Functional And Structural Magnetic Resonance Imaging With 3.0T In Patients With Primary Angle-Closure Glaucoma

Studies based on histological and neuroimaging of glaucoma recently have shown that glaucoma is not only a class of eye diseases,but also a group of neurodegenerative changes involving the entire visual pathway.There is an urgent need to find a method that can accurately evaluate the whole visual pathway to evaluate the severity and monitor the efficacy of primary angle-closure glaucoma(PACG).At present,there are limitations in the diagnosis of glaucoma,that is,it is not possible to diagnose glaucoma at the early stage of retinal injury.In addition,the examination of ophthalmic devices is limited to changes in the eyeball,while there is nothing that can be done about changes in the whole visual pathway involved in the back of the eyeball.With the rapid development of Magnatic Resonance Imaging(MRI)technology,new imaging analysis methods keep emerging.Multi-mode MRI combining morphology and function has the advantages of non-invasive,high spatial resolution,strong repeatability and high reflection localization,and has been widely used in the research of glaucoma.In this study,resting magnetic resonance imaging was used to analyze the changes in the visual pathway in PACG patients from the perspective of structural and functional neuroimaging,and to evaluate the changes and their correlation with ophthalmic parameters.This paper was divided into four parts,as follows:Section ? Frequency-dependent neural activity in primary angle-closure glaucomaObjective:This study aimed to investigate the frequency-dependent spontaneous neural activity in PACG using the amplitude of low-frequency fluctuations(ALFF)method.Methods:In total,52 PACG individuals(twenty-four males and twenty-eight females)and 52 normal sighted controls(NS)(twenty-four males and twenty-eight females)closely matched in age,sex,and education underwent resting-state magnetic resonance imaging scans.A repeated-measures analysis of variance(ANOVA)and post-hoc two-sample t-tests were conducted to analyze the different ALFF values in two different frequency bands(slow-4,0.027-0.073?Hz and slow-5,0.010-0.027?Hz)between two groups.The Pearson's correlation analysis was conducted to reveal the relationship between the mean ALFF values and clinical variables in the PACG group.Results:Compared to NS group,the PACG group had high ALFF values in the right inferior occipital gyrus and low ALFF values in the left middle occipital gyrus,left precentral and left postcentral gyrus in the slow-4 band.The PACG group had high ALFF values in the right inferior occipital gyrus and low ALFF values in the left inferior parietal lobule,left postcentral gyrus and right precentral/postcentral gyrus in the slow-5 band.Specifically,we found that the abnormal ALFF values in the bilateral posterior cingulate gyrus and bilateral precuneus were higher in the slow-4than in the slow-5 band,whereas ALFF in the bilateral frontal lobe,right fusiform,right cerebellum posterior lobe were higher in the slow-4 than in the slow-5 band.The greater mean ALFF values of the right inferior occipital gyrus was associated with the smaller RNFL thickness and the greater VF in PACG group in the slow-4band.Conclusion:Our results high lighted the fact that individuals in PACG groups showed abnormal spontaneous neural activities in the visual cortices,sensorimotor cortices,frontal lobe,frontoparietal network and default mode network at two frequency bands,which might indicate the impaired vision and cognition and emotion function in PACG individuals.These findings offer important insight into the understanding the neural mechanism of PACG.Section? Frequency-specific oscillations synchronization in primary angle-closure glaucomaObjective:Previous studies demonstrated that primary angle-closure glaucoma(PACG)individuals were associated with alterations in cerebral function and structure.Whereas the local oscillations synchronization in different bands changes occurring in PACG individuals were not well understood.The purpose of this study was to investigate frequency-dependent local oscillations synchronization in PACG using regional homogeneity(Re Ho)method.Methods:In total,37 PACG individuals(twenty males and seventeen females)and 37 normal sighted controls(NS)(twenty males and seventeen females)closely matched in age,sex,and education underwent resting-state magnetic resonance imaging scans.We investigate the different Re Ho values in two different frequency bands(slow-4,0.027-0.073?Hz and slow-5,0.010-0.027?Hz)between two groups with a repeated-measures analysis of variance(ANOVA)and post-hoc two-sample t-tests methods using Statistical Parametric Mapping SPM12 software.The pearson correlation analysis was conducted to reveal the relationship between the mean Re Ho values and visual function(Best corrected visual acuity,BCVA and visual field,VF)and optical coherence tomography(OCT)testing(retinal nerve fiber layer thickness,RNFL thickness)in PACG group.Results:Compared to NS group,the PACG group showed increased Re Ho values in the bilateral superior medial frontal lobe in the slow-4 band.The PACG group exhibited decreased Re Ho values in the right calcarine in the slow-5 band.Specifically,we found that the abnormal Re Ho values in the right superior frontal lobe were greater in the slow-4 than in the slow-5 band,whereas Re Ho in the left calcarine,right pallidum,left Inferior occipital gyrus,left superior occipital gyrus,left postcentral/angular gyrus,left paracentral lobule,left superior parietal gyrus and right precuneus gyrus were greater in the slow-5 than in the slow-4 band.In the slow-5 band,The mean Re Ho values of the right calcarine showed a positive correlation with the RNFL thickness and negative correlation with the VF of PACG.Conclusion:Our results demonstrated that PACG groups showed abnormal local oscillations synchronization in visual network,sensorimotor network and default mode network at two frequency bands(slow-4 and slow-5 band).Moreover,the local oscillations synchronization in slow-5 band showed closely relationship with the severity of PACG individuals.These findings offer a novel technology to assess the neural mechanism of PACG.The frequency factor should be taken into consideration in exploration of local oscillations synchronization to understand the neural mechanism of PACG.Section? Abnormal resting-state functional connectivity within the default mode network subregions in primary angle-closure glaucoma Objective:The aim of this study was to explore the functional connectivity(FC)differences between the paired default mode network(DMN)subregions in patients with Primary angle-closure glaucomaa(PACG).Methods:In total,47 PACG individuals(twenty males and twenty-seven females)and 47 normal sighted controls(NS)(twenty males and twenty-seven females)closely matched in age,sex,and education underwent resting-state magnetic resonance imaging scans.SPM8 software and seed-based region of interest rs-FC method were used to analyze the connectivity between each pair of subregions within the DMN between the PACG and the NS.Results:Compared with the NS,the PACG showed significant decreased region-toregion FC between the right medial temporal lobe(MTL)and the left hippocampus formation(HF)(t =-3.12,P = 0.002),and between the left medial temporal lobe and the right hippocampus formation(t =-2.297,P = 0.024).Conclusion:PACG showed disrupted FC within the DMN subregions.It suggests that DMN may be involved in the pathogenesis of PACG.The decreased functional connectivity of MTL.R-HF.L and MTL.L-HF.R may be the potential pathogenesis of cognitive and emotional dysfunction in PACG patients.Section ? A voxel-based morphometric 3.0T MRI study in primary angle-closure glaucomaObjective:The aim of this study was to explore the whole-brain gray matter volume(GMV)difference between primary angle closure glaucoma(PACG)patients and health controls(HCs)using a voxel-based morphometry method.Methods:In total,47 PACG individuals(twenty males and twenty-seven females)and 47 normal sighted controls(NS)(twenty males and twenty-seven females)closely matched in age,sex,and education underwent resting-state magnetic resonance imaging scans.We investigated the different GMV values between two groups.The MRI data were processed using SPM8 software in voxel-based morphometry method.Results:Compared with HCs,PACG showed decreased gray matter volume in bilateral cerebellum posterior lobe?left insula?right superior temporal gyrus?left middle temporal gyrus?right middle frontal gyrus and increased gray matter volume in right insula?right middle frontal gyrus.Conclusion:We demonstrated that PACG patients showed altered brain structure in visual pathway regions and emotional system,which might provide some useful informations to explore the neural mechanisms of impaired long distance vision?emotional and cognitive disorder in PACG.