Signal Amplification By Reversible Exchange (SABRE) is a method based on the transfer of parahydrogen (p-H2) polarization to the substrate nuclei due to the constant exchange of p-H2 and ligands over metallic Ir center of metal-organic complex. Generated levels of polarization provide the higher signal of the ligand. In the experiments, when SABRE process occurs in high magnetic field polarization from hydrogen atoms of p-H2 can be transferred to heteronuclei of the substrate using SLIC-SABRE pulse sequence, which generates the conditions of level anti-crossings.
We combined SLIC-SABRE method for polarization with FLASH (fast low angle shot) or SPI (single point imaging) pulse sequence for imaging. As a result, 15N MRI of 15N-labelled pyridine (15N-Py) and nicotinamide (15N-NA) was obtained. Imaging time using FLASH pulse sequence (< 1 second) in two orders smaller comparing with SPI (≈6 minutes for 15N-Py and 27 minutes for 15N-NA). Therefore, despite lower spatial resolution (0.15×2.4 mm2/pixel for 15N-Py and 0.3×4.8 mm2/pixel for 15N-NA using FLASH; 0.6×0.6 mm2/pixel using SPI) FLASH pulse sequence is more suitable for 15N MRI in biomedicine because of the necessity of shorter imaging time.
Consequently, FLASH was used for imaging of 4-aminopyride (fampridine) and dimethylaminopyridine (DMAP) with natural abundance of 15N nuclei. Fampridine is a drug used for treatment of multiple sclerosis. 15N NMR of fampridine and DMAP showed 15N polarization level ≈8% that allowed to do 15N MRI. The resulted images had spatial resolution 0.3×2.4 mm2/pixel which was enough to observe 1.6 mm capillary through which p-H2 was supplied. Signal-to-noise ratio was equal 49 and 109 for DMAP and fampridine correspondingly. This work is the first demonstration of 15N MRI of biomolecules with natural abundance of 15N nuclei using SLIC-SABRE for polarization.
This work was supported by grant from RSF #17-73-20030.