Biomedical signal analysis in automatic classification problems

A lo largo de la última década hemos asistido a un desarrollo sin precedentes de las tecnologías de la salud. Los avances en la informatización, la creación de redes, las técnicas de imagen, la robótica, las micro/nano tecnologías, y la genómica, han contribuido a aumentar significativamente la cantidad y diversidad de información al alcance del personal clínico para el diagnóstico, pronóstico, tratamiento y seguimiento de los pacientes. Este aumento en la cantidad y diversidad de datos clínicos requiere del continuo desarrollo de técnicas y metodologías capaces de integrar estos datos, procesarlos, y dar soporte en su interpretación de una forma robusta y eficiente. En este contexto, esta Tesis se focaliza en el análisis y procesado de señales biomédicas y su uso en problemas de clasificación automática. Es decir, se focaliza en: el diseño e integración de algoritmos para el procesado automático de señales biomédicas, el desarrollo de nuevos métodos de extracción de características para señales, la evaluación de compatibilidad entre señales biomédicas, y el diseño de modelos de clasificación para problemas clínicos específicos. En la mayoría de casos contenidos en esta Tesis, estos problemas se sitúan en el ámbito de los sistemas de apoyo a la decisión clínica, es decir, de sistemas computacionales que proporcionan conocimiento experto para la decisión en el diagnóstico, pronóstico y tratamiento de los pacientes. Una de las principales contribuciones de esta tesis consiste en la evaluación de la compatibilidad entre espectros de resonancia magnética (ERM) obtenidos mediante dos tecnologías de escáneres de resonancia magnética coexistentes en la actualidad (escáneres de 1.5T y de 3T). Esta compatibilidad se evalúa en el contexto de clasificación automática de tumores cerebrales. Los resultados obtenidos en este trabajo sugieren que los clasificadores existentes basados en datos de ERM de 1.5T pueden ser aplicables a casos obtenidos con la nueva tecnologFuster García, E. (2012). Biomedical signal analysis in automatic classification problems [Tesis doctoral]. Editorial Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/17176Palanci

A Novel Approach to Improve the Planning of Adaptive and Interactive Sessions for the treatment of Major Depression

[EN] Human Computer Interaction (HCI) is a research field which aims to improve the relationship between users and interactive computer systems. A main objective of this research area is to make the user experience more pleasant and efficient, minimizing the barrier between the users' cognition of what they want to accomplish and the computer's understanding of the user's tasks, by means of userfriendly, useful and usable designs. A bad HCI design is one of the main reasons behind user rejection of computer-based applications, which in turn produces loss of productivity and economy in industrial environments. In the eHealth domain, user rejection of computer-based systems is a major barrier to exploiting the maximum benefit from those applications developed to support the treatment of diseases, and in the worst cases a poor design in these systems may cause deterioration in the clinical condition of the patient. Thus, a high level of personalisation of the system according to users' needs is extremely important, making it easy to use and contributing to the system's efficacy, which in turn facilitates the empowerment of the target users. Ideally, the content offered through the interactive sessions in these applications should be continuously assessed and adapted to the changing condition of the patient. A good HCI design and development can improve the acceptance of these applications and contribute to promoting better adherence levels to the treatment, preventing the patient from further relapses. In this work, we present a mechanism to provide personalised and adaptive daily interactive sessions focused on the treatment of patients with Major Depression. These sessions are able to automatically adapt the content and length of the sessions to obtain personalised and varied sessions in order to encourage the continuous and long-term use of the system. The tailored adaptation of session content is supported by decision-making processes based on: (i) clinical requirements; (ii) the patient's historical data; and (iii) current responses from the patient. We have evaluated our system through two different methodologies: the first one performing a set of simulations producing different sessions from changing input conditions, in order to assess different levels of adaptability and variability of the session content offered by the system. The second evaluation process involved a set of patients who used the system for 14 to 28 days and answered a questionnaire to provide feedback about the perceived level of adaptability and variability produced by the system. The obtained results in both evaluations indicated good levels of adaptability and variability in the content of the sessions according to the input conditions.E. Fuster Garcia acknowledges the financial support from the "Torres Quevedo" program (Spanish Ministry of Economy and Competitiveness) co-funded by the European Social Fund (PTQ-12-05693), and the financial support from the Universitat Politecnica de Valencia under the Grant "Ayudas Para la Contratacion de Doctores para el Acceso al Sistema Espanol de Ciencia, Tecnologia e Innovacion" (PAID-10-14).Bresó Guardado, A.; Martínez Miranda, JC.; Fuster García, E.; García Gómez, JM. (2016). A Novel Approach to Improve the Planning of Adaptive and Interactive Sessions for the treatment of Major Depression. International Journal of Human-Computer Studies. 87:80-91. https://doi.org/10.1016/j.ijhcs.2015.11.003S80918

Promoting the Use of Numerical Computing Tools among Students of Agricultural Engineering

[EN] This paper presents a didactic methodology for introducing students in the application of numerical computing tools for reference evapotranspiration estimation. Students learn a specific application of this software within their field of future professional competencies. Specifically, the session focuses on the application of these tools for assessing reference evapotranspiration according to two standard non-calibrated methods, as well as on proposing an improved version for the local climatic scenario. Through this specific practical application, students should become aware of the computing possibilities offered by this software in this specific subject in comparison to the time-consuming conventional procedures usually adopted. The lecturer should stress the generalizability of the training acquired by the students for solving specific real problems that they might find in other subjects, as well as in their professional future as agricultural engineers.Martí Pérez, PC.; Fuster García, E.; Royuela, A.; Turegano Pastor, JV. (2017). Promoting the Use of Numerical Computing Tools among Students of Agricultural Engineering. International Journal of Information and Education Technology. 7(1):60-65. doi:10.18178/ijiet.2017.7.1.842S60657

Non-local spatially varying finite mixture models for image segmentation

[EN] In this work, we propose a new Bayesian model for unsupervised image segmentation based on a combination of the spatially varying finite mixture models (SVFMMs) and the non-local means (NLM) framework. The probabilistic NLM weighting function is successfully integrated into a varying Gauss¿Markov random field, yielding a prior density that adaptively imposes a local regularization to simultaneously preserve edges and enforce smooth constraints in homogeneous regions of the image. Two versions of our model are proposed: a pixel-based model and a patch-based model, depending on the design of the probabilistic NLM weighting function. Contrary to previous methods proposed in the literature, our approximation does not introduce new parameters to be estimated into the model, because the NLM weighting function is completely known once the neighborhood of a pixel is fixed. The proposed model can be estimated in closed-form solution via a maximum a posteriori (MAP) estimation in an expectation¿maximization scheme. We have compared our model with previously proposed SVFMMs using two public datasets: the Berkeley Segmentation dataset and the BRATS 2013 dataset. The proposed model performs favorably to previous approaches in the literature, achieving better results in terms of Rand Index and Dice metrics in our experiments.This study is partially supported by Secretaria de Estado de Investigacion, Desarrollo e Innovacion (DPI2016-80054-R, TIN2013-43457-R) and Agencia Valenciana de la Innovacion (INNVAL10/18/048). E.F.G was supported by the European Union's Horizon 2020 research and innovation programme under the Marie Skodowska-Curie grant agreement (No. 844646) and also acknowledges the support of NVIDIA GPU Grant Program.Juan -Albarracín, J.; Fuster García, E.; Juan, A.; Garcia-Gomez, JM. (2021). Non-local spatially varying finite mixture models for image segmentation. Statistics and Computing. 31(1):1-10. https://doi.org/10.1007/s11222-020-09988-w11031

Aprendizaje activo mediante juego de roles en Ingeniería Biomédica: negociando la adquisición de un sistema de información hospitalaria

[ES] La asignatura Sistemas de Información y Telemedicina I del Grado en Ingeniería Biomédica de la Universitat Politècnica de València ofrece a los alumnos competencias en el ámbito de la informática aplicada a la medicina. Entre sus resultados de aprendizaje encontramos el diseñar y gestionar un sistema de información hospitalaria. Estos resultados requieren definir e integrar múltiples componentes software especializados en distintos dominios médicos, con una compleja interacción entre ellos, y con variabilidad asociada a las características de cada hospital. Presentamos una nueva propuesta de aprendizaje activo mediante juego de roles en la que los alumnos, representando a jefes de distintos servicios de un hospital y compañías de software, negocian la adquisición de un nuevo componente de sistemas de información en función de las necesidades de su departamento y globales al hospital, interiorizando el diseño del mismo e interacciones entre componentes, y trabajando competencias transversales como trabajo en equipo y liderazgo y comunicación efectiva. Hacia una mejora continua, recogemos mediante cuestionarios on-line retroalimentación de los alumnos sobre la actividad. Aplicada desde el curso 2018-19, la actividad ha demostrado su efectividad, cumpliendo los resultados de aprendizaje, con una buena apreciación del aprendizaje recibido por los alumnos, y una elevada tasa de retroalimentación.[EN] The Health Information Systems and Telemedicine I course of the Degree in Biomedical Engineering of the Universitat Politècnica de València, Spain, offers students competences in the field of computer science applied to medicine. Among its learning outcomes is the design and management of a hospital information system. These learning outcomes require the definition and integration of multiple software components specialized in different medical and management domains, with a complex interaction between them, and with variability associated with the characteristics of each hospital. Active learning through role-playing is a learning strategy that is well suited for learning these types of competences. We present a new proposal for active learning through role-playing in which students, representing heads of the different services of a hospital and software companies, negotiate the acquisition of a new component of information systems according to the needs of their department and global needs to the hospital, internalizing the design of components and their interactions, while working transversal competences such as teamwork and leadership and effective communication, among others. Additionally, towards a continuous improvement, after the session we collect through voluntary on-line questionnaires the students' opinions about the activity and about the perceived learning. Applied since the 2018-19 academic year, the activity has demonstrated its effectiveness, accomplishing the pedagogical objectives of the subject, with a good appreciation of the learning received by the students, and presenting a high rate of feedback.Sáez, C.; Fuster-García, E.; Ferri, P.; García-Gómez, JM. (2020). Aprendizaje activo mediante juego de roles en Ingeniería Biomédica: negociando la adquisición de un sistema de información hospitalaria. En IN-RED 2020: VI Congreso de Innovación Educativa y Docencia en Red. Editorial Universitat Politècnica de València. 516-526. https://doi.org/10.4995/INRED2020.2020.11949OCS51652

Lack of Benefit of Extending Temozolomide Treatment in Patients with High Vascular Glioblastoma with Methylated MGMT

[EN] Despite the complete treatment with surgery, chemotherapy and radiotherapy, patients with glioblastoma have a devasting prognosis. Although the role of extending temozolomide treatment has been explored, the results are inconclusive. Recent evidence suggested that tumor vascularity may be a modulating factor in combination with methylation of O6-methylguanine-DNA methyltransferase (MGMT) promotor gene on the effect of temozolomide-based therapies, opening new possibilities for personalized treatments. Before proposing a prospective interventional clinical study, it is necessary to confirm the beneficial effect of the combined effect of MGMT methylation and moderate tumor vascularity, as well as the lack of benefit of temozolomide in patients with a highly vascular tumor.In this study, we evaluated the benefit on survival of the combination of methylation of O6-methylguanine-DNA methyltransferase (MGMT) promotor gene and moderate vascularity in glioblastoma using a retrospective dataset of 123 patients from a multicenter cohort. MRI processing and calculation of relative cerebral blood volume (rCBV), used to define moderate- and high-vascular groups, were performed with the automatic ONCOhabitats method. We assessed the previously proposed rCBV threshold (10.7) and the new calculated ones (9.1 and 9.8) to analyze the association with survival for different populations according to vascularity and MGMT methylation status. We found that patients included in the moderate-vascular group had longer survival when MGMT is methylated (significant median survival difference of 174 days, p = 0.0129*). However, we did not find significant differences depending on the MGMT methylation status for the high-vascular group (p = 0.9119). In addition, we investigated the combined correlation of MGMT methylation status and rCBV with the prognostic effect of the number of temozolomide cycles, and only significant results were found for the moderate-vascular group. In conclusion, there is a lack of benefit of extending temozolomide treatment for patients with high vascular glioblastomas, even presenting MGMT methylation. Preliminary results suggest that patients with moderate vascularity and methylated MGMT glioblastomas would benefit more from prolonged adjuvant chemotherapy.M.A-T was supported by DPI2016-80054-R (Programa Estatal de Promocion del Talento y su Empleabilidad en I+D+i). This work was partially supported by the ALBATROSS project (National Plan for Scientific and Technical Research and Innovation 2017-2020, No. PID2019-104978RB-I00). This study was partially funded by the Fundacio La Marato TV3 (665/C/2013) (http://www.ccma.cat/tv3/marato/projectes-financats/2012/231/ Accessed on 8th September 2021). (JMGG); H2020-SC1-2016-CNECT Project (No. 727560) (JMGG), and H2020-SC1-BHC-2018-2020 (No. 825750) (JMGG). EFG was supported by the European Unions Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 844646 and South-Eastern Norway Regional Health Authority Grant 2021057.Álvarez-Torres, MDM.; Fuster García, E.; Balaña, C.; Puig, J.; Garcia-Gomez, JM. (2021). Lack of Benefit of Extending Temozolomide Treatment in Patients with High Vascular Glioblastoma with Methylated MGMT. Cancers. 13(21):1-14. https://doi.org/10.3390/cancers13215420S114132

Interferometric method of determining the refraction index of two-dimensional sonic crystals

[EN] Sonic crystals are defined as materials consisting of periodic distributions of acoustic scatterers in another medium with different elastic properties. These materials present two main acoustical features: they present ranges of frequencies where the acoustic wave propagation is forbidden and, moreover, they can be used to construct acoustical refractive devices. We present here an interferometric method of characterizing directly the refraction index of these materials. We focused our research on sonic crystals constructed with a periodic distribution of rigid cylinders in air. The interferometric method used is based on the acoustical analog of an optical device called Fresnel’s biprism. Our numerical predictions are in good agreement with the experimental results obtained and allow us to estimate the refraction index for very low frequencies. Moreover, in this range we show the nonlinear behavior in the dispersion relation refraction index versus frequency. Finally, we analyze the relationship between the refraction index and some typical sonic crystal parameters. In view of the results we can conclude that this method offers certain advantages with respect to the classical method used to obtain the refraction index in sonic crystals with airborne propagation: the phase delay method.This work has been partially supported by the Spanish Ministry of Science and Education Project No. MAT2007-03097 and partially supported by Generalitat Valenciana Project GV/2007/191. We would like to thank the R+D +i Linguistic Assistance Office at the Universidad Politécnica de Valencia for their help in revising this paper.Romero García, V.; Fuster García, E.; García-Raffi, LM.; Sánchez Pérez, JV.; Uris Martínez, A. (2007). Interferometric method of determining the refraction index of two-dimensional sonic crystals. Physical Review B. 75:2243051-2243058. https://doi.org/10.1103/PhysRevB.75.224305S224305122430587

A phenomenological model for sonic crystals based on artificial neural networks

[EN] A phenomenological model that simulates the acoustic attenuation behavior of sonic crystals is developed in this paper. The input of the model is a set of parameters that characterizes each experimental setup, and the output is a simulation of the associated attenuation spectrum. The model consists of a combination of a multiresolution analysis based on wavelet functions and a set of artificial neural networks. An optimized coupling of these tools allows us to drastically reduce the experimental data needed, and to obtain a fast computational model that can be used for technological purposes. © 2006 Acoustical Society of America.This research has been partially supported by the Generalitat Valenciana Spain, under Grant No. GV04B-371, by Comisión Interministerial de Ciencia y Tecnología of Spain, under Grant No. BFM2003-02302, and by Comisión Interministerial de Ciencia y Tecnología of Spain, Contract No. MAT 2003-04993-03.Fuster García, E.; Romero García, V.; Sánchez Pérez, JV.; García Raffi, LM.; Sánchez Pérez, EA. (2006). A phenomenological model for sonic crystals based on artificial neural networks. Journal of the Acoustical Society of America. 120(2):636-641. https://doi.org/10.1121/1.2217127S636641120

Local detection of microvessels in IDH-wildtype glioblastoma using relative cerebral blood volume: an imaging marker useful for astrocytoma grade 4 classification

[EN] Background The microvessels area (MVA), derived from microvascular proliferation, is a biomarker useful for high-grade glioma classification. Nevertheless, its measurement is costly, labor-intense, and invasive. Finding radiologic correlations with MVA could provide a complementary non-invasive approach without an extra cost and labor intensity and from the first stage. This study aims to correlate imaging markers, such as relative cerebral blood volume (rCBV), and local MVA in IDH-wildtype glioblastoma, and to propose this imaging marker as useful for astrocytoma grade 4 classification. Methods Data from 73 tissue blocks belonging to 17 IDH-wildtype glioblastomas and 7 blocks from 2 IDH-mutant astrocytomas were compiled from the Ivy GAP database. MRI processing and rCBV quantification were carried out using ONCOhabitats methodology. Histologic and MRI co-registration was done manually with experts' supervision, achieving an accuracy of 88.8% of overlay. Spearman's correlation was used to analyze the association between rCBV and microvessel area. Mann-Whitney test was used to study differences of rCBV between blocks with presence or absence of microvessels in IDH-wildtype glioblastoma, as well as to find differences with IDH-mutant astrocytoma samples. Results Significant positive correlations were found between rCBV and microvessel area in the IDH-wildtype blocks (p < 0.001), as well as significant differences in rCBV were found between blocks with microvascular proliferation and blocks without it (p < 0.0001). In addition, significant differences in rCBV were found between IDH-wildtype glioblastoma and IDH-mutant astrocytoma samples, being 2-2.5 times higher rCBV values in IDH-wildtype glioblastoma samples. Conclusions The proposed rCBV marker, calculated from diagnostic MRIs, can detect in IDH-wildtype glioblastoma those regions with microvessels from those without it, and it is significantly correlated with local microvessels area. In addition, the proposed rCBV marker can differentiate the IDH mutation status, providing a complementary non-invasive method for high-grade glioma classification.This work was funded by grants from the National Plan for Scientific and Technical Research and Innovation 2017-2020, No. PID2019-104978RB-I00) (JMGG); H2020-SC1-2016-CNECT Project (No. 727560) (JMGG), and H2020SC1-BHC-2018-2020 (No. 825750) (JMGG). M.A.T was supported by DPI201680054-R (Programa Estatal de Promocion del Talento y su Empleabilidad en I + D + i). EFG was supported by the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 844646. The funding body played no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.Álvarez-Torres, MDM.; Fuster García, E.; Juan-Albarracín, J.; Reynes, G.; Aparici-Robles, F.; Ferrer Lozano, J.; Garcia-Gomez, JM. (2022). Local detection of microvessels in IDH-wildtype glioblastoma using relative cerebral blood volume: an imaging marker useful for astrocytoma grade 4 classification. BMC Cancer. 22(1):1-13. https://doi.org/10.1186/s12885-021-09117-411322

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