Thalamic Nuclei Volumes and Their Relationships to Neuroperformance in Multiple Sclerosis: A Cross-Sectional Structural MRI Study

Abstract

Background: Although reduced thalamic volume is associated with multiple sclerosis (MS)-related clinical impairment, the role of individual thalamic nuclei remains poorly understood.

Purpose/hypothesis: To test whether individual thalamic nuclei volumes are more strongly associated with clinical disability than the whole thalamic volume.

Study type: Retrospective analysis of a prospective dataset.

Subjects: A total of 108 MS patients and 48 age- and sex-matched healthy controls (HCs) FIELD STRENGTH: 3T.

Sequences: 3D T₁ -weighted inversion recovery spoiled gradient echo; 2D T₂ -weighted fluid-attenuated inversion recovery spin echo; 2D dual-echo proton density-weighted/T₂ -weighted spin echo.

Assessments: Clinical assessments included the Expanded Disability Status Scale (EDSS), Nine-Hole Peg Test (9HPT), Timed 25-Foot Walk (T25FW), Symbol Digit Modalities Test (SDMT), Brief Visuospatial Memory Test-Revised (BVMTR), and the California Verbal Learning Test (CVLT2). FreeSurfer provided anterior, intralaminar, lateral, medial, ventral, posterior, and total volumes.

Statistical tests: False discovery rate-corrected partial correlations (controlling for age, sex, and education) to assess the relationships between volumes and neuroperformance.

Results: Compared to HCs, MS patients presented with lower thalamic nuclei volumes (P < 0.05) except for the intralaminar nucleus (P = 0.279) and scored worse on all neuroperformance scales (P ≤ 0.05) except for CVLT2 (P = 0.151). All nuclei except intralaminar were associated with EDSS (correlation coefficient range: -0.233 to -0.395), SDMT (range: 0.247-0.423), and 9HPT (range: -0.232 to -0.303) (all P < 0.05). BVMTR was associated with anterior (r = 0.319), lateral (r = 0.31), and medial (r = 0.304) volumes (all P < 0.05). T25FW correlated with ventral (r = -0.392) and total (r = -0.309) volumes (both P < 0.05), with the latter being significantly greater (P < 0.05).

Data conclusion: Assessing individual nuclei volume can aid in unraveling the relationship between thalamic pathology and disparate aspects of MS-related disability.

Level of evidence: 2 TECHNICAL EFFICACY STAGE: 2.

Keywords: atrophy; cognition; multiple sclerosis; thalamus.

Figure 1.

In the top row, slices are shown depicting thalamic nuclei segmentation in a representative multiple sclerosis patient. Anterior nuclei are shown in green, intralaminar nuclei are shown in dark blue, lateral nuclei are shown in purple, medial nuclei are shown in yellow, posterior nuclei are shown in light blue and ventral nuclei are shown in red. The bottom row depicts the same segmentations in a three-dimensional view.

Figure 2.

In the top row, slices are shown depicting the original T1-weighted image (left) and corresponding thalamic nuclei segmentation (right) in a representative multiple sclerosis patient. Intralaminar nuclei are shown in dark blue, medial nuclei are shown in yellow, posterior nuclei are shown in light blue and ventral nuclei are shown in red. The bottom row shows the corresponding co-registered fluid-attenuated inversion recovery (FLAIR) image (left) and T2-weighted image (right). Note the pure thalamic lesion, indicated by the white arrow, which is hypointense on the T1 and hyperintense on the FLAIR and T2-weighted images. This lesion was not isolated to a single thalamic nucleus, but rather affected the intralaminar, posterior, and ventral nuclei.