Is visual activation associated with changes in cerebral high-energy phosphate levels?

Abstract

Phosphorus magnetic resonance spectroscopy (31P MRS) has been employed before to assess phosphocreatine (PCr) and other high-energy phosphates in the visual cortex during visual stimulation with inconsistent results. We performed functional 31P MRS imaging in the visual cortex and control regions during a visual stimulation paradigm at an unprecedented sensitivity, exploiting a dedicated RF coil design at a 7 T MR system. Visual stimulation in a 3 min 24 s on–off paradigm in eight young healthy adults generated a clear BOLD effect with traditional 1H functional MRI in the visual cortex (average z score 9.9 ± 0.2). However, no significant event-related changes in any of the 31P metabolite concentrations, linewidths (7.9 ± 1.8 vs 7.8 ± 1.9 Hz) or tissue pH (7.07 ± 0.13 vs 7.06 ± 0.07) were detectable. Overall, our study of 31P MRSI in 15 cm3 voxels had a detection threshold for changes in PCr, Pi and γ-ATP between stimulation and rest of 5, 17 and 10%, respectively. In individual subjects, the mean coefficients of variance for PCr and Pi levels of control voxels were 6 ± 3 and 19 ± 8% (three time point average of 3 min 24 s). Altogether this indicates that energy supply for neuronal activation at this temporal resolution does not drain global PCr resources.

Simultaneous detection of metabolite concentration changes, water BOLD signal and pH changes during visual stimulation in the human brain at 9.4T

“…20–23 The observed downregulation of PCr during stimulation is consistent with some phosphorus ( 31 P) fMRS studies in the human brain, 24–27 while others did not observe this downregulation. 28–31 31 P fMRS studies not only report contradictory results on metabolite concentration changes but also for pH estimates. While some studies report that intracellular pH did not change due to human brain activation, 28,29,32,33 others report a rise in pH 34, 35 or a decrease.…”

Brain Energy Metabolism in Two States of Mind Measured by Phosphorous Magnetic Resonance Spectroscopy

“…However, brain activation in 31 P-MRS is difficult to observe. Research study by van de Bank et al ( 2018 ) showed no change in 31 P-MRS metabolites during visual stimulation in 7T. This emphasizes the difficulties in 31 P-MRS, especially in "lower" magnetic field strengths like 3T.…”

“…Khlebnikov et al ( 2017 ) report on difficulties surrounding the detection of changes in pH during visual stimuli with existing technologies. van de Bank et al ( 2018 ) also found no change in pH in 31 P-MRS during visual stimulation. Hendriks et al ( 2019 ) proposed a new method for measuring pH in mitochondrial or extracellular compartments during visual stimulus.…”

“…Activation studies with 31 P-MRS are relatively unreliable and not sensitive. Even studies at higher magnetic field strengths like 7 T failed to find any difference during brain activation (van de Bank et al, 2018 ). Technical difficulties in 31 P-MRS imaging are well known (Liu et al, 2017 ).…”

SNR optimized 31P functional MRS to detect mitochondrial and extracellular pH change during visual stimulation

“…Two recent studies have been published that include high SNR 31 P MRSI protocols at 7 T. The first study does not observe any change in highenergy phosphates due to a visual stimulation, 35 but on the other hand does not include the downfield Pi peak in their analysis. The second study specifically targets the downfield Pi peak and shows the influences of the blood and CSF pool on this peak.…”