Dual-modal super-resolution ultrasound and NIR-II fluorescence imaging of ischemic stroke with ICG-doped porous PLGA microspheres

Abstract

Ischemic stroke, resulting from the obstruction of blood flow to the brain, remains a leading cause of morbidity and mortality worldwide. Traditional imaging modalities, such as magnetic resonance imaging and computed tomography, while effective for identifying stroke locations, are often limited in their ability to detect early pathological changes due to constraints in spatial resolution and sensitivity. This study introduces a novel dual-modal imaging approach that employs indocyanine green-doped porous poly (lactic-co-glycolic acid) (PLGA) microspheres (ICG-pPLGA MPs) for super-resolution ultrasound and near-infrared II (NIR-II) fluorescence imaging of ischemic stroke. The porous structure of ICG-pPLGA MPs enhances their stability, prolongs their circulation time, and improves ultrasound contrast compared to commercial lipid microbubbles. Additionally, the NIR-II fluorescence allows for high-resolution and noninvasive visualization of superficial vasculature. In a rat model of ischemic stroke, we demonstrate the capability of ICG-pPLGA MPs to achieve high-resolution imaging of cerebrovascular structures and functions, surpassing the imaging performance of standard diffusion-weighted imaging. Our findings underscore the potential of this dual-modal imaging technique using ICG-pPLGA MPs to accurately characterize microvascular changes during ischemic events, thus offering valuable insights for early diagnosis and therapeutic monitoring.