Performance evaluation of electrode design and material for a large animal electrical impedance tomography belt

Background Electrical impedance tomography (EIT) produces lung ventilation images via a thoracic electrode belt. Robust electrode design and material, providing low electrode skin contact impedance (SCI), is needed in veterinary medicine. The aim of this study was to compare three EIT electrode designs and materials. Methods Simulations of cylindrical, rectangular and spiked electrode designs were used to evaluate electrode SCI as a function of electrode size, where skin contact was uneven. Gold-plated washers (EGW), zinc-plated rivets (EZR) and zinc-galvanised spikes (EZS) were assigned randomly on two interconnected EIT belts. Gel was applied to the cranial or caudal belt and placed on 17 standing cattle. SCI was recorded at baseline and 3, 5, 7, 9 and 11 minutes later. Results Simulations that involved electrodes with a greater skin contact area had lower and more uniform SCI. In cattle, SCI decreased with all electrodes over time (p < 0.01). Without gel, no difference was found between EGW and EZS, while SCI was higher for EZR (p < 0.03). With gel, SCI was lower in EGW and EZR (p < 0.026), with the SCI in EGW being the lowest (p < 0.01). Limitations Low numbers of animals and static electrode position may affect SCI. Conclusions Electrode design is important for EIT measurement, with larger electrode designs able to compensate for the use of less conductive materials. Gel is not necessary to achieve acceptable SCI in large animals

Use of Electrical Impedance Tomography (EIT) to estimate tidal volume in Anaesthetized horses undergoing elective surgery

This study explores the application of electric impedance tomography (EIT) to estimate tidal volume (VT) by measuring impedance change per breath (∆Zbreath). Seventeen healthy horses were anaesthetised and mechanically ventilated for elective procedures requiring dorsal recumbency. Spirometric VT (VTSPIRO) and ∆Zbreath were recorded periodically; up to six times throughout anaesthesia. Part 1 assessed these variables at incremental delivered VT of 10, 12 and 15 mL/kg. Part 2 estimated VT (VTEIT) in litres from ∆Zbreath at three additional measurement points using a line of best fit obtained from Part 1. During part 2, VT was adjusted to maintain end-tidal carbon dioxide between 45–55 mmHg. Linear regression determined the correlation between VTSPIRO and ∆Zbreath (part 1). Estimated VTEIT was assessed for agreement with measured VTSPIRO using Bland Altman analysis (part 2). Marked variability in slope and intercepts was observed across horses. Strong positive correlation between ∆Zbreath and VTSPIRO was found in each horse (R2 0.9–0.99). The agreement between VTEIT and VTSPIRO was good with bias (LOA) of 0.26 (−0.36–0.88) L. These results suggest that, in anaesthetised horses, EIT can be used to monitor and estimate VT after establishing the individual relationship between these variables

Regional ventilation distribution and dead space in anaesthetized horses treated with and without continuous positive airway pressure: novel insights by electrical impedance tomography and volumetric capnography

Objective: The aim of this study was to evaluate the effect of continuous positive airway pressure (CPAP) on regional distribution of ventilation and dead space in anaesthetized horses. Study design: Randomized, experimental, crossover study. Animals: A total of eight healthy adult horses. Methods: Horses were anaesthetized twice with isoflurane in 50% oxygen and medetomidine as continuous infusion in dorsal recumbency, and administered in random order either CPAP (8 cmH2O) or NO CPAP for 3 hours. Electrical impedance tomography (and volumetric capnography (VCap) measurements were performed every 30 minutes. Lung regions with little ventilation [dependent silent spaces (DSSs) and nondependent silent spaces (NSSs)], centre of ventilation (CoV) and dead space variables, as well as venous admixture were calculated. Statistical analysis was performed using multivariate analysis of variance and Pearson correlation. Results: Data from six horses were statistically analysed. In CPAP, the CoV shifted to dependent parts of the lungs (p < 0.001) and DSSs were significantly smaller (p < 0.001), while no difference was seen in NSSs. Venous admixture was significantly correlated with DSS with the treatment time taken as covariate (p < 0.0001; r = 0.65). No differences were found for any VCap parameters. Conclusions and clinical relevance: In dorsally recumbent anaesthetized horses, CPAP of 8 cmH2O results in redistribution of ventilation towards the dependent lung regions, thereby improving ventilation-perfusion matching. This improvement was not associated with an increase in dead space indicative for a lack in distension of the airways or impairment of alveolar perfusion

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

oai:repository.mdx.ac.uk:y1752Endotracheal 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 ventilationmechanics in specific cases

Thoracic Electrical Impedance Tomography—The 2022 Veterinary Consensus Statement

Electrical impedance tomography (EIT) is a non-invasive real-time non-ionising imaging modality that has many applications. Since the first recorded use in 1978, the technology has become more widely used especially in human adult and neonatal critical care monitoring. Recently, there has been an increase in research on thoracic EIT in veterinary medicine. Real-time imaging of the thorax allows evaluation of ventilation distribution in anesthetised and conscious animals. As the technology becomes recognised in the veterinary community there is a need to standardize approaches to data collection, analysis, interpretation and nomenclature, ensuring comparison and repeatability between researchers and studies. A group of nineteen veterinarians and two biomedical engineers experienced in veterinary EIT were consulted and contributed to the preparation of this statement. The aim of this consensus is to provide an introduction to this imaging modality, to highlight clinical relevance and to include recommendations on how to effectively use thoracic EIT in veterinary species. Based on this, the consensus statement aims to address the need for a streamlined approach to veterinary thoracic EIT and includes: an introduction to the use of EIT in veterinary species, the technical background to creation of the functional images, a consensus from all contributing authors on the practical application and use of the technology, descriptions and interpretation of current available variables including appropriate statistical analysis, nomenclature recommended for consistency and future developments in thoracic EIT. The information provided in this consensus statement may benefit researchers and clinicians working within the field of veterinary thoracic EIT. We endeavor to inform future users of the benefits of this imaging modality and provide opportunities to further explore applications of this technology with regards to perfusion imaging and pathology diagnosis

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy

Pathogenic Germline Variants in 10,389 Adult Cancers

We conducted the largest investigation of predisposition variants in cancer to date, discovering 853 pathogenic or likely pathogenic variants in 8% of 10,389 cases from 33 cancer types. Twenty-one genes showed single or cross-cancer associations, including novel associations of SDHA in melanoma and PALB2 in stomach adenocarcinoma. The 659 predisposition variants and 18 additional large deletions in tumor suppressors, including ATM, BRCA1, and NF1, showed low gene expression and frequent (43%) loss of heterozygosity or biallelic two-hit events. We also discovered 33 such variants in oncogenes, including missenses in MET, RET, and PTPN11 associated with high gene expression. We nominated 47 additional predisposition variants from prioritized VUSs supported by multiple evidences involving case-control frequency, loss of heterozygosity, expression effect, and co-localization with mutations and modified residues. Our integrative approach links rare predisposition variants to functional consequences, informing future guidelines of variant classification and germline genetic testing in cancer. A pan-cancer analysis identifies hundreds of predisposing germline variants

Oncogenic Signaling Pathways in The Cancer Genome Atlas

Genetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tumor types. Using mutations, copy-number changes, mRNA expression, gene fusions and DNA methylation in 9,125 tumors profiled by The Cancer Genome Atlas (TCGA), we analyzed the mechanisms and patterns of somatic alterations in ten canonical pathways: cell cycle, Hippo, Myc, Notch, Nrf2, PI-3-Kinase/Akt, RTK-RAS, TGFb signaling, p53 and beta-catenin/Wnt. We charted the detailed landscape of pathway alterations in 33 cancer types, stratified into 64 subtypes, and identified patterns of co-occurrence and mutual exclusivity. Eighty-nine percent of tumors had at least one driver alteration in these one alteration potentially targetable by currently available drugs. Thirty percent of tumors had multiple targetable alterations, indicating opportunities for combination therapy

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types