The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme [FP7/2007-2013] / ERC grant agreement [337333]. The research of SvV and GJB is supported by a VIDI grant [91711384] from ZonMw, the Netherlands Organization for Health Research and Development.

使用尸检标本和活体 MR图像此协议是符合当地法规并经大学医学中心的乌得勒支（UMCU）的当地机构审查委员会。 1.磁共振引导皮质Microinfarcts的组织病理学检验<ol><li> 体外 MRI <ol><li>在处理脑组织，一定要穿戴手套和适当的防护服。 </li><li>根据研究问题，选择合适的，最好是10毫米厚，福尔马林固定大脑板。大脑板对本文均来自UMCU的神经病理学部门，VU大学医学中心（VUMC），根据已知的阿尔茨海默氏症的病理。 <ol><li>通过浸渍在10％的福尔马林福尔马林固定全脑为至少3-4周，在切割之前。切大脑进入冠状板，包含两个半球。 </li><li>对于验尸扫描，选择例如三个脑SLA每脑BS，从正面，颞顶骨和脑的枕骨区域采取。当前协议是为使用三个冠状脑板坯优化，含有两个半球，在一个扫描会话。 </li></ol></li><li>取脑板坯的照片在两侧（背和尾），并采取谨慎音符（或使草图）在容器中，并在扫描器板坯的取向的，购买的共定位的组织学的MRI。 </li><li>填写一个特制的容器（ 图1） -在这种情况下，一个适合MR磁头线圈中-用10％福尔马林保鲜室温。如果从流体MRI信号是不希望使用全氟聚醚（PFPE）润滑剂用合适的密度，而不是福尔马林（如的Fomblin或热传导液PFPE）。确保处理福尔马林时使用一个流柜。 </li><li>当放置在容器中的大脑砖，一定要避免气泡。轻轻去除大部分气泡萨基纳克的组织，或者通过手，或者使用振动筛或超声波浴中。 </li><li>确保板坯不能在容器内移动，并限制所需要的流体的量，通过使用更小的容器，以保持板坯到位（ 图1）。 </li><li>覆盖容器用塑料或封口膜，以防止蒸发，并保护从潜在污染（图2）对MR（头）线圈。 </li><li>使用全身7T MRI扫描器与适当的线圈。在这个协议中一个双重的发送和32通道接收头线圈被使用。 </li><li>将容器中的磁头线圈，裹在毛巾或手术底垫，以防止流体的潜在溢出。确保容器不能移动，并且该板保持在水平位置（图2）。 </li><li>运行可通过使用适当的垫补工具被用于高分辨率扫描，正确B0不均匀的规划的调查扫描，并校准RF功​​率以获得正确的翻转角（少数板坯需要更少的功率相比在体内扫描整个头部的）根据制造商的协议。 </li><li>计划调查扫描高分辨率收购，以确保大脑板坯完全包含在场-的图。扫描脑板坯O / N与表1中所示的分辨率高的收购，这是用于离体成像优化。这里提出的获取协议包括具有各向同性分辨率为0.4mm，以及一个T2 *加权的图像以0.18毫米的各向同性分辨率的三维FLAIR，T2和T1加权图像。 </li><li>自动识别软件进程，可能会中断扫描，如运行O / N自动向上日期，或末梢神经的刺激警告，并确保扫描仪的程序不会被这些中断。 </li><li>监控扫描仪O / N为可能确认的弹出窗口，可能会中断扫描，通过使用例如VPN连接。</li><li>返回第二天上午（后在当前的协议大约12小时的总扫描时间）。存放于福尔马林大脑砖，清理。 </li><li>保存图像到外部硬盘。 </li></ol></li></ol><img alt="图1" src="/files/ftp_upload/53125/53125fig1.jpg" /> 图1.制备福尔马林固定脑板坯进行事后扫描在7T的MRI。甲专门建造的有机玻璃容器中填充为10％福尔马林或全氟聚醚（PFPE）润滑剂，如果从该流体的MRI信号是不希望的。三个10毫米厚的福尔马林固定冠状脑板坯放置在容器中。较小的容器用来保持板坯到位。用胶带将第二容器的第一个，以防止移动。 <img alt="图2" src="/files/ftp_upload/53125/53125fig2.jpg" /> 图2.放置在7T头部线圈的专用容器。盖上容器用塑料或封口膜，以防止福尔马林的蒸发。将容器，包在毛巾或手术焊，在7T磁共振扫描仪的头部线圈。确保容器不能移动，并且该板保持在水平位置。 <ol start="2"><li>组织病理学<ol><li>确定可能的皮质中药注射剂 - 或感兴趣的其他病变 - 对采集的图像。这些病变组织学分析的目标。当心工件，如验尸组织损伤（有时因削减出现在大脑砖的表面）或长期福尔马林保存的文物（ 如粗MRI低信号代表神经纤维的改变8）。 注:皮质中药注射剂的不同病理亚型有不同的MR特性。有关的CMI亚型进一步的细节，读者可参考最近的体外研究7。 </li><li>房颤之三确定的MR图像可能皮质中药注射剂，试样的病理验证感兴趣的区域。请一定要切出一个区域，包括解剖标志，用于组织病理学磁共振成像以后匹配。执行标准组织病理学，作为跟随（但其他的方法也可能适用）。 </li><li>切出的约30×20×5毫米3含有可能皮层的CMI的区域。 </li><li>为了获得准确的采样，通过切片厚度的磁共振图像，以及组织架构估计病变的部位。手动切割组织略高于估计病灶位置以限制是需要靶向病变连续切片（石蜡包埋后）的量。 </li><li>确保采样组织适合一个组织盒。放置表面要在盒切割面朝下。 </li><li>保留所有组织盒中10％的甲醛，直至组织处理。 </li><li>过程中组织进行石蜡包埋。这通常涉及脱水组织，通过一系列梯度酒精（例如，70％至95％至100％）浴，并清除在二甲苯的组织的的一种自动化过程。 </li><li>嵌入石蜡块中的组织。保证嵌入后的表面进行切割朝上。 </li><li>切4-6微米连续切片用切片机，直至靶疾患检索。 </li><li>浮动的37℃水浴表面上的部分。安装在载玻片上的部分。放置一个变暖块上的滑动来接合组织，以在玻璃上。商店幻灯片O / N在室温。 </li><li>执行的第一个部分一个合适的染色（ 如 H＆E染色），让相邻的空白部分用于再使用 （例如，免疫组化）。 </li><li>盖玻片的H＆E染色切片，用一滴安装选择介质。轻轻放下防滑，避免产生气泡。 </li><li>研究使用光学显微镜的部分中，在一个适当的磁nification。部分比较先前获得的MR图像。 </li></ol></li></ol> 2.评估皮质Microinfarcts 对体内7T磁共振成像<ol><li>在您感兴趣的患者群体进行7T的MRI，使用如6所述的体内 MRI方案（其包括至少一个三维FLAIR）。 </li><li>评估如在下面的步骤中详述的体内 7T MR图像皮质中药注射剂，使用以下7T评级标准中药注射剂:皮质中药注射剂是高信号上FLAIR（具有或不具有低信号中心），高信号在T2，低信号在T1，可检测的上的至少两个视图的脑（例如，矢状和横向）的，仅限于皮质，从血管周围间隙不同，具有最大尺寸≤4毫米6,7。 </li><li>使用接口具有三个图像的观众，同时查看FLAIR，T1和T2的图像，例如，MeVisLab（图3）。该平台异体WS地将多个观众，并把可能的病变部位的位置标记。 </li><li>首先评估一个半球FLAIR上矢状视图。屏幕全皮质的高信号病灶。任何hyperintens病变≤4毫米是一个可能的CMI。通过点击每一个可能的CMI位置标记。 </li><li>重复另一半球。 </li><li>验证在T1和T2的所有标记的​​位置。丢弃一个位置，如果它不是低信号T1或高信号在T2。 </li><li>评估横向视图中，FLAIR，T1和T2。丢弃一个位置，如果它是不可见的。检查中如有疑问冠状视图。 </li><li>当心MRI伪影和解剖变异（尤其是脑沟的边缘）。 </li><li>保存标记。 </li></ol><img alt="图3" src="/files/ftp_upload/53125/53125fig3.jpg" /> 图3.示例图像浏览平台皮质microinfarcts的评估。接口时，INTegrated在MeVisLab。这个程序允许同时将多个观众，矢状/横向/冠状方向之间轻松切换，并把和节省可能的病变位置标记。 （不同的标记，可以选择不同类型的病灶）。 3.评估皮质Microinfarcts 对体内3T MRI <ol><li>获取您感兴趣的患者人群的3T磁共振图像。现有的数据也可以只要该MR成像协议中包含的至少一个三维T1和一个FLAIR和T2使用。 </li><li>评估皮质中药注射剂上，如下面的步骤中详述的体内 3T MR图像，使用以下3T评级标准中药注射剂:皮质中药注射剂是低信号在T1（等信号与CSF），可检测的至少两个视图的大脑（例如矢状和横向），限制到皮质，从血管周围间隙不同，具有最大尺寸≤4毫米。 <ol><li>探索一个hypoint的位置恩瑟皮质病变发现T1的风格和T2加权像。评价病变为可能的皮质CMI如果该位置上的天赋和T2高或等信号（与灰质）。丢弃病变如果在同一位置一低信号被发现在T2，表示T1低信号病变或者是由于出血性病变，血管，或工件。如有疑问，请查看位置上的T2 *加权图像9。 </li></ol></li><li>使用相同的接口，如上所述。 </li><li>首先评估一个半球在T1矢状视图。屏幕全皮质局灶性低信号病变。任何低信号病​​灶≤4毫米是一个可能的CMI。通过点击每一个可能的CMI位置标记。 </li><li>重复另一半球。 </li><li>评估横向T1，同时核实横向FLAIR和T2的所有标记的​​位置。关于该位置作为一个可能的CMI如果是高信号或等信号的FLAIR和T2。放弃一个位置我F IT似乎是一个假象或解剖变异。丢弃的位置，如果它是低信号T2。 </li><li>当心工件看起来像在T1加权图像中药注射剂，特别是在其中将出现在几个相邻的脑回，注意沟的边缘大脑的"边缘"的环状假象，注意大血管中的颞叶（在两极）。最后，建议丢弃在组织可能皮质中药注射剂在靠近较大皮质梗塞。 </li><li>保存标记。 </li></ol>

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The authors have nothing to disclose.

中药注射剂已经​​吸引了越来越多的关注，在过去的几年里。证据尸检研究中获得越来越多的身体已经确定中药注射剂的重要贡献者与年龄有关的认知能力下降和痴呆4,5。中药注射剂是现在检测的7T，也3T MRI检查。优化和评估协议，这些病变的标准化将支持迅速执行稳健和有效的CMI检测的队列研究在世界各地。这将使中药注射剂的老化，脑血管疾病的上下文中的临床相关的在未来的临床...

超高场7特斯拉（T）MRI检查的患者研究中的应用正在迅速发展1。本文介绍7T磁共振脑血管疾病的老化人脑的范围内有代表性的应用程序。脑血管疾病是认知衰退和痴呆的主要原因。这对血管性痴呆贡献经常涉及脑的小血管，如动脉，小静脉和毛细血管。因此，它被称为脑小血管疾病（SVD）2。因为脑小血管太小捕获与常规MRI，SVD只有后果- 即，所得到的组织损伤-可以被可视化。这包括白质高信号，脑微出血和腔隙性梗死3。 SVD的其他重要表现是脑microinfarcts（CMIS）4。尸检研究报道的中药注射剂在VASC高患病率ular痴呆和阿尔茨海默氏病5。然而，由于它们的小尺寸（范围从50微米到几个毫米）他们逃过检测上常规MRI 4,5。 7T的MRI提供具有改进的信号与噪声比和对比度，这使得某些结构和病变超越常规MRI的检测极限的检测高分辨率的图像。因此，该技术应用于检测中药注射剂。为了找出可能的中药注射剂，多在体内 7T核磁共振成像扫描了以前的病变筛查与尺寸&lt;缺血性一致5毫米的影像学特征。这种病变可以可靠地在皮层被识别。这些联络拉长病变呈高信号的7T FLAIR（0.8毫米各向同性体素），受限于皮层，似乎从皮质表面延伸，高信号，在T2（0.7毫米各向同性体素），以及低信号T1（1.0毫米各向同性体素）。经证实，这些病变是使用皮质中药注射剂MR引导组织病理学方法在验尸人脑组织6,7。 在此， 离体 MRI方案，提出了用在以前的研究中对皮质中药注射剂的组织病理学验证。其次，提供了用于皮质中药注射剂在体内对7T的MRI评估准则。最后，皮质中药注射剂在7T的评估已被翻译为更广泛地提供3T MRI，并提供指导如何识别3T MRI皮质中药注射剂。

<table><tbody><tr><td>Fomblin / Galden PFPE</td><td>Solvay Solexis, Bollate, Italy</td><td></td><td></td></tr><tr><td>7T MR system</td><td>Philips Healthcare, Cleveland, OH, USA</td><td></td><td></td></tr><tr><td>32-channel receive head coil</td><td>Nova Medical, Wilmington, MA, USA</td><td></td><td></td></tr><tr><td>MeVisLab</td><td>MeVis Medical Solutions AG, Bremen, Germany</td><td></td><td></td></tr></tbody></table>

assessing cortical cerebral microinfarcts on high resolution mr images

脑microinfarcts频繁发现在验尸人脑，并与认知能力下降和痴呆。由于其尺寸小​​是具有挑战性的研究他们在临床MRI扫描。这是最近证实，皮质microinfarcts可以采用高磁场强度（7T），核磁共振成像扫描仪来描述。在此基础上的经验，这些病变的比例也较低分辨率的3T MRI可见。这些研究结果证实与死后的人脑组织的体外成像，伴随着可能的皮质microinfarcts病理组织学检验。 这里离体成像协议，提出，用于验证的MR观察脑微血管病理组织学评估的目的。此外，提供了用于在两个体内 7T和3T MR图像皮质microinfarcts的评估准则。这些准则为研究人员提供W¯¯第i个工具率在体内图像较大患者样本皮质microinfarcts，进一步揭开其临床意义的认知功能减退和老年痴呆症，并在这些病变作为一种新型的脑小血管疾病的生物标志物。

高分辨率和在7T提供获得离体序列的高图像质量的印象<a href="https://www.jove.com/files/ftp_upload/53125/53125fig4.mp4" target="_blank">这里（图4）。</a>这是一个三维的T2 *加权的离体的扫描，以0.18毫米的各向同性分辨率。组织来源于一个84岁的痴呆症的女性经病理证实为阿尔茨海默氏症和严重的脑淀粉样血管病（CAA）。图像的细节允许皮质微血管病理的鉴定。 T2 *是易感的铁，以及空气。该组织含有...

Watch this Scientific Journal Video about Assessing Cortical Cerebral Microinfarcts on High Resolution MR Images at JoVE.com

Assessing Cortical Cerebral Microinfarcts on High Resolution MR Images

高分辨率体外 7T磁共振成像协议提出，在验尸人脑组织进行微血管病变的MR引导组织病理学检验。此外，提供了用于在体内对7T皮质microinfarcts以及3T MR图像的评估准则。

评估皮层脑Microinfarcts高分辨率核磁共振图像

Cerebral microinfarcts are frequent findings in the post-mortem human brain, and are related to cognitive decline and dementia. Due to their small sizes ...

assessing-cortical-cerebral-microinfarcts-on-high-resolution-mr-images

Research

JoVE Journal

Medicine

13.4K 次观看.  University Medical Center Utrecht. 高分辨率体外 7T磁共振成像协议提出，在验尸人脑组织进行微血管病变的MR引导组织病理学检验。此外，提供了用于在体内对7T皮质microinfarcts以及3T MR图像的评估准则。 

视频: Assessing Cortical Cerebral Microinfarcts on High Resolution MR Images

Focal Cerebral Ischemia Model by Endovascular Suture Occlusion of the Middle Cerebral Artery in the Rat

Stroke is the leading cause of disability and the third leading cause of death in adults worldwide1. In human stroke, there exists a highly variable clinical state; in the development of animal models of focal ischemia, however, achieving reproducibility of experimentally induced infarct volume is essential. The rat is a widely used animal model for stroke due to its relatively low animal husbandry costs and to the similarity of its cranial circulation to that of humans2,3. In humans, the middle cerebral artery (MCA) is most commonly affected in stroke syndromes and multiple methods of MCA occlusion (MCAO) have been described to mimic this clinical syndrome in animal models. Because recanalization commonly occurs following an acute stroke in the human, reperfusion after a period of occlusion has been included in many of these models. In this video, we demonstrate the transient endovascular suture MCAO model in the spontaneously hypertensive rat (SHR). A filament with a silicon tip coating is placed intraluminally at the MCA origin for 60 minutes, followed by reperfusion. Note that the optimal occlusion period may vary in other rat strains, such as Wistar or Sprague-Dawley. Several behavioral indicators of stroke in the rat are shown. Focal ischemia is confirmed using T2-weighted magnetic resonance images and by staining brain sections with 2,3,5-triphenyltetrazolium chloride (TTC) 24 hours after MCAO.

Surgical induction of ischemic brain damage in the rat is a widely used model for stroke research. Here we demonstrate the induction of focal cerebral ischemia by occlusion of the middle cerebral artery. Visualization of the resulting infarct by histological staining and magnetic resonance imaging is also shown.

焦距脑缺血模型大鼠大脑中动脉的血管内缝合闭塞

Stroke is the leading cause of disability and the third leading cause of death in adults worldwide1. In human stroke, there exists a highly variable ...

科研

神经科学

How to Measure Cortical Folding from MR Images: a Step-by-Step Tutorial to Compute Local Gyrification Index

Cortical folding (gyrification) is determined during the first months of life, so that adverse events occurring during this period leave traces that will be identifiable at any age. As recently reviewed by Mangin and colleagues2, several methods exist to quantify different characteristics of gyrification. For instance, sulcal morphometry can be used to measure shape descriptors such as the depth, length or indices of inter-hemispheric asymmetry3. These geometrical properties have the advantage of being easy to interpret. However, sulcal morphometry tightly relies on the accurate identification of a given set of sulci and hence provides a fragmented description of gyrification. A more fine-grained quantification of gyrification can be achieved with curvature-based measurements, where smoothed absolute mean curvature is typically computed at thousands of points over the cortical surface4. The curvature is however not straightforward to comprehend, as it remains unclear if there is any direct relationship between the curvedness and a biologically meaningful correlate such as cortical volume or surface. To address the diverse issues raised by the measurement of cortical folding, we previously developed an algorithm to quantify local gyrification with an exquisite spatial resolution and of simple interpretation. Our method is inspired of the Gyrification Index5, a method originally used in comparative neuroanatomy to evaluate the cortical folding differences across species. In our implementation, which we name local Gyrification Index (lGI1), we measure the amount of cortex buried within the sulcal folds as compared with the amount of visible cortex in circular regions of interest. Given that the cortex grows primarily through radial expansion6, our method was specifically designed to identify early defects of cortical development.
In this article, we detail the computation of local Gyrification Index, which is now freely distributed as a part of the FreeSurfer Software (<a href="http://surfer.nmr.mgh.harvard.edu/">http://surfer.nmr.mgh.harvard.edu/</a>, Martinos Center for Biomedical Imaging, Massachusetts General Hospital). FreeSurfer provides a set of automated reconstruction tools of the brain's cortical surface from structural MRI data. The cortical surface extracted in the native space of the images with sub-millimeter accuracy is then further used for the creation of an outer surface, which will serve as a basis for the lGI calculation. A circular region of interest is then delineated on the outer surface, and its corresponding region of interest on the cortical surface is identified using a matching algorithm as described in our validation study1. This process is repeatedly iterated with largely overlapping regions of interest, resulting in cortical maps of gyrification for subsequent statistical comparisons (Fig. 1). Of note, another measurement of local gyrification with a similar inspiration was proposed by Toro and colleagues7, where the folding index at each point is computed as the ratio of the cortical area contained in a sphere divided by the area of a disc with the same radius. The two implementations differ in that the one by Toro et al. is based on Euclidian distances and thus considers discontinuous patches of cortical area, whereas ours uses a strict geodesic algorithm and include only the continuous patch of cortical area opening at the brain surface in a circular region of interest.

Measuring gyrification (cortical folding) at any age represents a window into early brain development. Hence, we previously developed an algorithm to measure local gyrification at thousands of points over the hemisphere1. In this paper, we detail the computation of this local gyrification index.

如何从MR图像测量皮质折叠：一个循序渐进的教程，以计算本地Gyrification指数

Cortical folding (gyrification) is determined during the first months of life, so that adverse events occurring during this period leave traces that will ...

医学

Brain Infarct Segmentation and Registration on MRI or CT for Lesion-symptom Mapping

In lesion-symptom mapping (LSM), brain function is inferred by relating the location of acquired brain lesions to behavioral or cognitive symptoms in a group of patients. With recent advances in brain imaging and image processing, LSM has become a popular tool in cognitive neuroscience. LSM can provide fundamental insights into the functional architecture of the human brain for a variety of cognitive and non-cognitive functions. A crucial step in performing LSM studies is the segmentation of lesions on brains scans of a large group of patients and registration of each scan to a common stereotaxic space (also called standard space or a standardized brain template). Described here is an open-access, standardized method for infarct segmentation and registration for the purpose of LSM, as well as a detailed and hands-on walkthrough based on exemplary cases. A comprehensive tutorial for the manual segmentation of brain infarcts on CT scans and DWI or FLAIR MRI sequences is provided, including criteria for infarct identification and pitfalls for different scan types. The registration software provides multiple registration schemes that can be used for processing of CT and MRI data with heterogeneous acquisition parameters. A tutorial on using this registration software and performing visual quality checks and manual corrections (which are needed in some cases) is provided. This approach provides researchers with a framework for the entire process of brain image processing required to perform an LSM study, from gathering of the data to final quality checks of the results.

Provided here is a practical tutorial for an open-access, standardized image processing pipeline for the purpose of lesion-symptom mapping. A step-by-step walkthrough is provided for each processing step, from manual infarct segmentation on CT/MRI to subsequent registration to standard space, along with practical recommendations and illustrations with exemplary cases.

脑梗死分割和登记在MRI或CT上的病变症状映射

In lesion-symptom mapping (LSM), brain function is inferred by relating the location of acquired brain lesions to behavioral or cognitive symptoms in a ...

行为学

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

The human hippocampus has been broadly studied in the context of memory and normal brain function and its role in different neuropsychiatric disorders has been heavily studied. While many imaging studies treat the hippocampus as a single unitary neuroanatomical structure, it is, in fact, composed of several subfields that have a complex three-dimensional geometry. As such, it is known that these subfields perform specialized functions and are differentially affected through the course of different disease states. Magnetic resonance (MR) imaging can be used as a powerful tool to interrogate the morphology of the hippocampus and its subfields. Many groups use advanced imaging software and hardware (&#62;3T) to image the subfields; however this type of technology may not be readily available in most research and clinical imaging centers. To address this need, this manuscript provides a detailed step-by-step protocol for segmenting the full anterior-posterior length of the hippocampus and its subfields: cornu ammonis (CA) 1, CA2/CA3, CA4/dentate gyrus (DG), strata radiatum/lacunosum/moleculare (SR/SL/SM), and subiculum. This protocol has been applied to five subjects (3F, 2M; age 29-57, avg. 37). Protocol reliability is assessed by resegmenting either the right or left hippocampus of each subject and computing the overlap using the Dice&#39;s kappa metric. Mean Dice&#39;s kappa (range) across the five subjects are: whole hippocampus, 0.91 (0.90-0.92); CA1, 0.78 (0.77-0.79); CA2/CA3, 0.64 (0.56-0.73); CA4/dentate gyrus, 0.83 (0.81-0.85); strata radiatum/lacunosum/moleculare, 0.71 (0.68-0.73); and subiculum 0.75 (0.72-0.78). The segmentation protocol presented here provides other laboratories with a reliable method to study the hippocampus and hippocampal subfields in vivo using commonly available MR tools.

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 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 ...

Lateral Chronic Cranial Window Preparation Enables In Vivo Observation Following Distal Middle Cerebral Artery Occlusion in Mice

Focal cerebral ischemia (i.e., ischemic stroke) may cause major brain injury, leading to a severe loss of neuronal function and consequently to a host of motor and cognitive disabilities. Its high prevalence poses a serious health burden, as stroke is among the principal causes of long-term disability and death worldwide1. Recovery of neuronal function is, in most cases, only partial. So far, treatment options are very limited, in particular due to the narrow time window for thrombolysis2,3. Determining methods to accelerate recovery from stroke remains a prime medical goal; however, this has been hampered by insufficient mechanistic insights into the recovery process. Experimental stroke researchers frequently employ rodent models of focal cerebral ischemia. Beyond the acute phase, stroke research is increasingly focused on the sub-acute and chronic phase following cerebral ischemia. Most stroke researchers apply permanent or transient occlusion of the MCA in mice or rats. In patients, occlusions of the MCA are among the most frequent causes of ischemic stroke4. Besides proximal occlusion of the MCA using the filament model, surgical occlusion of the distal MCA is probably the most frequently used model in experimental stroke research5. Occlusion of a distal (to the branching of the lenticulo-striate arteries) MCA branch typically spares the striatum and primarily affects the neocortex. Vessel occlusion can be permanent or transient. High reproducibility of lesion volume and very low mortality rates with respect to the long-term outcome are the main advantages of this model. Here, we demonstrate how to perform a chronic cranial window (CW) preparation lateral to the sagittal sinus, and afterwards how to surgically induce a distal stroke underneath the window using a craniotomy approach. This approach can be applied for sequential imaging of acute and chronic changes following ischemia via epi-illuminating, confocal laser scanning, and two-photon intravital microscopy.

Lateral Chronic Cranial Window Preparation Enables In Vivo Observation Following Distal Middle Cerebral Artery Occlusion in Mice

Surgical occlusion of a distal middle cerebral artery branch (MCAo) is a frequently used model in experimental stroke research. This manuscript describes the basic technique of permanent MCAo, combined with the insertion of a lateral cranial window, which offers the opportunity for longitudinal intravital microscopy in mice.

横向慢性颅窗口准备启用<em&gt;在体内</em&gt;观察继末节小鼠大脑中动脉闭塞

Focal cerebral ischemia (i.e., ischemic stroke) may cause major brain injury, leading to a severe loss of neuronal function and consequently to a host 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 ...

Combined Near-infrared Fluorescent Imaging and Micro-computed Tomography for Directly Visualizing Cerebral Thromboemboli

Direct thrombus imaging visualizes the root cause of thromboembolic infarction. Being able to image thrombus directly allows far better investigation of stroke than relying on indirect measurements, and will be a potent and robust vascular research tool. We use an optical imaging approach that labels thrombi with a molecular imaging thrombus marker&#160;&#8212; a Cy5.5 near-infrared fluorescent (NIRF) probe that is covalently linked to the fibrin strands of the thrombus by the fibrin-crosslinking enzymatic action of activated coagulation factor XIIIa during the process of clot maturation. A micro-computed tomography (microCT)-based approach uses thrombus-seeking gold nanoparticles (AuNPs) functionalized to target the major component of the clot: fibrin. This paper describes a detailed protocol for the combined in vivo microCT and ex vivo NIRF imaging of thromboemboli in a mouse model of embolic stroke. We show that in vivo microCT and fibrin-targeted glycol-chitosan AuNPs (fib-GC-AuNPs) can be used for visualizing both in situ thrombi and cerebral embolic thrombi. We also describe the use of in vivo microCT-based direct thrombus imaging to serially monitor the therapeutic effects of tissue plasminogen activator-mediated thrombolysis. After the last imaging session, we demonstrate by ex vivo NIRF imaging the extent and the distribution of residual thromboemboli in the brain. Finally, we describe quantitative image analyses of microCT and NIRF imaging data. The combined technique of direct thrombus imaging allows two independent methods of thrombus visualization to be compared: the area of thrombus-related fluorescent signal on ex vivo NIRF imaging vs. the volume of hyperdense microCT thrombi in vivo.

This protocol describes the application of combined near-infrared fluorescent (NIRF) imaging and micro-computed tomography (microCT) for visualizing cerebral thromboemboli. This technique allows the quantification of thrombus burden and evolution. The NIRF imaging technique visualizes fluorescently labeled thrombus in excised brain, while the microCT technique visualizes thrombus inside living animals using gold-nanoparticles.

结合近红外荧光成像和微计算机断层扫描直接可视化脑血栓

Direct thrombus imaging visualizes the root cause of thromboembolic infarction. Being able to image thrombus directly allows far better investigation of ...

Advanced Diffusion Imaging in The Hippocampus of Rats with Mild Traumatic Brain Injury

Mild traumatic brain injury (mTBI) is the most common type of acquired brain injury. Since patients with traumatic brain injury show a tremendous variability and heterogeneity (age, gender, type of trauma, other possible pathologies, etc.), animal models play a key role in unraveling factors that are limitations in clinical research. They provide a standardized and controlled setting to investigate the biological mechanisms of injury and repair following TBI. However, not all animal models mimic the diffuse and subtle nature of mTBI effectively. For example, the commonly used controlled cortical impact (CCI) and lateral fluid percussion injury (LFPI) models make use of a craniotomy to expose the brain and induce widespread focal trauma, which are not commonly seen in mTBI. Therefore, these experimental models are not valid to mimic mTBI. Thus, an appropriate model should be used to investigate mTBI. The Marmarou weight drop model for rats induces similar microstructural alterations and cognitive impairments as seen in patients who sustain mild trauma; therefore, this model was selected for this protocol. Conventional computed tomography and magnetic resonance imaging (MRI) scans commonly show no damage following a mild injury, because mTBI induces often only subtle and diffuse injuries. With diffusion weighted MRI, it is possible to investigate microstructural properties of brain tissue, which can provide more insight into the microscopic alterations following mild trauma. Therefore, the goal of this study is to obtain quantitative information of a selected region-of-interest (i.e., hippocampus) to follow up disease progression after obtaining a mild and diffuse brain injury.

The overall goal of this procedure is to obtain quantitative microstructural information of the hippocampus in a rat with mild traumatic brain injury. This is done using an advanced diffusion-weighted magnetic resonance imaging protocol and region-of-interest based analysis of parametric diffusion maps.

轻度创伤性脑损伤大鼠海马学的高级扩散成像

Mild traumatic brain injury (mTBI) is the most common type of acquired brain injury. Since patients with traumatic brain injury show a tremendous ...

Quantification of Cerebral Perfusion using Laser Speckle Imaging and Infarct Volume using MRI in a Pre-clinical Model of Posterior Circulation Stroke

Background: Basilar artery occlusion (BAO) is a subset of posterior circulation stroke that carries a mortality as high as 90%.&#160; The current clinical standard to diagnose ischemic stroke include computerized tomography (CT), CT angiography and perfusion and magnetic resonance imaging (MRI). Large animal pre-clinical models to accurately reflect the clinical disease as well as methods to assess stroke burden and evaluate treatments are lacking.
Methods: We describe a canine model of large vessel occlusion (LVO) stroke in the posterior circulation, and developed a laser speckle imaging (LSI) protocol to monitor perfusion changes in real time.&#160; We then utilized high b-value DWI (b=1800s/mm2) MRI to increase detection sensitivity. We also evaluated the ability of magnetic resonance angiography (MRA) to assess arterial occlusion and correlate with DSA. Finally, we verified infarct size from apparent diffusion coefficient (ADC) mapping with histology.&#160;
Results:&#160; Administration of thromboembolism occluded the basilar artery as tracked by DSA (n=7).&#160; &#160;LSI correlated with DSA, demonstrating a reduction in perfusion after stroke onset that persisted throughout the experiment, allowing us to monitor perfusion in real time.&#160; DWI with an optimized b-value for dogs illustrated the stroke volume and allowed us to derive ADC and magnetic resonance angiography (MRA) images. The MRA performed at the end of the experiment correlated with DSA performed after occlusion. Finally, stroke burden on MRI correlated with histology.
Conclusions: Our studies demonstrate real time perfusion imaging using LSI of a canine thromboembolic LVO model of posterior circulation stroke, which utilizes multimodal imaging important in the diagnosis and treatment of ischemic stroke.

A canine model of LVO stroke was utilized to develop laser speckle imaging to monitor cerebral perfusion in real-time.&#160; Diffusion-weighted MRI was optimized to image infarct volume utilizing a high b-value, enabling ADC and MRA, correlated with DSA at the time of stroke.&#160; Finally, ADC reconstructions correlated with histological findings.

Background: Basilar artery occlusion (BAO) is a subset of posterior circulation stroke that carries a mortality as high as 90%.&#160; The current clinical ...

评估皮层脑Microinfarcts高分辨率核磁共振图像

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