Neuromelanin-Sensitive MRI

Sasaki, Makoto; Shibata, Eri; Kudo, Kohsuke; Tohyama, Koujiro

doi:10.1007/s00062-008-8018-4

Cited by 47 publications

(29 citation statements)

References 28 publications

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“…The T 1 WI images presented more distinct boundaries than the T 2 * weighted sequences, which appeared as arch shapes between the SN and the crus cerebri. However, the magnetization transfer T 1 WI could not visually depict NM-related contrasts in the SNc as previously reported with 3T MRI23789.…”

Section: Resultsmentioning

confidence: 55%

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

Lee

Baek

Song

et al. 2016

Sci Rep

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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...

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Section: Resultsmentioning

confidence: 55%

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

Lee

Baek

Song

et al. 2016

Sci Rep

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“…Neuromelanin works as a paramagnet when it is combined with ferrous material [3,6]. Neuromelanin-sensitive MRI may underestimate SNc volume because of ferrous accumulation in the SNc of PD patients [17].…”

Section: Discussionmentioning

confidence: 99%

“…There are several studies which report investigation of the SNc using neuromelanin-sensitive MRI [6][7][8]. However, most of the previous reports used a 2 5 dimensional (2D) fast spin echo (FSE) sequence, which provides subjective measurements of signal or volume using user-defined region-of-interest (ROI).…”

Section: Introductionmentioning

confidence: 99%

3D neuromelanin-sensitive magnetic resonance imaging with semi-automated volume measurement of the substantia nigra pars compacta for diagnosis of Parkinson’s disease

et al. 2013

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Purpose: Neuromelanin-sensitive MRI has been reported to be used in the diagnosis of Parkinson's disease (PD), which results from loss of dopamine-producing cells in the substantia nigra pars compacta (SNc). In this study, we aimed to apply a 3D turbo field echo (TFE) sequence for neuromelanin-sensitive MRI and to evaluate the diagnostic performance of semi-automated method for measurement of SNc volume in patients with PD.Methods: We examined 18 PD patients and 27 healthy volunteers (control subjects). A 3D TFE technique with off-resonance magnetization transfer pulse was used for neuromelanin-sensitive MRI on a 3T scanner. The SNc volume was semi-automatically measured using a region-growing technique at various thresholds (ranging from 1.66 to 2.48), with the signals measured relative to that for the superior cerebellar peduncle.Receiver operating characteristic (ROC) analysis was performed at all thresholds. Intra-rater reproducibility was evaluated by intraclass correlation coefficient (ICC).Results: The average SNc volume in the PD group was significantly smaller than that in the control group at all the thresholds (P < 0.01, student t test). At higher thresholds (>2.0), the area under the curve of ROC (Az) increased (0.88). In addition, we observed balanced sensitivity and specificity (0.83 and 0.85, respectively). At lower thresholds, sensitivity tended to increase but specificity reduced in comparison with that at higher thresholds. ICC was larger than 0.9 when the threshold was over 1.86.Conclusions: Our method can distinguish the PD group from the control group with high sensitivity and specificity, especially for early stage of PD.

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“…A T1-weighted fast spin echo (FSE) sequence with an off resonance magnetization transfer pre-pulse (MT-T1-weighted) at 11,100 Hz, with TE/TR 5 9.0/2,582 ms, NSA 5 4, FOV 5 180 3 180 3 7 mm 3 , and 0.6 mm isotropic resolution was also acquired in 7:47 minutes; the contrast in a similar scan at 3 T has previously been ascribed to neuromelanin. 9,10 Images were coregistered using FLIRT (FSL, FMRIB, Oxford, UK) and visually examined.…”

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confidence: 99%

Visualization of nigrosome 1 and its loss in PD

Blazejewska

Schwarz²,

Pitiot³

et al. 2013

Neurology

220

255

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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

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Neuromelanin-Sensitive MRI

Cited by 47 publications

References 28 publications

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

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

3D neuromelanin-sensitive magnetic resonance imaging with semi-automated volume measurement of the substantia nigra pars compacta for diagnosis of Parkinson’s disease

Visualization of nigrosome 1 and its loss in PD

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