The Comparison Of Multimodal Mri About Brain Alternation Between Patients With Multiple Sclerosis And Neuromyelitis Optica Spectrum Disorder

PART 1 THE RELATIONSHIP BETWEEN CHOROID PLEXUS VOLUME AND BRAIN ATROPHY IN PATIENTS WITH MULTIPLE SCLEROSIS AND NEUROMYELITIS OPTICA SPECTRUM DISORDERPurpose: To investigate the differences of choroid plexus volume,ventricular system volume,cortex thickness of sulcus,cortex thickness of gyrus,deep gray matter volume between multiple sclerosis(MS)and neuromyelitis optica spectrum disorder(NMOSD)and further analyze the correlation between choroid plexus volume and whole brain tissue atrophy.Materials and Methods: A total of 51 patients with MS,42 patients with NMOSD,and 56 health controls(HC)were recruited and of these 20 patients with NMOSD and 25 patients with MS were also studied at follow-up.T2-FLAIR,3DT1 image data and clinical data of all subjects were collected.Free Surfer software was used to quantify the whole brain tissue.The differences of whole brain tissue between MS and NMOSD patients at baseline and follow-up were compared,including: volume values of 5 ventricular systems and choroid plexus;the total volume of 14 brain structures;cortical thickness of 74 brain regions in the left and right cerebral hemispheres;volume of 16 deep gray matter.And the correlation between bilateral choroid plexus volume and global brain atrophy was further explored.Results:(1)Results of cross-sectional study: compared to HC,MS showed higher choroid plexus volume(p<0.001),NMOSD showed not significant difference in choroid plexus volume(p>0.05).MS and NMOSD showed different pattern of whole brain atrophy.MS had widespread atrophy in the whole brain(including cortical atrophy,deep gray matter atrophy,p<0.001,FDR corrected),and the cortical atrophy range of sulcus area(61%,41/67)was larger than that of gyrus area(43%,29/67)in MS.NMOSD showed the moderate brain atrophy(including deep gray matter atrophy,p<0.001,FDR corrected).There were widespread correlations between the choroid plexus volume and cerebral cortex thickness in MS(p<0.05,r=-0.292~-0.538,FDR corrected)and NMOSD(p<0.05,r=-0.325~-0.572,FDR corrected).(2)Results of longitudinal study: there was no significant difference in the follow-up interval time between MS patients(1.37 years)and NMOSD patients(1.25 years)(p> 0.05).The EDSS scores were slightly aggravated in MS(p=0.001)and NMOSD(p=0.017).The volume of T2 lesions wereincreased in MS(p=0.026)and NMOSD(p=0.013).The volume of deep gray matter was reduced in MS(p<0.001,FDR corrected),but there was no significant aggravation of brain atrophy in NMOSD(p>0.05).Conclusion: MS showed extensive brain atrophy with increased volume of bilateral choroid plexus,and NMOSD showed only local brain atrophy.The whole brain atrophy of MS showed that the atrophy range of sulcus area was larger than that of gyrus area.In addition,the progressive atrophy in short-term follow-up was shown in MS but not in NMOSD.PART 2 THE DIFFERENT PATTERN OF WHITE MATTER MICROSTRUCTURE DAMAGE BETWEEN MULTIPLE SCLEROSIS AND NEUROMYELITIS OPTICA SPECTRUM DISORDER: A CROSS-SECTIONAL AND FOLLOW-UP OF TRACT-BASED SPATIAL STATISTICS STUDYPurpose: To investigate the difference of DTI parameter abnormalities between MS and NMOSD based on Track-Based Spatial Statistics(TBSS).Materials and Methods: The subjects in this part were the same as the first part of this study.T2-FLAIR,3DT1 and DTI image data and clinical related data of all subjects were collected.In the present combined cross-sectional and longitudinal study,the novel DTI technique of TBSS was used to investigate the difference of DTI parameter abnormalities between MS and NMOSD.Results:(1)Results of cross-sectional study: reduced fractional anisotropy(FA),increased mean diffusivity(MD),axial diffusivity(AD)and radial diffusivity(RD)were observed in patients with MS(p<0.05)and reduced FA was shown in NMOSD(p<0.05)compared to HC.The abnormality of DTI parameters were greater in patients with MS than that in patients with NMOSD(p< 0.05,TFCE corrected).(2)Results of longitudinal study: There were significantly reduced FA,and increased MD and RD in patients with MS(p< 0.05),but no significant changes in patients with NMOSD(p> 0.05).Conclusion: Both MS and NMOSD have microstructure damage in white matter,while the progressive change in brain microstructural properties is observed in patients with MS but may not in patients with NMOSD in a short-term follow-up.PART 3 THE DIFFERENCE MICROSTRUCTURE DAMAGE OF NORMAL-APPEARING WHITE MATTER AND WHITE MATTER LESION BETWEEN MULTIPLE SCLEROSIS AND NEUROMYELITIS OPTICA SPECTRUM DISEASESPurpose: To investigate the microstructure difference of normalappearing white matter(NAWM)and white matter lesion in the 20 white matter tracts between MS and NMOSD and their clinical significance.Materials and Methods: The subjects in this part were the same as the first part of this study.T2-FLAIR,3DT1 and DTI image data and clinical related data of all subjects were collected.The whole white matter was further segmented into NAWM and T2-lesions in patient groups.Furthermore,the values of FA,MD,AD and RD were computed from the DTI data.Finally,the twenty principal white matter tracts were extracted from the DTI data.The correlations with clinical variables were investigated.Results: Compared to NMOSD,the lower NAMW and higher lesion volume were shown in MS.MS had microstructure damage of NAWM in20 tracts(p<0.05,FDR corrected)and NMOSD had microstructure damage of NAWM in 7 tracts(p<0.05,FDR corrected),with more damage of NAWM in 20 tracts in MS compared to NMOSD.NMOSD had more microstructure damage in 3 tracts of lesion(p<0.05,FDR corrected),but similar microstructure in 17 tracts compared to MS.The microstructure of NAWM in MS(p<0.05,r=-0.68~0.71,FDR corrected)and NMOSD(p<0.05,r=-0.72~0.72,FDR corrected)and microstructure of lesion(p<0.05,r=-0.69~0.97,FDR corrected)in MS were associated with lesion volume and clinical parameters.The DTI parameters of 13 NAWM in MS(p<0.05,r=-0.42~0.80,FDR corrected)and 5 NAWM in NMOSD(p<0.05,r=-0.61~0.89,FDR corrected)were correlated with the DTI parameters of lesion in the same tract.Conclusion: Patients with MS have more microstructural damage in NAWM and similar damage in T2 lesion compared to patients with NMOSD.Both MS and NMOSD may have the mechanism of Wallerian degeneration induced by lesions to NAWM.PART 4 THE DIFFERENT PATTERN OF STRUCTURE AND FUNCTIONAL NETWORK BETWEEN MULTIPLE SCLEROSIS AND NEUROMYELITIS OPTICA SPECTRUM DISEASES BASED ON GRAPY ANALYSISPurpose: To investigate the differences of structural and functional network abnormalitis between MS and NMOSD at cross-sectional and follow-up.Materials and Methods: The subjects in this part were the same as the first part of this study.T2-FLAIR,3DT1,DTI and BOLD image data and clinical data of all subjects were collected.The fiber number network based on DTI of whole brain was constructed by Metrix3 software,and the functional network was constructed by GRETNA software.The topological attribute differences between structural network and functional network in the three groups were analyzed,including global efficiency,local efficiency,clustering coefficient,shortest distance,rich club connection,feeder connection and peripheral connection.The longidtudinal of the topological of networks in MS and NMOSD were analyzed.Results:(1)Results of cross-sectional study: In DTI structure network,compared to HC and NMOSD groups,the global efficiency,local efficiency and clustering coefficient of MS group were decreased(p<0.05,FDR corrected),and the shortest path was increased(p<0.05,FDR corrected),but there was no significant difference between NMOSD and HC group.Compared with HC,the rich-club connection,feeder connection and peripheral connection in MS group were reduced(p<0.05,FDR corrected).In functional network,compared with HC and NMOSD,MS group showed increased rich-club connectivity(p<0.05,FDR corrected).The DTI network parameters in MS(p<0.05,r=-0.319~-0.745,FDR corredted)and NMOSD(p<0.05,r=-0.491~0.656,FDR corrected)showed correlations with lesions volume and clinical data.(2)Results of longitudinal study: there was no significant difference in the structural network and functional network between MS and NMOSD(p>0.05,FDR corrected).Conclusion: The different damage patterns of structural and functional networks are different between MS and NMOSD patients.MS have decreased DTI network efficiency with the increased functional network connection.NMOSD is mainly characterized by slight efficiency reduction of DTI network efficient.In the short-term follow-up,neither of them have the signs of progressive network destruction.PART 5 THE DIFFERENCE OF SHORT,MIDDLE AND LONG CONNECTION FIBERS BETWEEN MULTIPLE SCLEROSIS AND NEUROMYELITIS OPTICA SPECTRUM DISEASESPurpose: To investigate the differences of short-distance connection,middle-distance connection and long-distance connection fibers between MS and NMOSD,and their correlation with whole brain tissue volume,structural network and functional network parameters.Materials and Methods: The subjects in this part were the same as the first part of this study.T2-FLAIR,3DT1,DTI and BOLD image data and clinical data of all subjects were collected.The whole brain fiber connection was constructed by Metrix3 software,and divided into three groups according to the length of all fiber bundles in HC group,including short-distance connecting fibers,middle-distance connection fibers and long-distance connecting fibers.The differences of the fiber number and FA among the three groups were compared.The correlations between the fiber number and FA value of each fiber and the whole brain tissue volume,structural network and functional network parameters were further analyzed.Results: Compared with HC and NMOSD groups,the total number of fiber in MS group was decreased,including the decreased number of long-distance connection fibers and middle-distance connection fibers(p<0.05,FDR corrected),but the number of short-distance connecting fiber was increased(p<0.05,FDR corrected).Compared with HC group,the FA values of three fibers in MS and NMOSD group were decreased(p<0.05,FDR corrected),and the decreased FA values in MS group was greater than that in NMOSD group(p<0.05,FDR corrected).In MS and NMOSD groups,there were correlations between the number of short-distance,longdistance connection fiber and the atrophy of whole brain tissue,structural network topological parameters(p<0.05,r=-0.594~0.699,FDR corrected).Conclusion: MS and NMOSD show different damage patterns of the short-,middle-and long-range connections.Both MS and NMOSD patients had microstructural damage in short-,middle-and long-range connections,but MS has specific reduction in the number of fiber in middle-and longdistance connections.Connection damage of different lengths in both MS and NMOSD may be associated with brain atrophy,whereas the fiber connection damage of MS can better explain the decrease of its network efficiency.