期刊
NEUROIMAGE-CLINICAL
卷 33, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.nicl.2021.102904
关键词
Multiple sclerosis; Lesion spatial distribution; Magnetic resonance imaging; Anisotropy; Caudality; SPACE-MS
类别
资金
- Junior Leader La Caixa Fellowship
- la Caixa Foundation [100010434]
- Merck Foundation
- ECTRIMS
- UK MS Society [77]
- European Union's Horizon 2020 research and innovation programme [634541]
- Engineering and Physical Sciences Research Council [EPSRC EP/R006032/1, M020533/1]
- Rosetrees Trust (UK)
- PREdICT (AstraZeneca in Spain)
- Guarantors of Brain
- National Institute for Health Research, University College London Hospitals Biomedical Research Centre
- ECTRIMS-MAGNIMS
- Guarantors of Brain Entry clinical fellowship
- International Progressive MS Alliance
- National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre
- Efficacy and Evaluation (EME) Programme, a Medical Research Council (MRC)
- National Institute for Health Research (NIHR) partnership and the Health Technology Assessment (HTA) Programme (NIHR)
- US National MS Society
- Rosetrees Trust
- National Institute for Health Research, University College London Hospitals, Biomedical Research Centre, London, UK
- Canadian MS society
- Actelion
- Biogen
- Novartis
- Roche
- National Institute for Health Research HTA
- MS Society of Great Britain
- Northern Ireland
- NIHR UCLH Biomedical Research Centre
- Wings for Life [169111]
- BRC [BRC704/CAP/CGW]
- UCL Global Challenges Research Fund (GCRF)
- MRC [MR/S026088/1]
- Ataxia UK
- [LCF/BQ/PI20/11760008]
- Medical Research Council [MR/S026088/1] Funding Source: researchfish
- H2020 Societal Challenges Programme [634541] Funding Source: H2020 Societal Challenges Programme
Predicting disability in progressive multiple sclerosis (MS) is challenging due to the lack of established quantitative metrics characterizing spatial distribution of white matter (WM) lesions. A novel approach, SPACE-MS, was introduced to quantitatively characterize spatial distributional features of brain MS lesions, showing that lesions in lower parts of the brain and more isotropic spreading of lesions are associated with clinical deterioration in progressive MS. This approach may be applicable to other conditions with brain WM lesions.
Predicting disability in progressive multiple sclerosis (MS) is extremely challenging. Although there is some evidence that the spatial distribution of white matter (WM) lesions may play a role in disability accumulation, the lack of well-established quantitative metrics that characterise these aspects of MS pathology makes it difficult to assess their relevance for clinical progression. This study introduces a novel approach, called SPACE-MS, to quantitatively characterise spatial distributional features of brain MS lesions, so that these can be assessed as predictors of disability accumulation. In SPACE-MS, the covariance matrix of the spatial positions of each patient's lesional voxels is computed and its eigenvalues extracted. These are combined to derive rotationally-invariant metrics known to be common and robust descriptors of ellipsoid shape such as anisotropy, planarity and sphericity. Additionally, SPACE-MS metrics include a neuraxis caudality index, which we defined for the whole-brain lesion mask as well as for the most caudal brain lesion. These indicate how distant from the supplementary motor cortex (along the neuraxis) the whole-brain mask or the most caudal brain lesions are. We applied SPACE-MS to data from 515 patients involved in three studies: the MS-SMART (NCT01910259) and MS-STAT1 (NCT00647348) secondary progressive MS trials, and an observational study of primary and secondary progressive MS. Patients were assessed on motor and cognitive disability scales and underwent structural brain MRI (1.5/3.0 T), at baseline and after 2 years. The MRI protocol included 3DT1-weighted (1x1x1 mm(3)) and 2DT2-weighted (1x1x3mm 3 ) anatomical imaging. WM lesions were semiautomatically segmented on the T2-weighted scans, deriving whole-brain lesion masks. After co-registering the masks to the T1 images, SPACE-MS metrics were calculated and analysed through a series of multiple linear regression models, which were built to assess the ability of spatial distributional metrics to explain concurrent and future disability after adjusting for confounders. Patients whose WM lesions laid more caudally along the neuraxis or were more isotropically distributed in the brain (i.e. with whole-brain lesion masks displaying a high sphericity index) at baseline had greater motor and/ or cognitive disability at baseline and over time, independently of brain lesion load and atrophy measures. In conclusion, here we introduced the SPACE-MS approach, which we showed is able to capture clinically relevant spatial distributional features of MS lesions independently of the sheer amount of lesions and brain tissue loss. Location of lesions in lower parts of the brain, where neurite density is particularly high, such as in the cerebellum and brainstem, and greater spatial spreading of lesions (i.e. more isotropic whole-brain lesion masks), possibly reflecting a higher number of WM tracts involved, are associated with clinical deterioration in progressive MS. The usefulness of the SPACE-MS approach, here demonstrated in MS, may be explored in other conditions also characterised by the presence of brain WM lesions.
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