Proton Magnetic Resonance Spectroscopy Reveals Medial Temporal Metabolic Abnormalities in Adolescents With History of Preterm Birth

Abstract

Prematurity is associated with volumetric reductions in specific brain areas such as the hippocampus and with metabolic changes that can be detected by spectroscopy. Short echo time (35 ms) Proton magnetic resonance spectroscopy ( 1 H MRS) was performed to assess possible medial temporal lobe metabolic abnormalities in 21 adolescents with preterm birth (mean age: 14.8, SD: 1.3) compared with an age-matched control sample (mean age: 14.8, SD: 1.6).1 H MRS spectra were analyzed with linear combination model fitting, obtaining the absolute metabolite concentrations for Creatine (Cr), and myo-inositol (Ins). In addition, the following metabolite sums were measured: total Cho (glycerophospho-choline ϩ phosphocholine), total N-acetyl-aspartate ϩ N-acetyl-aspartylglutamate (NA), and total Glx (glutamate ϩ glutamine). A stereological analysis was performed to calculate hippocampal volume. Absolute Cr, and total NA values were decreased in the preterm group (p ϭ 0.016; p ϭ 0.002, respectively). The preterm also showed a hippocampal reduction (p Ͻ 0.0001). Significant relationships were found between gestational age and different metabolites and the hippocampal volume. Moreover, hippocampal volume correlated with brain metabolites in the whole sample. Results demonstrate that prematurity affects medial temporal lobe metabolites, and that the alteration is related to structural changes, suggesting that the cerebral changes persist until adolescence. (Pediatr Res 64: 572-577, 2008) I n vivo proton magnetic resonance spectroscopy ( 1 H MRS) is a neurochemical technique used to investigate specific brain metabolites, which can expand on the structural and functional information obtained by other neuroimaging techniques. Volumetric magnetic resonance imaging (MRI) analyses of subjects with history of preterm birth showed temporal gray matter (GM) reductions (1) and hippocampal changes that persist until the adolescence (2,3).A previous study reported that preterms evaluated at 40 gestational weeks showed increased N-acetyl-aspartate (NAA) compared with the concentrations at birth, and that the levels at the second examination did not differ from those of the full-term control group (4). These data suggest that metabolic decreases in the immature brain may normalize. In addition, a study in adolescents with preterm birth (Ͻ30 wk of gestation) found a NAA/Cho ϩ Creatine (Cr) reduction in the right temporal lobe in a subsample of preterms (n ϭ 9) compared with full-term subjects, suggesting a persistent deficit (5).No investigations to date have assessed abnormalities in the absolute metabolic concentrations by means of the userindependent frequency domain-fitting program LCModel in a healthy preterm sample at long-term or their relationship with hippocampal volumetric atrophy. The goal of our study was to determine whether single-voxel 1 H MRS is able to detect alterations in the medial temporal lobe region in adolescents with preterm birth and normal MRI. We hypothesized that volume reduction of the hippocampus could ...

Anterior Cingulate and Frontal Lobe White Matter Spectroscopy in Early Childhood of Former Very LBW Premature Infants

“…Thus, the diffusion tensor imaging and 1H-MRS data from this cohort suggests that prematurity may cause long-term disruption of white matter tracts as well as possible neurometabolic changes. In a different group of subjects, 1H-MRS of the hippocampus at a mean age of 15 years in former premature children showed significant decreases in absolute concentrations of NAA and Cr as well as ratios of NAA/Cho and Cr/Cho (18). However it is not clear how prematurity may affect the neurometabolic profile of younger children.…”

“…Robertson et al (16) reported abnormal elevations of the metabolite ratios mI/Cr and lactate/Cr in preterm infants with white matter damage when performed at term, although the only study evaluating developmental outcome after prematurity failed to demonstrate a correlation between neonatal 1H-MRS and Bayley motor scores at 18 to 24 months of age (17). Two groups have reported 1H-MRS in adolescents who were former premature children, showing significant depression of NAA and Cr in the hippocampus (18) and a trend for lower NAA/Cho, lower NAA/Cr and higher Cho/Cr ratios in left frontal lobe white matter (19). We are not aware of any studies using 1H-MRS in early childhood to evaluate the neurometabolic sequelae of prematurity.…”

Extremely Preterm Birth Outcome: A Review of Four Decades of Cognitive Research

“…A higher likelihood of brain and lateral ventricular volume alterations has been associated with supratentorial lesions, including of sensorimotor and parieto-occipital regions (Peterson et al 2003). Abnormalities also involve the hippocampus (Gimenez et al 2004;Gimenez et al 2008;Isaacs et al 2000;Thompson et al 2008), and cerebellum, including hemorrhagic cerebellar injury (Limperopoulos et al 2005) and abnormal cerebellar growth (Allin et al 2001). Immature cerebrovascular systems compromise cerebral blood flow autoregulation, supply, and perfusion, including to cerebral white matter (Volpe 2008).…”

Hippocampal Volume and Memory and Learning Outcomes at 7 Years in Children Born Very Preterm

“…Most studies within the VPT literature have utilized manual segmentation, and have reported reduced hippocampal volume in VPT infants (Lodygensky et al, 2008; Thompson et al, 2008), children (Isaacs et al, 2000; Lodygensky et al, 2005), and adolescents (Abernethy, Palaniappan, & Cooke, 2002; Nosarti et al, 2002). Although fewer studies have employed voxel-based morphometry, reduced hippocampal volumes in adolescents (Gimenez et al, 2008) and young adults (Lawrence et al, 2010) born VPT have also been noted using this methodology.…”