Diffusion tensor imaging changes of the cortico-thalamic-striatal tracts correlate with fatigue and disability in people with relapsing-remitting MS

Abdulaziz Alshehri; Nikitas Koussis; Oun Al-Iedani; Jameen Arm; Ibrahim Khormi; Stasson Lea; Rodney Lea; Saadallah Ramadan; Jeannette Lechner-Scott

doi:10.1016/j.ejrad.2023.111207

Diffusion tensor imaging changes of the cortico-thalamic-striatal tracts correlate with fatigue and disability in people with relapsing-remitting MS

Eur J Radiol. 2024 Jan:170:111207. doi: 10.1016/j.ejrad.2023.111207. Epub 2023 Nov 18.

Authors

Abdulaziz Alshehri¹, Nikitas Koussis², Oun Al-Iedani³, Jameen Arm⁴, Ibrahim Khormi⁵, Stasson Lea⁶, Rodney Lea⁶, Saadallah Ramadan⁷, Jeannette Lechner-Scott⁸

Affiliations

¹ School of Health Sciences, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, Australia; Hunter Medical Research Institute, 1 Kookaburra circuit, New Lambton Heights, NSW 2305, Australia; Department of Radiology, King Fahad University Hospital, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
² Hunter Medical Research Institute, 1 Kookaburra circuit, New Lambton Heights, NSW 2305, Australia; School of Psychological Sciences, College of Engineering, Science and Environment, University of Newcastle, Callaghan, NSW 2308, Australia.
³ Hunter Medical Research Institute, 1 Kookaburra circuit, New Lambton Heights, NSW 2305, Australia; School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, Australia.
⁴ School of Health Sciences, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, Australia; Hunter Medical Research Institute, 1 Kookaburra circuit, New Lambton Heights, NSW 2305, Australia.
⁵ School of Health Sciences, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, Australia; Hunter Medical Research Institute, 1 Kookaburra circuit, New Lambton Heights, NSW 2305, Australia; College of Applied Medical Sciences, University of Jeddah, Jeddah, Saudi Arabia.
⁶ Hunter Medical Research Institute, 1 Kookaburra circuit, New Lambton Heights, NSW 2305, Australia.
⁷ School of Health Sciences, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, Australia; Hunter Medical Research Institute, 1 Kookaburra circuit, New Lambton Heights, NSW 2305, Australia. Electronic address: Saadallah.ramadan@newcastle.edu.au.
⁸ Hunter Medical Research Institute, 1 Kookaburra circuit, New Lambton Heights, NSW 2305, Australia; Department of Neurology, John Hunter Hospital, New Lambton Heights, Newcastle, 2305, Australia; School of Medicine and Public Health, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, Australia.

PMID: 37988961
DOI: 10.1016/j.ejrad.2023.111207

Abstract

Purpose: To investigate how the microstructural neural integrity of cortico-thalamic-striatal (CTS) tracts correlate with fatigue and disability over time. The primary outcome was diffusion tensor imaging (DTI) metrics change over time, and the secondary outcome was correlations with fatigue and disability in people with RRMS (pw-RRMS).

Methods: 76 clinically stable pw-RRMS and 43 matched healthy controls (HCs). The pw-RRMS cohort consisted of three different treatment subgroups. All participants underwent disability, cognitive, fatigue and mental health assessments. Structural and diffusion scans were performed at baseline (BL) and 2-year follow-up (2-YFU) for all participants. Fractional anisotropy (FA), mean, radial and axial diffusivities (MD, RD, AD) of normal-appearing white matter (NAWM) and white matter lesion (WML) in nine tracts-of-interests (TOIs) were estimated using our MRtrix3 in-house pipeline.

Results: We found significant BL and 2-YFU differences in most diffusion metrics in TOIs in pw-RRMS compared to HCs (p_FDR ≤ 0.001; false-detection-rate (FDR)-corrected). There was a significant decrease in WML diffusivities and an increase in FA over the follow-up period in most TOIs (p_FDR ≤ 0.001). Additionally, there were no differences in DTI parameters across treatment groups. AD and MD were positively correlated with fatigue scores (r ≤ 0.33, p ≤ 0.01) in NAWM-TOIs, while disability (EDSS) was negatively correlated with FA in most NAWM-TOIs (|r|≤0.31, p ≤ 0.01) at both time points. Disability scores correlated with all diffusivity parameters (r ≤ 0.29, p ≤ 0.01) in most WML-TOIs at both time points.

Conclusion: Statistically significant changes in diffusion metrics in WML might be indicative of integrity improvement over two years in CTS tracts in clinically stable pw-RRMS. This finding represents structural changes within lesioned tracts. Measuring diffusivity in pw-RRMS affected tracts might be a relevant measure for future remyelination clinical trials.

Keywords: Cortico-thalamic-striatal (CTS); Diffusion tensor imaging (DTI); Disability; Fatigue; Multiple Sclerosis (MS); TractSeg.

MeSH terms

Brain / pathology
Diffusion Magnetic Resonance Imaging / methods
Diffusion Tensor Imaging / methods
Humans
Multiple Sclerosis, Relapsing-Remitting* / complications
Neoplasm Recurrence, Local / pathology
White Matter* / diagnostic imaging
White Matter* / pathology