H-SynEx: Using synthetic images and ultra-high resolution ex vivo MRI for hypothalamus subregion segmentation

The hypothalamus is a small structure located in the center of the brain and is involved in significant functions such as sleeping, temperature, and appetite control. Various neurological disorders are also associated with hypothalamic abnormalities. Automated image analysis of this structure from brain MRI is thus highly desirable to study the hypothalamus in vivo. However, most of the automated segmentation tools currently available focus exclusively on T1w images. In this study, we introduce H-SynEx, a machine learning method for automated segmentation of hypothalamic subregions that generalizes across different MRI sequences and resolutions without retraining. H-synEx was trained with synthetic images built from label maps derived from ultra-high resolution ex vivo MRI scans, allowing finer-grained manual segmentation when compared with 1 mm isometric in vivo images. We validated our method using Dice Coefficient (DSC) and Average Hausdorff distance (AVD) across in vivo images from six different datasets with six different MRI sequences (T1, T2, proton density, quantitative T1, fractional anisotropy, and FLAIR). Statistical analysis compared hypothalamic subregion volumes in controls, Alzheimer's disease (AD), and behavioral variant frontotemporal dementia (bvFTD) subjects using the Area Under the Receiver Operating Characteristic curve (AUROC) and the Wilcoxon rank sum test. Our results show that H-SynEx successfully leverages information from ultra-high resolution scans to segment in vivo from different MRI sequences. Our automated segmentation was able to discriminate controls versus patients with Alzheimer's disease on FLAIR images with 5 mm spacing. H-SynEx is openly available at https://github.com/liviamarodrigues/hsynex.