Multi-modal Brain MRI in Subjects with PD and iRBD

Abstract

Idiopathic rapid eye movement sleep behavior disorder (iRBD) is a condition that often evolves into Parkinson's disease (PD). Therefore, by monitoring iRBD it is possible to track the neurodegeneration of individuals who may progress to PD. Here we aimed at piloting the characterization of brain tissue properties in mid-brain subcortical regions of 10 healthy subjects, 8 iRBD, and 9 early-diagnosed PD. We used a battery of magnetic resonance imaging (MRI) contrasts at 3 T, including adiabatic and non-adiabatic rotating frame techniques developed by our group, along with diffusion tensor imaging (DTI) and resting-state fMRI. Adiabatic T_1ρ and T_2ρ, and non-adiabatic RAFF4 (Relaxation Along a Fictitious Field in the rotating frame of rank 4) were found to have lower coefficient of variations and higher sensitivity to detect group differences as compared to DTI parameters such as fractional anisotropy and mean diffusivity. Significantly longer T_1ρ were observed in the amygdala of PD subjects vs. controls, along with a trend of lower functional connectivity as measured by regional homogeneity, thereby supporting the notion that amygdalar dysfunction occurs in PD. Significant abnormalities in reward networks occurred in iRBD subjects, who manifested lower network strength of the accumbens. In agreement with previous studies, significantly longer T_1ρ occurred in the substantia nigra compacta of PD vs. controls, indicative of neuronal degeneration, while regional homogeneity was lower in the substantia nigra reticulata. Finally, other trend-level findings were observed, i.e., lower RAFF4 and T_2ρ in the midbrain of iRBD subjects vs. controls, possibly indicating changes in non-motor features as opposed to motor function in the iRBD group. We conclude that rotating frame relaxation methods along with functional connectivity measures are valuable to characterize iRBD and PD subjects, and with proper validation in larger cohorts may provide pathological signatures of iRBD and PD.

Keywords: DTI; Parkinson's disease; functional connectivity; iRBD; rotating frame MRI.

Figure 1

Regions of interest used for the analysis of the relaxation, DTI and functional data from one representative control subject. Masks identifying the regions of interest were transferred to standard space for visualization purposes. SNc, substantia nigra pars compacta; SNr, substantia nigra pars reticulata.

Figure 2

Substantia nigra ROIs (SNr, in blue, and SNc, in red) overlaid on T2-w images and adiabatic T_1ρ, and T_2ρ maps from one representative control subject. Images are shown either without (top row) or with (bottom row) the overlay of the ROIs.

Figure 3

Representative maps of T_1ρ, T_2ρ, RAFF4, FA, and MD from one each of a control, iRBD and PD subject. ROIs of interest visible on the selected slices are also shown superimposed on the T1-weighted (T1w) images, including thalamus (beige), pallidum (dark blue), putamen (light blue), caudate (red), and accumbens (yellow).

Figure 4

Group summaries of T_1ρ, T_2ρ, RAFF4, FA, MD, ReHo and network strength. N = 10, 8, 9 in the control, iRBD and PD groups, respectively, for T_1ρ, T_2ρ, and RAFF4, whereas N = 9, 8, 9 for FA and MD, and N = 10, 8, 8 for network strength and ReHo. Data shown as mean ± SD. ^* and ^** indicate, respectively, p < 0.05 and p < 0.005 with age-adjustments after Holm's correction (gray: iRBD vs. controls; black: PD vs. controls). Asterisks within a box indicate p < 0.05 after correcting FDR for multiple testing (7 modalities).