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Development of Motion-Model Ultrasound Localization Microscopy to Support Breast Cancer Diagnosis and Therapy Monitoring in Patients

Subject Area Medical Physics, Biomedical Technology
Term from 2013 to 2024
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 233312120
 
Final Report Year 2025

Final Report Abstract

Ultrasound (US) imaging is routinely applied in breast cancer diagnostics and for the dignity assessment of suspect lesions. Supported by the DFG, we developed a contrast-enhanced super-resolution US method, which permits the reconstruction of the vasculature at a resolution beyond the diffraction limit by localizing and tracking individual microbubbles (MBs) in US video sequences. This technique, now referred to as ultrasound localization microscopy (ULM), enables the detailed assessment of the vascular architecture in tumours, but also of functional parameters like blood flow velocities or directions, as well as of derived parameters such as relative blood volume and perfusion. We further contributed to this rapidly developing technique by basic research on the systematic evaluation of single processing steps and by theoretical considerations and statistical modelling. In the first funding period, we could show in mice that a radiomics analysis of ULM data/images allows the discrimination of different tumour types. Additionally, we were the first who proved the clinical applicability of ULM using commercial US devices. In the second funding period, due to the more challenging conditions of clinical measurements (e.g., non-rigid and out-ofplane motion, limited measurement times and MB dose, administration of MBs), several processing steps and the measurement protocols had to be refined for a robust application. Based on this, we showed that ULM allows to gain insight into vascular changes induced by therapeutic US in mice and patients with triple-negative breast cancer (TNBC). Currently, we are finalizing a study on monitoring of neoadjuvant (i.e., presurgical) therapy in patients with particularly aggressive breast cancer. As most patients do not achieve a so-called pathological complete response (pCR, i.e., complete disappearance of cancer cells in the primary tumour), there is a high need for a modality that allows to identify patients with a low predisposition for a pCR, either early during therapy or, ideally, before the start of therapy. Here, we showed that pCR patients tend to have a more pronounced and homogeneous vessel network as well as a higher vessel tortuosity at the beginning. In contrast to non-pCR patients, who did not show apparent changes during chemotherapy, ULM features of pCR patients tended to moderately change throughout chemotherapy. This is a particularly important finding, since the current gold standard in therapy monitoring, i.e., the decrease in tumour size, did not allow to differentiate between both groups.

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