High-resolution diffusion tensor imaging in the substantia nigra of de novo Parkinson disease

Abstract

Background: In the midbrain of patients with Parkinson disease (PD), there is a selective loss of dopaminergic neurons in the ventrolateral and caudal substantia nigra (SN). In a mouse model of PD, investigators have administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and found that measures derived using diffusion tensor imaging (DTI) were correlated with the number of dopamine neurons lost following intoxication.

Methods: Twenty-eight subjects (14 with early stage, untreated PD and 14 age- and gender-matched controls) were studied with a high-resolution DTI protocol at 3 Tesla using an eight-channel phase array coil and parallel imaging to study specific segments of degeneration in the SN. Regions of interest were drawn in the rostral, middle, and caudal SN by two blinded and independent raters.

Results: Fractional anisotropy (FA) was reduced in the SN of subjects with PD compared with controls (p < 0.001). Post hoc analysis identified that reduced FA for patients with PD was greater in the caudal compared with the rostral region of interest (p < 0.00001). A receiver operator characteristic analysis in the caudal SN revealed that sensitivity and specificity were 100% for distinguishing patients with PD from healthy subjects. Findings were consistent across both raters.

Conclusions: These findings provide evidence that high resolution diffusion tensor imaging in the substantia nigra distinguishes early stage, de novo patients with Parkinson disease (PD) from healthy individuals on a patient by patient basis and has the potential to serve as a noninvasive early biomarker for PD.

Figure 1 Procedure used to draw regions of interest in the substantia nigra (A) B0 image with the red nucleus and substantia nigra. This slice was first identified. (B) B0 slice just inferior to the slice shown in A, and this slice is where we drew the three regions of interest. (C) shows the fractional anisotropy image and (D) shows the colormap of the same slice in B. The region of interest for the cerebral peduncle is also shown. (E) Larger image of the three regions of interest in the rostral, middle, and caudal substantia nigra as well as the region of interest in the cerebral peduncle. All images were generated in DtiStudio.

Figure 2 Differences between groups Mean fractional anisotropy across patients with Parkinson disease (green) and healthy control subjects (black) in the rostral, middle, and caudal region of the substantia nigra. Error bars represent ± 1 SD.

Figure 3 Differences between individual subjects (A) Fractional anisotropy values from rater 1 for patients with Parkinson disease (PD) (green) and healthy controls (black) from the caudal region of interest. The black symbol represents the average plus/minus 1 SD for control subjects. The green symbol represents the average plus/minus 1 SD for patients with PD. (B) Same as in A but data are from rater 2. (C) Receiver operating characteristic plots from the rostral (blue), middle (green), and caudal (red) region of interest. The caudal region had the greatest sensitivity and specificity.