Visualization of nigrosome 1 and its loss in PD

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. Many MRI studies have reported Parkinson disease (PD)-associated changes in the substantia nigra (SN). 1 However, delineating the boundaries and assessing neurodegeneration in the SN remains challenging. 2 Recently developed ultra-high-field MRI systems produce very high spatial resolution T2*-weighted images providing detailed SN morphologic information. Correlation of high-resolution MRI data and histology 3 may enable a more precise definition of the boundaries and substructures of the SN in vivo, and hence a more accurate demonstration of PD pathology.The SN is divided into the pars compacta (SNpc), which is densely packed with neuromelanin-containing dopaminergic cells, and the pars reticulata (SNpr), which is formed by loose aggregations of GABAergic medium and large neurons. 4 The majority of neurons in the SNpc project to the neostriatum (putamen and caudate nucleus). Five distinct subgroups of dopaminecontaining neurons in calbindin-negative zones within the SNpc, nigrosomes, have been identified using immunostaining for calbindin D 28K . 5 The largest, nigrosome 1, is lens-shaped and situated along the rostral/caudal axis of the SN in its dorsal part, at caudal and intermediate levels ( figure 8 of Damier et al. 5 ; figure e-1 on the Neurology ® Web site at www.neurology.org). Postmortem (PM) studies have shown dopaminergic neuronal loss in PD to be higher in the

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

“…Absence of this MRI feature resulted in 85.7% sensitivity and 100% specificity to detect PD. We suggest that this MRI feature reported at 7T MRI using T2*-weighted sequences 1 can also be detected at 3T using SWI sequences and that absence of this MRI feature might have potential for diagnosing PD.…”

“…Editors' Note: The inability to visualize nigrosome 1 on a 7T brain MRI is suggestive of Parkinson disease, as described by Blazejewska 1 identified a hyperintense ovoid area within the dorsolateral border of the otherwise hypointense pars compacta of the substantia nigra (SNc) in healthy controls (HC) and the absence of this MRI feature 2 in patients with Parkinson disease (PD) using T2*-weighted 7T MRI. Moreover, the postmortem 7T MRI with histopathologic correlations suggested that this MRI feature corresponded to nigrosome 1.…”

Nigrosome 1 Detection at 3T MRI for the Diagnosis of Early-Stage Idiopathic Parkinson Disease: Assessment of Diagnostic Accuracy and Agreement on Imaging Asymmetry and Clinical Laterality

“…By using 7T [3][4][5][6] and 3T MR imaging, 7,8 recent studies demonstrated that nigrosome 1 can serve as a surrogate biomarker for IPD. Schwarz et al 7 obtained high-resolution 3D gradient recalled-echo imaging (voxel size, 0.55 ϫ 0.55 ϫ 0.7 mm) in an imaging plane parallel to the splenium-genu line at 3T.…”

“…Although we enrolled only patients with clinically well-established IPD, the specificity of our study was lower (84.6%) than that in the studies with 7T MR imaging (87.5%-96.2%). 5,6,9 Thus, a more specific imaging biomarker that could give confirmation to patients with clinical suspicion of parkinsonism is still needed. 21,22 On the basis of our results of a relatively lower specificity than that of previous studies, nigrosome 1 detection at 3T MR imaging should be further improved to serve as a confirmatory test of IPD.…”

“…2 Recently, a few researchers have tried to visualize the nigrosome 1 area with 7T MR imaging and demonstrated its feasibility as an imaging biomarker for the diagnosis of IPD. [3][4][5][6] The results, however, had a limited clinical utility because of low availability of 7T MR imaging. Hence, several studies have tried to translate nigrosome 1 detection to 3T MR imaging, which is widely available.…”