CCLG3
Glycine: a potential non-invasive biomarker of malignancy in childhood brain tumours by in-vivo 1H MRS and ex-vivo high-resolution magic-angle spinning NMR
Nigel Davies1, Martin Wilson1, Kal Natarajan2, Yu Sun1, Leslie MacPherson3, Marie-Anne Brundler3, Theodoros Arvanitis1, Richard Grundy4, Andrew Peet1
1University of Birmingham, UK, 2University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK, 3Birmingham Children's Hospital NHS Foundation Trust, Birmingham, UK, 4University of Nottingham, UK
Background
The clinical management of childhood brain tumours would benefit from the identification of non-invasive prognostic biomarkers. Metabolite profiles derived from in-vivo MRS are a potential source of such information. In-vitro MRS studies of tumour tissue have indicated that glycine (Gly) is abundant in high-grade brain tumours [1-3], but Gly is usually not measured in vivo due to the strong spectral overlap with myo-inositol. The aim of this study was to investigate the quantitation of Gly in paediatric brain tumours using clinical in vivo MRS and its potential as a non-invasive biomarker of malignancy.
Method
Single-voxel MRS was performed using PRESS (TR 1500 ms, TE 30 ms / 135 ms) on a 1.5 Tesla scanner for 48 children with suspected brain tumours confirmed as (19 WHO grade III and IV, 18 WHO grade I and II, 11 unbiopsied). Both short-TE and long-TE MRS was performed on 33 children. Additionally, short-TE MRS and high-resolution magic-angle spinning (HRMAS) of matched tissue samples was acquired for 15 children.
Results
The inclusion of Gly in the analysis led to improved MRS metabolite fits for both short-TE and long-TE MRS (P<0.05). The Gly concentrations estimated from short-TE MRS were significantly correlated with the long-TE values (R=0.91, P<0.001). The Gly estimated concentration was significantly higher in high-grade versus low-grade tumours for both short-TE (P<1e-6) and long-TE (P=0.003) MRS. This was consistent with the tissue HRMAS results, which showed a significantly higher Gly/(mI + Gly) ratio in high-grade tumours (P<0.05) and a significant correlation with the in vivo Gly/(mI + Gly) ratio (P<0.05).
Conclusion
This study suggests that Gly can be reliably detected in childhood brain tumours using both short-TE and long-TE MRS on a clinical MRI scanner. Furthermore, Gly has been shown to be a potentially useful non-invasive biomarker of grade in childhood brain tumours.
References
[1] Kinoshita Y H, et al. Neurosurgery 1994; 35: 606-614.
[2] Carpinelli G et al. Anticancer Res. 1996; 16: 1559-1563.
[3] Kinoshita Y and Yokota A. NMR Biomed. 1997; 10: 2-12.
