Related Experiment Video
Updated: Aug 26, 2026
Standardized Data Acquisition for Neuromelanin-Sensitive Magnetic Resonance Imaging of the Substantia Nigra
Published on: September 8, 2021
NODDI-derived U-Fiber MRI Markers for Risk Stratification of Progression Independent of Relapse Activity in
Yixian Li1, Zichun Yan1, Zhuowei Shi1
1Department of Radiology, The First Affiliated Hospital of Medical University, Chongqing, China (Y.L., Z.Y., Z.S., Q.Z., F.Y., K.Z., X.D., B.Y., R.Y., Y.L.).
Rationale And Objectives:
Progression independent of relapse activity (PIRA) contributes to disability accumulation in relapsing-remitting multiple sclerosis (RRMS), but magnetic resonance imaging (MRI) markers of its microstructural substrate remain unclear. We evaluated whether U-fiber metrics derived from neurite orientation dispersion and density imaging and diffusion tensor imaging are associated with subsequent PIRA and may support MRI-based risk stratification.
Materials And Methods:
This single-center longitudinal study included 138 patients with RRMS who underwent 3 T brain MRI and were followed for a median of 3.0 years. PIRA required an Expanded Disability Status Scale (EDSS) worsening confirmed over 6 months; events preceded by a relapse within 90 days or followed by a relapse before the 6-month confirmation assessment were excluded. Metrics were extracted from 16 atlas-based superficial U-fiber bundles. Candidate variables underwent univariable screening, variance inflation factor filtering, and exploratory multivariable logistic regression to construct a reduced model. Performance was assessed using five-fold cross-validation, calibration, Brier score, decision curve analysis, and continuous net reclassification improvement (NRI).
Results:
PIRA developed in 35 patients (25.4%). Symbol Digit Modalities Test (SDMT), EDSS, right occipitotemporal neurite density index (NDI), right parietotemporal NDI, and right occipitotemporal FA were retained. The reduced model achieved an AUC of 0.793 (95% confidence interval [CI], 0.693-0.893) and a Brier score of 0.143. Adding U-fiber metrics improved reclassification beyond SDMT and EDSS (continuous NRI, 0.518; 95% CI, 0.138-0.882; p = 0.006).
Conclusion:
Advanced diffusion MRI-derived U-fiber metrics may complement clinical measures for exploratory PIRA risk stratification in RRMS and warrant validation in independent multicenter cohorts.
