Treatment-aware Diffusion Probabilistic Model for Longitudinal MRI Generation and Diffuse Glioma Growth Prediction

Diffuse gliomas are malignant brain tumors that grow widespread through the brain. The complex interactions between neoplastic cells and normal tissue, as well as the treatment-induced changes often encountered, make glioma tumor growth modeling challenging. In this paper, we present a novel end-to-end network capable of generating future tumor masks and realistic MRIs of how the tumor will look at any future time points for different treatment plans. Our approach is based on cutting-edge diffusion probabilistic models and deep-segmentation neural networks. We included sequential multi-parametric magnetic resonance images (MRI) and treatment information as conditioning inputs to guide the generative diffusion process. This allows for tumor growth estimates at any given time point. We trained the model using real-world postoperative longitudinal MRI data with glioma tumor growth trajectories represented as tumor segmentation maps over time. The model has demonstrated promising performance across a range of tasks, including the generation of high-quality synthetic MRIs with tumor masks, time-series tumor segmentations, and uncertainty estimates. Combined with the treatment-aware generated MRIs, the tumor growth predictions with uncertainty estimates can provide useful information for clinical decision-making.Comment: 13 pages, 10 figures, 2 tables, 2 agls, preprints in the IEEE trans. format for submission to IEEE-TM

Fusing actigraphy signals for outpatient monitoring

[EN] Actigraphy devices have been successfully used as effective tools in the treatment of diseases such as sleep disorders or major depression. Although several efforts have been made in recent years to develop smaller and more portable devices, the features necessary for the continuous monitoring of outpatients require a less intrusive, obstructive and stigmatizing acquisition system. A useful strategy to overcome these limitations is based on adapting the monitoring system to the patient lifestyle and behavior by providing sets of different sensors that can be worn simultaneously or alternatively. This strategy offers to the patient the option of using one device or other according to his/her particular preferences. However this strategy requires a robust multi-sensor fusion methodology capable of taking maximum profit from all of the recorded information. With this aim, this study proposes two actigraphy fusion models including centralized and distributed architectures based on artificial neural networks. These novel fusion methods were tested both on synthetic datasets and real datasets, providing a parametric characterization of the models' behavior, and yielding results based on real case applications. The results obtained using both proposed fusion models exhibit good performance in terms of robustness to signal degradation, as well as a good behavior in terms of the dependence of signal quality on the number of signals fused. The distributed and centralized fusion methods reduce the mean averaged error of the original signals to 44% and 46% respectively when using simulated datasets. The proposed methods may therefore facilitate a less intrusive and more dependable way of acquiring valuable monitoring information from outpatients.This work was partially funded by the European Commission: Help4Mood (Contract No. FP7-ICT-2009-4: 248765). E. FusterGarcia acknowledges Programa Torres Quevedo from Ministerio de Educacion y Ciencia, co-founded by the European Social Fund (PTQ-12-05693).Fuster García, E.; Bresó Guardado, A.; Martínez Miranda, JC.; Rosell-Ferrer, J.; Matheson, C.; García Gómez, JM. (2015). Fusing actigraphy signals for outpatient monitoring. Information Fusion. 23:69-80. https://doi.org/10.1016/j.inffus.2014.08.003S69802

Multi-parametric MR Imaging Biomarkers Associated to Clinical Outcomes in Gliomas: A Systematic Review

[EN] Purpose: To systematically review evidence regarding the association of multi-parametric biomarkers with clinical outcomes and their capacity to explain relevant subcompartments of gliomas. Materials and Methods: Scopus database was searched for original journal papers from January 1st, 2007 to February 20th , 2017 according to PRISMA. Four hundred forty-nine abstracts of papers were reviewed and scored independently by two out of six authors. Based on those papers we analyzed associations between biomarkers, subcompartments within the tumor lesion, and clinical outcomes. From all the articles analyzed, the twenty-seven papers with the highest scores were highlighted to represent the evidence about MR imaging biomarkers associated with clinical outcomes. Similarly, eighteen studies defining subcompartments within the tumor region were also highlighted to represent the evidence of MR imaging biomarkers. Their reports were critically appraised according to the QUADAS-2 criteria. Results: It has been demonstrated that multi-parametric biomarkers are prepared for surrogating diagnosis, grading, segmentation, overall survival, progression-free survival, recurrence, molecular profiling and response to treatment in gliomas. Quantifications and radiomics features obtained from morphological exams (T1, T2, FLAIR, T1c), PWI (including DSC and DCE), diffusion (DWI, DTI) and chemical shift imaging (CSI) are the preferred MR biomarkers associated to clinical outcomes. Subcompartments relative to the peritumoral region, invasion, infiltration, proliferation, mass effect and pseudo flush, relapse compartments, gross tumor volumes, and high-risk regions have been defined to characterize the heterogeneity. For the majority of pairwise cooccurrences, we found no evidence to assert that observed co-occurrences were significantly different from their expected co-occurrences (Binomial test with False Discovery Rate correction, alpha=0.05). The co-occurrence among terms in the studied papers was found to be driven by their individual prevalence and trends in the literature. Conclusion: Combinations of MR imaging biomarkers from morphological, PWI, DWI and CSI exams have demonstrated their capability to predict clinical outcomes in different management moments of gliomas. Whereas morphologic-derived compartments have been mostly studied during the last ten years, new multi-parametric MRI approaches have also been proposed to discover specific subcompartments of the tumors. MR biomarkers from those subcompartments show the local behavior within the heterogeneous tumor and may quantify the prognosis and response to treatment of gliomas.This work was supported by the Spanish Ministry for Investigation, Development and Innovation project with identification number DPI2016-80054-R.Oltra-Sastre, M.; Fuster García, E.; Juan -Albarracín, J.; Sáez Silvestre, C.; Perez-Girbes, A.; Sanz-Requena, R.; Revert-Ventura, A.... (2019). 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Automated Glioblastoma Segmentation Based on a Multiparametric Structured Unsupervised Classification

Automatic brain tumour segmentation has become a key component for the future of brain tumour treatment. Currently, most of brain tumour segmentation approaches arise from the supervised learning standpoint, which requires a labelled training dataset from which to infer the models of the classes. The performance of these models is directly determined by the size and quality of the training corpus, whose retrieval becomes a tedious and time-consuming task. On the other hand, unsupervised approaches avoid these limitations but often do not reach comparable results than the supervised methods. In this sense, we propose an automated unsupervised method for brain tumour segmentation based on anatomical Magnetic Resonance (MR) images. Four unsupervised classification algorithms, grouped by their structured or non-structured condition, were evaluated within our pipeline. Considering the non-structured algorithms, we evaluated K-means, Fuzzy K-means and Gaussian Mixture Model (GMM), whereas as structured classification algorithms we evaluated Gaussian Hidden Markov Random Field (GHMRF). An automated postprocess based on a statistical approach supported by tissue probability maps is proposed to automatically identify the tumour classes after the segmentations. We evaluated our brain tumour segmentation method with the public BRAin Tumor Segmentation (BRATS) 2013 Test and Leaderboard datasets. Our approach based on the GMM model improves the results obtained by most of the supervised methods evaluated with the Leaderboard set and reaches the second position in the ranking. Our variant based on the GHMRF achieves the first position in the Test ranking of the unsupervised approaches and the seventh position in the general Test ranking, which confirms the method as a viable alternative for brain tumour segmentation.EFG was supported by Programa Torres Quevedo, Ministerio de Educacion y Ciencia, co-funded by the European Social Fund (PTQ-1205693). EFG, JMGG, and JVM were supported by Red Tematica de Investigacion Cooperativa en Cancer, (RTICC) 2013-2016 (RD12/0036/0020). JMGG was supported by Project TIN2013-43457-R: Caracterizacion de firmas biologicas de glioblastomas mediante modelos no-supervisados de prediccion estructurada basados en biomarcadores de imagen, co-funded by the Ministerio de Economia y Competitividad of Spain; CON2014001 UPV-IISLaFe: Unsupervised glioblastoma tumor components segmentation based on perfusion multiparametric MRI and spatio/temporal constraints; and CON2014002 UPV-IISLaFe: Empleo de segmentacion no supervisada multiparametrica basada en perfusion RM para la caracterizacion del edema peritumoral de gliomas y metastasis cerebrales unicas, funded by Instituto de Investigacion Sanitaria H. Universitario y Politecnico La Fe. This work was partially supported by the Instituto de Aplicaciones de las Tecnologias de la Informacion y las Comunicaciones Avanzadas (ITACA). Veratech for Health S.L. provided support in the form of salaries for author EF-G, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of this author is articulated in the "author contributions" section. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.Juan Albarracín, J.; Fuster García, E.; Manjón Herrera, JV.; Robles Viejo, M.; Aparici, F.; Marti-Bonmati, L.; García Gómez, JM. (2015). Automated Glioblastoma Segmentation Based on a Multiparametric Structured Unsupervised Classification. PLoS ONE. 10(5):1-20. https://doi.org/10.1371/journal.pone.0125143S120105Wen, P. Y., Macdonald, D. R., Reardon, D. A., Cloughesy, T. F., Sorensen, A. G., Galanis, E., … Chang, S. M. (2010). Updated Response Assessment Criteria for High-Grade Gliomas: Response Assessment in Neuro-Oncology Working Group. 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Higher vascularity at infiltrated peripheral edema differentiates proneural glioblastoma subtype

Background and purpose Genetic classifications are crucial for understanding the heterogeneity of glioblastoma. Recently, perfusion MRI techniques have demonstrated associations molecular alterations. In this work, we investigated whether perfusion markers within infiltrated peripheral edema were associated with proneural, mesenchymal, classical and neural subtypes. Materials and methods ONCOhabitats open web services were used to obtain the cerebral blood volume at the infiltrated peripheral edema for MRI studies of 50 glioblastoma patients from The Cancer Imaging Archive: TCGA-GBM. ANOVA and Kruskal-Wallis tests were carried out in order to assess the association between vascular features and the Verhaak subtypes. For assessing specific differences, Mann-Whitney U-test was conducted. Finally, the association of overall survival with molecular and vascular features was assessed using univariate and multivariate Cox models. Results ANOVA and Kruskal-Wallis tests for the maximum cerebral blood volume at the infiltrated peripheral edema between the four subclasses yielded false discovery rate corrected p-values of <0.001 and 0.02, respectively. This vascular feature was significantly higher (p = 0.0043) in proneural patients compared to the rest of the subtypes while conducting Mann-Whitney U-test. The multivariate Cox model pointed to redundant information provided by vascular features at the peripheral edema and proneural subtype when analyzing overall survival. Conclusions Higher relative cerebral blood volume at infiltrated peripheral edema is associated with proneural glioblastoma subtype suggesting underlying vascular behavior related to molecular composition in that area

Fusing actigraphy signals for outpatient monitoring

Actigraphy devices have been successfully used as effective tools in the treatment of diseases such as sleep disorders or major depression. Although several efforts have been made in recent years to develop smaller and more portable devices, the features necessary for the continuous monitoring of outpatients require a less intrusive, obstructive and stigmatizing acquisition system. A useful strategy to overcome these limitations is based on adapting the monitoring system to the patient lifestyle and behavior by providing sets of different sensors that can be worn simultaneously or alternatively. This strategy offers to the patient the option of using one device or other according to his/her particular preferences. However this strategy requires a robust multi-sensor fusion methodology capable of taking maximum profit from all of the recorded information. With this aim, this study proposes two actigraphy fusion models including centralized and distributed architectures based on artificial neural networks. These novel fusion methods were tested both on synthetic datasets and real datasets, providing a parametric characterization of the models' behavior, and yielding results based on real case applications. The results obtained using both proposed fusion models exhibit good performance in terms of robustness to signal degradation, as well as a good behavior in terms of the dependence of signal quality on the number of signals fused. The distributed and centralized fusion methods reduce the mean averaged error of the original signals to 44% and 46% respectively when using simulated datasets. The proposed methods may therefore facilitate a less intrusive and more dependable way of acquiring valuable monitoring information from outpatients.Peer Reviewe

Automatic tumour class isolation process.

<p>Automatic tumour class isolation process.</p