Sze R W, Chan C B, Dardzinski B J, Dunn S, Sanbe A, Schmithorst V, Robbins J, Holland S K, Strife J L
Department of Radiology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
Pediatr Radiol. 2001 Feb;31(2):55-61. doi: 10.1007/s002470000365.
Scientists are now able to alter the genetics of vertebrate embryos routinely to produce animal models of human developmental diseases. However, our understanding of structural changes in these animal models is limited by current methodologies. Histological techniques, although providing great anatomic detail, display only "static" data (one time point only) in two dimensions. Ultrasound may be used to generate continuous time course data, but is limited by interobserver variation, limited acoustic windows, and relatively low resolution.
To apply the high resolution, non-destructive, and three-dimensional acquisition capabilities of magnetic resonance (MR) microscopy to compare the hearts of normal mice versus an established transgenic mouse model of dilated cardiomyopathy.
Transgenic mice exhibiting dilated cardiomyopathy were developed via the introduction of a mutated, heart-specific gene (myosin light chain). Postmortem cardiac imaging was performed on the transgenic mice and normal controls. MR imaging was performed on a Bruker 3T imaging magnet using a custom radiofrequency coil following contrast perfusion of the atrial and ventricular chambers. Image resolution was 156 microm isotropic voxels. MR images were compared to gross pathologic specimens. Imaging data were post-processed using custom software to calculate the volumes of the atria and ventricles and to display the three-dimensional morphology of the chambers and myocardium.
Of the seven mice scanned, four exhibited normal right atrial (average = 14.8 microl +/- 1.4), left atrial (average = 8.5 microl +/-0.3), right ventricular (average = 12.9 microl +/-2.7), and left ventricular (average 3.3 microl +/-0.5) volumes. Three mice exhibited dilatation of the right and left cardiac chambers (RA average = 23.9 microl +/-5.6; LA average = 15.9 microl +/-4.8; RV average = 32.5 microl +/- 6.8; LV average 24.0 microl +/-1.4). The gross morphology was verified upon autopsy of the animals and correlated with the animal's genotype. The differences in volumes between the normal and dilated cardiomyopathy mice were statistically significant (P values ranged from 0.001 to 0.024 for the different chambers).
MR microscopy is a potentially useful tool for developmental biology research. The imaging of mouse hearts is feasible, and these methods provide quantitative and qualitative morphologic data of a mouse model of dilated cardiomyopathy not available using traditional methods.
科学家现在能够常规地改变脊椎动物胚胎的基因，以制造人类发育疾病的动物模型。然而，我们对这些动物模型结构变化的理解受到当前方法的限制。组织学技术虽然能提供详细的解剖细节，但仅在二维层面显示“静态”数据（仅一个时间点）。超声可用于生成连续的时间进程数据，但受观察者间差异、有限的声学窗口和相对较低的分辨率限制。
应用磁共振（MR）显微镜的高分辨率、非破坏性和三维采集能力，比较正常小鼠与已建立的扩张型心肌病转基因小鼠模型的心脏。
通过引入突变的心脏特异性基因（肌球蛋白轻链）培育出表现出扩张型心肌病的转基因小鼠。对转基因小鼠和正常对照进行死后心脏成像。在心房和心室进行对比剂灌注后，使用定制射频线圈在布鲁克3T成像磁体上进行MR成像。图像分辨率为各向同性体素156微米。将MR图像与大体病理标本进行比较。使用定制软件对成像数据进行后处理，以计算心房和心室的体积，并显示腔室和心肌的三维形态。
在扫描的7只小鼠中，4只的右心房（平均 = 14.8微升±1.4）、左心房（平均 = 8.5微升±0.3）、右心室（平均 = 12.9微升±2.7）和左心室（平均3.3微升±0.5）体积正常。3只小鼠表现出左右心腔扩张（右心房平均 = 23.9微升±5.6；左心房平均 = 15.9微升±4.8；右心室平均 = 32.5微升±6.8；左心室平均24.0微升±1.4）。对动物进行尸检时证实了大体形态，并与动物的基因型相关。正常小鼠和扩张型心肌病小鼠之间的体积差异具有统计学意义（不同腔室的P值范围为0.001至0.024）。
MR显微镜是发育生物学研究中一种潜在有用的工具。对小鼠心脏进行成像可行，这些方法提供了传统方法无法获得的扩张型心肌病小鼠模型的定量和定性形态学数据。
