RESUMO
Abnormal cell membrane metabolism is associated with many neuropsychiatric disorders. Free phosphomonoesters and phosphodiesters, which can be detected by in vivo 31P magnetic resonance spectroscopy (MRS), are important cell membrane building blocks. However, the quantification of phosphoesters has been highly controversial even in healthy individuals due to overlapping signals from macromolecule membrane phospholipids (MP). In this study, high signal-to-noise ratio (SNR) cerebral 31P MRS spectra were acquired from healthy volunteers at both 3 and 7 Tesla. Our results indicated that, with minimal spectral interference from MP, the [phosphocreatine (PCr)]/[phosphocholine (PC) + glycerophosphocholine (GPC)] ratio measured at 7 Tesla agreed with its value expected from biochemical constraints. In contrast, the 3 Tesla [PCr]/[PC+GPC] ratio obtained using standard spectral fitting procedures was markedly smaller than the 7 Tesla ratio and than the expected value. The analysis suggests that the commonly used spectral model for MP may fail to capture its complex spectral features at 3 Tesla, and that additional prior knowledge is necessary to reliably quantify the phosphoester signals at low magnetic field strengths when spectral overlapping is significant.
Assuntos
Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Ressonância Magnética Nuclear Biomolecular/métodos , Adolescente , Adulto , Idoso , Mapeamento Encefálico/instrumentação , Estudos de Viabilidade , Voluntários Saudáveis , Humanos , Imageamento por Ressonância Magnética/instrumentação , Masculino , Pessoa de Meia-Idade , Ressonância Magnética Nuclear Biomolecular/instrumentação , Fosfocreatina/análise , Fósforo/administração & dosagem , Fosforilcolina/análise , Adulto JovemRESUMO
X-linked creatine transporter deficiency (CTD) is one of the three types of cerebral creatine deficiency disorders. CTD arises from pathogenic variants in the X-linked gene SLC6A8. We report the first phosphorus (31 P) MRS study of patients with CTD, where both phosphocreatine and total creatine concentrations were found to be markedly reduced. Despite the diminished role of creatine and phosphocreatine in oxidative phosphorylation in CTD, we found no elevation of lactate or lowered pH, indicating that the brain energy supply still largely relied on oxidative metabolism. Our results suggest that mitochondrial function is a potential therapeutic target for CTD.