Investigation of the Energy Metabolism with 31P Spectroscopy

How is the distribution of high-energy phosphates in the brain influenced by activity or pathology?

The energy metabolism in the cells is largely handled by phosphorus metabolites. Mainly PCr and ATP are well-known high-energy phosphates that are easily visible in ³¹P-MR spectra. In addition, the resonance of NAD (Nicotinamide adenine dinucleotide), which is oxidized during the process of ATP formation by oxidative phosphorylation, may give important information on mitochondrial function.
³¹P-spectroscopy benefits threefold from the ultra-high field strength at 9.4 T: First, the increased sensitivity makes acquisition of spectra with sufficient SNR possible for smaller, better localized volumes and within acceptable time. Second, the higher spectral dispersion allows better separating and quantifying closely positioned peaks like those of NADH and NAD+. Finally, in contrast to most other nuclei in MR spectroscopy, the longitudinal relaxation time T₁ decreases with increasing field, causing further advantages in SNR.
While in the muscle, activation causes large changes in the distribution of some high-energy phosphates, the effect of stimulation on the concentration of phosphorus metabolites is disputed. Using highly sensitive receive arrays and optimized sequences, we are taking advantage of the high field strength to observe phosphorus spectra at rest and during visual stimulation.
However, also pathologies, in which the energy metabolism in the mitochondria is impeded, may cause alterations in the phosphorus spectrum. This is especially the case in some variants of Parkinson’s disease. Using similar techniques as in the fMRS study, we are looking at the phosphorus spectra of Parkinson patients and age-matched healthy subjects both at rest and with a stimulation protocol, with a special focus on differences in the distributions of the metabolites NADH and its oxidized form NAD+. The small amplitude of those peaks, as well as their close proximity and their position at the slope of the much larger α-ATP resonance make their quantification difficult, giving a special advantage to ultra-high field MRS.