Breast cancer is the second most frequently diagnosed cancer and the second cancer killer in U.S. women. Due to recent advances in medical imaging, efficient screening and early detection of breast cancer have resulted to lower morbidity from the disease. Because of the successful detection of breast cancer at an early stage, treatment techniques have also improved. The premise of ablation techniques is that, if a tumor and its normal-tissue margin can be destroyed in situ, instead of being removed, the impact on the disease should be equivalent. In addition, if the mortality associated with operative intervention can be avoided, then the outcome using localized treatments may be more advantageous. Ablation techniques are therefore slowly emerging as less invasive, but equally effective, in the treatment of early-stage breast cancer, with High-Intensity Focused Ultrasound (HIFU) being the only truly noninvasive, nonionizing, extracorporeal technique. HIFU has been applicable in the treatment of early-stage breast cancer with zero re-occurrence or skin damage (Huber et al. 2001;Hynynen et al. 2001). However, its translation to the clinic has been hindered in part by the extremely costly and slow monitoring MR-based methods used albeit their high image quality. Thus, there is currently a need for a simple, cost-efficient device that can reliably monitor HIFU treatment. In order to ensure its translation and reduce the cost of monitoring of HIFU monitoring while maintaining all its advantages, we have developed the radiation-force technique of Harmonic Motion Imaging (HMI) that can be used seamlessly in conjunction with HIFU for tumor ablation monitoring, namely HMI for Focused Ultrasound (HMIFU). HMIFU is thus an 1) entirely noninvasive (non-contact), 2) simple to implement, 3) real-time, 4) precise (estimating displacements of 1-10 microns), 5) fully integratable, and 6) low-cost technique for localized detection and in situ thermal treatment planning and monitoring of early-stage breast cancer. The general objective of the proposed study is to develop, optimize and test a real-time HMIFU system for tumor ablation and monitoring by utilizing the tumor's change in viscoelasticity property estimation during heating in phantom, ex vivo and in vivo murine and human applications. The underlying hypothesis is that the tumor and thermal lesion have sufficiently distinct mechanical properties compared to the normal tissue so that the system can treat and monitor the treatment of such a tumor.
The specific aims of the proposed study are thus to: 1) implement an all ultrasound-based system for real-time thermal ablation generation and monitoring and test in phantom and post-surgical breast specimens;2) apply HMIFU and assess its performance in animal tumor models in vivo;and 3) demonstrate initial clinical feasibility in human subjects with breast cancer in vivo. In summary, HMIFU can constitute a simple, noninvasive, real-time and low-cost monitoring technique for benign or early-stage breast tumors. More importantly, it may prove to be an important option to women without limited, focal disease, for whom less invasive and more focal treatment is most beneficial with minimized mortality and risk.

Public Health Relevance

An ultrasound-based, integrated system will be optimized for real-time localization and monitoring of tumor ablation in vivo. This will constitute a simple, low-cost, noninvasive and real-time method for simultaneous, fast and effective tumor detection and treatment. This new method may prove to be an important option offered to older women with early-stage breast tumors.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB014496-03
Application #
8461153
Study Section
Special Emphasis Panel (ZRG1-SBIB-J (80))
Program Officer
Lopez, Hector
Project Start
2011-07-01
Project End
2015-04-30
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
3
Fiscal Year
2013
Total Cost
$335,452
Indirect Cost
$123,277
Name
Columbia University (N.Y.)
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
049179401
City
New York
State
NY
Country
United States
Zip Code
10027
Payen, Thomas; Palermo, Carmine F; Sastra, Stephen A et al. (2016) Elasticity mapping of murine abdominal organs in vivo using harmonic motion imaging (HMI). Phys Med Biol 61:5741-54
Han, Yang; Wang, Shutao; Hibshoosh, Hanina et al. (2016) Tumor characterization and treatment monitoring of postsurgical human breast specimens using harmonic motion imaging (HMI). Breast Cancer Res 18:46
Grondin, Julien; Payen, Thomas; Wang, Shutao et al. (2015) Real-time Monitoring of High Intensity Focused Ultrasound (HIFU) Ablation of In Vitro Canine Livers Using Harmonic Motion Imaging for Focused Ultrasound (HMIFU). J Vis Exp :e53050
Vappou, Jonathan; Hou, Gary Y; Marquet, Fabrice et al. (2015) Non-contact, ultrasound-based indentation method for measuring elastic properties of biological tissues using harmonic motion imaging (HMI). Phys Med Biol 60:2853-68
Han, Yang; Hou, Gary Yi; Wang, Shutao et al. (2015) High intensity focused ultrasound (HIFU) focal spot localization using harmonic motion imaging (HMI). Phys Med Biol 60:5911-24
Chen, Hong; Hou, Gary Y; Han, Yang et al. (2015) Harmonic motion imaging for abdominal tumor detection and high-intensity focused ultrasound ablation monitoring: an in vivo feasibility study in a transgenic mouse model of pancreatic cancer. IEEE Trans Ultrason Ferroelectr Freq Control 62:1662-73
Chen, Jiangang; Hou, Gary Y; Marquet, Fabrice et al. (2015) Radiation-force-based estimation of acoustic attenuation using harmonic motion imaging (HMI) in phantoms and in vitro livers before and after HIFU ablation. Phys Med Biol 60:7499-512
Hou, Gary Y; Marquet, Fabrice; Wang, Shutao et al. (2015) High-intensity focused ultrasound monitoring using harmonic motion imaging for focused ultrasound (HMIFU) under boiling or slow denaturation conditions. IEEE Trans Ultrason Ferroelectr Freq Control 62:1308-19
Hou, Gary Y; Provost, Jean; Grondin, Julien et al. (2014) Sparse matrix beamforming and image reconstruction for 2-D HIFU monitoring using harmonic motion imaging for focused ultrasound (HMIFU) with in vitro validation. IEEE Trans Med Imaging 33:2107-17
Shahmirzadi, Danial; Hou, Gary Y; Chen, Jiangang et al. (2014) ExýýVivo characterization of canine liver tissue viscoelasticity after high-intensity focused ultrasound ablation. Ultrasound Med Biol 40:341-50

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