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

Abstract

SummaryEnergy metabolism of the human visual cortex was investigated by performing 31P functional MRS.IntroductionThe human brain is known to be the main glucose demanding organ of the human body and neuronal activity can increase this energy demand. In this study we investigate whether alterations in pH during activation of the brain can be observed with MRS, focusing on the mitochondrial inorganic phosphate (Pi) pool as potential marker of energy demand.MethodsSix participants were scanned with 16 consecutive 31P‐MRSI scans, which were divided in 4 blocks of 8:36 minutes of either rest or visual stimulation. Since the signals from the mitochondrial compartments of Pi are low, multiple approaches to achieve high SNR 31P measurements were combined. This included: a close fitting 31P RF coil, a 7 T‐field strength, Ernst angle acquisitions and a stimulus with a large visual angle allowing large spectroscopy volumes containing activated tissue.ResultsThe targeted resonance downfield of the main Pi peak could be distinguished, indicating the high SNR of the 31P spectra. The peak downfield of the main Pi peak is believed to be connected to mitochondrial performance. In addition, a BOLD effect in the PCr signal was observed as a signal increase of 2–3% during visual stimulation as compared to rest. When averaging data over multiple volunteers, a small subtle shift of about 0.1 ppm of the downfield Pi peak towards the main Pi peak could be observed in the first 4 minutes of visual stimulation, but no longer in the 4 to 8 minute scan window. Indications of a subtle shift during visual stimulation were found, but this effect remains small and should be further validated.ConclusionOverall, the downfield peak of Pi could be observed, revealing opportunities and considerations to measure specific acidity (pH) effects in the human visual cortex.

Ni(II) Ions May Target the Entire Melatonin Biosynthesis Pathway—A Plausible Mechanism of Nickel Toxicity

“…Based on the above analysis, our results imply that the enzymes from the melatonin biosynthesis pathway, acetylserotonin O -methyltransferase in particular, are the toxicological targets for Ni(II) ions. It seems especially possible because melatonin is synthesized in mitochondria, which are known to contain pH more basic than the cytoplasm [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ].…”

“…The cleavage is pH-dependent, and Ni(II) ions break proteins relatively slowly at pH 7.4, but much more rapidly in locations with higher pH [ 7 ]. Interestingly, pH values in the mitochondrial matrix are high enough [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ] to facilitate Ni(II)-assisted hydrolysis of the peptide bond.…”

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

“…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. Using this method, they showed a minimal shift of the downfield Pi peak toward the main Pi peak during visual stimuli, but these changes remained small and the authors recommended further validation.…”

Short‐term meditation training influences brain energy metabolism: A pilot study on 31P MR spectroscopy

“…As the changes in our group are minimal (yet significant) and the PCr/Pi ratio shows different behavior in the basal ganglia and occipital and temporal regions, the relevance of these changes remains unclear. Normally, energy metabolism of the brain and intracellular pH levels is controlled chiefly through a buffer process of the CO 2 /HCO 3 system, which would explain only small changes in pH detectable in 31 P‐MRS (Hendriks et al., 2019).…”