Alterations and Associations Between Magnetic Susceptibility of the Basal Ganglia and Diffusion Properties in Alzheimer's Disease

Abstract

This study adopted diffusion tensor imaging to detect alterations in the diffusion parameters of the white matter fiber in Alzheimer's disease (AD) and used quantitative susceptibility mapping to detect changes in magnetic susceptibility. However, whether the changes of susceptibility values due to excessive iron in the basal ganglia have correlations with the alterations of the diffusion properties of the white matter in patients with AD are still unknown. We aim to investigate the correlations among magnetic susceptibility values of the basal ganglia, diffusion indexes of the white matter, and cognitive function in patients with AD. Thirty patients with AD and nineteen healthy controls (HCs) were recruited. Diffusion indexes of the whole brain were detected using tract-based spatial statistics. The caudate nucleus, putamen, and globus pallidus were selected as regions of interest, and their magnetic susceptibility values were measured. Compared with HCs, patients with AD showed that there were significantly increased axial diffusivity (AxD) in the internal capsule, superior corona radiata (SCR), and right anterior corona radiata (ACR); increased radial diffusivity (RD) in the right anterior limb of the internal capsule, ACR, and genu of the corpus callosum (GCC); and decreased fractional anisotropy (FA) in the right ACR and GCC. The alterations of RD values, FA values, and susceptibility values of the right caudate nucleus in patients with AD were correlated with cognitive scores. Besides, AxD values in the right internal capsule, ACR, and SCR were positively correlated with the magnetic susceptibility values of the right caudate nucleus in patients with AD. Our findings revealed that the magnetic susceptibility of the caudate nucleus may be an MRI-based biomarker of the cognitive dysfunction of AD and abnormal excessive iron distribution in the basal ganglia had adverse effects on the diffusion properties of the white matter.

Keywords: Alzheimer’s disease; basal ganglia; diffusion tensor imaging; magnetic susceptibility; quantitative susceptibility mapping; tract-based spatial statistics.

FIGURE 1

The above four pictures are the same slice of the same patient. The raw and unprocessed DICOM image (A) obtained from the MRI machine. Sensitive information, such as the patient’s name, check number, and date of birth, has been covered with black. The magnitude image (B) and QSM image (C) were obtained by the post-processing of the STI Suite software, respectively. This image (D) was obtained after drawing the regions of interest (ROIs) based on the C image. Six ROIs were drawn manually on QSM images. Red, dark blue, purple, green, yellow, and light blue are the right caudate nucleus, right putamen, right globus pallidus, left caudate nucleus, left putamen, and left globus pallidus, respectively. R, right; L, left.

FIGURE 2

Clusters showing significant difference in axial diffusivity (AxD) values between the AD group and the HC group. The red clusters were attached to the axial images of the mean FA skeleton (green), showing significantly increased AxD values in the AD group compared with the HC group (AD > HC; FWE corrected P < 0.05). FWE, family wise error; AD, Alzheimer’s disease; HC, healthy controls.

FIGURE 3

Intergroup comparisons of AxD values, RD values, and FA values between the AD group (red) and the HC group (blue). AxD values, RD values, and FA values of clusters were statistically different between the two groups before FWE correction. AxD, axial diffusivity; RD, radial diffusivity; FA, fractional anisotropy; AD, Alzheimer’s disease; HC, healthy controls.

FIGURE 4

Comparisons of susceptibility values in the basal ganglia between the AD group (red) and the HC group (blue). The susceptibility values of the bilateral caudate nucleus were significantly higher in the AD group than in the HC group (P < 0.001). R, right; L, left; Cau, caudate nucleus; Puta, putamen; Glob, globus pallidus.

FIGURE 5

Correlations between RD values, FA values, and cognitive scales in patients with AD. The mean RD values of cluster 2 have negative correlations with MMSE scores (A) and MoCA scores (B) after FDR correction (r = −0.491, P = 0.007; r = −0.532, P = 0.003). The mean FA values of cluster 1 have positive correlations with MMSE scores (C) and MoCA scores (D) after FDR correction (r = 0.507, P = 0.005; r = 0.528, P = 0.003). RD, radial diffusivity; FA, fractional anisotropy; MMSE, Mini-Mental State Examination; MoCA, Montreal Cognitive Assessment.

FIGURE 6

Correlations between the susceptibility values of the right caudate nucleus and MMSE scores, between the susceptibility values of the right caudate nucleus and the AxD values of cluster 2 in patients with AD. The susceptibility values of the right caudate nucleus have a negative correlation with MMSE scores after FDR correction (A) (r = −0.404, P = 0.033). The mean AxD values of cluster 2 have a positive correlation with the susceptibility values of the right caudate nucleus after FDR correction (B) (r = 0.444, P = 0.016). MMSE, Mini-Mental State Examination; AxD, axial diffusivity; R_Cau, right caudate nucleus.