title: 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.
authors.affiliation: Service de Neuroradiologie, AP-HM Timone, Aix-Marseille Université, Marseille, France.|Service de Radiopédiatrie-Imagerie 2, CHU de Strasbourg, Hôpital de Hautepierre, Strasbourg, France.|Laboratoire ICube, UMR 7357, FMTS, Université de Strasbourg-CNRS, Strasbourg, France.
authors.forename: Meriam
authors.initials: M
authors.lastname: Koob
authors.affiliation: Aix-Marseille Université, CNRS, Centre de Résonance Magnétique Biologique et Médicale, UMR 7339, Faculté de Médecine la Timone, Marseille, France.
authors.forename: Angèle
authors.initials: A
authors.lastname: Viola
authors.affiliation: Aix-Marseille Université, CNRS, Centre de Résonance Magnétique Biologique et Médicale, UMR 7339, Faculté de Médecine la Timone, Marseille, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Le Fur
authors.affiliation: Aix-Marseille Université, CNRS, Centre de Résonance Magnétique Biologique et Médicale, UMR 7339, Faculté de Médecine la Timone, Marseille, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Viout
authors.affiliation: Laboratoire CREATIS, CNRS UMR 5220, Inserm U1044, Université Claude Bernard Lyon I, INSA-Lyon, Lyon, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Ratiney
authors.affiliation: Aix-Marseille Université, CNRS, Centre de Résonance Magnétique Biologique et Médicale, UMR 7339, Faculté de Médecine la Timone, Marseille, France.
authors.forename: Sylviane
authors.initials: S
authors.lastname: Confort-Gouny
authors.affiliation: Aix-Marseille Université, CNRS, Centre de Résonance Magnétique Biologique et Médicale, UMR 7339, Faculté de Médecine la Timone, Marseille, France.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Cozzone
authors.affiliation: Service de Neuroradiologie, AP-HM Timone, Aix-Marseille Université, Marseille, France.|Aix-Marseille Université, CNRS, Centre de Résonance Magnétique Biologique et Médicale, UMR 7339, Faculté de Médecine la Timone, Marseille, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Girard
mesh_terms: D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D003401:Creatine / Q000378:metabolism; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D019102:Infant, Very Low Birth Weight; D008297:Male; D009778:Occipital Lobe / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D066244:Proton Magnetic Resonance Spectroscopy; D012189:Retrospective Studies; D013654:Taurine / Q000378:metabolism; D013702:Temporal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D047929:Term Birth; D013788:Thalamus / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D066127:White Matter / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D005973:Glutamine; D013654:Taurine; D018698:Glutamic Acid; D003401:Creatine