Clinical Pilot Application of Super-Resolution US Imaging in Breast Cancer

Ultrasound localization microscopy of renal tumor xenografts in chicken embryo is correlated to hypoxia

“…We evaluated the utility of ULM imaging on a chicken embryo chorioallantoic membrane tumor xenograft model of renal cell carcinoma. Consistent with other research groups 26,28,29 , we demonstrated that ULM provides a dataset that is rich in both structural (anatomy, morphology) and physiological (velocity, flow rate) metrics at the scale that is approaching the microvascular level in tumors. In particular, the assessment of vascular tortuosity and corresponding correlation to intratumoral hypoxia are enticing, given that tissue hypoxia has been shown to be predictive of poor outcomes across a broad spectrum of disease states.…”

“…They produced a tumor classifier on the basis of ULM morphological and physiological parameters to discriminate intratumoral vascular phenotypes. They then applied their motion-model ULM technique to a clinical proof of concept study on patients with breast cancer, and then later extended this clinical pilot study in a report by Dencks et al 29 . Although ULM has shown great promise in characterizing and classify tumor microvasculature, the application of ULM for measurement tumor hypoxia is relatively unexplored, which is surprising given that conventional CEUS has been shown to provide surrogate biomarkers for intratumoral oxygenation 30 .…”

Super-resolution Ultrasound Imaging

“…Standard localization-based techniques for ULM rely on sufficient separability of microbubbles, placing an upper bound on the allowable concentration. Depending on the desired image fidelity, this in turn places a substantial lower bound on the acquisition time, typically being on the order of minutes Dencks et al 2018Dencks et al , 2019Hingot et al 2019). By introducing other trade-offs, super-resolution ultrasound can be performed faster through different strategies exploiting structured illumination (Ilovitsh et al 2018) or the signal structure.…”

“…These methods were applied to pre-clinical tumor xenografts for successful differentiation of tumor types in a radiomics analysis based on quantitative parameters of vessel morphology (Opacic et al 2018). Additionally, the clinical feasibility of the method was illustrated for chemotherapy monitoring of breast cancer (Opacic et al 2018;Dencks et al 2018Dencks et al , 2019. An example of microbubble tracking analysis of a contrast-enhanced ultrasound scan of a patient with breast cancer is illustrated in Figure 8.…”

“…This is less critical for superficial lesions in the skin or the muscle as well as for the brain but becomes highly relevant for abdominal organs such as liver, kidney, spleen and pancreas. Motion correction in the image plane has been implemented (Hingot et al 2017;Harput et al 2018;Dencks et al 2018Dencks et al , 2019 and needs to be further refined in future studies. However, motion that occurs orthogonal to the image plane remains a challenge.…”