High-Resolution Low-Field Molecular Magnetic Resonance Imaging of Hyperpolarized Liquids

We demonstrate the feasibility of microscale molecular imaging using hyperpolarized proton and carbon-13 MRI contrast media and low-field (47.5 mT) preclinical scale (38 mm i.d.) 2D magnetic resonance imaging (MRI). Hyperpolarized proton images with 94 x 94 mu m(2) spatial resolution and hyperpolarized carbon-13 images with 250 x 250 mu m(2) in-plane spatial resolution were recorded in 48 s (largely limited by the electronics response), surpassing the in-plane spatial resolution (i.e., pixel size) achievable with micro-positron emission tomography (PET). These hyperpolarized proton and C-13 images were recorded using large imaging matrices of up to 256 x 256 pixels and relatively large fields of view of up to 6.4 x 6.4 cm(2). C-13 images were recorded using hyperpolarized 1-C-13-succinate-d(2) (30 mM in water, %P-13C = 25.8 +/- 5.1% (when produced) and %P-13C = 14.2 +/- 0.7% (when imaged), T-1 = 74 +/- 3 s), and proton images were recorded using 1H hyperpolarized pyridine (100 mM in methanol-d(4), %PH = 0.1 +/- 0.02% (when imaged), T-1 = 11 +/- 0.1 s). Both contrast agents were hyperpolarized using parahydrogen (>90% para-fraction) in an automated 5.75 mT parahydrogen induced polarization (PHIP) hyperpolarizer. A magnetized path was demonstrated for successful transportation of a C-13 hyperpolarized contrast agent (1-C-13-succinate-d(2), sensitive to fast depolarization when at the Earths magnetic field) from the PHIP polarizer to the 47.5 mT low-field MRI. While future polarizing and low-field MRI hardware and imaging sequence developments can further improve the low-field detection sensitivity, the current results demonstrate that microscale molecular imaging in vivo is already feasible at low (<50 mT) fields and potentially at low (similar to 1 mM) metabolite concentrations.