Contributions
Abstract: P790
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Introduction: Advanced imaging techniques can provide insights in the inflammatory and pathological processes. Here, we used Neurite Orientation Dispersion and Density Imaging (NODDI) and 23Na MRI to investigate early changes in the normal and lesional brain tissue of patients at onset of a clinically isolated syndrome (CIS).
Aims: (i)To compare the NODDI metrics and the total sodium concentration (tNA) between CIS patients and healthy controls (HCs);(ii)To determine the association between MRI metrics and clinical parameters;(iii) To compare differences in NODDI metrics and tNA between lesions and normal-appearing white matter (NAWM) in CIS patients .
Methods: We recruited 39 CIS patients (within 3 months from onset) and 14 healthy controls (HCs) age and gender matched. We scored EDSS, Brief Cognitive Assessment for MS and the Multiple Sclerosis Functional Composite score. All subjects underwent 3T brain MRI with structural images, post gadolinium scans and multi-shell DW imaging and 23Na MRI. We computed T2 hyperintense and T1 hypointense lesion volumes and brain segmentation was performed using GIF. We calculated tNa and NODDI indexes (orientation dispersion, which measures the variability of neurite orientations; and neurite density, which reflects the density of axons and dendrites) in brain tissues and T2 lesions. Linear regression models were used in our analysis adjusting for age, gender and brain volumes.
Results: 30(77%) patients had T2 hyperintense lesions (median vol. 3.1 mL;range 0-42); 11(28%) patients showed enhancing lesions and 21(54%) T1 hypointense lesions (median vol. 0.3 mL; range 0-6.2). In patients, neurite density index was lower in T2 hyperintense lesions than in their NAWM (0.44vs0.59,p< 0.0001) independently of the presence of enhancing lesions, and was negatively associated with T2 lesion volume (p=0.01), T1 lesion volume (p=0.04) and PASAT score (p=0.01).tNA was higher in T2 hyperintense lesions than in NAWM (43.8vs31mM, p=0.0001),independently of the presence of enhancing lesion, but did it not correlate with lesion volumes.
Conclusions: Sodium accumulation in MS lesions is known as a marker of acute inflammation and axonal loss. At CIS onset, it seems to be related to early pathological processes, occurring irrespective of blood-brain barrier permeability and fiber loss. Neurite density index confirms to be a potential further marker of axonal loss and demyelination independently correlated with clinical parameters.
Disclosure: SC has nothing to disclose; FP is funded by the National Institute for Health Research University College London Hospitals Biomedical Research Centre (NIHR BRC UCLH/UCL High Impact Initiative) and Bioclinica Inc.; ID has nothing to disclose ;CT has received an ECTRIMS post-doctoral research fellowship in 2015. She has also received honoraria and support for travelling from Bayer-Schering, Teva, erck-Serono and Serono Foundation, Biogen, Sanofi-Aventis, Novartis, and Ismar Healthcare; MY has nothing to disclose; FG is funded by the H2020-EU.3.1 CDS-QUAMRI grant (ref.: 634541) and received support from the UCL Grand Challenge Studentships scheme; BSS has nothing to disclose; BK has nothing to disclose; SO has nothing to disclose; CGWK is on the editorial board of Functional Neurology and receives research grants (PI and co-applicant) from ISRT, EPSRC, Wings for Life, UK MS Society, Horizon2020, Biogen and Novartis; AT has received speaker honoraria from Biomedia, Sereno Symposia International Foundation, Bayer and meeting expenses from Biogen Idec.; OC received research funding from: UK and National MS Societies, Rosetrees trust, and NIHR UCLH BRC. She is consultant for Novartis, Roche, and Teva. She is an Associate Editor for Neurology.
Abstract: P790
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Introduction: Advanced imaging techniques can provide insights in the inflammatory and pathological processes. Here, we used Neurite Orientation Dispersion and Density Imaging (NODDI) and 23Na MRI to investigate early changes in the normal and lesional brain tissue of patients at onset of a clinically isolated syndrome (CIS).
Aims: (i)To compare the NODDI metrics and the total sodium concentration (tNA) between CIS patients and healthy controls (HCs);(ii)To determine the association between MRI metrics and clinical parameters;(iii) To compare differences in NODDI metrics and tNA between lesions and normal-appearing white matter (NAWM) in CIS patients .
Methods: We recruited 39 CIS patients (within 3 months from onset) and 14 healthy controls (HCs) age and gender matched. We scored EDSS, Brief Cognitive Assessment for MS and the Multiple Sclerosis Functional Composite score. All subjects underwent 3T brain MRI with structural images, post gadolinium scans and multi-shell DW imaging and 23Na MRI. We computed T2 hyperintense and T1 hypointense lesion volumes and brain segmentation was performed using GIF. We calculated tNa and NODDI indexes (orientation dispersion, which measures the variability of neurite orientations; and neurite density, which reflects the density of axons and dendrites) in brain tissues and T2 lesions. Linear regression models were used in our analysis adjusting for age, gender and brain volumes.
Results: 30(77%) patients had T2 hyperintense lesions (median vol. 3.1 mL;range 0-42); 11(28%) patients showed enhancing lesions and 21(54%) T1 hypointense lesions (median vol. 0.3 mL; range 0-6.2). In patients, neurite density index was lower in T2 hyperintense lesions than in their NAWM (0.44vs0.59,p< 0.0001) independently of the presence of enhancing lesions, and was negatively associated with T2 lesion volume (p=0.01), T1 lesion volume (p=0.04) and PASAT score (p=0.01).tNA was higher in T2 hyperintense lesions than in NAWM (43.8vs31mM, p=0.0001),independently of the presence of enhancing lesion, but did it not correlate with lesion volumes.
Conclusions: Sodium accumulation in MS lesions is known as a marker of acute inflammation and axonal loss. At CIS onset, it seems to be related to early pathological processes, occurring irrespective of blood-brain barrier permeability and fiber loss. Neurite density index confirms to be a potential further marker of axonal loss and demyelination independently correlated with clinical parameters.
Disclosure: SC has nothing to disclose; FP is funded by the National Institute for Health Research University College London Hospitals Biomedical Research Centre (NIHR BRC UCLH/UCL High Impact Initiative) and Bioclinica Inc.; ID has nothing to disclose ;CT has received an ECTRIMS post-doctoral research fellowship in 2015. She has also received honoraria and support for travelling from Bayer-Schering, Teva, erck-Serono and Serono Foundation, Biogen, Sanofi-Aventis, Novartis, and Ismar Healthcare; MY has nothing to disclose; FG is funded by the H2020-EU.3.1 CDS-QUAMRI grant (ref.: 634541) and received support from the UCL Grand Challenge Studentships scheme; BSS has nothing to disclose; BK has nothing to disclose; SO has nothing to disclose; CGWK is on the editorial board of Functional Neurology and receives research grants (PI and co-applicant) from ISRT, EPSRC, Wings for Life, UK MS Society, Horizon2020, Biogen and Novartis; AT has received speaker honoraria from Biomedia, Sereno Symposia International Foundation, Bayer and meeting expenses from Biogen Idec.; OC received research funding from: UK and National MS Societies, Rosetrees trust, and NIHR UCLH BRC. She is consultant for Novartis, Roche, and Teva. She is an Associate Editor for Neurology.