In vivo analysis of mechanism for neuronal regeneration in damaged brain by using multi-nuclear, multi-modality MRI methods

我们开发了多模态磁共振成像（MRI）技术来分析受损大脑中的神经元再生。这些是；(1)利用超快速扩散加权成像获得的扩散张量图像进行光纤跟踪成像方法；(2)锰增强MRI（MEMRI）神经元激活成像方法。该方法基于神经元活化过程中Mn离子与Ca离子结合进入神经元细胞的理论；(3)二维磁共振光谱（2D-MRS），可以精确分析损伤脑内的各种脑代谢物；(4)动脉自旋标记法灌注成像；(4)利用血管内水信号作为示踪剂进行脑无创灌注成像（动脉自旋标记法）。MRI设备为实验MRI机（4.7T Bruker Biospec和TOT Varian INOVA300SWB）和人体全身MRI机（1.5T GE Signa Horizon， 1.5T Siemens Symphony和3.0T GE Signa Horizon）。在光纤跟踪成像方法中，基于扩散张量方向的图像清晰地显示了光纤方向的三维分布。在脑梗死的病例中，纤维断裂被证实。MEMRI方法在大鼠嗅丛、视神经和视辐射中清晰地显示出神经元纤维。该方法还清晰地显示了皮层的6层。该方法可以根据神经细胞的激活情况直接检测神经元的方向和大脑结构。2D-MRS、2D-JPRESS和2D-COSY分别在1.5T和3.0T的临床MRI设备上进行开发。采用2D-MRS方法获得了常规MRS法检测不到的脑代谢物，如谷氨酰胺/谷氨酸、谷胱甘肽、苏氨酸和GABA。2D-MRS从代谢的角度检查受损脑的生存能力是有用的。动脉自旋标记法灌注成像有助于无创检测脑血流变化，结合弥散加权成像有助于了解脑梗死半暗区生存能力。综上所述，多模态MR方法是一种独特的、有用的无创检测损伤脑组织和神经细胞功能再生的方法。由于MRI方法中评估脑功能和代谢的技术还比较多，需要进一步的研究。少

We have developed multi-modality magnetic resonance imaging(MRI) techniques for analysis of neuronal regeneration in damaged brain. Those are ; (1)Fiber tracking imaging method by using diffusion tensor images obtained from ultra-fast diffusion weighted imaging ; (2)Neuronal activation imaging method by using manganese-enhanced MRI(MEMRI). This method depends on the theory that Mn ion can enter into neuronal cell in conjunction with Ca ion during the neuronal activation ; (3)Two dimensional MR spectroscopy(2D-MRS) by which various brain metabolites can be analyzed precisely in damaged brain ; (4)Perfusion imaging using arterial spin tagging method, (4)Non-invasive perfusion imaging of the brain by using water signal in the vessel as a tracer(Arterial spin tagging method). MRI devices used were experimental MRI machines (4.7T Bruker Biospec and TOT Varian INOVA300SWB) and a whole body MRI machine for human(1.5T GE Signa Horizon, 1.5T Siemens Symphony and 3.0T GE Signa Horizon).In fiber … More tracking imaging method, three dimensional distribution of fiber orientation was clearly demonstrated by the images based on diffusion tensor direction. Disconnection of fiber was demonstrated in cases of cerebral infarction. In MEMRI method, neuronal fibers were clearly demonstrated in rat olfactory grove, optic nerve and optic radiation. Also the six cortical layers were clearly demonstrated by this method. This method is useful to detect the neuronal orientation and brain structure directly based on the nerve cell activation. In 2D-MRS, 2D-JPRESS and 2D-COSY were developed on 1.5T and 3.0T clinical MRI devices. Brain metabolites which could not be detected by conventional MRS method were obtained by those 2D-MRS method, such as glutamine/glutamate, glutathione, threonine and GABA. 2D-MRS is useful to examine the viability of damaged brain from the metabolic point of view. The perfusion imaging using arterial spin tagging method was useful to detect the cerebral blood flow change non-invasively, and the combination with diffusion weighted imaging is useful to know the viability of penumbra region in cerebral infarction.In conclusion, the multi-modality MR methods are unique and useful to examine the regeneration of damaged brain tissue and nerve cell function non-invasively. Since there are still more techniques in MRI methods to evaluate the brain function and metabolism, further research should be continued. Less