Quantitative susceptibility mapping in atypical Parkinsonisms

Abstract

Background and purpose: Differential diagnosis between Parkinson's disease (PD) and Atypical Parkinsonisms, mainly Progressive Supranuclear Palsy (PSP) and Multiple System Atrophy (MSA), remains challenging. The low sensitivity of macroscopic findings at imaging might limit early diagnosis. The availability of iron-sensitive MR techniques and high magnetic field MR scanners provides new insights in evaluating brain structures in degenerative parkinsonisms. Quantitative Susceptibility Mapping (QSM) allows quantifying tissue iron content and could be sensitive to microstructural abnormalities which precede the appearence of regional atrophy. We measured the magnetic susceptibility (χ) of nigral and extranigral regions in patients with PD, PSP and MSA to evaluate the potential utility of the QSM technique for differential diagnosis.

Materials and methods: 65 patients (36 PD, 14 MSA, 15 PSP) underwent clinical and radiological evaluation with 3 T MRI. QSM maps were obtained from GRE sequences. ROI were drawn on substantia nigra (SN), red nucleus (RN), subthalamic nucleus (STN), putamen, globus pallidus and caudate. χ values were compared to detect inter-group differences.

Results: The highest diagnostic accuracy for PSP (area under the ROC curve, AUC, range 0.9-0.7) was observed for increased χ values in RN, STN and medial part of SN whereas in MSA (AUC range 0.8-0.7) iron deposition was significantly higher in the putamen, according to the patterns of pathological involvement that characterize the different diseases.

Conclusion: QSM could be used for iron quantification of nigral and extranigral structures in all degenerative parkinsonisms and should be tested longitudinally in order to identify early microscopical changes.

Keywords: Iron; Neurodegeneration; Parkinsonism; Susceptibility.

Fig. 1

Summary of Regions of Interest (ROIs). In the upper row: on the left it is reported the axial susceptibility map image of the midbrain with two ROIs drawn on the medial and lateral part of the right SN at level I (SNImed and SNIlat, respectively); on the right, three ROIs are drawn on the ventral, intermediate and dorsal layer of right SN at level II (SNIIventr, SNIIint and SNIIdors, respectively). In the middle row: a susceptibility map image of the midbrain is shown in the coronal plane: ROI delineates the right subthalamic nucleus. In the bottom row: on the left the axial susceptibility map image passing trough the foramen of Monro shows ROIs surrounding the caudate, putamen, globus pallidus. On the right the axial susceptibility map image passing trough the midbrain shows the placement of a circular ROI at the level of the maximum diameter of the red nucleus and of a reference ROI in the sub-cortical white matter of the right occipital lobe (black dot).

Fig. 2

Axial QSM images passing through the foramen of Monro showing the caudate, putamen, globus pallidus comparing patients with PD (left), MSA (middle) and PSP (right). Window of susceptibility values: - 100, + 300 parts per billion (ppb).

Fig. 3

Axial QSM images passing through the midbrain at the level of the maximum diameter of the red nucleus comparing patients with PD (left), MSA (middle) and PSP (right). Window of susceptibility values: - 100, + 300 parts per billion (ppb).

Fig. 4

Coronal QSM images of the midbrain showing subthalamic nucleus and substantia nigra of patients with PD (left), MSA (middle) and PSP (right). Window of susceptibility values: - 100, + 300 parts per billion (ppb).

Graph 1

Comparison of mean susceptibility values of nigral (A) and extranigral (B) ROIs. The layout of columns corresponds to the layout of each ROI as reported in Fig. 1. STN: subthalamic nucleus; RN: red nucleus; SNImed: medial ROI of substantia nigra at level I; SNIlat: lateral ROI of substantia nigra at level I; SNIIventr: ventral ROI of substantia nigra at level II, SNIIint: intermediate ROI of substantia nigra at level II, SNIIdors: dorsal ROI of substantia nigra at level II; ppb: parts per billion; Δχ: relative susceptibility value.