Investigation of the energy metabolism with ³¹P spectroscopy

How are the concentrations of high-energy phosphates in the brain influenced by activity or pathology?

The energy metabolism in the cells is largely handled by phosphorus metabolites. High-energy phosphates like PCr and ATP visible in 31P-MR spectra, while 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 distributions of some high-energy phosphates, the effect of activation on the concentration of phosphorus metabolites in the brain is disputed. Using highly sensitive receive arrays and optimized CSI sequences, we are taking advantage of the high field strength to observe phosphorus spectra at rest and during visual stimulation.
Preliminary results indicate that changes in the 31P spectra due to visual activation, if present at all, may be too small to be detected even with the superior spatial resolution and SNR that the high field and the highly optimized multi-channel coils developed in-house.

Functional 31P spectroscopy with visual stimulation: Left: Visualization of the distribution of the observed signal in the visual cortex of a subject. Right: Spectra during stimulation and rest show little differences. — Functional ³¹P spectroscopy with visual stimulation: Left: Visualization of the distribution of the observed signal in the visual cortex of a subject. Right: Spectra during stimulation and rest show little differences.

Functional ³¹P spectroscopy with visual stimulation: Left: Visualization of the distribution of the observed signal in the visual cortex of a subject. Right: Spectra during stimulation and rest show little differences.

Since phosphorus spectroscopy has the potential of observing the energy metabolism, it could be a great tool for detecting mitochondrial dysfunction, as assumed 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 at two regions in the brain by acquiring spectra with very high SNR and spectral resolution, with the goal of observing the concentrations of the metabolites NADH and its oxidized form NAD+. The small amplitude of those peaks, as well as their close proximity and their positions at the slope of the much larger α-ATP resonance make their quantification

31P spectrum from the motor cortex of a healthy, older subject. The NAD-signals are found at the right flank of the α-ATP line. The zoom-in shows subtle differences in the NAD+/NADH ratio between young and older subjects. — ³¹P spectrum from the motor cortex of a healthy, older subject. The NAD-signals are found at the right flank of the α-ATP line. The zoom-in shows subtle differences in the NAD⁺/NADH ratio between young and older subjects.

³¹P spectrum from the motor cortex of a healthy, older subject. The NAD-signals are found at the right flank of the α-ATP line. The zoom-in shows subtle differences in the NAD⁺/NADH ratio between young and older subjects.

Publications:

Proc. Intl. Soc. Mag. Reson. Med. 26, 3993 (2018)
Proc. Intl. Soc. Mag. Reson. Med. 26, 3994 (2018)
Proc. Intl. Soc. Mag. Reson. Med. 30, 1365 (2022)

Investigation of the energy metabolism with 31P spectroscopy

Publications:

Investigation of the energy metabolism with ³¹P spectroscopy