Patent Publication Number: US-2011074442-A1

Title: Method and device using shortened square wave waveforms in synchronous signal processing

Description:
TECHNICAL FIELD 
     The invention relates to methods of synchronous signal processing using shortened square wave waveforms. The method is particularly suitable for impedance measurements, e.g., of bioobjects such as tissues, organs, muscles, etc. 
     BACKGROUND ART 
     Impedance measurements are widely used for characterizing parameters of materials and substances, tissue parameters in biology and medicine, and even cell cultures [1]. When characterizing biological and medical parameters of tissue segments, electrical impedance is often called electrical bioimpedance (EBI) [2]. It could be measured at several different frequencies (multifrequency measurements), and sometimes also from multiple locations (multisite measurements) in order to derive multidimensional picture of tissue parameters under examination. EBI (in many cases together with visual inspection, temperature measurements etc.) gives valuable information, useful in formulating a diagnosis and providing proper medical care to the patient. It can be used for monitoring human heart functionality in pacemakers, during surgery, or for restoring normal blood flow after surgery. These measurements are usually conducted using synchronous signal processing. Same method enables measurement of low-level signals with lock-in amplifiers, and is used in different network analyzers. Classically sinusoidal excitation is used, and Fast Fourier Transformation (FFT) or similar is used for spectral separation. It enables determination of magnitude and phase of the response signal compared to the excitation signal, and gives relatively good results, depending on the quality of the excitation signal and signal processing algorithms. Typical signal chain for synchronous measurements is shown on  FIG. 1 , in which sine wave signals are used classically. Summing stage could be omitted, however in some circumstances compensation could improve resolution of the result. For out of the body applications size and energy consumption are not necessarily important, even though it is generally desirable to keep the energy consumption at minimum. Situation changes dramatically in case of implantable devices, such as pacemakers. Both analog circuitry and digital signal processing tend to consume a lot of energy. Also, size of the device should be kept as small as possible. 
     Instead of the sinusoidal signals, other waveforms can be used, provided that correlation between measurement results with sinusoidal signals can be shown with acceptable accuracy and repeatability. In wearable and implantable devices square wave excitation [3] can be used mainly because it is energy efficient, easy to generate, and easy to process. Substantial energy savings can be achieved at higher level of reliability (corresponds to reduced number of components). However, higher harmonics of non-sinusoidal waveforms cause errors, which need to be dealt with, or ideally suppressed [4]. Well-known solution is band pass filtering of the excitations signal [5]. Alternatively good results can be achieved by using different piecewise continuous approximations of sinusoidal signals [6]. Drawback associated with later approach is that harmonics content is very sensitive to level accuracy, and usually needs adjustments. Random and pseudo-random binary sequences are investigated, and maximum length sequences (MLS) are reported to give good results for high-speed impedance measurement of small particles in microfluidic cytometer [7]. Unfortunately it also involves rather complex signal processing at later stage including fast M-sequence transform (FMT), as well as FFT, before impedance information can be determined. 
     Systematic errors introduced by higher harmonics of simple square wave signals can be drastically reduced by modifying the rectangular waveforms [8]. In case of shortening each rectangular half period of the excitation and reference signals by 30° and 18° correspondingly by introducing a section with zero amplitude at each end of the half period of the signals (see  FIG. 2 ) the errors from higher odd harmonics can be reduced more than order of magnitude in comparison with regular rectangular waves. 
     Spectra of these signals can be expressed as the Fourier series of odd harmonics: 
     
       
         
           
             
               
                 
                   
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     where A is the amplitude of the rectangular signal. In order to remove 3rd and 5th harmonics from the rectangular signal (as they cause the most significant errors) following simple conditions are valid for choosing the zero value intervals β:
         for the 3rd harmonic 3·β=π/2 must be fulfilled, which means that β=30°   for the 5th harmonic 5·β=π/2 must be fulfilled, which shows that β=18°.       

     Synchronous demodulation is sensitive only to higher harmonics, which are existing simultaneously in both, the excitation and reference signals, such as the 7th, 11th, 13th, 17th, 19th, 23rd, 29th, and 31th in case of 30°/18° shortened signals. 
     In some cases, these simultaneously existing higher harmonics have negligible effect on measurement accuracy. Impact of higher harmonics of the excitation and reference signals to the multiplication result in case of 30°/18° shortened signals can be seen in  FIG. 3A . As a result, impact of the 5 th , 9 th , 15 th , 21 st , 25 th , and 27 th  higher harmonics is absent.  FIG. 3B  is introduced for comparison with using of simple square waves. 
     However, there is a need for for higher accuracy than the prior art can offer. For example, the impact of the 7 th  harmonic has remained too substantial for providing precision measurements. 
     SUMMARY OF THE INVENTION 
     The objective of the invention is a method for impedance measurements comprising introducing a first modified rectangular signal into an object such as bioobject, e.g., a tissue, receiving a response signal from said object, introducing said response signal and a second modified rectangular signal into a synchronous detector, whereas either said first modified rectangular signal or said second modified rectangular signal, or both signals are so modified as to remove certain higher harmonics from the signals. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a typical signal chain for synchronous measurements of impedance, where sinusoidal signals are traditionally used; 
         FIG. 2  depicts modified rectangular wave waveforms to be used in a set up of  FIG. 1  instead of sinusoidal signals, wherein the rectangular half periods of rectangular wave waveforms are shortened at each end by 18° and 30° respectively; 
         FIG. 3A  depicts the system where the invented method can be used.  FIG. 3B  illustrates generating the excitation signal according to the invention.  FIG. 3C  illustrates generating a reference signal according to the invention.  FIG. 3D  illustrates alternative set up for generating reference signal. 
         FIG. 4  comparatively show the higher harmonics present in different waveforms at the exit of the synchronous detector: 18°/30° shortened signal pair of  FIG. 2  (white columns), an ordinary 50/50 duty cycle rectangular wave (dotted lines) and for signals shown in  FIGS. 7A and 7B  (black columns) 
         FIG. 5  depicts a modified rectangular wave signal, generated by summing three modified rectangular wave waveforms, shortened by 18°, 30°and 42° respectively ( FIG. 5A ) and resulting spectral composition ( FIG. 5B ); 
         FIG. 6  depicts a spectral view of modified rectangular wave waveforms, generated by summing three modified rectangular signals with adding coefficients 1, −0.5 and 0.5 ( FIG. 6A ) and with coefficients 1, 1, 1 ( FIG. 6B ); 
         FIG. 7  depicts a half periods of waveforms with adding coefficients 1, −0.5 and 0.5 ( FIG. 7A ) and with coefficients 1, 1 and 1 ( FIG. 7B ); 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTIONS 
     The invention is now described with references to enclosed figures. 
       FIG. 2  depicts the principal set up where the invented method can be used. An excitation signal  1  is introduced into an object  2  such as bioobject, for example, a tissue. The excitation signal 2 can be any periodic signal with known frequency and harmonic content, such as sinusoidal signal, triangular signal, a rectangular signal that is modified as known from the art, e.g., as shown in  FIG. 1B , or any of the modified rectangular signals according to this invention (see  FIGS. 5 and 7 ). 
     A response signal  3 , corresponding to the excitation signal  1  is then received from the object  2  and introduced into synchronous detecting means  6 , such as a synchronous detector. Synchronous detector  6  is used, e.g., for inphase signal and detector  7  for quadrature channel. A reference signal  4  (for inphase channel; reference signal  5  for quadrature channel) is also introduced into the synchronous detector. The reference signal is a modified rectangular signal according to this invention. “Modified rectangular signal” can be best described comparing to traditional rectangular signal. The traditional rectangular signal has amplitude A and period T so that the signal has value A during one of the half periods T/2 and value −A during the other half period T/2. Such signal has harmonic content represented by equation (1) above in the case, where the zero state is absent (β=0°). The modified rectangular signal also has period T and amplitude A. However, each half period of the modified rectangular signal comprises zero amplitude segments (β≠0°), i.e., segments during which the value of the signal is zero. Such signal has a harmonic content improved compared to traditional rectangular signal in that at least one higher harmonic is at least partially suppressed. 
     For example, in known art, using signals as shown in  FIG. 2  the suppression of the impact of the 7 th  harmonic is roughly 5 dB compared to square wave, but it is still remains high. However, as it turns out that signals could be considerably improved without almost any added complexity in their generating. Such the signal has zero value during first 18° segment, value A (e.g., unit value 1) during following 12° segment, zero value during the yet following 12° segment, value A during the next 96° segment, then zero value for 12° segment, value A for 12° segment and zero value during the last 18° segment of the half period T/2. The second half period is symmetrical to the first half period, having value −A instead of value A. 
     Such the signal can be easily generated by summing up three signals—the signals having the same shape as the signals Vref and Vexc shown in  FIG. 2 , and a third signal that is shortened similarly by 42° at the beginning and end of each half period. Appears that when summing 18° shortened signal with + sign, 30° shortened signal with − sign, and 42° shortened signal with + sign, the new waveform ( FIG. 5A ) is free from both the 3rd and 5th harmonics. Resulting spectrum of such signal can be seen in  FIG. 5B . 
     Even 7th harmonic has been somewhat reduced compared to the traditional square wave, however, the higher harmonics on the other hand are relatively high. The harmonic content of the signal can be further improved with changing the addition coefficients from 1, −1, 1 to 1, −0.5, 0.5. Resulting spectrum can be seen in  FIG. 6A , and waveform on  FIG. 7A . Appearing 3rd and 9th harmonics could pose a problem, however in case of suitably chosen signal pair it is possible to eliminate them from the multiplication result. Good candidate for such a pairing signal is sum of 18°, 30° and 42° shortened signals with +1 coefficients. Resulting spectrum can be seen on  FIG. 6B , and waveform on  FIG. 6B . In order to show the difference two different multiplication results can be seen on  FIG. 7 : multiplication result of 30°/18° shortened signal pair compared to multiplication result of last two discussed signals. 
     Though the impact of the 7th harmonic is still present, the role of it has been reduced considerably (about 30 times, as it is discussed in example 1). 
     EXAMPLES 
     Example 1 
     According to the first embodiment of the invention, the excitation signal  1  is a first modified rectangular signal, having improved harmonic content. Such excitation signal  1  is formed by adding three subsignals  101 ,  102  and  103  by summing means  13  (see  FIG. 3A ). The subsignals and corresponding excitation signal  1  are shown in  FIG. 7A  and the spectrum of this signal is shown in  FIG. 6A . 
     In this embodiment, similarly, the reference signal  4  to be introduced into synchronous detector  6  is generated by adding three subsignals  401 ,  402  and  403  by summing means  14  (see  FIG. 3C ). The subsignals and corresponding reference signal is shown in  FIG. 7B  and the spectrum of this signal is depicted in  FIG. 6B . 
     Even though the signal depicted in  FIG. 7A  is more preferred as excitation signal as it has higher excitation energy, in principle, also the signal shown in  FIG. 7B  used as the excitation signal and signal shown in  FIG. 7A  as the reference signal. 
     Impact of the higher harmonics is characterized by the spectrum of their multiplication product in  FIG. 4 . The role of the 7 th  harmonic is reduced 29 dB (from −38dB to −67 dB) or about 30 times compared to prior art. Also the role of 11 th  harmonic is reduced by 14 dB (near to 5 times). The role of 19 th  harmonic is reduced by 13 dB (about 4.5 times) and the role of 23 rd  harmonic is suppressed to negligible (lower than −70dB). 
     Alternatively, a set up according to  FIG. 3D  can be used for generating the reference signal. Instead of first summing up the subsignals  401  to  403 , first the subsignals are introduced into synchronous detectors  61  to  63  respectively, and then the resulting signals are summed in summing means  15 . 
     Example 2  
     According to the second embodiment of the invention, the excitation signal is a rectangular signal, or alternatively, a modified rectangular signal know from the art. Our invention improves the measurement results considerably also in the case when one of the used two signals is a traditional rectangular one, but the other is modified according to the embodiment of our invention. In this case the most preferable modified signal is given in  FIG. 5A , the spectrum of which does not contain the 3 rd  and the 5 th  higher harmonics. As a result, the impact of these higher harmonics is absent. 
     Example 3 
     According to the third embodiment, a sinusoidal excitation signal is used. Our invention improves the signal-to-noise ratio and gives more exact measurement results even then, when the excitation signal is a traditional sine wave. The embodiment of improvement is based on the fact that zero value state of the reference signal impedes both the response signal and accompanied noise. When the noise level is high then the segment of impeded noise can be higher than the segment of sine wave. The most reasonable modified signal is a simple modification of the signal shown in  FIG. 2  with the zero state segment is not 18° or 30° but preferably 22.5°, which value 360°/16 is very near to the mathematical optimum is 21.4° 
     Signal Processing and Generation 
     Signal processing using shortened square wave pulses in real measurement is straightforward. In case of 30°/18° shortened signals one of them, for example 18° shortened signal, is used for excitation current generation, while other, in this case 30° shortened signal, for multiplication. In reality it is enough to just cumulatively add samples from 30° to 150°, and sub-tract samples from 210° to 330° to get real part of the impedance, and add samples from 120° to 240°, and subtract samples from 0° to 60° and 300° to 360° to get imaginary part of the impedance under examination. If it is done for integer number of signal periods signal to noise ratio could be further improved. Undersampling is also easily accomplished, if needed. In simplest from 61/n*60 ratio should be maintained between sampling and signal forming clocks. 
     There is very little added complexity with discussed summed signals. In case of real part calculation samples between 30° to 42°, 138° to 150°, 210° to 222°, and 318° to 330° should be divided by two before summing, which in digital terms means simple shifting. For imaginary part same is valid, just location of the samples to be divided are shifted 90° from previously discussed. Signal forming for excitation is similarly simple. It is worth noting here that compared to piecewise continuous approximations of sinusoidal signals (known in the art), the method according to the invention using equal levels is much more feasible in digital domain of signal generation. 
     Replacing strictly sinusoidal signals with pulse waves in bioimpedance measurement device leads to measurement errors caused by higher harmonics. While it is not possible to eliminate these errors, usage of different carefully selected shortened pulse waves for excitation and for demodulation can minimize their impact to measurement results. Clear advantage in terms of simplicity of realization, together with very low current consumption, can be achieved due to the nature of such pulses. Just selecting correct samples, possibly shifting them, and then adding together can accomplish numerical synchronous demodulation. New, still simple, waveforms can be introduced by performing simple binary weighted additions on basic three level waveforms. It improves spectral purity of the signal processing, and reduces errors introduced by higher harmonics. The 3rd, 5th and 9th harmonics are still missing from the result, and impact of the 7th harmonic is reduced by almost 30 dB. Contemporary technology is well suited for practical realization of small form factor and energy efficient measurement devices based on introduced signals. Results can be used in clinical experiments or ultimately for improving wearable and implantable devices using EBI as vital source of information. 
     The work was supported by grants no. 7212 and 7243 of Estonian Science Foundation, and also by Enterprise Estonia through the Competence Center ELIKO. 
     REFERENCES 
     [1] Cheung K, Gawad S, Renaud P (2005) Impedance Spectroscopy Flow Cytometry: On-Chip Label-Free Cell Differentiation. Wiley-Liss, Cytometry Part A 65A, 124-132. 
     [2] Grimnes S, Martinsen ØG (2000) Bioimpedance and Bioelectricity Basics. Academic Press, London. 
     [3] Webster J G (Ed.) (1995) Design of Cardiac Pacemakers. IEEE Press, New York. 
     [4] Meade M L (1989) Lock-in Amplifiers: Principles and Applications. Peregrinus, London. 
     [5] Yfifera A, Leger G, Rodriguez-Villegas E O, Muñoz J M, Rueda Ivorra A A, Gomez R, Noguera N, Aguiló J (2002) An integrated circuit for tissue impedance measure, in Proc. of the IEEE EMBS Special Topic Conference on Microtechnologies in Medicine and Biology, 2002, pp. 88-93. 
     [6] Min M, Parve T, Kukk V, Kuhlberg A (2002) An Implantable Analyzer of Bio-Impedance Dynamics: Mixed Signal Approach. IEEE Transactions on Instrumentation and Measurement, Vol. 51, No. 4, August 2002, pp 674-678. 
     [7] Sun T, Holmes D, Gawad S, Green N, Morgan H (2007) High speed multi-frequency impedance analysis of single particles in a microfluidic cytometer using maximum length sequences. Royal Society of Chemistry, Lab Chip 7, 1034-1040. 
     [8] Min M, Parve T (2007) Improvement of Lock-in Electrical Bio-Impedance Analyzer for Implantable Medical Devices. IEEE Transactions on Instrumentation and Measurement, Vol. 56, No. 3, June 2007, pp 968-974. 
     Although this invention is described with respect to a set of aspects and embodiments, modifications thereto will be apparent to those skilled in the art. The foregoing description of the embodiments of the invention has been presented for the purposes of illustration and description. It is not intended to be exhaustive or to limit the invention to the precise form disclosed. Many modifications and variations are possible in light of this disclosure. It is intended that the scope of the invention be limited not by this detailed description, but rather by the claims appended hereto.