Motion Artifacts Reduction for Noninvasive Hemodynamic Monitoring of Conscious Patients Using Electrical Impedance Tomography: A Preliminary Study.

Electrical impedance tomography (EIT) can monitor the real-time hemodynamic state of a conscious and spontaneously breathing patient noninvasively. However, cardiac volume signal (CVS) extracted from EIT images has a small amplitude and is sensitive to motion artifacts (MAs). This study aimed to develop a new algorithm to reduce MAs from the CVS for more accurate heart rate (HR) and cardiac output (CO) monitoring in patients undergoing hemodialysis based on the source consistency between the electrocardiogram (ECG) and the CVS of heartbeats. Two signals were measured at different locations on the body through independent instruments and electrodes, but the frequency and phase were matched when no MAs occurred. A total of 36 measurements with 113 one-hour sub-datasets were collected from 14 patients. As the number of motions per hour (MI) increased over 30, the proposed algorithm had a correlation of 0.83 and a precision of 1.65 beats per minute (BPM) compared to the conventional statical algorithm of a correlation of 0.56 and a precision of 4.04 BPM. For CO monitoring, the precision and upper limit of the mean ∆CO were 3.41 and 2.82 L per minute (LPM), respectively, compared to 4.05 and 3.82 LPM for the statistical algorithm. The developed algorithm could reduce MAs and improve HR/CO monitoring accuracy and reliability by at least two times, particularly in high-motion environments.

Electrospun Rubber Nanofiber Web-Based Dry Electrodes for Biopotential Monitoring.

This study aims to find base materials for dry electrode fabrication with high accuracy and without reducing electrode performance for long-term bioelectric potential monitoring after electroless silver plating. Most applications of dry electrodes that have been developed in the past few decades are restricted by low accuracy compared to commercial Ag/AgCl gel electrodes, as in our previous study of PVDF-based dry electrodes. In a recent study, however, nanoweb-based chlorinated polyisoprene (CPI) and poly(styrene-b-butadiene-b-styrene) (SBS) rubber were selected as promising candidates due to their excellent elastic properties, as well as their nanofibril nature, which may improve electrode durability and skin contact. The electroless silver plating technique was employed to coat the nanofiber web with silver, and silver nanoweb(AgNW)-based dry electrodes were fabricated. The key electrode properties (contact impedance, step response, and noise characteristics) for AgNW dry electrodes were investigated thoroughly using agar phantoms. The dry electrodes were subsequently tested on human subjects to establish their realistic performance in terms of ECG, EMG monitoring, and electrical impedance tomography (EIT) measurements. The experimental results demonstrated that the AgNW dry electrodes, particularly the SBS-AgNW dry electrodes, performed similarly to commercial Ag/AgCl gel electrodes and were outperformed in terms of long-term stability.

Toll-Like Receptors: Expression and Roles in Otitis Media.

Otitis media is mainly caused by upper respiratory tract infection and eustachian tube dysfunction. If external upper respiratory tract infection is not detected early in the middle ear, or an appropriate immune response does not occur, otitis media can become a chronic state or complications may occur. Therefore, given the important role of Toll-like receptors (TLRs) in the early response to external antigens, we surveyed the role of TLRs in otitis media. To summarize the role of TLR in otitis media, we reviewed articles on the expression of TLRs in acute otitis media (AOM), otitis media with effusion (OME), chronic otitis media (COM) with cholesteatoma, and COM without cholesteatoma. Many studies showed that TLRs 1-10 are expressed in AOM, OME, COM with cholesteatoma, and COM without cholesteatoma. TLR expression in the normal middle ear mucosa is absent or weak, but is increased in inflammatory fluid of AOM, effusion of OME, and granulation tissue and cholesteatoma of COM. In addition, TLRs show increased or decreased expression depending on the presence or absence of bacteria, recurrence of disease, tissue type, and repeated surgery. In conclusion, expression of TLRs is associated with otitis media. Inappropriate TLR expression, or delayed or absent induction, are associated with the occurrence, recurrence, chronicization, and complications of otitis media. Therefore, TLRs are very important in otitis media and closely related to its etiology.

CaSR-Mediated hBMSCs Activity Modulation: Additional Coupling Mechanism in Bone Remodeling Compartment.

Near the bone remodeling compartments (BRC), extracellular calcium concentration (Ca2+o) is locally elevated and bone marrow stromal cells (BMSCs) close to the BRC can be exposed to high calcium concentration. The calcium-sensing receptor (CaSR) is known to play a key role in maintaining extracellular calcium homeostasis by sensing fluctuations in the levels of extracellular calcium (Ca2+o). When human BMSCs (hBMSCs) were exposed to various calcium concentrations (1.8, 3, 5, 10, 30 mM), moderate-high extracellular calcium concentrations (3-5 mM) stimulated proliferation, while a high calcium concentration (30 mM) inhibited the proliferation. Exposure to various calcium concentrations did not induce significant differences in the apoptotic cell fraction. Evaluation of multi-lineage differentiation potential showed no significant difference among various calcium concentration groups, except for the high calcium concentration (30 mM) treated group, which resulted in increased calcification after in vitro osteogenic differentiation. Treatment of NPS2143, a CaSR inhibitor, abolished the stimulatory effect on hBMSCs proliferation and migration indicating that CaSR is involved. These results suggest that the calcium concentration gradient near the BRC may play an important role in bone remodeling by acting as an osteoblast-osteoclast coupling mechanism through CaSR.

Integrated EIT system for functional lung ventilation imaging.

BACKGROUND: Electrical impedance tomography (EIT) has been used for functional lung imaging of regional air distributions during mechanical ventilation in intensive care units (ICU). From numerous clinical and animal studies focusing on specific lung functions, a consensus about how to use the EIT technique has been formed lately. We present an integrated EIT system implementing the functions proposed in the consensus. The integrated EIT system could improve the usefulness when monitoring of mechanical ventilation for lung protection so that it could facilitate the clinical acceptance of this new technique. METHODS: Using a custom-designed 16-channel EIT system with 50 frames/s temporal resolution, the integrated EIT system software was developed to implement five functional images and six EIT measures that can be observed in real-time screen view and analysis screen view mode, respectively. We evaluated the performance of the integrated EIT system with ten mechanically ventilated porcine subjects in normal and disease models. RESULTS: Quantitative and simultaneous imaging of tidal volume (TV), end-expiratory lung volume change ([Formula: see text]EELV), compliance, ventilation delay, and overdistension/collapse images were performed. Clinically useful parameters were successfully extracted including anterior/posterior ventilation ratio (A/P ratio), center of ventilation ([Formula: see text], [Formula: see text]), global inhomogeneity (GI), coefficient of variation (CV), ventilation delay and percentile of overdistension/collapse. The integrated EIT system was demonstrated to suggest an optimal positive end-expiratory pressure (PEEP) for lung protective ventilation in normal and in the disease model of an acute injury. Optimal PEEP for normal and disease model was 2.3 and [Formula: see text], respectively. CONCLUSIONS: The proposed integrated approach for functional lung ventilation imaging could facilitate clinical acceptance of the bedside EIT imaging method in ICU. Future clinical studies of applying the proposed methods to human subjects are needed to show the clinical significance of the method for lung protective mechanical ventilation and mechanical ventilator weaning in ICU.

Cell-Surface Engineering for Advanced Cell Therapy.

Stem cells opened great opportunity to overcome diseases that conventional therapy had only limited success. Use of scaffolds made from biomaterials not only helps handling of stem cells for delivery or transplantation but also supports enhanced cell survival. Likewise, cell encapsulation can provide stability for living animal cells even in a state of separateness. Although various chemical reactions were tried to encapsulate stolid microbial cells such as yeasts, a culture environment for the growth of animal cells allows only highly biocompatible reactions. Therefore, the animal cells were mostly encapsulated in hydrogels, which resulted in enhanced cell survival. Interestingly, major findings of chemistry on biological interfaces demonstrate that cell encapsulation in hydrogels have a further a competence for modulating cell characteristics that can go beyond just enhancing the cell survival. In this review, we present a comprehensive overview on the chemical reactions applied to hydrogel-based cell encapsulation and their effects on the characteristics and behavior of living animal cells.

Non-destructive label-free continuous monitoring of in vitro chondrogenesis via electrical conductivity and its anisotropy.

Non-destructive label-free continuous monitoring of in vitro tissue culture is an unmet demand in tissue engineering. Noting that different compositions of cartilage lead to different electrical tissue properties, we propose a new method to measure the electrical conductivity and its anisotropy during in vitro chondrogenesis. We used a conductivity tensor probe with 17 electrodes and a bio-impedance spectroscopy (BIS) device to measure the conductivity values and the anisotropy ratios at the bottom and top surfaces of the tissue samples during the culture period of 6 weeks. Clearly distinguishing glycosaminoglycans (GAGs), collagen, and also various mixtures of them, the measured conductivity value and the estimated tissue anisotropy provide diagnostic information of the depth-dependent tissue structure and compositions. Continuously monitoring the individual tissue during the entire chondrogenesis process without any adverse effect, the proposed method may significantly increase the productivity of cartilage tissue engineering.

Real-time conductivity imaging of temperature and tissue property changes during radiofrequency ablation: an ex vivo model using weighted frequency difference.

We demonstrated the feasibility of time difference and weighted frequency difference conductivity imaging for real-time monitoring of temperature distribution and ablation region estimation during radiofrequency (RF) ablation. The electrical conductivity spectrum of biological tissue reflects mobility of ions in intra- and extra-cellular fluids and changes in cellular morphology induced by heating. The time series conductivity spectra were measured in an ex vivo bovine liver by a high-speed electrical impedance tomography (EIT) system. The EIT system was protected by filters to suppress RF energy and allow interleaved real-time imaging. We recorded time and weighted frequency-difference conductivity images and direct temperature variations at the ablation region and control region during 8 min ablation and for the following 66 min of cooling. Conductivity variation in regions of interest was compared with temperature recordings. Contours of conductivity change were visualized and compared to estimate the ablation area. EIT images confirmed increase of conductivity at all frequencies and loss of frequency conductivity change associated with loss of cellular structure. Time difference conductivity images showed changes due to both heating during ablation and heat dissipation following ablation together with tissue property changes. Weighted frequency-difference images presented persistent changes following heating due to the morphological change in the ablation zone.

Electrical impedance imaging system using FPGAs for flexibility and interoperability.

BACKGROUND: Modern EIT systems require simultaneously operating multiple functions for flexibility, interoperability, and clinical applicability. To implement versatile functions, expandable design and implementation tools are needed. On the other hand, it is necessary to develop an ASIC-based EIT system to maximize its performance. Since the ASIC design is expensive and unchangeable, we can use FPGAs as a prior step to the digital ASIC design and carefully classify which functions should be included in the ASIC. In this paper, we describe the details of the FPGA design adopted in the KHU Mark2.5 EIT system. METHODS: We classified all functions of the KHU Mark2.5 EIT system into two categories. One is the control and processing of current injection and voltage measurement. The other includes the collection and management of the multi-channel data with timing controls for internal and external interconnections. We describe the implementation of these functions in two kinds of FPGAs called the impedance measurement module (IMM) FPGA and the intra-network controller FPGA. RESULTS: We present functional and timing simulations of the key functions in the FPGAs. From phantom and animal imaging experiments, we show that multiple functions of the system are successfully implemented in the FPGAs. As examples, we demonstrate fast multi-frequency imaging and ECG-gated imaging. CONCLUSION: Given an analog design of a parallel EIT system, it is important to optimize its digital design to minimize systematic artifacts and maximize performance. This paper described technical details of the FPGA-based fully parallel EIT system called the KHU Mark2.5 with numerous functions needed for clinical applications. Two kinds of FPGAs described in this paper can be used as a basis for future EIT digital ASIC designs for better application-specific human interface as well as hardware performance.

Conductivity image enhancement in MREIT using adaptively weighted spatial averaging filter.

BACKGROUND: In magnetic resonance electrical impedance tomography (MREIT), we reconstruct conductivity images using magnetic flux density data induced by externally injected currents. Since we extract magnetic flux density data from acquired MR phase images, the amount of measurement noise increases in regions of weak MR signals. Especially for local regions of MR signal void, there may occur excessive amounts of noise to deteriorate the quality of reconstructed conductivity images. In this paper, we propose a new conductivity image enhancement method as a postprocessing technique to improve the image quality. METHODS: Within a magnetic flux density image, the amount of noise varies depending on the position-dependent MR signal intensity. Using the MR magnitude image which is always available in MREIT, we estimate noise levels of measured magnetic flux density data in local regions. Based on the noise estimates, we adjust the window size and weights of a spatial averaging filter, which is applied to reconstructed conductivity images. Without relying on a partial differential equation, the new method is fast and can be easily implemented. RESULTS: Applying the novel conductivity image enhancement method to experimental data, we could improve the image quality to better distinguish local regions with different conductivity contrasts. From phantom experiments, the estimated conductivity values had 80% less variations inside regions of homogeneous objects. Reconstructed conductivity images from upper and lower abdominal regions of animals showed much less artifacts in local regions of weak MR signals. CONCLUSION: We developed the fast and simple method to enhance the conductivity image quality by adaptively adjusting the weights and window size of the spatial averaging filter using MR magnitude images. Since the new method is implemented as a postprocessing step, we suggest adopting it without or with other preprocessing methods for application studies where conductivity contrast is of primary concern.

Design of a microscopic electrical impedance tomography system for 3D continuous non-destructive monitoring of tissue culture.

BACKGROUND: Non-destructive continuous monitoring of regenerative tissue is required throughout the entire period of in vitro tissue culture. Microscopic electrical impedance tomography (micro-EIT) has the potential to monitor the physiological state of tissues by forming three-dimensional images of impedance changes in a non-destructive and label-free manner. We developed a new micro-EIT system and report on simulation and experimental results of its macroscopic model. METHODS: We propose a new micro-EIT system design using a cuboid sample container with separate current-driving and voltage sensing electrodes. The top is open for sample manipulations. We used nine gold-coated solid electrodes on each of two opposing sides of the container to produce multiple linearly independent internal current density distributions. The 360 voltage sensing electrodes were placed on the other sides and base to measure induced voltages. Instead of using an inverse solver with the least squares method, we used a projected image reconstruction algorithm based on a logarithm formulation to produce projected images. We intended to improve the quality and spatial resolution of the images by increasing the number of voltage measurements subject to a few injected current patterns. We evaluated the performance of the micro-EIT system with a macroscopic physical phantom. RESULTS: The signal-to-noise ratio of the developed micro-EIT system was 66 dB. Crosstalk was in the range of -110.8 to -90.04 dB. Three-dimensional images with consistent quality were reconstructed from physical phantom data over the entire domain. From numerical and experimental results, we estimate that at least 20 × 40 electrodes with 120 µm spacing are required to monitor the complex shape of ingrowth neotissue inside a scaffold with 300 µm pore. CONCLUSION: The experimental results showed that the new micro-EIT system with a reduced set of injection current patterns and a large number of voltage sensing electrodes can be potentially used for tissue culture monitoring. Numerical simulations demonstrated that the spatial resolution could be improved to the scale required for tissue culture monitoring. Future challenges include manufacturing a bioreactor-compatible container with a dense array of electrodes and a larger number of measurement channels that are sensitive to the reduced voltage gradients expected at a smaller scale.

Reconstruction of dual-frequency conductivity by optimization of phase map in MREIT and MREPT.

BACKGROUND: The spectroscopic conductivity distribution of tissue can help to explain physiological and pathological status. Dual frequency conductivity imaging by combining Magnetic Resonance Electrical Property Tomography (MREPT) and Magnetic Resonance Electrical Impedance Tomography (MREIT) has been recently proposed. MREIT can provide internal conductivity distributions at low frequency (below 1 kHz) induced by an external injecting current. While MREPT can provide conductivity at the Larmor frequency related to the strength of the magnetic field. Despite this potential to describe the membrane properties using spectral information, MREPT and MREIT techniques currently suffer from weak signals and noise amplification as they both reply on differentiation of measured phase data. METHODS: We proposed a method to optimize the measured phase signal by finding weighting factors according to the echo signal for MREPT and MREIT using the ICNE (Injected current nonlinear encoding) multi-echo pulse sequence. Our target weights are chosen to minimize the measured noise. The noise standard deviations were precisely analyzed for the optimally weighted magnetic flux density and the phase term of the positive-rotating magnetic field. To enhance the quality of dual-frequency conductivity images, we applied the denoising method based on the reaction-diffusion equation with the estimated noise standard deviations. A real experiment was performed with a hollow cylindrical object made of thin insulating film with holes to control the apparent conductivity using ion mobility and an agarose gel cylinder wrapped in an insulating film without holes to show different spectroscopic conductivities. RESULTS: The ability to image different conductivity characteristics in MREPT and MREIT from a single MR scan was shown by including the two objects with different spectroscopic conductivities. Using the six echo signals, we computed the optimized weighting factors for each echo. The qualities of conductivity images for MREPT and MREIT were improved by optimization of the phase map. The proposed method effectively reduced the random noise artifacts for both MREIT and MREPT. CONCLUSION: We enhanced the dual conductivity images using the optimally weighted magnetic flux density and the phase term of positive-rotating magnetic field based on the analysis of the noise standard deviations and applying the optimization and denoising methods.

Fast conductivity imaging in magnetic resonance electrical impedance tomography (MREIT) for RF ablation monitoring.

PURPOSE: This study shows the potential of magnetic resonance electrical impedance tomography (MREIT) as a non-invasive RF ablation monitoring technique. MATERIALS AND METHODS: We prepared bovine muscle tissue with a pair of needle electrodes for RF ablation, a temperature sensor, and two pairs of surface electrodes for conductivity image reconstructions. We used the injected current non-linear encoding with multi-echo gradient recalled echo (ICNE-MGRE) pulse sequence in a series of MREIT scans for conductivity imaging. We acquired magnetic flux density data induced by externally injected currents, while suppressing other phase artefacts. We used an 8-channel RF head coil and 8 echoes to improve the signal-to-noise ratio (SNR) in measured magnetic flux density data. Using the measured data, we reconstructed a time series of 180 conductivity images at every 10.24 s during and after RF ablation. RESULTS: Tissue conductivity values in the lesion increased with temperature during RF ablation. After reaching 60 °C, a steep increase in tissue conductivity values occurred with relatively little temperature increase. After RF ablation, tissue conductivity values in the lesion decreased with temperature, but to values different from those before ablation due to permanent structural changes of tissue by RF ablation. CONCLUSION: We could monitor temperature and also structural changes in tissue during RF ablation by producing spatio-temporal maps of tissue conductivity values using a fast MREIT conductivity imaging method. We expect that the new monitoring method could be used to estimate lesions during RF ablation and improve the efficacy of the treatment.

Electrical impedance spectroscopy for electro-mechanical characterization of conductive fabrics.

When we use a conductive fabric as a pressure sensor, it is necessary to quantitatively understand its electromechanical property related with the applied pressure. We investigated electromechanical properties of three different conductive fabrics using the electrical impedance spectroscopy (EIS). We found that their electrical impedance spectra depend not only on the electrical properties of the conductive yarns, but also on their weaving structures. When we apply a mechanical tension or compression, there occur structural deformations in the conductive fabrics altering their apparent electrical impedance spectra. For a stretchable conductive fabric, the impedance magnitude increased or decreased under tension or compression, respectively. For an almost non-stretchable conductive fabric, both tension and compression resulted in decreased impedance values since the applied tension failed to elongate the fabric. To measure both tension and compression separately, it is desirable to use a stretchable conductive fabric. For any conductive fabric chosen as a pressure-sensing material, its resistivity under no loading conditions must be carefully chosen since it determines a measurable range of the impedance values subject to different amounts of loadings. We suggest the EIS method to characterize the electromechanical property of a conductive fabric in designing a thin and flexible fabric pressure sensor.

Feasibility of magnetic resonance electrical impedance tomography (MREIT) conductivity imaging to evaluate brain abscess lesion: in vivo canine model.

PURPOSE: To show the feasibility of magnetic resonance electrical impedance tomography (MREIT) conductivity imaging in terms of its capability to provide new contrast information of abscess lesion and characterize time-course variations before and after the induction of brain abscess. MATERIALS AND METHODS: Brain abscess was induced in healthy beagles by a direct inoculation method using Staphylococcus pseudintermedius. After the induction, four electrodes were attached on the head and the dog was placed inside the magnetic resonance imaging (MRI) bore. Using a current source, we injected a current of amplitude 5 mA and a pulse width of 81 msec. A multi-echo ICNE pulse sequence was used to obtain the magnetic flux density (Bz ) data. RESULTS: The relative conductivity contrast ratios (rCCR, %) of abscess lesion were significantly changed by the postinduction time (P < 0.01). The rCCRs of central abscess lesions were higher than the surrounding area at 6, 12, and 18 hours (P < 0.01). Over 12 hours, the relationship between the induction time and rCCR showed a positive correlation followed by a negative correlation (P < 0.01). CONCLUSION: We performed in vivo disease model animal experiments to validate the MREIT technique providing conductivity information of tissues in situ to be utilized in clinical applications.

Reconstruction of Fibrocartilage with Fibrous Alignment of Type I Collagen in Scaffold-Free Manner.

For functional reconstruction of fibrocartilage, it is necessary to reproduce the essential mechanical property exhibited by natural fibrocartilage. The distinctive mechanical property of fibrocartilage is originated from the specific histological features of fibrocartilage composed of highly aligned type I collagen (Col I) and an abundant cartilaginous matrix. While the application of tensile stimulation induces highly aligned Col I, our study reveals that it also exerts an antichondrogenic effect on scaffold-free tissues constructed with meniscal chondrocytes (MCs) and induces downregulation of Sox-9 expression and attenuated glycosaminoglycan production. Modulation of mechanotransduction by blocking nuclear translocation of Yes-associated protein (YAP) ameliorated the antichondrogenic effect in the presence of tensile stimulation. Since MCs subjected to mechanical doses either by surface stiffness or tensile stimulation showed reversibility of YAP status even after a long-term exposure to mechanotransduction, fibrocartilage tissue was constructed by sequentially inducing tissue alignment by tensile stimulation followed by inducing cartilaginous matrix production in a tension-released state. The minimal tensile dose to constitute durable tissue alignment was screened by investigating the alignment of cytoskeleton and Col I after culturing the scaffold-free tissue constructs with various tensile doses (10% static tension for 1, 3, 7, and 10 days) followed by maintaining in a released state for 5 days. Fluorescence-conjugated phalloidin binding and immunofluorescence of Col I indicated that the duration of static tension for more than 7 days resulted in durable tissue alignment for at least 5 days in the tension-released state. The tissues subjected to tensile stimulation for 7 days followed by 14 days in a released state in chondrogenic media resulted in abundant cartilaginous matrix as well as uniaxial anisotropic alignment. Our results show that the optimized tensile dose can facilitate the successful reconstruction of fibrocartilage by modulating the characteristics of matrix production by MCs.

Real-Time Measurements of Relative Tidal Volume and Stroke Volume Using Electrical Impedance Tomography with Spatial Filters: A Feasibility Study in a Swine Model Under Normal and Reduced Ventilation.

Continuous monitoring of both hemodynamic and respiratory parameters would be beneficial to patients, e.g., those in intensive care unit. The objective of this exploratory animal study was to test the feasibility of simultaneous measurements of relative tidal volume (rTV) and relative stroke volume (rSV) using an electrical impedance tomography (EIT) device equipped with a new real-time source separation algorithm implemented as two spatial filters. Five pigs were anesthetized and mechanically ventilated. The supplied tidal volume from a mechanical ventilator was reduced to 70, 50 and 30% from the 100% normal volume to simulate hypoventilation. The respiratory volume signal and cardiac volume signal were generated by applying the spatial filters to the acquired EIT data, from which values of rTV and rSV were extracted. The measured rTV values were compared with the TV values from the mechanical ventilator using the four-quadrant concordance analysis method. For changes in TV, the concordance rate in each animal ranged from 81.8% to 100%, while it was 92.5% when the data from all five animals were pooled together. When the measured rTV values for each animal were scaled to the absolute TVEIT values in mL using the TVVent data from the mechanical ventilator, the smallest 95% limits of agreement (LoA) were - 6.04 and 7.44 mL for the 70% ventilation level, and the largest 95% LoA were - 18.1 and 19.4 mL for the 50% ventilation level. The percentage error between TVEIT and TVVent was 10.3%. Although similar statistical analyses on rSV data could not be performed due to limited intra-animal variability, changes in rSV values measured by the EIT device were comparable to those measured by an invasive hemodynamic monitor. In this animal study, we were able to demonstrate the feasibility of an EIT device for noninvasive and simultaneous measurements of rTV and rSV in real time. However, the performance of the real-time source separation method needs to be further validated on animals and human subjects, particularly over a wide range of SV values. Future clinical studies are needed to assess the potential usefulness of the new method in dynamic cardiopulmonary monitoring and explore other clinical applications.

Measurement of extracellular volume fraction using magnetic resonance-based conductivity tensor imaging.

Conductivity tensor imaging (CTI) using MRI is an advanced method that can non-invasively measure the electrical properties of living tissues. The contrast of CTI is based on underlying hypothesis about the proportionality between the mobility and diffusivity of ions and water molecules inside tissues. The experimental validation of CTI in both in vitro and in vivo settings is required as a reliable tool to assess tissue conditions. The changes in extracellular space can be indicators for disease progression, such as fibrosis, edema, and cell swelling. In this study, we conducted a phantom imaging experiment to test the feasibility of CTI for measuring the extracellular volume fraction in biological tissue. To mimic tissue conditions with different extracellular volume fractions, four chambers of giant vesicle suspension (GVS) with different vesicle densities were included in the phantom. The reconstructed CTI images of the phantom were compared with the separately-measured conductivity spectra of the four chambers using an impedance analyzer. Moreover, the values of the estimated extracellular volume fraction in each chamber were compared with those measured by a spectrophotometer. As the vesicle density increased, we found that the extracellular volume fraction, extracellular diffusion coefficient, and low-frequency conductivity decreased, while the intracellular diffusion coefficient slightly increased. On the other hand, the high-frequency conductivity could not clearly distinguish the four chambers. The extracellular volume fraction measured by the spectrophotometer and CTI method in each chamber were quite comparable, i.e., (1.00, 0.98 ± 0.01), (0.59, 0.63 ± 0.02), (0.40, 0.40 ± 0.05), and (0.16, 0.18 ± 0.02). The prominent factor influencing the low-frequency conductivity at different GVS densities was the extracellular volume fraction. Further studies are needed to validate the CTI method as a tool to measure the extracellular volume fractions in living tissues with different intracellular and extracellular compartments.

High density trans-admittance mammography development and preliminary phantom tests.

BACKGROUND: Malignant breast tumor tissue has a significantly different electrical impedance spectrum than surrounding normal tissues. This has led to the development of impedance imaging as a supplementary or alternative method to X-ray mammography for screening and assessment of breast cancers. However low spatial resolution and poor signal to noise ratio has limited the clinical application. METHODS: In order to improve spatial resolution we developed a trans-admittance mammography (TAM) system including an array of 60×60 current sensing electrodes. We adopted a similar setup to X-ray mammography where the breast is situated between two holding plates. The top plate is a large solid metal electrode for applying a sinusoidal voltage over a range of frequencies from 50 Hz to 500 kHz. The bottom plate has 3600 current sensing electrodes that are kept at the ground potential. Currents are generated from the top voltage-applying electrode and spread throughout the breast, entering the TAM system through the array of current sensing electrodes on the bottom plate. The TAM system measures the exit currents through 6 switching modules connected to 600 electrodes each. Each switching module is connected to 12 ammeter channels which are switched sequentially to 50 of the 600 electrodes each measurement time. Each ammeter channel is comprised of a current-to-voltage converter, a gain amplifier, filters, an analog to digital converter, and a digital phase sensitive demodulator. RESULTS: We found an average noise level of 38 nA, amplitude stability of less than 0.2%, crosstalk of better than -60 dB and 70 dB signal to noise ratio over all channels and operating frequencies. Images were obtained in time difference and frequency difference modes in a saline phantom. CONCLUSION: We describe the design, construction, and calibration of a high density TAM system in detail. Successful high resolution time and frequency difference images showed regions of interest with the expected admittivity changes in the frequency spectrum.

Biomaterials for Cell-Surface Engineering and Their Efficacy.

Literature in the field of stem cell therapy indicates that, when stem cells in a state of single-cell suspension are injected systemically, they show poor in vivo survival, while such cells show robust cell survival and regeneration activity when transplanted in the state of being attached on a biomaterial surface. Although an attachment-deprived state induces anoikis, when cell-surface engineering technology was adopted for stem cells in a single-cell suspension state, cell survival and regenerative activity dramatically improved. The biochemical signal coming from ECM (extracellular matrix) molecules activates the cell survival signal transduction pathway and prevents anoikis. According to the target disease, various therapeutic cells can be engineered to improve their survival and regenerative activity, and there are several types of biomaterials available for cell-surface engineering. In this review, biomaterial types and application strategies for cell-surface engineering are presented along with their expected efficacy.