Principal Investigator: Nick Todd, Ph.D., Post-doctoral Researcher, Department of Radiology, University of Utah

Co-Investigators: Dennis Parker, Ph.D., Professor of Radiology, University of Utah; Rares Salomir, Ph.D., Research Scientist, University of Geneva

Award: $100,000

Funding Period: June 1, 2010 - September 30, 2011

Abstract: The aim of this proposal is to implement MR temperature measurement techniques that accelerate data acquisition speed and are robust to motion-related errors. Collaboration between the research groups at the University of Utah and the University of Geneva will facilitate the transmission, implementation, and further development of these site-specific MR temperature measurement techniques and will accelerate the two goups' respective goals of using MRgHIFU to treat tumors in breast and liver.

Progress Report: 6-month progress report; Final progress report

Publications:

1. The effects of spatial sampling choices on MR temperature measurements

2. Reconstruction of fully 3-D high spatial and temporal resolution MR temperature maps for retrospective applications

Principal Investigator: Tyrone Porter, Ph.D., Assistant Professor of Mechanical Engineering, Boston University

Co-Investigator: Nathan McDanold, Ph.D., Assistant Professor of Radiology, Harvard Medical School, Brigham and Women's Hospital

Award: $100,000

Funding Period: January 1, 2010 - August 31, 2011

Abstract: The toxic effects of doxorubicin (DOX) on the heart limit the dose that can be administered systemically for the treatment of solid tumors. Targeted delivery of DOX to solid tumors will localize its cytotoxic effects, and improve its therapeutic index. This can be achieved by encapsulating DOX in temperature-sensitive liposomes and triggering release via ultrasound-induced heating in tumors. These DOX-loaded liposomes (diameter < 200 nm) can extravasate through leaky tumor vasculature and accumulate in the tumor interstitium. High intensity focused ultrasound can be used to heat the tumors noninvasively and trigger DOX release from the temperature-sensitive liposomes. By coencapsulating manganese sulfate in the liposomes, MRI can be used to monitor temperature-induced drug release from the liposomes. Manganese is a molecule that self-quenches when encapsulated in liposomes, but provides a strong MR signal when released. Thus, MR imaging can be used to provide feedback control of the transducer output to ensure sufficient heating and optimal DOX release at the breast tumor site. MRI-guided localized delivery of DOX to solid tumors will potentially raise the therapeutic index of DOX, thus reducing the required dose and frequency of drug administered systemically for tumor regression.

Progress Reports: 6-month progress report

Principal Investigators: Peter Eby, M.D., Assistant Professor of Radiology, University of Washington (December 1, 2009 - December 31, 2010); Norman J. Beauchamp, Jr., Professor and Chairman of Radiology, University of Washington (January 1 - Novembe 30, 2011)

Co-Investigators: Vijayakrishna K. Gadi, M.D., Ph.D., Department of Medicine, Division of Medical Oncology, University of Washington; Michael R. Bailey, Ph.D., Senior Research Engineer, Applied Physics Lab, University of Washington

Award: $100,000

Funding Period: December 1, 2009 - November 30, 2011

Abstract: The purpose of this study is to test the ability of MR-guided Focused Ultrasound (MRgFU) to ablate breast adenocarcinoma in situ in a mouse model and induce a significant systemic and local anti-tumor immune response. Growing evidence indicates that ablation of cancer in vivo can cause immune stimulation and produce a potent anti-tumor response. An unmet need in the treatment of breast cancer is the reduction of morbidity, time and cost of chemotherapy and radiation therapy. We propose to address this problem by using MRgFU to ablate tumors in a mouse model of breast cancer and measure the immune response. The quantitative data from this study may provide an alternative treatment approach for breast cancer that is cheaper, faster and less toxic than current therapeutic options thereby accelerating FDA approval and implementation of MRgFU into clinical practice.

Progress Report: 6-month progress report