Concurrent optoacoustic tomography and magnetic resonance imaging of resting-state functional connectivity in the mouse brain

Resting-state functional connectivity (rsFC) has been essential to elucidate the intricacy of brain organization, further revealing clinical biomarkers of neurological disorders. Although functional magnetic resonance imaging (fMRI) remains a cornerstone in the field of rsFC recordings, its interpretation is often hindered by the convoluted physiological origin of the blood-oxygen-level-dependent (BOLD) contrast affected by multiple factors. Here, we capitalize on the unique concurrent multiparametric hemodynamic recordings of a hybrid magnetic resonance optoacoustic tomography platform to comprehensively characterize rsFC in female mice. The unique blood oxygenation readings and high spatio-temporal resolution at depths provided by functional optoacoustic (fOA) imaging offer an effective means for elucidating the connection between BOLD and hemoglobin responses. Seed-based and independent component analyses reveal spatially overlapping bilateral correlations between the fMRI-BOLD readings and the multiple hemodynamic components measured with fOA but also subtle discrepancies, particularly in anti-correlations. Notably, total hemoglobin and oxygenated hemoglobin components are found to exhibit stronger correlation with BOLD than deoxygenated hemoglobin, challenging conventional assumptions on the BOLD signal origin.