31P-MRS of healthy human brain: revealing the hidden PME signals under phosphoethanolamine and phosphocholine resonances at 7T

Abstract

PurposeFor decades, it has been common practice to quantify brain phosphomonoester (PME) 31P signals by a two-component model composed of phosphoethanoamine (PE) and phosphcholine (PC). This study presented the evidence of hidden PME (h-PME) signals and their selective detections toward accurate quantification of PE and PC.MethodsGaussian lineshape analysis was modeled to reveal h-PME. Inversion-recovery (IR) sequence was employed to null the PE and PC resonances for selective detection of h-PME. The fully-relaxed 31P spectra after h-PME correction were used to quantify PE, PC and other brain metabolites in a group of 16 healthy subjects.ResultsSpectral lineshape analysis and IR modulation revealed previously overlooked h-PME signals underlying sharp PE and PC resonances. The h-PME signals appeared as a broad “bump” (LW1/2: 105 ± 25 Hz, N = 16), leading to poor spectral resolution between PE and PC. Fast relaxing h-PME signals, tentatively assigned to blood 2,3-DPG, were selectively detectable using IR sequence at an optimal inversion delay of 5.8 s. In fully relaxed 31P spectra, h-PME measured 44 ± 9 % of the total PME signal, equivalent to 1.36 ± 0.39 mM in single phosphoryl unit, compared to 1.41 ± 0.23 mM for PE and 0.31± 0.10 mM for PC.ConclusionHidden PME signals are a significant constitute of PME signals in human brain 31P spectra, and need to be taken into account for quantifying PE and PC as biomarkers of altered phospholipid metabolism in brain pathologies.

ATP line splitting in association with reduced intracellular magnesium and pH: a brain 31P MR spectroscopic imaging (MRSI) study of pediatric patients with myelin oligodendrocyte glycoprotein antibody‐associated disorders (MOGADs)

“…Nine major P metabolites are easily detectable, including phosphocholine (PC), phosphoethanolamine (PE), P i , glycerophosphoethanolamine (GPE), glycerophosphocholine (GPC), PCr, ATP, NAD(H) (nicotinamide adenine dinucleotide, a combination of the oxidized form NAD + and the reduced form NADH) and MM (a unspecified macromolecule). Additional signals, tentatively assigned to blood 2,3-diphosphoglycerate (2,3-DPG), are also present in PME region, as identified by lineshape analysis according to recent findings 47,48. A unique feature of these voxel spectra is the observation of a clear β-ATP shoulder peak.…”

“…Circulating blood cells in deep and peripheral brain may contribute orientation‐dependent ATP signals from cross‐slice and through‐plane voxel contamination via the spatial response function 70 . Most recent studies show that the cerebral vascular space, despite its low relative volume (~6 mL blood/100 mL brain tissue at rest), 71 may contribute metabolite signals in brain 31 P MR spectra, including P i (Reference 31) and 2,3‐DPG 47,48 . This latter metabolite has been incorporated into our data analysis, as marked in Figure 2 and listed in Table S1 (Supporting Information).…”

“…70 Most recent studies show that the cerebral vascular space, despite its low relative volume ($6 mL blood/100 mL brain tissue at rest), 71 may contribute metabolite signals in brain 31 P MR spectra, including P i (Reference 31) and 2,3-DPG. 47,48 This latter metabolite has been incorporated into our data analysis, as marked in Figure 2 and listed in Table S1 (Supporting Information). It should be noted that a potential contribution from a blood source to brain ATP signals may have significant implications not only for Mg 2+ measurements in MOGAD but also for general application of brain 31 P MRS, and therefore requires further exploration.…”