Parahydrogen-induced polarization and spin order transfer in ethyl pyruvate at high magnetic fields

Nuclear magnetic resonance has experienced great advances in developing and translating hyperpolarization methods into procedures for fundamental and clinical studies. Here, we propose the use of a wide-bore NMR for large-scale (volume- and concentration-wise) production of hyperpolarized media using parahydrogen-induced polarization. We discuss the benefits of radio frequency-induced parahydrogen spin order transfer, we show that 100% polarization is theoretically expected for homogeneous B0 and B1 magnetic fields for a three-spin system. Moreover, we estimated that the efficiency of spin order transfer is not significantly reduced when the B1 inhomogeneity is below ± 5%; recommendations for the sample size and RF coils are also given. With the latest breakthrough in the high-yield synthesis of 1-13C-vinyl pyruvate and its deuterated isotopologues, the high-field PHIP-SAH will gain increased attention. Some remaining challenges will be addressed shortly.

Hydrogenation. Before hydrogenation, the tube with the VP sample was placed in a hot water bath of 55 o C for 30 s. Then it was placed in the MRI and hydrogenation started within 10 s.
Hydrogenation is realized by flushing 90.5% pH2 at 10 bar through the solution. 100 PSI backpressure valve is connected to the outlet of the NMR tube. The solution was bubbled for 5-20 s, then SOT was applied after 2 s of settling down the liquid. 22 s and 7 s of hydrogenation time reported in the text is the sum of 20 s and 5 s of bubbling and 2 seconds of settling down.
Before all the following manipulations we measured one 13 C spectrum using a 5 o flipping angle. This was used to control hyperpolarization levels.

Polarizer MRI
9.4 T high-resolution wide-bore micro-imager (9 cm bore, WB400, Avance NEO Bruker) with 25 mm 1  Before SOT, the spectrometer was shimmed and tuned using the same tube but without a capillary. 1 H FLASH images of the tube filled with 1 mL chloroform are shown in Figure 4-A. 1  2. ESOTHERIC in a three-spin system of 1-13 C-EP-d6h2 Figure S1. ESOTHERIC-Ref SOT applied to 1-13 C-EP-d6h2: sequence itself (a), polarization isosurface as a function of , and for P=95% (b), and effect of flipping angle deviation from nominal value on P for n=1 (c), n=5 (d) with composite refocusing pulses ( ) and n=1 (e), n=5 (f) with a single pulse refocusing ( → ). The polarization of 99.7% 1-13 C-EP-d6 was reached at 1 = 3 = 166 ms, 2 = 70 ms. The longest diameters of isosurface are 66 ms for 1 and 3 , and 28 ms for 2 . To compensate for diffusion in the inhomogeneous magnetic field, multiple refocusing blocks are required; here calculations neglect diffusion, convection, and in homogeneous magnetic fields with ideal RF pulses. Note that a composite refocusing pulse is necessary to compensate for B1 inhomogeneity and deviation of flipping angle from the nominal value (compare (d) and (e)). Although it seems that n=1 is superior to n=5 cases, the convection and diffusion in the inhomogeneous field is not included in the simulations and must be considered for better justification of the refocusing choice. The polarization of 58% 1-13 C-EP-d3 was reached at 1 = 165 ms, 2 = 71.0 ms, 3 = 100 ms. The largest diagonals in at 1 , 2 , and 3 directions are 112 ms, 48 ms, and 73 ms. To compensate for diffusion in the inhomogeneous magnetic field, multiple refocusing blocks are required; here calculations neglect diffusion, convection, and in homogeneous magnetic fields with ideal RF pulses. Note that a composite refocusing pulse is necessary to compensate for B1 inhomogeneity and deviation of flipping angle from the nominal value (compare (d) and (e)). Although it seems that n=1 is superior to n=5 cases, the convection and diffusion in the inhomogeneous field is not included in the simulations and must be considered for better justification of the refocusing choice. The polarization of 15.4% 1-13 C-EP-h8 was reached at 1 = 142 ms, 2 = 28 ms, 3 = 70 ms. The largest diagonals in at 1 , 2 , and 3 directions are 28 ms, 20 ms, and 54 ms. To compensate for diffusion in the inhomogeneous magnetic field, multiple refocusing blocks are required; here calculations neglect diffusion, convection, and in homogeneous magnetic fields with ideal RF pulses. Note that a composite refocusing pulse is necessary to compensate for B1 inhomogeneity and deviation of flipping angle from the nominal value (compare (d) and (e)). Although it seems that n=1 is superior to n=5 cases, the convection and diffusion in the inhomogeneous field is not included in the simulations and must be considered for better justification of the refocusing choice. S-10 9. ESOTHERIC efficiency in inhomogeneous B1 field of 5 mm BBFO probe Table S1. Effect of B1 field inhomogeneity of 5 mm BBFO probe on SOT efficiency for EP-d6h2, EP-d3h5 and EP-h8. Four refocusing schemes were considered: single 180 o refocusing pulse and composite pulse with number of refocusing elements n=1 and 5. The B1 inhomogeneity for 200 μL sample is negligible for SOT efficiency. The same distribution was assumed for both 1 H and 13 C B1 fields. The used distributions are given on Figure S7D.

12.
Distribution of 1 H B1 field in 25 mm 1 H/ 13 C imaging probe along Z-axis Figure S11. B1 field mapping for a 25 mm 1 H/ 13 C imaging probe. (A) Scheme of a 10 mm NMR tube (here 513-7PVH-7 was used) in the NMR probe (note that it is rotated 90 o ). (B) Scheme of excitation-acquisition experiment with the switch on gradient before excitation. Length of the pulse, t, was varied from 0 to 199 μs with the step of 1 μs. (C) One exemplary measurement (from top to bottom): NMR spectrum of 1 mL acetone with the small flipping angle and gradient 0.1%. Note that here 3-axis 2.5 mic gradient system was used and only Z-gradient was applied. Then each point of the phased spectrum was fitted with the sine decay function: sin( 1 /2π) − / +