Detection of elevated levels of taurine and creatine in the brain of hypoxic-ischemic newborn rat using a magnetic resonance spin echo full intensity acquired localization sequence.

BACKGROUND

Neonatal hypoxic-ischemic encephalopathy (HIE) is a major perinatal neurological disorder with limited objective early diagnostic markers, while conventional point resolved selective spectroscopy (PRESS)-based 1H-magnetic resonance spectroscopy (1H-MRS), though widely used, is suboptimal for detecting short-T2 metabolites critical to early brain injury assessment. This study aimed to investigate the feasibility of spin echo full intensity acquired localization (SPECIAL) spectra on newborn rat brain with HIE model, and to explore the reliable metabolic markers in rat brain and compare the spectra acquired by magnetic resonance (MR) SPECIAL spectra and PRESS spectra.

METHODS

Six male newborn rats were used for making HIE model induced by unilateral common carotid artery ligation followed by hypoxia. Hippocampal damage in the HIE model rat was confirmed by hematoxylin and eosin (HE) staining. T2-weighted anatomical images and 1H-MRS, including SPECIAL sequence and PRESS sequence, were performed with an animal 7-T MR scanner. Absolute concentrations of metabolites, including N-acetylaspartate (NAA), creatine + phosphocreatine (Cr + PCr), inositol (Ins), taurine (Tau), glycerophosphocholine + phosphocholine (GPC + PCh), glutamine + glutamate (Glu + Gln), lactate + macromolecule methyl at 1.4 ppm + lipid methyl at 1.3 ppm (Lac + MM14 + Liq13) on lateral and contralateral hippocampal and thalamic regions, were quantified. The possible differences of metabolites concentration between the brain area corresponding to the ligation side and the contralateral side were compared. Meanwhile, full width at half maximum (FWHM), signal-to-noise ratio (SNR), and fitting error [standard deviation (SD)] of metabolites acquired from the two kinds of spectra in bilateral brain regions were also compared. Finally, the relationship of metabolites from the two kinds of spectra was explored and compared.

RESULTS

SPECIAL MR spectra are feasible in newborn HIE rat brain corresponding to the ligation side with higher spectral resolution compared with PRESS spectra. Elevated levels of Tau and Cr + PCr were found in the right hippocampus by SPECIAL spectra (P<0.05), and increased levels of Cr + PCr, Lac + MM14 + Liq13, and decreased NAA were observed by PRESS spectra (P<0.05). More correlations between metabolites were found from SPECIAL spectra than PRESS spectra, including Tau and Cr + PCr (r=0.7, P<0.01), Glu + Gln and Cr + PCr (r=0.75, P<0.01), GPC + PCh and Cr + PCr (r=0.63, P<0.01), and Lac + MM14 + Liq13 and Cr + PCr (r=0.54, P=0.03).

CONCLUSIONS

The use of SPECIAL sequences could provide more information on metabolic changes in the HIE rat brain, and Tau and Cr + PCr may be considered as reliable metabolic markers for earlier and accurate assessments of the damage of hypoxic-ischemic.