Glioblastoma: Vascular Habitats Detected at Preoperative Dynamic Susceptibility-weighted Contrast-enhanced Perfusion MR Imaging Predict Survival

[EN] Purpose: To determine if preoperative vascular heterogeneity of glioblastoma is predictive of overall survival of patients undergoing standard-of-care treatment by using an unsupervised multiparametric perfusion-based habitat-discovery algorithm. Materials and Methods: Preoperative magnetic resonance (MR) imaging including dynamic susceptibility-weighted contrast material-enhanced perfusion studies in 50 consecutive patients with glioblastoma were retrieved. Perfusion parameters of glioblastoma were analyzed and used to automatically draw four reproducible habitats that describe the tumor vascular heterogeneity: high-angiogenic and low-angiogenic regions of the enhancing tumor, potentially tumor-infiltrated peripheral edema, and vasogenic edema. Kaplan-Meier and Cox proportional hazard analyses were conducted to assess the prognostic potential of the hemodynamic tissue signature to predict patient survival. Results: Cox regression analysis yielded a significant correlation between patients' survival and maximum relative cerebral blood volume (rCBV(max)) and maximum relative cerebral blood flow (rCBF(max)) in high-angiogenic and low-angiogenic habitats (P < .01, false discovery rate-corrected P < .05). Moreover, rCBF(max) in the potentially tumor-infiltrated peripheral edema habitat was also significantly correlated (P < .05, false discovery rate-corrected P < .05). Kaplan-Meier analysis demonstrated significant differences between the observed survival of populations divided according to the median of the rCBV(max) or rCBF(max) at the high-angiogenic and low-angiogenic habitats (log-rank test P < .05, false discovery rate-corrected P < .05), with an average survival increase of 230 days. Conclusion: Preoperative perfusion heterogeneity contains relevant information about overall survival in patients who undergo standard-of-care treatment. The hemodynamic tissue signature method automatically describes this heterogeneity, providing a set of vascular habitats with high prognostic capabilities.Study supported by H2020 European Institute of Innovation and Technology (POC-2016.SPAIN-07) and Universitat Politecnica de Valencia (PAID-10-14). J.J.A., E.F.G., and J.M.G.G. supported by Secretaria de Estado de Investigacion, Desarrollo e Innovacion (DPI2016-80054-R, TIN2013-43457-R). E.F.G. supported by CaixaImpulse program from Fundacio Bancaria "la Caixa" (LCF/TR/CI16/10010016). E.F.G and A.A.B. supported by the Universitat Politecnica de Valencia Instituto Investigacion Sanitaria de La Fe (C05).Juan -Albarracín, J.; Fuster García, E.; Pérez-Girbés, A.; Aparici-Robles, F.; Alberich Bayarri, A.; Revert Ventura, AJ.; Martí Bonmatí, L.... (2018). Glioblastoma: Vascular Habitats Detected at Preoperative Dynamic Susceptibility-weighted Contrast-enhanced Perfusion MR Imaging Predict Survival. Radiology. 287(3):944-954. https://doi.org/10.1148/radiol.2017170845S944954287

Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Background: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation: Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding: UK Medical Research Council and Health Technology Assessment Programme

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. Journal of Clinical Oncology, 28(11), 1963-1972. doi:10.1200/jco.2009.26.3541Bauer, S., Wiest, R., Nolte, L.-P., & Reyes, M. (2013). A survey of MRI-based medical image analysis for brain tumor studies. Physics in Medicine and Biology, 58(13), R97-R129. doi:10.1088/0031-9155/58/13/r97Dolecek, T. A., Propp, J. M., Stroup, N. E., & Kruchko, C. (2012). CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2005-2009. Neuro-Oncology, 14(suppl 5), v1-v49. doi:10.1093/neuonc/nos218Gordillo, N., Montseny, E., & Sobrevilla, P. (2013). State of the art survey on MRI brain tumor segmentation. Magnetic Resonance Imaging, 31(8), 1426-1438. doi:10.1016/j.mri.2013.05.002Verma, R., Zacharaki, E. I., Ou, Y., Cai, H., Chawla, S., Lee, S.-K., … Davatzikos, C. (2008). Multiparametric Tissue Characterization of Brain Neoplasms and Their Recurrence Using Pattern Classification of MR Images. Academic Radiology, 15(8), 966-977. doi:10.1016/j.acra.2008.01.029Jensen, T. R., & Schmainda, K. M. (2009). Computer-aided detection of brain tumor invasion using multiparametric MRI. Journal of Magnetic Resonance Imaging, 30(3), 481-489. doi:10.1002/jmri.21878Breiman, L. (2001). Machine Learning, 45(1), 5-32. doi:10.1023/a:1010933404324Wagstaff KL. Intelligent Clustering with instance-level constraints. PhD Thesis, Cornell University. 2002.Fletcher-Heath, L. M., Hall, L. O., Goldgof, D. B., & Murtagh, F. R. (2001). Automatic segmentation of non-enhancing brain tumors in magnetic resonance images. Artificial Intelligence in Medicine, 21(1-3), 43-63. doi:10.1016/s0933-3657(00)00073-7Nie, J., Xue, Z., Liu, T., Young, G. S., Setayesh, K., Guo, L., & Wong, S. T. C. (2009). Automated brain tumor segmentation using spatial accuracy-weighted hidden Markov Random Field. Computerized Medical Imaging and Graphics, 33(6), 431-441. doi:10.1016/j.compmedimag.2009.04.006Zhu, Y., Young, G. S., Xue, Z., Huang, R. Y., You, H., Setayesh, K., … Wong, S. T. (2012). Semi-Automatic Segmentation Software for Quantitative Clinical Brain Glioblastoma Evaluation. Academic Radiology, 19(8), 977-985. doi:10.1016/j.acra.2012.03.026Zhang, Y., Brady, M., & Smith, S. (2001). Segmentation of brain MR images through a hidden Markov random field model and the expectation-maximization algorithm. IEEE Transactions on Medical Imaging, 20(1), 45-57. doi:10.1109/42.906424Vijayakumar, C., Damayanti, G., Pant, R., & Sreedhar, C. M. (2007). Segmentation and grading of brain tumors on apparent diffusion coefficient images using self-organizing maps. Computerized Medical Imaging and Graphics, 31(7), 473-484. doi:10.1016/j.compmedimag.2007.04.004Prastawa, M., Bullitt, E., Moon, N., Van Leemput, K., & Gerig, G. (2003). Automatic brain tumor segmentation by subject specific modification of atlas priors1. Academic Radiology, 10(12), 1341-1348. doi:10.1016/s1076-6332(03)00506-3Gudbjartsson, H., & Patz, S. (1995). The rician distribution of noisy mri data. Magnetic Resonance in Medicine, 34(6), 910-914. doi:10.1002/mrm.1910340618Buades, A., Coll, B., & Morel, J. M. (2005). A Review of Image Denoising Algorithms, with a New One. Multiscale Modeling & Simulation, 4(2), 490-530. doi:10.1137/040616024Manjón, J. V., Coupé, P., Martí-Bonmatí, L., Collins, D. L., & Robles, M. (2009). Adaptive non-local means denoising of MR images with spatially varying noise levels. Journal of Magnetic Resonance Imaging, 31(1), 192-203. doi:10.1002/jmri.22003Sled, J. G., Zijdenbos, A. P., & Evans, A. C. (1998). A nonparametric method for automatic correction of intensity nonuniformity in MRI data. IEEE Transactions on Medical Imaging, 17(1), 87-97. doi:10.1109/42.668698Tustison, N. J., Avants, B. B., Cook, P. A., Yuanjie Zheng, Egan, A., Yushkevich, P. A., & Gee, J. C. (2010). N4ITK: Improved N3 Bias Correction. IEEE Transactions on Medical Imaging, 29(6), 1310-1320. doi:10.1109/tmi.2010.2046908Manjón, J. V., Coupé, P., Buades, A., Collins, D. L., & Robles, M. (2010). MRI Superresolution Using Self-Similarity and Image Priors. International Journal of Biomedical Imaging, 2010, 1-11. doi:10.1155/2010/425891Rousseau, F. (2010). A non-local approach for image super-resolution using intermodality priors☆. Medical Image Analysis, 14(4), 594-605. doi:10.1016/j.media.2010.04.005Protter, M., Elad, M., Takeda, H., & Milanfar, P. (2009). Generalizing the Nonlocal-Means to Super-Resolution Reconstruction. IEEE Transactions on Image Processing, 18(1), 36-51. doi:10.1109/tip.2008.2008067Manjón, J. V., Coupé, P., Buades, A., Fonov, V., Louis Collins, D., & Robles, M. (2010). Non-local MRI upsampling. Medical Image Analysis, 14(6), 784-792. doi:10.1016/j.media.2010.05.010Kassner, A., & Thornhill, R. E. (2010). Texture Analysis: A Review of Neurologic MR Imaging Applications. American Journal of Neuroradiology, 31(5), 809-816. doi:10.3174/ajnr.a2061Ahmed, S., Iftekharuddin, K. M., & Vossough, A. (2011). Efficacy of Texture, Shape, and Intensity Feature Fusion for Posterior-Fossa Tumor Segmentation in MRI. IEEE Transactions on Information Technology in Biomedicine, 15(2), 206-213. doi:10.1109/titb.2011.2104376Lloyd, S. (1982). Least squares quantization in PCM. IEEE Transactions on Information Theory, 28(2), 129-137. doi:10.1109/tit.1982.1056489Dunn, J. C. (1973). A Fuzzy Relative of the ISODATA Process and Its Use in Detecting Compact Well-Separated Clusters. Journal of Cybernetics, 3(3), 32-57. doi:10.1080/01969727308546046Bezdek, J. C. (1981). Pattern Recognition with Fuzzy Objective Function Algorithms. doi:10.1007/978-1-4757-0450-1Hammersley, JM, Clifford, P. Markov fields on finite graphs and lattices. 1971.Komodakis, N., & Tziritas, G. (2007). Approximate Labeling via Graph Cuts Based on Linear Programming. IEEE Transactions on Pattern Analysis and Machine Intelligence, 29(8), 1436-1453. doi:10.1109/tpami.2007.1061Komodakis, N., Tziritas, G., & Paragios, N. (2008). Performance vs computational efficiency for optimizing single and dynamic MRFs: Setting the state of the art with primal-dual strategies. Computer Vision and Image Understanding, 112(1), 14-29. doi:10.1016/j.cviu.2008.06.007Fonov, V., Evans, A. C., Botteron, K., Almli, C. R., McKinstry, R. C., & Collins, D. L. (2011). Unbiased average age-appropriate atlases for pediatric studies. NeuroImage, 54(1), 313-327. doi:10.1016/j.neuroimage.2010.07.033Fonov, V., Evans, A., McKinstry, R., Almli, C., & Collins, D. (2009). Unbiased nonlinear average age-appropriate brain templates from birth to adulthood. NeuroImage, 47, S102. doi:10.1016/s1053-8119(09)70884-5Klein, A., Andersson, J., Ardekani, B. A., Ashburner, J., Avants, B., Chiang, M.-C., … Parsey, R. V. (2009). Evaluation of 14 nonlinear deformation algorithms applied to human brain MRI registration. NeuroImage, 46(3), 786-802. doi:10.1016/j.neuroimage.2008.12.037AVANTS, B., EPSTEIN, C., GROSSMAN, M., & GEE, J. (2008). Symmetric diffeomorphic image registration with cross-correlation: Evaluating automated labeling of elderly and neurodegenerative brain. Medical Image Analysis, 12(1), 26-41. doi:10.1016/j.media.2007.06.004Saez C, Robles M, Garcia-Gomez JM. Stability metrics for multi-source biomedical data based on simplicial projections from probability distribution distances. Statistical Methods in Medical Research 2014; In press

Improving the estimation of prognosis for glioblastoma patients by MR based hemodynamic tissue signatures

This is the peer reviewed version of the following article: Fuster García, Elíes, Juan -Albarracín, Javier, García-Ferrando, Germán Adrián, Martí-Bonmatí, Luis , Aparici-Robles , F, Garcia-Gomez, Juan M. (2018). Improving the estimation of prognosis for glioblastoma patients by MR based hemodynamic tissue signatures.NMR in Biomedicine, 31, 12. DOI: 10.1002/nbm.4006, which has been published in final form at http://doi.org/10.1002/nbm.4006. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving[EN] Advanced MRI and molecular markers have been raised as crucial to improve prognostic models for patients having glioblastoma (GBM) lesions. In particular, different MR perfusion based markers describing vascular intrapatient heterogeneity have been correlated with tumor aggressiveness, and represent key information to understand tumor resistance against effective therapies of these neoplasms. Recently, hemodynamic tissue signature (HTS) markers based on MR perfusion images have been demonstrated to be useful for describing the heterogeneity of GBM at the voxel level, as well as demonstrating significant correlations with the patient's overall survival. In this work, we analyze the abilities of these markers to improve the conventional prognostic models based on clinical, morphological, and demographic features. Our results, in both the regression and classification tests, show that inclusion of the HTS markers improves the reliability of prognostic models. The HTS method is fully automatic and it is available for research use at http://www.oncohabitats.upv.es.Fundacio Bancaria la Caixa, Grant/Award Number: LCF/TR/CI16/10010016; H2020 European Institute of Innovation and Technology, Grant/Award Number: POC-2016.SPAIN-07; Ministerio de Ciencia, Innovacion y Universidades - Gobierno de Espana, Grant/Award Number: DPI2016-80054-R and TIN2013-43457-R; Universitat Politecnica de Valencia/Instituto de Investigacion Sanitaria La Fe, Grant/Award Number: C05Fuster García, E.; Juan -Albarracín, J.; García-Ferrando, GA.; Martí-Bonmatí, L.; Aparici-Robles, F.; Garcia-Gomez, JM. (2018). Improving the estimation of prognosis for glioblastoma patients by MR based hemodynamic tissue signatures. NMR in Biomedicine. 31(12). https://doi.org/10.1002/nbm.4006S311

Example of new skull stripping.

<p>From left to right column: original BRATS 2013 patient image, resultant image after the new skull stripping and the remaining residual.</p

Example of feature extraction and dimensionality reduction from a patient of the BRATS 2013 dataset.

<p>Example of feature extraction and dimensionality reduction from a patient of the BRATS 2013 dataset.</p

Automatic tumour class isolation process.

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

Patient tissue probability maps computation and lesion area correction.

<p>Patient tissue probability maps computation and lesion area correction.</p