Purpose: Hyperpolarized Nuclear Magnetic Resonance (NMR) is a non-toxic, non-radioactive method for assessing tissue metabolism and other physiologic properties. Hyperpolarization allows for over 10,000-fold signal enhancement relative to conventional NMR and MRI. Methods: We have worked on different modalities of hyperpolarization for novel in vivo applications, including Parahydrogen Induced Polarization (PHIP), Dynamic Nuclear Polarization (DNP) (13C), continuous flow DNP of water (1H) as well as low temperature DNP of silicon nanoparticles (29Si). Results: a) By PHIP, we have hyperpolarized diethylsuccinate and use this endogenous compound to image the downstream metabolites of TCA cycle in real time in rodents within a minute [1]. Efforts are underway to fingerprint the 13C resonances of the TCA cycle metabolome in different cancer models in vivo and correlate that with the gene expression patterns. We have also developed DNP-based Chemical Reaction-Induced Multi-molecular Polarization (CRIMP) to generate multiple hyperpolarized agents to study multiple biochemical pathways and functions [2]. b) Employing water hyperpolarized via continuous flow DNP, we were able to obtain perfusion contrast for (1H) MRI thereby providing localized angiography of rat models in vivo [3]. The sensitivity gain of hyperpolarized water rivals that of gadolinium-based contrast agents. c) We have demonstrated direct in vivo MRI of hyperpolarized 29Si nuclei in silicon particles [4]. 29Si hyperpolarization was achieved via low temperature DNP utilizing the naturally occurring silicon dioxide defects at the particle surface, and showed a longitudinal relaxation time of over 40 mins. Efforts are underway to employ this technique for non-invasive virtual colonoscopy to detect polyps at an early stage as well as functionalize the nanoparticle surface for targeted molecular imaging of cancers in vivo. Conclusion: The three different hyperpolarized imaging modalities have opened up the possibilities for visualizing metabolism and other molecular events in real time wherein the local status of cancer can be interrogated on the time scale of seconds to minutes where both early detection as well as the monitoring of cancer therapy can be accomplished. References: [1] Zacharias, et al. J Am Chem Soc 2012, 134: 934-43. [2] Lee, et al. Chem Comm 2014, 50: 13030-33. [3] Lingwood, et al. Radiology 2012, 265: 418-25. [4] Cassidy, et al. Nature Nanotech 2013, 8: 363-68.

Real-time metabolic and molecular imaging In vivo by NMR hyperpolarization

249th National Meeting (2015)

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