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

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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.