Correlation between pathology and neuromelanin MR imaging in Parkinson’s disease and dementia with Lewy bodies

Kitao, Shinichiro; Matsusue, Eiji; Fujii, Shinya; Miyoshi, Fumito; Kaminou, Toshio; Kato, Shinsuke; Ito, Hisao; Ogawa, Toshihide

doi:10.1007/s00234-013-1199-9

Cited by 103 publications

(96 citation statements)

References 17 publications

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“…NM containing structures can be identified in the NM-sensitive images (NM-MRI) as areas of hyperintensity. A direct comparison between post-mortem NM-MRI and neuropathological findings has shown that NM-MRI signal intensity in the SN is closely associated with the quantity of NM-containing neurons (Kitao et al, 2013), supporting the link between NM-MRI hyperintensity with the presence of NM.…”

Section: Introductionmentioning

confidence: 96%

“…MRI techniques sensitive to NM (Sasaki et al, 2006; Kitao et al, 2013; Miyoshi et al, 2013; Ogisu et al, 2013; Ohtsuka et al, 2014) and iron (Graham et al, 2000; Martin et al, 2008; Baudrexel et al, 2010; Schweser et al, 2011; Lotfipour et al, 2012; Ulla et al, 2013) have been found to provide information about SN degeneration with potential applications as biomarkers of PD (Kashihara et al, 2011; Schwarz et al, 2011; Matsuura et al, 2013; Miyoshi et al, 2013; Castellanos et al, 2015). NM containing structures can be identified in the NM-sensitive images (NM-MRI) as areas of hyperintensity.…”

Section: Introductionmentioning

confidence: 99%

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Neuromelanin Imaging and Dopaminergic Loss in Parkinson's Disease

Isaias¹,

Trujillo

Summers

et al. 2016

Front. Aging Neurosci.

150

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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Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Neuromelanin Imaging and Dopaminergic Loss in Parkinson's Disease

Isaias¹,

Trujillo

Summers

et al. 2016

Front. Aging Neurosci.

150

151

View full text Add to dashboard Cite

show abstract

“…Part of our motivation for investigating the qMT properties of the SNc lay in seeking to understand the mechanism behind the hyperintensity of NM-containing structures in NM-MRI, a technique that has attracted interest as a potential means of quantifying neuronal loss in the SNc of patients with PD [16]. In particular, apart from the locus coeruleus, which also contains NM, both white matter and other grey matter structures of the brainstem, including the RN, appear hypointense relative to the SNc in NM-MRI.…”

Section: Discussionmentioning

confidence: 99%

“…Neuromelanin-sensitive MRI (NM-MRI) techniques [5] have shown notable contrast between the SNc and surrounding brain tissues, with a number of studies indicating that NM-MRI may be used to detect alterations to SNc morphology, even in early stages of PD [6–15]. Moreover, a direct comparison between post-mortem NM-MRI and neuropathology findings [16] found NM-MRI signal intensity in the SNc to be closely associated with the quantity of NM-containing neurons. However, the mechanism by which the presence of NM might give rise to signal hyperintensities on MRI, and the nature of the relationship between the loss of hyperintensity with advancing PD severity is still unclear.…”

Section: Introductionmentioning

confidence: 99%

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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“…Using T1-weighted neuromelanin MR imaging, for example, a reduced signal intensity in the locus coeruleus was demonstrated in late PD patients [9]. Signal reduction directly correlated with the amout of neuromelanin-containing neurons in autopsied brains [10].…”

Section: Introductionmentioning

confidence: 98%

A novel computerized algorithm to detect microstructural brainstem pathology in Parkinson’s disease using standard 3 Tesla MR imaging

et al. 2014

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Increased deposition of α-synuclein in Parkinson's disease (PD) is known to be prominent in the brainstem and discussed to be clinically relevant for motor and non-motor features. Whether structural magnetic resonance imaging is capable to detect degraded tissue microstructure caused by increased deposition of α-synuclein at this predilection site in PD remains unclear. We hypothesize that microstructural degradation in the brainstem leads to a reduced T1 contrast provoking standard tissue segmentation engines to misclassify tissue as additional grey matter in regions predominantly composed of white matter. High-resolution T1-weighted three-dimensional magnetization prepared rapid gradient echo (MPRAGE) imaging at 3 Tesla in fifty-two PD patients with mild-to-moderate disease severity and in forty age- and gender-matched healthy controls was performed. A dedicated computerized algorithm that comprises standard tissue segmentation in combination with a statistical test was set up that evaluates grey matter composition on voxel level. The algorithm detected a single significant cluster of voxels with enhanced grey matter (cluster volume is 1,368 mm(3), p < 0.05 corrected for false discovery rate) in the pontomedullary junction of the brainstem in PD patients as compared to healthy controls. Furthermore, absolute grey matter volume was significantly higher in the brainstem of the PD group compared to healthy controls. We conclude that this cluster may reflect α-synuclein induced microstructural brainstem pathology in PD.

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Correlation between pathology and neuromelanin MR imaging in Parkinson’s disease and dementia with Lewy bodies

Abstract: Based on the direct correlation between postportem NmMRI and neuropathological findings, signal intensity in the SNc is closely related to the quantity of neuromelanin-containing neurons but is not influenced by iron deposition.

Cited by 103 publications

References 17 publications

Neuromelanin Imaging and Dopaminergic Loss in Parkinson's Disease

Neuromelanin Imaging and Dopaminergic Loss in Parkinson's Disease

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

A novel computerized algorithm to detect microstructural brainstem pathology in Parkinson’s disease using standard 3 Tesla MR imaging

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