Visualization of nigrosome 1 and its loss in PD: pathoanatomical correlation and in vivo 7 T MRI

Abstract

Objective: This study assessed whether high-resolution 7 T MRI allowed direct in vivo visualization of nigrosomes, substructures of the substantia nigra pars compacta (SNpc) undergoing the greatest and earliest dopaminergic cell loss in Parkinson disease (PD), and whether any disease-specific changes could be detected in patients with PD.

Methods: Postmortem (PM) midbrains, 2 from healthy controls (HCs) and 1 from a patient with PD, were scanned with high-resolution T2*-weighted MRI scans, sectioned, and stained for iron and neuromelanin (Perl), TH, and calbindin. To confirm the identification of nigrosomes in vivo on 7 T T2*-weighted scans, we assessed colocalization with neuromelanin-sensitive T1-weighted scans. We then assessed the ability to depict PD pathology on in vivo T2*-weighted scans by comparing data from 10 patients with PD and 8 age- and sex-matched HCs.

Results: A hyperintense, ovoid area within the dorsolateral border of the otherwise hypointense SNpc was identified in the HC brains on in vivo and PM T2*-weighted MRI. Location, size, shape, and staining characteristics conform to nigrosome 1. Blinded assessment by 2 neuroradiologists showed consistent bilateral absence of this nigrosome feature in all 10 patients with PD, and bilateral presence in 7/8 HC.

Conclusions: In vivo and PM MRI with histologic correlation demonstrates that high-resolution 7 T MRI can directly visualize nigrosome 1. The absence of nigrosome 1 in the SNpc on MRI scans might prove useful in developing a neuroimaging diagnostic test for PD.

Figures

Figure 1. Comparison of the histology and postmortem MRI of the substantia nigra in healthy controls and patients with Parkinson disease

Four samples from 3 brainstems of 2 healthy subjects and 1 parkinsonian subject (HC1, HC2, PD1) containing the substantia nigra at a level below the red nucleus. First 4 rows show pairs of superimposed masks: calbindin with TH (first), iron with TH (second), iron with calbindin (third), and iron with neuromelanin (fourth) (the colored text on the right side indicates the meanings of the colors on the masks). Slice of the 3D MRI dataset (fifth row, 0.3 × 0.3 × 0.3 mm3 voxels) and the same slice with overlapped masks represent the different regions (sixth row). All masks and images were coregistered to the Perl stain image.

Figure 2. Nigrosome 1 in vivo in iron- (T2*-weighted) and neuromelanin- (MT-T1-weighted) sensitive 7 T MRI

Example of 2 coregistered, high-resolution, in vivo images of a healthy control (HC) (49 years old) shows the substantia nigra and nigrosome 1 (white arrows). In the T2*-weighted image (left, 0.3 × 0.3 × 0.3 mm3 voxels), the nigrosome is hyperintense due to its low iron content; in the MT-T1-weighted sequence (right, 0.6 × 0.6 × 0.6 mm3 voxels), the nigrosome is hyperintense due to its high neuromelanin content.

Figure 3. Nigrosome 1 in high-resolution T2*-weighted in vivo MRI: 7 T vs 3 T

T2*-weighted images obtained in 7 T (0.35 × 0.35 × 1.00 mm3 voxels, left, 65 years old) and 3 T (0.43 × 0.43 × 1.5 mm3 voxels, right, 31 years old) on a healthy subject show the hyperintense structure that we have identified as nigrosome 1 (white arrows) within the hypointense region of the midbrain.

Figure 4. Substantia nigra in in vivo T2*-weighted 7 T MRI, nigrosome 1: Present in healthy controls, absent in Parkinson disease

Example slices taken from the in vivo T2*-weighted scans (0.35 × 0.35 × 1.00 mm3 voxels) show the substantia nigra in healthy controls (HC, top row) and patients with Parkinson disease (PD, bottom row). Nigrosome 1 (white arrow) is visible in all HC, but no patients with PD.