Three-dimensional MR microscopy of a transgenic mouse model of dilated cardiomyopathy

Background. Scientists are now able to alter the genetics of vertebrate emb ryos routinely to produce animal models of human developmental diseases. Ho wever, our understanding of structural changes in these animal models is li mited 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. Objective. To apply the high resolution, non-destructive, and three-dimensi onal acquisition capabilities of magnetic resonance (MR) microscopy to comp are the hearts of normal mice versus an established transgenic mouse model of dilated cardiomyopathy. Materials and methods. Transgenic mice exhibiting dilated cardiomyopathy we re developed via the introduction of a mutated, heart-specific gene (myosin light chain). Postmortem cardiac imaging was performed on the transgenic m ice and normal controls. MR imaging was performed on a Bruker 3T imaging ma gnet using a custom radiofrequency coil following contrast perfusion of the atrial and ventricular chambers. Image resolution was 156 mum isotropic vo xels. MR images were compared to gross pathologic specimens. Imaging data w ere postprocessed using custom software to calculate the volumes of the atr ia and ventricles and to display the three-dimensional morphology of the ch ambers and myocardium. Results. Of the seven mice scanned, four exhibited normal right atrial (ave rage = 14.8 mul +/- 1.4), left atrial (average = 8.5 mul +/- 0.3), right ve ntricular (average = 12.9 mul +/- 2.7), and left ventricular (average 3.3 m ul +/- 0.5) volumes. Three mice exhibited dilatation of the right and left cardiac chambers (RA average = 23.9 mul +/- 5.6; LA average = 15.9 mul +/- 4.8; RV average = 32.5 mul +/- 6.8; LV average 24.0 mul +/- 1.4). The gross morphology was verified upon autopsy of the animals and correlated with th e animal's genotype. The differences in volumes between the normal and dila ted cardiomyopathy mice were statistically significant (P values ranged fro m 0.001 to 0.024 for the different chambers). Conclusion. MR microscopy is a potentially useful tool for developmental bi ology research. The imaging of mouse hearts is feasible, and these methods provide quantitative and qualitative morphologic data of a mouse model of d ilated cardiomyopathy not available using traditional methods.