The Neuromelanin-related T2* Contrast in Postmortem Human Substantia Nigra with 7T MRI

Abstract

High field magnetic resonance imaging (MRI)-based delineation of the substantia nigra (SN)and visualization of its inner cellular organization are promising methods for the evaluation of morphological changes associated with neurodegenerative diseases; however, corresponding MR contrasts must be matched and validated with quantitative histological information. Slices from two postmortem SN samples were imaged with a 7 Tesla (7T) MRI with T 1 and T 2 * imaging protocols and then stained with Perl's Prussian blue, Kluver-Barrera, tyrosine hydroxylase, and calbindin immunohistochemistry in a serial manner. The association between T 2 * values and quantitative histology was investigated with a co-registration method that accounts for histology slice preparation. The ventral T 2 * hypointense layers between the SNr and the crus cerebri extended anteriorly to the posterior part of the crus cerebri, which demonstrates the difficulty with an MRI-based delineation of the SN. We found that the paramagnetic hypointense areas within the dorsolateral SN corresponded to clusters of neuromelanin (NM). These NM-rich zones were distinct from the hypointense ventromedial regions with high iron pigments. Nigral T 2 * imaging at 7T can reflect the density of NM-containing neurons as the metal-bound NM macromolecules may decrease T 2 * values and cause hypointense signalling in T 2 * imaging at 7T.Identifying and characterizing the anatomic architecture of the substantia nigra (SN) has important clinical implications for the evaluation of structural changes associated with neurodegenerative conditions, such as Parkinson's disease (PD) [1][2][3] . The SN is subdivided into two histologically distinct regions, the ventral pars reticulata (SNr) and the dorsal pars compacta (SNc). The SNc is composed of neuromelanin (NM)-containing dopaminergic neurons, which are affected early in PD [1][2][3] . Numerous attempts have been made to visualize substructure morphology of the SN and to assess the neurodegenerative changes using various magnetic resonance imaging (MRI) signal contrasts 2,3 . For example, iron-sensitive MR sequences have great potential to define the boundaries and shape of the SN 2-4 as the local deposition of iron alters magnetic field inhomogeneities and appears hypointense in T 2 or T 2 * -weighted images (T 2 *WI) due to the shortening of transverse relaxation times 2,5 . By taking advantage of region-specific iron content within the SN, the area of lower T 2 * -weighted signal intensity is assigned to the SNr based on the histological observation of elevated iron concentration in that region 3,5,6 . NM-sensitive T 1 -weighted fast spin echo technique in in vivo 3T MRI studies allows the visualization of the SNc via hyperintense areas 2,3,[7][8][9] . NM within the dopaminergic neurons is speculated to generate paramagnetic T 1 -shortening effects on combining with metals, such as iron and copper 2,3,7,10 . While NM-containing dopaminergic neurons are densely distributed in the SNc, they form clusters of cells that penetra...

MRI supervised and unsupervised classification of Parkinson's disease and multiple system atrophy

“…Similarly, all brain regions with a difference in MD corresponded to a mean diffusivity increase in MSA patients. The spatial localization of MR changes was in keeping with previous single MR parameter studies: VBM‐studies, MR relaxometry, and DTI studies in patients with PD and MSA.…”

In vivo measurements of irreversible and reversible transverse relaxation rates in human basal ganglia at 7 T: making inferences about the microscopic and mesoscopic structure of iron and calcification deposits

“…This leads to irreversible transverse relaxation, whereas reversible transverse relaxation results from field variations that only reach significance over distances greater than the diffusion length—in what Fernández‐Seara and Wehrli call the mesoscopic scale—since a refocusing pulse will successfully refocus spin populations diffusing through such inhomogeneities. Therefore, an increase in both irreversible and reversible transverse relaxation rates with presumed iron content, as observed here and in other studies, implies that these iron deposits cause both microscopic and mesoscopic field variations, suggesting a rather “heterogeneous” geometry for these deposits; indeed, evidence for a heterogeneous distribution of iron is seen in histological studies of basal ganglia, lending further credence to the idea that MRI might eventually provide a non‐invasive means to probe the cellular distribution of iron …”

“…* Therefore, an increase in both irreversible and reversible transverse relaxation rates with presumed iron content, as observed here and in other studies, 42,43 implies that these iron deposits cause both microscopic and mesoscopic field variations, suggesting a rather "heterogeneous" geometry for these deposits; indeed, evidence for a heterogeneous distribution of iron is seen in histological studies of basal ganglia, 44 lending further credence to the idea that MRI might eventually provide a non-invasive means to probe the cellular distribution of iron. 40,45 Turning now to the individual with calcifications in the globus pallidus, we see that the irreversible transverse relaxation rate in this structure is very much in line with what would be expected based on the predicted iron level for that age, but that the reversible relaxation rate is dramatically higher than expected (see Figures 5a and c). This suggests that the calcifications in this individual primarily induce mesoscopic rather than microscopic field variations.…”

In vivo detection of lateral–ventral tier nigral degeneration in Parkinson's disease

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