Development and Translation of Hyperpolarized Carbon-13 Cancer Imaging for Therapy Response Monitoring – from Animals to Humans
- Author(s): Zhu, Zihan
- Advisor(s): Vigneron, Daniel B.
- et al.
Hyperpolarized 13C metabolic imaging is an emerging medical imaging modality with powerful potential of probing a variety of diseases. With the recent technical breakthrough of dissolution dynamic nuclear polarization, the signal-to-noise ratio of 13C substrates enhanced drastically, enabling in vivo detection of metabolism, perfusion, pH, diffusion, and etc. The recent phase I and phase II human studies of hyperpolarized [1 – 13C]pyruvate on cancer patients have shown safety and feasibility of this new technique.
This dissertation focuses on the development and application of novel hyperpolarized 13C metabolic imaging techniques to monitor therapy response, with a particular emphasis on the bioengineering technical developments required for clinical translations. In the first two chapters of this dissertation, preclinical studies on cancer therapy response monitoring with different therapy regimes, different imaging sequences, at different field strengths were successfully performed. These studies showed positive results for the capability of hyperpolarized 13C metabolic imaging for detecting and monitoring response to therapy, with correlations of histology staining. Clinical translation to cancer patients imaging requires special considerations, such as larger imaging volume, respiratory motion, spatial resolution limit for tumor size, coil peak power limit, and etc. Specifically, a new 13C transceiver coil was built for human liver metastases imaging, along with a rapid spectroscopy MR sequence for rapid data acquisition and a respiratory bellow to record motion. Additionally, to allow more uniform excitation, large volume acquisition, and parallel imaging capabilities, multi-channel coils were used with specially developed analysis methods for some patient studies. Effective coil combination methods were explored and evaluated, and an innovative method was developed for easy and efficient data combination of hyperpolarized 13C spectroscopy and imaging data.