Ultrasound Localization Microscopy for Breast Cancer Imaging in Patients: Protocol Optimization and Comparison with Shear Wave Elastography

Objective: Ultrasound localization microscopy (ULM) has gained increasing attention in recent years because of its ability to visualize blood vessels at super-resolution. The field of oncology, in particular, could benefit from detailed vascular characterization, for example, for diagnosis and therapy monitoring. This study was aimed at refining ULM for breast cancer patients by optimizing the measurement protocol, identifying translational challenges and combining ULM and shear wave elastography. Methods: We computed ULM images of 11 patients with breast cancer by recording contrast-enhanced ultrasound (CEUS) sequences and post-processing them in an offline pipeline. For CEUS, two different doses and injection speeds of SonoVue were applied. The best injection protocol was determined based on quantitative parameters derived from so-called occurrence maps. In addition, a suitable measurement time window was determined, also considering the occurrence of motion. ULM results were compared with shear wave elastography and histological vessel density. Results: At the higher dose and injection speed, the highest number of microbubbles, number of tracks and vessel coverage were achieved, leading to the most detailed representation of tumor vasculature. Even at the highest concentration, no significant overlay of microbubble signals occurred. Motion significantly reduced the number of usable frames, thus limiting the measurement window to 3.5 min. ULM vessel coverage was comparable to the histological vessel fraction and correlated significantly with mean tumor elasticity. Conclusion: The settings for microbubble injection strongly influence ULM images, thus requiring optimized protocols for different indications. Patient and examiner motion was identified as the main translational challenge for ULM.