High-resolution low-field molecular magnetic resonance imaging of hyperpolarized liquids.

Abstract

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 × 94 μm2 spatial resolution and hyperpolarized carbon-13 images with 250 × 250 μm2 in-plane spatial resolution were recorded in 4–8 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 13C images were recorded using large imaging matrices of up to 256 × 256 pixels and relatively large fields of view of up to 6.4 × 6.4 cm2. 13C images were recorded using hyperpolarized 1-13C-succinate-d2 (30 mM in water, %P13C = 25.8 ± 5.1% (when produced) and %P13C = 14.2 ± 0.7% (when imaged), T1 = 74 ± 3 s), and proton images were recorded using 1H hyperpolarized pyridine (100 mM in methanol-d4, %PH = 0.1 ± 0.02% (when imaged), T1 = 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 13C hyperpolarized contrast agent (1-13C-succinate-d2, sensitive to fast depolarization when at the Earth’s 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 (∼1 mM) metabolite concentrations.