Evaluation Of The Characteristic Of Brain Iron Deposition And Clinical Relavance By Quantitative Susceptibility Mapping In Parkinson’s Disease

Objective:Excessive intracranial iron deposition has been demonstrated to play a vital role in Parkinson’s disease(PD),and is relevant to motor symptoms,but there is no consensus of opinions on the correlation between iron deposition and non-motor symptoms.The purpose of this study is to explore the characteristic of PD patients on iron deposition in brain nuclei and the inherent correlation between cranial iron accumulation and clinical motor and non-motor symptoms using quantitative susceptiblity mapping(QSM).Method:This study selected 33 patients with Parkinson’s disease(PD)and 11 age-and gender-matched controls.After detailed medical history collection,all subjects underwent 3.0T brain MRI and were measured magnetic values in regions of interest,including substantia nigra,red nucleus,head of the caudate nucleus,globus pallidus,putamen.All PD patients were assessed of clinical statements using the Unified Parkinson’s Rating Scale(UPDRS),Mini-mental State Examination(MMSE),Hamilton Anxiety Scale(HAMA)and Hamilton Depression Scale(HAMD).The differences of QSM values within ROIs between groups were assessed by 2-tailed T-test.Using Spearman correlation analyses to investigate the link between the magnetic susceptibility in ROIs and clinical scores of PD patients.Furthermore,PD patients with Hoehn-Yahr(H-Y)stage<2.5 and H-Y≥2.5 were classified into mild severity-stage and advanced severity-stage PD groups.Then according to different dominant motor symptoms and UPDRS scores,PD patients were grouped into three subgroups as tremor-dominant PD(TD),akinetic/rigid dominant PD(AR)and mixed type PD(M),for the purpose to compare the pattern of iron deposition and the relationship between subgroups’ magnetic susceptibility values and their clinical characteristics.Results:(1)Compared with the control group,the QSM values of substantia nigra,nucleus rubra and nucleus putamen in PD group were significantly higher(86.30±16.62 vs 66.76±14.63,p=0.001;79.28±20.61 vs 58.94± 17.96,p=0.006;38.73±9.63 vs 28.33±7.51,p=0.003)compared to the CG group.(2)According to the severity of PD,PD was divided into MSP and ASP subgroups.The results showed that iron deposition in the substantia nigra of ASP subgroup was higher than that in CG and MSP subgroups,with statistical difference(p=0.001,p<0.01;p=0.015,p<0.05).There was no statistical difference between iron deposition in the substantia nigra of MSP subgroup and that in the CG subgroup.The difference was(p=0.765);while the red nucleus iron deposition in MSP subgroup and ASP subgroup was significantly higher than that in control group(p=0.015,p=0.012);it is noteworthy that,although there was no significant difference between PD group and control group(p=0.059),the results of further subgroup comparison showed that the QSM value in ASP subgroup was significantly different from that in CG group and MSP subgroup(p=0.008,p<0.01;p=0.02,p<0.05);iron deposition in the putamen was significantly higher in MSP and ASP subgroups than in the control group(p=0.018,p=0.004),but there was no significant difference between MSP and ASP subgroups(p=0.852).(3)Further comparisons were made between the three subtypes of clinical main motor symptoms:substantia nigra,TD,AR and M subtypes of substantia nigra QSM and the control group,and the results were statistically significant(p=0.028,p=0.012,P=0.001);iron deposition of TD and AR subtypes in the red nucleus was significantly different from that in the control group(p=0.014,p=0.018);and in the pallidum,Q deposition in the M subtype was significantly different from that in the control group(p=0.014,P=0.018).Compared with the control group,the SM value was statistically significant(p=0.01),and the QSM value of AR and M subtypes in the putamen was significantly different(p=0.003,p=0.012).(4)The correlation analysis showed that iron deposition in substantia nigra was positively correlated with H-Y stage,UPDRS-Ⅲ score and HAMD(r=0.377,p=0.031;r=0.422,p=0.015;r=0.491,p=0.004);QSM value in globus pallidus was positively correlated with H-Y stage and UPDRS-Ⅲ score(r=0.454,p=0.008,p<0.01;r=0.404,p=0.02,p<0.05).Further subgroup analysis showed that QSM value of substantia nigra was positively correlated with MMSE score in TD subtypes(r=0.771,p=0.025,p<0.05);QSM value of substantia nigra in AR subtype was positively correlated with H-Y stage(r=0.614,p=0.025,p<0.05),UPDRS-Ⅲ score(r=0.792,p=0.001,p<0.01),HAMD(r=0.751,p=0.003,p<0.01),and MNMSS score(r=0.674,p=0.016,p<0.05),HAMA(r=0.691,p=0.013,p<0.05)were positively correlated with SN iron content in the M subtype.In addition,QSM in red nucleus was positively correlated with HAMA score in TD subgroup(r=0.743,P=0.035,p<0.05);QSM in globus pallidus in AR subgroup was positively correlated with UPDRSIII(r=0.677,p=0.011,p<0.05),HAMD score(r=0.588,p=0.034,p<0.05).Conclusion:QSM technique can be used for quantitative assessment of brain iron deposition in PD.Compared with the control group,the iron deposition of the substantia nigra,red nucleus and putamen of PD patients was significantly increased,especially iron accumulation of substantia nigra in middle and late stage of PD severity was significantly higher than that of the control group.Moreover,iron deposition in SN and GP were progressive,which are positively related to the severity of PD disease,UPDRSⅢ.In addition,the iron deposition in regional brain may relevant to somee of the non-motor symptoms of PD,such as depression.Compared the QSM values of different nuclei in each subgroup with clinical data,the results showed that the more severe of the PD condition,and in the akinetic/rigid dominant subtypes of PD may be may be more affected by iron deposition in brain.