Magnetic Resonance Imaging and Spectroscopy of Rodent Models of Disease

脑磁共振光谱是形态学成像研究的一个很好的辅助手段。我们使用这种方法来定义xrcc1缺陷（KO）小鼠的小脑代谢物，在这种小鼠中，缺乏这种碱基切除修复和单链断裂修复的关键参与者。进行磁共振成像和光谱分析。在成像实验中，发现两组的小脑体积没有差异。在光谱实验中，我们能够通过使用TE = 135 ms编辑脂质信号，允许清楚地描绘胆碱，肌酸和NAA。NAA神经元标记在两组间无差异。对于神经元活力的MRI体积测量和MR光谱测量，在XRCC1 KO动物中发现了更大的数据变异性。总的来说，尽管在XRCC1 KO表型中表现出小脑共济失调，但我们发现正常和KO动物的小脑体积或小脑神经元活力没有差异。因此，尽管保留了这些重要的脑表型参数，但共济失调表型仍然存在。我们将继续完善我们的技术，并将其应用于其他疾病模型。

MR spectroscopy of brain is an excellent adjunct to morphologic imaging studies. We used this approach to define cerebellar metabolites in the XRCC1-deficient (KO) mouse, in which this key participant in base excision repair and single-strand break repair is lacking. Both MR imaging and spectroscopic analyses were performed. In the imaging experiments, cerebellar volume was found not to differ between the two groups. In the spectroscopy experiments, we were able to edit lipid signal by use of a TE = 135 ms, permitting clear delineation of choline, creatine, and NAA. No difference in the NAA neuronal marker was observed between the two groups. For both MRI volume measurements and MR spectroscopic measurements of neuronal viability, a larger variability in the data was seen in the XRCC1 KO animals. Overall, in spite of the cerebellar ataxia demonstrated in the XRCC1 KO phenotype, we found no differences in cerebellar volume or in cerebellar neuronal viability between the normal and KO animals. Thus, the ataxic phenotype is present in spite of preservation of these important parameters of brain phenotype. We will continue to refine our techniques and apply them to other disease models. Further work involves studies of brain structural changes and cerebral blood flow in mouse models of Alzheimer's disease and in dietary interventions, including the ketogenic diet and caloric restriction. We are currently generating preliminary results for the dietary intervention study.