Abstract
Microvascular dysfunction plays a pivotal role in numerous diseases, often preceding clinical symptoms and structural changes. Ultrasound localization microscopy (ULM) is an emerging ultrasound imaging modality that enables in vivo visualization of microvascular structures with unprecedented resolution. This narrative review aimed to examine the recent clinical applications of ULM and its role in biomarker development. It was conducted following PRISMA 2020 guidelines and included 33 articles published up to November 2025, focusing on ULM in human studies. Inclusion criteria targeted studies evaluating ULM's clinical applications and biomarkers. Data extraction encompassed imaging protocols, biomarkers and outcomes, with study quality assessed using the Newcastle-Ottawa Scale. ULM demonstrates significant promise across various organs. In kidney applications, ULM and its novel variant, sensing ULM, identified glomeruli and microvascular density as biomarkers for kidney disease and allograft dysfunction. In the brain, transcranial ULM enabled microvascular mapping with a resolution of 25 μm, aiding the evaluation of Moyamoya disease. ULM has also shown potential in detecting inflammatory changes in the carotid artery, myocardial microcirculation and testicular vascular architecture. Oncology applications include monitoring tumor vascularity and therapy response, revealing early microvascular changes undetectable by conventional imaging. Future technical improvements, such as higher-frame-rate clinical scanners, real-time data processing and clinical 3D imaging capabilities, are necessary to overcome current limitations. To conclude, ULM is on the verge of clinical translation, offering significant potential for developing microvascular biomarkers across various tissues and diseases. The medical community must now adopt and refine ULM applications and establish their role in routine clinical practice.