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Efficient drug delivery remains a significant challenge in modern medicine and pharmaceutical research. Micrometer-scale robots have recently emerged as a promising solution to enhance the precision of drug administration through remotely controlled navigation within microvascular networks. Real-time tracking is crucial for accurate guidance and confirmation of target arrival. However, deep-tissue monitoring of microscopic structures in vivo is limited by the sensitivity and spatiotemporal resolution of current bioimaging techniques. In this study, biocompatible microrobots are synthesized by incorporating indocyanine green and iron oxide nanoparticles onto copper phosphate microflowers using a layer-by-layer approach, enhancing optoacoustic contrast and enabling magnetic navigation. Magnetic control of these particles under optoacoustic guidance is demonstrated in vivo. Furthermore, super-resolution optoacoustic imaging, achieved through individual particle tracking, is shown to enable the characterization of microvascular structures and quantification of blood flow. The combination of the microflowers' high carrying capacity, in vivo actuation, and high-resolution tracking capabilities opens new opportunities for precise microvascular targeting and localized administration of theranostic agents via intravascular routes., (© 2025 Wiley‐VCH GmbH.)

Introduction: Transcranial pulse stimulation (TPS) is increasingly being investigated as a promising potential treatment for Alzheimer's disease (AD). Although the safety and preliminary clinical efficacy of TPS short pulses have been supported by neuropsychological scores in treated AD patients, its fundamental mechanisms are uncharted., Methods: Herein, we used a multi-modal preclinical imaging platform combining real-time volumetric optoacoustic tomography, contrast-enhanced magnetic resonance imaging, and ex vivo immunofluorescence to comprehensively analyze structural and hemodynamic effects induced by TPS. Cohorts of healthy and AD transgenic mice were imaged during and after TPS exposure at various per-pulse energy levels., Results: TPS enhanced the microvascular network, whereas the blood-brain barrier remained intact following the procedure. Notably, higher pulse energies were necessary to induce hemodynamic changes in AD mice, arguably due to their impacted vessels., Discussion: These findings shed light on cerebrovascular dynamics induced by TPS treatment, and hence are expected to assist improving safety and therapeutic outcomes., Highlights: ·Transcranial pulse stimulation (TPS) facilitates transcranial wave propagation using short pulses to avoid tissue heating. ·Preclinical multi-modal imaging combines real-time volumetric optoacoustic (OA) tomography, contrast-enhanced magnetic resonance imaging (CE-MRI), and ex vivo immunofluorescence to comprehensively analyze structural and hemodynamic effects induced by TPS. ·Blood volume enhancement in microvascular networks was reproducibly observed with real-time OA imaging during TPS stimulation. ·CE-MRI and gross pathology further confirmed that the brain architecture was maintained intact without blood-brain barrier (BBB) opening after TPS exposure, thus validating the safety of the procedure. ·Higher pulse energies were necessary to induce hemodynamic changes in AD compared to wild-type animals, arguably due to their pathological vessels., (© 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Optoacoustic imaging offers label-free multi-parametric characterization of cerebrovascular morphology and hemodynamics at depths and spatiotemporal resolution unattainable with optical microscopy. Effective imaging depth can greatly be enhanced by employing photons in the second near-infrared (NIR-II) window. However, diminished absorption by hemoglobin along with a lack of suitable contrast agents hinder an efficient application of the technique in this spectral range. Herein, copper sulfide (CuS) micro- and nano-formulations for multi-scale optoacoustic imaging in the NIR-II window are introduced. Dynamic contrast enhancement induced by intravenously administered CuS nanoparticles facilitated visualization of blood perfusion in murine cerebrovascular networks. The individual calcium carbonate microparticles carrying CuS are further shown to generate sufficient responses to enable super-resolution microvascular imaging and blood flow velocity mapping with localization optoacoustic tomography., (© 2024 The Author(s). Small Methods published by Wiley‐VCH GmbH.)