| Objective: To investigate the modality of structural modification of brain grey matter in Alzheimer’s disease(AD) with the application of voxel based morphometry(VBM).To investigate the definite abnormal site of brain network in AD and understand the mechanism of both damage and compensation of the neural network applying resting-state functional MRI(rs-f MRI).Toinvestigate the spatial distribution of abnormal brain areas and corresponding metabolic changes in patients with AD using multivoxel ~1H proton-magnetic resonance spectroscopy(~1H-MRS).Materials and Methods: Sixteen AD patients and sixteen healthy volunteers performed 3DT1 WI, rs-f MRI and multivoxel ~1H-MRSexamination. The difference of cerebral grey matter volume(GMV), amplitude of low-frequency fluctuation(ALFF),regional homogeneity(Re Ho),functional connectivity(FC) and between AD group and healthy control(HC) group was compared. The absolute concentration and relative content of N-acetylaspartate(NAA), creatine(Cr), choline(Cho),myo-inositol(MI) and Glx were calculated within VOI.The difference of metabolite concentration between AD group and HCgroup was compared. Correlation analysis was to measure the relativity between moltimodal MRI index and clinical mini-mental state examination(MMSE) score.Results:(1)Conventional MRI(c MRI) demonstrated that compared with the HC group, cortex of bilateral frontal and temporal lobe was obvious thinning and the hippocampus was atrophic in varying degrees in AD group.VBM showed that compared with the HC group, the cortical GMV in AD group had a significant decrease in the bilateral cingulate gyrus, superior frontal gyrus, middle frontal gyrus, superior temporal gyrus, lingual gyrus, left precentral/postcentral gyrus, parahippocampal gyrus, temporal pole, orbital gyrus and right superior parietal lobule, the subcortical GMV in AD group had a significant decrease in the bilateral putamen, globus pallidus, candate nucleus, amygdala and hippocampus.The GMV of cingulate gyrus was positively correlated with putamen counterpart.(2) Compared with the HC group, the ALFF in AD group had a significant decrease in bilateral posterior cingulate gyrus/precuneus, prefrontal lobe, temporal pole, inferior parietal lobule and increase in bilateral hippocampus, parahippocampal gyrus, vermis, left dorsal thalamus and right caudate nucleus. ALFF had a positive correlation with MMSE in bilateral cingulate gyrus, precuneus and negative correlation with MMSE in left insular, middle temporal gyrus and parahippocampal gyrus. Compared with the HC group, the Re Ho in AD group had a significant decrease in bilateral posterior cingulate gyrus/precuneus, inferior parietal lobule, right insular, caudate nucleus and increase in bilateral lingual gyrus,fusiform gyrus, right parahippocampal gyrus and hippocampus. Re Ho had a positive correlation with MMSE in bilateral cuneus, calcarine and precuneus and negative correlation with MMSE in left inferior temporal gyrus and hippocampus. Compared with the HC group, the FC in AD group had a significant decrease in bilateral posterior cingulate gyrus/precuneus, inferior parietal lobule, middle temporal gyrus and left hippocampus,medial prefrontal cortex. FC had a positive correlation with MMSE in left medial prefrontal cortex,superior frontal gyrus and middle frontal gyrus.(3)Comparion of metabolite index in right VOI:Compared with the HC group, the AD group displayed significantly lower NAA, NAA/Cr, NAA/MI and higher MI, MI/Cr levels in posterior cingulate gyrus, significantly lower NAA, Glx levels in occipital lobe cortex, significantly lower NAA and higher Cho levels in dorsal thalamus.Comparion of metabolite index in left VOI:Compared with the HC group, the AD group displayed significantly lower NAA, NAA/Cr, NAA/MI, Glx/Cr and higher MI/Cr levels in posterior cingulate gyrus, significantly lower NAA and higher Cho/Cr levels in occipital lobe cortex, significantly lower NAA and higher Cho levels in lateral ventricle paratrigonal white matter, significantly lower Glx and higher Cho levels in dorsal thalamus. NAA/Cr was positively correlated with Glx/Cr in left posterior cingulate gyrus in AD group.Conclusion:(1)VBM can reflect the subtle change of morphology of brain tissue in AD and serve as the important supplementary measure for c MRI.(2)The grey matter structure was injured and involving the cortical and subcortical region, mainly located in the limbic system and basal ganglion.(3)The cingulate gyrus was significant correlated with putamen, prompt that there may be a structural association between limbic system and basal ganglion.(4)There were several brain regions with abnormal ALFF, Re Ho and FC within DMN. ALFF, Re Ho and FC were decrease among bilateral posterior cingulate gyrus/precuneus, inferior parietal lobule and medial prefrontal cortex, suggested that they may be the definite abnormal sites of DMN.(5)The increase ALFF and Re Ho may be both take part in the neural compensatory mechanism of structural damage in hippcampus.(6) The damage of FC between left hippcampus and posterior cingulate gyrus, while the ALFF of left hippcampus was increase obviously, thisphenomenonwas coincidence with “hippcampus disconnection hypothesis”, speculated that increase functional activity of hippocampus itself may be participate in the neural compensatory mechanism of impaired FC between hippocampus and DMN in AD group.(7)The abnormal ALFF, Re Ho and FC of DMN related brain areas in AD patients were correlated with clinical MMSE score, further revealed that rs-f MRI index can serve as biomarker for monitoring AD progress and evaluating the effect of durg treatment.(8)There were several abnormally metabolic brain areas in AD. Posterior cingulate gyrus manifested a kind of pattern that NAA, NAA/Cr, NAA/MI were decrease, whereas MI, MI/Cr were increase, which had no significant correlation.(9)Both grey and white matter displayed significantly increase Cho concentration, suggested structural damage of cytomembrane and demyelination simultaneously existed in many brain areas.(10) The grey matter mainly showed decrease Glx and Glx/Cr, involving both cortex and subcortex structures.(11)NAA/Cr was correlated with Glx/Cr in left posterior cingulate gyrus in AD patients, indicating the loss of neuron interacted with structural and functional impairment of synapse. |