Functional Hypothalamic MR Spectroscopy at 7 Tesla: Metabolic Shifts in Response to Food Image Stimuli and Associations With Hypothalamic Volume and Body Mass Index

• Ultra-high field 7T MRS enables detailed in vivo study of the hypothalamus • Functional MRS reveals stimulus-related hypothalamic metabolite changes • Subregion-specific volumes show distinct metabolite associations • BMI is linked to hypothalamic metabolic responses to food cues • Provides novel biomarkers for appetite regulation and obesity risk The hypothalamus plays a central role in regulating hunger and satiety, yet human in vivo studies have been limited by its small size. The advent of high-field MRI has expanded opportunities to examine hypothalamic metabolic function and fine structural detail. In this proof-of-concept study, we utilised 7 Tesla MR spectroscopy and structural T1-weighted MRI to investigate relationships between hypothalamic metabolites, subregional volumes, and BMI. Participants also completed a functional MRS paradigm using a block design with food image and rest conditions. Eighteen participants completed baseline hypothalamic MRS (mean age 32 ± 5.9 years; 8 female; mean BMI 27 ± 6.9). At baseline, higher tissue-corrected PCr concentrations were significantly associated with greater right tubular inferior hypothalamic volume (p < 0.01). Seventeen participants also underwent functional MRS (mean age 32 ± 5.7; 7 female; mean BMI 27 ± 6.6). During the active task condition (viewing food images), tissue-corrected and water-referenced PCr and PCho+GPC (p < 0.05) increased relative to baseline, with Ins showing a trend towards increase (p < 0.1). Compared with rest spectra, Glc+Tau showed a trend towards reduction in the active condition (p < 0.1). In the active condition, higher Cr and PCho+GPC were significantly associated with BMI (p < 0.05). These findings provide early human in vivo evidence linking hypothalamic metabolite concentrations to subregion-specific volumes, BMI and food-cue processing. Increases in high-energy phosphate and choline-containing metabolites during stimulation, alongside BMI-related metabolic variation, suggest dynamic hypothalamic metabolic responsivity relevant to appetite and energy-regulation pathways.