Axonal injury in the cerebral normal-appearing white matter of patients with multiple sclerosis is related to concurrent demyelination in lesions but not to concurrent demyelination in normal-appearing white matter. Neuroimage

Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, Montreal, Quebec, Canada H3A 2B4.
NeuroImage (Impact Factor: 6.36). 02/2006; 29(2):637-42. DOI: 10.1016/j.neuroimage.2005.07.017
Source: PubMed


We assessed axonal injury and demyelination in the cerebral normal-appearing white matter (NAWM) of MS patients in a pilot study using proton magnetic resonance spectroscopic imaging and quantitative magnetization transfer (MT) imaging. Resonance intensities of N-acetylaspartate (NAA) relative to creatine (Cr) were measured in a large central brain volume. NAA/Cr in NAWM was estimated by regression of the NAA/Cr in each voxel against white matter fraction and extrapolation to a white matter fraction of 1. The fractional size of the semi-solid pool (F) was obtained from the binary spin bath model of MT by computing the model parameters from multiple MT-weighted and relaxometry acquisitions. F in NAWM was significantly smaller in the patients [0.109 (0.009)] relative to controls [0.123 (0.007), P = 0.011], but did not differ between RR [0.1085] and SP [0.1087] patients [P > 0.99]. NAA/Cr and F in the NAWM were not correlated (r = 0.16, P > 0.7), mainly due to a lack of variation in F among patients. This may indicate a floor to the extent of myelin pathology that can occur in NAWM before a lesion appears, or that axonal damage is not strictly related to demyelination. The correlation between NAWM NAA/Cr and T2w lesion volume was not significant (P > 0.1). However, dividing the lesion volumes by the mean F in T2w lesions resulted in a quantity that correlated well with NAWM NAA/Cr (r = -0.78, P = 0.038), possibly reflecting the association of Wallerian degeneration in the NAWM with axonal transection associated with demyelination within lesions.

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    • "Also known as the “clinico-radiological paradox” [6], this mismatch is probably due to the insensitivity of T2-weighted MRI measures to detect subtle histopathological alterations in NAWM. This argument has contributed to the development of new quantitative MR methods including MR spectroscopic imaging (MRSI) [7] and diffusion tensor imaging (DTI) [8] that present better sensitivity and/or specificity to characterize diffuse alterations in MS. "
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    ABSTRACT: Diffusion tensor imaging (DTI) and MR spectroscopic imaging (MRSI) provide greater sensitivity than conventional MRI to detect diffuse alterations in normal appearing white matter (NAWM) of Multiple Sclerosis (MS) patients with different clinical forms. Therefore, the goal of this study is to combine DTI and MRSI measurements to analyze the relation between diffusion and metabolic markers, T2-weighted lesion load (T2-LL) and the patients clinical status. The sensitivity and specificity of both methods were then compared in terms of MS clinical forms differentiation. MR examination was performed on 71 MS patients (27 relapsing remitting (RR), 26 secondary progressive (SP) and 18 primary progressive (PP)) and 24 control subjects. DTI and MRSI measurements were obtained from two identical regions of interest selected in left and right centrum semioval (CSO) WM. DTI metrics and metabolic contents were significantly altered in MS patients with the exception of N-acetyl-aspartate (NAA) and NAA/Choline (Cho) ratio in RR patients. Significant correlations were observed between diffusion and metabolic measures to various degrees in every MS patients group. Most DTI metrics were significantly correlated with the T2-LL while only NAA/Cr ratio was correlated in RR patients. A comparison analysis of MR methods efficiency demonstrated a better sensitivity/specificity of DTI over MRSI. Nevertheless, NAA/Cr ratio could distinguish all MS and SP patients groups from controls, while NAA/Cho ratio differentiated PP patients from controls. This study demonstrated that diffusivity changes related to microstructural alterations were correlated with metabolic changes and provided a better sensitivity to detect early changes, particularly in RR patients who are more subject to inflammatory processes. In contrast, the better specificity of metabolic ratios to detect axonal damage and demyelination may provide a better index for identification of PP patients.
    PLoS ONE 03/2012; 7(3-e32525). DOI:10.1371/journal.pone.0032525 · 3.23 Impact Factor
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    • "MBC is distinct from the other methods because, as a multispectral technique, it uses T1w, T2w, and PDw images. While multiple tissue classifiers are available (Khayati et al., 2008; Van Leemput et al., 2001; Zijdenbos et al., 1998), we chose MBC for its robustness, having been run on thousands of scans with minimal failures and having been shown to work well on subjects with lesions (Ghassemi et al., 2008; Levesque et al., 2005; Narayanan et al., 2006; Sled et al., 2004; Tartaglia et al., 2002). MBC requires the following inputs: intensity rangenormalized (Nyul et al., 2000) multispectral images, spatial probability anatomic maps of CSF, GM, and WM, and a tissue/intensity-specific conditional probability. "
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    ABSTRACT: Several methods exist and are frequently used to quantify grey matter (GM) atrophy in multiple sclerosis (MS). Fundamental to all available techniques is the accurate segmentation of GM in the brain, a difficult task confounded even further by the pathology present in the brains of MS patients. In this paper, we examine the segmentations of six different automated techniques and compare them to a manually defined reference standard. Results demonstrate that, although the algorithms perform similarly to manual segmentations of cortical GM, severe shortcomings are present in the segmentation of deep GM structures. This deficiency is particularly relevant given the current interest in the role of GM in MS and the numerous reports of atrophy in deep GM structures.
    NeuroImage 10/2010; 52(4):1261-7. DOI:10.1016/j.neuroimage.2010.05.029 · 6.36 Impact Factor
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    • "Malgré des avancées très importantes dans la compréhension des phénomènes pathologiques de la SEP [4], il n'existe pas encore de marqueur, qu'il soit clinique, biologique ou radiologique , permettant de prédire l'évolution de la SEP. C'est pourquoi, d'autres techniques d'IRM comme le transfert de magnétisation [5], l'imagerie spectroscopique [6] ou plus récemment l'IRM de tenseur de diffusion (DTI) ont été développées pour tenter de répondre à ce manque de spécificité [7]. En effet, la DTI permet, d'une part, d'évaluer et de visualiser par tractographie l'état des connectivités axonales [8] et, d'autre part, de quantifier différents paramètres caractéristiques de la diffusivité tissulaire comme la diffusivité moyenne (MD), la fraction d'anisotropie (FA), et les diffusivités axiales (␭a) et radiales (␭r) [9]. "
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    ABSTRACT: L’imagerie par résonance magnétique (IRM) constitue l’examen paraclinique essentiel pour le diagnostic de la sclérose en plaques (SEP) et la prise en charge du patient. Il permet de mettre en évidence le caractère inflammatoire de la maladie que l’on peut quantifier par la charge lésionnelle. Néanmoins, l’IRM anatomique ne permet pas de prédire l’évolution de la SEP. C’est pourquoi, nous proposons d’évaluer de nouveaux marqueurs physiopathologiques par imagerie de tenseur de diffusion (DTI) afin de quantifier différents paramètres caractéristiques de la diffusivité tissulaire comme la diffusivité moyenne (MD), la fraction d’anisotropie (FA), et les diffusivités axiales (λa) et radiales (λr). La détermination des ces paramètres dans deux régions de la substance blanche apparemment normale (SBAN), en l’occurrence le corps calleux (CC) et la SB semi-ovale (SBs) ont montré des altérations significatives chez les patients SEP avec des différences entre les formes cliniques. Parmi ces résultats, il faut noter l’élévation plus importante de la diffusivité radiale qui constitue probablement un marqueur très sensible de l’atteinte myélinique. De plus, ces modifications de diffusivité sont corrélées avec la charge lésionnelle, ce qui montre l’importance de ce facteur dans l’évaluation des processus inflammatoires. En conclusion, la DTI est donc un outil très sensible pour la caractérisation physiopathologique de la SEP qui peut apporter de nouveaux marqueurs permettant une meilleure compréhension de l’évolution clinique du patient et une adaptation de l’approche thérapeutique.
    IRBM 09/2009; 30(4):179–183. DOI:10.1016/j.irbm.2009.05.001 · 0.52 Impact Factor
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