Regional Metabolic Assessment of Human Brain during Development by Proton Magnetic Resonance Spectroscopy In Vivo and by High-Performance Liquid Chromatography/Gas Chromatography in Autopsy Tissue

Abstract

To study the course of regional metabolite concentrations during early brain development, we measured in vivo metabolites [N-acetyl-aspartate (NAA), choline-containing compounds, and myoinositol (M-Ino)] in the precentral area of the cerebrum by short echo-time single volume proton magnetic resonance spectroscopy and compared in vivo established spectroscopic data with classic chromatographic data (HPLC) on age-corresponding autopsy tissue in different regions of the brain. In autopsy tissue, regional (frontal lobe, precentral area, basal ganglia, thalamus) and age-dependent differences of the concentration of creatine, NAA, and M-Ino were determined. In vivo measurement of NAA by proton magnetic resonance spectroscopy shows a significant increase of NAA by increasing postconceptional age. M-Ino shows a weak correlation and a nonsignificant decrease with increasing postconceptional age. Choline shows no age-dependent changes. Creatine concentrations measured by HPLC in different regions of the developing brain at autopsy showed an age-dependent increase that was identical for the left and right side and similar for the precentral area and frontal lobe and more pronounced for the basal ganglia and thalamus. Comparison of the results obtained by the two methods shows agreement for the age-dependent changes and the absolute concentration of M-Ino. NAA determined in autopsy tissue by HPLC is significantly lower than that measured in vivo by proton magnetic resonance spectroscopy. A comparison of the concentrations measured by HPLC in frontal lobe, basal ganglia, and thalamus with the results obtained from the precentral area showed significant regional differences in all measured metabolites. These results define important age-dependent changes detected with both methods and further indicate limitations of both methods that have to be considered when presenting absolute concentration values.

Cerebral Structure and Metabolism and Long-Term Outcome in Small-for-Gestational-Age Preterm Neonates

“…The finding that no differences in NAA/Cho could be demonstrated between SGA and AGA infants seems to indicate that no differences in neuronal density or function are present between the two groups, despite fetal compromise in SGA infants. The increase of NAA/Cho ratios in cerebral tissue as a result of maturation was previously described in detail and is confirmed in the present study (14,(31)(32)(33)(34).…”

Predictors of 30-Month Outcome after Perinatal Depression: Role of Proton MRS and Socioeconomic Factors

“…This is consistent with the observation by this group and others that abnormalities of lactate and, more variably, NAA are associated with neurodevelopmental outcome at 12 mo of age (1, 2, 11-16), although this association was not found by others. Decreases and increases in NAA reflect neuronal integrity (17)(18)(19)(20). As diminished NAA/choline after perinatal depression was most strongly associated with outcome at 30 mo of age, our findings suggest that abnormality of neuronal integrity is the most important neonatal predictor of 30-mo outcome.…”

Ion-Pairing High-Performance Liquid Chromatographic Method for the Detection of N-Acetylaspartate and N-Acetylglutamate in Cerebral Tissue Extracts

“…In fact, although the actual biological role of NAA is still a matter of debate, it seems well established that its cerebral concentration may vary in different experimental pathologies, such as reversible global brain ischemia (1), brain tumors (2), stroke (3), and neurodegenerative disorders (4,5). Due to its relative cerebral abundance (6 to 10 mol/g wet wt) and to its localization within neurons, NAA can be detected by magnetic resonance spectroscopy and several attempts are currently underway to correlate the eventual NAA variations and human cerebral pathologies, mainly because of its suspected relationship with neuronal death (6,7). In past years, some HPLC methods for NAA determination have been developed, most of them based on the use of anionic exchange columns and UV detection of NAA at 210 nm wavelength (8,9).…”