31P-MRS of healthy human brain: ATP synthesis, metabolite concentrations, pH, and T1 relaxation times

The conventional method for measuring brain ATP synthesis is P-31 saturation transfer (ST), a technique typically dependent on prolonged pre-saturation with -ATP. In this study, ATP synthesis rate in resting human brain is evaluated using EBIT (exchange kinetics by band inversion transfer), a technique based on slow recovery of -ATP magnetization in the absence of B-1 field following co-inversion of PCr and ATP resonances with a short adiabatic pulse. The unidirectional rate constant for the P-i -ATP reaction is 0.21 +/- 0.04s(-1) and the ATP synthesis rate is 9.9 +/- 2.1mmolmin(-1)kg(-1) in human brain (n = 12 subjects), consistent with the results by ST. Therefore, EBIT could be a useful alternative to ST in studying brain energy metabolism in normal physiology and under pathological conditions. In addition to ATP synthesis, all detectable P-31 signals are analyzed to determine the brain concentration of phosphorus metabolites, including UDPG at around 10ppm, a previously reported resonance in liver tissues and now confirmed in human brain. Inversion recovery measurements indicate that UDPG, like its diphosphate analogue NAD, has apparent T-1 shorter than that of monophosphates (P-i, PMEs, and PDEs) but longer than that of triphosphate ATP, highlighting the significance of the P-31-P-31 dipolar mechanism in T-1 relaxation of polyphosphates. Another interesting finding is the observation of approximately 40% shorter T-1 for intracellular P-i relative to extracellular P-i, attributed to the modulation by the intracellular phosphoryl exchange reaction P-i -ATP. The sufficiently separated intra- and extracellular P-i signals also permit the distinction of pH between intra- and extracellular environments (pH7.0 versus pH7.4). In summary, quantitative P-31 MRS in combination with ATP synthesis, pH, and T-1 relaxation measurements may offer a promising tool to detect biochemical alterations at early stages of brain dysfunctions and diseases. Copyright (c) 2015 John Wiley & Sons, Ltd.