The Study Of Quantitative Susceptibility Mapping About Brain Iron Deposition On Parkinson's Disease

OBJECTIVES 1)To assess the feasibility of quantitative assessment on deep grey matter nuclei iron deposition by drawing regions of intererest(ROIs)on susceptibitly maps manually.2)To assess iron variations in multiple deep grey matter nuclei in early idiopathic PD using quantitative susceptibility mapping(QSM).3)To test the hypothesis that DN iron may be elevated in tremor dominant PD patients using QSM.4)To assess the diagnostic performance of the Nigrosome-1 for PD based on on susceptibility maps.5)We employ QSM images to develop an improved dentate nucleus atlas for use in imaging studies.MATERIALS AND METHODS Thirty-five healthy volunteers were recruited in the first part.A three-dimensional 8-echo GRE sequence was acquired on a 3.0 T MR system for each subject.Then QSM was reconstructed based on phase maps,and R₂^*was calculated based on magnitude maps.Two neuro-radiologists drew ROIs which include the head of caudate nuclei,putamen,globus pallidus,substantia nigra,and red neuclei on susceptitbility maps seprerately.Intraclass correlation coefficient was calculated to assess the inter-rate reliability of the two neuro-radiologists segmenting ROIs on susceptibility maps.Pearson's correlation analysis was applied between susceptibility values in different ROIs and the previously published iron concentrations for these brain regions.In addition,forty-four early idiopathic Parkinson's disease(PD)patients and 35 age-and gender-matched healthy controls were recruited for the second part study.MRI scanning and image analyses are the same as the first part.The inter-group differences of susceptibility and R₂^*value within ROIs were calculated by performing analyses of covariance(ANCOVA).The correlations between regional iron deposition and the clinical features were explored in early PD patients by performing Pearson analyses.In the third part,forty-three patients with PD[19 tremor dominant(TD)/24 akinetic-rigid dominant(AR)]and 48 healthy gender-and age-matched controls were recruited.Nineteen(TD:13;AR:6)PD patients were drug na?ve.16-echo GRE data were collected for each subject on a 3.0 T MR system.Inter-group susceptibility differences in bilateral DN were investigated by performing ANCOVA,and Pearson analyses between clinical features and susceptibility values were also examined.In the fourth part,two cohorts were analyzed retrospectively.They are Cohort I(all subjects from Part I,8-echo GRE)and Cohort II(all subjects from Part II,16-echo GRE).Two neuro-radiologists evaluated the visibility of Nigrosome-1 on susceptibility maps separately blind to the diagnosis of each subject.There are three rating types:present,possible present,and absent.Then all the subjects were classified into three groups based on the visibility of Nigrosome-1:normal group,PD group,and non-diagnositc group.At last,the diagnostic performance was assessed against clinical dianogsis as gold standard.In the last part,thirty-eight healthy volunteers were reruited and 16-echo gradient echo data were collected for each subject on a 3.0 T MR system.QSM were reconstructed.DN was segmented in susceptibility images semi-automatically by using thresholding method.The resulting DN masks from QSM DN volume were transformed to T1 space and then transformed to MRI common space(Montreal Neurological Institute,MNI).At last,they were averaged to generate the DN probability atlas in MNI space.RESULTS 1)ICCs for absolute agreement between raters with respect to all the segmented ROIs were greater than 0.81.Susceptibility values and R₂^*values within ROIs were positively correlated with iron concentrations,respectively(QSM:r=0.969,p=0.007;R₂^*:r=0.831,p=0.041).2)Susceptibility values were found to be elevated within bilateral SN(ipsilateral:p<0.001;ontralateral:p<0.001)and RN contralateral(p=0.002)to the most affected limb in early PD patients compared with healthy controls.The finding of increased susceptibility in bilateral SN is consistent with work on a subgroup of patients at the earliest clinical detectable state(Hoehn&Yahr,Stage I).However,increased R₂^*values were only seen within SN contralateral(p=0.004)to the most affected limb in the PD group when compared with controls.Furthermore,bilateral SN magnetic susceptibility positively correlated with disease duration(ipsilateral:r=0.3915,p<0.01;contralateral:r=0.3470,p<0.05)and UPDRS-III scores(ipsilateral:r=0.3865,p<0.05;contralateral:r=0.3678,p<0.05)in early PD.3)In contrast to the AR group,the TD group was found to have increased susceptibility in the bilateral DN(ipsilateral:p=0.016;contralateral:p=0.015),when compared to healthy controls.In addition,susceptibility was positively correlated with tremor score in drug naive PD patients(ipsilateral:r=0.69,p=0.003;contralateral:r=0.60,p=0.01).4)In Cohort I,42/44 PD and 10/35 control,and in Corhort II,42/43 PD and 29/48control were correctly classified.Diagnostic accuracy of Cohort I was:sensitivity 95.5%,specificity 28.6%,positive predictive value(PPV)65.6%,negative predictive value(NPV)100%and accrucy 66%,while in Cohort II,the diagnostic accuracy was:sensitivity 97.7%,specificity 60.4%,PPV 75%,NPV 100%and accrucy 78%.5)The center of mass of the left and right sides of the QSM-based DN atlas in MNI space was(-13.8 mm,-55.8 mm,-36.4 mm)and(13.8 mm,-55.7 mm,-36.4 mm),respectively.The maximal overlap and mean overlap of the DN atlas with the individually segmented DNs in this cohort was 100%and 39.3%,respectively.CONCLUSIONS It is feasible and reliable to quantitatively assess iron deposition in deep grey matter nuclei by drawing ROIs manually on susceptibility maps.Furthermore,in contrast to R₂^*,the susceptibility value is more directly correlated to the brain iron level.The findings support the potential value of QSM as a non-invasive quantitative biomarker of early PD,and indicate that iron load within DN may make an important contribution to motor phenotypes in PD.Moreover,our results suggest that TD and AR phenotypes of PD can be differentiated on the basis of the susceptibility of the DN at least on the group level.Assessing the visibility of Nigrosome-1 on QSM has potential to become a diatnostic tool for nigral degeneration in PD.Using QSM,an improved atlas for the dentate nuclear has been generated.The atlas can be applied to investigate the role of DN in tremor-dominant Parkinson's disease.