Superresolution US Breast Cancer Imaging

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

Ultrasound imaging is routinely applied in breast cancer screening and for the dignity assessment of suspect lesions. Supported by the DFG, we developed a super-resolution contrast-enhanced ultrasound method called motion model ultrasound localization microscopy (mULM), which tracks individual microbubbles in video sequences and generates images of the vasculature at a resolution beyond the diffraction limit.
The mULM method enables an accurate assessment of the vascular architecture in tumors, individual blood vessel velocities and flow directions, and the quantification of relative blood volume and perfusion. Previously, we showed in mouse xenograft tumors that this method allows to extract various morphometric parameters and combined with a radiomics analysis supports the automated discrimination of different tumor types.

In this project, we aim to adapt and develop mULM and ultrasound-based radiomics for the application in patients and to advance the technique to 3D acquisition and tracking. In a preliminary analysis of clinical datasets, we were already able to extract super-resolution data of vascular tracks. However, several technical challenges for the robust application in a clinical setting emerged: in particular, patient motion and the lower image resolution together with increased slice thickness and non-optimized injection protocols allowed only to use short image sequences and to extract a reduced number of tracks.

Thus, in an initial step, the mULM methodology will be refined and adapted for its application in breast imaging on clinical ultrasound devices. Subsequently, the 2D mULM method will be applied to monitor breast cancers’ responses to neoadjuvant chemotherapy. Its accuracy will be compared to conventional contrast-enhanced ultrasound data analyses. Furthermore, we strive to advance the method from 2D to full 3D acquisition with a real-time volumetric scanner and compare both approaches in a small cohort of patients with breast tumors of different dignity. To exploit the full potential of mULM data analysis, algorithms will be developed and implemented that allow the automated extraction and clustered analysis of the vascular features. Measurements of similarity as well as cluster analysis will be performed to automatically group the patients. Thus, this project will be a first contribution to the clinical translation of multiparametric super-resolution ultrasound and open the way for ultrasound-based radiomics analysis.

Project Information

Project start
1. July 2013
Project end
30. June 2023
Funded by
German Research Foundation
Project Number
233312120

Publications

4873706 FWI9YJCI 1 ieee 50 date 2657 https://www.mt.rub.de/wp-content/plugins/zotpress/
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S. Dencks, M. Piepenbrock, and G. Schmitz, “Velocity Filtering with a Median Filter Better Preserves Small Vessels for Ultrasound Localization Microscopy,” in 2021 IEEE International Ultrasonics Symposium (IUS), Sep. 2021, pp. 1–4. doi: 10.1109/IUS52206.2021.9593882.
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M. Piepenbrock, D. Koretskaia, G. Schmitz, and S. Dencks, “3D Microbubble Localization with a Convolutional Neural Network for Super-Resolution Ultrasound Imaging,” in 2021 IEEE International Ultrasonics Symposium (IUS), Sep. 2021, pp. 1–4. doi: 10.1109/IUS52206.2021.9593473.
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M. Piepenbrock, S. Dencks, and G. Schmitz, “Tissue Motion Estimation of Contrast Enhanced Ultrasound Images with A Stable Principal Component Pursuit,” in 2021 IEEE 18th International Symposium on Biomedical Imaging (ISBI), Apr. 2021, pp. 1642–1645. doi: 10.1109/ISBI48211.2021.9434155.
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A. Rix et al., “Effects of contrast-enhanced ultrasound treatment on neoadjuvant chemotherapy in breast cancer,” Theranostics, vol. 11, no. 19, pp. 9557–9570, 2021, doi: 10.7150/thno.64767.
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M. Piepenbrock, S. Dencks, and G. Schmitz, “Microbubble Tracking with a Nonlinear Motion Model,” presented at the 2020 IEEE International Ultrasonics Symposium (IUS), Sep. 2020, pp. 1–4. doi: 10.1109/IUS46767.2020.9251581.
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S. Dencks, M. Piepenbrock, and G. Schmitz, “Assessing Vessel Reconstruction in Ultrasound Localization Microscopy by Maximum Likelihood Estimation of a Zero-Inflated Poisson Model,” IEEE Trans Ultrason Ferroelectr Freq Control, vol. 67, no. 8, pp. 1603–1612, Aug. 2020, doi: 10.1109/TUFFC.2020.2980063.
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K. Christensen-Jeffries et al., “Super-resolution Ultrasound Imaging,” Ultrasound Med Biol, vol. 46, no. 4, pp. 865–891, Apr. 2020, doi: 10.1016/j.ultrasmedbio.2019.11.013.
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M. Piepenbrock, A. Brieden, S. Dencks, and G. Schmitz, “Advancing the Feasible Microbubble Concentration in Super-Resolution,” presented at the IEEE International Ultrasonics Symposium (IUS), Oct. 2019, pp. 388–391. doi: 10.1109/ULTSYM.2019.8925761.
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M. Piepenbrock, S. Dencks, and G. Schmitz, “Reliable Motion Estimation in Super-Resolution US by Reducing the Interference of Microbubble Movement,” presented at the IEEE International Ultrasonics Symposium (IUS), Oct. 2019, pp. 384–387. doi: 10.1109/ULTSYM.2019.8925566.
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S. Dencks, M. Piepenbrock, and G. Schmitz, “Maximum-Likelihood Estimation to Assess the Degree of Reconstruction of Microvasculature from Super-Resolution US Imaging,” in 2019 IEEE International Ultrasonics Symposium (IUS), Oct. 2019, pp. 376–379. doi: 10.1109/ULTSYM.2019.8925640.
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S. Dencks et al., “Clinical Pilot Application of Super-Resolution US Imaging in Breast Cancer,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control, vol. 66, no. 3, pp. 517–526, 2019, doi: 10.1109/TUFFC.2018.2872067.
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M. Piepenbrock, S. Dencks, and G. Schmitz, “Performance of Foreground-Background Separation Algorithms for the Detection of Microbubbles in Super-Resolution Imaging,” presented at the 2018 IEEE International Ultrasonics Symposium (IUS), Oct. 2018, pp. 1–4. doi: 10.1109/ULTSYM.2018.8579815.
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S. Dencks et al., “Relative Blood Volume Estimation from Clinical Super-Resolution US Imaging in Breast Cancer,” presented at the 2018 IEEE International Ultrasonics Symposium (IUS), Oct. 2018, pp. 1–4. doi: 10.1109/ULTSYM.2018.8580013.
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A. Rix et al., “Advanced Ultrasound Technologies for Diagnosis and Therapy,” J Nucl Med, vol. 59, no. 5, pp. 740–746, May 2018, doi: 10.2967/jnumed.117.200030.
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T. Opacic et al., “Motion model ultrasound localization microscopy for preclinical and clinical multiparametric tumor characterization,” Nature Communications, vol. 9, no. 1, p. 1527, Apr. 2018, doi: 10.1038/s41467-018-03973-8.
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B. Theek, T. Opacic, D. Mockel, G. Schmitz, T. Lammers, and F. Kiessling, “Automated Generation of Reliable Blood Velocity Parameter Maps from Contrast-Enhanced Ultrasound Data,” Contrast media & molecular imaging, vol. 2017, 2017, doi: 10.1155/2017/2098324.
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S. Dencks, D. Ackermann, and G. Schmitz, “Evaluation of bubble tracking algorithms for super-resolution imaging of microvessels,” presented at the IEEE International Ultrasonics Symposium, Sep. 18, 2016.
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I. Spivak et al., “Low-Dose Molecular Ultrasound Imaging with E-Selectin-Targeted PBCA Microbubbles,” Mol. Imaging Biol., vol. 18, no. 2, pp. 180–190, Apr. 2016, doi: 10.1007/s11307-015-0894-9.
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D. Ackermann and G. Schmitz, “Detection and Tracking of Multiple Microbubbles in Ultrasound B-mode Images,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control, vol. 63, no. 1, pp. 72–82, 2016, doi: 10.1109/TUFFC.2015.2500266.
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D. Ackermann and G. Schmitz, “Super-resolution velocity estimation in microvessels using Multiple Hypothesis Tracking,” presented at the IEEE International Ultrasonics Symposium (IUS), Oct. 2015, pp. 1–4. doi: 10.1109/ULTSYM.2015.0219.
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D. Ackermann and G. Schmitz, “Reconstruction of flow velocity inside vessels by tracking single microbubbles with an MCMC data association algorithm,” presented at the IEEE International Ultrasonics Symposium (IUS), Jul. 2013, pp. 627–630. doi: 10.1109/ULTSYM.2013.0162.
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M. Siepmann et al., “Phase shift variance imaging - a new technique for destructive microbubble imaging,” IEEE Trans. Ultrason., Ferroelectr., Freq. Control, vol. 60, no. 5, pp. 909–923, 2013, doi: 10.1109/TUFFC.2013.2648.

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