Imaging Lactate Metabolism in Breast Cancer with Hyperpolarized 13C Magnetic Resonance Imaging

Breast cancer is a heterogeneous disease. Some patients attain prolonged control with first-line therapies, while others present with highly aggressive, treatment resistant malignancies. Second- and third-line treatments often carry the risk of severe, potentially life threatening side effects and only a minority patients ultimately live longer because of them. The difficulty of identifying which patients would be likely to benefit from which combination of drugs, as well as separating those whose disease is responding to their treatment from those whose is not, contributes to the provision of ineffective care. Hyperpolarized 13C magnetic resonance imaging is an emerging modality that can detect lactate production associated with reprogrammed metabolism in cancer. Changes in 13C lactate signal following treatment may be a valuable early indication of disease response and may help guide treatment decisions. While clinical translation of hyperpolarized 13C MRI has been steadily progressing, there are currently no published studies assessing the value of imaging lactate with hyperpolarized 13C MRI for better understanding and treating patients with breast cancer. In this dissertation, three technical works are presented to address the needs of robust 13C imaging for clinical translation. 13C MRI requires separate radio frequency transmit and receive hardware called RF coils that have been designed to operate at the 13C rather than 1H resonant frequency. RF coils must also conform to the anatomy under investigation. In order to perform 13C imaging in breast, a 13C breast coil system was devised and constructed. While the speed afforded by echo-planar imaging makes it an attractive technique for meeting the strict constraints of 13C MRI, off-resonance magnetization can lead to geometric distortion and spatial misregistration of imaging data. A dual-echo technique is proposed as an approach to account for sources of distortion. Volumetric encoding is highly desirable in order to allow comparison of 13C lactate signals from diseased and normal tissues, but larger regions require more time to encode and this can limit the temporal resolution of dynamic acquisitions. A pseudo-random undersampling scheme is proposed in order to reduce encoding time requirements and improve coverage.Ph.D