In the developing brain, metabolites concentrations such as NAA, choline and myo-inositol show dynamic change. We can use 1H-MRS to measure such metabolite concentrations. It is important to know such signature for the precise evaluation of neonatal brain pathology, particularly in hypoxic-ischemic encephalopathy. 1H-MRS is also a powerful tool for the diagnosis and disease monitoring forpediatric neuro-metabolic diseases.
In the developing brain, metabolites concentrations such as NAA, choline and myo-Inositol show dynamic change. We have used 1H-MRS routinely since 2009 and found very useful.
We have published metabolites concentration changes in preterm neonates from corrected age of 30 weeks [1], and relatively higher neonatal lactate concentration than those in children [2], both are important for the precise evaluation of neonatal brain pathology, particularly in hypoxic-ischemic encephalopathy (HIE). In neonatal HIE, low absolute NAA, creatine, and high glutamine plus glutamate and lactate concentrations within 4 days reveled excellent prognostic biomarkers as well as lactate/NAA, lactate/choline and lactate/create. NAA and creatine concentrations decreased in 7-14 days in HIE neonate with poor outcome, whereas high lactate and glutamine plus glutamate tended to be transient. These results suggest us the importance of early treatment.
In neuro-metabolic diseases, we could make diagnoses of several cases of Creatine transporter deficiency from deficient Creatine peaks [3], and a Sojgren-Larsen disease from large elevation of 1.3 ppm lipid peak although they almost had no significant MRI abnormalities [4]. Quantification of metabolites using LCModel revealed abnormal elevation of GABA in an encephalopathic infant leading to the diagnosis of GABA transaminase deficiency [5]. A conspicuous peak of 0.9 ppm from branched amino acids confirmed the diagnosis of Maple syrup urine disease in two encephalopathic neonates[6]. In addition to the MR findings of cerebellar atrophy and lenticular calcification, reduced choline and myo-inositol peaks leads the diagnosis of Folate transporter deficiency in two siblings. In the latter 3 disorders, changes of their spectral abnormalities well-reflected disease condition from the treatments.
1. Tomiyasu M, Aida N, Endo M, et al. Neonatal brain metabolite concentrations: an in vivo magnetic resonance spectroscopy study with a clinical MR system at 3 Tesla. PLoS One. 2013;8(11):e82746.
2. Tomiyasu M, Aida N, Shibasaki J, Tachibana Y, Endo M, Nozawa K, Shimizu E, Tsuji H, Obata T. Normal lactate concentration range in the neonatal brain. Magn Reson Imaging. 2016 Nov;34(9):1269-1273.
3. Osaka H, Takagi A, Tsuyusaki Y, Wada T, Iai M, Yamashita S, Shimbo H, Saitsu H, Salomons GS, Jakobs C, Aida N, Toshihiro S, Kuhara T, Matsumoto N. Contiguous deletion of SLC6A8 and BAP31 in a patient with severe dystonia and sensorineural deafness. Mol Genet Metab. 2012 May;106(1):43-7
4. Tachibana Y, Aida N, Enomoto K, Iai M, Kurosawa K. A case of Sjögren-Larsson syndrome with minimal MR imaging findings facilitated by proton spectroscopy. Pediatr Radiol. 2012 Mar;42(3):380-2.
5. Tsuji M, Aida N, Obata T, Tomiyasu M, Furuya N, Kurosawa K, Errami A, Gibson KM, Salomons GS, Jakobs C, Osaka H. A new case of GABA transaminase deficiency facilitated by proton MR spectroscopy. J Inherit Metab Dis. 2010 Feb;33(1):85-90. 2. Sato T, Muroya K, Hanakawa J, Asakura Y, Aida N, Tomiyasu M, Tajima G, Hasegawa T, Adachi M. Neonatal case of classic maple syrup urine disease: usefulness of (1) H-MRS in early diagnosis. Pediatr Int. 2014 Feb;56(1):112-5.
6. Sato T, Muroya K, Hanakawa J, Asakura Y, Aida N, Tomiyasu M, Tajima G, Hasegawa T, Adachi M. Neonatal case of classic maple syrup urine disease: usefulness of (1) H-MRS in early diagnosis. Pediatr Int. 2014 Feb;56(1):112-5. doi: 10.1111/ped.12211