A Magnetic Resonance Imaging Research Of KIBRA Gene Polymorphism's Effect On Brain Microstructure Among The Healthy Young

Objective:To explore the relationship between KIBRA gene polymorphism and brain microstructure among the healthy youngin.diffusion tensor imaging(DTI)and Diffusional Kurtosis Imaging(DKI).Materials and methods::Enrollment criteria:Healthy young volunteers aged 18-30 years;(2)Right-handedly assessed by the Chinese Expert Hand Scale;(3)Chinese native speakers of the Han nationality;(4)Normal vision or corrected visual acuity and Colorblindness;(5)No history of physical,mental,or endocrine diseases;(6)No history of drug or alcohol abuse;(7)No medications being taken;(8)Contraindications without MRI;(9)Conventional cranial MRI scans rule out organic disease.A total of 100 healthy young Chinese subjects(mean age:25±1.54 years;ranging 23-28 years;60 females,40 males;Careful screening was performed to ensure that all participants were free of any lifetime history of psychiatric or neurological illness,psychiatric treatment,or drug or alcohol abuse,and MR contraindications.To avoid population stratification artifacts,only Chinese Han with right-hand were included.5 ml of peripheral blood was collected to check the C/T allele polymorphism of the KIBRA gene rs 17070145;These subjects were divided into two groups including 53 TT homozygotes and 47 C-allele carriers(37 CT and 10 CC carriers)according to the KIBRA genotypes.All the participants had a routine MRI T2WI scanning,3D-T1 scanning,DTI scanning,DKI scanning.The process of DTI:Firstly,image preprocessing:the original DICOM dates were converted into a NII format by using the dcm2niigui software.Eddy current-induced distortion and motion artifacts were corrected using affine alignment of each diffusion weighted image using FMRIB's diffusion toolbox(FSL 4.0,http://www.fmrib.ox.ac.uk/fsl).After skull-stripping,DTIFIT software was used to calculate AxD,RD,MD,FA.Each subject's FA map was non-linearly registered to the MNI spatial average FA template map(FMRIB-58).The registered the FA map was compressed to generate an average FA skeleton map.Each of the registered FA maps was then projected to the average FA skeleton map to generate the respective FA skeleton.The FA mapof each subject was non-linearly registered to the AxD,RD and MD maps and the parameter maps for each index after registration were generated and then projected onto the average FA fiber skeleton.The process of DKI:the preprocession of DKI was same with DTI.For each subject,the T1-weighted image was segmented into GM,WM and cerebrospinal fluid to generate a mask in Rest.Diffusional Kurtosis Estimator(http://www.nitrc.org/projects/dke)was implemented to calculate the diffusion and kurtosis tensors including mean kurtosis(MK),axial kurtosis(AK),radial kurtosis(RK),kurtosis fractional anisotropy(KFA)as well as fractional anisotropy(FA),mean diffusivity(MD),axial diffusivity(AD),and radial diffusivity(RD).Statistical analysis,the voxel-based whole-brain non-parametric statistical comparison(randomize)was performed to detect WM differences in all DTI diffusion between TT homozygotes and C-allele carriers.The ranking value was set to 5000 P<0.05(threshold-free Cluster enhancement,TFCE).Two-sample tests were applied to detect WM and GM differences in all DKI diffusion and kurtosis parameters between TT homozygotes and C-allele carriers in SPM8.Results:DTI results:based on the TBSS method.there was no difference in all diffusion parameters between the KIBRA-TT homozygote and the KIBRA-C group with P<0.05(TFCE correction).DKI results:based on DKI,no significant differences was found between KIBRA TThomozygotes and C-allele carriers in all diffusion and kurtosis parameters with P value<0.05(FDR cor).However,we investigated several differences between the two groups using a relatively loose threshold(P<0.001 uncorrected with a minimum cluster size 10).Group differences in Whiter matter(WM)Compared with TT homozygotes,KIBRA C-allele carriers showed increased AD,MD,RD,decreased AK and MK in right postcentral gyrus WM.And we found increased AD,MD,RD and decreased KFA in right periventricular WM in KIBRA C-allele carriers..Group differences in gray matter(GM)Relative to TT homozygotes,KIBRA C-allele carriers showed increased AD,MD,RD in right postcentral gyrus and right insula,decreased AK,MK in right postcentral gyrus,as well as decreased FA,KFA in right caudate head.The results are listed in Table 2.Moreover,KIBRA C-allele carriers showed increased MK and RK in the left parahippocampus,compared to TT homozygotes.Conclusion:In this study,the application of magnetic resonance DTI and DKI technology did not find a significant effect of KIBRA gene polymorphism on the brain microstructure of healthy young people.However,under the relatively loose threshold,many important brain regions have differences in diffusion kurtosis indicators.Whether the differences are significant with age still needs further verification.