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bioRxiv · 10.64898/2026.04.30.722008

3D-PAULM: Integrated Photoacoustic Tomography and Ultrasound Localization Microscopy for Multiparametric Brain and Tumor Imaging

Xu, Y.·Yao, R.·Sheng, H.·Wang, N.·Yu, X.·Cai, X.·Cai, J.·Luo, J.·Li, J.·Yang, W.·Song, P.·Verkhusha, V.·Yao, J.
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Abstract

Understanding processes such as blood-brain barrier (BBB) disruption and tumor progression can greatly benefit from simultaneous molecular, functional, and hemodynamic imaging in deep tissue, yet few existing imaging modalities can provide all three in a single system. Here, we present an integrated imaging platform that combines 3D photoacoustic tomography with ultrasound localization microscopy (3D-PAULM) to enable intrinsically co-registered, multiparametric imaging. 3D-PAULM unifies multispectral photoacoustic molecular imaging, ultrasound B-mode imaging, microbubble-enhanced power Doppler, and ultrasound localization microscopy, and concurrently measures blood oxygenation, blood perfusion, microvascular flow dynamics, and molecular probes from near-infrared dyes and photoswitchable phytochromes. We apply 3D-PAULM to quantify BBB leakage in focal ischemia and systemic inflammation, and to perform high-sensitivity molecular imaging of solid tumors alongside functional mapping of tumor hypoxia and super-resolved vascular remodeling. Together, these results establish 3D-PAULM as a versatile platform for integrated functional and molecular imaging in deep tissue.

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Xu, Y., Yao, R., Sheng, H., Wang, N., Yu, X., Cai, X., Cai, J., Luo, J., Li, J., Yang, W., Song, P., Verkhusha, V., Yao, J.. 2026-05-05. 3D-PAULM: Integrated Photoacoustic Tomography and Ultrasound Localization Microscopy for Multiparametric Brain and Tumor Imaging. https://doi.org/10.64898/2026.04.30.722008

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