Photoacoustic imaging of human brain function through intact adult skulls

Abstract

Blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) has revolutionized noninvasive imaging of human brain function, but it indirectly senses deoxyhemoglobin through water-proton relaxation and relies on bulky, costly, noisy, enclosed, superconducting-magnet scanners. In contrast, photoacoustic computed tomography (PACT) directly probes hemoglobin absorption using a more compact, lower-cost, quieter, open, magnet-free system. However, functional PACT of the adult human brain has so far been demonstrated only after surgical skull removal, because the skull strongly attenuates optical and acoustic signals. Here, we demonstrate non-invasive transcranial functional PACT (T-fPACT) through the intact adult skull. A densely packed, high-channel-count (3,072-element) hemispherical ultrasonic array provides near-$2π$-steradian simultaneous acquisition, enabling high sensitivity and single-shot three-dimensional imaging at 20 Hz that eliminates motion blurring. Participant-specific stabilization further enables measurement of small task-evoked hemodynamic responses over the entire task duration. In healthy adults, T-fPACT localized responses to expected sensorimotor regions, distinguished task-specific motor representations, and yielded consistent localizations across repeated task runs and visits. Comparison with high-field (7 T) fMRI showed spatially corresponding functional regions, while dual-wavelength imaging revealed distinct hemoglobin-weighted responses. These findings overcome the long-standing skull barrier in human brain PACT and establish non-invasive, rapid volumetric photoacoustic imaging of brain function.