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 T1 and T2* imaging protocols and then stained with Perl’s Prussian blue, Kluver-Barrera, tyrosine hydroxylase, and calbindin immunohistochemistry in a serial manner. The association between T2* values and quantitative histology was investigated with a co-registration method that accounts for histology slice preparation. The ventral T2* 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 T2* imaging at 7T can reflect the density of NM-containing neurons as the metal-bound NM macromolecules may decrease T2* values and cause hypointense signalling in T2* imaging at 7T.
Highlights
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]
We identified one of the main histological components that contribute to T2*-sensitive contrast by using the co-registration of postmortem magnetic resonance imaging (MRI) and histological data
Signal loss on T2*-weighted images (T2*WI) may be attributable to paramagnetic macromolecules, both NM and iron pigments, within the SN4
Summary
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]. 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]. Postmortem 7T T2*WI, in combination with histological correlations and in vivo data, can directly depict the pockets of high signal intensity in the dorsal SN corresponding to nigrosome 1, which is known to be the structure most vulnerable to degeneration in PD1,3,11. In PD, the loss of hyperintense nigrosome 1 and the expansion of signal hypointensity were each identified as a result of the loss of dopaminergic neurons and an increase in iron content within nigrosome 13,5,6,11. T2* maps for an unbiased quantification of distinct physical tissue properties[16] were generated and directly correlated with quantitative histology, such as densities of NM and iron pigments[17]
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