Three-dimensional aperture-driven photoacoustic tomography (3D-ADPAT)

As a powerful modality for biomedical research, photoacoustic computed tomography (PACT) offers the combination of optical specificity and acoustic penetration for in vivo visualization. However, its performance is limited by a trade-off between ultrasound detection aperture and sensitivity, compromising image contrast, resolution, and penetration depth. Here, we introduce three-dimensional aperture-driven photoacoustic tomography (3D-ADPAT) to overcome these limitations, synergistically combining a high–numerical-aperture focused ultrasonic transducer (HNA-FUT) with a phase-inverted focusing-equivalent reconstruction (PIFER) algorithm. This approach yields ~2.21-fold enhancement in spatial resolution and ~10-fold increase in contrast-to-noise ratio. 3D-ADPAT’s performance was validated through comprehensive simulations and phantom studies and further confirmed by in vivo whole-body imaging that resolved deep-seated anatomies and tracked small-molecule metabolic pathways. Furthermore, a barrel-shaped array–based 3D-ADPAT implementation was designed, supporting dynamic imaging within a large field of view or across variable spatiotemporal scales. In summary, 3D-ADPAT provides a powerful tool for advanced photoacoustic systems, promising to accelerate frontier biomedical research.