Abstract： Objective To evaluate gray matter volume,white matter volume and FA value changes in amyatrophic lateral sclerosis(ALS)patients by voxel-based morphometry(VBM)and voxel-based diffusion tensor analysis(VBDTA).Methods Thirty-nine definite or probable ALS patients diagnosed by El Escorial standard and 39 healthy controls were recruited and underwent conventional MR scans and the neuropsychological evaluation.The 3D FSPGR T_1WI and DTI data were collected on GE Medical 3.0 T MRI system.The 3D T_1 structural images were normalized,segmented and smoothed,and then VBM analysis was performed.DTI data were acquired from 76 healthy controls,and FA map template was made.FA maps generated from the DTI data of ALS patients and healthy controls were normalized to the FA map template for voxel-based analysis.ANCOVA was applied,controlling with age and total intracranial volume for VBM and age for VBDTA.A statistical threshold of P＜0.01(uncorrected)and cluster level of more than continuous 20 voxels determined significance.Results Statistical results showed no significant difference in the global volumes of gray matter and white matter,total intracranial volumes and gray matter fraction between ALS patients and healthy controls,but the white matter fraction of ALS patients(0.29±0.02)was significantly less than that of healthy controls(0.30±0.02)statistically(P=0.003).There was significant reduction of gray matter volumes in bilateral superior frontal gyri and precentral gyri,right middle frontal gyrus,right middle and inferior temporal gyrus,left superior occipital gyms and cuneus and left insula in ALS patients when compared with healthy controls;and the regional reduction of white matter volumes in ALS patients mainly located in genu of corpus callosum,bilateral medial frontal gyri,paracentral lobule and insula,right superior and middle frontal gyrus and left postcentral gyrus.VBDTA showed decrease in FA values in bilateral parahipocampal gyri and cingulate gyri in ALS patients compared with healthy controls.Conclusions VBM and VBDTA analysis results suggest that ALS is not simply a motor neuron disease but a multisystem disorder;and VBDTA has a potential value for the detection of FA value changes of cingulate and parahippocampal gyral white matter in suspected cognitive impairment of ALS patients.