DOI 10.1007/s10527-015-9524-8 Biomedical Engineering, Vol. 49, No. 3, September, 2015, pp. 174177. Translated from Meditsinskaya Tekhnika, Vol. 49, No. 3, MayJun., 2015, pp. 3538. Original article submitted March 27, 2015.

Influence of Spectral Composition of Probing Signal on Electroimpedance Measurements of Biological Object V. V. Epifantsev1* and V. A. Ustyuzhanin2

The possibility of expanding diagnostic capabilities in electrical impedance imaging using probing signals of dif ferent shape is described. A block diagram of a hardware–software complex that implements this feature is pre sented. Additionally, the results of test experiments on both biological objects and in equivalent circuits are pre sented.

Introduction Medical diagnostic equipment is characterized by constant improvement of methods, equipment, and reso lution of ultrasound, Xray, and magnetic resonance diag nostics. All these diagnostic methods, thanks to excellent resolution and despite high cost and, in some cases, the presence of the harmful effects on the human body, are widely used in hospitals around the world. In addition to these methods of assessing biological tissues, an electrical impedance method based on the study of electric current passing through biological tissue is used. However, com pared to rapid development of the traditional methods of diagnosis, electrical impedance imaging has not yet found wide application in medical practice, and only in the last decade are more researchers are paying attention to the method. This is due to new technical developments in the field of electronics and increased computing power in sig nal processing. Furthermore, traditional methods of diag nosis reached their basic limitations and develop mainly in the direction of reducing the harmful effects on the biological object, as well as reducing the cost of equip ment and, consequently, the cost of services, without compromising quality. Rheography and its variants (plethysmography, sphygmography, etc.) based on the detection of imped ance changes associated with cardiac activity are the most well established and wellstudied among currently used 1

BITSERVICE Ltd., Chita, Russia; Email: support@bitservice.org Transbaikal State University, Chita, Russia. * To whom correspondence should be addressed. 2

and developed areas of electrical diagnostics. The next most common area is the study of body composition (cal culation of volumes of intra and extracellular fluid vol ume of adipose tissue) by measuring the electrical resist ance at high and low frequencies. The most promising and perhaps popular in the near future areas of electrical impedance diagnostics are electrical impedance tomogra phy (EIT) and electrical impedance spectroscopy (EIS). EIT is reconstruction of image of internal media of the studied object according to distribution of electric current conduction in the medium, generally based on imped ance measurements at one or two frequencies, calculation of an average of the active and reactive components of the electrical impedance of the biological object, and drawing images of the internal environment of the object using special algorithm and a particular model. The model usu ally has a large number of assumptions related to the complex structure of biological objects. EIS involves the most comprehensive assessment of the electrical properties of biological tissue. Since it implies the study of electrical resistance over a wide fre quency range of probing current, it enables detection of the slightest pathological changes in biological objects. Various types of biological tissue, as well as its various states (healthy or diseased), differ in structure: cell mem branes structure, their integrity, and intra and extracellu lar content. All of these parameters influence electrical properties of tissue. When performing electrical impedance studies, one is interested not only in the impedance value at a certain frequency, but also in the dependence of the resistance of the biological object on the current frequency. In this

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Influence of Spectral Composition of Probing Signal on Electroimpedance

case, it is possible to use several generators of probing cur rent of different frequencies, and switch them on the studied object, but the measurements for each frequency are separated in time. As is known, the resistance of a bio logical object varies with time (it is affected by heart activity, breathing movements, etc.), so the measure ments obtained this way cannot be correlated. Using sig nal consisting of multiple frequency components and means of ensuring sufficient speed of registration of such signal, it is possible to solve this problem and to reduce the measurement time. Furthermore, using such signal enables simultaneous investigation of different types of biological tissues at the site of the biological object.

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PC

DAC (as gene rator of prob ing current)

Microprocessor control unit

Electrodes Electrode commutation unit

ADC

Channel multiplexing unit Object

Measurement unit

Control unit of multi plexor and ADC syn chronization

Hardware–Software EIS Complex Analysis of existing methods and instruments for assessment of the state of biological tissues by measuring electrical impedance resulted in development of a hard ware–software complex for studies of electrical charac teristics of various biological tissues. The developed device has broad capabilities in assessing these character istics. It reproduces the majority of methods using electri cal impedance of biological tissue as a diagnostic factor by applying appropriate software and selecting appropriate electrodes. The possibility to set current frequency over a wide range (from 0 to 10 MHz with 1Hz step) as well as to set various forms of signal and then to use appropriate methods for processing measurements enables using the hardware–software complex for the evaluation of the developed methods of highly specialized diagnostic sys tems based on measurement of electrical parameters of biological tissues. Electrical impedance spectroscopy can give much information about the state of a particular biological tis sue, but only in comparison with healthy tissue, which is associated primarily with the multicomponent composi tion, complex organization of biological structures, as well as different approaches to conduct these studies. Typically, differences in research techniques include the use of vari ous measuring circuits (such as potentiometric, bridge, etc.), and in the selection of the frequency range in which the study is conducted. Usually research groups use one or more sinewave signals of certain frequency, where switch ing of the studied object to the sources of signals of various frequencies is used for studying the frequency relation ships. Grimnes and Martinsen [5] discussed the use of dif ferent polyharmonic signals to study the dispersion of the impedance of biological objects, such as: – signal consisting of the sum of several sine signals with frequencies set by the researcher;

Fig. 1. Block diagram of electrical impedance spectroscopy com plex for biological tissues.

– square waveform signal, which consists of a large number of harmonics with amplitude decreasing with increasing frequency; – “white noise” signal having the same spectral den sity over a wide range of frequencies. Use of each of these signals has both advantages and disadvantages. In developing its own diagnostic system, we were not been able to determine the shape of the prob ing agent due to lack of information and decided to cre ate a system able to perform research of electrical imped ance of biological tissue using any desired signal. Figure 1 shows a block diagram of the developed system [6]. The complex shown in Fig. 1 is controlled using a PC–MCU (microprocessor controlling unit) pair. The PC creates an array of data, forming a probing signal, and it transmits them to the DAC (digitaltoanalog convert er). Information about the electrode configuration switching enters the MCU, whereupon the PC waits for data from the ADC and transmits the signal to the MCU on the launch of the experiment. Upon receipt of this sig nal, the MCU generates control pulses for units of switching, multiplexing, and control of the multiplexors and ADC synchronization. After the measurements, the MCU sends to the PC a signal on the end of the meas urement; the PC processes the signal and calculates the dispersion of the impedance of the object. Processing of the recorded signals can be presented in three stages: 1) discrete Fourier transform; 2) search for frequency components; 3) calculation of impedance and phase shift for each found component. Some specifications of the hardware−software com plex are:

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– type of signal: complex shape, according to a pre determined numerical sequence; – frequency range of the probing current: effective from 1 Hz to 25 MHz, possible measurements at frequen cies from 25 to 125 MHz with increasing error; – proven measurement range of active and reactive components of electrical impedance – from 0 to 100,000 Ω; – number of measurement channels – 8, each of which can be used for both supplying and measuring of the probing signal; – maximum measurement time for the 8 channels – 0.1 s; – effective value of the probing current with load of 500 Ω and DC – not more than 5.4 mA.

a

f, Hz

b

f, Hz

Experiment First experiments had the goal of defining which probing signals were most informative for measurements and had the smallest error in calculation of impedance dispersion of the studied object. Measurements were per formed on the equivalent circuit of a biological object (Fig. 2a), as well as on the biological object, wherein the ratings of the equivalent circuit were averaged for the val ues given in various sources [13]. The values of the equivalent circuit R2 = R4 = 3 kΩ simulate the resistance of the skin; R5 = 600 Ω simulate resistance of the inter nal environment of the biological object; C1 = C3 = 50 nF simulates the capacity of the skin for an electrode with area of 1 cm2. In the experiment, only the internal resistance of the medium is considered active and only due to interstitial fluid. The measurements were per

Fig. 3. Spectrum of the signal consisting of sum of eight harmon ics (a); spectrum of square wave signal (b).

formed according to the scheme shown in Fig. 2b, where in R1 was known resistance that was connected to the cir cuit to equalize the amplitudes U1 and U2 to reduce errors due to the ADC. R2 and R3 are reference (known) resistances. Two signals were used as the probing current during the measurement: one consisting of the sum of eight har monics with similar amplitudes, and a sequence of 1 μs rectangular pulses at frequency 10 kHz. Their spectral composition is shown in Fig. 3.

Results

a

b

Recorder (ADC)

Generator Object

Fig. 2. Equivalent circuit of a biological object (a); measuring cir cuit (b).

Figure 4 shows the results of measuring the electrical impedance of the equivalent circuit and the biological object and theoretical calculation of the impedance of the equivalent circuit. For measurements, the signals whose spectra are shown in Fig. 3 were used as the probing cur rent. The results revealed that the optimal information value is in the rectangular signals and the signal acquired by summing eight harmonics. These signals provide a rather complete picture of the dependence of the imped ance on the frequency of the probing current. Large error, comparable with the measured values, was detected when a signal having the same spectral density at all frequencies was used as the probing agent. Thus, use of the “white noise” signal without additional hardware and digital pro cessing is not possible. The use of several sinusoidal sig nals of different frequencies was considered due to the

Influence of Spectral Composition of Probing Signal on Electroimpedance

a Z, Ω

1. Electric impedance of biological object 2. Electric impedance of equivalent circuit 3. Theoretical impedance of equivalent circuit

b

f, Hz Z, Ω

1. Electric impedance of biological object 2. Electric impedance of equivalent circuit 3. Theoretical impedance of equivalent circuit

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When assessing the impedance of the biological object, one can say that electrical characteristics of healthy biological tissue are due to its capacitive proper ties not only in place of contact with the electrode, but across the whole path of the electrical current. The developed hardware–software complex allows realtime study of electrical impedance dispersion between two electrodes with refresh rate of the results up to 30 times per second, as well continuous monitoring of electrical characteristics of an object over a large range of frequencies with the ability to record and store results for their further interpretation. Experimental measurements on various types of equivalent circuits showed that the complex is ready for examining electrical characteristics of biological tissues and can be used in various fields of medicine, such as anesthesiology, traumatology, oncolo gy, etc.

REFERENCES f, Hz Fig. 4. Results of measurements and calculations of electrical impedance: a) signal consisting of sum of eight harmonics as probing current; b) sequence of rectangular pulses as probing cur rent.

increased number of measurements and timeconsuming procedure to obtain a complete picture of dependence of the electrical resistance on the frequency. The advantage of using the sum of harmonics is that the user can select particular frequencies. For example, when measuring using a rectangular signal, the range 0 10 kHz was excluded from the calculation; for the sum of harmonics, the probing current included frequency com ponent of 10 Hz, and the impedance of the biological object at this frequency exceeded 50 kΩ.

1. Levchenko O.V., Contactless Impedance in the Diagnosis and Monitoring of Cerebral Edema: author’s abstract of PhD thesis [in Russian], Moscow State University of Medicine and Dentistry, Moscow (2004). 2. Smirnov A.V., Tsvetkov A.A., Tuikin S.A., Proc. 8th Sci. Pract. Conf. “Diagnosis and Treatment of Disorders of the Cardiovascular System Regulation”, Moscow, March 22, 2006, pp. 2630. 3. Bobokhonov A.S., Heymets G.I., Ataullakhanova D.M., Nikolaev D.V., Oshchepkova E.V., Rogoza A.N., 8th Sci. Pract. Conf., Main Clinical Hospital of the Russian Ministry of Internal Affairs, Moscow (2006), pp. 156161. 4. Nikolaev D.V., Smirnov A.V., Tarnakin A.G., Gvozdikova E.A., Proc. 4th Sci. Pract. Conf. “Diagnostics and Treatment of Disorders of the Cardiovascular System Regulation”, Moscow, March 23, 2002, pp. 198204. 5. Grimnes S., Martinsen O.G., Bioimpedance and Bioelectricity Basics, Academic Press (2000). 6. Ustyuzhanin V.A., Epifantsev V.V., Ishkov A.A., Device for Impedance Spectroscopy of Biological Objects. Utility model patent of the Russian Federation 100894, Transbaikal State University, No. 2010130514; appl. 20.07.2010.