ATP line splitting in association with reduced intracellular magnesium and pH: a brain ³¹P MR spectroscopic imaging (MRSI) study of pediatric patients with myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGADs)

Over the past four decades, ATP, the obligatory energy molecule for keeping all cells alive and functioning, has been thought to contribute only one set of signals in brain ³¹P MR spectra. Here we report for the first time the observation of two separate β-ATP peaks in brain spectra acquired from patients with myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGADs) using 3D MRSI at 7 T. In voxel spectra with β-ATP line splitting, these two peaks are separated by 0.46 ± 0.18 ppm (n = 6). Spectral lineshape analysis indicates that the upper field β-ATP peak is smaller in relative intensity (24 ± 11% versus 76 ± 11%), and narrower in linewidth (56.8 ± 10.3 versus 41.2 ± 10.3 Hz) than the downfield one. Data analysis also reveals a similar line splitting for the intracellular inorganic phosphate (P_i) signal, which is characterized by two components with a smaller separation (0.16 ± 0.09 ppm) and an intensity ratio (26 ± 7%:74 ± 7%) comparable to that of β-ATP. While the major components of P_i and β-ATP correspond to a neutral intracellular pH (6.99 ± 0.01) and a free Mg²⁺ level (0.18 ± 0.02 mM, by Iotti's conversion formula) as found in healthy subjects, their minor counterparts relate to a slightly acidic pH (6.86 ± 0.07) and a 50% lower [Mg²⁺] (0.09 ± 0.02 mM), respectively. Data correlation between β-ATP and P_i signals appears to suggest an association between an increased [H⁺] and a reduced [Mg²⁺] in MOGAD patients.