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Quantitative susceptibility mapping of the midbrain in Parkinson's disease.

ABSTRACT: Parkinson's disease (PD) is marked pathologically by dopamine neuron loss and iron overload in the substantia nigra pars compacta. Midbrain iron content is reported to be increased in PD based on magnetic resonance imaging (MRI) R2* changes. Because quantitative susceptibility mapping is a novel MRI approach to measure iron content, we compared it with R2* for assessing midbrain changes in PD.Quantitative susceptibility mapping and R2* maps were obtained from 47 PD patients and 47 healthy controls. Midbrain susceptibility and R2* values were analyzed by using both voxel-based and region-of-interest approaches in normalized space, and analyzed along with clinical data, including disease duration, Unified Parkinson's Disease Rating Scale (UPDRS) I, II, and III subscores, and levodopa-equivalent daily dosage. All studies were done while PD patients were "on drug."Compared with controls, PD patients showed significantly increased susceptibility values in both right (cluster size?=?106?mm(3)) and left (164?mm(3)) midbrain, located ventrolateral to the red nucleus that corresponded to the substantia nigra pars compacta. Susceptibility values in this region were correlated significantly with disease duration, UPDRS II, and levodopa-equivalent daily dosage. Conversely, R2* was increased significantly only in a much smaller region (62?mm(3)) of the left lateral substantia nigra pars compacta and was not significantly correlated with clinical parameters.The use of quantitative susceptibility mapping demonstrated marked nigral changes that correlated with clinical PD status more sensitively than R2*. These data suggest that quantitative susceptibility mapping may be a superior imaging biomarker to R2* for estimating brain iron levels in PD.

SUBMITTER: Du G

PROVIDER: S-EPMC5315570 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Quantitative susceptibility mapping of the midbrain in Parkinson's disease.

Du Guangwei G Liu Tian T Lewis Mechelle M MM Kong Lan L Wang Yi Y Connor James J Mailman Richard B RB Huang Xuemei X

Movement disorders : official journal of the Movement Disorder Society 20150912 3

<h4>Background</h4>Parkinson's disease (PD) is marked pathologically by dopamine neuron loss and iron overload in the substantia nigra pars compacta. Midbrain iron content is reported to be increased in PD based on magnetic resonance imaging (MRI) R2* changes. Because quantitative susceptibility mapping is a novel MRI approach to measure iron content, we compared it with R2* for assessing midbrain changes in PD.<h4>Methods</h4>Quantitative susceptibility mapping and R2* maps were obtained from 4 ...[more]

PMID: 26362242

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Project description:ObjectiveTo investigate the utility of quantitative susceptibility mapping (QSM) and diffusion kurtosis imaging (DKI) as complementary tools in characterizing pathological changes in the deep grey nuclei in early Parkinson's disease (PD) and their clinical correlates to aid in diagnosis of PD.MethodPatients with a diagnosis of PD made within a year and age-matched healthy controls were recruited. All participants underwent clinical evaluation using the Unified Parkinson's Disease Rating Scale (MDS-UPDRS III) and Hoehn & Yahr stage (H&Y), and brain 3 T MRI including QSM and DKI. Regions-of-interest (ROIs) in the caudate nucleus, putamen, globus pallidus, and medial and lateral substantia nigra (SN) were manually drawn to compare the mean susceptibility (representing iron deposition) and DKI indices (representing restricted water diffusion) between PD patients and healthy controls and in correlation with MDS-UPDRS III and H&Y, focusing on susceptibility value, mean diffusivity (MD) and mean kurtosis (MK).ResultsThere were forty-seven PD patients (aged 68.7 years, 51% male, disease duration 0.78 years) and 16 healthy controls (aged 67.4 years, 63% male). Susceptibility value was increased in PD in all ROIs except the caudate, and was significantly different after multiple comparison correction in the putamen (PD: 64.75 ppb, HC: 44.61 ppb, p = 0.004). MD was significantly higher in PD in the lateral SN, putamen and caudate, the regions with the lowest susceptibility value. In PD patients, we found significant association between the MDS-UPDRS III score and susceptibility value in the putamen after correcting for age and sex (β = 0.21, p = 0.003). A composite DKI-QSM diagnostic marker based on these findings successfully differentiated the groups (p < 0.0001) and had "good" classification performance (AUC = 0.88).ConclusionsQSM and DKI are complementary tools allowing a better understanding of the complex contribution of iron deposition and microstructural changes in the pathophysiology of PD.

Project description:The primary aim of the present study was to evaluate abnormal iron distribution in specific regions of the brains in patients with Parkinson's disease (PD) using quantitative susceptibility mapping (QSM) and R2* mapping, and to compare the diagnostic performances of QSM and R2* mapping in differentiating patients with PD with that in normal controls. A total of 25 patients with idiopathic PD and 28 sex-and age-matched normal controls were included in the present study and their brains investigated using a 3T scanner. Magnetic resonance imaging techniques, namely, QSM and R2* mapping, were applied to generate susceptibility and R2* values. The differences in susceptibility and R2* values in deep grey matter nuclei between patients with PD and the normal controls were compared using independent samples t-tests. The abilities of QSM and R2* mapping to classify patients with PD and normal controls were analyzed using receiver operating characteristic curves. Correlation analyses between imaging parameters (e.g. susceptibility and R2* values) and clinical feature (disease severity assessed using the Hoehn and Yahr score) were performed. The intra-class correlation coefficient (ICC) for susceptibility (ICC=0.977; P<0.001) and R2* (ICC=0.945; P<0.001) values between two neuro-radiologists were >0.81, showing excellent inter-rater agreement. The susceptibility values were significantly increased in the substantia nigra (SN) and red nucleus, but were decreased in the putamen of patients with PD compared with that in the corresponding brain regions of normal controls. However, increased R2* values were observed only in the SN in patients with PD. QSM showed higher sensitivity and specificity compared with R2* mapping to separate the patients with PD from the normal controls. There were no significant correlations between the susceptibility/R2* values and clinical features in all targeted regions of the brains in patients with PD. In conclusion, both QSM and R2* mapping are feasible to calculate the iron levels in human brains, and QSM provides a more sensitive and accurate method to assess regional abnormal iron distribution in patients with PD.

Dataset Information

Quantitative susceptibility mapping of the midbrain in Parkinson's disease.

Publications

Quantitative susceptibility mapping of the midbrain in Parkinson's disease.

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