In-Patient Repeatability and Sensitivity Study of Multi-Plane Super-Resolution Ultrasound in Breast Cancer

Abstract Purpose Super-resolution ultrasound (SRUS) is a promising imaging modality for detecting early microvascular changes after cancer treatment, offering advantages over tumour-size methods to evaluate response. For clinical application, it is crucial to assess repeatability of SRUS-derived biomarkers and their sensitivity to post-treatment changes. Experimental Design Clinical data were collected from breast cancer patients undergoing radiotherapy. 24 repeatability scans were conducted, and 11 participants underwent SRUS response assessment at 2-weeks and 6-months post-radiotherapy. Ultrafast CEUS acquisitions sampled four imaging planes of each tumour, generating 2D SRUS maps of microvascular structure and dynamics. SRUS-derived quantitative parameters were extracted, with repeatability assessed using the Repeatability Coefficient (RC). Changes in quantitative parameters were analysed post-radiotherapy, and the RC defined significant changes. SRUS-derived quantitative parameters were compared to histopathological CD31 staining of biopsy samples. Results The RCs of SRUS quantitative parameters improved when averaged over more imaging planes, indicating improved repeatability. Significant changes in SRUS quantitative parameters were observed at 2-weeks post-RT in 5/11 participants. In contrast, only 1/11 participants showed significant tumour size changes. By 2-weeks or 6-months post-RT, significant changes in SRUS quantitative parameter were detected in all participants, while significant changes in tumour size were observed in 6/11 participants. Among 10 participants with corresponding CD31 vessel counts, 7 showed a correlation between the direction of change in histopathological vessel count scores and SRUS vessel density. Conclusions This repeatability and response assessment study establishes multi-plane SRUS as a robust and sensitive tool for detecting early tumour microvascular changes in patients undergoing treatment. Funding CRUK Convergence Science Centre, Kortuc Inc., NHS, NIHR, ICiC, IAA.