Abstract:
A biofeedback method and apparatus for applying a physical action to a subject for treatment purposes and for other applications is disclosed. The method and apparatus disclosed include the steps of coordinating the physical action to systolic upstroke and diastolic drain cycles of subject&#39;s peripheral blood flow. Coordination to the cycles of blood flow synchronizes the treatment action with homoeostatic rhythms of the body, which along with automatic dose individualization substantially enhance efficiency and predictability of the treatment effect. The method and apparatus are also used for diagnostic purposes.

Description:
BACKGROUND OF THE INVENTION 
     The present invention relates to a method of and an apparatus for a biofeedback feedback for individual co-ordination of physical factors applied to a subject for treatment purposes among other applications with physiological parameters of the subject. 
     Continued metabolism is the common denominator of life. Biological systems require energy for continual metabolism, functioning and restoration. Normal cellular metabolism provides energy and homeostatic heat for nominal biological system function. The study of many biological objects proves that cellular metabolism and almost all homeostatic processes are oscillating, and the oscillations are determined by the state of system itself/Malik M.,  Heart Rate Variability , NY, 1995; Friedman H., Lubart R., Proc. SPIE, Vol.2630, pp.60-64, 1996/The oscillations are driven by complex of mechanisms having non-linear nature and are reflected by time-varying properties such as intermittent synchronization/Mainardi L. T. et all, IEEE Engineering in Medicine and Biology, Vol.16,No 6, pp.64-75, 1997/That means that metabolic and homeostatic oscillations do not interfere or summarize, and they are synchronized/Landa P. S. and Rosenblum M. G., Priroda, No 8,pp.18-27,1992/. Intermittent coupling in normal function of biological systems is displayed by a dynamic hierarchy of biological rhythms that continuously vary in time. The struggle between the time-domain processes of separate mechanisms on the one hand to persist in their intrinsic behavior and, on the other hand, to pursue the coordinated by non-linear mechanisms time-domain rhythm leads to a phenomenon known as a dynamic chaos/West A. J.,  Fractal Physiology and Chaos in Medicine , NY, 1990/. 
     Injury and disease cause disturbances of different physiological rhythms and alter the general structure of dynamic chaos. The key of such chaotic behavior of biological systems lies in a fact that they have extreme sensitivity to the temporal behavior of a perturbing factor acting simultaneously on several homeostatic levels/Olsen L, F. and Degn H., Rev. of Biophysics, Vol.10, No 2, pp163-225, 1985/Oscillations of such factor not being coordinated with the temporal dynamics of metabolic and homeostatic processes may effect at the moments when their energetic requirements may not be able to maintain. As a result, it initiates unspecific reaction of an organism directed either to restoring the initial state or to transformation in a new unpredictable state. Physical action such as ultrasound, electromagnetic waves, laser and X-ray radiation simultaneously effect several homeostatic levels of a biological system and not being coordinated with their temporal dynamics have low predictability of the treatment effect. Besides, predetermined doses that usually are used in physical, laser and radiotherapy are far from individual, and that markedly decreases the treatment effectiveness. 
     The biofeedback methods and systems for co-ordination an individual&#39;s physiologic functioning and applied physical action are well known in the art. Conventional biofeedback techniques can be classified in two groups. The first one involves a mental modifying of an individual&#39;s physiological functioning by providing “feed-back” of their physiological activities. Known instruments of this category provide indication of the heart rate/U.S. Pat. No. 4,450,843 issued May 29, 1984 to Barney et all; U.S. Pat. No. 5,007,430 issued Apr. 16, 1991/, brain waves/U.S. Pat. No. 4,031,884 issued Jun. 28, 1977 to Henzel et al/, blood pulse waves/U.S. Pat No. 4,450,843 to Barney et all; U.S. Pat. No. 5,475,725 issued Dec. 12, 1995 to Nakamura et al/. Biofeedback methods and systems of other type in this group convert measurable physiological activities of an individual into feedback signals comprising an auditory or visual stimulus/U.S. Pat No. 4,883,067 issued November 1989 to Knispel et al/. 
     These feedback techniques have well known limitations. The feedback signal normally indicates only a time average of the relevant physiological activity and has no direct effect on ongoing biological processes involved in a disease and, therefore, can not produce a true real time feedback control. Further, the pathway by which feedback signals control an individual&#39;s physiological functioning includes such low predictable parameter as emotional state of the individual. Besides, the success of the treatment sufficiently depends on education and professional skills of the instructor that learn the individual how to control physiological function. 
     Biofeedback techniques of second group have opposite direction of controlling and control the factor applied to the individual being treated. Various patents disclose these instruments. Most of them directly control the factors effecting only one ongoing process involved in a disease. U.S. Pat. No. 5,522,854 issued Jun. 4, 1996 to Ideker et al discloses a method and apparatus for biofeedback stimulating an implanted electrostimulator. Provided by monitoring the symphatetic and parasymphatetic nerve activity biosignals are processed to produce treatment through electric shock at the moments of detection of the states of high risk arrhythmia. Similar biofeedback system delivering electrical stimuli directly to cardiac tissue is disclosed in U.S. Pat. No. 5,447,520 issued Sep. 5, 1995 to Spano et al. According to this invention the timing of intervals between heart beat pulsation in response to a single stimulus intervention is performed during approximately 5 to 60 seconds. At this time the dynamic behavior of a chaotic regime is evaluated according to a special algorithm. At high risk moments of arrhythmia determined by this algorithm biofeedback signals control tissue stimulus injector. 
     An important advantage of these inventions is that they produce feedback signals in a real time. However, their application is limited by sensitivity to only one level of cardiac control, and controlling is provided only after a cardiac event has already occurred. Much more wider sensing or therapeutic vigilance with progressively higher degrees of therapy is disclosed by U.S. Pat. No. 5,749,900 issued May 12, 1998 to Schroeppel et al. The feedback signals are derived from comparison of evaluated numbers of the heart rate variability with previously stored one, and according therapy regimes are initiated. 
     All above described techniques related to the second group provide control of the physical factor effecting only one physiologic parameter, which is monitored. Being used for controlling the action of multilevel action in physical, laser and radiotherapy these techniques do not provide synchronization of the action simultaneously with several homeostatic levels of an organism and, therefore, cannot enhance reproducibility of the treatment effect and effectiveness of the treatment. Perhaps the only one feedback system, which is able to synchronize physical factor of multilevel action is disclosed by USSR Patent 1,481,920 issued Nov. 14, 1986 to Zaguskin et all. According to the patent the cell biorhythms are determined at the first step. Then the physical action applied to the biological object is modulated by at least three frequencies selected from a measured cell rhythm spectrum. It is believed that synchronization of the factor with several frequencies of the cell rhythm is adequate to synchronization to rhythms of all homeostatic processes. Not dealing with biological aspect of this method it should be just mentioned that measurement of the cell rhythms in vitro principally prevents biofeedback control in a real time. 
     In view of the foregoing, there has been no biofeedback method or apparatus for synchronization of the physical factor applied to a subject for treatment purposes with biological rhythms of several homeostatic processes simultaneously. 
     It is believed that co-ordination of the interaction between homeostatic rhythms and their intermittent synchronization is reflected in peripheral blood pulse circulation/Goldberger A. L. and West B. J.,  Fractals in Physiology and Medicine , Yale J. of Biology and Medicine, Vol.60,pp421-435, 1987./Being a multisystem blood supplies oxygen and nutrients and clear metabolic waste products. A complex neural and neuro-hormonal mechanisms controlled by Central and Autonomic Nervous Systems co-ordinate the peripheral blood flow with rhythms of metabolic and homeostatic processes/Bayevsky R. M.,  Prognosis of Boundary States between Norm and Pathology , Medicine, Moscow, 1979./Thus, blood flow through the body is adjusted to the momentary harmony of biological rhythms by combination of regional and higher level control mechanisms, and any factor, which is synchronized with blood flow will be co-ordinate to it too. Unfortunately, there has been no biofeedback technique available for synchronization the factor applied to a subject with cycles of its peripheral blood flow. 
     Usually these cycles are derived from a pulsatile component (a.c.) of the photoplethysmographic (PPG) signal sensing from a subject. Along with a small a.c. component attributable to light attenuation changes resulting from blood volume changes during cardiac cycle the PPG signal contains a large nonpulsatile component (d.c.) regarded to light attenuation produced by fixed elements in the tissue. Because the d.c. component does not contain information about blood flow it has to be removed of the signal. In conventional biofeedback technique the d.c. component is subtracted by blocking with a capacitive blocking element. Such elimination of the d.c. component cause—strong distortion of the remaining a.c. component and the distortion depends on the a.c. amplitude variations. Thus, the distortion varies from a subject to subject and even from pulse to pulse. That makes locating the points of discrimination between different cycles in pulse wave of blood flow very hard. 
     Conventional pulse oxymeters are also used for the PPG signal and for locating the discriminating points/ Design of Pulse Oximeters , Edited by J. G. Webster, Publ. By Institute of Physics Publishing, Bristol and Philadelphia, 1997L The signal for calculation of the blood oxygen saturation is derived from the same pulse wave. Along with removing me d.c. component of the signal by blocking/U.S. Pat. No. 4,305,401 issued Dec. 15, 1981 to M. Reissmueller et al/the U.S. Pat. No. 4,800,495 issued Jan. 24, 1989 to R. Smith discloses the pulse oxymeter with programmable elimination of the d.c. component by offset amplifier that offsets a portion of the d.c. component of the PPG signal. To achieve utilization of entire dynamic range of the current-to-voltage converter this pulse employs a complex procedure of signal digital construction-reconstruction. The primary problem of such elimination is that it leaves the a.c. pulsatile component centered not enough close to zero level. That makes it hard to identify the discriminating points in pulse wave. This problem remains also when elimination is performed accordingly by the U.S. Pat. No. 4,086,915 issued May 2, 1978 to Kofsky et. al. 
     SUMMARY OF THE INVENTION 
     Accordingly, it is an object of present invention to provide a method of and an apparatus for a bioresonance for individual coordination of physical factors applied to a subject for treatment purposes, which avoid the disadvantages of the prior art. 
     In keeping with these objects and with others which will become apparent hereinafter, one feature of present invention resides, briefly stated, in a method of and an apparatus for a biofeedback, in accordance with which a physical action is applied to a subject for treatment purposes in coordination of cycles of arterial blood pulse flow of a subject. 
     It is a further object of the invention to provide a method and apparatus for automatic individualization the dose of action of the applied action. 
     As it is well known the temporal dynamics of peripheral blood flow comprises cycles of arterial systolic upstroke and diastolic drain/Hole J. W.,  Human Anatomy and Physiology , Brown Company Publishing., 1982./Almost all factors being used in physical therapy, laser and radiotherapy such as ultrasound, electromagnetic waves, laser radiation, etc. are directed to restoring the cell process and tissue regeneration and require synchronization to systolic upstroke cycles. However, there exist some particular factors such as for example, X-ray, massage, which principally require synchronization with diastolic drain cycles due to direct (massage) or indirect effect on blood circulation (side effect of X-ray irradiation). 
     It is easy to show that synchronization of the physical action acting on a subject with the cycles of arterial pulse flow provides also an opportunity for automatic individualization the dose receiving by an organism. Generally under receiving by an organism dose D one understand the product of intensity of acting physical factor I by time of exposure t: 
     
       
         D=I t  
       
     
     In pulse mode the dose depends on the ratio η of the pulse width  T  to pulse period T: 
     
       
         D p =I t  T /T=I t/η 
       
     
     Synchronization makes parameters  T  and T, and therefore the dose D individual. In this regard, simply by synchronizing the action applied to a subject with the subject&#39;s cycles of arterial blood flow an opportunity of automatic dose individualization is provided. 
     Being synchronized to a subject&#39;s cycles of arterial pulse bloood flow the physical action much less disturbs the hierarchy of homeostatic and metabolic rhythms and thus provide markedly more predictable and effective treatment. 
     It is an additional object of the invention to provide a method and apparatus for synchronization of two action simultaneously applied to the individual being treated with different cycles of its arterial pulse blood flow. 
     It is another object of the present invention to provide a signal conditioning circuit with automatic elimination the d.c. component prior the amplification. 
     In keeping with these objects and with others which will become apparent hereinafter, one feature of the present invention resides in a new method and apparatus for synchronization the physical action applied to a subject for treatment purposes among other applications in accordance with systolic influx or/and diastolic drain cycles of subject&#39;s pulse blood flow. As it was described above, the synchronization to the cycles of subject&#39;s peripheral blood flow co-ordinates the physical factor with temporal dynamics of homeostatic rhythms that decrease occurring negative homeostatic reactions on treatment. Besides, the synchronization provides automatic individualization of the dose of the physical factors action on a living body that also sufficiently enhances reproducibility and effectiveness of the treatment. 
     The present invention is based on locating the points of discrimination between systolic upstroke and diastolic descent portions of the pulse wave derived from the PPG signal. Although the present invention describes a method and apparatus which employ the PPG principle of blood pulse wave detection, it in no case is not intended to be limited only by photo-electrical detection of the pulse waves. Many types of pulse wave detectors such as piezoelectric transducers, crystal microphones, Doppler ultrasound, etc. can be used to detect the pulse wave. 
     In the present invention the synchronization is provided by controlling a source of the physical action by means of synchronous to systolic upstroke and diastolic descent time in each pulse wave feedback signals derived from time intervals between the points of discrimination these cycles. In a preferred embodiment the discriminating points are the points of maximum systolic upstroke rate and systolic peak points. 
     The method of the present invention comprises the steps of sensing the arterial blood pulse waves, selecting in each pulse wave the systolic blood influx and diastolic blood drain cycles, generating in the first channel biofeedback signals synchronously to systolic upstroke time and in the second channel biofeedback signals synchronously to diastolic drain time, synchronizing the physical action by controlling by biofeedback signals from the first or second channel. 
     In a preferred embodiment the sensing of arterial blood pulse waves is utilized by deriving the PPG signals from a sensor disposed in contact with the body at the nearest to the affixed area location where the pulse waves can be detected. The method involves locating in each pulse waveform the points of maximum rate of systolic blood influx and systolic peak points by differentiating twice the blood pulse waveform with respect to time and selecting the systolic upstroke time intervals by locating the zero-crossings of the first and second differentiated waves. Generating the biofeedback signals is utilized by generating square pulse signals with the pulse width equal to the time of corresponding cycles and being synchronous to the pulse waves. 
     According to the present invention an apparatus locates the discriminating points in the pulse waveform of the PPG signal derived by a sensor of either transmission or reflection type, and generates feedback square waves synchronously to systolic upstroke or diastolic descent times. For accurate locating of the discriminating points an improved signal conditioning circuit which is automatically removes not pulsating d.c. component of the signal prior amplification is provided. 
     The invented unique biofeedback method and apparatus provide synchronization and dose individualization of a wide variety of the physical action applied in physical therapy laser and radiotherapy and enhanced effectiveness and predictability of treatment over wide spectrum of diseases. The apparatus is relatively simple and cheap and can be used as an interface to any of existing physical therapy, laser and radiotherapy equipment. The benefits of the invention are particularly high when it is used for combined treatment by two physical factors simultaneously such as, for example, radiotherapy along with mechanical pulse squeezing of the blood from targeted area. Synchronization of the irradiation and squeezing cycles with blood diastolic drain intervals and additional laser biostimulation synchronously to systolic influx time allow to increase available dose of irradiation and markedly enhance the success of the treatment. 
     The novel features which are considered as characteristic for the present invention are set forth in particular in the appended claims. The invention itself, however, both as to its construction and its method of operation, together with additional objects and advantages thereof, will be best understood from the following description of specific embodiments when read in connection with the accompanying drawings. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1 shows a sequence of steps of the process of synchronization the physical factor applied to the individual being treated according to the invention; 
     FIG. 2 shows the cycles of arterial pulse blood flow and illustrates formation of the photoplethysmographic signals; 
     FIG. 3 illustrates the location of the discriminating points in pulse wave and corresponding signals in the output channels. 
     FIG. 4 is a graphical illustration of the signal transformation to according a preferred embodiment of the invention; 
     FIG. 5 shows different types of arterial blood pulse waveforms; 
     FIG. 6 is an illustration of translating the waveforms of the signals according to a preferred embodiment; 
     FIG. 7 is a detailed block diagram of a sequence of steps involved in the method of synchronization according a preferred embodiment; 
     FIG. 8 illustrates the embodiment of synchronization by locating in pulse wave of either systolic peak points or points of maximum of systolic upstroke rate; 
     FIG. 9 is a block diagram of a biofeedback apparatus according to the present invention; 
     FIG.10 is a block diagram of conventional conditioning circuits. 
     FIG. 11 is a schematic diagram of a conventional subtractor the d.c. component of the signal prior to amplification. 
     FIG. 12 is schematic diagram of a preferred embodiment of signal conditioning circuit. 
     FIG. 12 is a graphical illustration of the signals produced by a conditioning circuit according to the preferred embodiment; 
     FIG. 13 is a graphical illustration of the signals produced by signal conditioning circuit according to a preferred embodiment of the present invention; 
     FIG. 14 is detailed block diagram a preferred embodiment of first peak detector; 
     FIG. 15 is a diagram of waveform transformation useful in explaining of a signal processing by a first peak detector; 
     FIG. 16 is a diagram of waveform transformation useful in explaining of a signal processing by a second peak detector; 
     FIG. 17 is a detailed block diagram of a processing circuit; 
     FIG. 18 illustrates waveform diagrams explaining signal convertion by a trigger; 
     FIG. 19 is a block diagram of processing and controlling circuits according to the other embodiment of the invention. 
     FIG. 20 is an illustration of waveform explaining signal translation by the circuit shown in FIG. 19; 
     FIG. 21 is a block diagram of processing and controlling circuits corresponding to another embodiment of the present invention; 
     FIG. 22 is a block diagram of utilization of conventional pulse oxymeters in the present invention; 
     FIG. 23 is a block diagram illustrating utilization of the present invention in radiotherapy; 
     FIG. 24 illustrates the waveforms of the signals useful for explaining of the utilization of the present invention in radiotherapy; and 
     FIG. 25 is a block diagram illustrating another utilization of the present invention in radiotherapy combined with laser irradiation. 
    
    
     DESCRIPTION OF PREFERRED EMBODIMENTS 
     A new method and apparatus are provided for synchronization the physical factor applied to a subject with treatment purposes among other applications with different cycles of arterial pulse blood flow. FIG. 1 shows a sequence of steps of the process of synchronization. The method involves sensing the peripheral blood pulse waves, selecting in each pulse waveform the systolic upstroke and diastolic descent cycles, generating feedback controlling signals synchronously either systolic upstroke or diastolic descent time and synchronization of the physical action applied to the individual being treated by controlling the source of applied physical action or appropriate modulator. The selection of the cycles of blood flow comprises locating the points discrimination between these cycles. Generating the feedback signals is utilized by deriving square pulse signals with pulse width equal to the time of corresponding cycles and being synchronous to the discriminating points. As it is illustrated in FIG. 1, the synchronization is utilized by controlling the physical action by feedback signals from the first or second channel. Controlling the physical action means modulating the source of the action or an external modulator by feedback signals from the first or second channels. It is assumed that the output of the source of the action is proportional to the intensity of feedback signals (if the feedback signal is zero, than the factor is “Off”, if the feedback signal is not zero, than the factor is “On”). In a particular case of factor, which cannot be turned On and Off by controlling signal the appropriate modulator is used to the same effect. 
     Since the PPG method enables to directly detect the blood pulse waves, it is used in preferred embodiment for sensing arterial blood pulse waves. However, the invention is not intended to be limited to any specific kind of sensor. Basically, as it is illustrated in FIG. 2, the PPG method involves sensing the effect of blood in tissue on the light passing therethrough. Arterial pulsation increases blood volume in tissue during systole and decrease during diastole. Because of light attenuation by blood absorption and scattering, the light emerging from the tissue is inversely proportional to the volume of blood in tissue/Grimblatov V. Proc. SPIE, Vol.3253, pp119-127, 1998/. Thus, the emergent light intensity will contain a pulsatile component (a.c.) caused by pulse waves of arterial blood and a constant component (d.c.) related to absorption and scattering of tissue inhomogeneities and chromophores such as bone, skin pigmentation, venous blood, etc. Each arterial blood pulse wave consists of systolic influx and diastolic drain cycles, which are limited by systolic onset and peak points on pulse waveform (correspondingly the points D and S in FIG.  2 ). These points are used in photoplethysmographic techniques that utilize the monitoring of blood pulse waves/U.S. Pat. No. 4,928,692 issued May 19, 1990 to Goodman et al). However, accurate location of systolic onset points is highly dependent upon valid pulse waveform typically detected by a sensor disposed on extremity or on the nose or ear. The pulse waveform can be distorted by motion of the body site where the sensor is affixed. Different approaches to elimination motion artifact have developed and various methods and instruments have been disclosed, but the problem still exist/Webster J. G.,  Design of Pulse Oximeters , IOP Publishing, 1997/. The systolic onset points are the most difficult for selecting because of sharp changing in the direction of the slope of the waveform. The use of an additional electrocardiograph (ECG) for gating the expecting moments of occurrence of these points (U.S. Pat. No. 5,485,847 issued Jan. 23, 1996 to Baker) or independent motion detector (U.S. Pat. No. 5,226,417 issued Jul. 13, 1993 to Swedlow) is not effective enough because the time delay between ECG waves and blood pulses varies individually and makes selection complicated and expensive. The other disadvantage of this approach is that selecting these points sharply limits the rate of changing of applied physical factor because any change of the factor with rate higher than the rate of blood influx will disrupt synchronization. In a preferred embodiment, it is used selecting the points of maximum systolic influx rate along with systolic peak points (points M and S in FIG.  2 ). Along with low sensitivity to motion artifact these points allow to sufficiently increase the rate of available changes of the applied factor and are easy for reliable detection. Accordingly, the generating of feedback signals corresponding to selected points comprises: 
     generating in the first channel electrical pulses with duration and occurrence equal to the duration between points of maximum rate of systolic influx and systolic peak points (intervals M-S in FIG. 3) and synchronously to the moments of occurrence of the points of maximal rate of systolic influx; 
     generating in the second channel electrical pulses with duration and occurrence equal to the duration between systolic peak points and points of maximal rate of systolic influx (intervals S-M in FIG. 3) and synchronously to the systolic peak points. 
     Locating these discriminating points involves differentiating twice the pulse waveform with respect to time and locating these points as the points of zero-crossing of the first and second derivatives as illustrated in FIG.  4 . Going from our study based on Kubelka-Munk theory (Grimblatov V. et all, Proc. SPIE, Vol. 2082 pp. 112-119,1993) the derivatives of the pulse waveform are substantially independent of the d.c. component and therefore, are less sensitive to motion artifacts. Published data and our study prove that pulse waveforms may have not only a systolic peak (see FIG.  5 ). In a preferred embodiment, to discriminate systolic peak from not systolic the amplitudes of the pulse waveform and first derivative wave are compared with predetermined reference signals (see FIG.  6 ). Detailed block diagram of a sequence of steps involved in the method according to the preferred embodiment of the present invention is shown in FIG.  7 . 
     Another embodiment of the invention is based on selecting the cycles of arterial pulse blood flow by locating onset and peak systolic points on the pulse waveforin (points D and S in FIG.  2 ). 
     Further embodiment of the invention is based on discriminating between systolic and diastolic cycles by means of determining the average time intervals between homologous points on pulse waveform and dividing the interval in a predetermined proportion. Our empirical observation confirm that the ratio of systolic to diastolic time is relatively stable and its variations from subject to subject fall in a consistently narrow region from 1/7 up to 1/5. That allows to provide discrimination between systolic and diastolic cycles simply by selecting pulse wave intervals. As illustrated in FIG. 8, it can be utilized either by locating only systolic peak points S on pulse waveform or only points of maximum. systolic upstroke rate M. Accordingly, the first type of this embodiment of the invention is based on locating S points by differentiating the pulse waveform with respect to time. After locating the peak points S next step is dividing the time interval between located points in a predetermined proportion for establishing two trains of pulses in two channels with pulse width ratio being equal to the predetermined proportion (see FIG.  8 ). In utilizing this embodiment of the invention on a subject initially an average pulse rate is derived by one of the conventional methods and an average pulse wave interval is calculated. Synchronizing the occurrence of pulses in channel  2  with the moments corresponding to S-points, and synchronizing the occurrence of pulses in channel  1  with the ends of pulses in channel  2  a synchronization of the biofeedback controlling signals with the cycles of arterial pulse blood flow is achieved. 
     The present invention also includes an apparatus utilizing the method of present invention. Referring the overall apparatus block diagram shown in FIG. 9, an apparatus  0  includes a sensor  1  further comprising a probe  6  including a light source  13  and a photodiode  15 , a signal conditioning circuit  7 , a signal processing circuit  2  comprising a first and a second peak detectors  8  and  9 , a controlling circuit  3  comprising a trigger  10  and signal power amplifiers  11  and  12 , and a power supply  4 . 
     The first component of the apparatus to be discussed in detail is the sensor  1 . The sensor includes a probe  6  and a signal conditioning circuit  7 . The probe employs a light emitting diode (LED)  13  to produce incident on blood content tissue  14  light and a photodiode  15  to detect light attenuated by transmitting through the tissue at infrared or other wavelength. The probe prevents orientation of the LED and photodiode with respect to a suitable portion of a subject&#39;s body. In the preferred embodiment LED emits light at 830 nm. However, the invention is not intended to be limited to any specific wavelength of light produced by LED or selected from a regular light source by special filtering. The LED is supplied by current from a power supply  4 . 
     The signal from the photodiode is received by signal conditioning circuit  7 . This circuit is responsible for three aspects of signal conditioning and as typically employed by pulse oxymeters, comprises three separate block as a is shown in FIG.  10 . First, amplifier  16  amplifies signal from photodiode  15 . Next, subtractor  17  removes from the signal the d.c. component, which does not contain information about pulse waves. Third, filter  18  eliminates form the signal the noise of various nature. Known in the art of PPG preamplifiers typically include a differential current-to-voltage amplifier  19  and a single-ended amplifier  20  (U.S. Pat. No. 4,800,495 issued Jan. 24, 1989 to R. Smith). Since photodiode generates an output current, the amplifier  19  translates this current into a voltage with amplification by single-ended amplifier  20 . The primary problem with conventional preamplifiers is that they amplify both components of the signal from photodiode, small a.c. component attributable to light attenuation changes resulting from blood volume changes during the cardiac cycle, and a large d.c. component considered for light attenuation produced by fixed elements in the tissue and not containing information about blood flow. Amplifying the substantial nonpulsatile component use up most of the dynamic range of the differential amplifier and saturates the gain. In this regard in order to provide needed amplification of the a.c. signal the elimination of large d.c. component is necessarily. A subtractor  17  accomplishes this removal. Conventional subtractors removes the d.c. component of signal by blocking with a capacitive blocking element (U.S. Pat. No. 4,759,369 issued Jul. 26, 1988 to Taylor et al) or by eliminating a substantial offset portion(U.S. Pat. No. 5,259,381 issued Nov. 9, 1993 to Cheung et al.,; U.S. Pat. No. 4,407,290 issued Oct. 4, 1983 to Wilber). Blocking the d.c. component by a capacitor partially differentiates signal and, therefore, substantially distorts the waveform of the pulse wave. These distortions depend on amplitudes of both components and vary even from a pulse to pulse. For this reason such devices can not provide the necessary accuracy of discriminating the cycles of pulse waves. 
     The removal of the d.c. component of the signal in prior art devices by offset voltage has two main disadvantages. First is that they eliminate the d.c. component after signal amplification and, therefore, do not resolve the above mentioned problem of gain saturation. Second disadvantage is that in the manner how the d.c. component is removed by offset voltage leaves the a.c. component . substantially out of zero level. That poses serious problem for accurate discrimination cycles in pulse wave. 
     The only subtractor that provides automatic elimination of d.c. component of signal prior to being amplified is disclosed in U.S. Pat. No. 4,086,915 issued May 2, 1978 to H. Kofsky. The particularity of the d.c. component elimination disclosed in this patent can be illustrated by a circuit in FIG.  11 . Referring to this figure, the signal from photodiode is applied in parallel to the plus terminal of differential amplifier and to the input of analogue to digital converter (AAD). In the A/D converter, the amplitude is converted to a digital word which is then converted back to an analogue signal in D/A converter, whose output is connected to the negative terminal of the amplifier. In the arrangement according to this patent the A/D converter is a low resolution converter with resolution less than the order of the a.c. amplitude. In the operation of the circuit it is assumed that the low resolution portion of the composite signal I pd  is always and entirely due to the d.c. component. Although this is not rigorously true, with this assumption the circuit provides an output signal sufficiently indicative of the a.c. component as given by 
     
       
         V=I pd (1−K)R f   
       
     
     where R f  is feedback resistance, and K is relative resolution of the A/D. 
     The main problem here is that for some reasons the entire signal varies from subject to subject and from pulse to pulse. That overdrives the A/D converter and requires to make less offset voltage. That immediately leaves the a.c. component out of zero level and as was discussed above makes hard to discriminate cycles in pulse wave. 
     Adoption of the signal conditioning circuit  2  according to a preferred embodiment of the present invention as it is shown in a schematic diagram in FIG. 12 enables to overcome the problem. As shown, a signal from a photodiode  15  is applied to negative terminals of a first and a second differential amplifier  21  and  22 . The output of differential amplifier  22  is then supplied to the negative terminal of an inverter-filter  23 . The signal outputted from the amplifier  23  is applied to input of the amplifier  21  through a feedback resistor R 2 . 
     Since the signal of photodiode  15  is a current I pd , it drives inputs of amplifiers  21  and  22  in different directions. Current flowing through the feedback resistor Rn creates a voltage at the output of amplifier  22  that is proportional to the light intensity as given by 
     
       
         V pd =(−I pd ).(−R f2 )=I pd .R f2   
       
     
     Here V pd  is a compose signal including both the a.c. and the d.c. components. This signal then is supplied to an inverter-filter  23 . The capacitor C, and feedback resistor R f3  create a filter, which blocks the a.c. component of the signal. So, the output voltage consists of only the d.c. component as given by 
     
       
         V d.c. =−(−I d.c. ).(−R f3 )=I d.c. .R f3   
       
     
     Through the resistor R 2  this compensation voltage is fed to the negative input of the current-to-voltage amplifier  21  to which is directly connected the output of a photodiode  25 . Thus, the current inputting into this terminal is given by 
     
       
         
           I 
           in 
           =I 
           pd 
           −I 
           d.c 
           =I 
           pd 
           −V 
           d.c 
           /R 
           2 
           =I 
           a.c. 
         
       
     
     and contains only the a.c. component. 
     The signal translating by a signal conditioning circuit according to a preferred embodiment is illustrated in FIG.  13 . Before the probe being positioned on a subject the voltage from the photodiode is zero and the compensation voltage is determined only by ambient light, which is made negligible by design of the probe. As the probe has positioned, the a.c. signal occurs along with growing of the voltage compensating the d.c. signal. So the elimination of the d.c. component of the signal is automatically provided prior the a.c. signal being amplified. That enables to use entire dynamic range of a current-to-voltage amplifier  21  for the a.c. amplification. Another benefit of this configuration is the automatic bringing the a.c. signal to zero-level voltage. That makes much easier accurate discrimination of the cycles in pulse waves. For elimination of the noises of various nature and smoothing the signal wavefonn the selected a.c. component further is fed to a filter  8 , which typically is a low pass amplifier. Compensating voltage can be also used for indication of the correct probe positioning by comparison with a predetermined level V 0 . When V d.c. &gt;V 0 , a special comparator allows the sensor to operate. 
     The output of the signal conditioning circuit  3  is next inputs to a signal processing circuit  2  for selecting in each inputting pulse wave the points of discrimination between systolic upstroke and diastolic descent portions. This circuit has two peak detectors  8  and  9  that output two trains of square waves corresponding to the moments of occurrence of the located discriminating points. 
     Referring to the drawing in more detail and to FIG. 14 in particular, the peak detectors  8  and  9  are identical as shown. Each of them includes a comparator  26 , a differentiator  24 , a zero cross detector  25  and a gate  27 . The output of signal conditioning circuit  3  is fed simultaneously to the differentiator  24  and and comparator  26  of the peak detector S. After being differentiated with respect to time by differentiator  26  the differentiation wave signal inputs to zero-cross detector, which actually is a comparator to zero level reference voltage V 1r  and produces a train of square pulses corresponding to each zero-crossing of the differentiation wave. The voltage level comparator  26  compares amplitude of an input pulse wave signal voltage with a preset reference voltage (threshold level) and outputs a train of square pulses corresponding to systolic peaks only. Setting by resister  28  the threshold level enables individual adjustment of the detecting level for selection of systolic peaks of the pulse wave signal with any waveform. Two trains of square pulse signals are translated in a train of square pulse signals with leading edges corresponding to systolic peak points S in pulse waves by a gate  27 . FIG. 15 is a graphical illustration of signal transformation by circuit FIG.  14 . 
     Second peak detector  9  comprises the same blocks as peak detector  8  with the same function and is connected to the output of the differentiator  24 . This peak detector produces a train of square pulse signals with leading edges corresponding to points of maximum rate of the systolic upstroke M in pulse waves. Corresponding waveform diagrams are illustrated in FIG.  16 . FIG. 17 is a block diagram of entire processing circuit  2 . 
     The outputs of first and second peak detectors  8  and  9  are next inputted to a controlling circuit  3  which can be simply a trigger  10  (see FIG.  9 ). The trigger  10  provides to the outputs feedback square pulse signals synchronously and with duration to time intervals between points M and S in channel  1  and in channel  2  synchronously and with duration to time intervals between points S and M. FIG. 18 illustrates corresponding waveform translations. 
     After power amplification by amplifiers  11  and  12  the signals from channel  1  or  2  alternately turn a source of physical factor  4  “On” and “Off”. It is assumed that the output of the source of physical factor is proportional to the intensity of control signal (if the signal is zero than the factor is “Off”, if the signal is not zero than the factor is “On”) In particular case of factor, which cannot be turned “Off” and “On” by controlling signals the appropriate modulator is used to the same effect. 
     Another embodiment of the present invention is based on empirical fact that the ratio of the systolic upstroke time to diastolic descent time has small changes from subject to subject which fall in a very narrow region from 1/7 to 1/5. FIG. 19 is a block diagram of processing and controlling circuits  2  and  3  according to this embodiment of the invention. The signal processing  2  comprises only one S -peak detector  8  connected to the output of sensor  1  and provides to the output a train of square pulse signals with interval being equal to the time interval between pulse waves. The outputted signals next are fed to a feedback controlling circuit. More specifically, the train of square pulse signals is fed to the input of a trigger pulse differentiator  29 , which decrease the effective width of the pulses outputted by peak detector  8 . Formed by the trigger pulse differentiator  29 , pulse signals are fed to the input of a timer  30  which can be a commercial timer NE 555 . Timer provides the output of a train of square pulse signals synchronously to inputted pulse signals and with a preset by resistor  31  pulse width. An alternative output formed by inverter  32  outputs a train of opposite square pulse signals. FIG. 20 illustrates the signal translation by a circuit represented by block diagram  17 . 
     The other type of this embodiment of the present invention utilizes locating the pulse wave interval as a time interval between M-points in neighboring pulse waves. The block diagram of processing and controlling circuits  2  and  3  of this type is shown in FIG.  21 . By comparing with FIG. 19 it is easy to see that the only difference of these circuits is that the pulse wave signals from sensor  1  are fed to an additional differentiator  33  which is similar to above described differentiator  24  and provides an output a differentiation wave. All other blocks in this type of embodiment are the same as shown in FIG.  19 . In utilizing this embodiment of the present invention on a subject, initially an average pulse rate N is derived by one of conventional methods (even manually) and an average pulse wave interval T is calculated as given: 
     
       
         T =60/N  
       
     
     Then by dividing the result of calculation in a proportion from range 1/7:1/5 the values for presetting the pulses&#39; width are determined and set. For example, if the average pulse rate is 60, the average pulse wave interval will be 1 sec, and the pulse widths for ratio 1/5 will be correspondingly 200 and 800 ms. 
     Further embodiment of the present invention is based on locating the systolic onset and peak points. This embodiment employs a conventional pulse oxymeter available for example from Ohmeda, Inc. as a source of signals corresponding to these points. Block diagram of the apparatus regarding this embodiment is shown in FIG.  22 . 
     The present invention provides a unique method and apparatus for improvement of current treatments, which use of different physical factors. 
     Pertinent utilization of the present invention is improvement of treatment of human tumors by radiotherapy alone or combined with adjuvant such as tissue compression or laser irradiation. As it is, blood flow in the tissue, including tumors, markedly influences the tissue damage by radiation because it supplies oxygen, the most potent modifier of radiation effect and limits the dose of irradiation. This fact clearly indicate that blood evacuation by squeezing the tissue synchronously to the diastolic times of blood flow and synchronization to this intervals the irradiation by means of the present invention is a cardinal improvement of radiotherapeutic technologies. FIG. 23 illustrates utilizing the present invention for combined radiological irradiation and tissue compression. The targeted area located, for example on a leg of a subject, is irradiated by a beam  38  controlled by a shutter  35 . This area is also compressed by a tissue compressing device  36 , and a sensor  1  of bioresonance feedback apparatus  0  of this invention is positioned on a toe of the subject. The shutter  35  and tissue compression device  36  are both connected to the same output of apparatus  0 . Controlled by apparatus  0  the tissue compression device  36  squeezes tissue and evacuate blood of the tissue synchronously to diastolic times of blood flow. Being synchronous to the same periods of time a radiological beam irradiates bloodless tissue, including tumor. Instead, during systolic periods either blood or tissue is not irradiated. Corresponding signals and time diagrams are shown in FIG.  24 . FIG. 25 shows a block diagram of utilization the present invention for radiotherapy combined with tissue squeezing and laser irradiation. An additional laser beam  39  is interrupted by a shutter  41  controlled by the systolic output of the apparatus  0 . 
     It will be understood that each of the elements described above, or two or more together, may also find a useful application in other types of constructions differing from the types described above. 
     While the invention has been illustrated and described as embodied in bioresonance feedback method and apparatus, it is not intended to be limited to the details shown, since various modifications and structural changes may be made without departing in any way from the spirit of the present invention. 
     Without further analysis, the foregoing will so fully reveal the gist of the present invention that others can, by applying current knowledge, readily adapt it for various applications without omitting features that, from the standpoint of prior art, fairly constitute essential characteristics of the generic or specific aspects of this invention.