Neurite dispersion: a new marker of multiple sclerosis spinal cord pathology?

Grussu, Francesco; Schneider, Torben; Tur, Carmen; Yates, Richard L.; Tachrount, Mohamed; Ianuş, Andrada; Yiannakas, Marios C.; Newcombe, Jia; Zhang, Hui; Alexander, Daniel C.; DeLuca, Gabriele C.; Wheeler-Kingshott, C

doi:10.1002/acn3.445

Cited by 259 publications

(287 citation statements)

References 51 publications

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“…Our observation suggests that the neurite loss is the main pathological process, but this needs further histological confirmation. We note however that Grussu et al 32 have demonstrated, in the tissue specimen of multiple sclerosis, that ODI correlated well with histological measures of neurite orientation dispersion, and NDI with histological measures of neurite density.…”

Section: Discussioncontrasting

confidence: 45%

Neurite density is reduced in the presymptomatic phase ofC9orf72disease

Wen

Zhang

Alexander

et al. 2018

J Neurol Neurosurg Psychiatry

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ObjectiveTo assess the added value of neurite orientation dispersion and density imaging (NODDI) compared with conventional diffusion tensor imaging (DTI) and anatomical MRI to detect changes in presymptomatic carriers of chromosome 9 open reading frame 72 (C9orf72) mutation.MethodsThe PREV-DEMALS (Predict to Prevent Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis) study is a prospective, multicentre, observational study of first-degree relatives of individuals carrying the C9orf72 mutation. Sixty-seven participants (38 presymptomatic C9orf72 mutation carriers (C9+) and 29 non-carriers (C9−)) were included in the present cross-sectional study. Each participant underwent one single-shell, multishell diffusion MRI and three-dimensional T1-weighted MRI. Volumetric measures, DTI and NODDI metrics were calculated within regions of interest. Differences in white matter integrity, grey matter volume and free water fraction between C9+ and C9− individuals were assessed using linear mixed-effects models.ResultsCompared with C9−, C9+ demonstrated white matter abnormalities in 10 tracts with neurite density index and only 5 tracts with DTI metrics. Effect size was significantly higher for the neurite density index than for DTI metrics in two tracts. No tract had a significantly higher effect size for DTI than for NODDI. For grey matter cortical analysis, free water fraction was increased in 13 regions in C9+, whereas 11 regions displayed volumetric atrophy.ConclusionsNODDI provides higher sensitivity and greater tissue specificity compared with conventional DTI for identifying white matter abnormalities in the presymptomatic C9orf72 carriers. Our results encourage the use of neurite density as a biomarker of the preclinical phase.Trial registration number NCT02590276.

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Section: Discussioncontrasting

confidence: 45%

Neurite density is reduced in the presymptomatic phase ofC9orf72disease

Wen

Zhang

Alexander

et al. 2018

J Neurol Neurosurg Psychiatry

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“…An unexpected result is the lower ODI values found in lesional tissue compared with HC WM and NAWM in MS subjects. However, a recent ex vivo combined MRI and pathological study found a similar trend of decreased ODI in MS spinal cord lesions (Grussu et al, 2015). Nevertheless, the ODI results in the lesions should be interpreted with caution given that, in the presence of severe axonal loss (as shown by low NDI), the degree of dispersion was estimated from only a small fraction of the signal in the tissue, which might have resulted in numerical instabilities in the NODDI model fit.…”

Section: Discussionmentioning

confidence: 97%

Sensitivity of multi-shell NODDI to multiple sclerosis white matter changes: a pilot study

Schneider¹,

Brownlee²,

Zhang³

et al. 2017

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SummaryDiffusion tensor imaging (DTI) is sensitive to white matter (WM) damage in multiple sclerosis (MS), not only in focal lesions but also in the normal-appearing WM (NAWM). However, DTI indices can also be affected by natural spatial variation in WM, as seen in crossing and dispersing white matter fibers. Neurite orientation dispersion and density imaging (NODDI) is an advanced diffusion-weighted imaging technique that provides distinct indices of fiber density and dispersion. We performed NODDI of lesion tissue and NAWM in five MS patients and five controls, comparing the technique with traditional DTI. Both DTI and NODDI identified tissue damage in NAWM and in lesions. NODDI was able to detect additional changes and it provided better contrast in MS-NAWM microstructure, because it distinguished orientation dispersion and fiber density better than DTI. We showed that NODDI is viable in MS patients and that it offers, compared with DTI parameters, improved sensitivity and possibly greater specificity to microstructure features such as neurite orientation.

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“…Furthermore, there is currently limited histopathological evidence to specifically validate NODDI metrics in human cortical grey matter. However, NODDI‐derived indices have been shown to closely correlate with histological counterparts on postmortem examination in the context of multiple sclerosis spinal cord lesions (Grussu et al, ). In addition, some discrepancies between the NODDI model and emerging multi‐shell diffusion techniques that utilize linear and spherical tensor encoding (as opposed to the single diffusion encoding approach of NODDI) have been reported (Lampinen et al, ).…”

Section: Discussionmentioning

confidence: 99%

Cortical microstructure in young onset Alzheimer's disease using neurite orientation dispersion and density imaging

Parker¹,

Slattery²,

Zhang³

et al. 2018

Human Brain Mapping

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Alzheimer's disease (AD) is associated with extensive alterations in grey matter microstructure, but our ability to quantify this in vivo is limited. Neurite orientation dispersion and density imaging (NODDI) is a multi‐shell diffusion MRI technique that estimates neuritic microstructure in the form of orientation dispersion and neurite density indices (ODI/NDI). Mean values for cortical thickness, ODI, and NDI were extracted from predefined regions of interest in the cortical grey matter of 38 patients with young onset AD and 22 healthy controls. Five cortical regions associated with early atrophy in AD (entorhinal cortex, inferior temporal gyrus, middle temporal gyrus, fusiform gyrus, and precuneus) and one region relatively spared from atrophy in AD (precentral gyrus) were investigated. ODI, NDI, and cortical thickness values were compared between controls and patients for each region, and their associations with MMSE score were assessed. NDI values of all regions were significantly lower in patients. Cortical thickness measurements were significantly lower in patients in regions associated with early atrophy in AD, but not in the precentral gyrus. Decreased ODI was evident in patients in the inferior and middle temporal gyri, fusiform gyrus, and precuneus. The majority of AD‐related decreases in cortical ODI and NDI persisted following adjustment for cortical thickness, as well as each other. There was evidence in the patient group that cortical NDI was associated with MMSE performance. These data suggest distinct differences in cortical NDI and ODI occur in AD and these metrics provide pathologically relevant information beyond that of cortical thinning.

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Neurite dispersion: a new marker of multiple sclerosis spinal cord pathology?

Cited by 259 publications

References 51 publications

Neurite density is reduced in the presymptomatic phase ofC9orf72disease

Neurite density is reduced in the presymptomatic phase ofC9orf72disease

Sensitivity of multi-shell NODDI to multiple sclerosis white matter changes: a pilot study

Cortical microstructure in young onset Alzheimer's disease using neurite orientation dispersion and density imaging

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