Multimodal Magnetic Resonance Imaging In Autism Spectrum Disorders And Alzheimer's Disease

Part 1:Principles of Multimodal Magnetic Resonance Imaging and Key Steps of Data ProcessingCombined analysis of multimodal magnetic resonance imaging can combine the advantages of various magnetic resonance imaging techniques and improve the comprehensive understanding of the pathophysiological characteristics of neurological diseases using their complementarity.In this paper,four magnetic resonance imaging techniques,QSM,rs-fMRI,DTI and ASL were used to study the patients with ASD and AD.This part mainly introduces the principle of these four magnetic resonance imaging techniques and the key steps of data processing.Part 2:Imaging Biomarkers for Brain Development in Children with Autism Spectrum Disorder Based on Multimodal Magnetic Resonance ImagingObjective:To compare the alterations of brain iron level,brain function,white matter fiber structure and cerebral blood flow between autism spectrum disorder(ASD)and healthy control using quantitative susceptibility mapping(QSM),diffusion tensor imaging(DTI),resting-state functional magnetic resonance imaging(rs-fMRI)and arterial spin labeling(ASL),Then to explore whether the abnormal imaging indicators values of ASD are correlated with the degree of brain development.Methods:In this single-center case-control study,20 children with ASD aged 3-8 years and fifteen healthy controls aged 3-8 years were recruited.Their clinical characteristic and rating scales were collected and all received QSM,rs-fMRI,DTI and ASL scan.We collected susceptibility values of brain regions in QSM,amplitude of low frequency fluctuation(ALFF)values and regional homogeneity(ReHo)values of brain regions in rs-fMRI,fractional anisotropy(FA)value and mean diffusivity(MD)value of white matter fiber in DTI and cerebral blood flow(CBF)values of brain regions in ASL.Symptoms of ASD were assessed by the Autism Behavior Checklist(ABC),and brain development was evaluated by the Gesell Development Scale(GDS).Two-sample t test was used to detect the difference of the imaging indicators values between ASD and healthy controls.Pair t-test was utilized to compare the imaging indicators between the left and right sides brain in ASD patients and healthy controls.In addition,Partial correlation analysis was conducted to investigate possible correlations between the imaging indicators values and GDS scores in ASD preschoolers.Results:Compared with healthy controls,the susceptibility values of bilateral red nuclei,bilateral frontal white matter and left temporal white matter were decreased(P=0.003,0.008,0.002,0.001,0.014)in patients with ASD.The susceptibility values of the caudate nucleus and thalamus presented significant asymmetry and the values of right side were significantly higher than left side in the preschoolers with ASD(P=0.005,0.005).The susceptibility values of the left thalamus was lower than that of the right in healthy controls(P=0.007).The ALFF values of superior frontal gyrus,middle frontal gyrus,medial frontal gyrus,inferior frontal gyrus and orbital inferior frontal gyrus were lower than those in healthy controls,and the ReHo values of medial frontal gyrus,precentral gyrus,left paracentral lobule and right supplementary motor area in ASD patients were higher than those in healthy controls.The FA values of bilateral Posterior thalamic radiation(include optic radiation),Inferior fronto-occipital fasciculus,and Inferior longitudinal fasciculus in ASD patients were lower than those in healthy controls(P=0.049,FWE adjusted),while the MD values of right Posterior thalamic radiation(include optic radiation),Superior corona radiata,Retrolenticular part of internal capsule,Inferior longitidinal fasciculus,Inferior fronto-occipital fasciculus,and Posterior corona radiata in ASD patients were higher than those in healthy controls(P=0.033,FWE adjusted).The CBF values in the right parietal,temporal and occipital lobes of ASD were higher than those in the left(P<0.05).In addition,the susceptibility values of the right globus pallidus were positively correlated with the Gesell-fine motor scale score(r=0.560,P=0.024),while there was no significant correlations found in other imaging indicators.Conclusions:QSM,rs-fMRI,DTI and ASL techniques can be used to study the changes of brain iron level,integrity of white matter fibers,brain function and cerebral blood flow in patients with ASD.In patients with ASD,there was an abnormal decrease of iron levels in several brain regions,abnormal activation in several brain regions,structural abnormality in several white matter fiber tracts.The iron level of the right globus pallidus was negatively correlated with the severity of disease in patients with ASD.Studies have shown that susceptibility values measured by QSM,ReHo and ALFF values measured by rs-fMRI,FA and MD values measured by DTI are expected to be potential imaging biomarkers for early diagnosis of ASD,and the susceptibility values of right globus pallidus is expected to be an imaging marker for the evaluation of neurodevelopmental severity in ASD patients.These findings provided new insights to future investigation of the pathophysiology of ASD,and provide neuroimaging evidence for objective and quantitative assessment of neurodevelopmental severity in patients with ASD.Part 3:Longitudinal Assessment of Cerebral Iron Level and Cerebral Blood Flow in Alzheimer's Disease Based on Multimodal Magnetic Resonance ImagingObjective:To longitudinally explore the one-year alterations of iron levels,brain function,white matter fiber structure and cerebral blood flow in patients with Alzheimer's disease(AD)utilizing QSM and ASL techniques.Methods:Initially,fifty-five patients with AD were enrolled in this prospective cohort study.Clinical characteristic,cognitive rating scale and QSM,ASL and 3D-T1 image were acquired.A total of fifteen patients completed the one-year follow-up.ROIs included bilateral globus pallidus,caudate nucleus,putamen,dentate nucleus,red nucleus,substantia nigra and hippocampus.The susceptibility values of all ROIs were obtained at baseline and one year later.Mini-Mental State Examination(MMSE)and Montreal Cognitive Assessment(MoCA)were used to assess the cognitive function of AD patients.Paired t-test was used to compare the baseline and one year later all imaging indicators values of regions of interest.In addition,Partial correlation analysis was utilized to calculate the potential correlations between all imaging indicators values and the cognitive rating scores in AD patients and explore whether the alterations of all imaging indicators values were correlated with the changes of cognitive function.Results:Compared with the baseline,the iron levels of the left putamen,left dentate nucleus and right hippocampus significantly increased at the one-year follow-up.The susceptibility values of the left red nucleus and right substantia nigra were negatively correlated with MMSE score(P=0.022,P=0.048),and the susceptibility value of the right hippocampus was positively correlated with MMSE score(P=0.047).There was no significant change in cerebral blood flow in each brain region within one year(P>0.05),and there was no significant correlation between cerebral blood flow in each brain region at baseline and the scores of MMSE and MOCA scales.Conclusions:The iron level in the left putamen,left dentate nucleus and right hippocampus of AD patients increased significantly within one year.The susceptibility values of left red nucleus and right substantia nigra were correlated with cognitive function scores,and relevant findings provide new insights for further study of the pathophysiological mechanisms of AD patients.