23 research outputs found

    Convex non-negative matrix factorization for brain tumor delimitation from MRSI data

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    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

    Spatio-spectral classification of hyperspectral images for brain cancer detection during surgical operations.

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    Surgery for brain cancer is a major problem in neurosurgery. The diffuse infiltration into the surrounding normal brain by these tumors makes their accurate identification by the naked eye difficult. Since surgery is the common treatment for brain cancer, an accurate radical resection of the tumor leads to improved survival rates for patients. However, the identification of the tumor boundaries during surgery is challenging. Hyperspectral imaging is a non-contact, non-ionizing and non-invasive technique suitable for medical diagnosis. This study presents the development of a novel classification method taking into account the spatial and spectral characteristics of the hyperspectral images to help neurosurgeons to accurately determine the tumor boundaries in surgical-time during the resection, avoiding excessive excision of normal tissue or unintentionally leaving residual tumor. The algorithm proposed in this study to approach an efficient solution consists of a hybrid framework that combines both supervised and unsupervised machine learning methods. Firstly, a supervised pixel-wise classification using a Support Vector Machine classifier is performed. The generated classification map is spatially homogenized using a one-band representation of the HS cube, employing the Fixed Reference t-Stochastic Neighbors Embedding dimensional reduction algorithm, and performing a K-Nearest Neighbors filtering. The information generated by the supervised stage is combined with a segmentation map obtained via unsupervised clustering employing a Hierarchical K-Means algorithm. The fusion is performed using a majority voting approach that associates each cluster with a certain class. To evaluate the proposed approach, five hyperspectral images of surface of the brain affected by glioblastoma tumor in vivo from five different patients have been used. The final classification maps obtained have been analyzed and validated by specialists. These preliminary results are promising, obtaining an accurate delineation of the tumor area

    Learning-based tumor segmentation using metabolic imaging features

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    The ultimate objective of brain tumor imaging is to distill patient-specific knowledge that guides therapy planning and medical care. Magnetic resonance imaging (MRI) is a prevailing technique to visualize tumors due to its excellent contrast of soft tissue and non-invasiveness. Decades of research have helped brain tumor segmentation performance dramatically. However, precise segmentation is still considered hard partly due to the limitation in resolution, signal-to-noise ratio, and possible artifacts. While some tumors are easier to delineate, more infiltrating ones like gliomas have ragged and obscure boundaries that are harder to define. In recognition of this hardship, researchers have started exploring the use of Proton Magnetic Resonance Spectroscopic Imaging (MRSI) for better tumor prognosis, diagnosis, and characterization. MRSI investigates the spatial distribution of metabolic changes by leveraging its unique temporal information. The wealth of this spectroscopic information is beneficial in classifying tumor subregions and aiding ongoing research investigations in tumor heterogeneity and related topics. Several studies have reported an increase in choline-containing compounds level and a reduced N-acetyl-aspartate level in brain tumors. Spectroscopic techniques can pick up these metabolic changes, and they might be the missing pieces of better MRI-based tumor segmentation solutions. This study shows a successful application of deep learning and MRSI to identify tumor and edema regions of human brains with glioblastomas. The deep learning framework of choice is nnU-Net. Most specialized solutions in applying deep neural models in the medical image domain depend on dataset properties and hardware constraints. nnU-Net is a framework that automatically adapts itself to various medical image segmentation tasks. Therefore, it ensures a fair comparison of experiments. This work shows an improved segmentation result after incorporating high-resolution metabolite maps derived from MRSI data acquired by the SPICE sequence. The high resolution, rapidness, and near whole-brain performance of SPICE should assist radiologists and oncologists in delimiting the pathological area better and providing more appropriate medical help

    Immune system-related changes in preclinical GL261 glioblastoma under TMZ treatment : Explaining MRSI-based nosological imaging findings with RT-PCR analyses

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    Altres ajuts: Centro de Investigación Biomédica en Red-Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN [http://www.ciber-bbn.es/en, accessed on 18 March 2021], CB06/01/0010). UAB Predoctoral training programme (14ª Convocatoria PIF-19612, predoctoral fellowships for P.C.-P.). 2018 XARDI 00016/IU68-013944 (XarTEC SALUT).Glioblastomas (GB) are brain tumours with poor prognosis even after aggressive therapy. Previous work suggests that magnetic resonance spectroscopic imaging (MRSI) could act as a biomarker of efficient immune system attack onto GB, presenting oscillatory changes. Glioma-associated microglia/macrophages (GAMs) constitute the most abundant non-tumour cell type within the GB and can be polarised into anti-tumour (M1) or pro-tumour (M2) phenotypes. One of the mechanisms to mediate immunosuppression in brain tumours is the interaction between programmed cell death-1 ligand 1 (PD-L1) and programmed cell death-1 receptor (PD-1). We evaluated the subpopulations of GAMs in responding and control GB tumours to correlate PD-L1 expression to GAM polarisation in order to explain/validate MRSI-detected findings. Mice were evaluated by MRI/MRSI to assess the extent of response to treatment and with qPCR for GAMs M1 and M2 polarisation analyses. M1/M2 ratios and PD-L1 expression were higher in treated compared to control tumours. Furthermore, PD-L1 expression was positively correlated with the M1/M2 ratio. The oscillatory change in the GAMs prevailing population could be one of the key causes for the differential MRSI-detected pattern, allowing this to act as immune system activity biomarker in future work

    Multivariate methods for interpretable analysis of magnetic resonance spectroscopy data in brain tumour diagnosis

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    Malignant tumours of the brain represent one of the most difficult to treat types of cancer due to the sensitive organ they affect. Clinical management of the pathology becomes even more intricate as the tumour mass increases due to proliferation, suggesting that an early and accurate diagnosis is vital for preventing it from its normal course of development. The standard clinical practise for diagnosis includes invasive techniques that might be harmful for the patient, a fact that has fostered intensive research towards the discovery of alternative non-invasive brain tissue measurement methods, such as nuclear magnetic resonance. One of its variants, magnetic resonance imaging, is already used in a regular basis to locate and bound the brain tumour; but a complementary variant, magnetic resonance spectroscopy, despite its higher spatial resolution and its capability to identify biochemical metabolites that might become biomarkers of tumour within a delimited area, lags behind in terms of clinical use, mainly due to its difficult interpretability. The interpretation of magnetic resonance spectra corresponding to brain tissue thus becomes an interesting field of research for automated methods of knowledge extraction such as machine learning, always understanding its secondary role behind human expert medical decision making. The current thesis aims at contributing to the state of the art in this domain by providing novel techniques for assistance of radiology experts, focusing on complex problems and delivering interpretable solutions. In this respect, an ensemble learning technique to accurately discriminate amongst the most aggressive brain tumours, namely glioblastomas and metastases, has been designed; moreover, a strategy to increase the stability of biomarker identification in the spectra by means of instance weighting is provided. From a different analytical perspective, a tool based on signal source separation, guided by tumour type-specific information has been developed to assess the existence of different tissues in the tumoural mass, quantifying their influence in the vicinity of tumoural areas. This development has led to the derivation of a probabilistic interpretation of some source separation techniques, which provide support for uncertainty handling and strategies for the estimation of the most accurate number of differentiated tissues within the analysed tumour volumes. The provided strategies should assist human experts through the use of automated decision support tools and by tackling interpretability and accuracy from different anglesEls tumors cerebrals malignes representen un dels tipus de càncer més difícils de tractar degut a la sensibilitat de l’òrgan que afecten. La gestió clínica de la patologia esdevé encara més complexa quan la massa tumoral s'incrementa degut a la proliferació incontrolada de cèl·lules; suggerint que una diagnosis precoç i acurada és vital per prevenir el curs natural de desenvolupament. La pràctica clínica estàndard per a la diagnosis inclou la utilització de tècniques invasives que poden arribar a ser molt perjudicials per al pacient, factor que ha fomentat la recerca intensiva cap al descobriment de mètodes alternatius de mesurament dels teixits del cervell, tals com la ressonància magnètica nuclear. Una de les seves variants, la imatge de ressonància magnètica, ja s'està actualment utilitzant de forma regular per localitzar i delimitar el tumor. Així mateix, una variant complementària, la espectroscòpia de ressonància magnètica, malgrat la seva alta resolució espacial i la seva capacitat d'identificar metabòlits bioquímics que poden esdevenir biomarcadors de tumor en una àrea delimitada, està molt per darrera en termes d'ús clínic, principalment per la seva difícil interpretació. Per aquest motiu, la interpretació dels espectres de ressonància magnètica corresponents a teixits del cervell esdevé un interessant camp de recerca en mètodes automàtics d'extracció de coneixement tals com l'aprenentatge automàtic, sempre entesos com a una eina d'ajuda per a la presa de decisions per part d'un metge expert humà. La tesis actual té com a propòsit la contribució a l'estat de l'art en aquest camp mitjançant l'aportació de noves tècniques per a l'assistència d'experts radiòlegs, centrades en problemes complexes i proporcionant solucions interpretables. En aquest sentit, s'ha dissenyat una tècnica basada en comitè d'experts per a una discriminació acurada dels diferents tipus de tumors cerebrals agressius, anomenats glioblastomes i metàstasis; a més, es proporciona una estratègia per a incrementar l'estabilitat en la identificació de biomarcadors presents en un espectre mitjançant una ponderació d'instàncies. Des d'una perspectiva analítica diferent, s'ha desenvolupat una eina basada en la separació de fonts, guiada per informació específica de tipus de tumor per a avaluar l'existència de diferents tipus de teixits existents en una massa tumoral, quantificant-ne la seva influència a les regions tumorals veïnes. Aquest desenvolupament ha portat cap a la derivació d'una interpretació probabilística d'algunes d'aquestes tècniques de separació de fonts, proporcionant suport per a la gestió de la incertesa i estratègies d'estimació del nombre més acurat de teixits diferenciats en cada un dels volums tumorals analitzats. Les estratègies proporcionades haurien d'assistir els experts humans en l'ús d'eines automatitzades de suport a la decisió, donada la interpretabilitat i precisió que presenten des de diferents angles

    Integration of magnetic resonance spectroscopic imaging into the radiotherapy treatment planning

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    L'objectif de cette thèse est de proposer de nouveaux algorithmes pour surmonter les limitations actuelles et de relever les défis ouverts dans le traitement de l'imagerie spectroscopique par résonance magnétique (ISRM). L'ISRM est une modalité non invasive capable de fournir la distribution spatiale des composés biochimiques (métabolites) utilisés comme biomarqueurs de la maladie. Les informations fournies par l'ISRM peuvent être utilisées pour le diagnostic, le traitement et le suivi de plusieurs maladies telles que le cancer ou des troubles neurologiques. Cette modalité se montre utile en routine clinique notamment lorsqu'il est possible d'en extraire des informations précises et fiables. Malgré les nombreuses publications sur le sujet, l'interprétation des données d'ISRM est toujours un problème difficile en raison de différents facteurs tels que le faible rapport signal sur bruit des signaux, le chevauchement des raies spectrales ou la présence de signaux de nuisance. Cette thèse aborde le problème de l'interprétation des données d'ISRM et la caractérisation de la rechute des patients souffrant de tumeurs cérébrales. Ces objectifs sont abordés à travers une approche méthodologique intégrant des connaissances a priori sur les données d'ISRM avec une régularisation spatio-spectrale. Concernant le cadre applicatif, cette thèse contribue à l'intégration de l'ISRM dans le workflow de traitement en radiothérapie dans le cadre du projet européen SUMMER (Software for the Use of Multi-Modality images in External Radiotherapy) financé par la Commission européenne (FP7-PEOPLE-ITN).The aim of this thesis is to propose new algorithms to overcome the current limitations and to address the open challenges in the processing of magnetic resonance spectroscopic imaging (MRSI) data. MRSI is a non-invasive modality able to provide the spatial distribution of relevant biochemical compounds (metabolites) commonly used as biomarkers of disease. Information provided by MRSI can be used as a valuable insight for the diagnosis, treatment and follow-up of several diseases such as cancer or neurological disorders. Obtaining accurate and reliable information from in vivo MRSI signals is a crucial requirement for the clinical utility of this technique. Despite the numerous publications on the topic, the interpretation of MRSI data is still a challenging problem due to different factors such as the low signal-to-noise ratio (SNR) of the signals, the overlap of spectral lines or the presence of nuisance components. This thesis addresses the problem of interpreting MRSI data and characterizing recurrence in tumor brain patients. These objectives are addressed through a methodological approach based on novel processing methods that incorporate prior knowledge on the MRSI data using a spatio-spectral regularization. As an application, the thesis addresses the integration of MRSI into the radiotherapy treatment workflow within the context of the European project SUMMER (Software for the Use of Multi-Modality images in External Radiotherapy) founded by the European Commission (FP7-PEOPLE-ITN framework)

    Tracking Therapy Response in Glioblastoma Using 1D Convolutional Neural Networks

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    Background: Glioblastoma (GB) is a malignant brain tumour that is challenging to treat, often relapsing even after aggressive therapy. Evaluating therapy response relies on magnetic resonance imaging (MRI) following the Response Assessment in Neuro-Oncology (RANO) criteria. However, early assessment is hindered by phenomena such as pseudoprogression and pseudoresponse. Magnetic resonance spectroscopy (MRS/MRSI) provides metabolomics information but is underutilised due to a lack of familiarity and standardisation. Methods: This study explores the potential of spectroscopic imaging (MRSI) in combination with several machine learning approaches, including one-dimensional convolutional neural networks (1D-CNNs), to improve therapy response assessment. Preclinical GB (GL261-bearing mice) were studied for method optimisation and validation. Results: The proposed 1D-CNN models successfully identify different regions of tumours sampled by MRSI, i.e., normal brain (N), control/unresponsive tumour (T), and tumour responding to treatment (R). Class activation maps using Grad-CAM enabled the study of the key areas relevant to the models, providing model explainability. The generated colour-coded maps showing the N, T and R regions were highly accurate (according to Dice scores) when compared against ground truth and outperformed our previous method. Conclusions: The proposed methodology may provide new and better opportunities for therapy response assessment, potentially providing earlier hints of tumour relapsing stages

    Sensing and Signal Processing in Smart Healthcare

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    In the last decade, we have witnessed the rapid development of electronic technologies that are transforming our daily lives. Such technologies are often integrated with various sensors that facilitate the collection of human motion and physiological data and are equipped with wireless communication modules such as Bluetooth, radio frequency identification, and near-field communication. In smart healthcare applications, designing ergonomic and intuitive human–computer interfaces is crucial because a system that is not easy to use will create a huge obstacle to adoption and may significantly reduce the efficacy of the solution. Signal and data processing is another important consideration in smart healthcare applications because it must ensure high accuracy with a high level of confidence in order for the applications to be useful for clinicians in making diagnosis and treatment decisions. This Special Issue is a collection of 10 articles selected from a total of 26 contributions. These contributions span the areas of signal processing and smart healthcare systems mostly contributed by authors from Europe, including Italy, Spain, France, Portugal, Romania, Sweden, and Netherlands. Authors from China, Korea, Taiwan, Indonesia, and Ecuador are also included
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