CFREE-uPIV: A contrast-free resolution-enhanced ultrasound particle image velocimetry for rapid microvascular flow...

Microvascular hemodynamic abnormalities are closely implicated in the onset and progression of many diseases, and often precede overt clinical symptoms, highlighting the importance of their early and quantitative assessment. However, existing approaches, typified by ultrasound localization microscopy (ULM), are constrained by the need for contrast agents and prolonged data acquisition time, restricting their applicability in special populations, including pregnant women and infants. To address this challenge, we propose a novel blood flow imaging framework, CFREE-uPIV, based on mean-shift theory and ultrasound speckle tracking. By constructing a high-resolution speckle field that characterizes the motion of blood-scattering particles and tracking speckle dynamics across consecutive temporal frames, CFREE-uPIV generates high-resolution vector flow fields that faithfully capture multiscale blood flow velocity, one of the most important hemodynamic parameters, without contrast enhancement. In vivo experiments in rats demonstrate that CFREE-uPIV effectively enhances the resolution of contrast-free ultrasound imaging (∼40 μm) and enables rapid and accurate vector flow estimation. Further validation in a hypoxic-ischaemic encephalopathy model underscores its clinical potential for detecting pathological blood flow alterations. Collectively, this study provides a novel approach for the rapid, contrast-free assessment of microvascular hemodynamics.