Ultrasound phase microscopy for rapid label-free super-resolution vascular imaging

Mapping deep microvascular structure and dynamics is essential for understanding organ function, neurovascular coupling and disease progression. Ultrasound localization microscopy (ULM) achieves super-resolution vascular imaging in deep tissue, but its dependence on exogenous contrast agents and prolonged stochastic tracking limits throughput and impedes the capture of transient hemodynamics. Here we introduce ultrasound phase microscopy (UPM), a label-free super-resolution ultrasound approach based on spatiotemporal phase decoding. UPM operates entirely on the receive side by converting motion-induced blood-signal phase shifts into sub-wavelength spatial gating through engineered phase gradients. A theoretical analysis shows that the effective gate width scales inversely with the square root of the signal-to-noise ratio, shifting the operative resolution boundary away from the classical diffraction limit. UPM achieves in vivo vascular resolution down to 4.8 µm without contrast agents. We apply UPM to whole-brain vascular mapping in a mouse model of Alzheimer’s disease, functional ultrasound imaging of visually evoked hemodynamics, and handheld renal imaging in vivo. UPM thus provides a rapid, contrast-free strategy for super-resolved vascular imaging in deep tissue.