Convex Non-Negative Matrix Factorization for Brain Tumor Delimitation from MRSI Data

Background Pattern Recognition techniques can provide invaluable insights in the field of neuro-oncology. This is because the clinical analysis of brain tumors requires the use of non-invasive methods that generate complex data in electronic format. Magnetic Resonance (MR), in the modalities of spectroscopy (MRS) and spectroscopic imaging (MRSI), has been widely applied to this purpose. The heterogeneity of the tissue in the brain volumes analyzed by MR remains a challenge in terms of pathological area delimitation. Methodology/Principal Findings A pre-clinical study was carried out using seven brain tumor-bearing mice. Imaging and spectroscopy information was acquired from the brain tissue. A methodology is proposed to extract tissue type-specific sources from these signals by applying Convex Non-negative Matrix Factorization (Convex-NMF). Its suitability for the delimitation of pathological brain area from MRSI is experimentally confirmed by comparing the images obtained with its application to selected target regions, and to the gold standard of registered histopathology data. The former showed good accuracy for the solid tumor region (proliferation index (PI)>30%). The latter yielded (i) high sensitivity and specificity in most cases, (ii) acquisition conditions for safe thresholds in tumor and non-tumor regions (PI>30% for solid tumoral region; ≤5% for non-tumor), and (iii) fairly good results when borderline pixels were considered. Conclusions/Significance The unsupervised nature of Convex-NMF, which does not use prior information regarding the tumor area for its delimitation, places this approach one step ahead of classical label-requiring supervised methods for discrimination between tissue types, minimizing the negative effect of using mislabeled voxels. Convex-NMF also relaxes the non-negativity constraints on the observed data, which allows for a natural representation of the MRSI signal. This should help radiologists to accurately tackle one of the main sources of uncertainty in the clinical management of brain tumors, which is the difficulty of appropriately delimiting the pathological area.

[1]  Franklyn A Howe,et al.  1H MR spectroscopy of brain tumours and masses , 2003, NMR in biomedicine.

[2]  Lutgarde M. C. Buydens,et al.  Application of independent component analysis to 1H MR spectroscopic imaging exams of brain tumours , 2005 .

[3]  Mitchel S Berger,et al.  3D MRSI for resected high-grade gliomas before RT: tumor extent according to metabolic activity in relation to MRI. , 2004, International journal of radiation oncology, biology, physics.

[4]  Chris H. Q. Ding,et al.  Convex and Semi-Nonnegative Matrix Factorizations , 2010, IEEE Transactions on Pattern Analysis and Machine Intelligence.

[5]  J. Cardoso,et al.  Blind beamforming for non-gaussian signals , 1993 .

[6]  S Van Huffel,et al.  Fast nosologic imaging of the brain. , 2007, Journal of magnetic resonance.

[7]  J. Suykens,et al.  Classification of brain tumours using short echo time 1H MR spectra. , 2004, Journal of magnetic resonance.

[8]  H. Sebastian Seung,et al.  Learning the parts of objects by non-negative matrix factorization , 1999, Nature.

[9]  Christian Jutten,et al.  Blind separation of sources, part I: An adaptive algorithm based on neuromimetic architecture , 1991, Signal Process..

[10]  M. Berger,et al.  Histopathological validation of a three-dimensional magnetic resonance spectroscopy index as a predictor of tumor presence. , 2002, Journal of neurosurgery.

[11]  Arend Heerschap,et al.  A chemometric approach for brain tumor classification using magnetic resonance imaging and spectroscopy. , 2003, Analytical chemistry.

[12]  Kristen Scott,et al.  Hyperpolarized 13C MR spectroscopic imaging can be used to monitor Everolimus treatment in vivo in an orthotopic rodent model of glioblastoma , 2012, NeuroImage.

[13]  P R Luyten,et al.  Detection of metabolic heterogeneity of human intracranial tumors in vivo by 1h nmr spectroscopic imaging , 1990, Magnetic resonance in medicine.

[14]  Radford M. Neal Pattern Recognition and Machine Learning , 2007, Technometrics.

[15]  Sabine Van Huffel,et al.  Multiproject–multicenter evaluation of automatic brain tumor classification by magnetic resonance spectroscopy , 2008, Magnetic Resonance Materials in Physics, Biology and Medicine.

[16]  J. Gallo,et al.  Differential effect of sunitinib on the distribution of temozolomide in an orthotopic glioma model. , 2009, Neuro-oncology.

[17]  Paulo J. G. Lisboa,et al.  Spectral decomposition methods for the analysis of MRS information from human brain tumors , 2011, The 2011 International Joint Conference on Neural Networks.

[18]  K. Shroyer,et al.  Annexin A2 Promotes Glioma Cell Invasion and Tumor Progression , 2011, The Journal of Neuroscience.

[19]  D. Louis Collins,et al.  Accurate, noninvasive diagnosis of human brain tumors by using proton magnetic resonance spectroscopy , 1996, Nature Medicine.

[20]  Sabine Van Huffel,et al.  Exploiting spatial information to estimate metabolite levels in two‐dimensional MRSI of heterogeneous brain lesions , 2011, NMR in biomedicine.

[21]  Erkki Oja,et al.  Independent component analysis: algorithms and applications , 2000, Neural Networks.

[22]  C. Arús,et al.  1H‐MRSI pattern perturbation in a mouse glioma: the effects of acute hyperglycemia and moderate hypothermia , 2010, NMR in biomedicine.

[23]  Sabine Van Huffel,et al.  Nosologic imaging of the brain: segmentation and classification using MRI and MRSI , 2009, NMR in biomedicine.

[24]  M Ala-Korpela,et al.  Automated classification of human brain tumours by neural network analysis using in vivo 1H magnetic resonance spectroscopic metabolite phenotypes. , 1996, Neuroreport.

[25]  Jong-Hwan Lee,et al.  A constrained alternating least squares nonnegative matrix factorization algorithm enhances task-related neuronal activity detection from single subject's fMRI data , 2011, 2011 International Conference on Machine Learning and Cybernetics.

[26]  Shigeo Abe DrEng Pattern Classification , 2001, Springer London.

[27]  P. Kleihues,et al.  The monoclonal antibody Ki-67 as a marker for proliferating cells in stereotactic biopsies of brain tumours , 2005, Acta Neurochirurgica.

[28]  Yuzhuo Su,et al.  Spectrum separation resolves partial‐volume effect of MRSI as demonstrated on brain tumor scans , 2008, NMR in biomedicine.

[29]  David G. Stork,et al.  Pattern Classification , 1973 .

[30]  D. Gadian NMR and its Applications to Living Systems , 1996 .

[31]  D K Pearl,et al.  Improving diagnostic accuracy and interobserver concordance in the classification and grading of primary gliomas , 1997, Cancer.

[32]  Aapo Hyvärinen,et al.  Fast and robust fixed-point algorithms for independent component analysis , 1999, IEEE Trans. Neural Networks.

[33]  Paul Sajda,et al.  Automated tissue segmentation and blind recovery of 1H MRS imaging spectral patterns of normal and diseased human brain , 2008, NMR in biomedicine.

[34]  Sarah J Nelson,et al.  Assessment of therapeutic response and treatment planning for brain tumors using metabolic and physiological MRI , 2011, NMR in biomedicine.

[35]  T. Shimazaki,et al.  [Mammalian neural stem cells]. , 2008, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme.

[36]  Babak Hassibi,et al.  Second Order Derivatives for Network Pruning: Optimal Brain Surgeon , 1992, NIPS.

[37]  C Arús,et al.  Perturbation of mouse glioma MRS pattern by induced acute hyperglycemia , 2008, NMR in biomedicine.

[38]  W. El-Deredy,et al.  Pattern recognition approaches in biomedical and clinical magnetic resonance spectroscopy: a review , 1997, NMR in biomedicine.

[39]  B. Scheithauer,et al.  The 2007 WHO classification of tumours of the central nervous system , 2007, Acta Neuropathologica.

[40]  H. Kettenmann,et al.  Glioblastoma-Induced Attraction of Endogenous Neural Precursor Cells Is Associated with Improved Survival , 2005, The Journal of Neuroscience.

[41]  Lucas C. Parra,et al.  Nonnegative matrix factorization for rapid recovery of constituent spectra in magnetic resonance chemical shift imaging of the brain , 2004, IEEE Transactions on Medical Imaging.

[42]  P. Paatero,et al.  Positive matrix factorization: A non-negative factor model with optimal utilization of error estimates of data values† , 1994 .

[43]  C. James,et al.  Detection of early response to temozolomide treatment in brain tumors using hyperpolarized 13C MR metabolic imaging , 2011, Journal of magnetic resonance imaging : JMRI.

[44]  Jisook Lee,et al.  Non-invasive quantification of brain tumor-induced astrogliosis , 2011, BMC Neuroscience.

[45]  Richard G Grundy,et al.  Histopathological grading of pediatric ependymoma: reproducibility and clinical relevance in European trial cohorts , 2011, Journal of Negative Results in BioMedicine.

[46]  S. Ortega-Martorell,et al.  Improving the classification of brain tumors in mice with perturbation enhanced (PE)-MRSI , 2010, Integrative biology : quantitative biosciences from nano to macro.

[47]  Daniel B Vigneron,et al.  In vivo molecular imaging for planning radiation therapy of gliomas: An application of 1H MRSI , 2002, Journal of magnetic resonance imaging : JMRI.

[48]  R. Barnard,et al.  The classification of tumours of the central nervous system. , 1982, Neuropathology and applied neurobiology.

[49]  Anil K. Jain Data clustering: 50 years beyond K-means , 2008, Pattern Recognit. Lett..

[50]  Chih-Jen Lin,et al.  Projected Gradient Methods for Nonnegative Matrix Factorization , 2007, Neural Computation.

[51]  Sylvie Grand,et al.  A new approach for analyzing proton magnetic resonance spectroscopic images of brain tumors: nosologic images , 2000, Nature Medicine.

[52]  C Arús,et al.  Robust discrimination of glioblastomas from metastatic brain tumors on the basis of single‐voxel 1H MRS , 2012, NMR in biomedicine.

[53]  T. Roberts,et al.  MR pulse sequences: what every radiologist wants to know but is afraid to ask. , 2006, Radiographics : a review publication of the Radiological Society of North America, Inc.

[54]  S. Torp,et al.  The clinical value of Ki-67/MIB-1 labeling index in human astrocytomas , 2008, Pathology & Oncology Research.

[55]  J. Kros Grading of Gliomas: The Road From Eminence to Evidence , 2011, Journal of neuropathology and experimental neurology.

[56]  David G. Stork,et al.  Pattern Classification (2nd ed.) , 1999 .