A calibration‐based approach to real‐time in vivo monitoring of pyruvate C₁ and C₂ polarization using the J_CC spectral asymmetry

Abstract

A calibration-based technique for real-time measurement of pyruvate polarization by partial integral analysis of the doublet from the neighbouring J-coupled carbon is presented. In vitro calibration data relating the C2 and C1 asymmetries to the instantaneous C1 and C2 polarizations, respectively, were acquired in blood. The feasibility of using the in vitro calibration data to determine the instantaneous in vivo C1 and C2 polarizations was demonstrated in the analysis of rat kidney and pig heart spectral data. An approach for incorporating this technique into in vivo protocols is proposed.

Sampling Hyperpolarized Molecules Utilizing a 1 Tesla Permanent Magnetic Field

“…We also observe intensity asymmetries in the doublet centered at 27 and 206 ppm. We attribute this asymmetry to differential polarization of the coupled 13 C nuclei, consistent with observations made previously31. While there has been much excitement for the translation of HP MRI to the clinic, the majority of hospital scanners operate at 1.5T32.…”

Doublet asymmetry for estimating polarization in hyperpolarized 13C–pyruvate studies

“…with the residual strong‐coupling characteristic of the J ‐coupling interaction between the C 1 and C 2 carbons. For [1,2‐ 13 C]Pyr, using J = 64 Hz and ( Ω I – Ω S )/2 π = 1152 Hz at 3 T and 25°C, the asymmetry parameter at thermal equilibrium is a C eq = sin θ = 0.056, as reported earlier …”

“…Zero‐order and first‐order phase correction was performed on the spectra, and the metabolite time courses were calculated by integrating the [1,2‐ 13 C]Pyr doublet peaks in absorption mode. Flip angle correction was applied to the integrated data, and the time evolution of the asymmetry parameter for the C 1 and C 2 doublet was computed using the definition a C = (inner peak − outer peak)/(inner peak + outer peak), as given in Reference . The center of the chemical shift between the two carbons is conventionally taken to be zero and the peaks closer to this center are considered “inner” peaks, whereas the peaks farther from the center are termed “outer”.…”

“…Defining a doublet asymmetry parameter a C = (inner peak − outer peak)/(inner peak + outer peak) based on the integral of the area under the doublet peaks, the C 2 doublet asymmetry is given by (see supplementary material) …”

“…The relationship between the instantaneous polarization and the asymmetry of the C 2 doublet, as measured by the asymmetry parameter a C2 = (inner peak − outer peak)/sum of both peaks, of [1,2‐ 13 C]Pyr in whole pig blood was used to estimate in vivo instantaneous C 1 polarization by Lau et al A paradoxical finding from this work was that the observed time evolution of a C2 did not appear to asymptotically approach the known thermal equilibrium value, and Lau et al proposed determining instantaneous polarization from a C2 ( t ) data based on an empirical calibration curve.…”