Direct visualization of Parkinson's disease by in vivo human brain imaging using 7.0T magnetic resonance imaging

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder resulting from progressive loss of dopaminergic neurons in the substantia nigra (SN) pars compacta. Therefore, imaging of the SN has been regarded to hold greatest potential for use in the diagnosis of PD. At the 7.0T magnetic resonance imaging (MRI), it is now possible to delineate clearly the shapes and boundaries of the SN. We scanned eight early and two advanced PD patients, along with nine age-matched control subjects, using a 7.0T MRI in an attempt to directly visualize the SN and quantify the differences in shape and boundaries of SN between PD subjects in comparison with the normal control subjects. In the normal controls, the boundaries between the SN and crus cerebri appear smooth, and clean "arch" shapes that stretch ventrally from posterior to anterior. In contrast, these smooth and clean arch-like boundaries were lost in PD subjects. The measured correlation analyses show that, in PD patients, there is age-dependent correlation and substantially stronger UPDRS motor score-dependent correlation. These results suggest that, by using 7.0T MRI, it appears possible to use these visible and distinctive changes in morphology as a diagnostic marker of PD.

Visualization of nigrosome 1 and its loss in PD

“…In many previous MRI studies, the boundaries of the SN and changes in PD have often been defined with reference to the high-iron, T2*-weighted hypointense region. 12,26,29 Our comparison of the Perl stain and PM T2*-weighted scan in HC confirmed the expected sensitivity of T2*-weighted MRI to iron, but closer inspection of the histology data shows that the high-iron region cannot be used to delineate the SN boundary. This does not affect the validity of previous MRI results regarding changes in the size, shape, or intensity of the high-iron region in PD, but questions its interpretation as corresponding to the SN.…”

“…23 T2*-weighted MRI provides excellent contrast in the midbrain due to its high iron content. [24][25][26] Previous magnetic resonance work has focused mostly on localizing and measuring characteristics of the whole SN [26][27][28] or distinguishing the SNpc and SNpr, 28,29 although there has been some inconsistency in the definition of boundaries and subareas of the SN in 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 3 0.3 3 0.3 mm 3 voxels), the nigrosome is hyperintense due to its low iron content; in the MT-T1-weighted sequence (right, 0.6 3 0.6 3 0.6 mm 3 voxels), the nigrosome is hyperintense due to its high neuromelanin content.…”

Glucocerebrosidase mutations and the pathogenesis of Parkinson disease

“…MRI with diffusion weighted imaging could help to distinguish patients with progressive supranuclear palsy or multiple system atrophy from those with PD. Findings from these techniques include changes in diffusivity or fractional anisotropy in the SN and the striatum on diffusiontensor MRI (Scherfler et al, 2006) and changes in the SN morphology on high-field MRI (Cho et al, 2011;; Kwon et al, 2012). Reductions seen in fractional anisotropy in the SN correlate with motor severity and therefore, may correlate with disease progression.…”

Genetics of Parkinson Disease

“…22,23 Iron, which has ferromagnetic properties and is excessively deposited in the substantia nigra of patients with PD, led many to believe that this could potentially be an imaging marker of the disease, especially with T2/T2* imaging. [24][25][26] In addition, more advanced MR imaging techniques have been evaluated, such as SWI 27,28 and magnetic transfer imaging. 29,30 One limitation of iron-based imaging is that it is nonspecific and may be seen in myriad normal or non-PD patients with parkinsonism.…”