WO2000024311A1 - Bioresonance feedback method and apparatus - Google Patents

Abstract

A bioresonance feedback method, and apparatus (0) for applying a physical factor to a subject.

Description

Description

BIORESONANCE FEEDBACK METHOD AND APPARATUS

Technical Field

The present invention relates to a method of and an apparatus for a bioresonance feedback for individual co-ordination of physical factors applied to a subject for treatment purposes among other applications with physiological parameters of the subject

Background Art

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 , Pπroda, 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, ppl63-225, 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 factors 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's physiologic functioning and applied physical factors 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's physiological functioning by providing "feed-back" of their physiological activities Known instruments of this category provide indication of the heart rate /US Patents 4,450 843 issued May 29, 1984 to Barney et all, 5,007,430 issued April 16, 1991/, brain waves / US Patent 4,031 ,884 issued June 28, 1977 to Henzel et al/, blood pulse waves / US Patents 4,450,843 to Barney et all, 5,475,725 issued December 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 / US Patent 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'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 US Patent 5,522,854 issued June 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 US Patent 5,447,520 issued September 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 US Patent 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 factors 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 November 14, 1986 to Zaguskm et all

According to the patent the cell biorhythms are determined at the first step Then the physical factor 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 /US Patent 4,305,401 issued December 15, 1981 to M Reissmueller et al/ the

US Patent 4,800, 495 issued January 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 US patent 4,086 915 issued May 2, 1978 to Kofsky et al

Disclosure of the Invention

Accordingly, it is an object of present invention to provide a method of and an apparatus for a bioresonance feedback 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 bioresonance feedback, in accordance with which a physical factor 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 individuahzation the dose of action of the applied factor 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 factor acting on a subject with the cycles of arterial pulse flow provides also an opportunity for automatic individuahzation 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 = 1 1

In pulse mode the dose depends on the ratio η of the pulse width T to pulse period T

D_p = I t τ /T = l t/η Synchronization makes parameters T and T, and therefore the dose D individual In this regard, simply by synchronizing the factor applied to a subject with the subject's cycles of arterial blood flow an opportunity of automatic dose individuahzation is provided

Being synchronized to a subject's cycles of arterial pulse blood flow the physical factor 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 factors 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 factor applied to a subject for treatment purposes among other applications in accordance with systolic influx or/and diastolic drain cycles of subject's pulse blood flow As it was described above, the synchronization to the cycles of subject's peripheral blood flow co-ordinates the action of the physical factor with temporal dynamics of homeostatic rhythms that decrease occurring negative homeostatic reactions on treatment Besides, the synchronization provides automatic individuahzation of the dose of the physical factor's 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 factor 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 uOstroke 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 factor 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 invent unique biofeedback method and apparatus provide synchronization and dose individuahzation of a wide variety of the physical factors 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 apphed 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 bioresonance feedback 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 conversion 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

Best Mode of Carrying Out the Invention 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 Figure I 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 factor applied to the individual being treated by controlling the source of applied physical factor 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 Figure 1 , the synchronization is utilized by controlling the physical factor by feedback signals from the first or second channel Controlling the physical factor means modulating the source of the factor or an external modulator by feedback signals from the first or second channels It is assumed that the output of the source of the factor 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 Figure 2, the PPG method involves sensing the effect of blood in tissue on the light passing there through 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 /GπmblatovV 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 in homogeneities and chromophores such as bone, skin pigmentation, venous blood, etc Each arterial blood pulse wave consists of systolic influx and diastolic dram cycles, which are limited by systo c 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 / US Patent 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 (US Patent 5,485,847 issued January 23, 1996 to Baker) or independent motion detector (US Patent 5,226,417 issued July 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 Figure 4 Going from our study based on Kubelka-Munk theory (GnmblatovV etall. Proc SPIE. Vol 2082 pp 112-119,1993) the derιvatιves ofthe 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 Figure 6) Detailed block diagram of a sequence of steps involved in the JO- 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 waveform (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-pomts, and synchronizing the occurrence of pulses in channel I 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'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 (US Patent 4,800, 495 issued January 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 (US Patent 4,759,369 issued July 26, 1988 to Taylor et al) or by eliminating a substantial offset portιon(US Patents 5,259,381 issued November 9 1993 to Cheung et al ,, 4,407,290 issued October 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 gam 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 US Patent 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 l_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 -Insufficiently indicative of the a.c component as given by

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 R₂

Since the signal of photodiode 15 is a current l_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

^Vpd ⁼ (^"lpd) (" Rf_) ⁼ lp ^' Rf2

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

Through the resistor R₂ 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

'in ⁼ lpd ^_ 'dc ⁼ 'pd " V_{d c}/ ₂ - l_{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 waveform 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 V₀ When V_{d c} > V₀, 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 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 ,mpιrιcal 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 NE555 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-pomts 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_ιs derived by one of conventional methods (even manually) and an average pulse wave interval J_ιs 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' 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

What is claimed as new and desired to be protected by Letters Patent is set forth in the appended claims

Claims

Claims

1 A bioresonance feedback method for applying a physical factor to a subject for medical purposes, comprising the step of coordinating applying of a physical factor to a subject with cycles of arterial blood pulse flow of the subject

2 A bioresonance feedback method as defined in claim 1 , wherein said coordinating includes sensing arterial blood pulse waves of a subject's body, selecting in each pulse wave a systolic influx and diastolic drain blood cycles, generating feedback signals in a first channel synchronously to the systolic influx cycles and in a second channel synchronously to diastolic drain cycles, and synchronizing the physical factor to said cycles by controlling the physical factor by feedback signals of the first and second channels

3 A bioresonance feedback method as defined in claim 2, wherein said sensing includes photo-electπcally detecting the pulse waves from a nearest to an effected area location where a pulse wave can be detected

4 A bioresonance feedback method as defined in claim 2, wherein said selecting includes locating in the pulse wave points of discrimination between said systolic upstroke and diastolic descent intervals

5 A bioresonance feedback method as defined in claim 4, wherein said generating includes providing square pulse signals in the first channel synchronously and with a pulse width being equal to occurrence and duration of the systolic upstroke intervals and in the second channels synchronously and with a pulse width being equal to occurrence and duration of the diastolic decent intervals

6 A bioresonance feedback method as defined in claim 2, wherein said sensing includes sensing the pulse waves by photoplethysmography

7 A bioresonance feedback method as defined in claim 4, wherein said locating the points of discrimination includes locating systolic peak points and points of maximum systolic upstroke rate

8 A bioresonance feedback method as defined in claim 4, wherein locating the points of discrimination includes locating a points of discrimination of systolic onset and systolic peak points

9 A bioresonance feedback method as defined in claim 4, wherein said locating the points of discrimination includes dividing an average time interval between pulse waves in a predetermined proportion

10 A bioresonance feedback method as defined in claim 9, wherein said dividing includes dividing a time interval between points of maximum systolic upstroke rate

11 A bioresonance feedback method as defined in claim 9, wherein said dividing includes dividing an interval between said systolic peak points

12 A bioresonance feedback method as defined in claim 9, wherein said dividing includes dividing in the predetermined proportion within a range from 1/7 to 1/5

13 A bioresonance feedback method as defined in claim 7, wherein said locating the points of maximum systolic upstream rate and systolic peak points includes differentiating twice the pulse wave with respect to time to produce first and second differentiated waves, comparing amplitudes of the pulse wave and the first differentiating wave with predetermined reference signals for discriminating the systolic peaks on the pulse wave and positive peaks in the first differentiated wave, detecting zero-crossing of the first and second differentiated waves, and locating the systolic peak points as points of the first differentiated wave zero-crossing within discriminated systolic peak and locating the points of maximum systolic upstroke rate as points of the second differentiated wave zero-crossing with discriminated positive peak of the first differentiated wave

14 An apparatus for application of a physical factor to a subject for medical purposes, comprising means for applying the physical factor to a subject in accordance with cycles of arterial blood pulse flow of the subject

15 An apparatus as defined in claim 14, wherein said applying means including a sensor for sensing blood pulses from a body of the subject comprising a probe with a source and a detector of electromagnetic radiation mounted with possibility for gripping a part of the body at a place where a portion of an electromagnetic radiation attenuated by blood content tissue is detectable, sensing means for producing an output signal corresponding to an alternative component of the attenuated electromagnetic radiation, a conditioning electronic circuit to which said probe is electrically connected, input conditioning means connected to said detector for removing a direct current component from a pulse wave signal and for smoothing an alternative component wave form, a processing electronic circuit to which said conditioning circuit electrically connected, input processing means connected to said signal conditioning circuit for locating on the pulse wave points of discrimination between systolic upstroke and diastolic descent intervals, locating means identifying time moments corresponding to the points on the pulse wave, a feedback controlling electronic circuit to which said processing circuit is electrically connected, input controlling means connected to said processing circuit for providing to first output channel square electrical pulses synchronously and with duration equal to occurrence and duration of systolic upstroke intervals and providing to a second output channel square electrical pulses synchronously and with duration equal to occurrence and duration of diastolic descent intervals, and a source of electrical energy to which said electronic circuits are electrically connected

16 An apparatus as defined in claim 15, wherein said source and said detector of electromagnetic radiation are light emitting diode and photodiode

17 An apparatus as defined in claim 15, wherein said conditioning circuit includes a first differential amplifier with a negative terminal to which said photodiode is electrically connected, a second differential amplifier with a negative terminal to which said photodiode is electrically connected, an inverter-filter to which said second differential amplifier is electrically connected and whose output is electrically connected through a resistor to said negative terminal of said first differential amplifier, and a filter to which an output of said first differential amplifier is electrically connected for eliminating noise and ambient-like signal

18 An apparatus as defined in claim 15, wherein said processing circuit includes a first peak detector to which said sensing circuit is electrically connected for detecting systolic upstroke peak points on the pulse wave, and a second peak detector to which said sensing circuit is also electrically connected for detecting points of maximal systolic upstroke rate on the pulse wave

19 An apparatus as defined in claim 18, wherein said feedback controlling circuit includes a trigger to which said first peak detector and said second peak detector are electrically connected, input triggering means for providing to said first output channel square electric pulses synchronously and with duration equal to occurrence and duration of the systolic upstroke intervals and providing to said second output channel square electric pulses synchronously and with duration equal to occurrence and duration of the diastolic decent intervals, and first and second power amplifier to which correspondingly are connected said first and second channels for power amplifying of the square electric pulses 20 An apparatus as defined in claim 15, wherein said processing circuit includes a first comparator to which said conditioning circuit and first source of reference signal are electrically connected, input comparing means for providing to the output square pulses corresponding to time intervals when amplitudes of the pulse waves of the alternative component are above a predetermined value of a first reference signal, a first differentiating circuit to which said conditioning circuit is electrically connected, input differentiating means for providing to the output a first differentiated wave, a first zero-cross detector to which said first differentiating circuit is electrically connected for detecting zero-crossing points of said first differentiated wave, a first logic gate to which said first zero-cross detector and said first comparator are electrically connected for selecting peak systolic points, a second comparator to which said first differentiating circuit and a second source of reference signal are electrically connected, input comparing means for providing to the output square pulses corresponding to time intervals which amplitudes of positive half wave of said first differentiated wave are above a predetermined value of the second reference signal, a second differentiating signal to which said first differenting circuit is electrically connected, input differentiating means for providing to the output a second differentiated wave, a second zero-cross detector to which said second differentiating circuit is electrically connected for detecting zero- crossing points of said second differentiated wave, and a second logic gate to which said second zero-cross detector and said second comparator are electrically connected for selecting points of maximal systolic upstroke rate

21 An apparatus as defined in claim 20, wherein said first and second logic gates are an AND gate

22 An apparatus as defined in claim 20, wherein said filter is a low pass filter

24 An apparatus as defined in claim 15, wherein said processing circuit includes only a systolic peak detector which is electrically connected to said sensor for producing a tram of square pulse signals synchronously to systolic peak points

25 An apparatus as defined in claim 24, wherein said controlling circuit includes a trigger pulse differentiator to which said peak detector is electrically connected for decreasing a pulse width, a timer to which said trigger pulse differentiator is electrically connected for providing to the output square pulse signals with pulse width which is equal to a predetermined portion of a time between pulse waves, and an mvertor to which said timer is electrically connected for establishing a second output for pulse signals having pulse width equal to a difference between time between pulse waves and a pulse width of signals in said first channel

26 An apparatus as defined in claim 25, wherein a predetermined quotient is within a range from 1/7 to 1/5

27 An apparatus as defined in claim 25, wherein said points of discrimination between the pulse waves are points of maximal systolic upstroke rate

28 An apparatus as defined in claim 25, wherein points of discrimination between the pulse waves are systolic peak points

29 An apparatus as defined in claim 15, wherein said sensor and said processing circuit are a pulse oxymeter

AMENDED CLAIMS

[received by the International Bureau on 3 April 2000 (03.04.00); original claims 1 and 14 replaced by new claims 1 and 14; remaining claims unchanged (1 page)]

1. (amended) A bioresonance feedback method used for medical

purposes, comprising the step of applying of a physical factor to a subject for medical purposes; and coordinating the applying with cycles of arterial blood pulse flow of the subject.

14. (amended) An apparatus for application of a physical factor to a subject for medical purposes, comprising means for applying the physical

factor to a subject; and means for coordinating the applying in accordance with cycles of arterial blood pulse flow of the subject.

STATEMENT UNDER ARTICLE 19

In the International Search Report .he Examiner indicated that in his opinion U.S. patent 5,694,939 to Cowings and U.S. patent no.5,577,510 to Chittum are documents of particular relevance, so that the claimed invention can not be considered to involve an Inventor's Statement when the document is combined with one or more other such documents, such combinations being obvious to a person skilled in the art.

U.S. patent no. 5,577,510 describes a biofeedback system for control of a subject's physiological variable such as heart rate by user's volitional control of the response on audio or video information about the level of the physiological variable accordingly to the trainer's recommendations by means of triggering a recorded message upon sensing a predetermined value of the physiological signal. Accordingly to the system described in this patient, a subject himself or herself controls the physiological variable accordingly to a

recorded message which is triggered when an average value of the physiological variable exceeds a predetermined level.

In accordance with the present invention the bioresonance feedback method and apparatus operate for control a physical factor applying

to a subject for medical purposes by automatic timing the applying physical factor to the cycles of a subject's arterial blood circulation by means of synchronization of the applying of the physical factor to the time and duration of cycles of subject's physiological variable such as arterial blood circulation. Therefore, in contrast to the solution disclosed in the reference, the applicant's invention automatically (not by volitional and emotional control) controls the physical factor (not the level of a subject's physiological variable) by timing the factor to a subject's arterial blood circulation (not by sensing the level of the physiological variable).

The comparative analysis of the present invention and the solution proposed in the reference is presented in the following table.

are completely different. Moreover, designed only for physiological training, the

system of the Patent 3 5,577,510 is not even applicable for medical purposes covered by the present invention. It is therefore believed to be clear that the present invention and the solution proposed in the reference, the above analysis is also true for the system described in the US Patent #5,594,93 which is a system for training a subject by means of his/her own volitional control of the physiological variable

in response on information about it and accordingly to the instructions of the trainer. The only one difference is that it comprises an additional trainer subsystem with a process for formation the baseline values of a several

physiological variables and selection the most sensitive parameter to send it tot he trainee along with instructions for self-training.

It is therefore submitted that the new features of present invention as defined in claims 1 and 14 clearly and patentably distinguish the present invention from the references applied by the Examiner.