Staff member

Manuel Lozano García

Postdoctoral Researcher
Biomedical Signal Processing and Interpretation
+34 934 020 559
Staff member publications

Lozano, M., Fiz, J. A., Jané, R., (2016). Automatic differentiation of normal and continuous adventitious respiratory sounds using ensemble empirical mode decomposition and instantaneous frequency IEEE Journal of Biomedical and Health Informatics 20, (2), 486-497

Differentiating normal from adventitious respiratory sounds (RS) is a major challenge in the diagnosis of pulmonary diseases. Particularly, continuous adventitious sounds (CAS) are of clinical interest because they reflect the severity of certain diseases. This study presents a new classifier that automatically distinguishes normal sounds from CAS. It is based on the multi-scale analysis of instantaneous frequency (IF) and envelope (IE) calculated after ensemble empirical mode decomposition (EEMD). These techniques have two major advantages over previous techniques: high temporal resolution is achieved by calculating IF-IE and a priori knowledge of signal characteristics is not required for EEMD. The classifier is based on the fact that the IF dispersion of RS signals markedly decreases when CAS appear in respiratory cycles. Therefore, CAS were detected by using a moving window to calculate the dispersion of IF sequences. The study dataset contained 1494 RS segments extracted from 870 inspiratory cycles recorded from 30 patients with asthma. All cycles and their RS segments were previously classified as containing normal sounds or CAS by a highly experienced physician to obtain a gold standard classification. A support vector machine classifier was trained and tested using an iterative procedure in which the dataset was randomly divided into training (65%) and testing (35%) sets inside a loop. The SVM classifier was also tested on 4592 simulated CAS cycles. High total accuracy was obtained with both recorded (94.6% ± 0.3%) and simulated (92.8% ± 3.6%) signals. We conclude that the proposed method is promising for RS analysis and classification.

Keywords: Diseases, Dispersion, Empirical mode decomposition, Feature extraction, Informatics, Support vector machines

Lozano, Manuel, Fiz, J. A., Jané, Raimon, (2016). Performance evaluation of the Hilbert–Huang transform for respiratory sound analysis and its application to continuous adventitious sound characterization Signal Processing 120, 99-116

Abstract The use of the Hilbert–Huang transform in the analysis of biomedical signals has increased during the past few years, but its use for respiratory sound (RS) analysis is still limited. The technique includes two steps: empirical mode decomposition (EMD) and instantaneous frequency (IF) estimation. Although the mode mixing (MM) problem of EMD has been widely discussed, this technique continues to be used in many RS analysis algorithms. In this study, we analyzed the MM effect in RS signals recorded from 30 asthmatic patients, and studied the performance of ensemble EMD (EEMD) and noise-assisted multivariate EMD (NA-MEMD) as means for preventing this effect. We propose quantitative parameters for measuring the size, reduction of MM, and residual noise level of each method. These parameters showed that EEMD is a good solution for MM, thus outperforming NA-MEMD. After testing different IF estimators, we propose Kay׳s method to calculate an EEMD-Kay-based Hilbert spectrum that offers high energy concentrations and high time and high frequency resolutions. We also propose an algorithm for the automatic characterization of continuous adventitious sounds (CAS). The tests performed showed that the proposed EEMD-Kay-based Hilbert spectrum makes it possible to determine CAS more precisely than other conventional time-frequency techniques.

Keywords: Hilbert–Huang transform, Ensemble empirical mode decomposition, Instantaneous frequency, Respiratory sounds, Continuous adventitious sounds

Lozano, M., Fiz, J. A., Jané, R., (2015). Análisis de sonidos adventicios continuos en pacientes asmáticos mediante el espectro de Hilbert CASEIB Proceedings XXXIII Congreso Anual de la Sociedad Española de Ingeniería Biomédica (CASEIB 2015) , Sociedad Española de Ingeniería Biomédica (Madrid, Spain) , 179-182

Los sonidos adventicios continuos (CAS) son uno de los principales síntomas del asma. Dada su importancia clínica, el análisis de estas señales requiere del uso de técnicas que permitan segmentarlas y caracterizarlas con una precisión alta. Sin embargo, la mayoría de técnicas propuestas anteriormente estaban basadas en el análisis de Fourier o wavelet, técnicas que tienen una resolución limitada a priori y son altamente dependientes de la amplitud de los CAS. En este estudio se presenta una técnica alternativa para el análisis de CAS basada en el espectro de Hilbert. El método presentado combina la descomposición empírica en modos por conjuntos con el estimador de Kay de la frecuencia instantánea, para obtener una representación tiempo-frecuencia con una alta concentración de energía y una resolución temporal y frecuencial elevada. Con el fin de mostrar las ventajas que ofrece el método presentado, se ha aplicado a cuatro señales de sonidos respiratorios registradas en pacientes asmáticos que contienen distintos tipos de CAS, reforzando la hipótesis confirmada en nuestro estudio previo de que el espectro de Hilbert permite segmentar y caracterizar los CAS con mayor precisión que otras técnicas tradicionales ampliamente utilizadas, como el espectrograma.

Navarro, S., Moleiro, V., Molina-Estevez, F. J., Lozano, M. L., Chinchon, R., Almarza, E., Quintana-Bustamante, O., Mostoslavsky, G., Maetzig, T., Galla, M., Heinz, N., Schiedlmeier, B., Torres, Y., Modlich, U., Samper, E., Río, P., Segovia, J. C., Raya, A., Güenechea, G., Izpisua-Belmonte, J. C., Bueren, J. A., (2014). Generation of iPSCs from genetically corrected Brca2 hypomorphic cells: Implications in cell reprogramming and stem cell therapy Stem Cells 32, (2), 436-446

Fanconi anemia (FA) is a complex genetic disease associated with a defective DNA repair pathway known as the FA pathway. In contrast to many other FA proteins, BRCA2 participates downstream in this pathway and has a critical role in homology-directed recombination (HDR). In our current studies, we have observed an extremely low reprogramming efficiency in cells with a hypomorphic mutation in Brca2 (Brca2Δ27/Δ27), that was associated with increased apoptosis and defective generation of nuclear RAD51 foci during the reprogramming process. Gene complementation facilitated the generation of Brca2Δ27/Δ27 induced pluripotent stem cells (iPSCs) with a disease-free FA phenotype. Karyotype analyses and comparative genome hybridization arrays of complemented Brca2Δ27/Δ27 iPSCs showed, however, the presence of different genetic alterations in these cells, most of which were not evident in their parental Brca2 Δ27/Δ27 mouse embryonic fibroblasts. Gene-corrected Brca2Δ27/Δ27 iPSCs could be differentiated in vitro toward the hematopoietic lineage, although with a more limited efficacy than WT iPSCs or mouse embryonic stem cells, and did not engraft in irradiated Brca2Δ27/Δ27 recipients. Our results are consistent with previous studies proposing that HDR is critical for cell reprogramming and demonstrate that reprogramming defects characteristic of Brca2 mutant cells can be efficiently overcome by gene complementation. Finally, based on analysis of the phenotype, genetic stability, and hematopoietic differentiation potential of gene-corrected Brca2Δ27/Δ27 iPSCs, achievements and limitations in the application of current reprogramming approaches in hematopoietic stem cell therapy are also discussed.

Keywords: Bone marrow aplasia, Cellular therapy, Fanconi anemia, Gene therapy, Hematopoietic stem cells, Induced pluripotent stem cells

Fiz, J. A., Jané, R., Lozano, M., Gómez, R., Ruiz, J., (2014). Detecting unilateral phrenic paralysis by acoustic respiratory analysis PLoS ONE 9, (4), e93595

The consequences of phrenic nerve paralysis vary from a considerable reduction in respiratory function to an apparently normal state. Acoustic analysis of lung sound intensity (LSI) could be an indirect non-invasive measurement of respiratory muscle function, comparing activity on the two sides of the thoracic cage. Lung sounds and airflow were recorded in ten males with unilateral phrenic paralysis and ten healthy subjects (5 men/5 women), during progressive increasing airflow maneuvers. Subjects were in sitting position and two acoustic sensors were placed on their back, on the left and right sides. LSI was determined from 1.2 to 2.4 L/s between 70 and 2000 Hz. LSI was significantly greater on the normal (19.3±4.0 dB) than the affected (5.7±3.5 dB) side in all patients (p = 0.0002), differences ranging from 9.9 to 21.3 dB (13.5±3.5 dB). In the healthy subjects, the LSI was similar on both left (15.1±6.3 dB) and right (17.4±5.7 dB) sides (p = 0.2730), differences ranging from 0.4 to 4.6 dB (2.3±1.6 dB). There was a positive linear relationship between the LSI and the airflow, with clear differences between the slope of patients (about 5 dB/L/s) and healthy subjects (about 10 dB/L/s). Furthermore, the LSI from the affected side of patients was close to the background noise level, at low airflows. As the airflow increases, the LSI from the affected side did also increase, but never reached the levels seen in healthy subjects. Moreover, the difference in LSI between healthy and paralyzed sides was higher in patients with lower FEV1 (%). The acoustic analysis of LSI is a relevant non-invasive technique to assess respiratory function. This method could reinforce the reliability of the diagnosis of unilateral phrenic paralysis, as well as the monitoring of these patients.

Lozano, M., Fiz, J., Jané, R., (2014). Análisis de la intensidad de los sonidos respiratorios para el diagnóstico de la parálisis frénica unilateral CASEIB Proceedings XXXII Congreso Anual de la Sociedad Española de Ingeniería Biomédica (CASEIB 2014) , Sociedad Española de Ingeniería Biomédica (Barcelona, Spain) , 1-4

(ISR) es una medida indirecta y no invasiva de la función respiratoria, que permite comparar la actividad en los dos hemitórax de los pacientes con parálisis frénica unilateral. Se registraron los sonidos y el flujo respiratorio en 10 hombres con parálisis frénica unilateral y 10 sujetos sanos (5 hombres/5 mujeres) en posición sentada. Se colocaron 2 micrófonos de contacto en la espalda, uno a cada lado de la columna. La ISR se calculó en el rango frecuencial 70-2000 Hz a partir de la densidad espectral de potencia y para flujos entre 1,2 y 2,4 l/s. Se encontró que las diferencias en la ISR media de los dos hemitórax era significativamente mayor en los pacientes (13.5 dB) que en los sujetos sanos (2.3 dB). Además, se comprobó que esa diferencia era mayor en pacientes con un volumen espiratorio forzado en el primer segundo menor. Por lo tanto, el análisis acústico de la ISR es una técnica no invasiva muy útil para valorar la función respiratoria. Esta técnica puede mejorar la fiabilidad en el diagnóstico de la parálisis frénica unilateral así como la monitorización a largo plazo de estos pacientes.

Lozano, M., Fiz, J. A., Jané, R., (2014). Analysis of normal and continuous adventitious sounds for the assessment of asthma IFMBE Proceedings XIII Mediterranean Conference on Medical and Biological Engineering and Computing 2013 (ed. Roa Romero, Laura M.), Springer International Publishing (London, UK) 41, 981-984

Assessment of asthma is a difficult procedure which is based on the correlation of multiple factors. A major component in the diagnosis of asthma is the assessment of BD response, which is performed by traditional spirometry. In this context, the analysis of respiratory sounds (RS) provides relevant and complementary information about the function of the respiratory system. In particular, continuous adventitious sounds (CAS), such as wheezes, contribute to assess the severity of patients with obstructive diseases. On the other hand, the intensity of normal RS is dependent on airflow level and, therefore, it changes depending on the level of obstruction. This study proposes a new approach to RS analysis for the assessment of asthmatic patients, by combining the quantification of CAS and the analysis of the changes in the normal sound intensity-airflow relationship. According to results obtained from three patients with different characteristics, the proposed technique seems more sensitive and promising for the assessment of asthma.

Keywords: Asthma, Bronchodilator response, Continuous adventitious sound, Respiratory sound intensity, Wheezes

Lozano, M., Fiz, J. A., Jané, R., (2013). Estimation of instantaneous frequency from empirical mode decomposition on respiratory sounds analysis Engineering in Medicine and Biology Society (EMBC) 35th Annual International Conference of the IEEE , IEEE (Osaka, Japan) , 981-984

Instantaneous frequency (IF) calculated by empirical mode decomposition (EMD) provides a novel approach to analyze respiratory sounds (RS). Traditionally, RS have been analyzed using classical time-frequency distributions, such as short-time Fourier transform (STFT) or wavelet transform (WT). However, EMD has become a powerful tool for nonlinear and non-stationary data analysis. IF estimated by EMD has two major advantages: its high temporal resolution and the fact that a priori knowledge of the signal characteristics is not required. In this study, we have estimated IF by EMD on real RS signals in order to identify continuous adventitious sounds (CAS), such as wheezes, within inspiratory sounds cycles. We show that there are differences in IF distribution among frequency scales of RS signal when CAS are within RS. Therefore, a new method for RS analysis and classification may be developed by combining both EMD and IF.

Lozano, M., Fiz, J.A., Jané, R., (2012). Análisis multicanal de sonidos respiratorios en acústica pulmonar: aplicación clínica en pacientes asmáticos Libro de Actas XXX CASEIB 2012 XXX Congreso Anual de la Sociedad Española de Ingeniería Biomédica (CASEIB2012) , Sociedad Española de Ingeniería Biomédica (San Sebastián, Spain) , 1-4

En este trabajo se ha visto que la evaluación de la potencia media de las señales de sonidos respiratorios antes y después de aplicar un fármaco broncodilatador puede reportar información importante sobre el estado y los cambios producidos en el sistema respiratorio. Se ha realizado y puesto a punto un protocolo de registro multicanal de acústica pulmonar mediante la colocación de 5 micrófonos de contacto: uno traqueal y cuatro micrófonos colocados en el tórax posterior. Mediante el análisis de las curvas intensidad-flujo respiratorio se han observado cambios significativos de intensidad a niveles de flujo elevados y en pacientes con una PBD negativa. Es en este grupo de pacientes, no respondedores, donde la técnica propuesta puede aportar información de interés clínico complementaria a la proporcionada por la espirometría clásica.

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