Minimally invasive lung tissue differentiation using electrical impedance spectroscopy: a comparison of the 3- and 4-electrode methods

Multiple imaging techniques are used for the diagnosis of lung diseases. The choice of a technique depends on the suspected diagnosis. Computed tomography (CT) of the thorax and positron emission tomography (PET) are imaging techniques used for the detection, characterization, staging and follow-up of lung cancer, and these techniques use ionizing radiation and are radiologist-dependent. Electrical impedance spectroscopy (EIS) performed through a bronchoscopic process could serve as a minimally invasive non-ionizing method complementary to CT and PET to characterize lung tissue. The aim of this study was to analyse the feasibility and ability of minimally invasive EIS bioimpedance measures to differentiate among healthy lung, bronchial and neoplastic lung tissues through bronchoscopy using the 3- and 4-electrode methods. Tissue differentiation was performed in 13 patients using the 4-electrode method (13 healthy lung, 12 bronchial and 3 neoplastic lung tissues) and the 3-electrode method (9 healthy lung, 10 bronchial and 2 neoplastic lung tissues). One-way analysis of variance (ANOVA) showed a statistically significant difference (P < 0.001) between bronchial and healthy lung tissues for both the 3- and 4-electrode methods. The 3-electrode method seemed to differentiate cancer types through changes in the cellular structures of the tissues by both the reactance (Xc) and the resistance (R). Minimally invasive measurements obtained using the 3-electrode method seem to be most suitable for differentiating between healthy and bronchial lung tissues. In the future, EIS using the 3-electrode method could be a method complementary to PET/CT and biopsy in lung pathology diagnosis.Peer ReviewedPostprint (author's final draft

Differentiation using minimally-invasive bioimpedance measurements of healthy and pathological lung tissue through bronchoscopy

Purpose: To use minimally-invasive transcatheter electrical impedance spectroscopy measurements for tissue differentiation among healthy lung tissue and pathologic lung tissue from patients with different respiratory diseases (neoplasm, fibrosis, pneumonia and emphysema) to complement the diagnosis at real time during bronchoscopic procedures. Methods: Multi-frequency bioimpedance measurements were performed in 102 patients. The two most discriminative frequencies for impedance modulus (|Z|), phase angle (PA), resistance (R) and reactance (Xc) were selected based on the maximum mean pair-wise Euclidean distances between paired groups. One-way ANOVA for parametric variables and Kruskal–Wallis for non-parametric data tests have been performed with post-hoc tests. Discriminant analysis has also been performed to find a linear combination of features to separate among tissue groups. Results: We found statistically significant differences for all the parameters between: neoplasm and pneumonia (p¿¿0.05) are found between neoplasm and fibrosis; fibrosis and pneumonia; and between healthy lung tissue and emphysema. Conclusion: The application of minimally-invasive electrical impedance spectroscopy measurements in lung tissue have proven to be useful for tissue differentiation between those pathologies that leads increased tissue and inflammatory cells and those ones that contain more air and destruction of alveolar septa, which could help clinicians to improve diagnosis.Peer ReviewedPostprint (published version

Minimally Invasive Lung Tissue Differentiation Using Electrical Impedance Spectroscopy : A Comparison of the 3- and 4-Electrode Methods

Altres ajuts: Secretariat d'Universitats i Recerca, Generalitat de Catalunya; the European Social Fund.Multiple imaging techniques are used for the diagnosis of lung diseases. The choice of a technique depends on the suspected diagnosis. Computed tomography (CT) of the thorax and positron emission tomography (PET) are imaging techniques used for the detection, characterization, staging and follow-up of lung cancer, and these techniques use ionizing radiation and are radiologist-dependent. Electrical impedance spectroscopy (EIS) performed through a bronchoscopic process could serve as a minimally invasive non-ionizing method complementary to CT and PET to characterize lung tissue. The aim of this study was to analyse the feasibility and ability of minimally invasive EIS bioimpedance measures to differentiate among healthy lung, bronchial and neoplastic lung tissues through bronchoscopy using the 3- and 4-electrode methods. Tissue differentiation was performed in 13 patients using the 4-electrode method (13 healthy lung, 12 bronchial and 3 neoplastic lung tissues) and the 3-electrode method (9 healthy lung, 10 bronchial and 2 neoplastic lung tissues). One-way analysis of variance (ANOVA) showed a statistically significant difference (P < 0.001) between bronchial and healthy lung tissues for both the 3- and 4-electrode methods. The 3-electrode method seemed to differentiate cancer types through changes in the cellular structures of the tissues by both the reactance (Xc) and the resistance (R). Minimally invasive measurements obtained using the 3-electrode method seem to be most suitable for differentiating between healthy and bronchial lung tissues. In the future, EIS using the 3-electrode method could be a method complementary to PET/CT and biopsy in lung pathology diagnosis

Using temporal electrical impedance spectroscopy measures to differentiate lung pathologies with the 3-electrode method

Minimally invasive lung bioimpedance measurements could serve in the future diagnosis of lung pathologies complementing biopsies and imaging techniques. Through the electrical impedance spectroscopy (EIS) technique using the 3-electrode method, distinction of lung pathologies could be possible depending on the state of the tissue. Since now, only averaged information has been used for the analysis of bioimpedance data in lungs. The aim of this study is to use temporal information to evaluate changes in the impedance signal due to the mechanism of ventilation and perfusion produced by the lungs. Preliminary results show: 1) correlation between ventilation and perfusion with the bioimpedance signal and 2) changes in the amplitude of the bioimpedance time signal depending on the pathology. As conclusion, together with cycled averaged data, temporal data could be useful for lung pathologies distinction.Postprint (published version

Effect of calibration for tissue differentiation between healthy and neoplasm lung using minimally invasive electrical impedance spectroscopy

his study proposes a calibration method and analyses the effect of this calibration in lung measures, using minimally invasive electrical impedance spectroscopy with the 3-electrode method, for tissue differentiation between healthy and neoplasm lung tissue. Tissue measurements were performed in 99 patients [54 healthy tissue and 15 neoplastic tissue samples obtained] with an indicated bronchoscopy. Statistically significant difference (P < 0.001) were found between healthy lung tissue and neoplasm lung tissue in bioimpedance parameters. The calibration of the bioimpedance measures with respect to a measure performed in bronchi reduces the inter-patient dispersion, increasing the sensitivity, decreasing the specificity and increasing the area below the ROC curve for three out of four impedance-derived estimators. Results also show that there are no significant differences between healthy lung tissue among smoker, non-smoker and ex-smoker samples, which was initially stated as a possible cause of EIS measurement dispersion in lungs.Peer ReviewedPostprint (published version

Espectrometria d'impedància elèctrica en temps real de teixit pulmonar in vivo i in situ. Correlació amb malalties pulmonars

Avaluació de l’efectivitat d’un sistema de diferenciació de teixits pulmonars basat en mesures de impedància elèctrica mitjançant procediments de broncoscòpia en teixit pulmonar humà in vivo i mínimament invasiu. Per la recollida de dades s’utilitza un catèter amb 4 elèctrodes, capaç d’aplicar un corrent elèctric i mesurar la tensió provocada, obtenint així la impedància a 26 freqüències i la temperatura interior. També es recullen dades fisiològiques pel processat i filtratge. Es desenvolupa un algorisme mitjançant el software Matlab, per l’estudi de dades d’impedància. Es determinen i es quantifiquen les diferències entre 3 conjunts de mostres, teixit bronquial i teixit alveolar sa i teixit alveolar patològic

Canine cardiopulmonary responses to one-lung ventilation during thoracoscopic diaphragmatic incision repair and two-lung ventilation during gasless laparoscopic diaphragmatic incision repair

Two minimally invasive surgical techniques for repair of diaphragmatic incisions and the cardiopulmonary responses during the surgical procedures were investigated in dogs;(1) The cardiopulmonary effects of one-lung ventilation (OLV) during thoracoscopic diaphragmatic incision repair (TDIR) and two-lung ventilation (TLV) for gasless laparoscopic diaphragmatic incision repair (GLDIR) in the dog were determined. The changes in cardiopulmonary function were less in the GLDIR with TLV group, although not statistically different from the TDIR with OLV. In addition, during OLV and thoracoscopy, right lung collapse with left lung ventilation may predispose to an increased risk of hypoxemia when compared to left lung collapse with right lung ventilation;(2) Two video-assisted surgical techniques are described for the repair of diaphragmatic incisions: (a) gasless laparoscopy with an abdominal lifting device and (b) thoracoscopy with one-lung ventilation. In this study, thoracoscopic approaches with OLV were feasible to repair the diaphragmatic incisions located in the ventral part of the right pars costalis and sternalis or left pars costalis and sternalis. Incisions that extended across the midline were more difficult to repair with this approach. The gasless laparoscopic approach was feasible to suture incisions located in the pars sternalis and ventral part of the right or left pars costalis. Incisions that extended across the midline were repairable with this approach. The two surgical approaches described have potential clinical application that would provide a reduction in pain and recuperation times from diaphragmatic hernia repair for clinical patients

Study and development of a novel radio frequency electromedical device for the treatment of peri-implantitis: experimental performance analysis, modelling of the electromagnetic interaction with tissues and in vitro and in vivo evaluation

La peri-implantite (PI) è una grave patologia che interessa tessuti peri-implantari molli e duri. Ad oggi, la prevenzione è l’unico mezzo per contrastarla. Recentemente, è stata sperimentata una terapia basata sulla somministrazione di corrente elettrica a radio frequenza (successo: 81%). Il trattamento è stato simulato numericamente, fornendo le distribuzioni di corrente (EC) e campo elettrico (EF) nei tessuti: l’effetto anti-infiammatorio è attribuibile alla EC, quello di rigenerazione ossea al EF. Sono state considerate le misure di bioimpedenza (BM) per individuare le infiammazioni; numericamente si sono osservati cambiamenti nel modulo di impedenza del 4-20% (secondo diversi parametri), anche più alti sperimentalmente (35% infiammazione, 56% PI). Le BM permettono quindi di identificare il tessuto da trattare. Per la ripetibilità, sono state considerate radici di denti naturali, numericamente e sperimentalmente; l’ordine di grandezza è lo stesso (qualche kΩ), anche se ci sono differenze legate alle condizioni di misura. La variabilità intra-soggetto è il 10% in uno stesso giorno, fino al 26% in giorni diversi; quella inter-soggetto è più alta. La sicurezza elettrica è stata attentamente esaminata e si sono individuate le direttive applicabili (IEC 60601-1, 60601-1-2 and 60601-2-2). Sono stati fatti test in vitro per valutare l’effetto della terapia sulla vitalità cellulare: non c’è un significativo aumento della necrosi (vitalità: 85% test, 94% controlli), l’effetto negativo principale è l’apoptosi. Sono stati numericamente indagati possibili effetti termici: non sono stati individuati riscaldamenti nocivi dei tessuti. Si è progettato un nuovo dispositivo (PeriCare®) per trattare la PI, con parti diagnostica (BM) e terapeutica. Si stanno progettando elettrodi specifici e realizzando il prototipo. Si sta compilando il fascicolo tecnico e pianificando i test di conformità, in vista della certificazione. Il dispositivo medico dovrebbe entrare nel mercato entro l’anno.Peri-implantitis is a severe disease affecting hard and soft peri-implant tissues. At present, prevention is the only means to contrast it. Recently, a therapy based on the administration of radio frequency electric current was experimented (success rate: 81%). The treatment was numerically simulated, providing the electric current (EC) and field (EF) distributions in peri-implant tissues: the anti-inflammatory effect can be associated to EC, the bone regeneration to the EF. Bioimpedance measurements (BM) were investigated to detect inflammation; changes in the measured impedance modulus are equal to 4-20% (depending on different parameters) from numerical results, also more evident experimentally (35% inflammation, 56% peri-implantitis). So, BM could allow to detect the tissue to be treated. To evaluate the repeatability, natural tooth roots were numerically and experimentally measured; the order of magnitude is the same (some kΩ), even if there are differences probably due to the measurement conditions. Intra-subject variability was of 10% in the same day, but up to 26% in different days; inter-subject variability was higher. The electrical safety was accurately taken into account. The applicable directives were individuated (IEC 60601-1, 60601-1-2 and 60601-2-2). In vitro tests were carried out to evaluate the effect of the therapy on cell vitality: there is not a significant increase in necrosis (vitality: 85% tests, 94% controls), the main negative effect is apoptosis. Possible thermal effects were numerically investigated: no dangerous tissue heating was observed. A new device for the peri-implantitis treatment, PeriCare®, was designed, with diagnostic (BM) and therapeutic parts. Proper electrodes are being designed and the prototype is being realized. The technical file is being compiled and the conformity verification tests are being planned towards the certification process. Hopefully, the medical device will be placed into the market within this year

Development of a novel probe integrated with a micro-structured impedance sensor for the detection of breast cancer

The work described in this thesis focuses on the development of an innovative bioimpedance device for the detection of breast cancer using electrical impedance as the detection method. The ability for clinicians to detect and treat cancerous lesions as early as possible results in improved patient outcomes and can reduce the severity of the treatment the patient has to undergo. Therefore, new technology and devices are continually required to improve the specificity and sensitivity of the accepted detection methods. The gold standard for breast cancer detection is digital x-ray mammography but it has some significant downsides associated with it. The development of an adjunct technology to aid in the detection of breast cancers could represent a significant patient and economic benefit. In this project silicon substrates were pattern with two gold microelectrodes that allowed electrical impedance measurements to be recorded from intact tissue structures. These probes were tested and characterised using a range of in vitro and ex vivo experiments. The end application of this novel sensor device was in a first-in-human clinical trial. The initial results of this study showed that the silicon impedance device was capable of differentiating between normal and abnormal (benign and cancerous) breast tissue. The mean separation between the two tissue types 4,340 Ω with p < 0.001. The cancer type and grade at the site of the probe recordings was confirmed histologically and correlated with the electrical impedance measurements to determine if the different subtypes of cancer could each be differentiated. The results presented in this thesis showed that the novel impedance device demonstrated excellent electrochemical recording potential; was biocompatible with the growth of cultured cell lines and was capable of differentiating between intact biological tissues. The results outlined in this thesis demonstrate the potential feasibility of using electrical impedance for the differentiation of biological tissue samples. The novelty of this thesis is in the development of a new method of tissue determination with an application in breast cancer detection