Multi-modal Magnetic Resonance Imaging Studies In Patients With Multiple System Atrophy

Objective: multiple system atrophy(MSA)is a kind of sporadic and progressive neurodegenerative disease.According to the typical clinical symptoms,MSA can be divided into two types: Parkinson’s disease(MSA-P)with tremor and rigidity,and cerebellar disease(MSA-C)with ataxia and postural gait instability.A large number of neuropathological evidences show that cerebellum is the most consistent injury site in MSA patients.Both MSA-P and MSA-C show structural and functional abnormalities in a wide range of cerebellar regions.It is suggested that cerebellar abnormalities may be involved in the progression of MSA.However,most of the previous studies have focused on the cerebellum as a whole.In fact,the cerebellum is not a main body of structure and function,in which the anterior cerebellar lobe(I-V)is related to movement,and the posterior cerebellar lobe(V-X)is related to the regulation of cognitive function.Different cerebellar subregions act on specific cerebral cortex through the cerebellar thalamic cortical loop to play a regulatory role in movement and cognition.It is difficult to summarize the overall information of the disease in the study of cerebellum level.Therefore,focusing on the study of cerebellar subregion and further exploring the possible effect of atrophy of cerebellar gray matter on cerebellar cerebral circuit will help to deepen the clinical understanding of the disease progress and motor and cognitive regulation of cerebellum in MSA patients,and provide pathophysiological signs for further revealing the causes of the differences between the clinical symptoms of the two subtypes of cerebellum,which is of far-reaching significance for clinical diagnosis and prognosis prediction.Multimodal MR imaging is a common research method and an important part of radiology.The main technologies include high-resolution structural MRI(3D-T1),blood oxygen level dependent functional MRI(BOLD-fMRI),etc.The 3D-T1 based SUIT(spatially unbounded intrinsic template)is a cerebellar high-definition template developed in recent years.It has the advantage of using automatic non-linear normalization method,with small individual spatial difference and keeping the anatomical details of small brain area,so as to realize more accurate quantification of cerebellar sub area.Compared with the whole brain voxel based morphometry(VBM)method,it is more accurate and sensitive to cerebellar changes.The method of functional connection based on resting state can analyze the interaction between cerebellum and other brain regions,and then we can get the brain regions with significant changes in functional connection with cerebellum;function and anatomy are closely related and inseparable,and the realization of brain function is based on anatomical connection.Therefore,this study will apply these technologies jointly,through structure and function.To explore the role of cerebellum in the subtypes of patients with multiple system atrophy and the role of cerebellum in cognitive impairment of patients with multiple system atrophy.Methods: 60 patients with multiple system atrophy were included in this study.The diagnosis of MSA patients was in line with the second edition of expert diagnosis consensus in 2008.At the same time,60 healthy volunteers from the same area were collected,and the control group matched with gender,age and education level.According to the unified multiple system atrophic Rating Scale(UMSARS)and the Unified Parkinson’s Disease Rating Scale(UPDRS),the patients were divided into MSA-P and MSA-C groups.All subjects used 3.0T MR(Siemens,Germany,magnum Verio),32 channel head coil scanning(the scanning sequence mainly includes 3d-t1,bold sequence),and collected UMSARS(Unified multiple system atrophy rating scale,UMSARS),UPDRS(Unified Parkinson’s disease rating scale,UPDRS),the Montreal Cognitive Rating Scale(the Montreal Cognitive a The scores of such scales as cessment,MOCA and MMSE were analyzed in clinical epidemiology.1.Structural MRI study of cerebellar subregion in patients with multiple system atrophy subtype: using the VBM imaging technology based on suit to analyze and compare the cerebellar subregion of MSA-P and MSA-C patients,and further analyze the correlation with clinical motor and cognitive scores.2.Functional magnetic resonance imaging of cerebellum brain in patients with multiple system atrophy subtype: FC imaging technology based on seed point was used to analyze and compare the cerebellum brain network of MSA-P and MSA-C patients,and to further analyze the correlation with clinical motor and cognitive scores.3.The study of global brain network imaging in patients with multiple system atrophy with cognitive impairment: combined FC imaging technology based on degree centrality and seed point,firstly,the brain areas of MSA patients with or without cognitive impairment with degree centrality change were analyzed and compared,and the brain areas directly related to cognitive change were obtained;then FC imaging based on degree centrality result was used as seed point Technology to analyze MSA patients with or without cognitive impairment.Results: 1.Structural MRI study of cerebellar subregion in MSA-C patients: compared with the normal control group,the main manifestations of MSA-C patients were the decrease of gray matter volume of anterior cerebellar lobe(lobles Ⅲ-V)and posterior cerebellar lobe(Crus Ⅰ,crus Ⅱ,loble VIII,loble Ⅸ).MSA-P patients showed the similar decrease and part of gray matter volume of anterior cerebellar lobe(lobles Ⅲ-Ⅴ).Atrophy of the posterior lobe of the cerebellum.Direct comparison of MSA-P and MSA-C patients showed that crus Ⅱ in the right cerebellum was the only abnormal sub region.Correlation analysis showed that the anterior lobe of cerebellum was related to the progress of disease and the severity of movement in MSA patients.Most of the posterior lobe of cerebellum was related to clinical cognitive function,and some of them were related to clinical motor score.2.Functional magnetic resonance imaging of cerebellum and brain in patients with multiple system atrophy subtypes: the methods of MSA-P,MSA-C and HC groups were analyzed and found that the resting functional connections of multiple brain regions were decreased,among which,compared with MSA-P and the normal control group,the FC of DMN,motor cortex,basal ganglia and limbic system regions were decreased.In MSA-C group,the functional connections of right insula,right superior temporal gyrus,parahippocampal gyrus,putamen and amygdala were decreased,and the areas of FC decreased were limited in the right cerebral hemisphere.The MSA-P of bilateral anterior cuneiform lobe,median cingulate cortex,right insular lobe and right superior temporal gyrus were significantly higher than that of MSA-C FC in patients with Parkinson’s and cerebellar MSA.The correlation analysis showed that MOCA score was positively correlated with right anterior cuneiform lobe,left prefrontal lobe,bilateral median cingulate cortex and right superior temporal gyrus(r = 0.50,P = 0.00 *).3.Compared with HC,patients with MSA-CI and those with MSA with normal cognition(MSA-NCI)exhibited lower DC values in the left calcarine and right postcentral regions and higher DC values in the bilateral caudate and left precuneus.There were significant differences in the DC values in the right mid-dle prefrontal gyrus between the MSA-CI and MSA-NCI groups.The mean DC values in the right middle prefrontal gyrus(RMPFG)were correlated with clinical cognitive severity.Consequently,we used this brain region as a seed in secondary seed-based FC analysis and observed FC changes within the right pre-cuneus,inferior parietal lobe,and right insula.Conclusion: the cerebellum is widely involved in the regulation of motor and cognitive function in MSA patients.The atrophy of Ⅳ-Ⅴ gray matter in the anterior lobe of cerebellum is related to the progress of disease and motor function injury in MSA patients.The decrease of gray matter volume in crus Ⅱ,part of cerebellum Ⅷ and Ⅸ in the posterior lobe of cerebellum is related to the cognitive atrophy of disease.MSA-P Most of the lesions were located in the posterior lobe of the cerebellum.In order to further understand the role of cerebellum in cognitive regulation of MSA patients,DC-FC method was used in this study.It was found that there were more areas of cerebellum atrophy in MSA patients with cognitive impairment.FC research based on these brain areas as seed points found that the decrease of cerebellum DMN functional connection,the increase of cerebellum inconsistent limbic system FC and MSA were the main causes of cognitive impairment in MSA patients.