Rigid Hollow Microparticles for Enhanced Focused Ultrasound Treatment Under Optoacoustic Guidance

The efficacy and safety of focused ultrasound (FUS) treatments can be significantly enhanced with microbubbles, but the common ultrasound contrast agents suffer from limited stability, short circulation times, and risks associated with inertial cavitation and jetting. Here, we demonstrate that rigid hollow microparticles enable controlled, targeted thermal treatments of deep tissues via FUS. These acoustically responsive agents exhibit properties comparable to microbubbles yet possess superior mechanical stability, prolonged circulation, and enhanced responsiveness. Characterized by a negative acoustic contrast factor, the hollow microparticles amplify FUS-induced effects-particularly localized hyperthermia-enabling precise, robust, and controllable thermal therapy. Tissue ablation experiments under optoacoustic imaging guidance demonstrate strong responsiveness to FUS, with histological analyses confirming a threefold increase in ablation volume compared with microparticle-free controls. Experimental and numerical results indicate that this enhanced efficacy arises from first-order acoustic effects and secondary mechanisms, including acoustic scattering and stable particle-to-particle interactions. Unlike microbubbles, hollow microparticles rely on non-cavitational heating, enabling predictable, dose-dependent thermal responses that improve safety and efficacy. The frequency-dependent response further highlights their multifunctional potential under varying acoustic conditions. These findings establish rigid hollow microparticles as stable, versatile acoustic agents that significantly advance the therapeutic scope and clinical utility of FUS therapies.