Comparison of Neurite Orientation Dispersion and Density Imaging and Two-Compartment Spherical Mean Technique Parameter Maps in Multiple Sclerosis

Abstract

Microestructura; Esclerosi múltiple; Tècnica de mitjana esfèrica

Microestructura; Esclerosis múltiple; Técnica de la media esférica

Microstructure; Multiple sclerosis; Spherical mean technique

Background: Neurite orientation dispersion and density imaging (NODDI) and the spherical mean technique (SMT) are diffusion MRI methods providing metrics with sensitivity to similar characteristics of white matter microstructure. There has been limited comparison of changes in NODDI and SMT parameters due to multiple sclerosis (MS) pathology in clinical settings. Purpose: To compare group-wise differences between healthy controls and MS patients in NODDI and SMT metrics, investigating associations with disability and correlations with diffusion tensor imaging (DTI) metrics. Methods: Sixty three relapsing-remitting MS patients were compared to 28 healthy controls. NODDI and SMT metrics corresponding to intracellular volume fraction (vin), orientation dispersion (ODI and ODE), diffusivity (D) (SMT only) and isotropic volume fraction (viso) (NODDI only) were calculated from diffusion MRI data, alongside DTI metrics (fractional anisotropy, FA; axial/mean/radial diffusivity, AD/MD/RD). Correlations between all pairs of MRI metrics were calculated in normal-appearing white matter (NAWM). Associations with expanded disability status scale (EDSS), controlling for age and gender, were evaluated. Patient-control differences were assessed voxel-by-voxel in MNI space controlling for age and gender at the 5% significance level, correcting for multiple comparisons. Spatial overlap of areas showing significant differences were compared using Dice coefficients. Results: NODDI and SMT show significant associations with EDSS (standardised beta coefficient −0.34 in NAWM and −0.37 in lesions for NODDI vin; 0.38 and −0.31 for SMT ODE and vin in lesions; p < 0.05). Significant correlations in NAWM are observed between DTI and NODDI/SMT metrics. NODDI vin and SMT vin strongly correlated (r = 0.72, p < 0.05), likewise NODDI ODI and SMT ODE (r = −0.80, p < 0.05). All DTI, NODDI and SMT metrics detect widespread differences between patients and controls in NAWM (12.57% and 11.90% of MNI brain mask for SMT and NODDI vin, Dice overlap of 0.42). Data Conclusion: SMT and NODDI detect significant differences in white matter microstructure between MS patients and controls, concurring on the direction of these changes, providing consistent descriptors of tissue microstructure that correlate with disability and show alterations beyond focal damage. Our study suggests that NODDI and SMT may play a role in monitoring MS in clinical trials and practice.

This study has received funding under the European Union's Horizon 2020 research and innovation programme under grant agreement No. 634541 (CDS-QuaMRI) and 666992. This study has also received support from the Engineering and Physical Sciences Research Council (EPSRC R006032/1, M020533/1, G007748, I027084, N018702), Spinal Research (UK), Wings for Life (Austria), Craig H. Neilsen Foundation (USA) for INSPIRED and UK Multiple Sclerosis Society (grants 892/08 and 77/2017). This study was supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. FP was supported by a Guarantors of Brain post-doctoral non-clinical fellowship. AT was supported by an MRC grant (MR/S026088/1). EK was supported from the NIHR Great Ormond Street Hospital Biomedical Research Centre. FG was currently supported by the investigator-initiated PREdICT study at the Vall d'Hebron Institute of Oncology (Barcelona), funded by AstraZeneca and CRIS Cancer Foundation. AstraZeneca was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.