1 H MRS has great potential for the clinical investigation of childhood brain tumours, but the low incidence in, and difficulties of performing trials on, children have hampered progress in this area. Most studies have used a long-TE, thus limiting the metabolite information obtained, and multivariate analysis has been largely unexplored. Thirty-five children with untreated cerebellar tumours (18 medulloblastomas, 12 pilocytic astrocytomas and five ependymomas) were investigated using a single-voxel short-TE PRESS sequence on a 1.5 T scanner. Spectra were analysed using LCModel TM to yield metabolite profiles, and key metabolite assignments were verified by comparison with high-resolution magic-angle-spinning NMR of representative tumour biopsy samples. In addition to univariate metabolite comparisons, the use of multivariate classifiers was investigated. Principal component analysis was used for dimension reduction, and linear discriminant analysis was used for variable selection and classification. A bootstrap cross-validation method suitable for estimating the true performance of classifiers in small datasets was used. The discriminant function coefficients were stable and showed that medulloblastomas were characterised by high taurine, phosphocholine and glutamate and low glutamine, astrocytomas were distinguished by low creatine and high N-acetylaspartate, and ependymomas were differentiated by high myo-inositol and glycerophosphocholine. The same metabolite features were seen in NMR spectra of ex vivo samples. Successful classification was achieved for glial-cell (astrocytoma þ ependymoma) versus non-glial-cell (medulloblastoma) tumours, with a bootstrap 0.632 þ error, e B.632þ , of 5.3%. For astrocytoma vs medulloblastoma and astrocytoma vs medulloblastoma vs ependymoma classification, the e B.632þ was 6.9% and 7.1%, respectively. The study showed that 1 H MRS detects key differences in the metabolite profiles for the main types of childhood cerebellar tumours and that discriminant analysis of metabolite profiles is a promising tool for classification. The findings warrant confirmation by larger multi-centre studies.
Good-quality short echo time MRS data can be collected routinely on children with brain tumours. Inos and Glut levels show greater variability between tumour types than NAA, Cho and Cr present at long echo times, providing improved tumour characterization. Inos/Cho levels differ between untreated and treated tumours and may be useful for treatment monitoring.
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