Evaluación no invasiva de la función muscular respiratoria mediante el análisis de la señal mecanomiográfica en pacientes con enfermedad pulmonar obstructiva crónica

El estudio y evaluación de la función muscular respiratoria en enfermedades respiratorias a través de técnicas no invasivas representa un tema de gran interés, dado que hasta la fecha no existen métodos satisfactorios aplicables en situaciones clínicas. En la enfermedad pulmonar obstructiva crónica (EPOC), el trabajo mecánico de los músculos respiratorios aumenta dando lugar a la fatiga, disminución de los movimientos de la caja torácica, y por tanto una disminución de la eficiencia muscular respiratoria. Es conocido que el músculo diafragma, principal responsable de la actividad mecánica respiratoria, al igual que otros músculos esqueléticos vibra lateralmente durante su contracción. De ahí, que estas vibraciones puedan ser registradas mediante micrófonos, sensores piezoeléctricos o acelerómetros posicionados encima de la pared inferior del pecho en la zona de aposición del diafragma con la caja torácica. El registro de estas vibraciones da lugar a la señal mecanomiográfica del diafragma (MMGdi). El principal objetivo de esta tesis ha sido el estudio y caracterización no invasiva de la función muscular respiratoria en pacientes con EPOC a través de la señal MMGdi registrada mediante acelerómetros posicionados entre el séptimo y octavo espacios intercostales, en la línea axilar izquierda y derecha del cuerpo durante la realización de los protocolos respiratorios de carga incremental progresiva y de flujo incremental progresivo. Para mejorar la estimación de la amplitud de la señal MMGdi se han propuesto tres nuevos índices, que tienen en cuenta la naturaleza aleatoria y el ruido asociado en las señales MMGdi, y están basados en: el algoritmo de Lempel-Ziv (LZM), la entropía aproximada (fApEn), y la entropía muestral (fSampEn). Todos ellos son calculados con intervalos de cuantificación fijos y empleando ventanas móviles. Los resultados obtenidos con éstos índices han permitido estimar con mayor fiabilidad y robustez la amplitud de las señales MMGdi, en relación a los métodos clásicos utilizados en el estudio de señales miográficas. El estudio del valor medio de los parámetros analizados ha mostrado, que existe una tendencia incremental de éste en los parámetros de amplitud, y una tendencia decreciente en los parámetros frecuenciales (frecuencias media y máxima), con el incremento de la carga y/o flujo. En este sentido, se ha observado que el valor medio es mayor cuanto mayor es la severidad del paciente con EPOC. Por otra parte, se ha observado que existe una fuerte correlación entre los parámetros de amplitud y la presión inspiratoria máxima en el protocolo de flujo incremental progresivo, con una tendencia decreciente con la severidad. Del mismo modo la eficiencia muscular respiratoria, evaluada como la relación entre la fuerza que producen los músculos respiratorios (la presión inspiratoria en boca) y lo que gastan o necesitan para producir esta presión (la vibración de los músculos respiratorios evaluada mediante las señales MMGdi), ha mostrado en general una tendencia decreciente con el aumento de la severidad. Finalmente, los resultados que se desprenden de esta tesis indican que el estudio de la señal MMGdi representa una herramienta útil con un gran potencial para evaluar el grado de la severidad presente en sujetos con EPOC y su relación con la debilidad de la musculatura respiratoria, y por tanto su aplicación en estudios clínicos podría ser de gran ayuda para evaluar el desarrollo de la EPOC.The study and evaluation of the respiratory muscles function in people who suffer from respiratory diseases can be evaluated through the use of noninvasive techniques. This is a topic of great interest considering there are currently no existing methods that can be successfully applied in clinical situations. In chronic obstructive pulmonary disease (COPD), the mechanical work of the respiratory muscles increases, which could lead to muscular fatigue, decreased movement of the ribcage, and, therefore, a decrease in the respiratory muscle efficiency. The diaphragm muscle is the principal muscle of inspiration and the main mechanical responsible for the ventilation. Similar to other skeletal muscles the diaphragm laterally vibrates during its contraction. These vibrations can be recorded by microphones, piezoelectric sensors or accelerometers, which are placed above the lower chest wall in the area of apposition of the diaphragm to the ribcage. The record of these vibrations is known as mechanomyographic signal of the diaphragm muscle (MMGdi). The main objective of this thesis has been the study and noninvasive characterization of the respiratory muscles function in patients with COPD. This characterization has been made possible through the use of MMGdi signals recorded by accelerometers placed between the seventh and eighth intercostals spaces on the left and right anterior axillary lines of the body during two respiratory protocols. The first protocol is called progressive incremental load protocol and the second one progressive incremental flow protocol. In this thesis three new indices have been proposed to improve the MMGdi amplitude estimation. These indices take into account the random nature and the associated noise in the MMGdi signals, and are based on the: Lempel-Ziv algorithm (MLZ), approximate entropy (fApEn), and sample entropy (fSampEn). All of them are calculated with fixed quantization intervals and using moving windows. The obtained results with these new indices have shown improved reliability and robustness in the MMGdi amplitude estimation in comparison with classic methods used to study myographic signals. The study of the mean value of the analyzed parameters has shown an increasing trend of the amplitude parameters and a decreasing trend of the frequency parameters (mean and maximum frequencies) with increasing load and/or flow. Furthermore, we found that there was a direct relationship between these mean values and the severity of COPD; hence, the greater the mean value, the greater the severity of COPD. Moreover, we have seen that there is a strong correlation between the amplitude parameters and the maximum inspiratory pressure in the progressive incremental flow protocol with a decreasing trend as the severity of the patients increases. Likewise, the respiratory muscle efficiency, evaluated as the ratio between the force produced by the respiratory muscles (mouth inspiratory pressure) and what they need to produce this pressure (the vibration of respiratory muscles assessed by MMGdi signals), has also shown a generally decreasing trend as the severity of patients increases. Finally, the results of this thesis suggest that the study of the MMGdi signal is a useful tool with great potential to assess the relationship between respiratory muscle weakness and the degree of severity in patients with COPD. Therefore, the application of this innovative tool in clinical studies may be helpful to assess the development of COPD

Surface mechanomyography and electromyography provide non-invasive indices of inspiratory muscle force and activation in healthy subjects

The current gold standard assessment of human inspiratory muscle function involves using invasive measures of transdiaphragmatic pressure (Pdi) or crural diaphragm electromyography (oesEMGdi). Mechanomyography is a non-invasive measure of muscle vibration associated with muscle contraction. Surface electromyogram and mechanomyogram, recorded transcutaneously using sensors placed over the lower intercostal spaces (sEMGlic and sMMGlic respectively), have been proposed to provide non-invasive indices of inspiratory muscle activation, but have not been directly compared to gold standard Pdi and oesEMGdi measures during voluntary respiratory manoeuvres. To validate the non-invasive techniques, the relationships between Pdi and sMMGlic, and between oesEMGdi and sEMGlic were measured simultaneously in 12 healthy subjects during an incremental inspiratory threshold loading protocol. Myographic signals were analysed using fixed sample entropy (fSampEn), which is less influenced by cardiac artefacts than conventional root mean square. Strong correlations were observed between: mean Pdi and mean fSampEn |sMMGlic| (left, 0.76; right, 0.81), the time-integrals of the Pdi and fSampEn |sMMGlic| (left, 0.78; right, 0.83), and mean fSampEn oesEMGdi and mean fSampEn sEMGlic (left, 0.84; right, 0.83). These findings suggest that sMMGlic and sEMGlic could provide useful non-invasive alternatives to Pdi and oesEMGdi for the assessment of inspiratory muscle function in health and disease.Peer ReviewedPostprint (published version

Influence of parameter selection in fixed sample entropy of surface diaphragm electromyography for estimating respiratory activity

Fixed sample entropy (fSampEn) is a robust technique that allows the evaluation of inspiratory effort in diaphragm electromyography (EMGdi) signals, and has potential utility in sleep studies. To appropriately estimate respiratory effort, fSampEn requires the adjustment of several parameters. The aims of the present study were to evaluate the influence of the embedding dimension m, the tolerance value r, the size of the moving window, and the sampling frequency, and to establish recommendations for estimating the respiratory activity when using the fSampEn on surface EMGdi recorded for different inspiratory efforts. Values of m equal to 1 and r ranging from 0.1 to 0.64, and m equal to 2 and r ranging from 0.13 to 0.45, were found to be suitable for evaluating respiratory activity. fSampEn was less affected by window size than classical amplitude parameters. Finally, variations in sampling frequency could influence fSampEn results. In conclusion, the findings suggest the potential utility of fSampEn for estimating muscle respiratory effort in further sleep studies.Peer ReviewedPostprint (published version

Engineered macroscale cardiac constructs elicit human myocardial tissue-like functionality

In vitro surrogate models of human cardiac tissue hold great promise in disease modeling, cardiotoxicity testing, and future applications in regenerative medicine. However, the generation of engineered human cardiac constructs with tissue-like functionality is currently thwarted by difficulties in achieving efficient maturation at the cellular and/or tissular level. Here, we report on the design and implementation of a platform for the production of engineered cardiac macrotissues from human pluripotent stem cells (PSCs), which we term “CardioSlice.” PSC-derived cardiomyocytes, together with human fibroblasts, are seeded into large 3D porous scaffolds and cultured using a parallelized perfusion bioreactor with custom-made culture chambers. Continuous electrical stimulation for 2 weeks promotes cardiomyocyte alignment and synchronization, and the emergence of cardiac tissue-like properties. These include electrocardiogram-like signals that can be readily measured on the surface of CardioSlice constructs, and a response to proarrhythmic drugs that is predictive of their effect in human patients.Peer ReviewedPostprint (published version

Relación entre la presión inspiratoria pico y la activación mecánica de los músculos inspiratorios durante respiración tranquila en pacientes con EPOC

En la enfermedad pulmonar obstructiva crónica (EPOC) la fuerza muscular inspiratoria (FMI) y la eficiencia mecánica de los músculos inspiratorios (EMMI) podrían verse reducidas como consecuencia de la hiperinsuflación. En este trabajo se registraron la presión inspiratoria en boca (PIpico) y la activación mecánica de los músculos inspiratorios en 10 pacientes EPOC severos y muy severos, durante respiración tranquila. Para determinar la activación mecánica de los músculos inspiratorios se empleó la señal mecanomiográfica diafragmática: MMGdi. La amplitud de la señal MMGdi fue estimada a través de índices lineales (ARV: valor rectificado medio) y no lineales (MLZ: Lempel-Ziv multiestado, y fSampEn: entropía muestral con valores de tolerancia fijos). Nuestra hipótesis es que el ratio entre PIpico, que refleja la FMI, y la amplitud de la señal MMGdi constituye una expresión de la EMMI. Los resultados obtenidos muestran ligeras diferencias entre la PIpico registrada en EPOC severos y muy severos, así como una correlación débil a moderada con los parámetros de función pulmonar y los índices estudiados. Sin embargo, mientras mayor es el grado de severidad (que supone un mayor grado de hiperinsuflación) mayor es el nivel de activación mecánica de los músculos inspiratorios. La activación mecánica de los músculos inspiratorios y la EMMI estimadas mediante MLZ estuvieron mejor correlacionadas con la función pulmonar que ARV y fSampEn. Por consiguiente, la estimación de la actividad mecánica del diafragma mediante el MLZ de la señal MMGdi podría mejorar la estimación no invasiva de la FMI y la EMMI, incluso para niveles muy bajos de esfuerzo inspiratorio.Peer ReviewedPostprint (author’s final draft

Evaluation of a wearable device to determine cardiorespiratory parameters from surface diaphragm electromyography

Using wearable devices in clinical routines could reduce healthcare costs and improve the quality of assessment in patients with chronic respiratory diseases. The purpose of this study is to evaluate the capability of a Shimmer3 wearable device device to extract reliable cardiorespiratory parameters from surface diaphragm electromyography (EMGdi). Twenty healthy volunteers underwent an incremental load respiratory test whilst EMGdi was recorded with a Shimmer3 wearable device (EMGdiW). Simultaneously, a second EMGdi (EMGdiL), the inspiratory mouth pressure (Pmouth) and the lead-I electrocardiogram (ECG) were recorded via a standard wired laboratory acquisition system. Different cardiorespiratory parameters have been extracted from both EMGdiW and EMGdiL signals.: heart rate, respiratory rate, respiratory muscle activity and mean frequency of EMGdi signals. Alongside these, similar parameters were also extracted from reference signals (Pmouth and ECG). High correlations were found between the data extracted from the EMGdiW and the reference signal data: heart rate (R = 0.947), respiratory rate (R = 0.940), respiratory muscle activity (R = 0.877), and mean frequency (R = 0.895). Moreover, similar increments in EMGdiW and EMGdiL activity were observed when Pmouth was raised, enabling the study of respiratory muscle activation. In summary, the Shimmer3 device is a promising and cost-effective solution for ambulatory monitoring of respiratory muscle function in chronic respiratory diseases.Postprint (author's final draft

Reducción de interferencia cardíaca en señales MMG diafragmáticas de un protocolo de carga incremental sostenida mediante filtrado adaptativo RLS

En este trabajo se aplicó el filtrado adaptativo empleando el algoritmo RLS para reducir la interferencia de origen cardíaco en las señales mecanomiográficas diafragmáticas (MMGdi) registradas durante un protocolo de carga incremental sostenida. La señal MMGdi fue dividida en tramos con y sin ruido cardíaco, CRC y SRC, respectivamente. En cada tramo se estudio el comportamiento de la densidad espectral de potencia (DEP), y los parámetros de amplitud RMS y ARV para cada una de las cargas inspiratorias que conforman el test. Los resultados obtenidos, empleando filtro adaptativo de orden =50, con el algoritmo RLS y valores de - = 1, permiten reducir considerablemente la interferencia cardíaca en las señales MMGdi.Postprint (published version

Evaluación de diferentes algoritmos adaptativos para la atenuación de la interferencia cardiaca en señales mecanomiográficas simuladas

El estudio de la señal mecanomiográfica del músculo diafragma (MMGdi) es una técnica utilizada para evaluar el esfuerzo muscular respiratorio. El estudio de la relación entre los parámetros de amplitud y frecuencia de esta señal con el esfuerzo respiratorio realizado es de gran interés para investigadores y médicos debido a su potencial de diagnóstico sobre la función muscular respiratoria. Las señales MMGdi se ven afectas por una componente interferente correspondiente a la actividad vibratoria cardíaca o interferencia mecanocardiográfica (MCG). Para reducir o atenuar esta actividad se puede utilizar una cancelación adaptativa de interferencias (CAI). En este trabajo se ha evaluado el esquema de CAI propuesto mediante una señal MMGdi sintética generada con amplitud y frecuencia controlada a la que se le ha añadido ruido MCG real adquirido durante apnea. El coeficiente de correlación de Pearson (r) entre la amplitud y la frecuencia teóricas, y la amplitud y la frecuencia evaluadas mediante el RMS y la frecuencia media del espectro, respectivamente, disminuye considerablemente cuando se añade el ruido cardíaco a la señal MMGdi sintética: pasa de 0.95 a 0.87 para la amplitud, y de 0.97 a 0.76 para la frecuencia. Con los algoritmos de CAI propuestos el efecto del ruido MCG sobre la actividad MMGdi se reduce considerablemente (r de 0.93 para la amplitud y 0.97 para la frecuencia media). El método de CAI propuesto en este trabajo es una técnica adecuada para atenuar la interferencia MCG en señales MMGdi.Postprint (published version

Evaluation of Respiratory Muscle Activity by Means of Concentric Ring Electrodes

© 2021 IEEE. Personal use of this material is permitted. Permissíon from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertisíng or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.[EN] Surface electromyography (sEMG) can be used for the evaluation of respiratory muscle activity. Recording sEMG involves the use of surface electrodes in a bipolar configuration. However, electrocardiographic (ECG) interference and electrode orientation represent considerable drawbacks to bipolar acquisition. As an alternative, concentric ring electrodes (CREs) can be used for sEMG acquisition and offer great potential for the evaluation of respiratory muscle activity due to their enhanced spatial resolution and simple placement protocol, which does not depend on muscle fiber orientation. The aim of this work was to analyze the performance of CREs during respiratory sEMG acquisitions. Respiratory muscle sEMG was applied to the diaphragm and sternocleidomastoid muscles using a bipolar and a CRE configuration. Thirty-two subjects underwent four inspiratory load spontaneous breathing tests which was repeated after interchanging the electrode positions. We calculated parameters such as (1) spectral power and (2) median frequency during inspiration, and power ratios of inspiratory sEMG without ECG in relation to (3) basal sEMG without ECG (R-ins/noise), (4) basal sEMG with ECG (R-ins/cardio) and (5) expiratory sEMG without ECG (R-ins/exp). Spectral power, R-ins/noise and R-ins/cardio increased with the inspiratory load. Significantly higher values (p < 0.05) of R-ins/cardio and significantly higher median frequencies were obtained for CREs. R-ins/noise and R-ins/exp were higher for the bipolar configuration only in diaphragm sEMG recordings, whereas no significant differences were found in the sternocleidomastoid recordings. Our results suggest that the evaluation of respiratory muscle activity by means of sEMG can benefit from the remarkably reduced influence of cardiac activity, the enhanced detection of the shift in frequency content and the axial isotropy of CREs which facilitates its placement.This work was supported in part by the CERCA Program/Generalitat de Catalunya, in part by the Secretaria d'Universitats i Recerca de la Generalitat de Catalunya under Grant GRC 2017 SGR 01770, in part by the Spanish Grants RTI2018-098472-B-I00, RTI2018-094449-A-I00-AR (MCIU/AEI/FEDER, UE) and DPI2015-68397-R (MINECO/FEDER), and in part by the Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN, Instituto de Salud Carlos III/FEDER). The first author was supported by the IFARHU-SENACYT Scholarship Program from the Panama Government under Grant 270-2012-273.Estrada-Petrocelli, L.; Torres, A.; Sarlabous, L.; Ràfols-De-Urquía, M.; Ye Lin, Y.; Prats-Boluda, G.; Jané, R.... (2021). Evaluation of Respiratory Muscle Activity by Means of Concentric Ring Electrodes. IEEE Transactions on Biomedical Engineering. 68(3):1005-1014. https://doi.org/10.1109/TBME.2020.3012385S1005101468

Virtual Reality-Based Early Neurocognitive Stimulation in Critically Ill Patients : A Pilot Randomized Clinical Trial

This study focuses on the application of a non-immersive virtual reality (VR)-based neurocognitive intervention in critically ill patients. Our aim was to assess the feasibility of direct outcome measures to detect the impact of this digital therapy on patients' cognitive and emotional outcomes. Seventy-two mechanically ventilated adult patients were randomly assigned to the "treatment as usual" (TAU, n = 38) or the "early neurocognitive stimulation" (ENRIC, n = 34) groups. All patients received standard intensive care unit (ICU) care. Patients in the ENRIC group also received adjuvant neurocognitive stimulation during the ICU stay. Outcome measures were a full neuropsychological battery and two mental health questionnaires. A total of 42 patients (21 ENRIC) completed assessment one month after ICU discharge, and 24 (10 ENRIC) one year later. At one-month follow-up, ENRIC patients had better working memory scores (p = 0.009, d = 0.363) and showed up to 50% less non-specific anxiety (11.8% vs. 21.1%) and depression (5.9% vs. 10.5%) than TAU patients. A general linear model of repeated measures reported a main effect of group, but not of time or group-time interaction, on working memory, with ENRIC patients outperforming TAU patients (p = 0.008, η 2 = 0.282). Our results suggest that non-immersive VR-based neurocognitive stimulation may help improve short-term working memory outcomes in survivors of critical illness. Moreover, this advantage could be maintained in the long term. An efficacy trial in a larger sample of participants is feasible and must be conducted