Assessment of cerebral metabolic and microstructural alterations in aging human brain and in patients by using an innovative whole brain 1H magnetic resonance spectroscopic technique in combination with quantitative magnetic resonance imaging

在第一个资助期（2015年4月1日至2017年3月31日），我们研究了正常老化对13个选定的特定脑区的主要脑代谢物NAA、Cho、tCr和脑组织T2弛豫时间的影响（Eylers等人，2016）。我们还通过确定脑组织体积分数以及大脑叶结构上NAA、Cho、tCr以及Glx和mI代谢物浓度的年龄相关变化，研究了健康老年人大脑中生理性神经元衰退的短回波时间全脑MR光谱成像（wbMRSI）（Ding等人，2016）。这两项研究都揭示了令人感兴趣的结果，这些结果使人们对健康老龄化大脑的生理过程有了新的认识，并且数据已经发表。但也存在一定的缺点：受回波时间长的限制在第一个子项目中，仅测量了主要代谢物NAA、Cho和tCr的特定局部代谢物分布（TE 70 ms），而不能考虑通常对不同病理条件敏感的代谢物Glx和mI;第二个子项目的结果是在大规模的大脑结构（八个大脑脑叶和小脑）中获得的，因此不适用于患者研究中经常感兴趣的小而特定的大脑结构。根据目前的建议，我们首先将联合收割机短回波时间wbMRSI与包括确定脑组织的T2和T1弛豫时间的qMR成像以及与体积MRI相结合来研究健康志愿者，目的是加强我们对健康老龄人脑中生理性神经元衰退的研究。所有参数测量将在多个大脑小的特定结构上进行，目的是研究人脑中不均匀的代谢和微结构老化效应，所收集的数据可用作研究弥漫性或多灶性代谢和微结构改变的脑疾病的参考数据。在第二个项目中，作为第一个应用程序的建立wbMRSI方法系统地研究一个病人组，我们计划研究神经代谢和微观结构的改变导致慢性神经毒性的钙调磷酸酶抑制剂在肝移植后的患者。在患者中发现的代谢和微结构改变将与神经心理测试的结果相关，并与健康对照组进行比较，以找到CNS功能缺陷的可能来源，这可能为将来改进临床治疗提供理由。

In the first funding period (from 01.04.2015 to 31.03.2017), we have studied normal aging effects on main brain metabolite NAA, Cho, tCr and brain tissue T2 relaxation times at 13 selected specific regions of brain interests (Eylers et al. 2016). We have also studied physiological neuronal decline in healthy aging human brain with short echo-time whole brain MR spectroscopic imaging (wbMRSI) by determining age-related changes in fractional volumes of brain tissue and in metabolite concentrations of not only NAA, Cho, tCr, but also Glx and mI over large brain lobar structures (Ding et al. 2016). Both studies revealed interested results that allowed new insight into the physiological process in healthy aging brain and the data have been published. However, there are certain weakness: Limited by used long echo time (TE 70 ms) in the first subproject specific local metabolite distributions were measured only for the main metabolites NAA, Cho, and tCr, whereas the metabolites Glx and mI that are often sensitive to different pathological conditions could not be considered; The results of the second subproject were obtained at large scale of brain structures (eight cerebral lobes and cerebellum), thus not applicable for small and specific brain structures that are often interested in patient study. With present proposal we are, at first, going to combine short echo time wbMRSI with qMR imaging including determinations of T2 and T1 relaxation times of brain tissue, as well as with volumetric MRI to study healthy volunteers, with the purpose to intensify our investigation of physiological neuronal decline in healthy aging human brain. All parameter measurements will be made at multiple brain small specific structures, with the aim to study inhomogeneous metabolic and microstructural aging effects in human brain, and the collected data could be used as reference data for studying brain disorders with diffuse or multifocal metabolic and microstructural alterations. In a second project, as a first application of the established wbMRSI method to study a patient group systematically, we plan to study neurometabolic and microstructural alterations resulted from chronic neurotoxicity of calcineurin inhibitors in patients after liver transplantation. The founded metabolic and microstructural alterations in patients will be related to the results of neuro-psychometric tests and compared to those of healthy controls to find possible origin of CNS functional deficits, which may give reason for improvement of the clinical therapy in the future.