Non-invasive hERG channel screening based on electrical impedance tomography and extracellular voltage activation (EIT-EVA).

hERG channel screening has been achieved based on electrical impedance tomography and extracellular voltage activation (EIT-EVA) to improve the non-invasive aspect of drug discovery. EIT-EVA screens hERG channels by considering the change in extracellular ion concentration which modifies the extracellular resistance in cell suspension. The rate of ion passing in cell suspension is calculated from the extracellular resistance Rex, which is obtained from the EIT measurement at a frequency of 500 kHz. In the experiment, non-invasive screening is applied by a novel integrated EIT-EVA printed circuit board (PCB) sensor to human embryonic kidney (HEK) 293 cells transfected with the human ether-a-go-go-related gene (hERG) ion channel, while the E-4031 antiarrhythmic drug is used for hERG channel inhibition. The extracellular resistance Rex of the HEK 293 cells suspension is measured by EIT as the hERG channels are activated by EVA over time. The Rex is reconstructed into extracellular conductivity distribution change Δσ to reflect the extracellular K+ ion concentration change Δc resulting from the activated hERG channel. Δc is increased rapidly during the hERG channel non-inhibition state while Δc is increased slower with increasing drug concentration cd. In order to evaluate the EIT-EVA system, the inhibitory ratio index (IR) was calculated based on the rate of Δc over time. Half-maximal inhibitory concentration (IC50) of 2.7 nM is obtained from the cd and IR dose-response relationship. The IR from EIT-EVA is compared with the results from the patch-clamp method, which gives R2 of 0.85. In conclusion, EIT-EVA is successfully applied to non-invasive hERG channel screening.

3D Multiparametric Photoacoustic Computed Tomography of Primary and Metastatic Tumors in Living Mice.

Photoacoustic computed tomography (PACT), an emerging imaging modality in preclinical cancer research, can provide multiparametric 3D information about structures, physiological functions, and pharmacokinetics. Here, we demonstrate the use of high-definition 3D multiparametric PACT imaging of both primary and metastatic tumors in living mice to noninvasively monitor angiogenesis, carcinogenesis, hypoxia, and pharmacokinetics. The high-definition PACT system with a 1024-element hemispherical ultrasound transducer array provides an isotropic spatial resolution of 380 µm, an effective volumetric field-of-view of 12.8 mm × 12.8 mm × 12.8 mm without scanning, and an acquisition time of <30 s for a whole mouse body. Initially, we monitor the structural progression of the tumor microenvironment (e.g., angiogenesis and vessel tortuosity) after tumor cell inoculation. Then, we analyze the change in oxygen saturation of the tumor during carcinogenesis, verifying induced hypoxia in the tumor's core region. Finally, the whole-body pharmacokinetics are photoacoustically imaged after intravenous injection of micelle-loaded IR780 dye, and the in vivo PACT results are validated in vivo and ex vivo by fluorescence imaging. By employing the premium PACT system and applying multiparametric analyses to subcutaneous primary tumors and metastatic liver tumors, we demonstrate that this PACT system can provide multiparametric analyses for comprehensive cancer research.

A non-invasive approach to skin cancer diagnosis via graphene electrical tattoos and electrical impedance tomography.

Objective.Making up one of the largest shares of diagnosed cancers worldwide, skin cancer is also one of the most treatable. However, this is contingent upon early diagnosis and correct skin cancer-type differentiation. Currently, methods for early detection that are accurate, rapid, and non-invasive are limited. However, literature demonstrating the impedance differences between benign and malignant skin cancers, as well as between different types of skin cancer, show that methods based on impedance differentiation may be promising.Approach.In this work, we propose a novel approach to rapid and non-invasive skin cancer diagnosis that leverages the technologies of difference-based electrical impedance tomography (EIT) and graphene electronic tattoos (GETs).Main results.We demonstrate the feasibility of this first-of-its-kind system using both computational numerical and experimental skin phantom models. We considered variations in skin cancer lesion impedance, size, shape, and position relative to the electrodes and evaluated the impact of using individual and multi-electrode GET (mGET) arrays. The results demonstrate that this approach has the potential to differentiate based on lesion impedance, size, and position, but additional techniques are needed to determine shape.Significance.In this way, the system proposed in this work, which combines both EIT and GET technology, exhibits potential as an entirely non-invasive and rapid approach to skin cancer diagnosis.

Development of a Compact Photoacoustic Tomography Imaging System with Dual Single-Element Transducers for Image Enhancement.

OBJECTIVE: This paper proposes a new photoacoustic computed tomography (PACT) imaging system employing dual ultrasonic transducers with different frequencies. When imaging complex biological tissues, photoacoustic (PA) signals with multiple frequencies are produced simultaneously; however, due to the limited bandwidth of a single-frequency transducer, the received PA signals with specific frequencies may be missing, leading to a low imaging quality. METHODS: In contrast to our previous work, the proposed system has a compact volume as well as specific selection of the detection center frequency of the transducer, which can provide a comprehensive range for the detection of PA signals. In this study, a series of numerical simulation and phantom experiments were performed to validate the efficacy of the developed PACT system. RESULTS: The images generated by our system combined the advantages of both high resolution and ideal brightness/contrast. CONCLUSION: The interchangeability of transducers with different frequencies provides potential for clinical deployment under the circumstance where a single frequency transducer cannot perform well.

System introduction and evaluation of the first Chinese chest EIT device for ICU applications.

Chest electrical impedance tomography (EIT) is a promising application which is used to monitor the ventilation and perfusion of the lung at the bedside dynamically. The aim of the study was to introduce the first Chinese made chest EIT device for ICU application (Pulmo EIT-100). The system design of the hardware and software was briefly introduced. The performance of the system was compared to PulmoVista 500 (Dräger Medical) in healthy volunteers. The EIT system Pulmo EIT-100 consists of impedance measurement module, power supply module, PC all-in-one machine, medical cart and accessories. The performance of the system current source and voltage measurement unit was tested. A total of 50 healthy lung volunteers were prospectively examined. Subjects were asked to perform repetitive slow vital capacity (SVC) maneuvers with a spirometer. EIT measurements were performed in the following sequence during each SVC with: (1) Pulmo EIT-100, (2) PulmonVista500, (3) Pulmo EIT-100 and (4) PulmonVista500. Linearity and regional ventilation distribution of the reconstructed images from two devices were compared. The output frequency stability of the current source was 2 ppm. The amplitude error within one hour was less than 0.32‰. The output impedance of the current source was about 50kΩ. The signal-to-noise ratio of each measurement channel was ≥ 60 dB. For fixed resistance measurements, the measured values drifted about 0.08% within one hour. For human subjects, the correlations between the spirometry volume and EIT impedance from two devices were both 0.99 ± 0.01. No statistical significances were found in the parameters investigated. The repeatability (variability) of measures from the same device was comparable. Our EIT device delivers reliable data and might be used for patient measurement in a clinical setting.

Semi-automatic stitching of filamentous structures in image stacks from serial-section electron tomography.

We present a software-assisted workflow for the alignment and matching of filamentous structures across a three-dimensional (3D) stack of serial images. This is achieved by combining automatic methods, visual validation, and interactive correction. After the computation of an initial automatic matching, the user can continuously improve the result by interactively correcting landmarks or matches of filaments. Supported by a visual quality assessment of regions that have been already inspected, this allows a trade-off between quality and manual labour. The software tool was developed in an interdisciplinary collaboration between computer scientists and cell biologists to investigate cell division by quantitative 3D analysis of microtubules (MTs) in both mitotic and meiotic spindles. For this, each spindle is cut into a series of semi-thick physical sections, of which electron tomograms are acquired. The serial tomograms are then stitched and non-rigidly aligned to allow tracing and connecting of MTs across tomogram boundaries. In practice, automatic stitching alone provides only an incomplete solution, because large physical distortions and a low signal-to-noise ratio often cause experimental difficulties. To derive 3D models of spindles despite dealing with imperfect data related to sample preparation and subsequent data collection, semi-automatic validation and correction is required to remove stitching mistakes. However, due to the large number of MTs in spindles (up to 30k) and their resulting dense spatial arrangement, a naive inspection of each MT is too time-consuming. Furthermore, an interactive visualisation of the full image stack is hampered by the size of the data (up to 100 GB). Here, we present a specialised, interactive, semi-automatic solution that considers all requirements for large-scale stitching of filamentous structures in serial-section image stacks. To the best of our knowledge, it is the only currently available tool which is able to process data of the type and size presented here. The key to our solution is a careful design of the visualisation and interaction tools for each processing step to guarantee real-time response, and an optimised workflow that efficiently guides the user through datasets. The final solution presented here is the result of an iterative process with tight feedback loops between the involved computer scientists and cell biologists. LAY DESCRIPTION: Electron tomography of biological samples is used for a three-dimensional (3D) reconstruction of filamentous structures, such as microtubules (MTs) in mitotic and meiotic spindles. Large-scale electron tomography can be applied to increase the reconstructed volume for the visualisation of full spindles. For this, each spindle is cut into a series of semi-thick physical sections, from which electron tomograms are acquired. The serial tomograms are then stitched and non-rigidly aligned to allow tracing and connecting of MTs across tomogram boundaries. Previously, we presented fully automatic approaches for this 3D reconstruction pipeline. However, large volumes often suffer from imperfections (ie physical distortions) caused by the image acquisition process, making it difficult to apply fully automatic approaches for matching and stitching of numerous tomograms. Therefore, we developed an interactive, semi-automatic solution that considers all requirements for large-scale stitching of microtubules in image stacks of consecutive sections. We achieved this by combining automatic methods, visual validation and interactive error correction, thus allowing the user to continuously improve the result by interactively correcting landmarks or matches of filaments. We present large-scale reconstructions of spindles in which the automatic workflow failed and where different steps of manual corrections were needed. Our approach is also applicable to other biological samples showing 3D distributions of MTs in a number of different cellular contexts.

Influence of noise-reduction techniques in sparse-data sample rotation tomographic imaging.

Data acquisition and processing is a critical issue for high-speed applications, especially in three-dimensional live cell imaging and analysis. This paper focuses on sparse-data sample rotation tomographic reconstruction and analysis with several noise-reduction techniques. For the sample rotation experiments, a live Candida rugosa sample is used and controlled by holographic optical tweezers, and the transmitted complex wavefronts of the sample are recorded with digital holographic microscopy. Three different cases of sample rotation tomography were reconstructed for dense angle with a step rotation at every 2°, and for sparse angles with step rotation at every 5° and 10°. The three cases of tomographic reconstruction performance are analyzed with consideration for data processing using four noise-reduction techniques. The experimental results demonstrate potential capability in retaining the tomographic image quality, even at the sparse angle reconstructions, with the help of noise-reduction techniques.

Multicentre study: reliability and repeatability of Scheimpflug system measurement in keratoconus.

PURPOSE: To assess the repeatability and reliability of the most important tomographic parameters for characterising keratoconus measured with a Pentacam HR (high resolution). METHODS: Overall, 230 eyes in 158 patients with keratoconus were analysed. We performed five consecutive corneal tomography examinations for each eye with a Pentacam HR in patients with keratoconus. Study eyes were classified into three groups depending on the maximum posterior elevation (max_BFS_post): grade 1 for cases of keratoconus with a max_BFS_post of 40 µm; grade 2 for those with a max_BFS_post of between 41 and 75 µm and grade 3 for those with a max_BFS_post of over 75 µm. We calculated the intraclass correlation coefficients (ICCs) and repeatability limits of parameters from tomography and aberrometry. RESULTS: All the parameters were found to have excellent ICCs (0.9). The repeatability limits for the key parameters were higher than 0.5D for the power parameters, 20° for the axis of corneal astigmatism and 10 µm for the thinnest corneal thickness. Further, we obtained repeatability limits of above 0.1 µm for the aberrometry values and overall greater than 15° for the coma axis. All the values increase with the severity of keratoconus, except for that of the coma axis which falls with keratoconus grade. CONCLUSIONS: The reliability indicated by ICCs supports the view that the Pentacam HR is useful for the diagnosis of keratoconus. The repeatability limits suggest that new criteria should be established for monitoring progression taking into account the real measurements that can be made using this system.

Corneal thickness evaluation in healthy eyes: Comparison between two different Scheimpflug devices.

PURPOSE: To evaluate the correlation between corneal thickness (CT) measurements obtained with two Scheimpflug devices, Pentacam HR and Precisio, and to elaborate, if necessary, a regression formula which could make these results comparable. DESIGN: Retrospective, Comparative, Observational study. SETTING: Department of Medicine, Surgery and Dentistry, "Scuola Medica Salernitana" University of Salerno, Italy. METHODS: One hundred twenty four healthy eyes of 124 volunteers (65 males; range: 20-32 years; mean age of 24.8 ± 1.7) were included in this study. CT was measured using Pentacam HR and Precisio in three different points: the pupil center (PC), the corneal apex (CA) and the thinnest point (TP). RESULTS: CT obtained with both devices at the PC, at the CA and at the TP showed a good correlation (r = 0.97, r = 0.97, r = 0.97, respectively), but Pentacam HR measurements were significantly thicker than those provided by Precisio (p < 0.01). The differences between Pentacam HR and Precisio were 21.9 ± 8.8 µm at the PC, 21.9 ± 8.9 µm at the CA, 19.1 ± 9.0 µm at the TP. The calculated regression formulas were: y = 0.9558x + 2.3196 for the PC, y = 0.9519x + 4.5626 for the CA, y = 0.9364x + 15.436 for the TP, where x is the CT measured with Pentacam HR and y is the Precisio measurement. CONCLUSIONS: The findings provided by this study highlight that Precisio measures thinner corneas compared to Pentacam HR. The identified regression formulas could be utilized to make interchangeable the results obtained with these two devices.

The experimental study of mouse liver in magneto-acousto-electrical tomography by scan mode.

Magneto-acousto-electrical tomography (MAET) is an imaging method coupled with sound field and magnetic field. The aim of this study is to present some novel experimental results of the mouse liver for the magneto-acousto-electrical tomography measured by two electrodes. The magnetic field in the space of 60 mm3 is about 300 mT which generate by two permanent magnets. A plane transducer with 2.25 MHz center frequency is utilized to generate acoustic waves inside the object. The signal is detected by two similar 1 mm copper foil electrodes. An amplifier is designed to receive the MAET signal, and the gain of the amplifier is adjusted to be 54 dB. The phantom used in this paper is a mouse liver surrounded by a gel phantom with the conductivity of 0.7 S m-1. The gel phantom with the conductivity of 0.7 S m-1 is used to simulate the liver tumor, and the normal mouse liver is filled in the phantom. A series of the MAET signals are detected by the electrodes when the transducer is moved on a pre-set line route, then a B-scan image is realized. The experimental system can provide more information about the tumor and the results show that the MAET is sensitive enough for the potential clinical application of tumor in animal or human.

High pulse energy fibre laser as an excitation source for photoacoustic tomography.

A custom fibre laser designed as an excitation source for biomedical photoacoustic tomography has been developed. It is based on a custom-drawn large core diameter fibre (200 µm) that enables high pulse energies (∼10 mJ) to be achieved. The system can provide variable pulse durations (10 - 500 ns) and pulse repetition frequencies (100 Hz - 1 kHz), as well as arbitrary pulse bursts according to specific user defined sequences. The system is also compact and does not require external water cooling. This, along with the flexibility in the temporal characteristics of its output that it offers, will aid the translation of photoacoustic imaging to practical application in medicine and biology.

3D finger vein biometric authentication with photoacoustic tomography.

Biometric authentication is the recognition of human identity via unique anatomical features. The development of novel methods parallels widespread application by consumer devices, law enforcement, and access control. In particular, methods based on finger veins, as compared to face and fingerprints, obviate privacy concerns and degradation due to wear, age, and obscuration. However, they are two-dimensional (2D) and are fundamentally limited by conventional imaging and tissue-light scattering. In this work, for the first time, to the best of our knowledge, we demonstrate a method of three-dimensional (3D) finger vein biometric authentication based on photoacoustic tomography. Using a compact photoacoustic tomography setup and a novel recognition algorithm, the advantages of 3D are demonstrated via biometric authentication of index finger vessels with false acceptance, false rejection, and equal error rates <1.23%, <9.27%, and <0.13%, respectively, when comparing one finger, a false acceptance rateimprovement>10× when comparing multiple fingers, and <0.7% when rotating fingers ±30.

Technologies for magnetic induction tomography sensors and image reconstruction in medical assisted diagnosis: A review.

Magnetic induction tomography (MIT) is a non-invasive and non-contact imaging technology, which can be used in medical diagnosis by reconstructing the electrical distribution of biological tissues. Unlike other large medical imaging equipment, the device of MIT is with small size and low cost. The theoretical basis of MIT is by measuring the phase difference of magnetic flux density generated around the imaging objects, analyzing the eddy current distribution, and then using the reconstruction algorithms to obtain the electrical characteristic distribution of the object. This review introduces the development of imaging systems and the reconstruction algorithms of MIT as a medical assisted diagnostic technology, including the optimal design of the sensors, the excitation methods of the system, the calculation methods of the eddy current, and the improved methods of different reconstruction algorithms.

Bladder Volume Monitoring Using Electrical Impedance Tomography With Simultaneous Multi-Tone Tissue Stimulation and DFT-Based Impedance Calculation Inside an FPGA.

In this article, a novel method for measuring the volume of the urinary bladder non-invasively is presented that relies on the principles dictated by Electrical Impedance Tomography (EIT). The electronic prototype responsible for injecting innocuous electrical currents to the lower abdominal region and measuring the developed voltage levels is fully described, as well as the computational models for resolution of the so-called Forward and Inverse Problems in Imaging. The simultaneous multi-tone injection of current provided by a high performance Field Programmable Gate Array (FPGA), combined with impedance estimation by the Discrete Fourier Transform (DFT) constitutes a novelty in Urodynamics with potential to monitor continuously the intravesical volume of patients in a much faster and comfortable way than traditional transurethral catheterization methods. The resolution of the Inverse Problem is performed by the Gauss-Newton method with Laplacian regularization, allowing to obtain a sectional representation of the volume of urine encompassed by the bladder and surrounding body tissues. Experimentation has been carried out with synthetic phantoms and human subjects with results showing a good correlation between the levels of abdominal admittivity acquired by the EIT system and the volume of ingested water.

A 1 MHz Miniaturized Electrical Impedance Tomography System for Prostate Imaging.

An ASIC for a high frequency electrical impedance tomography (EIT) imaging system for prostate cancer screening is presented. The ASIC enables a small form-factor architecture, which ensures high signal-to-noise ratio (SNR) at MHz frequencies. The 4-channel ASIC was designed and fabricated in a standard CMOS 0.18- µm technology and integrates a novel current driver for current stimulus, instrumentation amplifier to interface with the tissue, VGA to provide variable gain and ADC with SPI interface for digitization. A prototype miniaturized EIT system was built and it was evaluated using a model transrectal imaging probe immersed into a tank filled with saline and a metal inclusion that demonstrated the open-domain problem of imaging prostate cancer lesion. The system maintained an SNR between 66 and 76 dB over the frequency range of 500 Hz to 1 MHz. Also, it produced reconstructed EIT images that depicted the presence of the small metal inclusion that modeled a prostate cancer imaging application.

A Comparative Study of Total Corneal Power Using a Ray Tracing Method Obtained from 3 Different Scheimpflug Camera Devices.

PURPOSE: We sought to assess the agreement of ray-traced corneal power values by 3 Scheimpflug tomographers tp construct the corresponding arithmetic adjustment factor in comparison with an automated keratometer (IOLMaster) and a conventional Placido-based topographer (Allegro Topolyzer). DESIGN: Prospective reliability analysis. METHODS: A total of 74 eyes from 74 healthy subjects who underwent corneal power measurements using Pentacam, Sirius, Galilei, IOLMaster, and Allegro Topolyzer were included. Ray-traced corneal power values, such as total corneal refractive power (TCRP), mean pupil power (MPP), total corneal power (TCP), mean keratometry (Km), and simulated keratometry (SimK) were recorded respectively and analyzed using one-way analysis of variance (ANOVA) and Bland-Altman plots. RESULTS: Among the 3 ray-traced corneal power values, TCRP and MPP did not differ significantly (P = 0.81), whereas TCP presented a slightly significant larger value (P < 0.001). Compared to Km or SimK, corneal power measurements by the ray tracing method exhibited significantly lower values (P < 0.001). Bland-Altman plots disclosed that the 3 Scheimpflug tomographers showed similar 95% limits of agreement after arithmetic adjustment compared with Km (-0.40 to 0.40 D, -0.39 to 0.39 D, and -0.35 to 0.34 D) or SimK (-0.50 to 0.51 D, -0.43 to 0.42 D, and -0.46 to 0.46 D). CONCLUSIONS: Ray-traced corneal power values obtained using 3 Scheimpflug tomographers with default diameter settings were similar, indicating that they could be used interchangeably in daily clinical practice. The 3 Scheimpflug tomographers were satisfactory in agreement after arithmetical adjustment compared with conventional automated keratometer or Placido-based topographer.

Screening Candidates for Refractive Surgery With Corneal Tomographic-Based Deep Learning.

Importance: Evaluating corneal morphologic characteristics with corneal tomographic scans before refractive surgery is necessary to exclude patients with at-risk corneas and keratoconus. In previous studies, researchers performed screening with machine learning methods based on specific corneal parameters. To date, a deep learning algorithm has not been used in combination with corneal tomographic scans. Objective: To examine the use of a deep learning model in the screening of candidates for refractive surgery. Design, Setting, and Participants: A diagnostic, cross-sectional study was conducted at the Zhongshan Ophthalmic Center, Guangzhou, China, with examination dates extending from July 18, 2016, to March 29, 2019. The investigation was performed from July 2, 2018, to June 28, 2019. Participants included 1385 patients; 6465 corneal tomographic images were used to generate the artificial intelligence (AI) model. The Pentacam HR system was used for data collection. Interventions: The deidentified images were analyzed by ophthalmologists and the AI model. Main Outcomes and Measures: The performance of the AI classification system. Results: A classification system centered on the AI model Pentacam InceptionResNetV2 Screening System (PIRSS) was developed for screening potential candidates for refractive surgery. The model achieved an overall detection accuracy of 94.7% (95% CI, 93.3%-95.8%) on the validation data set. Moreover, on the independent test data set, the PIRSS model achieved an overall detection accuracy of 95% (95% CI, 88.8%-97.8%), which was comparable with that of senior ophthalmologists who are refractive surgeons (92.8%; 95% CI, 91.2%-94.4%) (P = .72). In distinguishing corneas with contraindications for refractive surgery, the PIRSS model performed better than the classifiers (95% vs 81%; P < .001) in the Pentacam HR system on an Asian patient database. Conclusions and Relevance: PIRSS appears to be useful in classifying images to provide corneal information and preliminarily identify at-risk corneas. PIRSS may provide guidance to refractive surgeons in screening candidates for refractive surgery as well as for generalized clinical application for Asian patients, but its use needs to be confirmed in other populations.

The influence of an electrical impedance tomography belt on lung function determined by spirometry in sitting position.

OBJECTIVE: The aim of the study was to examine whether an electrical impedance tomography (EIT) electrode belt changed the lung function in healthy volunteers and patients with respiratory muscle weakness (RMW) and chronic obstructive pulmonary disease (COPD). APPROACH: In total, thirty subjects were included (10 healthy volunteers, 10 subjects with RMW, maximum inspiratory pressure < 40 cmH2O, and 10 COPD, grade I-IV). Spirometry measurements were conducted in a sitting position once a day at similar times on two consecutive days. Slow expiratory vital capacity (VC), forced vital capacity (FVC) and maximum voluntary ventilation (MVV) manoeuvres were performed. On day 1, spirometry was performed without the EIT electrode belt, and on day 2, the belt was attached to the thorax. MAIN RESULTS: Lung function was not influenced by the electrode belt in healthy subjects. The test-retest reliability in the healthy group was 0.89, 0.89 and 0.85 for VC, FVC and MVV, respectively. On the other hand, all investigated parameters were significantly decreased in the RMW group (VC, 51.3 ± 18.0 versus 46.5 ± 18.0% predicted, without versus with EIT belt, p< 0.01; FVC, 51.7 ± 19.0 versus 45.8 ± 18.1% predicted, p< 0.01; MVV, 41.0 ± 20.0 versus 38.8 ± 19.6% predicted, p< 0.01). VC and MVV also decreased significantly in the COPD group (VC, 77.4 ± 20.5 versus 74.6 ± 18.8% predicted, p< 0.05; MVV, 57.4 ± 15.7 versus 54.4 ± 12.5% predicted, p< 0.05). SIGNIFICANCE: An EIT electrode belt could reduce lung volumes in subjects with pre-existing lung diseases. Comparing lung function acquired with an electrode belt to corresponding values obtained without the belt should be avoided.