The authors have no acknowledgements.

这项研究是在所有参与中心经当地机构审查委员会。在多中心临床试验的所有受试者提供书面知情同意参与eTRIS在各自的机构。 1.图像采集<ol><li>执行使用专门的相控阵线圈MRV 1.5 T或3个T全身扫描仪的磁共振成像诸如末梢血管线圈，体基质线圈或径流线圈。与其他身体矩阵线圈或脊柱线圈一起使用这些线圈。如果没有合适的专门的线圈可用，用身体代替线圈。 注:使用市售的扫描仪，如西门子交响乐，奏鸣曲等。 <ol><li>屏幕主题，扫描前审查MRI安全调查问卷。有变更将成为一个袍子。 </li></ol></li><li>放置在受试者的注射造影剂的肘前静脉的静脉内线路。按照标准安全PROCedures注射钆造影剂。 </li><li>仰卧，在MRI机器和位置适当的线圈区域上脚先地位的地方接受扫描。安全使用的线圈绑带魔术贴需要。 <ol><li>法尔胜主体的腿/脚，以防止运动伪影在MRI扫描。 </li><li>打开定心激光和移动台，直到激光横梁就位于被检者的膝盖（髌骨）所示。接受这个位置的扫描的等角点移动患者台到扫描器孔的中心位置。 </li></ol></li><li>测量肌酐清除率（CrCl），并确定要用于根据受试者体重的造影剂的剂量。如果肌酐清除率&lt;30毫升/分钟，但被排除在研究。用于与CRCL"30毫升/分钟但小于45毫升/分钟的个人，0.01毫摩尔/千克的造影剂的使用。为个人提供的CrCl&gt;45毫升/分钟但&lt;60毫升/分钟，0.02毫摩尔/千克gadofo的sveset被注入。对于具有正常肾功能（肌酐清除率"60毫升/分钟）的个体，0.03毫摩尔/公斤（0.12毫升/公斤）gadofosveset磷酸三钠的剂量使用。一种MRI兼容动力注射器被用来将造影剂注入。 </li><li>如表1所示和在MRI方案一节中所述进行双腿和下部骨盆在单个检查会话持续大约60分钟的双侧成像。 注:匿名图像传送到一个​​中心芯实验室进行分析前的患者数据。 </li></ol> 2. MRI协议<ol><li>通过选择从协议窗口每个协议步骤，并将其拖动到执行列表执行从扫描器控制台成像协议。一旦准备就绪，按扫描/执行或等效按钮运行序列。 </li><li>获得2D梯度回波中旬小牛使用表1中的序列参数，在三个正交轴来基于图像序列上述髂嵴和使用作为本地化/侦察兵。 </li><li>如表1中指定执行的每个段中飞行（TOF）的血管造影扫描时间 注意:这些扫描也用作定位器，以区分从静脉动脉作为长循环的造影剂是用在稳定状态在此协议。这种观点动脉树是相当有限的，只是为了帮助图像分析员从静脉血管区分动脉和不作为一个成熟的血管造影。 </li><li>为了避免在采集成像体积的劣势和优越的程度较差的图像质量，收购三家冠状40厘米段脚在3D T1加权梯度回波扫描头方向×10厘米的重叠。 注意:这些三个段包括:一）中小腿到膝盖以上b）中膝盖大腿/下部骨盆和c）大腿/骨盆腹图1示出了样本图像与三个采集位置。说明。 </li><li>急慢性静脉血栓形成区分，收购T1W直接血栓成像（DTHI），并在表1中使用参数3D梯度回波（GRE）序列。 注意:这些3次扫描也可以作为对MRV收购预增强扫描。这些收购的覆盖程度是相同的，在图中所示的三个位置中获取的初始定位器1。GRE序列也对各种扫描平台和跨成像的场强容易实施的。 </li></ol><img alt="图1" src="/files/ftp_upload/52761/52761fig1.jpg" /> 图1:表示用于成像的3站采集地点样本图像的视图在冠状方向和轴向方向上的场为40cm的每个床位置[采集:（中小腿到膝盖以上），（以上膝盖大腿/骨盆），（大腿/骨盆<html>以腹部），每个床位之间10厘米重叠。 （ 一 ）轴向图像; （二）矢状图像和（c）冠状图像。红色箭头表示DVT。 <a href="https://www.jove.com/files/ftp_upload/52761/52761fig1highres.jpg" target="_blank">请点击此处查看该图的放大版本。</a> <ol start="6"><li>施用造影剂（gadofosveset磷酸三钠）以0.03毫摩尔/公斤（0.12毫升/千克）静脉内入受试者的剂量为2毫升/秒的速率，用20ml生理盐水冲洗。让造影剂循环5分钟，以确保在血池的稳定状态。 </li><li>获得MRV图像;在3个地点交造影3D梯度回波序列如前所述。 见表1和表2序列参数。使用这些图像，以确定所述血栓的位置和大小。 </li></ol>文件/ ftp_upload / 52761 / 52761table1.jpg"/&gt; 表1:用造影剂，gadofosveset磷酸三钠，包括直接血栓成像下肢磁共振造影协议。 <img alt="表2" src="/files/ftp_upload/52761/52761table2.jpg" /> 表2:在协议获取的每个序列的特定摄像参数。 <ol start="8"><li>扫描完成后，从核磁共振成像扫描仪主题，并采取了静脉线。要求如有更改了礼服和退出设施。 </li></ol> 3.图像分析<ol><li>执行图像分析的专用图像分析工作站运行FDA批准的开源图像处理软件如OsiriX MD 20上，由受过训练的2图像分析。确保分析师有一个最低的每次3年的工作经验。 </li><li>转移到图像之前短暂致盲所有图片分析师工作站进行分析。 </li><li>确保放射科医师评估为血栓的存在和位置的每个MRI扫描。提供放射科医师的评估到图像分析以用作整个分析的指导方针。 </li><li>通过选择"导入"加载从受试者到图像处理软件的两个MRI访问所有DICOM图像，并比较该两个成像的时间点的MRV系列的每个受试者，以确保整个时间点足够空间覆盖和注册。 <ol><li>选择浏览器的"3D MPR"工具提供图像数据的同时浏览的3正交视图（轴向，冠状，矢状和）。 注:该图像处理软件的3D MPR模式使感兴趣的血管的观看。 </li></ol></li><li>分析以下的船只，如果DVT存在:髂外，股总，股浅，股深，腘动脉​​，胫前，胫后I＆二，腓肠肌I＆II，和腓I＆II脉。所有分析仅限于存在于从两个时间点的图像的血管的区域。 </li><li>评估每个静脉与已知的DVT的图像的质量作为一个0-5级表示由放射科医生的评估，有0-2个是无法分析和3-5是可分析的同时为DTHI和MRV序列。对于评分系统的崩溃见图2。 </li></ol><img alt="图2" src="/files/ftp_upload/52761/52761fig2.jpg" /> 图2:用于评估图像的质量与已知的DVT每个感兴趣的静脉评分系统的崩溃。 <ol start="7"><li>对于MRV分析，逐一分析每个容器。经过三维曲面多平面重建，使用下面的每一个静脉，通过跟踪分析师的中心线轮廓，产生弯曲的路径，每个静脉并保存到文件。 <ol><li>建立在三维空间中的血栓的位置。从弯曲的MPR平面，3D贝塞尔路径将被显示出来。 </li><li>通过选择"创模"的"轮廓路径"工具划定静脉的中心线。 </li><li>地方点上反复任何正交的MPR视图拉直感兴趣的整个容器中。 </li><li>进行调整，必要时，以确保船舶完全伸直在"编辑模式" </li><li>当轮廓路径准确圈定在血管中心线，节省通过选择"曲线路径"图标导出文件</li><li>产生1毫米轴向切片垂直于弯曲路径并保存为DICOM文件（ 图3）。观察该曲线路径，拉直容器，以及相应的轴位图像从MRV图像量化DVT。 注:在3D曲面MPR阅读器渲染这些图像必须被我出口Ñ​​DICOM格式并添加到数据库中作为一个新的一系列图像。 </li></ol></li></ol><img alt="图3" src="/files/ftp_upload/52761/52761fig3.jpg" /> 图3:对MRV序列所示样品的DVT（ⅰ，左图）曲线路径（黄线）示出了轮廓随后静脉被分析。 （ 二 ，中间面板）整了整船只沿中心线船只被分析（红色虚线）（ 三 ，右图）显示轴位片垂直静脉用黄线（A，B，C）上的纵向部分指示的位置被分析。 <a href="https://www.jove.com/files/ftp_upload/52761/52761fig3highres.jpg" target="_blank">请点击此处查看该图的放大版本。</a> <ol start="7"><li><ol start="7"><li>对这些轴向DICOM图像，手动分段区域息，通过使用"封闭多边形的ROI工具"涵盖了血栓（ 见图4）。保存利益的地区，通过选择"保存此系列的所有ROI"位于"投资回报率"，以文件下拉菜单，节省投资回报率指标通过导航到"插件"菜单中，选择"工具的投资回报率"，其次是"出口的ROI "。这应该被保存在一个CSV格式。 </li></ol></li></ol><img alt="图4" src="/files/ftp_upload/52761/52761fig4.jpg" /> 图4:利息（绿色）手动分割区域显示包含在轴向格式化DICOM图像血栓 <a href="https://www.jove.com/files/ftp_upload/52761/52761fig4highres.jpg" target="_blank">请点击此处查看该图的放大版本。</a> <ol start="7"><li><ol start="8"><li>乘以芳计算血栓体积<html> EA通过使用内置MATLAB脚本定制的切片厚度（1毫米）每个切片分析上。通过在每个容器中加入血栓体积计算每个科目的总体积血栓。 </li></ol></li><li>对于DTHI分析，找出新鲜血栓明亮区域由MRV分割的DVT区域内造影前的T1W 3D梯度回波扫描13。 <ol><li>上轴向预对比度的图像，通过绘制的感兴趣区（ROI）手动如图5区域计算的新鲜血栓的体 ​​积。在图6中，表示DVT通过DTHI与MRV图像一起测量样本图像被描绘。 </li><li>打开彼此并排的造影前的和后的对比序列。选择"轴"的观点，并划定明亮区域的沿采用"封闭的多边形ROI工具"的船只。 </li></ol></li></ol>ES / ftp_upload / 52761 / 52761fig5.jpg"/&gt; 图5:对DTHI成像序列所示样品DVT（一 ）冠状图像，（B）轴向图像，和（c）的轴向图象，显示的兴趣（绿色）区域追踪预对比度图像周围新鲜血栓（蓝色箭头）。的DTHI图像获取的注入造影剂之前，依靠血栓的气象 - 血红蛋白含量，以产生亮信号。 <img alt="图6" src="/files/ftp_upload/52761/52761fig6.jpg" /> 图6:关于DTHI成像序列中所示样品的DVT左侧图板显示的MRV图像与表示总DVT（绿色箭头）信号空隙。相应DTHI图像明亮信号指示的新鲜血栓（蓝色箭头）存在右侧面板显示。 <a href="https://www.jove.com/files/ftp_upload/52761/52761fig6highres.jpg" target="_blank">请点击此处查看</a>更大的版本这个数字。 重现性4.评估<ol><li>评估十受试者的一个子集用于该分析的再现性。 </li><li>如上所述，通过两个独立的图像分析（伯和仲读者）评估观察者间变异性进行分析， </li><li>确保第一分析来评估结果的内观察员变异后三个月初级读者还执行第二图像分析。 </li><li>计算内部类相关系数（ICC）和执行奥特曼分析来评估国米和内部观察员可重复性。开展了一个样本t检验来寻找偏见奥特曼分析。 ICC&gt; 0.9和奥特曼分析没有偏差，被认为是可以接受的。 </li></ol>

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<li>Rosset, A., Spadola, L., Ratib, O. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((OsiriX%3A+an+open-source+software+for+navigating+in+multidimensional+DICOM+images%5BTitle%5D)+AND+%22J+Digit+Imaging%22%5BJournal%5D)">OsiriX: an open-source software for navigating in multidimensional DICOM images.</a> J Digit Imaging. 17, 205-216 (2004).</li>
<li>Ouriel, K., Greenberg, R. K., Green, R. M., Massullo, J. M., Goines, D. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((A+volumetric+index+for+the+quantification+of+deep+venous+thrombosis%5BTitle%5D)+AND+%22J+Vasc+Surg%22%5BJournal%5D)">A volumetric index for the quantification of deep venous thrombosis.</a> J Vasc Surg. 30, 1060-1066 (1999).</li>
<li>Elias, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((A+single+complete+ultrasound+investigation+of+the+venous+network+for+the+diagnostic+management+of+patients+with+a+clinically+suspected+first+episode+of+deep+venous+thrombosis+of+the+lower+limbs%5BTitle%5D)+AND+%22Thromb+Haemost%22%5BJournal%5D)">A single complete ultrasound investigation of the venous network for the diagnostic management of patients with a clinically suspected first episode of deep venous thrombosis of the lower limbs.</a> Thromb Haemost. 89, 221-227 (2003).</li>
<li>Farahmand, S., Farnia, M., Shahriaran, S., Khashayar, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((The+accuracy+of+limited+B-mode+compression+technique+in+diagnosing+deep+venous+thrombosis+in+lower+extremities%5BTitle%5D)+AND+%22Am+J+Emerg+Med%22%5BJournal%5D)">The accuracy of limited B-mode compression technique in diagnosing deep venous thrombosis in lower extremities.</a> Am J Emerg Med. 29, 687-690 (2011).</li>
<li>Thomas, S. M., Goodacre, S. W., Sampson, F. C., van Beek, E. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Diagnostic+value+of+CT+for+deep+vein+thrombosis%3A+results+of+a+systematic+review+and+meta-analysis%5BTitle%5D)+AND+%22Clin+Radiol%22%5BJournal%5D)">Diagnostic value of CT for deep vein thrombosis: results of a systematic review and meta-analysis.</a> Clin Radiol. 63, 299-304 (2008).</li>
<li>Heverhagen, J. T., Krombach, G. A., Gizewski, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Application+of+Extracellular+Gadolinium-based+MRI+Contrast+Agents+and+the+Risk+of+Nephrogenic+Systemic+Fibrosis%5BTitle%5D)+AND+%22Rofo%22%5BJournal%5D)">Application of Extracellular Gadolinium-based MRI Contrast Agents and the Risk of Nephrogenic Systemic Fibrosis.</a> Rofo. , (2014).</li>
<li>Alhadad, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Safety+aspects+of+gadofosveset+in+clinical+practice+-+analysis+of+acute+and+long-term+complications%5BTitle%5D)+AND+%22Magn+Reson+Imaging%22%5BJournal%5D)">Safety aspects of gadofosveset in clinical practice - analysis of acute and long-term complications.</a> Magn Reson Imaging. , (2014).</li>
</ol>

Venkatesh Mani has received research grants from Novartis. Nadia Alie, Sarayu Ramachandran, Cecilia Besa, Philip Robson and Bachir Taouli have nothing to disclose. Michele Mercuri and Michael Grosso are employees of Daiichi Sankyo. Greg Piazza has received research grants from Daiichi Sankyo, BMS, EKOS, and the Thrombosis Research Institute. Samuel Goldhaber has received grants from BMS, Daiichi Sankyo, EKOS, NHLBI and the Thrombosis Research Institute. He is a consultant for Ariad, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Genentech, Janssen, Merck, Pfizer and Portola. Zahi Fayad has received research grants from Daiichi Sankyo, Roche, GlaxoSmithKline, Merck, VBL Therapeutics, Novartis, Bristol-Myers Squibb, and Via Pharmaceuticals.

使用gadofosveset磷酸三钠作为造影剂，用分析的定量血栓的体积在多中心良好的重现性，本研究证实深静脉血栓形成的定量的可行性磁共振造影。要计算总成交量血栓的主要方法使用后对比MRV扫描来测量体积血栓。所使用的二次方法是直接血栓成像方法（DTHI），它利用会见血红蛋白的存在内的新鲜血栓产生一个明亮的信号在T1W MR图像13,14。在MRV音量措施高度重复性。该DTHI方法有较少的重现?...

静脉血栓栓塞（VTE）每年影响1在美国300,000-600,000人。深静脉血栓（DVT）是静脉血栓栓塞的最常见的表现，且最常见的影响小腿，大腿或盆腔静脉。诊断，管理和后续的科目DVT不能仅仅根据临床检查，因为这种疾病的症状和体征非特异性2,3。而验血（如D-二聚体）可以帮助排除DVT的诊断，成像要求建立DVT 4的存在。压缩超声（CUS）是目前在疑似急性DVT诊断中最常用的成像试验。 CUS价格低廉，具有较高的敏感性和特异性检测急性深静脉血栓形成5。然而，CUS不能可靠地评估深静脉肾盂6。此外，CUS不能直接量化血栓数量和组成，区分betw时非常重要EEN急性深静脉血栓形成和慢性DVT（不太可能栓塞）和治疗功效7的评价（肺栓塞（PE）的潜在来源）。 不像计算机断层扫描（CT），磁共振成像（MRI）不提供电离辐射，并且因此适合于串行检查以评价血栓进化或消退。与CUS相比，MRI可检测盆腔DVT和能够更精确地定义近端（腘静脉及以上）和远端腿（下面腘静脉）的DVT 8，以更好地评估PE的风险。 MRI可表征血栓的年龄和组织，并可能有助于慢性DVT 9-11（参更新）区分严重。血栓的体积，以评估治疗的疾病演变和响应的一个重要指标，定量与磁共振成像是可行的。当前的磁共振造影协议注射钆（Gd）造影剂12之后执行。这些小分子量分子迅速外渗注射后，并且需要仔细定时拍摄需要正确的形象化13,14血栓静脉强化阶段。 概念验证的研究，edoxaban减少血栓影像学研究（eTRIS），采用开放式标签设计，调查的疗效和每天10天edoxaban 90毫克，一次安全，其次是edoxaban 60毫克，每天一次治疗急性，症状性DVT（ClinicalTrials.gov标识符:NCT01662908）。 eTRIS地址是否edoxaban单一治疗，而没有伴随的低分子量肝素（LMW肝素）在开始治疗的时间，比用低分子量肝素/华法林治疗的受试者与DVT标准治疗更有效的评估，从百分比（％）变化在基线量血栓/尺寸（通过MRI测量）在14-21天。 eTRIS的另一个目标是开发和验证一个简单的MR在DVT血栓体积的量化静脉造影（MRV）的图像采集和分析的协议。为了克服所面临的多中心设置当前MRV协议的一些挑战，我们利用最近FDA批准的，长循环，钆血池造影剂（gadofosveset三钠）。相比，使用细胞外基于Gd的螯合物（ 例如，钆DTPA）为MRV，gadofosveset具有显著较长的循环时间，这允许使用更简单的MR采集方案，而不采集的任何定时。 Gadofosveset磷酸三钠是静脉注射后15,16循环2-3小时的血池MRI造影剂。它的安全性是类似于那些传统的血管外胞外MRI造影剂17。它使血管历时1小时的稳态成像。因此，图像采集不依赖于操作时序对比剂注射后是必需的。另外的优点使用这种造影剂的是，它是一个小分子（分子量857道尔顿）18，并可以渗透甚至完全闭塞血栓的两侧，从而提供了DVT的优异对比度从周围区域上的MRV和启用DVT的定量计算卷。以前的研究已经建立了使用使用gadofosveset磷酸三钠19卷MR插值屏气检查（VIBE）静脉造影可视化脉间信度。在这里，我们使用类似的方法在一个多中心临床试验的设置来评价深静脉血栓形成和使用的DVT通过MRI作为终点测量的音量。 eTRIS提供了理想的平台来评估这里提出的MRV成像方法的分析的可行性和再现性，使用长循环基于Gd的血池造影剂，用于评估DVT卷。我们还评估使用的直接血栓成像（DTHI）的方法来量化的新鲜DVT之前的程度在注射造影剂。 随机分组后在36小时首次进入edoxaban单药治疗组或肝素/华法林组，随机分组后14〜21天之间的第二:在研究过程中进行的两个MRI检查。所有图像的分析由集中式核心实验室进行。新鲜血栓体积是从一个直接血栓成像（DTHI）在腿部和下部骨盆注射任何造影剂之前进行计算。总血栓体积（新鲜和旧）由交对比度磁共振造影（MRV）的腿部和下部骨盆静脉的图像来计算。

<table><tbody><tr><td>Ablavar (gadofosveset trisodium)</td><td>Lantheus</td><td></td><td>Contrast Agent</td></tr><tr><td>1.5 T or 3 T Scanners</td><td>GE, Siemens, or Phillips</td><td></td><td>GE (Horizon, Signa, Hdx, 750), Siemens (Symphony, Avanto, Sonata, Trio, Aera) or Philips (Intera, Achieva)</td></tr></tbody></table>

a multicenter mri protocol for the evaluation and quantification of deep vein thrombosis

我们评估了磁共振造影（MRV）与gadofosveset量化总血栓量的变化作为一个多中心随机对照研究治疗效果的主要标准有肝素/华法林治疗方案为急性，症状性下肢深静脉血栓形成比较单一edoxaban（DVT方法）治疗。我们还用一个直接的血栓成像方法（DTHI，不使用造影剂），以量化新鲜血栓。然后，我们试图评估的分析方法，并采用3D磁共振造影和直接血栓成像的深静脉血栓形成的多中心试验设定的定量应用的可重复性。从参加edoxaban血栓减少影像学研究（eTRIS）中随机选择10个受试者，在整个下肢深静脉系统总血栓体积双侧定量。受试者采用3D-T1W梯度回波序列之前（直接成像牛逼hrombus成像，DTHI）和注射的0.03毫摩尔/千克gadofosveset磷酸三钠（磁共振造影，MRV）的后5分钟。在DVT对相应的轴向，弯曲的多平面重组图像的边缘由两名观察员手动划定获得静脉血栓的体积测量。 MRV被用于计算总的DVT体积，而DTHI用于计算新鲜血栓的体积。组内相关（ICC）和布兰德Altman分析进行对比国米和内部观察员变异分析。国际刑事法院间内和观察员变异性优（0.99和0.98，P &lt;0.001），与对MRV影像奥特曼分析没有偏向。对于DTHI图像，结果略低（ICC = 0.88和0.95，P &lt;0.001），与偏见对奥特曼地块国际观察员的结果。这项研究表明血栓量估计在使用MRV与gadofosveset磷酸三钠DVT的可行性，具有良好的区域内和在之三观察员重复性的多中心。

对于重复性的评估，基准的目的和后续扫描，汇集和分析不同的案件。从10个随机选择的科目（各2浏览次数），有59艘DVT使用MRV的方法确定29艘，确定了DTHI新鲜血栓。在对重复性指标分析这10个随机选择的科目的子集，没有船只DVT被认为是未分析的质量（定义为主观评分0-2为MRV和DTHI图像）。由MRV对比度测定的平均总血栓体积（与血栓识别每个单独的容器的体积的总和）为3.13±6.23厘米3为初?...

Watch this Scientific Journal Video about A Multicenter MRI Protocol for the Evaluation and Quantification of Deep Vein Thrombosis at JoVE.com

A Multicenter MRI Protocol for the Evaluation and Quantification of Deep Vein Thrombosis

The goal of this study is to use magnetic resonance venography with long-circulating gadolinium-based contrast agent and direct thrombus imaging for quantitative evaluation of DVT volume in a multicenter, clinical trial setting. Inter- and intra-observer variability assessments were conducted, and reproducibility of the protocol was determined.

深静脉血栓形成的评价和定量的多中心MRI协议

We evaluated a magnetic resonance venography (MRV) approach with gadofosveset to quantify total thrombus volume changes as the principal criterion for ...

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Research

JoVE Journal

Medicine

17.1K 次观看.  Icahn School of Medicine at Mount Sinai. The goal of this study is to use magnetic resonance venography with long-circulating gadolinium-based contrast agent and direct thrombus imaging for quantitative evaluation of DVT volume in a multicenter, clinical trial setting. Inter- and intra-observer variability assessments were conducted, and reproducibility of the protocol was determined.

视频: A Multicenter MRI Protocol for the Evaluation and Quantification of Deep Vein Thrombosis

Stenosis of the Inferior Vena Cava: A Murine Model of Deep Vein Thrombosis

Deep vein thrombosis (DVT) and its devastating complication, pulmonary embolism, are a severe health problem with high mortality. Mechanisms of thrombus formation in veins remain obscure. Lack of mobility (e.g., after surgery or long-haul flights) is one of the main factors leading to DVT. The pathophysiological consequence of the lack of mobility is blood flow stagnation in venous valves. Here, a model is described that mimics such flow disturbance as a thrombosis-driving factor. In this model, partial flow restriction (stenosis) in the inferior vena cava (IVC) is created. Closure of about 90% of the IVC lumen for 48 h results in development of thrombi structurally similar to those in humans. The similarities are: i) most of the thrombus volume is red, i.e., consists of red blood cells and fibrin, ii) presence of a white part (lines of Zahn), iii) non-denuded endothelial monolayer, iv) elevated plasma D-Dimer levels, and v) possibility to prevent thrombosis by low molecular weight heparin. Limitations include variable size of thrombi and the fact that a certain percentage of wild-type mice (0 - 35%) may not produce a thrombus. In addition to visual observation and measurement, thrombi may be visualized by non-invasive technologies, such as ultrasonography, which allows for monitoring the dynamics of thrombus development. At shorter time points (1 - 6 h), intravital microscopy may be applied to directly observe events (e.g., recruitment of cells to the vessel wall) preceding thrombus formation. Use of this method by several teams around the world has made it possible to uncover basic mechanisms of DVT initiation and identify potential targets that might be beneficial for its prevention.

We describe here stenosis in the inferior vena cava as a murine model of deep vein thrombosis. This model recapitulates blood flow restriction, one of the major triggers of venous thrombosis in humans.

下腔静脉狭窄: 深静脉血栓形成的小鼠模型

Deep vein thrombosis (DVT) and its devastating complication, pulmonary embolism, are a severe health problem with high mortality. Mechanisms of thrombus ...

科研

免疫与感染

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 ...

医学

Deep Vein Thrombosis Induced by Stasis in Mice Monitored by High Frequency Ultrasonography

Venous thrombosis is a common condition affecting 1 - 2% of the population, with an annual incidence of 1 in 500. Venous thrombosis can lead to death through pulmonary embolism or results in the post-thrombotic syndrome, characterized by chronic leg pain, swelling, and ulceration, or in chronic pulmonary hypertension resulting in significant chronic respiratory compromise. This is the most common cardiovascular disease after myocardial infarction and ischemic stroke and is a clinical challenge for all medical disciplines, as it can complicate the course of other disorders such as cancer, systemic disease, surgery, and major trauma.
Experimental models are necessary to study these mechanisms. The stasis model induces consistent thrombus size and a quantifiable amount of thrombus. However, it is necessary to systematically ligate side branches of the inferior vena cava to avoid variability in thrombus sizes and any erroneous data interpretation. We have developed a non-invasive technique to measure thrombus size using ultrasonography. Using this technique, we can assess thrombus development and resolution over time in the same animal. This approach limits the number of mice required for quantification of venous thrombosis consistent with the principle of replacement, reduction, and refinement of animals in research. We have demonstrated that thrombus weight and histological analysis of thrombus size correlate with measurement obtained with ultrasonography. Therefore, the current study describes how to induce deep vein thrombosis in mice using the inferior vena cava stasis model and how to monitor it using high frequency ultrasound.

The present protocol describes the steps to obtain venous thrombosis using a stasis model. In addition, we are using a non-invasive method to measure thrombus formation and resolution over time.

高频超声监测小鼠瘀血致深静脉血栓形成

Venous thrombosis is a common condition affecting 1 - 2% of the population, with an annual incidence of 1 in 500. Venous thrombosis can lead to death ...

In Vivo Tracking of Edema Development and Microvascular Pathology in a Model of Experimental Cerebral Malaria Using Magnetic Resonance Imaging

Cerebral malaria is a sign of severe malarial disease and is often a harbinger of death. While aggressive management can be life-saving, the detection of cerebral malaria can be difficult. We present an experimental mouse model of cerebral malaria that shares multiple features of the human disease, including edema and microvascular pathology. Using magnetic resonance imaging (MRI), we can detect and track the blood-brain barrier disruption, edema development, and subsequent brain swelling. We describe multiple MRI techniques that can visualize these pertinent pathological changes. Thus, we show that MRI represents a valuable tool to visualize and track pathological changes, such as edema, brain swelling, and microvascular pathology, in vivo.

In Vivo Tracking of Edema Development and Microvascular Pathology in a Model of Experimental Cerebral Malaria Using Magnetic Resonance Imaging

We describe a mouse model of experimental cerebral malaria and show how inflammatory and microvascular pathology can be tracked in vivo using magnetic resonance imaging.

使用磁共振成像实验性脑疟疾模型中的水肿发育​​和微血管病理学的体内追踪

Cerebral malaria is a sign of severe malarial disease and is often a harbinger of death. While aggressive management can be life-saving, the detection of ...

An In vitro System to Gauge the Thrombolytic Efficacy of Histotripsy and a Lytic Drug

Deep vein thrombosis (DVT) is a global health concern. The primary approach to achieve vessel recanalization for critical obstructions is catheter-directed thrombolytics (CDT). To mitigate caustic side effects and the long treatment time associated with CDT, adjuvant and alternative approaches are under development. One such approach is histotripsy, a focused ultrasound therapy to ablate tissue via bubble cloud nucleation. Pre-clinical studies have demonstrated strong synergy between histotripsy and thrombolytics for clot degradation. This report outlines a benchtop method to assess the efficacy of histotripsy-aided thrombolytic therapy, or lysotripsy.
Clots manufactured from fresh human venous blood were introduced into a flow channel whose dimensions and acousto-mechanical properties mimic an iliofemoral vein. The channel was perfused with plasma and the lytic&#160;recombinant tissue-type plasminogen activator. Bubble clouds were generated in the clot with a focused ultrasound source designed for the treatment of femoral venous clots. Motorized positioners were used to translate the source focus along the clot length. At each insonation location, acoustic emissions from the bubble cloud were passively recorded, and beamformed to generate passive cavitation images. Metrics to gauge treatment efficacy included clot mass loss (overall treatment efficacy), and the concentrations of D-dimer (fibrinolysis) and hemoglobin (hemolysis) in the perfusate. There are limitations to this in vitro design, including lack of means to assess in vivo side effects or dynamic changes in flow rate as the clot lyses. Overall, the setup provides an effective method to assess the efficacy of histotripsy-based strategies to treat DVT.

Histotripsy-aided lytic delivery or lysotripsy is under development for the treatment of deep vein thrombosis. An in vitro procedure is presented here to assess the efficacy of this combination therapy. Key protocols for the clot model, image guidance, and assessment of treatment efficacy are discussed.

测量组织直肠炎和莱蒂克药物血栓分析功效的体外系统

Deep vein thrombosis (DVT) is a global health concern. The primary approach to achieve vessel recanalization for critical obstructions is ...

生物工程

Quantitative MRI of Endothelial Permeability and (Dys)function in Atherosclerosis

Cardiovascular diseases are the leading causes of death worldwide. A permeable/leaky and dysfunctional endothelium is considered the earliest marker of vascular damage and thought to drive atherosclerosis. A method to identify these changes in vivo would be desirable in the clinic. Magnetic resonance imaging (MRI)-based tools and other technologies have enabled a profound understanding of the role of the endothelium in cardiovascular diseases and risk in vivo. There is, however, a need for reproducible and simple approaches for extracting quantifiable data reflective of endothelial damage from a single imaging study. A non-invasive, easy-to-implement, and quantitative MRI workflow was developed to acquire and analyze images that allow the quantification of two imaging biomarkers of arterial endothelial damage (leakiness/permeability and dysfunction). Here, the protocol describes the application of this method in the brachiocephalic artery of atherosclerotic ApoE-/- mice using a clinical MRI scanner. First, late gadolinium enhancement (LGE) and Modified Look-Locker Inversion Recovery (MOLLI) T1 mapping protocols to quantify endothelial leakage using an albumin-binding probe are described. Second, anatomic, and quantitative blood flow sequences to measure endothelial dysfunction, in response to acetylcholine are described. Importantly, the method outlined here allows the acquisition of high-spatial-resolution 3D images with large volumetric coverage enabling accurate segmentation of vessel wall structures to improve inter- and intra-observer variability and to increase reliability and reproducibility. Additionally, it provides quantitative data without the need for high-temporal resolution for complex kinetic modeling, making it model-independent and even allowing for imaging of highly mobile vessels (coronary arteries). Therefore, the approach simplifies and expedites data analysis. Finally, this method can be implemented on different scanners, can be extended to image different arterial beds, and is clinically applicable for use in humans. This method could be used to diagnose and treat patients with atherosclerosis by adopting a precision-medicine approach.

<meta charset="utf8"></head><body>动脉粥样硬化内皮通透性和功能障碍的定量 MRI

We have developed an accurate, non-invasive, and easy-to-use method to quantify endothelial permeability and dysfunction in the arteries using Magnetic Resonance Imaging (MRI), named qMETRIC. This technique enables assessing vascular damage and cardiovascular risk associated with atherosclerosis in preclinical models and humans.

动脉粥样硬化内皮通透性和（不良）功能的定量 MRI

Cardiovascular diseases are the leading causes of death worldwide. A permeable/leaky and dysfunctional endothelium is considered the earliest marker of ...

Cardiac Magnetic Resonance for the Evaluation of Suspected Cardiac Thrombus: Conventional and Emerging Techniques

We present the conventional cardiac magnetic resonance (CMR) protocol for evaluating a suspected thrombus and highlight emerging techniques.&#160;The appearance of a mass on certain magnetic resonance (MR) sequences can help differentiate a thrombus from competing diagnoses such as a tumor. T1 and T2 signal characteristics of a thrombus are related to the evolution of hemoglobin properties. A thrombus typically does not enhance following contrast administration, which also helps differentiation from a tumor. We also highlight the emerging role of T1 mapping in the evaluation of a thrombus, which can add another level of support in diagnosis. Prior to any CMR exam, patient screening and interviews are critical to ensure safety and to optimize patient comfort. Effective communication during the exam between the technologist and the patient promotes proper breath holding technique and higher quality images. Volumetric post processing and structured reporting are helpful to ensure that the radiologist answers the ordering services&#39; question and communicates these results effectively. Optimal pre-MR safety evaluation, CMR exam execution, and post exam processing and reporting allow for delivery of high quality radiological service in the evaluation of a suspected cardiac thrombus.

The goal of this article is to describe how cardiac magnetic resonance can be used for the evaluation and diagnosis of a suspected cardiac thrombus. The method presented will describe data acquisition as well as the pre-procedure and post-procedure protocol.

心脏磁共振评估疑似心脏血栓:常规和新兴技术

We present the conventional cardiac magnetic resonance (CMR) protocol for evaluating a suspected thrombus and highlight emerging techniques.&#160;The ...

Image Acquisition Method for the Sonographic Assessment of the Inferior Vena Cava

Over the past several decades, clinicians have incorporated several applications of diagnostic point-of-care ultrasound (POCUS) into medical decision-making. Among the applications of POCUS, imaging the inferior vena cava (IVC) is practiced by a wide variety of specialties, such as nephrology, emergency medicine, internal medicine, critical care, anesthesiology, pulmonology, and cardiology. Although each specialty uses IVC data in slightly different ways, most medical specialties, at minimum, attempt to use IVC data to make predictions about intravascular volume status. While the relationship between IVC sonographic data and intravascular volume status is complex and highly context-dependent, all clinicians should collect the sonographic data in standardized ways to ensure repeatability. This paper describes standardized IVC image acquisition including patient positioning, transducer selection, probe placement, image optimization, and the pitfalls and limitations of IVC sonographic imaging.&#160;This paper also describes the commonly performed anterior IVC long-axis view and three other views of the IVC that can each provide helpful diagnostic information when the anterior long-axis view is difficult to obtain or interpret.

Point-of-care ultrasound evaluation of the inferior vena cava (IVC) is commonly utilized to identify, among other things, the volume status. Imaging should be performed systematically to ensure repeatability. This manuscript reviews the methods and pitfalls of sonographic IVC examination.

一种下腔静脉超声评估的图像采集方法

Over the past several decades, clinicians have incorporated several applications of diagnostic point-of-care ultrasound (POCUS) into medical ...

Point-Of-Care Ultrasound Screening for Proximal Lower Extremity Deep Venous Thrombosis

Acute lower extremity deep venous thrombosis (DVT) is a serious vascular disorder that requires accurate and early diagnosis to prevent life-threatening sequelae. While whole leg compression ultrasound with color and spectral Doppler is commonly performed in radiology and vascular labs, point-of-care ultrasound (POCUS) is becoming more common in the acute care setting. Providers appropriately trained in focused POCUS can perform a rapid bedside examination with high sensitivity and specificity in critically ill patients. This paper describes a simplified yet validated approach to POCUS by describing a three-zone protocol for lower extremity DVT POCUS image acquisition. The protocol explains the steps in obtaining vascular images at six compression points in the lower extremity. Beginning at the level of the proximal thigh and moving distally to the popliteal space, the protocol guides the user through each of the compression points in a stepwise manner: from the common femoral vein to the femoral and deep femoral vein bifurcation, and, finally, to the popliteal vein. Further, a visual aid is provided that may assist providers during real-time image acquisition. The goal in presenting this protocol is to help make proximal lower extremity DVT exams more accessible and efficient for POCUS users at the patient&#39;s bedside.

Traditionally, lower extremity deep venous thrombosis (DVT) is diagnosed by radiology-performed venous duplex ultrasound. Providers appropriately trained in focused point-of-care ultrasound (POCUS) can perform a rapid bedside examination with high sensitivity and specificity in critically ill patients. We describe the scanning technique for focused POCUS DVT lower extremity examination.

下肢近端深静脉血栓形成的即时超声筛查

Acute lower extremity deep venous thrombosis (DVT) is a serious vascular disorder that requires accurate and early diagnosis to prevent life-threatening ...

深静脉血栓形成的评价和定量的多中心MRI协议

摘要

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下腔静脉狭窄: 深静脉血栓形成的小鼠模型

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

高频超声监测小鼠瘀血致深静脉血栓形成

使用磁共振成像实验性脑疟疾模型中的水肿发育和微血管病理学的体内追踪

测量组织直肠炎和莱蒂克药物血栓分析功效的体外系统

动脉粥样硬化内皮通透性和（不良）功能的定量 MRI

动脉粥样硬化内皮通透性和（不良）功能的定量 MRI

心脏磁共振评估疑似心脏血栓:常规和新兴技术

一种下腔静脉超声评估的图像采集方法

下肢近端深静脉血栓形成的即时超声筛查

深静脉血栓形成的评价和定量的多中心MRI协议

摘要

探索更多视频

下腔静脉狭窄: 深静脉血栓形成的小鼠模型

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

高频超声监测小鼠瘀血致深静脉血栓形成

使用磁共振成像实验性脑疟疾模型中的水肿发育​​和微血管病理学的体内追踪

测量组织直肠炎和莱蒂克药物血栓分析功效的体外系统

动脉粥样硬化内皮通透性和（不良）功能的定量 MRI

动脉粥样硬化内皮通透性和（不良）功能的定量 MRI

心脏磁共振评估疑似心脏血栓:常规和新兴技术

一种下腔静脉超声评估的图像采集方法

下肢近端深静脉血栓形成的即时超声筛查

使用磁共振成像实验性脑疟疾模型中的水肿发育和微血管病理学的体内追踪