Thalamic energy dysfunction is associated with thalamo-cortical tract damage in multiple sclerosis: A diffusion spectroscopy study

Vito A.G. Ricigliano, Matteo Tonietto, Raffaele Palladino, Emilie Poirion, Alberto De Luca, Francesca Branzoli, Geraldine Bera, Elisabeth Maillart, Bruno Stankoff, Benedetta Bodini

Research output: Contribution to journalArticlepeer-review


Background: Diffusion-weighted 1H magnetic resonance spectroscopy (DW-MRS) allows to quantify creatine-phosphocreatine brain diffusivity (ADC(tCr)), whose reduction in multiple sclerosis (MS) has been proposed as a proxy of energy dysfunction. Objective: To investigate whether thalamic ADC(tCr) changes are associated with thalamo-cortical tract damage in MS. Methods: Twenty patients with MS and 13 healthy controls (HC) were enrolled in a DW-MRS and DW imaging (DWI) study. From DW-MRS, ADC(tCr) and total N-acetyl-aspartate diffusivity (ADC(tNAA)) were extracted in the thalami. Three thalamo-cortical tracts and one non-thalamic control tract were reconstructed from DWI. Fractional anisotropy (FA), mean (MD), axial (AD), and radial diffusivity (RD), reflecting microstructural integrity, were extracted for each tract. Associations between thalamic ADC(tCr) and tract metrics were assessed using linear regression models adjusting for age, sex, thalamic volume, thalamic ADC(tNAA), and tract-specific lesion load. Results: Lower thalamic ADC(tCr) was associated with higher MD and RD of thalamo-cortical projections in MS (MD: p = 0.029; RD: p = 0.017), but not in HC (MD: p = 0.625, interaction term between thalamic ADC(tCr) and group = 0.019; RD: p = 0.320, interaction term = 0.05). Thalamic ADC(tCr) was not associated with microstructural changes of the control tract. Conclusion: Reduced thalamic ADC(tCr) correlates with thalamo-cortical tract damage in MS, showing that pathologic changes in thalamic energy metabolism are associated with structural degeneration of connected fibers.

Original languageEnglish
Pages (from-to)528-538
Number of pages11
JournalMultiple Sclerosis
Issue number4
Publication statusPublished - Apr 2021
Externally publishedYes


  • diffusion tensor imaging
  • diffusion-weighted spectroscopy
  • energy dysfunction
  • Multiple sclerosis
  • neurodegeneration
  • tractography


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