Simultaneous imaging of locus coeruleus and substantia nigra with a quantitative neuromelanin MRI approach

Chen, Xiangchuan; Huddleston, Daniel E.; Langley, Jason; Ahn, Sinyeob; Barnum, Christopher J.; Factor, Stewart A.; Levey, Aĺlan I.; Hu, Xiaoping

doi:10.1016/j.mri.2014.07.003

Cited by 118 publications

(174 citation statements)

References 21 publications

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“…Thus a further contrast mechanism must be involved. Several observations have led to the suggestion of an association between MT and NM-MRI contrast [18, 20, 22]. Consistent with previous qMT studies [33, 40], our results show PSR and MTR values follow the same trend between healthy brain tissues (low in GM, intermediate in SNc and higher in RN and WM), reflecting the important role of PSR in determining MTR.…”

Section: Discussionsupporting

confidence: 92%

“…Further, we have not attempted to limit the effects of partial volume effects on qMT values obtained from the SNc. In defining the SNc ROIs, we adapted an approach previously used in several NM-MRI studies [12, 21, 22]; nonetheless the sensitivity of small structures such as the SNc to partial volume and motion should be considered in defining ROIs in future studies. As well, in the above discussion we have considered to the structures adjacent to the brainstem having PSR values that match those of the SNc as being representative of grey matter.…”

Section: Discussionmentioning

confidence: 99%

“…Bilateral regions of interest (ROIs) in the SNc were segmented from the NM-MRI images using a thresholding method similar to [12, 21, 22] in the 3D Slicer software package (version 4.3.1, http://www.slicer.org). In brief, a reader, blinded to the clinical status of the subjects, first defined circular (4 mm diameter) background ROIs in the cerebral crus (CC) on the left and right sides.…”

Section: Methodsmentioning

confidence: 99%

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Pool size ratio of the substantia nigra in Parkinson’s disease derived from two different quantitative magnetization transfer approaches

et al. 2017

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Purpose We sought to measure quantitative magnetization transfer (qMT) properties of the substantia nigra pars compacta (SNc) in patients with Parkinson’s disease (PD) and healthy controls (HCs) using a full qMT analysis and determine whether a rapid single-point measurement yields equivalent results for pool size ratio (PSR). Methods Sixteen different MT-prepared MRI scans were obtained at 3T from sixteen PD patients and eight HCs, along with B1, B0 and relaxation time maps. Maps of PSR, free and macromolecular pool transverse relaxation times ( T2f, T2m) and rate of MT exchange between pools ( kmf) were generated using a full qMT model. PSR maps were also generated using a single-point qMT model requiring just two MT-prepared images. qMT parameter values of the SNc, red nucleus, cerebral crus and grey matter were compared between groups and methods. Results PSR of the SNc was the only qMT parameter to differ significantly between groups (p<0.05). PSR measured via single-point analysis was less variable than with the full MT model, provided slightly better differentiation of PD patients from HCs (area under curve 0.77 vs. 0.75) with sensitivity and specificity of 0.87, and was better than transverse relaxation time in distinguishing PD patients from HCs (area under curve 0.71, sensitivity 0.87 and specificity 0.50). Conclusions The increased PSR observed in the SNc of PD patients may provide a novel biomarker of PD, possibly associated with an increased macromolecular content. Single-point PSR mapping with reduced variability and shorter scan times relative to the full qMT model appears clinically feasible.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Pool size ratio of the substantia nigra in Parkinson’s disease derived from two different quantitative magnetization transfer approaches

et al. 2017

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“…As in previous studies (Nakane et al, 2008; Keren et al, 2009; Kitao et al, 2013; Ogisu et al, 2013; Chen et al, 2014), magnetization transfer preparation was used to improve the observable NM contrast. The oblique axial slices of the NM-MRI scan were defined perpendicular to the floor of the fourth ventricle, and covered approximately from the posterior commissure to the inferior pontine border.…”

Section: Methodsmentioning

confidence: 99%

Neuromelanin Imaging and Dopaminergic Loss in Parkinson's Disease

Isaias¹,

Trujillo

Summers

et al. 2016

Front. Aging Neurosci.

147

151

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Parkinson's disease (PD) is a progressive neurodegenerative disorder in which the major pathologic substrate is a loss of dopaminergic neurons from the substantia nigra. Our main objective was to determine the correspondence between changes in the substantia nigra, evident in neuromelanin and iron sensitive magnetic resonance imaging (MRI), and dopaminergic striatal innervation loss in patients with PD. Eighteen patients and 18 healthy control subjects were included in the study. Using neuromelanin-MRI, we measured the volume of the substantia nigra and the contrast-to-noise-ratio between substantia nigra and a background region. The apparent transverse relaxation rate and magnetic susceptibility of the substantia nigra were calculated from dual-echo MRI. Striatal dopaminergic innervation was measured as density of dopamine transporter (DAT) by means of single-photon emission computed tomography and [123I] N-ω-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) tropane. Patients showed a reduced volume of the substantia nigra and contrast-to-noise-ratio and both positively correlated with the corresponding striatal DAT density. The apparent transverse relaxation rate and magnetic susceptibility values of the substantia nigra did not differ between patients and healthy controls. The best predictor of DAT reduction was the volume of the substantia nigra. Clinical and imaging correlations were also investigated for the locus coeruleus. Our results suggest that neuromelanin-MRI can be used for quantifying substantia nigra pathology in PD where it closely correlates with dopaminergic striatal innervation loss. Longitudinal studies should further explore the role of Neuromelanin-MRI as an imaging biomarker of PD, especially for subjects at risk of developing the disease.

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“…A dysfunctional LC-NE system could further prevent patients from registering salient signals demanding action, which may explain action-selection deficits and contribute to Parkinson's diseaserelated apathy. Neuroimaging evidence of LC-NE involvement in Parkinson's disease has been sparse to date, due to the difficulty inherent in imaging a small, brainstem region [92], but among the many neurotransmitter systems affected in Parkinson's disease [93,94], noradrenaline's characteristics stand out as markedly relevant to the study of cognitive function.…”

Section: The Noradrenergic Systemmentioning

confidence: 99%

Apathy and noradrenaline

Loued-Khenissi

Preuschoff

2015

Current Opinion in Neurology

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The search for PD-MCI biomarkers has employed an array of neuroimaging techniques, but still yields divergent findings. This may be due in part to MCI's broad definition, encompassing heterogeneous cognitive domains, only some of which are affected in Parkinson's disease. Most domains falling under the MCI umbrella include fronto-dependent executive functions, whereas others, notably learning, rely on the basal ganglia. Given the deterioration of the nigrostriatal dopaminergic system in Parkinson's disease, it has been the prime target of PD-MCI investigation. By testing well defined cognitive deficits in Parkinson's disease, distinct functions can be attributed to specific neural systems, overcoming conflicting results on PD-MCI. Apart from dopamine, other systems such as the neurovascular or noradrenergic systems are affected in Parkinson's disease. These factors may be at the basis of specific facets of PD-MCI for which dopaminergic involvement has not been conclusive. Finally, the impact of both dopaminergic and noradrenergic deficiency on motivational states in Parkinson's disease is examined in light of a plausible link between apathy and cognitive deficits.

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Simultaneous imaging of locus coeruleus and substantia nigra with a quantitative neuromelanin MRI approach

Cited by 118 publications

References 21 publications

Pool size ratio of the substantia nigra in Parkinson’s disease derived from two different quantitative magnetization transfer approaches

Pool size ratio of the substantia nigra in Parkinson’s disease derived from two different quantitative magnetization transfer approaches

Neuromelanin Imaging and Dopaminergic Loss in Parkinson's Disease

Apathy and noradrenaline

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