# White matter structural changes in the visual pathway of thyroid-associated ophthalmopathy patients: a free water and multi-shell diffusion imaging study

## TL;DR

This study uses advanced MRI techniques to detect white matter changes in the visual pathways of patients with thyroid-associated ophthalmopathy and links these changes to mental health.

## Contribution

The study introduces the use of free water and NODDI metrics to detect white matter microstructural changes in TAO patients.

## Key findings

- TAO patients showed altered FW and NODDI metrics in white matter compared to healthy controls.
- ODI had the highest diagnostic accuracy among the metrics tested.
- Microstructural changes correlated with anxiety, depression, and quality of life scores.

## Abstract

Compared to single-shell diffusion tensor imaging (DTI), free water (FW) and neurite orientation dispersion and density imaging (NODDI) offer a more comprehensive evaluation of microstructural alterations in cerebral white matter (WM), particularly in detecting crossing fibers. However, research utilizing multi-shell diffusion imaging to investigate thyroid-associated ophthalmopathy (TAO) remains limited. This study employs FW and NODDI to investigate microstructural changes in the white matter of the visual pathways in patients with TAO.

Multi-shell diffusion magnetic resonance imaging (dMRI) scans were performed on 45 patients with TAO and 31 age- and sex-matched healthy controls (HC). Tract-based spatial statistics (TBSS) analysis was conducted using eight FW and NODDI-derived metrics to identify group differences in white matter microstructure. Furthermore, correlations between these microstructural changes and clinical measures were examined.

TBSS analysis revealed that, compared to HC, patients with TAO exhibited lower free-water corrected fractional anisotropy (fwFA) and free-water corrected axial diffusivity (fwAD), while free-water corrected mean diffusivity (fwMD), free-water corrected radial diffusivity (fwRD), and orientation dispersion index (ODI) were significantly increased (p < 0.05, FWE). Notably, ODI demonstrated the highest area under the curve (AUC) among these metrics. Furthermore, fwFA, fwAD, fwMD, fwRD, and ODI showed significant correlations with the Hamilton Anxiety Rating Scale (HAMA), Hamilton Depression Rating Scale (HAMD), and the Graves’ Orbitopathy Quality of Life Questionnaire (GO-QOL2) scores.

This study suggests that abnormalities in the white matter microstructure of TAO patients can be detected through the complementary use of FW and NODDI metrics, and it is revealed that these changes may have an impact on mental health.