强度区域。标记CA4 / DG称为SR / SL / SM内的中心腔中，如在步骤3.5.1。 </li><li> UNCAL海马头（SR / SL / SM）：标签海马钩回约10片作为海马头部过渡到海马体。在钩回，标号低强度区的中心SR / SL / SM（若这是很难看，通过分割线2-3的体素宽向上的中心钩回的）12近似解剖学。 </li><li> UNCAL海马头（CA2 / CA3，CA4 / DG）：画线的SR / SL / SM沿钩回的infero侧向/ supero-中轴部分的上边缘。标签上面这条线CA2 / CA3 12所有灰质。标签下面这条线（在SR / SL / SM的两侧）为CA4 / DG 12任何未标记的灰质。 </li></ol></li><li> 片F：海马体：继续申请步骤3.6.1-3.6.2描述的边界。 </li><li> 切片G：海马尾1：继续申请步骤3.6.1-3.6.2描述的规则。下托-CA1边界成为从内侧缘CA4 / DG 12,22的infero-内侧方向延伸的45度角行。 </li><li> 片H：海马尾2：一旦束状回中不再能够从海马formatio区分N，标签的整个外层CA1区，此的SR / SL内的低强度区/ SM（如在以前的切片），和任何剩余的灰质在中间CA4 / DG 12,22。 </li><li> 切片我：最靠后的切片：一旦黑暗SR / SL / SM是海马结构的中心不再可见，标签，整个结构CA1 12,22。 </li></ol> 4，协议的可靠性<ol><li>从执行最初分割等待约一个月之后再分割或右侧每个受试者的左海马。段一直以来，海马的整个前后长度的子场，试图按照协议规定的一致是可能的。 </li><li>计算原始和resegmented卷之间的骰子的河童： <img alt="式（1）" src="/files/ftp_upload/51861/51861eq1.jpg" /> 其中k =骰子的κ和A和B的标签卷。 </li></ol>

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S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Volumetric+Analysis+of+Medial+Temporal+Lobe+Subregions+in+Development+Amnesia+using+High-Resolution+Magnetic+Resonance+Imaging.">Volumetric Analysis of Medial Temporal Lobe Subregions in Development Amnesia using High-Resolution Magnetic Resonance Imaging.</a> Hippocampus. 23 (10), 855-860 (2013).</li><li>Park, M. T. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Derivation+of+high-resolution+MRI+atlases+of+the+human+cerebellum+at+3T+and+segmentation+using+multiple+automatically+generated+templates.">Derivation of high-resolution MRI atlases of the human cerebellum at 3T and segmentation using multiple automatically generated templates.</a> NeuroImage. 95, 217-231 (2014).</li><li>Pipitone, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Multi-atlas+Segmentation+of+the+Whole+Hippocampus+and+Subfields+Using+Multiple+Automatically+Generated+Templates.">Multi-atlas Segmentation of the Whole Hippocampus and Subfields Using Multiple Automatically Generated Templates.</a> NeuroImage. 101, 494-512 (2014).</li><li>Pluta, J., Yushkevich, P., Das, S., Wolk, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In+vivo+analysis+of+hippocampal+subfield+atrophy+in+mild+cognitive+impairment+via+semi-automatic+segmentation+of+T2-weighted+MRI.Journal+of+Alzheimer's+Disease.">In vivo analysis of hippocampal subfield atrophy in mild cognitive impairment via semi-automatic segmentation of T2-weighted MRI.Journal of Alzheimer's Disease.</a> 31 (1), 85-99 (2012).</li><li>Pruessner, J. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Volumetry+of+hippocampus+and+amygdala+with+high-resolution+MRI+and+three-+dimensional+analysis+software:+minimizing+the+discrepancies+between+laboratories.">Volumetry of hippocampus and amygdala with high-resolution MRI and three- dimensional analysis software: minimizing the discrepancies between laboratories.</a> Cereb Cortex. 10 (4), 433-442 (2000).</li><li>Sabuncu, M. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+dynamics+of+cortical+and+hippocampal+atrophy+in+Alzheimer+disease.">The dynamics of cortical and hippocampal atrophy in Alzheimer disease.</a> Archives of Neurology. 68 (8), 1040-1048 (2011).</li><li>Scoville, W. B., Milner, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Loss+of+recent+memory+after+bilateral+hippocampal+lesions.">Loss of recent memory after bilateral hippocampal lesions.</a> J. Neuropsych. and Clin. Neurosci. 12 (1), 103-113 (1957).</li><li>Toga, A. W., Thompson, P. M., Mori, S., Amunts, K., Zilles, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Towards+multimodal+atlases+of+the+human+brain.">Towards multimodal atlases of the human brain.</a> Nat. Rev. Neurosci. 7 (12), 952-966 (2006).</li><li>van Leemput, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Automated+segmentation+of+hippocampal+subfields+from+ultra-high+resolution+in+vivo.">Automated segmentation of hippocampal subfields from ultra-high resolution in vivo.</a> MRI. Hippocampus. 19 (6), 549-557 (2009).</li><li>Winterburn, J. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+novel+in+vivo+atlas+of+human+hippocampal+subfields+using+high-resolution+3+T+magnetic+resonance+imaging.">A novel in vivo atlas of human hippocampal subfields using high-resolution 3 T magnetic resonance imaging.</a> NeuroImage. 74, 254-265 (2013).</li><li>Wisse, L. E. M., Gerritsen, L., Zwanenburg, J. J. M., Kuijf, H. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Subfields+of+the+hippocampal+formation+at+7+T+MRI:+in+vivo.+volumetric+assessment.">Subfields of the hippocampal formation at 7 T MRI: in vivo. volumetric assessment.</a> NeuroImage. 61 (4), 1043-1049 (2012).</li><li>Yelnik, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+three-dimensional,+histological+and+deformable+atlas+of+the+human+basal+ganglia.+I.+Atlas+construction+based+on+immunohistochemical+and+MRI+data.">A three-dimensional, histological and deformable atlas of the human basal ganglia. I. Atlas construction based on immunohistochemical and MRI data.</a> NeuroImage. 34 (2), 618-638 (2007).</li><li>Yushkevich, P. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+high-resolution+computational+atlas+of+the+human+hippocampus+from+postmortem+magnetic+resonance+imaging+at+9.4+T.">A high-resolution computational atlas of the human hippocampus from postmortem magnetic resonance imaging at 9.4 T.</a> NeuroImage. 44 (2), 385-398 (2009).</li><li>Yushkevich, P. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Quantitative+Comparison+of+21+Protocols+for+Labeling+Hippocampal+Subfields+and+Parahippocampal+Subregions+in+In+Vivo+MRI:+Towards+a+Harmonized+Segmentation+Protocol.">Quantitative Comparison of 21 Protocols for Labeling Hippocampal Subfields and Parahippocampal Subregions in In Vivo MRI: Towards a Harmonized Segmentation Protocol.</a> NeuroImage. , (2015).</li></ol>

The authors have no conflicts of interest to declare.

在MR图像海马子分割很好的体现在文献中。但是，现有的协议排除的海马20,23,33,35部，仅适用于定影图像37，或要求超高场扫描仪进行图像采集35,37。这个手稿提供一个分割协议，它包括海马五个主要分部（CA1，CA2 / CA3，CA4 /齿状回，SR / SL / SM，并下托），并跨越结构的整个前 - 后长度。完整的分段地图集可在公众网上（cobralab.ca/atlases/Hippocampus）来。这项工作是适用于神经?...

海马是与情节记忆，空间导航和其他认知功能10,31相关联的广泛研究的内侧颞叶结构。其在神经变性和神经精神障碍，如阿尔茨海默氏症，精神分裂症和双相情感障碍的作用是证据充分的4,5,18,24,30。本手稿的目标是提供额外的细节，以对在3T获得高分辨率磁共振（MR）图像对人海马子场察看34出版的手册分割协议。此外，视频分量随本手稿将提供给研究者谁希望实现自己的数据集的协议进一步的帮助。 海马可以基于观察到的在组织学制备的验尸cytoarchitectonic差异分为子场标本12,22。这种事后的标本定义GROU次为识别和海马子区研究真理。然而这种性质的制剂需要专门的技术和设备进行染色，并且通过固定的组织的可用性是有限的，尤其是在患病人群在体内成像具有主体大得多池的优点，并且还提供了机会为后续后续研究和人群观察变化。虽然它已被证明在T2加权体外的MR图像，信号强度反映蜂窝密度13，它仍然是难以确定仅仅使用MR信号强度的子场之间的无可争议的边界。因此，已经开发了许多不同的方法用于识别MR图像组织学级别的细节。 一些团体努力重建和数字化组织的数据集，然后用这些重建以及图像配准技术本地化海马子neuroanatOMY 在体内 MR 1,2,8,9,14,15,17,32。虽然这是一个有效的技术映射一个版本的病理基础事实直接到MR图像，这种性质的重建都难以完成。的项目，如这些是由完整的内侧颞叶标本，组织学技术，组织学处理期间的数据丢失，并固定和体内大脑之间的基本形态的不一致的可用性的限制。其他团体已使用高场扫描仪（7T或9.4T），以努力获得在体内或离体的影像具有足够小（0.20-0.35毫米各向同性）的体素尺寸的可视化空间定位，用于在图像对比度的差异推断子区35,37之间的界限。即使在7T-9.4T和用这样一个小的体素尺寸，海马子场cytoarchitectonic特征是不可见的。这样，手动分段协议已经开发了一pproximate对MR图像已知的组织界限。这些协议通过解释本地图像对比度的差异并限定几何规则（如直线和角），相对于可见光的结构确定的子场边界。虽然在高场强拍摄的图像能够提供详细的洞察海马子场，高场扫描仪是尚未在临床或研究设置常见，因此7T和9.4T协议目前具有有限的适用性。类似的协议已被开发用于收集在3T和4T扫描器11,20,21,23,24,25,28,33图像。许多这些协议是基于与在冠状面子1毫米体素的体素的尺寸的图像，但具有大的切片厚度（0.8-3毫米）11,20,21,23,25,28,33或大间切片的距离20,28，这两个导致各个子场的体积的估计中一个显著测量偏差。另外，许多现有的3T的协议排除的子场中的所有海马头部或尾部20,23,25,33的全部或部分，或不提供的重要子结构（即，结合 DG与CA2 / CA3或不包括地层radiatum /腔隙/ moleculare详细分割在CA）11,20,21,23,24,25,28,33。因此，有必要在该领域的协议，可以可靠地在整个头部，身体和海马的尾部是基于在临床和研究设置通常可获得的一个扫描器确定相关子场的详细描述。努力目前由海马子区组（www.hippocampalsubfields.com）正在进行协调实验室之间海马子场分割过程，类似于现有的协调工作对整个海马分割6，以及比较21的现有协议的初始纸最近发表38 。从这个小组的工作将进一步阐明最佳分割PROCE的既定程序。 这份手稿提供了详细的书面和视频指令的可靠实现高分辨率3T磁共振成像被温特和他的同事34前面所述的海马子分段协议。该协议对整个海马五个图像健康对照组和五个海马子字段（CA1，CA2 / CA3，CA4 /齿状回，地层radiatum /腔隙/ moleculare和下脚）得到落实。这些分割的图像都可以在公网上（cobralab.ca/atlases/Hippocampus）来。该协议与划分图像将是谁希望学习详细的海马神经解剖学磁共振图像组非常有用。

<table border="0">
	<tbody>
		<tr>
			<td>Discovery MR750 3T</td>
			<td>GE</td>
			<td>NA</td>
			<td>Or equivalent 3T scanner</td>
		</tr>
		<tr>
			<td>Minc Tool Kit</td>
			<td>McConnell Brain Imaging Center, Montreal Neurological Institute</td>
			<td>NA</td>
			<td>Open source: http://www.bic.mni.mcgill.ca/ServicesSoftware/ServicesSoftwareMincToolKit</td>
		</tr>
	</tbody>
</table>

high-resolution in vivo manual segmentation protocol for human hippocampal subfields using 3t magnetic resonance imaging

人类海马已被广泛研究了记忆和正常脑功能及其在不同的神经精神疾病作用方面一直在大力研究。虽然许多成像研究治疗海马为单一神经解剖结构，它是，在实际上，有一个复杂的三维几何形状的几个子场组成。因此，它是已知的，这些子场执行专门的功能，并通过不同的疾病状态的过程中差异的影响。磁共振（MR）成像，可作为一种强大的工具来询问海马和其子场的形态。许多集团利用先进的成像软件和硬件（&gt; 3T），以图像的子场;然而这种类型的技术可能不是在大多数研究和临床成像中心容易获得。为了满足这一需求，该手稿提供了一个详细的一步一步的协议分割全前后长度CORNU ammonis（CA）1，CA2 / CA3，CA4 /齿状回（DG），地层radiatum /腔隙/ moleculare（SR / SL / SM）和下脚：海马及其子区。该协议已经被应用到五个主题（3F，2M; 29-57岁，平均37）。协议的可靠性是由再分割或右侧每个受试者的左海马和计算使用骰子的卡伯度量重叠评估。平均骰子的卡帕（范围）在五个主题是：整海马，0.91（0.90-0.92）; CA1，0.78（0.77-0.79）; CA2 / CA3，0.64（0.56-0.73）; CA4 /齿状回，0.83（0.81-0.85）;地层radiatum /腔隙/ moleculare，0.71（0.68-0.73）;和下托0.75（0.72-0.78）。这里提出的分割协议提供其他实验室与研究使用常用的MR工具海马和海马子场体内的可靠方法。

。结果从协议可靠性测试总结于表2对于整个双侧海马，平均空间交叠由骰子的卡伯测定为0.91和0.90的范围内- 0.92。子场卡伯值范围为0.64（CA2 / CA3）至0.83（CA4 /齿状回）。平均体积为所有子场和整个海马列于表3中。卷在整个海马范围从2456.72-3325.02毫米3。该CA2 / CA3是最小的子场在208.33毫米3，而CA1是最大的857.46毫米3。 <p class="jove_conte...

Watch this Scientific Journal Video about High-resolution In Vivo Manual Segmentation Protocol for Human Hippocampal Subfields Using 3T Magnetic Resonance Imaging at JoVE.com

High-resolution In Vivo Manual Segmentation Protocol for Human Hippocampal Subfields Using 3T Magnetic Resonance Imaging

The goal of this manuscript is to study the hippocampus and hippocampal subfields using MRI. The manuscript describes a protocol for segmenting the hippocampus and five hippocampal substructures: cornu ammonis (CA) 1, CA2/CA3, CA4/dentate gyrus, strata radiatum/lacunosum/moleculare, and subiculum.

高分辨率<em&gt;在体内</em&gt;使用3T磁共振成像手动分割协议为人类海马子字段

The human hippocampus has been broadly studied in the context of memory and normal brain function and its role in different neuropsychiatric disorders has ...

high-resolution-vivo-manual-segmentation-protocol-for-human

Research

JoVE Journal

Neuroscience

High-resolution In Vivo Manual Segmentation Protocol for Human Hippocampal Subfields Using 3T Magnetic Resonance Imaging

9.2K 次观看.  University of Toronto. The goal of this manuscript is to study the hippocampus and hippocampal subfields using MRI. The manuscript describes a protocol for segmenting the hippocampus and five hippocampal substructures: cornu ammonis (CA) 1, CA2/CA3, CA4/dentate gyrus, strata radiatum/lacunosum/moleculare, and subiculum. 

视频: High-resolution In Vivo Manual Segmentation Protocol for Human Hippocampal Subfields Using 3T Magnetic Resonance Imaging

Magnetic Resonance Spectroscopy of live Drosophila melanogaster using Magic Angle Spinning

High-Resolution Magic Angle Spinning (HRMAS) proton magnetic resonance spectroscopy (1H-MRS) is a novel non-destructive technique that improves spectral line-widths and allows high-resolution spectra to be obtained from extracts, intact cells, cell cultures, and more importantly intact tissue to investigate relationships between metabolites and cellular processes. In vivo HRMAS 1H-MRS studies have yet to be reported in the live fruit fly Drosophila melanogaster. Drosophila, as a simpler genetic organism, allows the multiple biological functions and various evolutionarily conserved signaling pathways to be examined at the whole organism level and it is a useful model for investigating genetics and physiology. To this end, we developed and implemented an in vivo HRMAS 1H-MRS method to investigate live Drosophila at 14.1 T. Here, we outline an HRMAS 1H-MRS protocol for the molecular characterization of Drosophila with a conventional MR spectrometer equipped with an HRMAS probe. This technique is a novel, in vivo, non-destructive Drosophila metabolite measurement approach, which enables the identification of disease biomarkers and thus may contribute to novel therapeutic development.

Magnetic Resonance Spectroscopy of live Drosophila melanogaster using Magic Angle Spinning

This technique enables the use of high-resolution magic angle spinning proton MR spectroscopy (HRMAS 1H-MRS) for molecular characterization of live Drosophila melanogaster with a conventional 14.1 tesla spectrometer equipped with an HRMAS probe.

生活磁共振波谱果蝇</em用魔角旋转

High-Resolution Magic Angle Spinning (HRMAS) proton magnetic resonance spectroscopy (1H-MRS) is a novel non-destructive technique that improves spectral ...

科研

神经科学

Multiple-mouse Neuroanatomical Magnetic Resonance Imaging

The field of mouse phenotyping with magnetic resonance imaging (MRI) is rapidly growing, motivated by the need for improved tools for characterizing and evaluating mouse models of human disease. MRI is an excellent modality for investigating genetically altered animals. It is capable of whole brain coverage, can be used in vivo, and provides multiple contrast mechanisms for investigating different aspects of neuranatomy and physiology. The advent of high-field scanners along with the ability to scan multiple mice simultaneously allows for rapid phenotyping of novel mutations.
Effective mouse MRI studies require attention to many aspects of experiment design. In this article, we will describe general methods to acquire quality images for mouse phenotyping using a system that images mice concurrently in shielded transmit/receive radio frequency (RF) coils in a common magnet (Bock et al., 2003). We focus particularly on anatomical phenotyping, an important and accessible application that has shown a high potential for impact in many mouse models at our imaging centre. Before we can provide the detailed steps to acquire such images, there are important practical considerations for both in vivo brain imaging (Dazai et al., 2004) and ex vivo brain imaging (Spring et al., 2007) that should be noted. These are discussed below.

Magnetic resonance imaging (MRI) has become an increasingly popular tool for examining the phenotype of genetically altered mice. This article illustrates the methods necessary to achieve high-throughput phenotyping of genetically altered mice using multiple-mouse MRI.

多鼠神经解剖学磁共振成像

The field of mouse phenotyping with magnetic resonance imaging (MRI) is rapidly growing, motivated by the need for improved tools for characterizing and ...

A Rapid Approach to High-Resolution Fluorescence Imaging in Semi-Thick Brain Slices

A fundamental goal to both basic and clinical neuroscience is to better understand the identities, molecular makeup, and patterns of connectivity that are characteristic to neurons in both normal and diseased brain. Towards this, a great deal of effort has been placed on building high-resolution neuroanatomical maps1-3. With the expansion of molecular genetics and advances in light microscopy has come the ability to query not only neuronal morphologies, but also the molecular and cellular makeup of individual neurons and their associated networks4. Major advances in the ability to mark and manipulate neurons through transgenic and gene targeting technologies in the rodent now allow investigators to 'program' neuronal subsets at will5-6. Arguably, one of the most influential contributions to contemporary neuroscience has been the discovery and cloning of genes encoding fluorescent proteins (FPs) in marine invertebrates7-8, alongside their subsequent engineering to yield an ever-expanding toolbox of vital reporters9. Exploiting cell type-specific promoter activity to drive targeted FP expression in discrete neuronal populations now affords neuroanatomical investigation with genetic precision.
Engineering FP expression in neurons has vastly improved our understanding of brain structure and function. However, imaging individual neurons and their associated networks in deep brain tissues, or in three dimensions, has remained a challenge. Due to high lipid content, nervous tissue is rather opaque and exhibits auto fluorescence. These inherent biophysical properties make it difficult to visualize and image fluorescently labelled neurons at high resolution using standard epifluorescent or confocal microscopy beyond depths of tens of microns. To circumvent this challenge investigators often employ serial thin-section imaging and reconstruction methods10, or 2-photon laser scanning microscopy11. Current drawbacks to these approaches are the associated labor-intensive tissue preparation, or cost-prohibitive instrumentation respectively.
Here, we present a relatively rapid and simple method to visualize fluorescently labelled cells in fixed semi-thick mouse brain slices by optical clearing and imaging. In the attached protocol we describe the methods of: 1) fixing brain tissue in situ via intracardial perfusion, 2) dissection and removal of whole brain, 3) stationary brain embedding in agarose, 4) precision semi-thick slice preparation using new vibratome instrumentation, 5) clearing brain tissue through a glycerol gradient, and 6) mounting on glass slides for light microscopy and z-stack reconstruction (Figure 1).
For preparing brain slices we implemented a relatively new piece of instrumentation called the 'Compresstome' VF-200 (http://www.precisionary.com/products_vf200.html). This instrument is a semi-automated microtome equipped with a motorized advance and blade vibration system with features similar in function to other vibratomes. Unlike other vibratomes, the tissue to be sliced is mounted in an agarose plug within a stainless steel cylinder. The tissue is extruded at desired thicknesses from the cylinder, and cut by the forward advancing vibrating blade. The agarose plug/cylinder system allows for reproducible tissue mounting, alignment, and precision cutting. In our hands, the 'Compresstome' yields high quality tissue slices for electrophysiology, immunohistochemistry, and direct fixed-tissue mounting and imaging. Combined with optical clearing, here we demonstrate the preparation of semi-thick fixed brain slices for high-resolution fluorescent imaging.

Here we describe a rapid and simple method to image fluorescently labeled cells in semi-thick brain slices. By fixing, slicing, and optically clearing brain tissue we describe how standard epifluorescent or confocal imaging can be used to visualize individual cells and neuronal networks within intact nervous tissue.

一个快速高分辨率的荧光成像的方法在半厚的脑片

A fundamental goal to both basic and clinical neuroscience is to better understand the identities, molecular makeup, and patterns of connectivity that are ...

High-resolution Functional Magnetic Resonance Imaging Methods for Human Midbrain

Functional MRI (fMRI) is a widely used tool for non-invasively measuring correlates of human brain activity. However, its use has mostly been focused upon measuring activity on the surface of cerebral cortex rather than in subcortical regions such as midbrain and brainstem. Subcortical fMRI must overcome two challenges: spatial resolution and physiological noise. Here we describe an optimized set of techniques developed to perform high-resolution fMRI in human SC, a structure on the dorsal surface of the midbrain; the methods can also be used to image other brainstem and subcortical structures.
High-resolution (1.2 mm voxels) fMRI of the SC requires a non-conventional approach. The desired spatial sampling is obtained using a multi-shot (interleaved) spiral acquisition1. Since, T2* of SC tissue is longer than in cortex, a correspondingly longer echo time (TE ~ 40 msec) is used to maximize functional contrast. To cover the full extent of the SC, 8-10 slices are obtained. For each session a structural anatomy with the same slice prescription as the fMRI is also obtained, which is used to align the functional data to a high-resolution reference volume.
In a separate session, for each subject, we create a high-resolution (0.7 mm sampling) reference volume using a T1-weighted sequence that gives good tissue contrast. In the reference volume, the midbrain region is segmented using the ITK-SNAP software application2. This segmentation is used to create a 3D surface representation of the midbrain that is both smooth and accurate3. The surface vertices and normals are used to create a map of depth from the midbrain surface within the tissue4.
Functional data is transformed into the coordinate system of the segmented reference volume. Depth associations of the voxels enable the averaging of fMRI time series data within specified depth ranges to improve signal quality. Data is rendered on the 3D surface for visualization.
In our lab we use this technique for measuring topographic maps of visual stimulation and covert and overt visual attention within the SC1. As an example, we demonstrate the topographic representation of polar angle to visual stimulation in SC.

This article describes techniques to perform high-resolution functional magnetic resonance imaging with 1.2 mm sampling in human midbrain and subcortical structures using a 3T scanner. Use of these techniques to resolve topographic maps of visual stimulation in the human superior colliculus (SC) is given as an example.

高分辨率人类中脑功能磁共振成像方法

Functional MRI (fMRI) is a widely used tool for non-invasively measuring correlates of human brain activity. However, its use has mostly been focused upon ...

A Comprehensive Protocol for Manual Segmentation of the Medial Temporal Lobe Structures

The present paper describes a comprehensive protocol for manual tracing of the set of brain regions comprising the medial temporal lobe (MTL): amygdala, hippocampus, and the associated parahippocampal regions (perirhinal, entorhinal,&#160;and parahippocampal proper). Unlike most other tracing protocols available, typically focusing on certain MTL areas (e.g., amygdala and/or hippocampus), the integrative perspective adopted by the present tracing guidelines allows for clear localization of all MTL subregions. By integrating information from a variety of sources, including extant tracing protocols separately targeting various MTL structures, histological reports, and brain atlases, and with the complement of illustrative visual materials, the present protocol provides an accurate, intuitive, and convenient guide for understanding the MTL anatomy. The need for such tracing guidelines is also emphasized by illustrating possible differences between automatic and manual segmentation protocols. This knowledge can be applied toward research involving not only structural MRI investigations but also structural-functional colocalization and fMRI signal extraction from anatomically defined ROIs, in healthy and clinical groups alike.

The present work provides a comprehensive set of guidelines for manually tracing the medial temporal lobe (MTL) structures. This protocol can be applied to research involving structural and/or combined structural-functional magnetic resonance imaging (MRI) investigations of the MTL, in both healthy and clinical groups.

一个全面协议的内侧颞叶结构的手动分割

The present paper describes a comprehensive protocol for manual tracing of the set of brain regions comprising the medial temporal lobe (MTL): amygdala, ...

Metabolomic Analysis of Rat Brain by High Resolution Nuclear Magnetic Resonance Spectroscopy of Tissue Extracts

Studies of gene expression on the RNA and protein levels have long been used to explore biological processes underlying disease. More recently, genomics and proteomics have been complemented by comprehensive quantitative analysis of the metabolite pool present in biological systems. This strategy, termed metabolomics, strives to provide a global characterization of the small-molecule complement involved in metabolism. While the genome and the proteome define the tasks cells can perform, the metabolome is part of the actual phenotype. Among the methods currently used in metabolomics, spectroscopic techniques are of special interest because they allow one to simultaneously analyze a large number of metabolites without prior selection for specific biochemical pathways, thus enabling a broad unbiased approach. Here, an optimized experimental protocol for metabolomic analysis by high-resolution NMR spectroscopy is presented, which is the method of choice for efficient quantification of tissue metabolites. Important strengths of this method are (i) the use of crude extracts, without the need to purify the sample and/or separate metabolites; (ii) the intrinsically quantitative nature of NMR, permitting quantitation of all metabolites represented by an NMR spectrum with one reference compound only; and (iii) the nondestructive nature of NMR enabling repeated use of the same sample for multiple measurements. The dynamic range of metabolite concentrations that can be covered is considerable due to the linear response of NMR signals, although metabolites occurring at extremely low concentrations may be difficult to detect. For the least abundant compounds, the highly sensitive mass spectrometry method may be advantageous although this technique requires more intricate sample preparation and quantification procedures than NMR spectroscopy. We present here an NMR protocol adjusted to rat brain analysis; however, the same protocol can be applied to other tissues with minor modifications.

The neurochemistry of mammalian brain is changed in many neurological and systemic diseases. Characteristic profiles of cerebral metabolites can be efficiently obtained based on crude extracts of brain tissue. To this end, high-resolution NMR spectroscopy is employed, enabling detailed quantitative analysis of metabolite concentrations (metabolomics).

大鼠脑组织被提取物的高分辨核磁共振代谢组学分析

Studies of gene expression on the RNA and protein levels have long been used to explore biological processes underlying disease. More recently, genomics ...

High-resolution Structural Magnetic Resonance Imaging of the Human Subcortex In Vivo and Postmortem

The focus of this study was to test the resolution limits of structural MRI of a postmortem brain compared to living human brains. The resolution of structural MRI in vivo is ultimately limited by physiological noise, including pulsation, respiration and head movement. Although imaging hardware continues to improve, it is still difficult to resolve structures on the millimeter scale. For example, the primary visual sensory pathways synapse at the lateral geniculate nucleus (LGN), a visual relay and control nucleus in the thalamus that normally is organized into six interleaved monocular layers. Neuroimaging studies have not been able to reliably distinguish these layers due their small size that are less than 1 mm thick.
The resolving limit of structural MRI, in a postmortem brain was tested using multiple images averaged over a long duration (~24 h). The purpose was to test whether it was possible to resolve the individual layers of the LGN in the absence of physiological noise. A proton density (PD)1 weighted pulse sequence was used with varying resolution and other parameters to determine the minimum number of images necessary to be registered and averaged to reliably distinguish the LGN and other subcortical regions. The results were also compared to images acquired in living human brains. In vivo subjects were scanned in order to determine the additional effects of physiological noise on the minimum number of PD scans needed to differentiate subcortical structures, useful in clinical applications.

High-resolution Structural Magnetic Resonance Imaging of the Human Subcortex In Vivo and Postmortem

Here we present a protocol to determine the minimum number images that needed to be registered and averaged to resolve subcortical structures and test whether the individual layers of the LGN could be resolved in the absence of physiological noise.

高分辨率结构磁共振人类皮质下的成像<I&gt;在体内</I&gt;与死亡

The focus of this study was to test the resolution limits of structural MRI of a postmortem brain compared to living human brains. The resolution of ...

A Magnetic Resonance Imaging Protocol for Stroke Onset Time Estimation in Permanent Cerebral Ischemia

MRI provides a sensitive and specific imaging tool to detect acute ischemic stroke by means of a reduced diffusion coefficient of brain water. In a rat model of ischemic stroke, differences in quantitative T1 and T2 MRI relaxation times (qT1 and qT2) between the ischemic lesion (delineated by low diffusion) and the contralateral non-ischemic hemisphere increase with time from stroke onset. The time dependency of MRI relaxation time differences is heuristically described by a linear function and thus provides a simple estimate of stroke onset time. Additionally, the volumes of abnormal qT1 and qT2 within the ischemic lesion increase linearly with time providing a complementary method for stroke timing. A (semi)automated computer routine based on the quantified diffusion coefficient is presented to delineate acute ischemic stroke tissue in rat ischemia. This routine also determines hemispheric differences in qT1 and qT2 relaxation times and the location and volume of abnormal qT1 and qT2 voxels within the lesion. Uncertainties associated with onset time estimates of qT1 and qT2 MRI data vary from &plusmn; 25 min to &plusmn; 47 min for the first 5 hours of stroke. The most accurate onset time estimates can be obtained by quantifying the volume of overlapping abnormal qT1 and qT2 lesion volumes, termed 'Voverlap' (&plusmn; 25 min) or by quantifying hemispheric differences in qT2 relaxation times only (&plusmn; 28 min). Overall, qT2 derived parameters outperform those from qT1. The current MRI protocol is tested in the hyperacute phase of a permanent focal ischemia model, which may not be applicable to transient focal brain ischemia.

A protocol for stroke onset time estimation in a rat model of stroke exploiting quantitative magnetic resonance imaging (qMRI) parameters is described. The procedure exploits diffusion MRI for delineation of the acute stroke lesion and quantitative T1 and T2 (qT1 and qT2) relaxation times for timing of stroke.

脑缺血中风发作时间估计的磁共振成像协议

MRI provides a sensitive and specific imaging tool to detect acute ischemic stroke by means of a reduced diffusion coefficient of brain water. In a rat ...

A Standardized Pipeline for Examining Human Cerebellar Grey Matter Morphometry using Structural Magnetic Resonance Imaging

Multiple lines of research provide compelling evidence for a role of the cerebellum in a wide array of cognitive and affective functions, going far beyond its historical association with motor control. Structural and functional neuroimaging studies have further refined understanding of the functional neuroanatomy of the cerebellum beyond its anatomical divisions, highlighting the need for the examination of individual cerebellar subunits in healthy variability and neurological diseases. This paper presents a standardized pipeline for examining cerebellum grey matter morphometry that combines high-resolution, state-of-the-art approaches for optimized and automated cerebellum parcellation (Automatic Cerebellum Anatomical Parcellation using U-Net Locally Constrained Optimization; ACAPULCO) and voxel-based registration of the cerebellum (Spatially Unbiased Infra-tentorial Template; SUIT) for volumetric quantification. 
The pipeline has broad applicability to a range of neurological diseases and is fully automated, with manual intervention only required for quality control of the outputs. The pipeline is freely available, with substantial accompanying documentation, and can be run on Mac, Windows, and Linux operating systems. The pipeline is applied in a cohort of individuals with Friedreich ataxia (FRDA), and representative results, as well as recommendations on group-level inferential statistical analyses, are provided. This pipeline could facilitate reliability and reproducibility across the field, ultimately providing a powerful methodological approach for characterizing and tracking cerebellar structural changes in neurological diseases.

A standardized pipeline is presented for examining cerebellum grey matter morphometry. The pipeline combines high-resolution, state-of-the-art approaches for optimized and automated cerebellum parcellation and voxel-based registration of the cerebellum for volumetric quantification.

一种使用结构磁共振成像检查人小脑灰质形态测量的标准化管道

Multiple lines of research provide compelling evidence for a role of the cerebellum in a wide array of cognitive and affective functions, going far beyond ...

在现实生活场景中实现人类视觉、认知和交互的设置

A Naturalistic Setup for Presenting Real People and Live Actions in Experimental Psychology and Cognitive Neuroscience Studies

Perception of others&#39; actions is crucial for survival, interaction, and communication. Despite decades of cognitive neuroscience research dedicated to understanding the perception of actions, we are still far away from developing a neurally inspired computer vision system that approaches human action perception. A major challenge is that actions in the real world consist of temporally unfolding events in space that happen &#34;here and now&#34; and are actable. In contrast, visual perception and cognitive neuroscience research to date have largely studied action perception through 2D displays (e.g., images or videos) that lack the presence of actors in space and time, hence these displays are limited in affording actability. Despite the growing body of knowledge in the field, these challenges must be overcome for a better understanding of the fundamental mechanisms of the perception of others&#39; actions in the real world. The aim of this study is to introduce a novel setup to conduct naturalistic laboratory experiments with live actors in scenarios that approximate real-world settings. The core element of the setup used in this study is a transparent organic light-emitting diode (OLED) screen through which participants can watch the live actions of a physically present actor while the timing of their presentation is precisely controlled. In this work, this setup was tested in a behavioral experiment. We believe that the setup will help researchers reveal fundamental and previously inaccessible cognitive and neural mechanisms of action perception and will be a foundation for future studies investigating social perception and cognition in naturalistic settings.

作者聚焦：在场景中使用真实人类演员进行自然主义实验室实验的新设置 

This study presents a naturalistic experimental setup that allows researchers to present real-time action stimuli, obtain response time and mouse tracking data while participants respond after each stimulus display, and change actors between experimental conditions with a unique system including a special transparent organic light-emitting diode (OLED) screen and light manipulation.

在实验心理学和认知神经科学研究中呈现真人和真人行为的自然主义设置

Perception of others&#39; actions is crucial for survival, interaction, and communication. Despite decades of cognitive neuroscience research dedicated to ...