Nahrendorf Matthias, Badea Cristian, Hedlund Laurence W, Figueiredo Jose-Luiz, Sosnovik David E, Johnson G Allan, Weissleder Ralph
Center for Molecular Imaging Research, Massachusetts General Hospital, Boston, MA, USA.
Am J Physiol Heart Circ Physiol. 2007 Jun;292(6):H3172-8. doi: 10.1152/ajpheart.01307.2006. Epub 2007 Feb 23.
The objective of this study was to determine the feasibility of delayed-enhancement micro-computed tomography (microCT) imaging to quantify myocardial infarct size in experimental mouse models. A total of 20 mice were imaged 5 or 35 days after surgical ligation of the left coronary artery or sham surgery (n=6 or 7 per group). We utilized a prototype microCT that covers a three-dimensional (3D) volume with an isotropic spatial resolution of 100 microm. A series of image acquisitions were started after a 200 microl bolus of a high-molecular-weight blood pool CT agent to outline the ventricles. CT imaging was continuously performed over 60 min, while an intravenous constant infusion with iopamidol 370 was started at a dosage of 1 ml/h. Thirty minutes after the initiation of this infusion, signal intensity in Hounsfield units was significantly higher in the infarct than in the remote, uninjured myocardium. Cardiac morphology and motion were visualized with excellent contrast and in fine detail. In vivo CT determination of infarct size at the midventricular level was in good agreement with ex vivo staining with triphenyltetrazolium chloride [5 days post-myocardial infarction (MI): r(2)=0.86, P<0.01; 35 days post-MI: r(2)=0.92, P<0.01]. In addition, we detected significant left ventricular remodeling consisting of left ventricular dilation and decreased ejection fraction. 3D cine microCT reliably and rapidly quantifies infarct size and assesses murine anatomy and physiology after coronary ligation, despite the small size and fast movement of the mouse heart. This efficient imaging tool is a valuable addition to the current phenotyping armamentarium and will allow rapid testing of novel drugs and cell-based interventions in murine models.
本研究的目的是确定延迟增强微型计算机断层扫描(microCT)成像在实验小鼠模型中量化心肌梗死面积的可行性。总共20只小鼠在左冠状动脉结扎手术或假手术后5天或35天进行成像(每组n = 6或7)。我们使用了一台原型microCT,其各向同性空间分辨率为100微米,可覆盖三维(3D)体积。在注射200微升高分子量血池CT造影剂以勾勒心室轮廓后,开始进行一系列图像采集。CT成像持续进行60分钟,同时以1毫升/小时的剂量开始静脉恒速输注碘帕醇370。在开始输注30分钟后,梗死区域的亨氏单位信号强度明显高于远处未受损的心肌。心脏形态和运动以出色的对比度和精细细节得以显现。在心室中部水平进行的体内CT梗死面积测定与离体氯化三苯基四氮唑染色结果高度一致[心肌梗死(MI)后5天:r(2)=0.86,P<0.01;MI后35天:r(2)=0.92,P<0.01]。此外,我们检测到显著的左心室重构,包括左心室扩张和射血分数降低。尽管小鼠心脏体积小且运动快,但3D电影microCT能够可靠且快速地量化梗死面积,并评估冠状动脉结扎后的小鼠解剖结构和生理功能。这种高效的成像工具是当前表型分析手段的一项有价值补充,将有助于在小鼠模型中快速测试新型药物和基于细胞的干预措施。