Name: noninvasive assessment of cardiac abnormalities in experimental autoimmune myocarditis by magnetic resonance microscopy imaging in the mouse
Uploaded: 2014-06-20T15:00:00.000+00:00
Duration: 12 min 24 s
Description: Watch this Scientific Journal Video about Noninvasive Assessment of Cardiac Abnormalities in Experimental Autoimmune Myocarditis by Magnetic Resonance Microscopy Imaging in the Mouse at JoVE.com

This work was supported by the National Institutes of Health (HL114669). CM is a recipient of a postdoctoral research fellowship grant awarded by the Myocarditis Foundation, NJ.

操守准则: 所有动物的程序均按照实验动物的护理和使用的指导原则进行，并经内布拉斯加林肯，内布拉斯加州林肯大学。 1，诱导实验性自身免疫性心肌炎<ol><li>通过在1x磷酸盐缓冲盐水中，以2 mg/1.5 ml的终浓度溶解MYHC-α334-352制备肽溶液。 </li><li>加入1无菌的1×PBS中的溶液，以含50μg冻干的PT，得到储备液浓度为50纳克/微升的小瓶中制备的百日咳毒素（PT）。取20微升的股票进入无菌1.5mL管中，加入980微升无菌1X PBS中，获得1纳克/微升的工作浓度。 </li><li>通过添加40毫克结核分枝杆菌 H37Rv的制备完全弗氏佐剂（CFA）（MTB）提取至10ml CFA，得到的终浓度5毫克/毫升。 </li><li>准备肽终审法院乳液。注:对于EAM感应，肽终审法院乳液给予150微升含100微克MYHC-α每334-352动物。例如，免疫10小鼠应用1.5毫升含1毫克MYHC-α334-352的肽-CFA乳液。 <ol><li>为了制备1.5ml乳液，分装750微升的MYHC-α334-352肽溶液在一个1.5mL管中，和CFA辅以山地车到另一个1.5mL管中。使用3毫升鲁尔乐注射器，吸取上述肽溶液第一，其次是终审法院/ MTB提取物。 </li><li>连接注射器向3路活塞和活栓的另一出口连接到一个空3毫升注射器。调节活塞的通畅使肽混合物，终审法院从一个注射器流向其他与合理性好。 </li><li>通过反复按压的内容从一个针筒到另一为〜1分钟，然后将整个组件在冰上〜3分钟混合。重复此程序至少10倍。 </li><li>通过仔细地放置一个极小的液滴上的静水中的100毫升的玻璃烧杯中，测定该乳液的一致性。液滴预计不会分散在水中。如果这样做，继续混合，直至所需的一致性的实现。 </li><li>从3毫升注射器转移乳剂的内容到1毫升Luer-Lok接头的注射器通过更换附加到与1-ml注射器的活塞的两个3毫升的注射器中的一个，并附加一个27½号针头至1ml注射器的。 </li></ol></li><li>注入150μL肽终审法院乳液的分割剂量皮下注射在六到八周龄雌性的A / J小鼠（〜每75微升）两腹股沟区域。 </li><li>施用100μl的PT悬浮液（100毫微克）的腹腔内每只动物在第0天和第2天免疫后。 </li><li>通过施用150微升肽终审法院乳液的分割剂量皮下注射入T的两侧，重复第7天免疫程序他胸骨（〜75每微升）。准备这个乳液新鲜如上。然后，在第21天，若使动物MRM成像，见步骤3。 </li></ol> 2，动物处理<ol><li>将每个小鼠在含有2％异氟醚-空气混合物与加热垫置于下方，以保持温暖麻醉诱导室，以及动物转移到一个专门设计的动物固定器（ 图1）。 </li><li>固定化的动物中的动物支架俯卧位，以便其口鼻部配合到鼻锥维持麻醉（ 图1）。固定小鼠的头部与一个咬合杆连接到鼠标的门牙。 </li><li>打开空气吹加热器插在扫描仪的垂直孔中，以在实验过程中保持动物的体温其出口软管。 </li><li>维持麻醉以0.5〜2％异氟烷以2 ml / min的整个成像会话期间的流速。确认用脚趾掐法麻醉，没有动静预期。 </li><li>设置的充气枕头传感器，鼠尾/踝光纤脉搏血氧饱和度传感器，和直肠温度探头监控呼吸，心脏速率和体温，分别为（ 图1）。注:心脏门控是通过脉搏血氧饱和度，这使得无创监测动脉血氧饱和度进行。脉搏血氧饱和度传感器应安装在左侧踝关节和脚应该固定用螺纹环和录音保持在传感器的脚踝。 MRM成像是通过选通的呼吸和心脏信号，而无需使用任何造影剂来实现。 </li></ol> 3，图像采集<ol><li>制备动物（ 图1）后，将鼠标在MRM扫描仪的中心，定位在视场（FOV），其中磁场均匀性是最大的中心心脏。注:大口径（89毫米）9.4Ŧ垂直孔磁铁装有100克/厘米三重轴梯度和一个4厘米无线电频率（RF）的成像线圈，是用于获得高分辨率的三维（3D）图像。注意:一定要非磁性物料中使用核磁共振成像扫描仪的时候。 </li><li>运行成像接口，并从"学习选项"菜单中选择"新探"。输入"mtune中"，在命令栏并运行它拉上了"调整图形用户界面"。然后选择"开始探头调整"，并点击"自动缩放"按钮。该调整GUI将改为显示RFsignal。使用远程调谐/匹配旋钮在线圈调谐RF线圈的质子共振频率（400兆赫）的端部。在"开始"选项卡进入"预扫描"页面通过点击相关按钮来运行的频率和功率校准。打标签的"学习垫片"的标签"&#39;上的XYZ（快速）按钮拉起垫补页面。转到垫片页面，选择所有的迭代，并创下垫片按钮来进行自动匀场。 </li><li>从成像界面中的"研究"选项卡本地化的小鼠心脏中选择一个侦察兵序列。在"采集"选项卡改变视场为35 mm 2，保持机器的默认设置。单击开始运行序列;调节动物座的位置，如果心脏是不是在视场中心，重新调谐射频线圈，并再次获得了球探的图像。 </li><li>点击"分析"选项卡上的"宝石"序列按钮，然后输入相应的"采集"选项卡上的采集参数，以获得两个正交平面沿短轴和心脏20,21的长轴。注:典型的采集参数的梯度回波扫描是:切片厚度1毫米;重复时间（TR），200毫秒;回波时间（TE），2.67毫秒（最小）;翻转角，25°;面内矩阵大小，128×128; FOV，22毫米2;多项收购，4;和1分30秒的一个近似的采集时间。 </li><li>在"高级"选项卡中选中"CINE"序列收集脉搏血氧仪门控短轴电影MR图像以测量左室解剖和功能参数。调整成像片的基础上，心脏的鼠标悬停和拖拽长轴切面的位置和角度。进入"采集"选项卡上的成像参数，以获得梯度回波电影序列:TR，500毫秒; TE，5毫秒; FOV 22 平方毫米;采集矩阵256×256;切片厚度为1mm;多项收购，8;帧数，6;和〜17分钟的采集时间。单击开始开始收购。 </li><li>转换使用图像处理软件的"I / O"选项卡将采集的图像以DICOM格式和相应的文件传输到数据中心进行处理。 </li><li>在成像过程结束时，所有嗷嗷小鼠从麻醉中的过滤器顶笼子内恢复。不要让老鼠无人看管，直到他们重新获得足够的意识，保持胸骨斜卧，并根据需要让他们继续深造。 </li></ol> 4，数据的心脏核磁共振显微成像分析<ol><li>使用分部软件分析的LV 19的解剖和功能参数。通过加载DICOM格式的电影影像到软件中使用"打开图像文件（S）"中的"文件"菜单的子菜单。在GUI上选择"MRGE&#39;作为成像技术，"日比"作为图像类型和&#39;短轴中心"作为图像视图平面。 </li><li>指定的时间范围，通过用于舒张末期和收缩末期的"设置当前期限为舒张末期"和"设置当前期限为收缩末期"分别在"编辑"菜单的子菜单。 </li><li>首先单击"LV"命令按钮，然后单击"远藤"和右下角面板上的"盈"命令按钮手动分别绘制左心室心内膜和心外膜。通过按相应的命令按钮，以增加计算的精度除去乳头肌。 </li><li>阅读LV的量化参数，如左室舒张末期容积，收缩末期容积，每搏输出量，以及右上角的面板上射血分数。点击"杂项"命令按钮，然后单击"测量卡尺"命令按钮来测量左室参数，如壁厚和心室内径22。 </li><li>单击"文件"菜单中的"保存两个图像堆栈和分割"子菜单来保存图像，包括分割，在&#39;垫&#39;格式需要重新处理的图像。 </li></ol>

<ol>
	<li>Heidenreich, 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=Forecasting+the+future+of+cardiovascular+disease+in+the+United+States:+a+policy+statement+from+the+American+Heart+Association.">Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart Association.</a> Circulation. 123 (8), 933-944 (2011).</li><li>Fujinami, R. S., 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=Molecular+mimicry,+bystander+activation,+or+viral+persistence:+infections+and+autoimmune+disease.">Molecular mimicry, bystander activation, or viral persistence: infections and autoimmune disease.</a> Clin Microbiol Rev. 19 (1), 80-94 (2006).</li><li>Cihakova, D., Rose, N. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pathogenesis+of+myocarditis+and+dilated+cardiomyopathy.">Pathogenesis of myocarditis and dilated cardiomyopathy.</a> Adv Immunol. 99, 95-114 (2008).</li><li>Donermeyer, D. 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=Myocarditis-inducing+epitope+of+myosin+binds+constitutively+and+stably+to+I-Ak+on+antigen-presenting+cells+in+the+heart.">Myocarditis-inducing epitope of myosin binds constitutively and stably to I-Ak on antigen-presenting cells in the heart.</a> J Exp Med. 182 (5), 1291-1300 (1995).</li><li>Gangaplara, 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=Coxsackievirus+B3+infection+leads+to+the+generation+of+cardiac+myosin+heavy+chain-alpha-reactive+CD4+T+cells+in+A/J+mice.">Coxsackievirus B3 infection leads to the generation of cardiac myosin heavy chain-alpha-reactive CD4 T cells in A/J mice.</a> Clin Immunol. 144 (3), 237-249 (2012).</li><li>Huber, S. A., Lodge, P. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Coxsackievirus+B-3+myocarditis+in+Balb/c+mice.+Evidence+for+autoimmunity+to+myocyte+antigens.">Coxsackievirus B-3 myocarditis in Balb/c mice. Evidence for autoimmunity to myocyte antigens.</a> Am J Pathol. 116 (1), 21-29 (1984).</li><li>Massilamany, 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=Identification+of+novel+mimicry+epitopes+for+cardiac+myosin+heavy+chain-alpha+that+induce+autoimmune+myocarditis+in+A/J+mice.">Identification of novel mimicry epitopes for cardiac myosin heavy chain-alpha that induce autoimmune myocarditis in A/J mice.</a> Cell Immunol. 271, 438-449 (2011).</li><li>Pummerer, C. 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=Identification+of+cardiac+myosin+peptides+capable+of+inducing+autoimmune+myocarditis+in+BALB/c+mice.">Identification of cardiac myosin peptides capable of inducing autoimmune myocarditis in BALB/c mice.</a> J Clin Invest. 97 (9), 2057-2062 (1996).</li><li>Rose, N. R., Hill, S. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+pathogenesis+of+postinfectious+myocarditis.">The pathogenesis of postinfectious myocarditis.</a> Clin Immunol Immunopathol. 80, (1996).</li><li>Saraste, 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=Coronary+flow+reserve+and+heart+failure+in+experimental+coxsackievirus+myocarditis.+A+transthoracic+Doppler+echocardiography+study.">Coronary flow reserve and heart failure in experimental coxsackievirus myocarditis. A transthoracic Doppler echocardiography study.</a> Am J Physiol Heart Circ Physiol. 291, (2006).</li><li>Altes, T. 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=Hyperpolarized+3He+MR+lung+ventilation+imaging+in+asthmatics:+preliminary+findings.">Hyperpolarized 3He MR lung ventilation imaging in asthmatics: preliminary findings.</a> J Magn Reson Imaging. 13 (3), 378-384 (2001).</li><li>Driehuys, B., 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=Small+animal+imaging+with+magnetic+resonance+microscopy.">Small animal imaging with magnetic resonance microscopy.</a> ILAR J. 49 (1), 35-53 (2008).</li><li>Smith, B. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Magnetic+resonance+microscopy+with+cardiovascular+applications.">Magnetic resonance microscopy with cardiovascular applications.</a> Trends Cardiovasc Med. 6 (8), 247-254 (1996).</li><li>Potter, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Magnetic+resonance+microscopy+approaches+to+molecular+imaging:+sensitivity+vs+specificity.">Magnetic resonance microscopy approaches to molecular imaging: sensitivity vs specificity.</a> J Cell Biochem Suppl. 39, 147-153 (2002).</li><li>Benveniste, H., Blackband, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=MR+microscopy+and+high+resolution+small+animal+MRI:+applications+in+neuroscience+research.">MR microscopy and high resolution small animal MRI: applications in neuroscience research.</a> Prog Neurobiol. 67, 393-420 (2002).</li><li>Epstein, F. H., 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=MR+tagging+early+after+myocardial+infarction+in+mice+demonstrates+contractile+dysfunction+in+adjacent+and+remote+regions.">MR tagging early after myocardial infarction in mice demonstrates contractile dysfunction in adjacent and remote regions.</a> Magn Reson Med. 48 (2), 399-403 (2002).</li><li>Gewalt, S. 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=MR+microscopy+of+the+rat+lung+using+projection+reconstruction.">MR microscopy of the rat lung using projection reconstruction.</a> Magn Reson Med. 29 (1), 99-106 (1993).</li><li>Kern, M. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> The cardiac catheterization handbook., Edn 5th. , (2011).</li><li>Heiberg, E., 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=Design+and+validation+of+Segment--freely+available+software+for+cardiovascular+image+analysis.">Design and validation of Segment--freely available software for cardiovascular image analysis.</a> BMC Med Imaging. 10, (2010).</li><li>Cranney, G. B., 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=Left+ventricular+volume+measurement+using+cardiac+axis+nuclear+magnetic+resonance+imaging.+Validation+by+calibrated+ventricular+angiography.">Left ventricular volume measurement using cardiac axis nuclear magnetic resonance imaging. Validation by calibrated ventricular angiography.</a> Circulation. 82 (1), 154-163 (1990).</li><li>Hiba, B., 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=Cardiac+and+respiratory+double+self-gated+cine+MRI+in+the+mouse+at+7+T.">Cardiac and respiratory double self-gated cine MRI in the mouse at 7 T.</a> Magn Reson Med. 55 (3), 506-513 (2006).</li><li>Bryant, D., 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=Cardiac+failure+in+transgenic+mice+with+myocardial+expression+of+tumor+necrosis+factor-alpha.">Cardiac failure in transgenic mice with myocardial expression of tumor necrosis factor-alpha.</a> Circulation. 97 (14), 1375-1381 (1998).</li><li>Neu, N., 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=Cardiac+myosin-induced+myocarditis+as+a+model+of+postinfectious+autoimmunity.">Cardiac myosin-induced myocarditis as a model of postinfectious autoimmunity.</a> Eur Heart J. 12 Suppl D, 117-120 (1991).</li><li>Neumann, D. 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=Induction+of+multiple+heart+autoantibodies+in+mice+with+coxsackievirus+B3-+and+cardiac+myosin-induced+autoimmune+myocarditis.">Induction of multiple heart autoantibodies in mice with coxsackievirus B3- and cardiac myosin-induced autoimmune myocarditis.</a> J Immunol. 152 (1), 343-350 (1994).</li><li>Rose, N. 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=Postinfectious+autoimmunity:+two+distinct+phases+of+coxsackievirus+B3-induced+myocarditis.">Postinfectious autoimmunity: two distinct phases of coxsackievirus B3-induced myocarditis.</a> Ann N Y Acad Sci. 475, 146-156 (1986).</li><li>Farmer, J. B., Levy, G. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+simple+method+for+recording+the+electrocardiogram+and+heart+rate+from+conscious+animals.">A simple method for recording the electrocardiogram and heart rate from conscious animals.</a> Br J Pharmacol Chemother. 32 (1), 193-200 (1968).</li></ol>

No conflicts of interests were declared.

这项研究描述为一种非侵入性工具，以确定心脏异常的影响与自身免疫性心肌炎小鼠的MRM过程及其效用。由于EAM的组织学特征类似于人类感染后心肌炎小鼠模型通常用来描绘心肌损伤23-25 ​​的免疫机制。但是，患有心肌炎动物出现临床表现正常，诊断是基于在组织学实验7终止进行。动物通常是牺牲在21天接种后。评估这样的疾病过程在单个时间点的限制使用这些模型，尤其是在...

心脏衰竭是死亡的主要原因，心肌炎是心脏衰竭的青春少年1一个最主要的原因。患有心肌炎患者大多没有症状和疾病自发缓解2。然而，那些受影响的10-20％可发展为慢性疾病，导致扩张性心肌病（DCM）3。各种动物模型已经发展到研究心肌炎的免疫发病机制。这种疾病可以通过免疫动物与心肌肌球蛋白重链（MYHC）-α或其免疫显性肽片段或通过与病原体如柯萨奇病毒B3 4-9感染诱导的心肌炎敏感的A / J和Balb / c小鼠。这项研究涉及MYHC-α在A / J小鼠334-352引起的心肌炎。尽管显示心肌浸润，心肌炎影响的动物出现临床表现正常;诊断依据心脏炎症7的组织学评价ND超声心动图10。 磁共振显微镜（MRM）是一种常用的方法，得到心血管成像具有高分辨率的三维平面上，允许的功能细节，以评估微小血管的水平（高达10微米直径），但分辨能力的这种电平是无法实现与常规的磁共振成像（MRI）扫描程序，其中，该分辨率通常是获得可达1毫米11-14。 MRM提供了一个优点，因为它允许获得的高分辨率图像，以及在疾病过程14的早期时间点获得的性能参数。在临床上，MRM成像已被广泛应用于研究的病变心脏，肺或脑部15-17功能参数。在这项研究中，显示了一个使用MRM技术作为一种非侵入性工具，以确定受影响的自身免疫性心肌炎的A / J小鼠的心脏异常。具体来说，T他MRM成像允许的功能参数如左室（LV）舒张末期容积和射血分数（EF）以合理的准确性18定量。各参数的定义如下:LV舒张末期容积，血容量在左心室的舒张周期的结束，和射血分数，每搏输出量/舒张末期容积。使用对通过磁共振扫描器19获取的处理符合DICOM标准的心血管图像而开发的免费提供的分类软件进行数据分析。该数据显示在心肌炎动物的增加左心室壁的厚度，对应于左室舒张末期容积，每搏输出量和射血分数下降，与健康小鼠这些功能参数进行比较。

<table><tbody><tr><td>Myhc-a 334-352 (DSAFDVLSFTAEEKAGVYK)</td><td>Neopeptide, Cambridge, MA</td><td></td><td>Store at 4 &amp;#176;C</td></tr><tr><td>CFA</td><td>Sigma Aldrich, St Louis, MO</td><td>5881</td><td>Store at 4 &amp;#176;C</td></tr><tr><td>MTB H37Rv extract</td><td>Difco Laboratories, Detroit, MI</td><td>231141</td><td>Store at 4 &amp;#176;C</td></tr><tr><td>PT</td><td>List Biologicals Laboratories, Campbell, CA</td><td>181</td><td>Store at 4 &amp;#176;C</td></tr><tr><td>1x PBS</td><td>Corning, Manassas, VA</td><td>21-040-CV</td><td>Store at 4 &amp;#176;C</td></tr><tr><td>Isoflurane</td><td>Piramal Healthcare, Mumbai, India</td><td>NDC66794-013-25</td><td></td></tr><tr><td>Female A/J mice</td><td>Jackson Laboratories, Bar Harbor, ME</td><td>646</td><td></td></tr><tr><td>Luer-lok sterile 1 ml syrringe</td><td>BD, Franklin Lakes, NJ</td><td>309628</td><td></td></tr><tr><td>Luer-lok sterile 3 ml syrringe</td><td>BD, Franklin Lakes, NJ</td><td>309657</td><td></td></tr><tr><td>Sterile needle, 18 G</td><td>BD, Franklin Lakes, NJ</td><td>305195</td><td></td></tr><tr><td>Sterile needle, 27 1/2 G</td><td>BD, Franklin Lakes, NJ</td><td>305109</td><td></td></tr><tr><td>3-way stopcock</td><td>Smiths Medical ASD, Inc. Dublin, OH</td><td>MX5311L</td><td></td></tr><tr><td>Kerlix gauze bandage rolls</td><td>Covidien, Mansfield, MA</td><td>6720</td><td></td></tr><tr><td>Kimwipes</td><td>Kimberly-Clark Professional, Roswell, GA</td><td>34155</td><td></td></tr><tr><td>Protouch Stockinette</td><td>Medline Industries, Mundelein, IL</td><td>30-1001</td><td></td></tr><tr><td>Sterile surgical scissors and forceps</td><td>INOX tool Corporation</td><td></td><td></td></tr><tr><td>Micro oven</td><td>GE Healthcare,&amp;nbsp;</td><td></td><td></td></tr><tr><td>ThermiPAQ hot and cold therapy system&amp;nbsp;</td><td>Theramics Corporation, Springfield, IL</td><td></td><td></td></tr><tr><td>Reptile heating lamp</td><td>Energy Savers Unlimited, Inc. Carson, CA</td><td></td><td></td></tr><tr><td>3M Transpore tapes</td><td>Target Corporation, MN</td><td></td><td></td></tr><tr><td>Up and Up Polymyxin B sulfate/Bacitracin/Neomycin sulfate antibiotic ointment</td><td>Target Corporation, MN</td><td></td><td></td></tr><tr><td>North Safety DeciDamp-2PVC foam ear plugs</td><td>North Safety Products, Smithfield, RI</td><td></td><td></td></tr><tr><td>Cotton tipped applicator, 6&amp;rsquo;&amp;rsquo; wooden stem&amp;nbsp;</td><td>Jorgensen Laboratories, Inc. Loveland, CO</td><td></td><td></td></tr><tr><td>Anesthesia induction chamber&amp;nbsp;</td><td>Summit Anesthesia Solutions, Ann Harbor, MI</td><td></td><td></td></tr><tr><td>Summit Anesthesia Support system for regulating flow of anesthesia&amp;nbsp;</td><td>Summit Anesthesia Solutions, Ann Harbor, MI</td><td></td><td></td></tr><tr><td>Specially designed animal holder</td><td>Agilent Technologies, Santa Clara, CA</td><td></td><td></td></tr><tr><td>Bickford&amp;nbsp;Omnicon F/Air&amp;nbsp;anesthesia gas filter unit&amp;nbsp;</td><td>A.M. Bickford, Inc. Wales Center, NY</td><td></td><td></td></tr><tr><td>Pulse-oximeter module, MR compatible small animal monitoring and gating system&amp;nbsp;</td><td>Small Animal Instruments, Inc. Stony Brook, NY</td><td></td><td></td></tr><tr><td>Oxygen cylinder&amp;nbsp;</td><td>Matheson-Tri Gas, North-Central Zone, Lincoln, NE</td><td></td><td></td></tr><tr><td>Gas regulator&amp;nbsp;</td><td>Western Medica, West Lake, OH</td><td></td><td></td></tr><tr><td>Signal breaking module, MR compatible small animal monitoring and gating system</td><td>Small Animal Instruments, Inc. Stony Brook, NY</td><td></td><td></td></tr><tr><td>9.4 T (400 MHz) 89 mm vertical core bore MR scanner</td><td>Agilent Technologies, Santa Clara, CA</td><td></td><td></td></tr><tr><td>4 cm millipede micro-imaging RF coil</td><td>Agilent Technologies, Santa Clara, CA</td><td></td><td></td></tr><tr><td>SAM PC monitor</td><td>Small Animal Instruments, Inc. Stony Brook, NY</td><td></td><td></td></tr><tr><td>Quantitative Medical Image analysis software</td><td>http://segment.heiberg.se;&amp;nbsp; Segment v1.8 R1430,&amp;nbsp; Medviso, Oresunds region, Sweden</td><td></td><td></td></tr><tr><td>Matlab software</td><td>The Mathworks, Inc.&amp;nbsp; Natick, MA</td><td></td><td></td></tr><tr><td>Computer-Unix operating system</td><td></td><td></td><td></td></tr></tbody></table>

noninvasive assessment of cardiac abnormalities in experimental autoimmune myocarditis by magnetic resonance microscopy imaging in the mouse

心肌炎是心肌的炎症，但对疾病的影响的那些表演的临床表现只〜10％。研究心肌损伤的免疫事件，心肌炎的各种小鼠模型已被广泛使用。这项研究涉及实验性自身免疫性心肌炎（EAM）诱导的心肌肌球蛋白重链（MYHC）-α的A / J小鼠334-352段;受影响的动物培养淋巴细胞性心肌炎，但没有明显的临床症状。在这个模型中，磁共振显微镜（MRM）作为一种非侵入性方式的实用程序来确定显示在免疫的动物MYHC-α334-352心脏结构和功能改变。 EAM和健康的小鼠用9.4 T（400兆赫）89 mm垂直芯孔扫描仪配备了4厘米千足虫射频成像探头和100克/厘米三轴梯度成像。从麻醉动物用梯度回波为基础的电影脉冲序列被收购心脏图像，和阿尼玛LS是由呼吸和脉搏血氧饱和度监测。该分析显示，增加心室壁在EAM小鼠的厚度，并相应减少心室的内部直径，当与正常小鼠相比较。该数据表明，在发炎的心脏形态和功能变化可能是由MRM非侵入性地监测在活的动物。总之，MRM提供评估引起的感染性疾病的药物的心肌损伤的进展和回归，以及响应于治疗的优点。

在这份报告中，显示MRM技术的实用程序作为一种非侵入性的方式来确定受影响的与EAM动物的心的结构和功能改变。心肌炎诱导在A / J小鼠进行免疫的动物在CFA 7 MYHC-α334-352，并且将动物进行的MRM实验第21天免疫后。在活的动物异氟烷麻醉下使用89毫米垂直孔磁铁配备了三轴梯度（最大强度100克/厘米）的MRM成像进行9.4 T（400 MHz为质子）。球探图像被收购的定位和定位小鼠心脏中的视场的中心?...

Watch this Scientific Journal Video about Noninvasive Assessment of Cardiac Abnormalities in Experimental Autoimmune Myocarditis by Magnetic Resonance Microscopy Imaging in the Mouse at JoVE.com

Noninvasive Assessment of Cardiac Abnormalities in Experimental Autoimmune Myocarditis by Magnetic Resonance Microscopy Imaging in the Mouse

This study demonstrates the successful establishment of magnetic resonance microscopy imaging as a non-invasive tool to assess the cardiac abnormalities in mice affected with autoimmune myocarditis. The data indicate that the technique can be used to monitor the disease-progression in live animals.

心脏异常的实验性自身免疫性心肌炎的无创性评估磁共振成像显微镜在鼠标

Myocarditis is an inflammation of the myocardium, but only ~10% of those affected show clinical manifestations of the disease. To study the immune events ...

noninvasive-assessment-cardiac-abnormalities-experimental-autoimmune

Research

JoVE Journal

Medicine

9.9K 次观看.  University of Nebraska-Lincoln. This study demonstrates the successful establishment of magnetic resonance microscopy imaging as a non-invasive tool to assess the cardiac abnormalities in mice affected with autoimmune myocarditis. The data indicate that the technique can be used to monitor the disease-progression in live animals.

视频: Noninvasive Assessment of Cardiac Abnormalities in Experimental Autoimmune Myocarditis by Magnetic Resonance Microscopy Imaging in the Mouse

High-frequency High-resolution Echocardiography: First Evidence on Non-invasive Repeated Measure of Myocardial Strain, Contractility, and Mitral Regurgitation in the Ischemia-reperfused Murine Heart

Ischemia-reperfusion (IR) was surgically performed in murine hearts which were then subjected to repeated imaging to monitor temporal changes in functional parameters of key clinical significance. Two-dimensional movies were acquired at high frame rate (8 kHz) and were utilized to estimate high-quality myocardial strain. Two-dimensional elastograms (strain images), as well as strain profiles, were visualized. Results were powerful in quantitatively assessing IR-induced changes in cardiac events including left-ventricular (LV) contraction, LV relaxation and isovolumetric phases of both pre-IR and post-IR beating hearts in intact mice. In addition, compromised sector-wise wall motion and anatomical deformation in the infarcted myocardium were visualized.  The elastograms were uniquely able to provide information on the following parameters in addition to standard physiological indices that are known to be affected by myocardial infarction in the mouse: internal diameters of mitral valve orifice and aorta, effective regurgitant orifice, myocardial strain (circumferential as well as radial), turbulence in blood flow pattern as revealed by the color Doppler movies and velocity profiles, asynchrony in LV sector, and changes in the length and direction of vectors demonstrating slower and asymmetrical wall movement. This work emphasizes on the visual demonstration of how such analyses are performed. 

High-frequency High-resolution Echocardiography: First Evidence on Non-invasive Repeated Measure of Myocardial Strain, Contractility, and Mitral Regurgitation in the Ischemia-reperfused Murine Heart 

High frequency Doppler ultrasound is a novel technology for assessing regional myocardial function. This work presents first evidence demonstrating applicability of this versatile imaging platform for the repeated measure of myocardial strain, dp/dt, and mitral regurgitation in the ischemia-reperfused (IR) murine heart.

高频超声心动图：非侵入性的反复测量小鼠心脏缺血再灌注心肌劳损，收缩力，二尖瓣关闭不全的第一个证据

Ischemia-reperfusion (IR) was surgically performed in murine hearts which were then subjected to repeated imaging to monitor temporal changes in ...

科研

医学

Assessment of Cardiac Function and Myocardial Morphology Using Small Animal Look-locker Inversion Recovery (SALLI) MRI in Rats

Small animal magnetic resonance imaging is an important tool to study cardiac function and changes in myocardial tissue. The high heart rates of small animals (200 to 600 beats/min) have previously limited the role of CMR imaging. Small animal Look-Locker inversion recovery (SALLI) is a T1 mapping sequence for small animals to overcome this problem 1. T1 maps provide quantitative information about tissue alterations and contrast agent kinetics. It is also possible to detect diffuse myocardial processes such as interstitial fibrosis or edema 1-6. Furthermore, from a single set of image data, it is possible to examine heart function and myocardial scarring by generating cine and inversion recovery-prepared late gadolinium enhancement-type MR images 1.
	The presented video shows step-by-step the procedures to perform small animal CMR imaging. Here it is presented with a healthy Sprague-Dawley rat, however naturally it can be extended to different cardiac small animal models.

Assessment of Cardiac Function and Myocardial Morphology Using Small Animal Look-locker Inversion Recovery SALLI MRI in Rats

Contrast enhanced cardiac magnetic resonance (CMR) imaging allows comprehensive in vivo assessment of the heart in small animal models of cardiovascular disease. Here we detail the procedures to perform CMR imaging, reconstruction and analysis using Small Animal Lock-Locker Inversion Recovery (SALLI) in rats.

使用小动物看更衣室反转恢复（SALLI）的MRI大鼠心脏功能和心肌形态学评估

Small animal magnetic resonance  imaging is an important tool to study cardiac function and changes in myocardial  tissue. The high heart rates of small ...

MRI and PET in Mouse Models of Myocardial Infarction

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

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

MRI和PET心肌梗死小鼠模型

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

In Vivo Quantitative Assessment of Myocardial Structure, Function, Perfusion and Viability Using Cardiac Micro-computed Tomography

The use of Micro-Computed Tomography (MicroCT) for in vivo studies of small animals as models of human disease has risen tremendously due to the fact that MicroCT provides quantitative high-resolution three-dimensional (3D) anatomical data non-destructively and longitudinally. Most importantly, with the development of a novel preclinical iodinated contrast agent called eXIA160, functional and metabolic assessment of the heart became possible. However, prior to the advent of commercial MicroCT scanners equipped with X-ray flat-panel detector technology and easy-to-use cardio-respiratory gating, preclinical studies of cardiovascular disease (CVD) in small animals required a MicroCT technologist with advanced skills, and thus were impractical for widespread implementation. The goal of this work is to provide a practical guide to the use of the high-speed Quantum FX MicroCT system for comprehensive determination of myocardial global and regional function along with assessment of myocardial perfusion, metabolism and viability in healthy mice and in a cardiac ischemia mouse model induced by permanent occlusion of the left anterior descending coronary artery (LAD).

In Vivo Quantitative Assessment of Myocardial Structure, Function, Perfusion and Viability Using Cardiac Micro-computed Tomography

This method outlines the use of Quantum Micro-Computed Tomography (MicroCT) to assess cardiac morphology, function, perfusion, metabolism and viability with iodinated contrast agent in mice with experimentally-induced myocardial ischemia. The technique can be applied for non-destructive high-throughput longitudinal in vivo imaging of various animal models of human heart disease.

在心肌结构，功能的体内定量评估，灌注与活力使用心脏微型计算机断层扫描

The use of Micro-Computed Tomography (MicroCT) for in vivo studies of small animals as models of human disease has risen tremendously due to the fact that ...

生物工程

Echocardiographic and Histological Examination of Cardiac Morphology in the Mouse

An increasing number of genetically modified mouse models has become available in recent years. Moreover, the number of pharmacological studies performed in mice is high. Phenotypic characterization of these mouse models also requires the examination of cardiac function and morphology. Echocardiography and magnetic resonance imaging (MRI) are commonly used approaches to characterize cardiac function and morphology in mice. Echocardiographic and MRI equipment specialized for use in small rodents is&#160;expensive and requires a dedicated space. This protocol describes cardiac measurements in mice using a clinical echocardiographic system with a 15 MHz human vascular probe. Measurements are performed on anesthetized adult mice. At least three image sequences are recorded and analyzed for each animal in M-mode in the parasternal short-axis view. Afterwards, cardiac histological examination is performed, and cardiomyocyte diameters are determined on hematoxylin-eosin- or wheat germ agglutinin (WGA)-stained paraffin sections. Vessel density is determined morphometrically after Pecam-1 immunostaining. The protocol has been applied successfully to pharmacological studies and different genetic animal models under baseline conditions, as well as after experimental myocardial infarction by the permanent ligation of the left anterior descending coronary artery (LAD). In our experience, echocardiographic investigation is limited to anesthetized animals and is feasible in adult mice weighing at least 25 g.

Echocardiographic examination is frequently used in mice. Expensive high-resolution ultrasound devices have been developed for this purpose. This protocol describes an affordable echocardiographic procedure combined with histological morphometric analyses to determine cardiac morphology.

超声心动图与小鼠心脏形态学的组织学检查

An increasing number of genetically modified mouse models has become available in recent years. Moreover, the number of pharmacological studies performed ...

Quantification of Mouse Heart Left Ventricular Function, Myocardial Strain, and Hemodynamic Forces by Cardiovascular Magnetic Resonance Imaging

Mouse models have contributed significantly to understanding genetic and physiological factors involved in healthy cardiac function, how perturbations result in pathology, and how myocardial diseases may be treated. Cardiovascular magnetic resonance imaging (CMR) has become an indispensable tool for a comprehensive in vivo assessment of cardiac anatomy and function. This protocol shows detailed measurements of mouse heart left ventricular function, myocardial strain, and hemodynamic forces using 7-Tesla CMR. First, animal preparation and positioning in the scanner are demonstrated. Survey scans are performed for planning imaging slices in various short- and long-axis views. A series of prospective ECG-triggered short-axis (SA) movies (or CINE images) are acquired covering the heart from apex to base, capturing end-systolic and end-diastolic phases. Subsequently, single-slice, retrospectively gated CINE images are acquired in a midventricular SA view, and in 2-, 3-, and 4-chamber views, to be reconstructed into high-temporal resolution CINE images using custom-built and open-source software. CINE images are subsequently analyzed using dedicated CMR image analysis software.
Delineating endomyocardial and epicardial borders in SA end-systolic and end-diastolic CINE images allows for the calculation of end-systolic and end-diastolic volumes, ejection fraction, and cardiac output. The midventricular SA CINE images are delineated for all cardiac time frames to extract a detailed volume-time curve. Its time derivative allows for the calculation of the diastolic function as the ratio of the early filling and atrial contraction waves. Finally, left ventricular endocardial walls in the 2-, 3-, and 4-chamber views are delineated using feature-tracking, from which longitudinal myocardial strain parameters and left ventricular hemodynamic forces are calculated. In conclusion, this protocol provides detailed in vivo quantification of the mouse cardiac parameters, which can be used to study temporal alterations in cardiac function in various mouse models of heart disease.

This study describes a comprehensive cardiovascular magnetic resonance imaging (CMR) protocol to quantify the left ventricular functional parameters of the mouse heart. The protocol describes the acquisition, post-processing, and analysis of the CMR images as well as assessment of different cardiac functional parameters.

通过心血管磁共振成像定量小鼠心脏左心室功能、心肌劳损和血流动力学力

Mouse models have contributed significantly to understanding genetic and physiological factors involved in healthy cardiac function, how perturbations ...

Quantification of Biventricular Function and Morphology by Cardiac Magnetic Resonance Imaging in Mice with Pulmonary Artery Banding

Right ventricular (RV) function and failure are major determinants of outcome in acquired and congenital heart diseases, including pulmonary hypertension. Assessment of RV function and morphology is complex, partly due to the complex shape of the RV. Currently, cardiac magnetic resonance (CMR) imaging is the golden standard for noninvasive assessment of RV function and morphology. The current protocol describes CMR imaging in a mouse model of RV pressure load induced by pulmonary artery banding (PAB). PAB is performed by placing a 6-0 suture around the pulmonary artery over a 23 G needle. The PAB gradient is determined using echocardiography at 2 and 6 weeks. At 6 weeks, the right and left ventricular morphology and function is assessed by measuring both end-systolic and end-diastolic volumes and mass by ten to eleven cine slices 1 mm thick using a 9.4 T magnetic resonance imaging scanner equipped with a 1,500 mT/m gradient. Representative results show that PAB induces a significant increase in RV pressure load, with significant effects on biventricular morphology and RV function. It is also shown that at 6 weeks of RV pressure load, cardiac output is maintained. Presented here is a reproducible protocol for the quantification of biventricular morphology and function in a mouse model of RV pressure load and may serve as a method for experiments exploring determinants of RV remodeling and dysfunction.

To understand the pathophysiology of right ventricular (RV) adaptation to abnormal loading, experimental models are crucial. However, assessment of RV dimensions and function is complex and challenging. This protocol provides a method to perform cardiac magnetic resonance imaging (CMR) as a noninvasive benchmark procedure in mice subjected to RV pressure load.

Right ventricular (RV) function and failure are major determinants of outcome in acquired and congenital heart diseases, including pulmonary hypertension. ...

Induction of Myocardial Infarction and Myocardial Ischemia-Reperfusion Injury in Mice

Acute myocardial infarction is a common cardiovascular disease with high mortality. Myocardial reperfusion injury can counteract the beneficial effects of heart reflow and induce secondary myocardial injury. A simple and reproducible model of myocardial infarction and myocardial ischemia-reperfusion injury is a good tool for researchers. Here, a customizable method to create a myocardial infarction (MI) model and MIRI by precision ligation of the left anterior descending coronary artery (LAD) through micromanipulation is described. Accurate and reproducible ligature positioning of the LAD helps obtain consistent results for heart injury. ST-segment changes can help to identify model accuracy. The serum level of cardiac troponin T (cTnT) is used to assess the myocardial injury, cardiac ultrasound is employed to evaluate the myocardial systolic function, and Evans-Blue/triphenyl tetrazolium chloride staining is used to measure infarct size. In general, this protocol reduces procedure duration, ensures controllable infarct size, and improves mouse survival.

Here we describe a simple and reproducible method that can induce myocardial infarction or myocardial ischemia-reperfusion injury in mice by precision ligation of the left anterior descending coronary artery through micromanipulation.

小鼠心肌梗死和心肌缺血再灌注损伤的诱导

Acute myocardial infarction is a common cardiovascular disease with high mortality. Myocardial reperfusion injury can counteract the beneficial effects of ...

An Experimental Model of Myocardial Infarction for Studying Cardiac Repair and Remodeling in Knockout Mice

Cardiovascular disease is the most prevalent cause of death in Western countries, with acute myocardial infarction (MI) being the most prevalent form. This paper describes a protocol for studying the role of galectin 3 (Gal-3) in the temporal evolution of cardiac healing and remodeling in an experimental animal model of MI. 
The procedures described include an experimental model of MI with a permanent coronary ligature in male C57BL/6J (control) and Gal-3 knockout (KO) mice, an echocardiography procedure to study cardiac remodeling and systolic function in vivo, a histological evaluation of interstitial myocardial fibrosis with picrosirius red-stained and rhodamine-conjugated lectin-stained sections for studying myocyte hypertrophy by the cross-sectional area (MCSA), and the quantification of infarct size and cardiac remodeling (scar thinning, septum thickness, and expansion index) by planimetry in slices stained with Masson's trichrome and triphenyl tetrazolium chloride. Gal-3 KO mice with MI showed disrupted cardiac remodeling and an increase in the scar thinning ratio and the expansion index. At the onset of MI, myocardial function and cardiac remodeling were also severely affected. At 4 weeks post MI, the natural evolution of fibrosis in infarcted Gal-3 KO mice was also affected. 
In summary, the experimental model of MI is a suitable model for studying the temporal evolution of cardiac repair and remodeling in mice with the genetic deletion of Gal-3 and other animal models. The lack of Gal-3 affects the dynamics of cardiac repair and disrupts the evolution of cardiac remodeling and function after MI.

Here, we describe an experimental model of myocardial infarction, an echocardiography procedure to study cardiac remodeling and function, and procedures for quantifying fibrosis and hypertrophy in picrosirius red-stained and rhodamine-stained sections, as well as the infarct size and expansion index in slices stained with Masson's trichrome.

Cardiovascular disease is the most prevalent cause of death in Western countries, with acute myocardial infarction (MI) being the most prevalent form. ...

Mesoscopic Optical Imaging of Whole Mouse Heart

Both genetic and non-genetic cardiac diseases can cause severe remodeling processes in the heart. Structural remodeling, such as collagen deposition (fibrosis) and cellular misalignment, can affect electrical conduction, introduce electromechanical dysfunctions and, eventually, lead to arrhythmia. Current predictive models of these functional alterations are based on non-integrated and low-resolution structural information. Placing this framework on a different order of magnitude is challenging due to the inefficacy of standard imaging methods in performing high-resolution imaging in massive tissue. In this work, we describe a methodological framework that allows imaging of whole mouse hearts with micrometric resolution. The achievement of this goal has required a technological effort where advances in tissue transformation and imaging methods have been combined. First, we describe an optimized CLARITY protocol capable of transforming an intact heart into a nanoporous, hydrogel-hybridized, lipid-free form that allows high transparency and deep staining. Then, a fluorescence light-sheet microscope able to rapidly acquire images of a mesoscopic field of view (mm-scale) with the micron-scale resolution is described. Following the mesoSPIM project, the conceived microscope allows the reconstruction of the whole mouse heart with micrometric resolution in a single tomographic scan. We believe that this methodological framework will allow clarifying the involvement of the cytoarchitecture disarray in the electrical dysfunctions and pave the way for a comprehensive model that considers both the functional and structural data, thus enabling a unified investigation of the structural causes that lead to electrical and mechanical alterations after the tissue remodeling.

We report a method for mesoscopic reconstruction of the whole mouse heart by combining new advancements in tissue transformation and staining with the development of an axially scanned light-sheet microscope.

全小鼠心脏的介观光学成像

Both genetic and non-genetic cardiac diseases can cause severe remodeling processes in the heart. Structural remodeling, such as collagen deposition ...