Automated quality control for proton magnetic resonance spectroscopy data using convex non-negative matrix factorization

Proton Magnetic Resonance Spectroscopy (1H MRS) has proven its diagnostic potential in a variety of conditions. However, MRS is not yet widely used in clinical routine because of the lack of experts on its diagnostic interpretation. Although data-based decision support systems exist to aid diagnosis, they often take for granted that the data is of good quality, which is not always the case in a real application context. Systems based on models built with bad quality data are likely to underperform in their decision support tasks. In this study, we propose a system to filter out such bad quality data. It is based on convex Non-Negative Matrix Factorization models, used as a dimensionality reduction procedure, and on the use of several classifiers to discriminate between good and bad quality data.Peer ReviewedPostprint (author's final draft

SpectraClassifier 1.0: a user friendly, automated MRS-based classifier-development system

Background: SpectraClassifier (SC) is a Java solution for designing and implementing Magnetic Resonance Spectroscopy (MRS)-based classifiers. The main goal of SC is to allow users with minimum background knowledge of multivariate statistics to perform a fully automated pattern recognition analysis. SC incorporates feature selection (greedy stepwise approach, either forward or backward), and feature extraction (PCA). Fisher Linear Discriminant Analysis is the method of choice for classification. Classifier evaluation is performed through various methods: display of the confusion matrix of the training and testing datasets; K-fold cross-validation, leave-one-out and bootstrapping as well as Receiver Operating Characteristic (ROC) curves. Results: SC is composed of the following modules: Classifier design, Data exploration, Data visualisation, Classifier evaluation, Reports, and Classifier history. It is able to read low resolution in-vivo MRS (single-voxel and multi-voxel) and high resolution tissue MRS (HRMAS), processed with existing tools (jMRUI, INTERPRET, 3DiCSI or TopSpin). In addition, to facilitate exchanging data between applications, a standard format capable of storing all the information needed for a dataset was developed. Each functionality of SC has been specifically validated with real data with the purpose of bug-testing and methods validation. Data from the INTERPRET project was used. Conclusions: SC is a user-friendly software designed to fulfil the needs of potential users in the MRS community. It accepts all kinds of pre-processed MRS data types and classifies them semi-automatically, allowing spectroscopists to concentrate on interpretation of results with the use of its visualisation tools

Pattern Recognition Analysis of MR Spectra

The need for multivariate analysis of magnetic resonance spectroscopy (MRS) data was recognized about 20 years ago, when it became evident that spectral patterns were characteristic of some diseases. Despite this, there is no generally accepted methodology for performing pattern recognition (PR) analysis of MRS data sets. Here, the data acquisition and processing requirements for performing successful PR as applied to human MRS studies are introduced, and the main techniques for feature selection, extraction, and classification are described. These include methods of dimensionality reduction such as principal component analysis (PCA), independent component analysis (ICA), non-negative matrix factorization (NMF), and feature selection. Supervised methods such as linear discriminant analysis (LDA), logistic regression (LogR), and nonlinear classification are discussed separately from unsupervised and semisupervised classification techniques, including k –means clustering. Methods for testing and metrics for gauging the performance of PR models (sensitivity and specificity, the ‘Confusion Matrix’, ‘k –fold cross-validation’, ‘Leave One Out’, ‘Bootstrapping’, the ‘Receiver Operating Characteristic curve’, and balanced error and accuracy rates) are briefly described. This article ends with a summary of the main lessons learned from PR applied to MRS to date

A machine learning pipeline for supporting differentiation of glioblastomas from single brain metastases

Machine learning has provided, over the last decades, tools for knowledge extraction in complex medical domains. Most of these tools, though, are ad hoc solutions and lack the systematic approach that would be required to become mainstream in medical practice. In this brief paper, we define a machine learning-based analysis pipeline for helping in a difficult problem in the field of neuro-oncology, namely the discrimination of brain glioblastomas from single brain metastases. This pipeline involves source extraction using k-Meansinitialized Convex Non-negative Matrix Factorization and a collection of classifiers, including Logistic Regression, Linear Discriminant Analysis, AdaBoost, and Random Forests.Peer ReviewedPostprint (published version

A comparison of non-negative matrix underapproximation methods for the decomposition of magnetic resonance spectroscopy data from human brain tumors

Altres ajuts: acords transformatius de la UABMagnetic resonance spectroscopy (MRS) is an MR technique that provides information about the biochemistry of tissues in a noninvasive way. MRS has been widely used for the study of brain tumors, both preoperatively and during follow-up. In this study, we investigated the performance of a range of variants of unsupervised matrix factorization methods of the non-negative matrix underapproximation (NMU) family, namely, sparse NMU, global NMU, and recursive NMU, and compared them with convex non-negative matrix factorization (C-NMF), which has previously shown a good performance on brain tumor diagnostic support problems using MRS data. The purpose of the investigation was 2-fold: first, to ascertain the differences among the sources extracted by these methods; and second, to compare the influence of each method in the diagnostic accuracy of the classification of brain tumors, using them as feature extractors. We discovered that, first, NMU variants found meaningful sources in terms of biological interpretability, but representing parts of the spectrum, in contrast to C-NMF; and second, that NMU methods achieved better classification accuracy than C-NMF for the classification tasks when one class was not meningioma

Classification, dimensionality reduction, and maximally discriminatory visualization of a multicentre 1H-MRS database of brain tumors

The combination of an Artificial Neural Network classifier, a feature selection process, and a novel linear dimensionality reduction technique that provides a data projection for visualization and which preserves completely the class discrimination achieved by the classifier, is applied in this study to the analysis of an international, multi-centre 1H-MRS database of brain tumors. This combination yields results that are both intuitively interpretable and very accurate. The method as a whole remains simple enough as to allow its easy integration in existing medical decision support systems.Peer ReviewedPostprint (published version

Non-negative matrix factorisation methods for the spectral decomposition of MRS data from human brain tumours

<p>Abstract</p> <p>Background</p> <p><it>In-vivo </it>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p

Automatic relevance source determination in human brain tumors using Bayesian NMF.

The clinical management of brain tumors is very sensitive; thus, their non-invasive characterization is often preferred. Non-negative Matrix Factorization techniques have been successfully applied in the context of neuro-oncology to extract the underlying source signals that explain different tissue tumor types, for which knowing the number of sources to calculate was always required. In the current study we estimate the number of relevant sources for a set of discrimination problems involving brain tumors and normal brain. For this, we propose to start by calculating a high number of sources using Bayesian NMF and automatically discarding the irrelevant ones during the iterative process of matrices decomposition, hence obtaining a reduced range of interpretable solutions. The real data used in this study come from a widely tested human brain tumor database. Simulated data that resembled the real data was also generated to validate the hypothesis against ground truth. The results obtained suggest that the proposed approach is able to provide a small range of meaningful solutions to the problem of source extraction in human brain tumors

The INTERPRET Decision-Support System version 3.0 for evaluation of Magnetic Resonance Spectroscopy data from human brain tumours and other abnormal brain masses.

Background Proton Magnetic Resonance (MR) Spectroscopy (MRS) is a widely available technique for those clinical centres equipped with MR scanners. Unlike the rest of MR-based techniques, MRS yields not images but spectra of metabolites in the tissues. In pathological situations, the MRS profile changes and this has been particularly described for brain tumours. However, radiologists are frequently not familiar to the interpretation of MRS data and for this reason, the usefulness of decision-support systems (DSS) in MRS data analysis has been explored. Results This work presents the INTERPRET DSS version 3.0, analysing the improvements made from its first release in 2002. Version 3.0 is aimed to be a program that 1st, can be easily used with any new case from any MR scanner manufacturer and 2nd, improves the initial analysis capabilities of the first version. The main improvements are an embedded database, user accounts, more diagnostic discrimination capabilities and the possibility to analyse data acquired under additional data acquisition conditions. Other improvements include a customisable graphical user interface (GUI). Most diagnostic problems included have been addressed through a pattern-recognition based approach, in which classifiers based on linear discriminant analysis (LDA) were trained and tested. Conclusions The INTERPRET DSS 3.0 allows radiologists, medical physicists, biochemists or, generally speaking, any person with a minimum knowledge of what an MR spectrum is, to enter their own SV raw data, acquired at 1.5 T, and to analyse them. The system is expected to help in the categorisation of MR Spectra from abnormal brain masses

Semi-supervised source extraction methodology for the nosological imaging of glioblastoma response to therapy.

Glioblastomas are one the most aggressive brain tumors. Their usual bad prognosis is due to the heterogeneity of their response to treatment and the lack of early and robust biomarkers to decide whether the tumor is responding to therapy. In this work, we propose the use of a semi-supervised methodology for source extraction to identify the sources representing tumor response to therapy, untreated/unresponsive tumor, and normal brain; and create nosological images of the response to therapy based on those sources. Fourteen mice were used to calculate the sources, and an independent test set of eight mice was used to further evaluate the proposed approach. The preliminary results obtained indicate that was possible to discriminate response and untreated/unresponsive areas of the tumor, and that the color-coded images allowed convenient tracking of response, especially throughout the course of therapy