Hippocampal subfields and thalamic nuclei associations with clinical outcomes in multiple sclerosis: An ultrahigh field MRI study

Tales Santini; Chenyi Chen; Wen Zhu; Jr-Jiun Liou; Elizabeth Walker; Shruthi Venkatesh; Nadim Farhat; Andrea Sajewski; Salem Alkhateeb; Manojkumar Saranathan; Zongqi Xia; Tamer S Ibrahim

doi:10.1016/j.msard.2024.105520

Hippocampal subfields and thalamic nuclei associations with clinical outcomes in multiple sclerosis: An ultrahigh field MRI study

Mult Scler Relat Disord. 2024 Feb 27:86:105520. doi: 10.1016/j.msard.2024.105520. Online ahead of print.

Authors

Affiliations

¹ Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States.
² Department of Neurology, University of Pittsburgh, Pittsburgh, PA, United States.
³ University of Massachusetts Chan Medical School, Worcester, MA, United States.
⁴ Department of Neurology, University of Pittsburgh, Pittsburgh, PA, United States. Electronic address: zxia1@post.harvard.edu.
⁵ Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States; Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, United States; Department of Radiology, University of Pittsburgh, Pittsburgh, PA, United States. Electronic address: tibrahim@pitt.edu.

PMID: 38582026
DOI: 10.1016/j.msard.2024.105520

Abstract

Background: Previous studies have shown that thalamic and hippocampal neurodegeneration is associated with clinical decline in Multiple Sclerosis (MS). However, contributions of the specific thalamic nuclei and hippocampal subfields require further examination.

Objective: Using 7 Tesla (7T) magnetic resonance imaging (MRI), we investigated the cross-sectional associations between functionally grouped thalamic nuclei and hippocampal subfields volumes and T1 relaxation times (T1-RT) and subsequent clinical outcomes in MS.

Methods: High-resolution T1-weighted and T2-weighted images were acquired at 7T (n=31), preprocessed, and segmented using the Thalamus Optimized Multi Atlas Segmentation (THOMAS, for thalamic nuclei) and the Automatic Segmentation of Hippocampal Subfields (ASHS, for hippocampal subfields) packages. We calculated Pearson correlations between hippocampal subfields and thalamic nuclei volumes and T1-RT and subsequent multi-modal rater-determined and patient-reported clinical outcomes (∼2.5 years after imaging acquisition), correcting for confounders and multiple tests.

Results: Smaller volume bilaterally in the anterior thalamus region correlated with worse performance in gait function, as measured by the Patient Determined Disease Steps (PDDS). Additionally, larger volume in most functional groups of thalamic nuclei correlated with better visual information processing and cognitive function, as measured by the Symbol Digit Modalities Test (SDMT). In bilateral medial and left posterior thalamic regions, there was an inverse association between volumes and T1-RT, potentially indicating higher tissue degeneration in these regions. We also observed marginal associations between the right hippocampal subfields (both volumes and T1-RT) and subsequent clinical outcomes, though they did not survive correction for multiple testing.

Conclusion: Ultrahigh field MRI identified markers of structural damage in the thalamic nuclei associated with subsequently worse clinical outcomes in individuals with MS. Longitudinal studies will enable better understanding of the role of microstructural integrity in these brain regions in influencing MS outcomes.

Keywords: 7 tesla; Clinical outcomes; Hippocampus; Magnetic resonance imaging; Multiple sclerosis; Nuclei; Subfields; T1 relaxation time; Thalamus; Ultrahigh field; Volumes.