Frequency-Division Multiplexing for Electrical Impedance Tomography in Biomedical Applications

Electrical impedance tomography (EIT) produces an image of the electrical impedance distribution of tissues in the body, using electrodes that are placed on the periphery of the imaged area. These electrodes inject currents and measure voltages and from these data, the impedance can be computed. Traditional EIT systems usually inject current patterns in a serial manner which means that the impedance is computed from data collected at slightly different times. It is usually also a time-consuming process. In this paper, we propose a method for collecting data concurrently from all of the current patterns in biomedical applications of EIT. This is achieved by injecting current through all of the current injecting electrodes simultaneously, and measuring all of the resulting voltages at once. The signals from various current injecting electrodes are separated by injecting different frequencies through each electrode. This is called frequency-division multiplexing (FDM). At the voltage measurement electrodes, the voltage related to each current injecting electrode is isolated by using Fourier decomposition. In biomedical applications, using different frequencies has important implications due to dispersions as the tissue's electrical properties change with frequency. Another significant issue arises when we are recording data in a dynamic environment where the properties change very fast. This method allows simultaneous measurements of all the current patterns, which may be important in applications where the tissue changes occur in the same time scale as the measurement. We discuss the FDM EIT method from the biomedical point of view and show results obtained with a simple experimental system

A New Concept for Medical Imaging Centered on Cellular Phone Technology

According to World Health Organization reports, some three quarters of the world population does not have access to medical imaging. In addition, in developing countries over 50% of medical equipment that is available is not being used because it is too sophisticated or in disrepair or because the health personnel are not trained to use it. The goal of this study is to introduce and demonstrate the feasibility of a new concept in medical imaging that is centered on cellular phone technology and which may provide a solution to medical imaging in underserved areas. The new system replaces the conventional stand-alone medical imaging device with a new medical imaging system made of two independent components connected through cellular phone technology. The independent units are: a) a data acquisition device (DAD) at a remote patient site that is simple, with limited controls and no image display capability and b) an advanced image reconstruction and hardware control multiserver unit at a central site. The cellular phone technology transmits unprocessed raw data from the patient site DAD and receives and displays the processed image from the central site. (This is different from conventional telemedicine where the image reconstruction and control is at the patient site and telecommunication is used to transmit processed images from the patient site). The primary goal of this study is to demonstrate that the cellular phone technology can function in the proposed mode. The feasibility of the concept is demonstrated using a new frequency division multiplexing electrical impedance tomography system, which we have developed for dynamic medical imaging, as the medical imaging modality. The system is used to image through a cellular phone a simulation of breast cancer tumors in a medical imaging diagnostic mode and to image minimally invasive tissue ablation with irreversible electroporation in a medical imaging interventional mode

Development of a CMOS-compatible PCR chip : comparison of design and system strategies

Altres ajuts: this work was partly funded by the Consejo Superior de Investigaciones Científicas (CSIC), by grant TIC97-0569 from the Comision Interministerial de Ciencia y Tecnología (CICYT).In the last decade research in chips for DNA amplification through the polymerase chain reaction (PCR) has been relatively abundant, but has taken very diverse approaches, leaving little common ground for a straightforward comparison of results. Here we report the development of a line of PCR chips that is fully compatible with complementary-metal-oxide-semiconductor (CMOS) technology and its revealing use as a general platform to test and compare a wide range of experimental parameters involved in PCR-chip design and operation. Peltier-heated and polysilicon thin-film driven PCR chips have been produced and directly compared in terms of efficiency, speed and power consumption, showing that thin-film systems run faster and more efficiently than Peltier-based ones, but yield inferior PCR products. Serpentine-like chamber designs have also been compared with standard rectangular designs and with the here reported rhomboidal chamber shape, showing that serpentine-like chambers do not have detrimental effects in PCR efficiency when using non-flow-through schemes, and that chamber design has a strong impact on sample insertion/extraction yields. With an accurate temperature control (±0.2 °C) we have optimized reaction kinetics to yield sound PCR amplifications of 25 µl mixtures in 20 min and with 24.4 s cycle times, confirming that a titrated amount of bovine albumin serum (BSA, 2.5 µg µl−1) is essential to counteract polymerase adsorption at chip walls. The reported use of a CMOS-compatible technological process paves the way for an easy adaption to foundry requirements and for a scalable integration of electro-optic detection and control circuitr

Non Thermal Irreversible Electroporation: Novel Technology for Vascular Smooth Muscle Cells Ablation

Non thermal Irreversible electroporation (NTIRE) is a new tissue ablation method that induces selective damage only to the cell membrane while sparing all other tissue components. Our group has recently showed that NTIRE attenuated neointimal formation in rodent model. The goal of this study was to determine optimal values of NTIRE for vascular smooth muscle cell (VSMC) ablation.33 Sprague-Dawley rats were used to compare NTIRE protocols. Each animal had NTIRE applied to its left common carotid artery using a custom-made electrodes. The right carotid artery was used as control. Electric pulses of 100 microseconds were used. Eight IRE protocols were compared: 1-4) 10 pulses at a frequency of 10 Hz with electric fields of 3500, 1750, 875 and 437.5 V/cm and 5-8) 45 and 90 pulses at a frequency of 1 Hz with electric fields of 1750 and 875 V/cm. Animals were euthanized after one week. Histological analysis included VSMC counting and morphometry of 152 sections. Selective slides were stained with elastic Van Gieson and Masson trichrome to evaluate extra-cellular structures. The most efficient protocols were 10 pulses of 3500 V/cm at a frequency of 10 Hz and 90 pulses of 1750 V/cm at a frequency of 1 Hz, with ablation efficiency of 89+/-16% and 94+/-9% respectively. Extra-cellular structures were not damaged and the endothelial layer recovered completely.NTIRE is a promising, efficient and simple novel technology for VMSC ablation. It enables ablation within seconds without causing damage to extra-cellular structures, thus preserving the arterial scaffold and enabling endothelial regeneration. This study provides scientific information for future anti-restenosis experiments utilizing NTIRE

Remote Electrical Stimulation by Means of Implanted Rectifiers

Miniaturization of active implantable medical devices is currently compromised by the available means for electrically powering them. Most common energy supply techniques for implants – batteries and inductive couplers – comprise bulky parts which, in most cases, are significantly larger than the circuitry they feed. Here, for overcoming such miniaturization bottleneck in the case of implants for electrical stimulation, it is proposed to make those implants act as rectifiers of high frequency bursts supplied by remote electrodes. In this way, low frequency currents will be generated locally around the implant and these low frequency currents will perform stimulation of excitable tissues whereas the high frequency currents will cause only innocuous heating. The present study numerically demonstrates that low frequency currents capable of stimulation can be produced by a miniature device behaving as a diode when high frequency currents, neither capable of thermal damage nor of stimulation, flow through the tissue where the device is implanted. Moreover, experimental evidence is provided by an in vivo proof of concept model consisting of an anesthetized earthworm in which a commercial diode was implanted. With currently available microelectronic techniques, very thin stimulation capsules (diameter <500 µm) deliverable by injection are easily conceivable

Contributions to the measurement of electrical impedance for living tissue ischemia injury monitoring

Aquesta tesi es centra en el desenvolupament i l'ús d'una sonda miniaturitzada de silici per a la mesura de la impedància elèctrica de teixits vius tous. El propòsit d'aquestes mesures d'impedància és la monitorització en temps real del dany isquèmic per a aplicacions com la cirurgia cardíaca o el trasplantament d'òrgans. Actualment, el rang de mètodes aplicables a nivell clínic per tal de detectar l'isquèmia tissular és limitat i no existeix cap mètode pràctic que permeti la quantificació en temps real de l'efecte d'aquesta isquèmia, això és, el dany isquèmic. En aquest sentit, la monitorització de la impedància elèctrica sembla esperançadora i el treball d'aquesta tesi contribueix al camp mitjançant el desenvolupament de nous instruments i mètodes i mitjançant l'aportació de noves dades experimentals i eines per a la comprensió de la relació entre la patofisiologia i la impedància elèctrica. Les principals contribucions d'aquesta tesi es resumeixen a continuació.En aquesta tesi, es descriu el desenvolupament d'una sonda que formada per quatre elèctrodes de platí (300 &#61549;m &#61620; 300 &#61549;m) a sobre d'un substrat de silici en forma d'agulla ( longitud d'inserció = 9 mm i secció de 600 &#61549;m &#61620; 500 &#61549;m). Els elèctrodes estan situats a una distància de separació no constant per tal de millorar la relació senyal-soroll i la resolució espacial. Es realitza una deposició electroquímica de platí negre sobre els elèctrodes per tal de reduir la impedància de la interfície i millorar la qualitat de les mesures. En el cas dels teixits vius, la banda freqüencial de mesura va dels 100 Hz fins als 100 kHz. Un mètode nou per a la mesura d'impedància a cinc elèctrodes es presenta i s'analitza. Amb aquest mètode, es pretén minimitzar l'error a baixes freqüències degut a l'elevada impedància de la interfície elèctrode-electròlit. Malauradament, encara que aquest mètode a cinc elèctrodes funciona, s'han trobat algunes limitacions que el fan quasi impracticable en el cas dels teixits vius.També es presenta el desenvolupament i l'ús d'un paquet de programari per a simular la impedància elèctrica dels teixits vius en les regions de dispersió &#61537; i &#61538;. Aquest programari es basa en la generació d'arxius SPICE a partir de l'especificació d'alguns paràmetres numèrics relacionats amb el teixit i el dibuix d'un mapa bi-dimensional que representa un tall de teixit. El resultat més significatiu d'aquest simulador és que és capaç d'obtenir respostes compatibles amb l'equació de Cole a partir d'un model basat únicament en resistències i capacitats.S'han realitzat diversos estudis experimental fent servir la sonda de silici. En aquesta tesi únicament es presenten els estudis amb ronyons de rata. Els resultats confirmen les principals observacions fetes anteriorment per altres investigadors que han treballat amb diferents animals, òrgans i protocols. Això vol dir, en termes generals, un increment significatiu de la magnitud de la impedància elèctrica a baixes freqüències (Addicionalment, aquesta tesi inclou un annex que tracta de facilitar la comprensió de la monitorització de la bioimpedància elèctrica a aquells amb formació en ciències de la vida.This thesis is focused on the development and use of a miniaturized silicon probe for electrical impedance measurements of soft living tissues. The purpose of those impedance measurements is to monitor the ischemia injury for applications such as cardiac surgery or organ transplantation.Currently, the range of clinically available methods to detect tissue ischemia is limited and there is not any practical method to quantify in an on-line manner the effect of such ischemia, that is, the ischemia injury. In this sense, electrical impedance monitoring seems very promising and this thesis contributes to the field by developing new instruments and methods and by providing novel experimental results and tools to understand the relation between pathophysiology and electrical impedance. The main contributions of this thesis are summarized below.In this thesis, it is presented the development of a silicon probe that consists of four platinum electrodes (300 &#61549;m &#61620; 300 &#61549;m) on a needle shaped silicon substrate (9 mm insertion length, 600 &#61549;m &#61620; 500 &#61549;m cross section). The electrodes are placed at non-constant separation distance in order to enhance signal-to-noise ratio and spatial resolution. An electrochemical deposition of platinum black on the electrodes is performed in order to reduce the interface impedance and improve the quality of the measurements. For living tissue measurements, the useful measurement band goes from 100 Hz to 100 kHz.A novel measurement method based on five electrodes is described and analyzed. It is intended to minimize errors at low frequencies caused by the high electrode-electrolyte interface impedances. Unfortunately, although this five-electrode method works, some limitations have been found that made almost impossible its implementation for living tissue measurements.It is also presented a custom developed software package to simulate the electrical impedance of living tissues at the &#61537; and &#61538; dispersion regions. It is based on the generation of a SPICE netlist from the specification of some numerical parameters concerning the tissue and a bi-dimensional map representing a slice of tissue. Some examples are provided to demonstrate its feasibility. The most significant result is that the simulator is able to obtain Cole compatible behaviours from models based on simple resistances and capacitances. Several experimental studies have been performed by using the silicon probe. In this thesis only the experiments carried out on rat kidneys are presented. The results confirm the main observations made by previous researchers working with other animals, organs and protocols. That is, in general terms, a significant increase of impedance magnitude at low frequencies (This thesis includes an annex that tries to facilitate the understanding of electrical bioimpedance monitoring for life-sciences practitioners.Another annex describes the instrumentation systems that were developed for electrical impedance measurements based on the four-electrode method

Electrochemical prevention of needle-tract seeding

Needle-tract seeding refers to the implantation of tumor cells by contamination when instruments, such as biopsy needles, are employed to examine, excise or ablate a tumor. The incidence of this iatrogenic phenomenon is low but it entails serious consequences. Here, as a new method for preventing neoplasm seeding, it is proposed to cause electrochemical reactions at the instrument surface so that a toxic microenvironment is formed. In particular, the instrument shaft would act as the cathode and the tissues would act as the electrolyte in an electrolysis cell. By employing numerical models and experimental observations reported by researchers on Electrochemical Treatment of tumors, it is numerically showed that a sufficiently toxic environment of supraphysiological pH can be created in a few seconds without excessive heating. Then, by employing an ex vivo model consisting of meat pieces, validity of the conclusions provided by the numerical model concerning pH evolution is confirmed. Furthermore, a simplified in vitro model based on bacteria, instead of tumor cells, is implemented for showing the plausibility of the method. Depending on the geometry of the instrument, suitable current densities will probably range from about 5 mA/cm2 to 200 mA/cm2 and the duration of DC current delivery will range from a few seconds to a few minutes.AI’s research is currently supported by a Ramón y Cajal fellowship from the Spanish Ministry for Science and Innovation

Two-port networks to model galvanic coupling for intrabody communications and power transfer to implants

Comunicació presentada a: BioCAS 2018, celebrada a Cleveland, Ohio, Estats Units d'Amèrica, del 17 al 19 d'octubre de 2018.Galvanic coupling, or more precisely, volume conduction, can be used to communicate with and to transfer power to electronic implants. Since no bulky components for power, such as coils or batteries, are required within the implants, this strategy can yield very thin devices suitable for implantation by injection. To design the circuitry of both the implants and the external systems, it is desirable to possess a model that encompasses the behavior of these circuits and also the volume conduction phenomenon. Here we propose to model volume conduction with a two-port network so that the whole system can be studied in circuit simulators. The two-port network consists only of three impedances whose values can be obtained through simple measurements or through numerical methods. We report a validation of this modeling approach in a geometrically simple in vitro setup that allowed us to determine the impedances of the two-port network not only by performing measurements or through a finite element method study but also through an analytical solution.Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 724244)

Remote electrical stimulation by means of implanted rectifiers

Miniaturization of active implantable medical devices is currently compromised by the available means for electrically/npowering them. Most common energy supply techniques for implants – batteries and inductive couplers – comprise bulky/nparts which, in most cases, are significantly larger than the circuitry they feed. Here, for overcoming such miniaturization/nbottleneck in the case of implants for electrical stimulation, it is proposed to make those implants act as rectifiers of high/nfrequency bursts supplied by remote electrodes. In this way, low frequency currents will be generated locally around the/nimplant and these low frequency currents will perform stimulation of excitable tissues whereas the high frequency currents/nwill cause only innocuous heating. The present study numerically demonstrates that low frequency currents capable of/nstimulation can be produced by a miniature device behaving as a diode when high frequency currents, neither capable of/nthermal damage nor of stimulation, flow through the tissue where the device is implanted. Moreover, experimental/nevidence is provided by an in vivo proof of concept model consisting of an anesthetized earthworm in which a commercial/ndiode was implanted. With currently available microelectronic techniques, very thin stimulation capsules (diameter/n,500 mm) deliverable by injection are easily conceivable.This author's research is currently supported by a Ramón y Cajal fellowship from the Spanish Ministry for Science and Innovation (RYC-2009-04271) and a Marie Curie International Reintegration Grant (256376 – “TAMIVIVE”) from the European Commission. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript