Screening and Monitoring Response to Treatment Using Subsecond Molecular Imaging and Hyperpolarized Contrast Agents

Abstract

We have been developing low-field MRI of breast cancer using hyperpolarized contrast agents capable of interrogating metabolic pathways in vivo. While this five-year project has several objectives, the main areas of focus according to the approved Statement of Work for Year 1 were (i) design and development of second-generation xenon-129 automated polarizer, and (ii) optimization of preclinical low-field MRI system. Our team has designed the polarizer and, through a series of prototyping efforts, began xenon-129 polarizer construction. While the polarizer construction and automation is to be finished in Year 2, we demonstrated very high level of xenon-129 polarization, including values approaching 100% for xenon-129 at densities needed to produce multi-gram quantities sufficient for clinical research: the ultimate goal of our efforts. Besides improving the polarization benchmarks over our first-generation polarizer (and any other polarizer operating in batch production mode) that is currently used in clinical research, the designed polarizer will also be significantly more automated, compact, and adaptable. We were also able to optimize our RF coil performance for the pre-clinical MRI system from the perspective of maximizing signal-to-noise ratios for carbon-13 imaging and proton imaging. Imaging studies on phantoms have been completed and we are now planning imaging experiments in tumor-bearing mice during the next Year of funding. The up-to-date results of both arms of the projects described above were presented at scientific conference meetings, and they are either already submitted as manuscripts to peer-reviewed scientific journals or will be prepared during Year 2. We have also demonstrated the in vivo utility of one metabolic carbon-13 contrast agent in an animal model of breast cancer. This tracer, 1-13C-phospholactate, is chosen to be evaluated in preclinical low-field MRI studies. Overall, our team significantly progressed with contrast agent validation, polarizing, and imaging instrumentation development, which will enable our long-term progress towards the ultimate goal of developing a suite of tools involving imaging, polarization, and chemistry of contrast agents for sub-second molecular imaging of breast cancer. 15. SUBJECT TERMS Low-field breast cancer MRI, molecular imaging, response to treatment, breast cancer screening 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON