Axonal water fraction as marker of white matter injury in primary-progressive multiple sclerosis: a longitudinal study

M. Margoni, M. Petracca, S. Schiavi, M. Fabian, A. Miller, F. D. Lublin, M. Inglese

Research output: Contribution to journalArticlepeer-review


Background and purpose: Diffuse white matter (WM) injury is prominent in primary-progressive multiple sclerosis (PP-MS) pathology and is a potential biomarker of disease progression. Diffusion kurtosis imaging allows the quantification of non-Gaussian water diffusion, providing metrics with high WM pathological specificity. The aim of this study was to characterize the pathological changes occurring in the normal-appearing WM of patients with PP-MS at baseline and at 1-year follow-up and to assess their impact on disability and short-term disease progression. Methods: A total of 26 patients with PP-MS and 20 healthy controls were prospectively enrolled. Diffusion kurtosis imaging single-shot echo-planar imaging (EPI) was acquired on a 3-T scanner (Philips Achieva, Best, The Netherlands) (voxel size, 2 × 2 × 2 mm3, 30 directions for each b-value = 1000, 2000 s/mm2 and one b = 0 s/mm2). A two-compartment biophysical model of WM tract integrity was used to derive spatial maps of axonal water fraction (AWF), intra-axonal diffusivity, extra-axonal axial and radial diffusivities (De,axial, De,radial) and tortuosity from the following WM tracts: corpus callosum (CC), corticospinal tract (CST) and posterior thalamic radiation (PTR). Results: At baseline, patients with PP-MS showed a widespread decrease of AWF, tortuosity and De,axial and an increase of De,radial in CC, CST and PTR (P ranging from 0.001 to 0.036). At 1-year follow-up, a significant AWF decrease was detected in the body of CC (P = 0.048), PTR (P = 0.008) and CST (P = 0.044). Baseline AWF values in CST significantly discriminated progressed from non-progressed patients (P = 0.021; area under the curve, 0.854). Conclusion: Based on its change over time and its relationship with disease progression, among the analyzed metrics, AWF seems the most sensitive metric of WM tissue damage in PP-MS and therefore it could be considered as a marker for monitoring disease progression.

Original languageEnglish
Pages (from-to)1068-1074
Number of pages7
JournalEuropean Journal of Neurology
Issue number8
Publication statusPublished - Aug 1 2019


  • axonal water fraction
  • diffusion kurtosis imaging
  • disease progression
  • magnetic resonance imaging
  • primary-progressive multiple sclerosis

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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