Investigating brain-heart interactions using resting-state fMRI and photon-counting micro-CT in aged APOE mice
Understanding the interplay between brain and heart function is critical for mapping systemic aging and risk for neurodegenerative and cardiovascular diseases. We combined resting-state functional MRI (rs-fMRI) and photon-counting computed tomography (PCCT) to assess how APOE genotype, sex, and environmental exposures modulate brain-heart interactions in aged mice. Group-level independent component analysis (ICA) of rs-fMRI revealed 12 spatially distinct brain networks, including sensorimotor, subcortical (thalamus, hypothalamus), and cerebellar regions. PCCT imaging provided multi-phase cardiac metrics, including ejection fraction, stroke volume, and atrial volumes, with CNN-based segmentation. Statistical modeling revealed associations between regional brain connectivity and cardiac traits. Connectivity in thalamic, hypothalamic, and cerebellar areas predicted heart rate and right ventricular filling. Graph-based network topology (e.g., path length, clustering coefficient) was modulated by diet, genotype, and sex, and correlated strongly with right atrial volumes. Canonical correlation analysis revealed sex- and genotype-dependent patterns of neurocardiac coupling, with APOE33 females exhibiting the strongest associations and APOE22 males the weakest. These results highlight distributed neural circuits involved in autonomic regulation and suggest some key roles in brain-heart synchrony. Our work establishes a multimodal platform to investigate systemic aging and enables the development of stratified imaging biomarkers across genetic backgrounds.
