title: Non-negative matrix factorisation methods for the spectral decomposition of MRS data from human brain tumours.
abstract: BACKGROUND
  In-vivo single voxel proton magnetic resonance spectroscopy (SV 1H-MRS), coupled with supervised pattern recognition (PR) methods, has been widely used in clinical studies of discrimination of brain tumour types and follow-up of patients bearing abnormal brain masses. SV 1H-MRS provides useful biochemical information about the metabolic state of tumours and can be performed at short (< 45 ms) or long (> 45 ms) echo time (TE), each with particular advantages. Short-TE spectra are more adequate for detecting lipids, while the long-TE provides a much flatter signal baseline in between peaks but also negative signals for metabolites such as lactate. Both, lipids and lactate, are respectively indicative of specific metabolic processes taking place. Ideally, the information provided by both TE should be of use for clinical purposes. In this study, we characterise the performance of a range of Non-negative Matrix Factorisation (NMF) methods in two respects: first, to derive sources correlated with the mean spectra of known tissue types (tumours and normal tissue); second, taking the best performing NMF method for source separation, we compare its accuracy for class assignment when using the mixing matrix directly as a basis for classification, as against using the method for dimensionality reduction (DR). For this, we used SV 1H-MRS data with positive and negative peaks, from a widely tested SV 1H-MRS human brain tumour database.
  
  
  RESULTS
  The results reported in this paper reveal the advantage of using a recently described variant of NMF, namely Convex-NMF, as an unsupervised method of source extraction from SV1H-MRS. Most of the sources extracted in our experiments closely correspond to the mean spectra of some of the analysed tumour types. This similarity allows accurate diagnostic predictions to be made both in fully unsupervised mode and using Convex-NMF as a DR step previous to standard supervised classification. The obtained results are comparable to, or more accurate than those obtained with supervised techniques.
  
  
  CONCLUSIONS
  The unsupervised properties of Convex-NMF place this approach one step ahead of classical label-requiring supervised methods for the discrimination of brain tumour types, as it accounts for their increasingly recognised molecular subtype heterogeneity. The application of Convex-NMF in computer assisted decision support systems is expected to facilitate further improvements in the uptake of MRS-derived information by clinicians.
authors.affiliation: Departament de Bioquímica i Biología Molecular, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain. P.J.Lisboa@ljmu.ac.uk
authors.forename: Sandra
authors.initials: S
authors.lastname: Ortega-Martorell
authors.forename: Paulo J G
authors.initials: PJ
authors.lastname: Lisboa
authors.forename: Alfredo
authors.initials: A
authors.lastname: Vellido
authors.forename: Margarida
authors.initials: M
authors.lastname: Julià-Sapé
authors.forename: Carles
authors.initials: C
authors.lastname: Arús
mesh_terms: D000465:Algorithms; D001932:Brain Neoplasms / Q000145:classification / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*; D016208:Databases, Factual; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D010363:Pattern Recognition, Automated / Q000379:methods*