Toward Reliable Thalamic Segmentation: a rigorous evaluation of automated methods for structural MRI

Automated thalamic nuclear segmentation has contributed towards a shift in neuroimaging analyses from treating the thalamus as a homogeneous, passive relay, to a set of individual nuclei, embedded within distinct brain-wide circuits. However, many studies continue to widely rely on FreeSurfers segmentation of T1-weighted structural MRIs, despite their poor intrathalamic nuclear contrast. Meanwhile, a convolutional neural network tool has been developed for FreeSurfer, using information from both diffusion and T1-weighted MRIs. Another popular thalamic nuclear segmentation technique is HIPS-THOMAS, a multi-atlas-based method that leverages white-matter-like contrast synthesized from T1-weighted MRIs. However, rigorous comparisons amongst methods remain scant, and the thalamic atlases against which these methods have been assessed have their own limitations. These issues may compromise the quality of cross-species comparisons, structural and functional connectivity studies in health and disease, as well as the efficacy of neuromodulatory interventions targeting the thalamus. Here, we report, for the first time, comparisons amongst HIPS-THOMAS, the standard FreeSurfer segmentation, and its more recent development, against two thalamic atlases as silver-standard ground-truths. We used two cohorts of healthy adults, and one cohort of patients in the chronic phase of autoimmune limbic encephalitis. In healthy adults, HIPS-THOMAS surpassed, not only the standard FreeSurfer segmentation, but also its more recent, diffusion-based update. The improvements made with the latter relative to the former were limited to a few nuclei. Finally, the standard FreeSurfer method underperformed, relative to the other two, in distinguishing between patients and healthy controls based on the affected anteroventral and pulvinar nuclei. In light of the above findings, we provide recommendations on the use of automated segmentation methods of the human thalamus using structural brain imaging.