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by Keyword: Non-invasive


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Rafols-de-Urquia, M., Estrada, L., Estevez-Piorno, J., Sarlabous, L., Jane, R., Torres, A., (2019). Evaluation of a wearable device to determine cardiorespiratory parameters from surface diaphragm electromyography IEEE Journal of Biomedical and Health Informatics Early Access

The use of 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 capacity of a Shimmer3 wearable 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), inspiratory mouth pressure (Pmouth) and lead-I electrocardiogram (ECG) were recorded via a standard wired laboratory acquisition system. Different cardiorespiratory parameters were 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 the ambulatory monitoring of respiratory muscle function in chronic respiratory diseases. IEEE

Keywords: Cardiorespiratory monitoring, Chronic respiratory diseases, Fixed sample entropy, Non-invasive respiratory monitoring, Surface diaphragm electromyography, Wearable wireless device


Sarlabous, L., Estrada, L., Cerezo-Hernández, A., Leest, Sietske V. D., Torres, A., Jané, R., Duiverman, M., Garde, Ainara, (2019). Electromyography-based respiratory onset detection in COPD patients on non-invasive mechanical ventilation Entropy 21, (3), 258

To optimize long-term nocturnal non-invasive ventilation in patients with chronic obstructive pulmonary disease, surface diaphragm electromyography (EMGdi) might be helpful to detect patient-ventilator asynchrony. However, visual analysis is labor-intensive and EMGdi is heavily corrupted by electrocardiographic (ECG) activity. Therefore, we developed an automatic method to detect inspiratory onset from EMGdi envelope using fixed sample entropy (fSE) and a dynamic threshold based on kernel density estimation (KDE). Moreover, we combined fSE with adaptive filtering techniques to reduce ECG interference and improve onset detection. The performance of EMGdi envelopes extracted by applying fSE and fSE with adaptive filtering was compared to the root mean square (RMS)-based envelope provided by the EMG acquisition device. Automatic onset detection accuracy, using these three envelopes, was evaluated through the root mean square error (RMSE) between the automatic and mean visual onsets (made by two observers). The fSE-based method provided lower RMSE, which was reduced from 298 ms to 264 ms when combined with adaptive filtering, compared to 301 ms provided by the RMS-based method. The RMSE was negatively correlated with the proposed EMGdi quality indices. Following further validation, fSE with KDE, combined with adaptive filtering when dealing with low quality EMGdi, indicates promise for detecting the neural onset of respiratory drive.

Keywords: Fixed sample entropy, Adaptive filtering, Root mean square, Diaphragm electromyography, Non-invasive mechanical ventilation, Chronic obstructive pulmonary disease


Lozano-García, M., Estrada, L., Jané, R., (2019). Performance evaluation of fixed sample entropy in myographic signals for inspiratory muscle activity estimation Entropy 21, (2), 183

Fixed sample entropy (fSampEn) has been successfully applied to myographic signals for inspiratory muscle activity estimation, attenuating interference from cardiac activity. However, several values have been suggested for fSampEn parameters depending on the application, and there is no consensus standard for optimum values. This study aimed to perform a thorough evaluation of the performance of the most relevant fSampEn parameters in myographic respiratory signals, and to propose, for the first time, a set of optimal general fSampEn parameters for a proper estimation of inspiratory muscle activity. Different combinations of fSampEn parameters were used to calculate fSampEn in both non-invasive and the gold standard invasive myographic respiratory signals. All signals were recorded in a heterogeneous population of healthy subjects and chronic obstructive pulmonary disease patients during loaded breathing, thus allowing the performance of fSampEn to be evaluated for a variety of inspiratory muscle activation levels. The performance of fSampEn was assessed by means of the cross-covariance of fSampEn time-series and both mouth and transdiaphragmatic pressures generated by inspiratory muscles. A set of optimal general fSampEn parameters was proposed, allowing fSampEn of different subjects to be compared and contributing to improving the assessment of inspiratory muscle activity in health and disease.

Keywords: Electromyography, Fixed sample entropy, Mechanomyography, Non-invasive physiological measurements, Oesophageal electromyography, Respiratory muscle


Marrugo-Ramírez, José, Mir, M., Samitier, Josep, (2018). Blood-based cancer biomarkers in liquid biopsy: A promising non-invasive alternative to tissue biopsy International Journal of Molecular Sciences , 19, (10), 2877

Cancer is one of the greatest threats facing our society, being the second leading cause of death globally. Currents strategies for cancer diagnosis consist of the extraction of a solid tissue from the affected area. This sample enables the study of specific biomarkers and the genetic nature of the tumor. However, the tissue extraction is risky and painful for the patient and in some cases is unavailable in inaccessible tumors. Moreover, a solid biopsy is expensive and time consuming and cannot be applied repeatedly. New alternatives that overcome these drawbacks are rising up nowadays, such as liquid biopsy. A liquid biopsy is the analysis of biomarkers in a non-solid biological tissue, mainly blood, which has remarkable advantages over the traditional method; it has no risk, it is non-invasive and painless, it does not require surgery and reduces cost and diagnosis time. The most studied cancer non-invasive biomarkers are circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and exosomes. These circulating biomarkers play a key role in the understanding of metastasis and tumorigenesis, which could provide a better insight into the evolution of the tumor dynamics during treatment and disease progression. Improvements in isolation technologies, based on a higher grade of purification of CTCs, exosomes, and ctDNA, will provide a better characterization of biomarkers and give rise to a wide range of clinical applications, such as early detection of diseases, and the prediction of treatment responses due to the discovery of personalized tumor-related biomarkers

Keywords: Liquid biopsy, Cancer, Biomarkers, Non-invasive, Circulant tumor DNA (ctDNA), Circulant tumor cells (CTC)


Estrada, L., Torres, A., Sarlabous, L., Jané, R., (2017). Influence of parameter selection in fixed sample entropy of surface diaphragm electromyography for estimating respiratory activity Entropy 19, (9), 460

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.

Keywords: Fixed sample entropy (fSampEn), Non-invasive respiratory monitoring, Respiratory activity, Respiratory effort, Surface diaphragm electromyography


Farré, R., Navajas, D., (2016). Forced oscillation: A poorly exploited tool for simply assessing respiratory function in children Respirology , 21, (6), 982-983

Guamán, Ana V., Carreras, Alba, Calvo, Daniel, Agudo, Idoya, Navajas, Daniel, Pardo, Antonio, Marco, Santiago, Farré, Ramon, (2012). Rapid detection of sepsis in rats through volatile organic compounds in breath Journal of Chromatography B , 881-882, 76-82

Background: Sepsis is one of the main causes of death in adult intensive care units. The major drawbacks of the different methods used for its diagnosis and monitoring are their inability to provide fast responses and unsuitability for bedside use. In this study, performed using a rat sepsis model, we evaluate breath analysis with Ion Mobility Spectrometry (IMS) as a fast, portable and non-invasive strategy. Methods: This study was carried out on 20 Sprague-Dawley rats. Ten rats were injected with lipopolysaccharide from Escherichia coli and ten rats were IP injected with regular saline. After a 24-h period, the rats were anaesthetized and their exhaled breaths were collected and measured with IMS and SPME-gas chromatography/mass spectrometry (SPME-GC/MS) and the data were analyzed with multivariate data processing techniques. Results: The SPME-GC/MS dataset processing showed 92% accuracy in the discrimination between the two groups, with a confidence interval of between 90.9% and 92.9%. Percentages for sensitivity and specificity were 98% (97.5–98.5%) and 85% (84.6–87.6%), respectively. The IMS database processing generated an accuracy of 99.8% (99.7–99.9%), a specificity of 99.6% (99.5–99.7%) and a sensitivity of 99.9% (99.8–100%). Conclusions: IMS involving fast analysis times, minimum sample handling and portable instrumentation can be an alternative for continuous bedside monitoring. IMS spectra require data processing with proper statistical models for the technique to be used as an alternative to other methods. These animal model results suggest that exhaled breath can be used as a point-of-care tool for the diagnosis and monitoring of sepsis.

Keywords: Sepsis, Volatile organic compounds, Ion mobility spectrometer, Rat model, Bedside patient systems, Non-invasive detection


Carreras, Alba, Wang, Yang, Gozal, David, Montserrat, Josep M., Navajas, Daniel, Farre, Ramon, (2011). Non-invasive system for applying airway obstructions to model obstructive sleep apnea in mice Respiratory Physiology & Neurobiology , 175, (1), 164-168

Obstructive sleep apnea (OSA) is characterized by recurrent upper airway obstructions during sleep. The most common animal model of OSA is based on subjecting rodents to intermittent hypoxic exposures and does not mimic important OSA features, such as recurrent hypercapnia and increased inspiratory efforts. To circumvent some of these issues, a novel murine model involving non-invasive application of recurrent airway obstructions was developed. An electronically controlled airbag system is placed in front of the mouse's snout, whereby inflating the airbag leads to obstructed breathing and spontaneous breathing occurs with the airbag deflated. The device was tested on 29 anesthetized mice by measuring inspiratory effort and arterial oxygen saturation (SaO(2)). Application of recurrent obstructive apneas (6s each, 120/h) for 6h resulted in SaO(2) oscillations to values reaching 84.4 +/- 2.5% nadir, with swings mimicking OSA patients. This novel system, capable of applying controlled recurrent airway obstructions in mice, is an easy-to-use tool for investigating pertinent aspects of OSA.

Keywords: Animal model, Upper airway Obstruction, Mouse model, Non-invasive system, Model sleep apnea, Respiratory disease


Dellaca, R. L., Gobbi, A., Govoni, L., Navajas, D., Pedotti, A., Farre, R., (2009). A novel simple Internet-based system for real time monitoring and optimizing home mechanical ventilation International Conference on Ehealth, Telemedicine, and Social Medicine: Etelemed 2009, Proceedings International Conference on eHealth, Telemedicine, and Social Medicine (ed. Conley E.C., Doarn, C., HajjamElHassani, A.), IEEE Compuer Soc (Cancun, Mexico) , 209-215

The dissemination of the available telemedicine systems for the optimization of home mechanical ventilation (HMV) is prevented by the need of complex infrastructures. We developed a device which, once connected to Internet through the mobile phone network, allows an authorized physician connected to Internet to monitor the ventilator signals and modify the settings in real-time without the need of external data servers. The system was evaluated during experiments performed by tele-controlling a mechanical ventilator in Barcelona from Milano. A bench study verified the reliability and robustness of the system while an in-vivo test showed that it was possible to monitor and tele-control the ventilator to maintain the oxygen saturation of a rat ventilated in Barcelona subjected to interventions. Given that the system avoids the need for any complex telemedicine architecture and allows an individual and independent ventilator tele-control, it can be a new helpful tool to optimize HMV.

Keywords: Home mechanical ventilation, Non-invasive mechanical ventilation, Telemedicine