TY - JOUR
T1 - Investigating Microstructural Changes in White Matter in Multiple Sclerosis
T2 - A Systematic Review and Meta-Analysis of Neurite Orientation Dispersion and Density Imaging
AU - Alotaibi, Abdulmajeed
AU - Podlasek, Anna
AU - AlTokhis, Amjad
AU - Aldhebaib, Ali
AU - Dineen, Rob A.
AU - Constantinescu, Cris S.
N1 - Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/9
Y1 - 2021/9
N2 - 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.
AB - 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.
KW - neurite orientation dispersion and density imaging
KW - NODDI
KW - multi-shell diffusion
KW - multi-compartment diffusion
KW - multiple sclerosis
KW - MS
UR - http://www.scopus.com/inward/record.url?scp=85114328825&partnerID=8YFLogxK
U2 - 10.3390/brainsci11091151
DO - 10.3390/brainsci11091151
M3 - Article
AN - SCOPUS:85114328825
SN - 2076-3425
VL - 11
JO - Brain sciences
JF - Brain sciences
IS - 9
M1 - 1151
ER -