Abstract
Multiple sclerosis (MS) is characterised by widespread damage of the central nervous system that includes alterations in normal-appearing white matter (NAWM) and demyelinating white matter (WM) lesions. Neurite orientation dispersion and density imaging (NODDI) has been proposed to provide a precise characterisation of WM microstructures. NODDI maps can be calculated for the Neurite Density Index (NDI) and Orientation Dispersion Index (ODI), which estimate orientation dispersion and neurite density. Although NODDI has not been widely applied in MS, this technique is promising in investigating the complexity of MS pathology, as it is more specific than diffusion tensor imaging (DTI) in capturing microstructural alterations. We conducted a meta-analysis of studies using NODDI metrics to assess brain microstructural changes and neuroaxonal pathology in WM lesions and NAWM in patients with MS. Three reviewers conducted a literature search of four electronic databases. We performed a random-effect meta-analysis and the extent of between-study heterogeneity was assessed with the I2 statistic. Funnel plots and Egger’s tests were used to assess publication bias. We identified seven studies analysing 374 participants (202 MS and 172 controls). The NDI in WM lesions and NAWM were significantly reduced compared to healthy WM and the standardised mean difference of each was −3.08 (95%CI −4.22 to (−1.95), p ≤ 0.00001, I2 = 88%) and −0.70 (95%CI −0.99 to (−0.40), p ≤ 0.00001, I2 = 35%), respectively. There was no statistically significant difference of the ODI in MS WM lesions and NAWM compared to healthy controls. This systematic review and meta-analysis confirmed that the NDI is significantly reduced in MS lesions and NAWM than in WM from healthy participants, corresponding to reduced intracellular signal fraction, which may reflect underlying damage or loss of neurites.
Highlights
Multiple sclerosis (MS) is an autoimmune disease that affects almost 2.5 million individuals worldwide, often in young adulthood [1] MS is characterised by widespread damage of the central nervous system that includes alterations in normal-appearing white matter (NAWM) and demyelinating white matter (WM) lesions [2]. 4.0/).Magnetic resonance imaging (MRI) plays an essential role in diagnosing and monitoring the disease course and the treatment effectiveness in MS
MRI-histopathological studies have confirmed a high correlation between the diffusion tensor imaging (DTI) changes and axonal count in WM lesions and NAWM, indicating that these abnormalities may reflect pathological alterations related to disability [16,17,18]
Conclusions reduced in MS lesions and NAWM than WM from healthy participants, which corresponds
Summary
Multiple sclerosis (MS) is an autoimmune disease that affects almost 2.5 million individuals worldwide, often in young adulthood [1] MS is characterised by widespread damage of the central nervous system that includes alterations in normal-appearing white matter (NAWM) and demyelinating white matter (WM) lesions [2]. 4.0/).Magnetic resonance imaging (MRI) plays an essential role in diagnosing and monitoring the disease course and the treatment effectiveness in MS. Many studies have reported reduced fractional anisotropy (FA) and increased mean diffusivity (MD) in NAWM in MS patients compared with healthy participants [9,10,11,12] and one meta-analysis has confirmed a significant reduction of FA that suggested a widespread WM damage in MS [13]. These abnormalities may occur early in MS [14], DTI changes in the NAWM in patients with MS are linked with significant disability [15]. DTI indices are affected by the orientation dispersion of fibres [19], which may lead to misinterpretation [20]
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