Creatine, Glutamine plus Glutamate, and Macromolecules Are Decreased in the Central White Matter of Premature Neonates around Term

Abstract

Preterm birth represents a high risk of neurodevelopmental disabilities when associated with white-matter damage. Recent studies have reported cognitive deficits in children born preterm without brain injury on MRI at term-equivalent age. Understanding the microstructural and metabolic underpinnings of these deficits is essential for their early detection. Here, we used diffusion-weighted imaging and single-voxel 1H magnetic resonance spectroscopy (MRS) to compare brain maturation at term-equivalent age in premature neonates with no evidence of white matter injury on conventional MRI except diffuse excessive high-signal intensity, and normal term neonates. Thirty-two infants, 16 term neonates (mean post-conceptional age at scan: 39.8±1 weeks) and 16 premature neonates (mean gestational age at birth: 29.1±2 weeks, mean post-conceptional age at scan: 39.2±1 weeks) were investigated. The MRI/MRS protocol performed at 1.5T involved diffusion-weighted MRI and localized 1H-MRS with the Point RESolved Spectroscopy (PRESS) sequence. Preterm neonates showed significantly higher ADC values in the temporal white matter (P<0.05), the occipital white matter (P<0.005) and the thalamus (P<0.05). The proton spectrum of the centrum semiovale was characterized by significantly lower taurine/H2O and macromolecules/H2O ratios (P<0.05) at a TE of 30 ms, and reduced (creatine+phosphocreatine)/H2O and (glutamine+glutamate)/H2O ratios (P<0.05) at a TE of 135 ms in the preterm neonates than in full-term neonates. Our findings indicate that premature neonates with normal conventional MRI present a delay in brain maturation affecting the white matter and the thalamus. Their brain metabolic profile is characterized by lower levels of creatine, glutamine plus glutamate, and macromolecules in the centrum semiovale, a finding suggesting altered energy metabolism and protein synthesis.

Altered brain metabolism contributes to executive function deficits in school-aged children born very preterm

“…in the centrum semiovale) have been reported previously in preterm neonates. 19 For early childhood, previous studies of preterm cohorts contrast our results: At age 3–4 years, Glx/Cr ratios in the left frontal periventricular white matter were found to be higher in children with very low-birth-weight (VLBW) compared to controls, although the group difference was driven by decreased Cr levels in the VLBW group rather than increased Glx. 30 At 4 and 6 years of age, no differences in frontal Glx concentrations were found between children born very preterm and term-born controls.…”

Brain creatine alteration and executive function deficits in children born very preterm

“…On top of that, location-specific changes in creatine levels could be considered by itself as a biomarker of impaired brain biochemistry and executive function deficit in VPT. Altered brain creatine levels in both the gray and white matter were reported in several studies with preterm newborns, including a sub-sample of premature infants with cerebellar and cerebral cortical brain injury, 3 premature-born infants without evidence of brain injury, 5 and premature neonates with normal conventional magnetic resonance imaging, 6 all suggesting altered energy homeostasis that may instigate a delay in brain maturation. It appears that developing brain deficient in creatine causes impoverished axonal networks and reduced synaptic density, 7 both recognized as pathophysiological substrates of executive function deficits.…”

Theoretical description of modern1H in Vivo magnetic resonance spectroscopic pulse sequences

“…When correcting the data yielded by a particular experiment for T 2 effects, it is therefore best practice to use relaxation times measured with the same sequence and field strength, if available. Metabolite T 2 has been estimated using PRESS, STEAM, ISIS, MEGA‐PRESS, Carr‐Purcell‐Meiboom‐Gill PRESS, LASER, Carr‐Purcell‐LASER, sLASER, MEGA‐sLASER, JPRESS, MRSI, MRF‐PRESS, and a technique that uses RF‐driven steady states to avoid the requirement to sample multiple TEs, called MARzss …”

“…When correcting the data yielded by a particular experiment for T 2 effects, it is therefore best practice to use relaxation times measured with the same sequence and field strength, if available. Metabolite T 2 has been estimated using PRESS, [148][149][150][151][152][153]161,162,164,165,[176][177][178][179][180][181][182][183][184][185][186][187][188][189][190][191][192][193][194] STEAM, [154][155][156][157][158][166][167][168][195][196][197][198] ISIS, 199 MEGA-PRESS, 200 Carr-Purcell-Meiboom-Gill PRESS, 194 LASER, 177,201 Carr-Purcell-LASER, 194 sLASER,…”