The clinical application of electrical impedance technology in the detection of malignant neoplasms: a systematic review.

BACKGROUND: Electrical impedance technology has been well established for the last 20 years. Recently research has begun to emerge into its potential uses in the detection and diagnosis of pre-malignant and malignant conditions. The aim of this study was to systematically review the clinical application of electrical impedance technology in the detection of malignant neoplasms. METHODS: A search of Embase Classic, Embase and Medline databases was conducted from 1980 to 22/02/2018 to identify studies reporting on the use of bioimpedance technology in the detection of pre-malignant and malignant conditions. The ability to distinguish between tissue types was defined as the primary endpoint, and other points of interest were also reported. RESULTS: 731 articles were identified, of which 51 reported sufficient data for analysis. These studies covered 16 different cancer subtypes in a total of 7035 patients. As the studies took various formats, a qualitative analysis of each cancer subtype's data was undertaken. All the studies were able to show differences in electrical impedance and/or related metrics between malignant and normal tissue. CONCLUSIONS: Electrical impedance technology provides a novel method for the detection of malignant tissue, with large studies of cervical, prostate, skin and breast cancers showing encouraging results. Whilst these studies provide promising insights into the potential of this technology as an adjunct in screening, diagnosis and intra-operative margin assessment, customised development as well as multi-centre clinical trials need to be conducted before it can be reliably employed in the clinical detection of malignant tissue.

Towards a System for Tracking Drug Delivery Using Frequency Excited Gold Nanoparticles.

Nanoparticle-based drugs are rapidly evolving to treat different conditions and have considerable potential. A new system based on the combination of electrical impedance tomography (EIT) imaging and a power amplifier with a RF coil has been developed to study the effect of gold nanoparticles (AuNPs) when excited in the MHz frequency range. We show that samples including AuNPs have a temperature increase of 1-1.5 °C due to the presence of RF excitation at 13.56 MHz which provides a higher rate of change for solutions without AuNPs. They also show more than a 50% increase in conductivity in difference imaging as the result of this excitation. The change for samples without AuNPs is 40%.

Analog Integrated Current Drivers for Bioimpedance Applications: A Review.

An important component in bioimpedance measurements is the current driver, which can operate over a wide range of impedance and frequency. This paper provides a review of integrated circuit analog current drivers which have been developed in the last 10 years. Important features for current drivers are high output impedance, low phase delay, and low harmonic distortion. In this paper, the analog current drivers are grouped into two categories based on open loop or closed loop designs. The characteristics of each design are identified.

Analysis and compensation for errors in electrical impedance tomography images and ventilation-related measures due to serial data collection.

Electrical impedance tomography (EIT) is increasingly being used as a bedside tool for monitoring regional lung ventilation. However, most clinical systems use serial data collection which, if uncorrected, results in image distortion, particularly at high breathing rates. The objective of this study was to determine the extent to which this affects derived parameters. Raw EIT data were acquired with the GOE-MF II EIT device (CareFusion, Höchberg, Germany) at a scan rate of 13 images/s during both spontaneous breathing and mechanical ventilation. Boundary data for periods of undisturbed tidal breathing were corrected for serial data collection errors using a Fourier based algorithm. Images were reconstructed for both the corrected and original data using the GREIT algorithm, and parameters describing the filling characteristics of the right and left lung derived on a breath by breath basis. Values from the original and corrected data were compared using paired t-tests. Of the 33 data sets, 23 showed significant differences in filling index for at least one region, 11 had significant differences in calculated tidal impedance change and 12 had significantly different filling fractions (p = 0.05). We conclude that serial collection errors should be corrected before image reconstruction to avoid clinically misleading results.

Clinical Utility of Ultrasound Imaging for Measuring Anterior Thigh Thickness after Anterior Cruciate Ligament Injury in an Individual Patient to Assess Postsurgery Outcome.

The present study investigated the clinical utility of ultrasound imaging (USI) for assessing changes in an individual's quadriceps muscle and subcutaneous fat (SF) thickness of the anterior thigh and their relative proportions. A patient was studied prior to and after anterior cruciate ligament reconstruction (ACLR) surgery and during rehabilitation. This case study involved an 18-year-old female recreational athlete with a complete tear of the anterior cruciate ligament (ACL). Tissue thickness (SF and quadriceps muscle) was measured from transverse USI of the anterior thigh before surgery, at weekly intervals during 12 weeks of postsurgery, and then every 2 weeks for the following 12 weeks (total of 21 measurement sets). Statistically significant differences presurgery to postrehabilitation were found for muscle thickness (p = 0.04) and SF tissue thickness (p = 0.04) measurements. There was no difference in muscle to fat ratio (p = 0.08). Changes in measurements greater than the reported minimal detectable change (MDC) demonstrate the sensitivity of the USI technique as an objective tool to assess clinically useful changes in an individual's anterior thigh muscle thickness post-ACLR surgery and during rehabilitation.

Effect of routine suction on lung aeration in critically ill neonates and young infants measured with electrical impedance tomography.

Endotracheal suctioning is a widely used procedure to remove secretions from the airways of ventilated patients. Despite its prevalence, regional effects of this maneuver have seldom been studied. In this study, we explore its effects on regional lung aeration in neonates and young infants using electrical impedance tomography (EIT) as part of the large EU-funded multicenter observational study CRADL. 200 neonates and young infants in intensive care units were monitored with EIT for up to 72 h. EIT parameters were calculated to detect changes in ventilation distribution, ventilation inhomogeneity and ventilation quantity on a breath-by-breath level 5-10 min before and after suctioning. The intratidal change in aeration over time was investigated by means of regional expiratory time constants calculated from all respiratory cycles using an innovative procedure and visualized by 2D maps of the thoracic cross-section. 344 tracheal suctioning events from 51 patients could be analyzed. They showed no or very small changes of EIT parameters, with a dorsal shift of the center of ventilation by 0.5% of the chest diameter and a 7% decrease of tidal impedance variation after suctioning. Regional time constants did not change significantly. Routine suctioning led to EIT-detectable but merely small changes of the ventilation distribution in this study population. While still a measure requiring further study, the time constant maps may help clinicians interpret ventilation mechanics in specific cases.

Bioimpedance imaging: an overview of potential clinical applications.

Electrical Impedance Tomography (EIT) is an imaging technique based on multiple bio impedance measurements to produce a map (image) of impedance or changes in impedance across a region. Its origins lay in geophysics where it is still used to today. This review highlights potential clinical applications of EIT. Beginning with a brief overview of the underlying principles behind the modality, it describes the background research leading towards the development of the application of EIT for monitoring pulmonary function, detecting and localising tumours and monitoring brain function.

Generation of Anatomically Inspired Human Airway Tree Using Electrical Impedance Tomography: A Method to Estimate Regional Lung Filling Characteristics.

The purpose of lung recruitment is to improve and optimize the air exchange flow in the lungs by adjusting the respiratory settings during mechanical ventilation. Electrical impedance tomography (EIT) is a monitoring tool that permits measurement of regional pulmonary filling characteristics or filling index (FI) during ventilation. The conventional EIT system has limitations which compromise the accuracy of the FI. This paper proposes a novel and automated methodology for accurate FI estimation based on EIT images of recruitable regional collapse and hyperdistension during incremental positive end-expiratory pressure. It identifies details of the airway tree (AT) to generate a correction factor to the FIs providing an accurate measurement. Multi-scale image enhancement followed by identification of the AT skeleton with a robust and self-exploratory tracing algorithm is used to automatically estimate the FI. AT tracing was validated using phantom data on a ground-truth lung. Based on generated phantom EIT images, including an established reference, the proposed method results in more accurate FI estimation of 65% in all quadrants compared with the current state-of-the-art. Measured regional filling characteristics were also examined by comparing regional and global impedance variations in clinically recorded data from ten different subjects. Clinical tests on filling characteristics based on extraction of the AT from the resolution enhanced EIT images indicated a more accurate result compared with the standard EIT images.

High Frame Rate Electrical Impedance Tomography System for Monitoring of Regional Lung Ventilation.

This paper describes the development of a compact high frame rate passive electrical impedance tomography system. The injected current amplitude and frequency can be adjusted to fit any EIT application. Measured results show that the system is capable of high frame rate of 89 fps and has power consumption of 1.7 W. It has automatic gain control that reduces noise and improves the quality of the measured EIT image. A comparison is made with other EIT systems to show the potential of the developed system. Clinical Relevance- The developed EIT system has application in the clinical assessment of neonatal and SARS-Co V-2 patients. In these applications there is an urgent need for a low cost bedside non-invasive imaging system to continuously monitor dynamic changes in regional lung ventilation.

Bronchodilator effect on regional lung function in pediatric viral lower respiratory tract infections.

Objective.Viral lower respiratory tract infections (LRTI) are the leading cause for acute admission to the intensive care unit in infants and young children. Nebulized bronchodilators are often used when treating the most severe cases. The aim of this study was to investigate the bronchodilator effect on respiratory mechanics during intensive care with electrical impedance tomography (EIT) and to assess the feasibility of EIT in this context.Approach.We continuously monitored the children with chest EIT for up to 72 h in an observational study design. The treatment decisions were done by clinical assessment, as the clinicians were blinded to the EIT information during data collection. In a retrospective analysis, clinical parameters and regional expiratory time constants determined by EIT were used to assess the effects of bronchodilator administration, especially regarding airway resistance.Main results.We included six children from 11 to 27 months of age requiring intensive care due to viral LRTI and receiving bronchodilator agents. Altogether 131 bronchodilator administrations were identified during EIT monitoring. After validation of the exact timing of events and EIT data quality, 77 administrations were included in the final analysis. Fifty-five bronchodilator events occurred during invasive ventilation and 22 during high-flow nasal cannulae treatment. Only 17% of the bronchodilator administrations resulted in a relevant decrease in calculated expiratory time constants.Significance.Continuous monitoring with EIT might help to optimize the treatment of LRTI in pediatric intensive care units. In particular, EIT-based regional expiratory time constants would allow objective assessment of the effects of bronchodilators and other respiratory therapies.

Cross-sectional chest circumference and shape development in infants.

OBJECTIVE: This study investigates the development of the thoracic cross-section at the nipple line level during the early stages of life. Unlike the descriptive awareness regarding chest development course, there exist no quantitative references concerning shape, circumference and possible dependencies to age, gender or body weight. The proposed mathematical relations are expected to help create guidelines for more realistic modelling and potential detection of abnormalities. One potential application is lung electrical impedance tomography (EIT) monitoring where accurate chest models are crucial in both extracting reliable parameters for regional ventilation function and design of EIT belts. Despite their importance, such reference data is not readily available for the younger age range due to insufficient data amid the regulations of neonatal imaging. RESULTS: Chest circumference shows the highest correlation to body weight following the relation [Formula: see text] where x is the body weight in grams and f(x) is the chest circumference in cm at the nipple line level. No statistically significant difference in chest circumference between genders was detected. However, the shape indicated signs of both age and gender dependencies with on average boys developing a more rectangular shape than girls from the age of 1 years and 9 months.

Locating Functionalized Gold Nanoparticles Using Electrical Impedance Tomography.

OBJECTIVE: An imaging device to locate functionalised nanoparticles, whereby therapeutic agents are transported from the site of administration specifically to diseased tissues, remains a challenge for pharmaceutical research. Here, we show a new method based on electrical impedance tomography (EIT) to provide images of the location of gold nanoparticles (GNPs) and the excitation of GNPs with radio frequencies (RF) to change impedance permitting an estimation of their location in cell models Methods: We have created an imaging system using quantum cluster GNPs as contrast agent, activated with RF fields to heat the functionalized GNPs, which causes a change in impedance in the surrounding region. This change is then identified with EIT. RESULTS: Images of impedance changes of around 80 ± 4% are obtained for a sample of citrate stabilized GNPs in a solution of phosphate-buffered saline. A second quantification was carried out using colorectal cancer cells incubated with culture media, and the internalization of GNPs into the colorectal cancer cells was undertaken to compare them with the EIT images. When the cells were incubated with functionalised GNPs, the change was more apparent, approximately 40 ± 2%. This change was reflected in the EIT image as the cell area was more clearly identifiable from the rest of the area. SIGNIFICANCE: EIT can be used as a new method to locate functionalized GNPs in human cells and help in the development of GNP-based drugs in humans to improve their efficacy in the future.

Prolonged Continuous Monitoring of Regional Lung Function in Infants with Respiratory Failure.

Rationale: Electrical impedance tomography (EIT) allows instantaneous and continuous visualization of regional ventilation and changes in end-expiratory lung volume at the bedside. There is particular interest in using EIT for monitoring in critically ill neonates and young children with respiratory failure. Previous studies have focused only on short-term monitoring in small populations. The feasibility and safety of prolonged monitoring with EIT in neonates and young children have not been demonstrated yet. Objectives: To evaluate the feasibility and safety of long-term EIT monitoring in a routine clinical setting and to describe changes in ventilation distribution and homogeneity over time and with positioning in a multicenter cohort of neonates and young children with respiratory failure. Methods: At four European University hospitals, we conducted an observational study (NCT02962505) on 200 patients with postmenstrual ages (PMA) between 25 weeks and 36 months, at risk for or suffering from respiratory failure. Continuous EIT data were obtained using a novel textile 32-electrode interface and recorded at 48 images/s for up to 72 hours. Clinicians were blinded to EIT images during the recording. EIT parameters and the effects of body position on ventilation distribution were analyzed offline. Results: The average duration of EIT measurements was 53 ± 20 hours. Skin contact impedance was sufficient to allow image reconstruction for valid ventilation analysis during a median of 92% (interquartile range, 77-98%) of examination time. EIT examinations were well tolerated, with minor skin irritations (temporary redness or imprint) occurring in 10% of patients and no moderate or severe adverse events. Higher ventilation amplitude was found in the dorsal and right lung areas when compared with the ventral and left regions, respectively. Prone positioning resulted in an increase in the ventilation-related EIT signal in the dorsal hemithorax, indicating increased ventilation of the dorsal lung areas. Lateral positioning led to a redistribution of ventilation toward the dependent lung in preterm infants and to the nondependent lung in patients with PMA > 37 weeks. Conclusions: EIT allows continuous long-term monitoring of regional lung function in neonates and young children for up to 72 hours with minimal adverse effects. Our study confirmed the presence of posture-dependent changes in ventilation distribution and their dependency on PMA in a large patient cohort. Clinical trial registered with www.clinicaltrials.gov (NCT02962505).

Exploiting the efficacy of Tyro3 and folate receptors to enhance the delivery of gold nanoparticles into colorectal cancer cells in vitro.

Colorectal cancer (CRC) is the fourth most common cancer in the world. Due to its asymptomatic nature, CRC is diagnosed at an advanced stage where the survival rate is <5%. Besides, CRC treatment using chemotherapy, radiotherapy and surgery often causes undesirable side-effects. As such, gold nanoparticles (GNPs) are envisaged in the field for the diagnosis and treatment of CRC. GNPs have unique physical, chemical and electrical properties at the nanoscale which make them suitable for application in biomedicine. However, for GNPs to become clinically effective, their internalisation efficiency in cancer cells must be enhanced. Folate receptor-α (FR) is overexpressed in CRC cells wherein FR helps in the uptake of folic acid within the cells. Tyro3, a novel tyrosine kinase receptor, drives cell proliferation and its overexpression is correlated with poor prognosis in CRC. Their upregulated expression in CRC cells relative to normal cells makes them an ideal target for GNPs using active targeting. Therefore, in this study receptors FR and Tyro3 were simultaneously targeted using specific antibody-coated GNPs in order to enhance the uptake and internalisation of GNPs in CRC cells in vitro. Four different types of coated-GNPs were synthesised GNPs-PEG, GNPs-anti-FR, GNPs-anti-Tyro3 and GNPs-anti-(FR + Tyro3) and incubated (0-50 ng) with three CRC cell lines namely CRL1790, CRL2159 and HCT116. Simultaneous targeting of these receptors by GNPs-anti-(FR + Tyro3) was found to be the most effective in internalisation in CRC cells compared with GNPs targeted singly to FR or Tyro3 (p <0.05). Besides this, results show that Tyro3 mediated similar internalisation efficacy to FR (p <0.05) in CRC cells using ICP-OES.

Thoracic shape changes in newborns due to their position.

The highly compliant nature of the neonatal chest wall is known to clinicians. However, its morphological changes have never been characterized and are especially important for a customised monitoring of respiratory diseases. Here, we show that a device applied on newborns can trace their chest boundary without the use of radiation. Such technology, which is easy to sanitise between patients, works like a smart measurement tape drawing also a digital cross section of the chest. We also show that in neonates the supine position generates a significantly different cross section compared to the lateral ones. Lastly, an unprecedented comparison between a premature neonate and a child is reported.

Model Selection Based Algorithm in Neonatal Chest EIT.

This paper presents a new method for selecting a patient specific forward model to compensate for anatomical variations in electrical impedance tomography (EIT) monitoring of neonates. The method uses a combination of shape sensors and absolute reconstruction. It takes advantage of a probabilistic approach which automatically selects the best estimated forward model fit from pre-stored library models. Absolute/static image reconstruction is performed as the core of the posterior probability calculations. The validity and reliability of the algorithm in detecting a suitable model in the presence of measurement noise is studied with simulated and measured data from 11 patients. The paper also demonstrates the potential improvements on the clinical parameters extracted from EIT images by considering a unique case study with a neonate patient undergoing computed tomography imaging as clinical indication prior to EIT monitoring. Two well-known image reconstruction techniques, namely GREIT and tSVD, are implemented to create the final tidal images. The impacts of appropriate model selection on the clinical extracted parameters such as center of ventilation and silent spaces are investigated. The results show significant improvements to the final reconstructed images and more importantly to the clinical EIT parameters extracted from the images that are crucial for decision-making and further interventions.

A Framework for Adapting Deep Brain Stimulation Using Parkinsonian State Estimates.

The mechanisms underlying the beneficial effects of deep brain stimulation (DBS) for Parkinson's disease (PD) remain poorly understood and are still under debate. This has hindered the development of adaptive DBS (aDBS). For further progress in aDBS, more insight into the dynamics of PD is needed, which can be obtained using machine learning models. This study presents an approach that uses generative and discriminative machine learning models to more accurately estimate the symptom severity of patients and adjust therapy accordingly. A support vector machine is used as the representative algorithm for discriminative machine learning models, and the Gaussian mixture model is used for the generative models. Therapy is effected using the state estimates obtained from the machine learning models together with a fuzzy controller in a critic-actor control approach. Both machine learning model configurations achieve PD suppression to desired state in 7 out of 9 cases; most of which settle in under 2 s.

Electrical impedance tomography reveals pathophysiology of neonatal pneumothorax during NAVA.

Pneumothorax is a potentially life-threatening complication of neonatal respiratory distress syndrome (RDS). We describe a case of a tension pneumothorax that occurred during neurally adjusted ventilatory assist (NAVA) in a preterm infant suffering from RDS. The infant was included in a multicenter study examining the role of electrical impedance tomography (EIT) in intensive care and therefore continuously monitored with this imaging method. The attending physicians were blinded for EIT findings but offline analysis revealed the potential of EIT to clarify the underlying cause of this complication, which in this case was heterogeneous lung disease resulting in uneven ventilation distribution. Instantaneous increase in end-expiratory lung impedance on the affected side was observed at time of the air leak. Real-time bedside availability of EIT data could have modified the treatment decisions made.

Towards a thoracic conductive phantom for EIT.

Phantom experiments are a crucial step for testing new hardware or imaging algorithms for electrical impedance tomography (EIT) studies. However, constructing an accurate phantom for EIT research remains critical; some studies have attempted to model the skull and breasts, and even fewer, as yet, have considered the thorax. In this study, a critical comparison between the electrical properties (impedance) of three materials is undertaken: a polyurethane foam, a silicone mixture and a thermoplastic polyurethane filament. The latter was identified as the most promising material and adopted for the development of a flexible neonatal torso. The validation is performed by the EIT image reconstruction of the air filled cavities, which mimic the lung regions. The methodology is reproducible for the creation of any phantom that requires a slight flexibility.