Photo-activated ultrasound localization imaging with laser-activated nanodroplets

Super-resolution ultrasound localization (UL) imaging enables microvascular visualization beyond the acoustic diffraction limit, but is limited by the short circulation time and uneven distribution of microbubbles. Here, we present photo-activated UL (PaUL) imaging using laser-triggered nanodroplets for super-resolved imaging with precise spatiotemporal control. We synthesized dual-contrast indocyanine green (ICG)-encapsulated perfluoropentane nanodroplets and developed a programmable activation and imaging sequence. PaUL imaging achieved 21 µm spatial resolution and enabled on-demand contrast generation by tuning laser fluence. Compared to conventional UL imaging, PaUL imaging provided 2.4× faster vascular reconstruction and 1.6× longer tracking lengths in hemodynamic mapping. Its extended circulation time allowed up to 3× more localization events across imaging windows exceeding 20 minutes. Overall, PaUL imaging offers flexible, high-resolution contrast and can be integrated with photoacoustic imaging to enhance multimodal capabilities. This technique holds promise for microvascular imaging and image-guided therapeutic applications such as targeted drug delivery.