Studies On Impedance Spectroscopy Measurement Methods And Characteristic Of Biological Tissues

The complex impedance of bio-tissue varies with the frequency of driven current change. For different tissue, the variations were very different. This characteristic of bio-tissue was called impedance spectroscopy. Because bio-tissue impedance spectroscopy showed a close relationship with the physiological activity and pathological states of bio-tissue, the physiological activity and states may be observed by measuring the bio-tissue impedance spectroscopy. Study on bio-tissue impedance spectroscopy is necessary for the resolution of the inverse problem and the electromagnetic energy distribution in models of animals and humans. It is also important to establish physical virtual human and physiological virtual human. Funded by National Natural Science Foundation of China (NSFC) for the research project "Studies on impedance spectroscopy characteristic of biological tissues", the basic researches on bio-tissue impedance spectroscopy have been done mentioned below.1 Set up the bio-tissue impedance spectroscopy measurement systemWe constructed an impedance spectroscopy measurement system basedon frequency response analyzer (Solartron S1260). The frequency analyzer provides current injection with different frequencies winthin 10μHz to 32MHz and voltage measurement circuit, its output signal is accurate and stable. The frequency, phase, waveform and amplitude of the output signal can be controlled by program. The frequency analyzer connecte and communicate with computer using GPIB (Programmable Instrumentation Interface Board). In order to minimize the noise, all the measurement system was located in an electric and magnetic shield chamber.We adopt four-terminal method for bio-tissues impedance spectroscopy measurement because it minimizes the error caused by polarization impedance at low frequencies. In the four-terminal configuration, the two electrodes used to sense the voltage difference are separate from the two for current injection. They are connected to an amplifier with high input impedance so that voltage across the polarization impedance on the voltage electrodes will be very small. This accurate bio-tissue impedance spectroscopy measurement systembased on frequency response analyzer is an innovation.2 Study on the methods of bio-tissue impedance spectroscopymeasurementA) Research of measurement frequency distribution in tissue impedancespectroscopy measurementIn the research of tissue impedance spectroscopy measurement, the author constructed a frequency sets that produce angularly equidistant points on the Nyquist loci. By the study of simulation data model, it is proved that, using the same quantity of frequency points, in comparison with the frequency sets that are logarithmic and quasi-linear, angularly equidistant frequency sets can improve the estimate accuracy of tissue electrical model parameters of a and f.B) Study on the operation methods and measurement sequence of thebio-tissues impedance spectroscopy measurementIn the bio-tissues impedance spectroscopy measurement, in order to get the accurate data, the measured animal should be in good condition, its physical parameters should be stable. Based on many experiment, we summarized the operation methods and measurement sequence of the bio-tissues impedance spectroscopy measurement: in the operation for exposing the measured tissues, blunt separate should be taken. During operating, the measured tissues should not be stained by the blood and secretion of skin and can not use water to rinse. Measurement sequence should be arranged following the principia as: the easy separated tissue should measure first. The slight hurt operation should be taken first.In order to ensure the accuracy of the bio-tissues impedance spectroscopy measurement, we designed the operation methods and measurement sequence normatively. This kind of study was not reported before. C ) Study on spatial resolution of four electrode arrayIt is well known that a four electrode arrangement buried in a homogeneous and isotropic medium of infinite extent provides accurate measurement of the specific impedance, however in vivo measurements are such that the medium is not homogeneous, isotropic, and of infinite extent. The specific impedance then measured is biased by the surrounding structure. How to minimize this error and improve spatial resolution of four electrode array is analyzed in this dissertation. Using the image technique and the equivalent circuit of our electrode array system, we study the spatial resolution of four electrode array. The result of analysis show: in order to improve the spatial resolution, the insert depth of measuring electrode should be 3 times to the distance of the potential electrode, and the plane of electrodes should parallel the medium plane.D) Research of effect of stray capacitance on measurement accuracy in bio-tissue impedance spectroscopy measurementIn the tissue impedance spectroscopy measurement, four-electrode methode are normally used. A measurement error caused by stray capacitance between lines of drive electrode and receive electrode is not a trivial problem. So using the equivalent circuit of our electrode system, we analyze the noise introduced by stray capacitance. With the stray capacitance value set as 10pF, 5pF, 1pF, OpF, the real and imaginary parts of the impedance at different frequencies are calculated using OrCAD Pspice. We reached the results: This stray capacitance introduces errors which increase with frequency and has more effect on the imaginary part than on the real part in the measurement frequency rangeThe results of our research suggest that, during practical in vivo bio-tissue impedance spectroscopy measurement, the measurement equipment should be placed reasonable in order to shorten the length of lead and reduce the error introduced by stray capacitance.3 Algorithm for extraction of tissue impedance spectroscopy characteristic parameters based on optimum methodThe measurement results of tissue impedance spectroscopy are often analyzed by using the characteristic parameters that relate to structural or physiological characteristics of the studied tissue. A new algorithm for extraction of tissue impedance spectroscopy parameters based on optimum method is proposed in this dissertation. It is based on the notion that the difference between measured and parameter values is randomly distributed with zero mean. The values of the unknown parameters are then deduced by minimizing the covariance matrix determinant. Tested on the simulation data model which characteristic parameters are known, the result show that the error of extracting parameters R₀, R_∞, α , f_c is 0.3%, 0.2%, 0.4% , 0.3% respectively. This proved that the new algorithm can extract the parameters effectually and accurately.4 Measurement of bio-tissue impedance spectroscopyA) Measurement and analysis of in vivo bio-tissue impedance spectroscopyWe measured the impedance spectroscopy of skeletal muscle, liver, spleen in vivo of rabbit based on our bio-tissue impedance spectroscopy system and technique. The results show: in the measurement frequency scope (1Hz-10MHz), the complex impedance locus of the tissue represent as a single peek curve. The impedance spectra changed remarkably with the variation of driven current frequency: With the increasing of driven frequency, the real part of bio-impedance decreased from low-frequency resistance(R₀) to high-frequency resistance(R_∞). The change is significant in mid-frequency band; the imaginary part of bio-impedance first increase from 0 to the maximum, then decrease to 0. It can be neglect in low-frequency band andhigh-frequency band.Different tissues show different impedance spectra characteristic. These difference can be observed by Cole-Cole diagram directly, and can also be represented in impedance spectra characteristics parameter, such as characteristic frequency(f_c), low-frequency resistance(R₀), high-frequency resistance(R_∞).For different tissues, the parameter of Ro is different remarkably. The value of Ro of kidney is small comparatively. The value of Ro of liver, spleen is 2.6 and 4.7 times larger than kidney respectively. For the skeletal muscle, the value of Ro measuring transversely is 1.6 times larger than that measuring longitudinally. The value of R_∞ of kidney, liver and spleen is is also different notably. The value of R_∞, of kidney is small comparatively. The value of Ro of liver, spleen is 2.5 and 6.5 times larger than kidney respectively. For the skeletal muscle, there is no notable different of the value of R_∞ , measuring either transversely or longitudinally. Comparing the different tissues, the value of the parameter f_c of transverse muscle is larger than that of longitudinal muscle. The f_c of kidney, liver and spleen is different notably. The value of f_cof liver is small comparatively. The value of f_c of kidney, spleen is 2 and 3.5 times larger than liver respectively. For the parameter of α, there is no notable different between different tissues.In the bio-tissue impedance spectroscopy measurement, many researchers only study tissue partly when necessary. There is no report that the whole important tissues were measured for one animal. In our measurement, all the tissues of rabbit were measured with the same methods and technique, so the data are mean for comparing. B) Measurement and analysis of in vitro bio-tissue impedance spectroscopyWe measured the impedance spectroscopy of rabbit tissues continually within 5 to 360 min after excision. During the procedure, the measurement interval is 10 min in the first 3 hours and 20 min in the last 3 hours. We calculated the resistivity and impedance spectra characteristics parameter.The resistivity of excised tissue changed remarkably in the time course after excision, and the changes of different tissues are different greatly. In generally, the resistivity increased continually in the first 50 min for all tissues, especially for low-frequency, the resistivity increment of liver, kidney and heart is remarkable, more than 90%. hi comparison, the resistivity changes of muscle by the time are slightly. For the high-frequency, resistivity also increased for all tissues, but the value changed slowly in comparison to low-frequency.The Cole-Cole model characteristic parameters change notably by the time. The value of Ro change great especially. For kidney, liver, spleen and heart, the value Ro reached 700% , 125%, 170% and 200% respectively at the 6 hour after excision. The change of a is less than 30% for all tissues. The changes of the value of f_c by the time are remarkably different for different tissues, for liver, kidney and heart, the value of f_c decreased continually andthe decrement reached 60% , 19%, 33% respectively at the end of the measurement. For muscle (longitudinal, transverse) and heart, the value of fc decreased firstly and then degan to increase and reached 145%, 155%, 125%at 6 hour after excision.C) Study on the relationship of tissues resistivity between in vivi and in vitro The measurement of in vivo bio-tissues impedance spectroscopy is difficult, especially for human tissues, and some time it is infeasible; but the in vitro measurement can be done easily comparing to in vivo measurement. Based on the results of in vivi and in vitro impedance spectroscopy of rabbit tissues, we studied the relationship of resistivity of tissue between in vivi and in vitro.We hypothesized that the resistivity of in vivo tissue equal the resistivity of in vitro tissue at the moment t=0 ('t' denote the time of tissue after excising). We can measured the resistivity of in vitro tissue at the moment t>0; and fit the data using mathematical method; then calculate the resistivity of in vitro tissue that can be considered as the resistivity of in vivo tissue.We fitted the in vitro impedance spectroscopy data of liver and kidney respectively; and then calculated the resistivity of in vivo tissues. The results show that the calculated resistivity is just within the 95% confidence interval of resistivity of in vivo tissues. Study on the relationship of resistivity between in vivi and in vitro is important for the in vivo tissues, especially for human tissues. This research is one of the innovations of this dissertation. 5 Setup the database of bio-tissues impedance spectroscopyIn the experiment, the measured data were saved in the specific format on the computer hard disk separately; other user can not read this kind of data; this is not helpful for data share and not facilitated for search. In this dissertation, using Visual C++6.0 program language, we set up the database of bio-tissues impedance spectroscopy with MS SQL SEVER 2000 as the background database manage system.