Characterisation of paediatric brain tumours by their MRS metabolite profiles

Author:

Gill Simrandip K.12,Rose Heather E. L.12ORCID,Wilson Martin12,Rodriguez Gutierrez Daniel3,Worthington Lara124,Davies Nigel P.124,MacPherson Lesley2,Hargrave Darren R.5,Saunders Dawn E.5,Clark Christopher A.6,Payne Geoffrey S.7ORCID,Leach Martin O.7,Howe Franklyn A.8,Auer Dorothee P.91011,Jaspan Tim911,Morgan Paul S.39,Grundy Richard G.9,Avula Shivaram12,Pizer Barry13,Arvanitis Theodoros N.214ORCID,Peet Andrew C.12ORCID

Affiliation:

1. Institute of Cancer and Genomic Sciences University of Birmingham Birmingham UK

2. Birmingham Children's Hospital NHS Foundation Trust Birmingham UK

3. Medical Physics, Nottingham University Hospital Queen's Medical Centre Nottingham UK

4. Department of Imaging and Medical Physics University Hospitals Birmingham NHS Foundation Trust Birmingham UK

5. Paediatric Oncology Unit Great Ormond Street Hospital For Sick Children London UK

6. Developmental Imaging and Biophysics Section, UCL Great Ormond Street Institute of Child Health University College London London UK

7. CRUK Cancer Imaging Centre The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust London UK

8. Neurosciences Research Section, Molecular and Clinical Sciences Research Institute, St George's University of London London UK

9. The Children's Brain Tumour Research Centre University of Nottingham Nottingham UK

10. Radiological Sciences, Department of Clinical Neuroscience University of Nottingham Nottingham UK

11. Neuroradiology, Nottingham University Hospital Queen's Medical Centre Nottingham UK

12. Department of Radiology Alder Hey Children's NHS Foundation Trust Liverpool UK

13. Department of Paediatric Oncology Alder Hey Children's NHS Foundation Trust Liverpool UK

14. Department of Electronic, Electrical and Systems Engineering University of Birmingham Birmingham UK

Abstract

Abstract1H‐magnetic resonance spectroscopy (MRS) has the potential to improve the noninvasive diagnostic accuracy for paediatric brain tumours. However, studies analysing large, comprehensive, multicentre datasets are lacking, hindering translation to widespread clinical practice. Single‐voxel MRS (point‐resolved single‐voxel spectroscopy sequence, 1.5 T: echo time [TE] 23–37 ms/135–144 ms, repetition time [TR] 1500 ms; 3 T: TE 37–41 ms/135–144 ms, TR 2000 ms) was performed from 2003 to 2012 during routine magnetic resonance imaging for a suspected brain tumour on 340 children from five hospitals with 464 spectra being available for analysis and 281 meeting quality control. Mean spectra were generated for 13 tumour types. Mann–Whitney U‐tests and Kruskal–Wallis tests were used to compare mean metabolite concentrations. Receiver operator characteristic curves were used to determine the potential for individual metabolites to discriminate between specific tumour types. Principal component analysis followed by linear discriminant analysis was used to construct a classifier to discriminate the three main central nervous system tumour types in paediatrics. Mean concentrations of metabolites were shown to differ significantly between tumour types. Large variability existed across each tumour type, but individual metabolites were able to aid discrimination between some tumour types of importance. Complete metabolite profiles were found to be strongly characteristic of tumour type and, when combined with the machine learning methods, demonstrated a diagnostic accuracy of 93% for distinguishing between the three main tumour groups (medulloblastoma, pilocytic astrocytoma and ependymoma). The accuracy of this approach was similar even when data of marginal quality were included, greatly reducing the proportion of MRS excluded for poor quality. Children's brain tumours are strongly characterised by MRS metabolite profiles readily acquired during routine clinical practice, and this information can be used to support noninvasive diagnosis. This study provides both key evidence and an important resource for the future use of MRS in the diagnosis of children's brain tumours.

Funder

Action Medical Research

Cancer Research UK

Engineering and Physical Sciences Research Council

National Institute for Health and Care Research

Little Princess Trust

Children's Cancer and Leukaemia Group

CHILDREN with CANCER UK

Publisher

Wiley

Reference44 articles.

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