Bock Nicholas A, Kovacevic Natasa, Lipina Tatiana V, Roder John C, Ackerman Susan L, Henkelman R Mark
Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, M5G 1X8, Canada.
J Neurosci. 2006 Apr 26;26(17):4455-9. doi: 10.1523/JNEUROSCI.5438-05.2006.
Magnetic resonance imaging and computer image analysis in human clinical studies effectively identify abnormal neuroanatomy in disease populations. As more mouse models of neurological disorders are discovered, such an approach may prove useful for translational studies. Here, we demonstrate the effectiveness of a similar strategy for mouse neuroscience studies by phenotyping mice with the cerebellar deficient folia (cdf) mutation. Using in vivo multiple-mouse magnetic resonance imaging for increased throughput, we imaged groups of cdf mutant, heterozygous, and wild-type mice and made an atlas-based segmentation of the structures in 15 individual brains. We then performed computer automated volume measurements on the structures. We found a reduced cerebellar volume in the cdf mutants, which was expected, but we also found a new phenotype in the inferior colliculus and the olfactory bulbs. Subsequent local histology revealed additional cytoarchitectural abnormalities in the olfactory bulbs. This demonstrates the utility of anatomical magnetic resonance imaging and semiautomated image analysis for detecting abnormal neuroarchitecture in mutant mice.
磁共振成像和计算机图像分析在人体临床研究中能有效识别疾病人群中的异常神经解剖结构。随着越来越多的神经疾病小鼠模型被发现,这种方法可能对转化研究有用。在此,我们通过对患有小脑叶缺损(cdf)突变的小鼠进行表型分析,证明了类似策略在小鼠神经科学研究中的有效性。利用体内多小鼠磁共振成像提高通量,我们对cdf突变体、杂合子和野生型小鼠组进行了成像,并对15个个体大脑中的结构进行了基于图谱的分割。然后我们对这些结构进行了计算机自动体积测量。我们发现cdf突变体的小脑体积减小,这在意料之中,但我们还在下丘和嗅球中发现了一种新的表型。随后的局部组织学检查显示嗅球中存在额外的细胞结构异常。这证明了解剖磁共振成像和半自动图像分析在检测突变小鼠异常神经结构方面的实用性。