MRI quantitative susceptibility mapping of the substantia nigra as an early biomarker for Lewy body disease

Abstract

Background and purpose: Neurodegeneration of the substantia nigra in Lewy body disease is associated with iron deposition, which increases the magnetic susceptibility of the substantia nigra on MRI. Our objective was to measure iron deposition in the substantia nigra in patients with probable dementia with Lewy bodies (pDLB) and patients who are at risk for pDLB by quantitative susceptibility mapping (QSM).

Methods: Participants included pDLB (n = 36), mild cognitive impairment with at least one core feature of DLB (MCI-LB; n = 15), idiopathic rapid eye movement sleep behavior disorder (iRBD; n = 11), and an age-and gender-matched clinically unimpaired control group (n = 102). QSM was derived from multi-echo 3D gradient recalled echo MRI at 3T, and groups were compared on mean susceptibility values of the substantia nigra and its relation to parkinsonism severity.

Results: Patients with pDLB had higher susceptibility in the substantia nigra compared to controls (p< 0.001) and MCI-LB (p = 0.043). The susceptibility of substantia nigra showed an increasing trend from controls to iRBD and MCI-LB, and to pDLB (p< 0.001). Parkinsonism severity was not associated with the mean susceptibility in the substantia nigra in the patient groups.

Conclusions: Our data suggested that QSM is sensitive to the increased magnetic susceptibility due to higher iron content in the substantia nigra in pDLB. The trend of increasing susceptibility from controls to iRBD and MCI-LB, and to pDLB suggests that iron deposition in the substantia nigra starts to increase as early as the prodromal stage in DLB and continues to increase as the disease progresses, independent of parkinsonism severity.

Keywords: dementia with Lewy bodies; iron; mild cognitive impairment; quantitative susceptibility mapping.

Fig 1:

Box-plots of magnetic susceptibility in substantia nigra across 4 groups. Box-plots show the magnetic susceptibility from left, right and bilateral substantia nigra in cognitive unimpaired controls (CU), patients with idiopathic rapid eye movement sleep behavior disorder (iRBD), mild cognitive impairment with DLB features (MCI-LB) and probable dementia with Lewy bodies (pDLB).

Fig 2:

Representative of quantitative susceptibility mapping images and regions of interests of the substantia nigra. Representative quantitative susceptibility mapping (QSM) images were from a cognitively unimpaired adult (CU) (male, 74 years old), a patient with idiopathic rapid eye movement sleep behavior disorder (iRBD) (male, 69 years old), a patient with mild cognitive impairment and clinical features of dementia with Lewy bodies (MCI-LB) (male, 71 years old) and a patient with probable DLB (pDLB) (male, 72 years old). The upper row shows QSM images in the ventral level of substantia nigra (inferior to the red nucleus) and lower row shows QSM images in the dorsal level of substantia nigra (adjacent to the red nucleus). ROIs are shown overlaid on the native space QSM image of CU from the left (purple) and right (yellow) hemispheres.