Project 2: Overhauser enhanced Magnetic Resonance Imaging. (OMRI) Summary: a) Overhauser enhanced MRI: In this technique, the polarization of the tissue water is accomplished in situ at very low magnetic fields. Earlier studies used a scanner, which is a combination of EPR (For hyperpolarizing) and MR imaging (for detection) using a contrast agent whose relaxation properties are linearly dependent on pO2. These studies demonstrated the quantitative pO2 imaging capabilities of this technique. We are exploring additional applications for OMRI in studying tumor physiology taking advantage of the inherent advantage of the process of dynamic nuclear polarization. Arterial spin labeling in MRI is a widely used technique in examining issues related to blood flow. This method has been adapted to OMRI where a portion of spins in an artery are prepared for detection in a region upstream of the tissue being perfused. The inherent advantage of OMRI over ASL in MRI is the available dynamic range in OMRI being greater than in MRI. In addition to detecting the paramagnetic species by OMRI, we are using these probes directly as T1 contrasting molecules in MRI and imaging their spatial distribution and their pharmacokinetic behavior in vivo. b) Metabolic Imaging using Dynamic Nuclear Polarization: Usually, MRI, in spite of the low intrinsic sensitivity, can successfully provide anatomic images by probing the magnetic properties if tissue water protons. The reason for this success is that there is abundant water (> 45 M) in tissue and, of all the nuclear spins, detecting the signals from water protons are relatively easier compared to all other nuclei. However, imaging other metabolites, especially carbon containing organic molecules in vivo is challenging, because of the weak magnetic moments of 13C and the low levels of metabolites (10 100 mM). Using exogenous tracers such as 13C labeled pyruvate and hyperpolarization, it is possible to image these molecules by 13C MRI and also monitor the metabolic breakdown of this molecule to other metabolites and identify them based on their characteristic NMR spectra. Since pyruvate is at a crucial junction of cellular energetics, it is possible, using this technique, to biochemically characterize the tissues using MRI. We have entered into a CRADA with GE Healthcare and installing the apparatus for hyperpolarization at the MRI facility.
