Longitudinal changes in free-water within the substantia nigra of Parkinson’s disease

Abstract

There is a clear need to develop non-invasive markers of substantia nigra progression in Parkinson's disease. We previously found elevated free-water levels in the substantia nigra for patients with Parkinson's disease compared with controls in single-site and multi-site cohorts. Here, we test the hypotheses that free-water levels in the substantia nigra of Parkinson's disease increase following 1 year of progression, and that baseline free-water levels in the substantia nigra predict the change in bradykinesia following 1 year. We conducted a longitudinal study in controls (n = 19) and patients with Parkinson's disease (n = 25). Diffusion imaging and clinical data were collected at baseline and after 1 year. Free-water analyses were performed on diffusion imaging data using blinded, hand-drawn regions of interest in the posterior substantia nigra. A group effect indicated free-water values were increased in the posterior substantia nigra of patients with Parkinson's disease compared with controls (P = 0.003) and we observed a significant group × time interaction (P < 0.05). Free-water values increased for the Parkinson's disease group after 1 year (P = 0.006), whereas control free-water values did not change. Baseline free-water values predicted the 1 year change in bradykinesia scores (r = 0.74, P < 0.001) and 1 year change in Montreal Cognitive Assessment scores (r = -0.44, P = 0.03). Free-water in the posterior substantia nigra is elevated in Parkinson's disease, increases with progression of Parkinson's disease, and predicts subsequent changes in bradykinesia and cognitive status over 1 year. These findings demonstrate that free-water provides a potential non-invasive progression marker of the substantia nigra.

Subcellular expression of aquaporin-4 in substantia nigra of normal and MPTP-treated mice

“…Notably, experimental data suggest that the toxin susceptibility of dopaminergic neurons depends on the level of AQP4 expression (Zhang et al 2016) and a recent report based on a diffusion MRI technique has shown increased levels of free water in SNpc of patients with PD (Ofori et al 2015b). There was a positive correlation between…”

“…Montreal Cognitive Assessment scores and free water values in SNpc (Ofori et al 2015a;Ofori et al 2015b). …”

Free water improves detection of changes in the substantia nigra in parkinsonism: A multisite study

“…fractional volume of the free-water compartment) in the substantia nigra is increased in PD compared with control subjects in both a single site cohort and the multi-site cohort from the Parkinson’s Progressive Marker Initiative (PPMI) 5 . Also, it was found that free-water in the substantia nigra increases over time in PD 9 , and is elevated in MSA and PSP 10 . While there is much promise in using a bi-tensor model, these sample sizes have been small, and there has not been a study directly comparing the utility of a bi-tensor model with the single-tensor model in the substantia nigra for PD, MSA, and PSP patients across several sites.…”

Novel Diffusion-Kurtosis-Informed Template Reduces Distortions due to Partial Volume Effects and Improves Statistical between-Group Comparisons

“…The FWE method, in contrast, allows one to map the relative free water fraction within a voxel as an additional contrast. A useful application of free water fraction mapping was demonstrated, for example, in studies of Parkinson's disease [70][71][72]. Nevertheless, as a pure correction method, the D-KIT revealed itself as simple and robust in efficiently reducing PVE along the tissue borders without paying the penalty of potential errors introduced by (non-trivial) fitting and regularisation procedures.…”