Measurement of unidirectional Pi to ATP flux in human visual cortex at 7 T by using in vivo 31P magnetic resonance spectroscopy

Abstract

Taking advantage of the high NMR detection sensitivity and the large chemical shift dispersion offered by ultra-high field strength of 7 T, the effect of magnetization transfer on inorganic phosphate (Pi) resonance during saturation of gamma-ATP resonance, mediated by the ATP synthesis reaction, was observed noninvasively in the human primary visual cortex by using in vivo 31P magnetic resonance spectroscopy. The unidirectional flux from Pi to ATP was measured by using progressive saturation transfer experiments. The cerebral ATP synthesis rate in the human primary visual cortex measured by 31P magnetic resonance spectroscopy in this study was 12.1 +/- 2.8 micromol ATP/g per min, which agreed well with the value that was calculated indirectly from the cerebral metabolic rate of glucose consumption reported previously.

Fig. 1.

Pulse sequence used for the saturation transfer experiments. Saturation pulse train with a duration of t_sat, constructed according to a B₁ insensitive selective train to obliterate signal (BISTRO) scheme, was used to saturate the γ-ATP resonance completely and was also applied downfield, symmetrically about the P_i resonance to serve as the control. TR was kept the same at 6.75 s regardless of t_sat. A hard excitation pulse (β)of200 μs was used. The symbols used in Eqs. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 to represent the longitudinal magnetization of P_i (M) at different time points are also defined here.

Fig. 2.

³¹P spectra acquired from a normal subject with (b) and without (c) complete saturation of the γ-ATP resonance (t_sat = 6.62 s), and the difference spectrum between the two (a). PDE, phosphodiesters; PME, phosphomonoesters.

Fig. 3.

The P_i region of the ³¹P spectra acquired with (Upper) and without (Lower) complete saturation of the γ-ATP resonance at saturation times (t_sat)of 0.62 s (a), 1.17 s (b), 1.71 s (c), 3.35 s (d), and 6.62 s (e) with constant TR of 6.75 s. The spectra shown were averaged spectra over four subjects, and the spectra from each individual subject were averaged with normalized PCr signal intensities.

Fig. 4.

Dependence of the ratio M_s/M_c on t_sat. M_s and M_c are the P_i signal intensities obtained in the saturation experiment and the control experiment, respectively. The solid line represents a least-square fit of the experimental data (•) to Eq. 11 (assuming β = 90°).