Abstract:
A system and method for predicting and avoiding a seizure in a patient. The system and method includes use of an implanted surface acoustic wave probe and coupled RF antenna to monitor temperature of the patient&#39;s brain, critical changes in the temperature characteristic of a precursor to the seizure. The system can activate an implanted cooling unit which can avoid or minimize a seizure in the patient.

Description:
CROSS-REFERENCE TO RELATED PATENT APPLICATIONS  
       [0001]     This application claims the benefit under 35 USC 119(e) of U.S. Application 60/721,911, filed Sep. 29, 2005, incorporated herein by reference in its entirety. 
     
    
       [0002]     The United States Government has certain rights in the invention pursuant to Contract No. W-31-109-ENG-38 between the U.S. Department of Energy and the University of Chicago operating Argonne National Laboratory. 
     
    
       [0003]     The present invention is generally related to a surface acoustic wave device for predicting seizures in a patient. More particularly the invention is related to a surface acoustic wave probe implanted into a patient for sensing temperature changes in the human brain, with certain temperature changes being characteristic of precursors to the onset of a seizure.  
         [0004]     Epilepsy is one type of neurological disorder which affects about 1% of the U.S. population, or 2.7 million Americans of all ages. This prevalence figure holds true for all industrialized countries, but it is much higher for underdeveloped countries with rates as high as 10%. Up to 40,000 Americans die each year from seizures in a country where medical care is the most advanced in the world; and this underscores the serious impact of this disease. Most people with epilepsy, although of normal intelligence, are either unemployed or sub-employed due primarily to the unpredictability of seizures. Despite current advances in drug therapy, only 15% of those treated by state of the art medications have neither seizures nor debilitating side effects. The negative impact of epilepsy on the lives of those who suffer from epilepsy and on their families and communities can be considerably lessened if the unpredictability of seizures is removed and innovative alternatives such as non-pharmacological treatments are developed.  
         [0005]     Early prediction of the onset of seizures is critical for implementing appropriate prevention measures such as by electrical excitation, cooling or drug therapy. A prediction window of 15 s to 180 s would allow time for effective use of appropriate prevention strategies. There have been attempts to monitor the electrical potentials between a pair of electrodes implanted in the brain to provide direct means of detecting neuronal activity. However, this technique has not been found very reliable because of the dynamic noise in the electrographic signals.  
       SUMMARY OF THE INVENTION  
       [0006]     A surface acoustic wave (SAW) sensor can be used to detect temperature changes in the human brain by implementation into seizure-prone areas of the brain. This is an indirect but a more reliable device and method to detect the onset of seizures with a precursor temperature change that follows commencement of abnormal neuronal activity in the epileptic zone of a patient&#39;s brain. For example, a characteristic temperature pattern is an initial dip of about 0.2-1° C. which is then followed by a rapid rise of about 3-4° in the seizure-prone areas of the brain.  
         [0007]     The subject SAW sensor can be implanted and configured to operate in a wireless mode and without a battery power source. The wireless SAW sensor includes a delay-line configuration coupled with an RF antenna that communicates with an outside interrogation unit. A transmitting inter-digital transducer (IDT) on the SAW sensor transforms the RF signal from the outside interrogation unit into surface acoustic waves. The waves propagate on the SAW substrate, which is the sensing region. The sound propagation parameters such as phase velocity and delay time vary with temperature. A receiver IDT on the SAW sensor converts the SAW signal into an RF signal, which is then transmitted back to the interrogation unit. The pseudo-wireless version consists of a wired SAW sensor implanted in the brain tissue and connected to a miniature transceiver unit mounted on or under the skull. A telemetry unit interrogates with the transceiver for collecting and monitoring the sensor parameters.  
         [0008]     The principal features of the invention therefore include without limitation: 
    1. Epileptic seizure onset detection is based on the method of monitoring temperature change, which may precede the chaotic electrical signals normally used in prediction of seizure activity;     2. Development of a dual SAW sensor scheme with a very high sensitivity of 1.4 millikelvin; and     3. Design of passive implantable SAW device for wireless operation, without need of a battery power source.    
 
         [0012]     Various aspects, features and advantages of the invention are described hereinafter and these and other improvements will be described in more detail hereinafter, including the drawings described below. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0013]      FIG. 1  illustrates an epilepsy control system disposed in a human;  
         [0014]      FIG. 2  illustrates details of the control system of  FIG. 1 ;  
         [0015]      FIG. 3  illustrates a schematic diagram of the SAW sensor;  
         [0016]      FIG. 4  illustrates a schematic of the phase method of operating the SAW sensor using a dual sensor arrangement;  
         [0017]      FIG. 5A  illustrates input and output oscillograms at T=24° C. for measurement of the SAW sensor and  FIG. 5B  illustrates the results for T=36° C.;  
         [0018]      FIG. 6A  illustrates SAW sensor temperature-phase shift dependence for a delay line at 434 MHz and  FIG. 6B  illustrates the dependence for using in a filter mode at 172 MHz;  
         [0019]      FIG. 7A  illustrates typical pulsed signal oscillograms for measurements of SAW sensor delay periods with a filter mode at 172 MHz and  FIG. 7B  illustrates an oscillogram for a delay line at 434 MHz;  
         [0020]      FIG. 8A  illustrates a signal oscillogram at the intermediate frequency from a reference channel (Channel  1 ) at 0° C. and measurement (Channel  2 ) of the SAW sensor at a measurement temperature of 41° C. and  FIG. 8B  shows the oscillogram at a temperature of 44° C.  
         [0021]      FIG. 9A  illustrates signal oscillograms at an intermediate frequency from the reference (full line) and measured values (dotted line) for the SAW sensor with a filter type sensor and carrier frequency at 172 MHz;  FIG. 9B  shows the change of phase shift with reference to  FIG. 9A  when the measurement sensor was heated by a filament lamp;  
         [0022]      FIG. 10  shows variation in phase difference in relation to temperature differences from  FIGS. 9A and 9B ;  
         [0023]      FIG. 11  illustrates a block diagram of a phase shift to temperature converter;  
         [0024]      FIGS. 12A and 12B  illustrate in a split drawing a phase shift-temperature converter basic circuit;  
         [0025]      FIG. 13  illustrates a schematic of a telemetry system at a frequency of 434 MHz (dipole antenna) where G is a high frequency generator with antenna; R 1  and R 2  are receiving antennae and T is a transmitting antenna;  
         [0026]      FIG. 14  illustrates a telemetry system at 434 MHz (zigzag antennae);  
         [0027]      FIG. 15  illustrates components of a simulation system for sensing temperature deviations;  
         [0028]      FIG. 16  illustrates a system with a dipole antenna in a simulation medium;  
         [0029]      FIG. 17  illustrates a flagpole type antenna in a simulation medium.  
         [0030]      FIG. 18A  is a photograph of a SAW sensor of the resonator type and  FIG. 18B  for an HF filter type;  
         [0031]      FIG. 19A  is a photograph of SAW sensor electrodes of the resonator type SAW sensor (in  FIG. 18A );  FIG. 19B  is for an HF filter type SAW sensor;  
         [0032]      FIG. 20  illustrates a high frequency oscillator block diagram with a frequency modulation of 434 MHz with item  1  a saw tooth generator, item  2  an HF oscillator and item  3  an HF amplifier;  
         [0033]      FIG. 21  illustrates calibration results for diode sensor that was used to calibrate the SAW sensor;  
         [0034]      FIG. 22  illustrates behavior of the oscillogram of the mixer output (F intermed ); and  
         [0035]      FIG. 23A  illustrates conductance as a function of frequency of grey and white brain substance;  FIG. 23B  illustrates permittivity or penetration for grey or white brain substance as a function of frequency; and  FIG. 23C  illustrates electromagnetic radiation penetration depth as a function of frequency for grey and white brain substance and muscle tissue. 
     
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS  
       [0036]     One form of the invention is shown in  FIG. 1  in conjunction with use in the human body and a surface acoustic wave (“SAW” hereinafter) sensor  10  is shown generally at  10 . As will be discussed hereinafter, a clinician may also choose to include a cooling implant  20  as a means of arresting seizures. In addition, a remote interrogation/control system  30  (hereinafter “control system  30 ”) is shown for control of the SAW sensor  10  and/or the cooling implant  20 .  
         [0037]     The precursors of a seizure are believed to be manifested by temperature changes in certain parts of the human brain  15 . This temperature change can be detected by the SAW sensor  10  and then characteristic data is transmitted to the control system  30  with a telemetric system  40  (see  FIG. 2 ). The control system  30  evaluates the temperature change information and can activate the cooling implant  20  which can help prevent onset of a seizure by cooling the seizure-prone area of the human brain.  
         [0038]     A more detailed drawing of the SAW sensor  10  is shown in  FIG. 3  and includes a substrate  50 , first antenna  60  coupled to first interdigital transducer  70  and a second antenna  80  coupled to a second interdigital transducer  90 . An interrogation signal  100  excites the first transducer  70  which outputs a surface acoustic wave  110  sensed by the second transducer  90  which provides via the second antenna  80  an output signal  120  characteristic of the acoustic wave sensed. For the system shown in  FIG. 4 , as the temperature being sensed changes, the phase of an RF signal changes in accordance with a relationship shown hereinafter and explained in detail. The first transducer  70  can function as the measurement sensor and disposed in the epileptogenic region and the second transducer  90  can function as a reference sensor disposed in a non-epileptogenic region. This arrangement minimizes the effect of RF source instabilities, corrects for the background fluctuations in pressure, motions, etc., maximizes the difference in temperature between the two regions (epileptogenic and non-epileptogenic regions), and allows for longer integration of signals and in turn providing higher sensitivity. Or, the reference sensor  90  may be kept in a constant temperature box outside the brain and the measurement sensor  70  in the brain. This arrangement amplifies the temperature changes in the brain with respect to a fixed temperature with attendant benefits of longer integration, etc.  
         [0039]     Use of the SAW sensor  10  is then based on varying conditions of propagation of surface acoustic waves in the substrate  50  when temperature, pressure, electric field and mechanical load change. Linear coefficients obtained for the measurable changes from different physical effects are given in Table 1:  
                           TABLE 1                                   Physical value   Linear coefficient                           Temperature   Up to 100 ppm/K           Pressure   2 ppm/kPa           Mass loading   30 ppm/μg · cm 2             Voltage   1 ppm/V           Electric field strength   30 ppm/V · μm −1                        
 
         [0040]     As can be seen by the sensitivity shown in Table 1, the temperature (T) can undergo substantial changes over a temperature value range 15-42° C. The principle of temperature measurement with the use of the SAW sensor  10  can be compared to characteristics of the SAW sensor  10  exciting an electric signal. If the substrate temperature changes, the following signal parameters therefore vary: 
        Amplitude;     Delay period;     Phase;     Resonance frequency.        
 
         [0045]     As shown in  FIG. 4 , a generator  130 , preferably operated at 439-429 MHz, which is linearly modulated with an inside frequency bandwidth of the SAW sensor  10 , is used as part of the measurement scheme. Generator output signals are passed to the SAW sensor  10  and then mixers. The SAW sensor “ref” box  140  has a delay time t 1  and its constant temperature is T 0 . SAW sensor “work” box  150  has delay time t 2  and measures temperature change ΔT with phase sensitivity  
         S   t     Δ   ⁢           ⁢   φ       =       ∂   φ       ∂   T           
 
 (phase degree of arc/° C.). A frequency modulated (FM) reference signal is passed to both of the SAW sensors  10  simultaneously:  
           E   0     ⁡     (   τ   )       =       E   0     ⁢   cos   ⁢           ⁢   2   ⁢     π   ⁡     (         (       f   0     +       b   ⁢           ⁢   τ     2       )     ⁢   τ     +     φ   0       )             
 
         [0046]     Echo-signal from each of the SAW sensors  10  is passed to mixer  160  or  170  and then to a signal processing board  180 :  
           E   1     ⁡     (   τ   )       =       E   1     ⁢   cos   ⁢           ⁢   2   ⁢           ⁢     π   ⁡     (         (       f   0     +       b   ⁡     (     τ   -     t   1       )       2       )     ⁢   τ     +     φ   0       )             
           E   2     ⁡     (   τ   )       =       E   2     ⁢   cos   ⁢           ⁢   2   ⁢           ⁢     π   ⁡     (         (       f   0     +       b   ⁡     (     τ   -     t   2       )       2       )     ⁢   τ     +     φ   0     +       1   360     ⁢       S   T     Δ   ⁢           ⁢   φ       ·   Δ     ⁢           ⁢   T       )             
 
         [0047]     At this moment reference signals also pass to the mixers:  
           E   01     ⁡     (   τ   )       =       E   01     ⁢   cos   ⁢           ⁢   2   ⁢           ⁢     π   ⁡     (         (       f   0     +       b   ⁢           ⁢   τ     2       )     ⁢   τ     +     φ   0       )             
           E   02     ⁡     (   τ   )       =       E   02     ⁢   cos   ⁢           ⁢   2   ⁢           ⁢     π   ⁡     (         (       f   0     +       b   ⁢           ⁢   τ     2       )     ⁢   τ     +     φ   0       )             
 
         [0048]     At the nonlinear mixers output we obtain signals at the intermediate frequencies bt 1 /2 and bt 2 /2:  
           A   1     ⁡     (   τ   )       =       A   1     ⁢   cos   ⁢           ⁢   2   ⁢           ⁢     π   ⁡     (         bt   1     2     ⁢   τ     )             
           A   2     ⁡     (   τ   )       =       A   2     ⁢   cos   ⁢           ⁢   2   ⁢           ⁢     π   ⁡     (           bt   2     2     ⁢   τ     +       1   360     ⁢       S   T     Δ   ⁢           ⁢   φ       ·   Δ     ⁢           ⁢   T       )             
 
         [0049]     Thus the methodology lets us transfer the phase shift S T   Δφ ·ΔT into the low frequency region. After digitizing these low frequency signals with the help of microcontroller, one can determine the value of the SAW sensor substrate temperature.  
         [0050]     Considering interrelation of time delay, t 0 , in the SAW sensor  10 , which appears as a result of relation between A 2 (τ) and other physical values, an intermediate frequency Ω φ =bt 2 /2 should be low enough to provide an opportunity to measure phase shift with the required accuracy. On the other hand, it must provide the required system operation speed (on the basis of the up-date available data on development of epileptic seizure, this should be about ≦1 sec. −/1/). Coefficient b≈Δω·Ω ω  is determined by the acoustic width of the SAW sensor bandwidth (Δω) and operation frequency of the saw-tooth voltage generator (Ω ω ). To estimate delay time t 2  one can take the signal delay time, t 0 , in the SAW sensor  10 .  
         [0051]     We can then obtain the relationship, linking parameters of the scheme (Ω ω ), SAW sensor(Δω and t 0 ) and the requirements, imposed on accuracy and operational speed of the temperature sensor (Ω φ ):
 
Ω φ ˜Ω ω ·Δω·t 0 
 
         [0052]     One can see that t 0  should not be considered in isolation from other characteristics of the system. In our case for Ω ω ≈1 kHz, Δω≈10 MHz, t 0 ≈0, 2 us (for conventional BIOFIL sensors) we obtain Ω ω ˜2 kHz, which seems an optimal value both from the viewpoint of sensitivity and operational speed.  
         [0053]     Consequently, delay period (t) at acoustic signal propagation depends on the SAW velocity (ν), distance between receiver and emitter (L) which is the distance between the first transducer  70  and the second transducer  90 :
 
 t=L/ν 
 
         [0054]     One the one hand temperature rise causes an increase of delay period at the expense of the substrate thermal expansion (L) and on the other hand, causes a delay period decrease at the expense of rise of sound velocity (ν). Temperature dependence of delay period is determined by the temperature coefficient:  
       α   =         1   t     ⁢       ⅆ   t       ⅆ   T         =         1   L     ⁢       ⅆ   L       ⅆ   T         -       1   v     ⁢       ⅆ   v       ⅆ   T                 
 
         [0055]     Under our conditions α does not depend on distance L and temperature.  
         [0056]     Example values of linear temperature coefficient α for different crystals at room temperature are given in Table 2:  
                               TABLE 2                                   Crystal   Cut type   α                           LiNbO 3     128 Y/X   75 ppm/K               Y/Z   94 ppm/K           LiTaO 3     X/112Y   18 ppm/K               36 Y/X   30 ppm/K           La 3 Ga 5 SiO 14     X/Y   24 ppm/K           SiO 2     ST-X    0 ppm/K                      
 
         [0057]     One can see from these values that for the SAW sensor  10 , it is more preferable to use substrates made from niobate and lithium. This material characteristics are presented in Table 3.  
                                                           TABLE 3                                       type of cut                    Y/Z   128° Y/X                            propagation velocity m/s   3488   3992           piezoelectric bond parameter* )  Δν/ν, %   2.41   2.72           Damping at 1 GHz, dB/mcs   1.07           bond with volume waves   Strong   weak                         * ) is effect of changing wave velocity because of surface metallization: Δν = ν m  − ν 0 , where ν 0 is  velocity on free surface, v m  is velocity on metallized surface, a large value Δν/ν usually allows to get small introduced losses.             
 
         [0058]     Changing of the substrate temperature by value ΔT, causes the delay period t 0  to be:
 
Δt≈at 0 ΔT
 
         [0059]     This delay value of the existing SAW devices is t 0 ˜1 microsec, with a required accuracy of temperature measurement ΔT=0.1K, α=94·10 −6 K −1  which is why the expected variation of delay period is:
 
 t≈ 94·10 −6 ×1·10 −6 ×0.1≈1·10 −11   s. 
 
         [0060]     This accuracy in measurement of time intervals with the help of electronics currently offered on the market cannot be achieved. This is why a carrier frequency phase change measurement which appears from time delay changing is a fundamental advantage of the SAW sensor  10 . When the delay period changes about Δt=1·10 −11 s and the exciting signal frequency f=430 MHz/ . . . /, the phase shift of the read-out signal relative to the exiting signal is:
 
Δφ≈fΔt·360°=4,3·10 8 ×1·10 −11 ×360°≈1.5°
 
         [0061]     The existing electronics market gives wide opportunities for creating devices with carrying frequency F c ≦100 MHz. That is why in order to measure phase shift Δφ˜1.5°, one should reduce the frequency of the signal, read out from the SAW sensor  10  by the heterodyning method for at least the value:  
           f   g     &lt;       F   c     ⁢       Δ   ⁢           ⁢   φ       360   0           =           10   8     ⁢     1.5   360       ≈     4   ·     10   5         =     0.4   ⁢           ⁢   MHz           
 
         [0062]     This task can be solved on the base of existing elements. To develop the SAW temperature sensor  10  for phase shift measurements it is necessary to measure experimentally an exact value of certain sensor sensitivity (phase sensitivity):  
         S   T     Δ   ⁢           ⁢   φ       =       ∂     (     Δ   ⁢           ⁢   φ     )         ∂   T           
 
         [0063]     In order to understand the physical structure of the SAW sensor  10 , the most significant physical characteristics are tabulated in Table 4 for typical values.  
                                         TABLE 4                                   Typical value   Devices for measurement                                    Operation frequency   100 ÷ 500 MHz   generator,               oscilloscope       bandwidth   ≈10 MHz   generator,               oscilloscope       Delay period   0.2 ÷ 10 us   High speed switch,               oscilloscope, generator       Depression coefficient in   1 ÷ 20 times   Generator, oscilloscope       the SAW sensor       Phase sensitivity   1 ÷ 200 phase   Thermal stable box,           degree of arc/° C.   thermometer, temperature               varying device                  
 
         [0064]     As noted hereinbefore, the general characteristic for determining an efficiency of the SAW sensor  10  as a temperature sensor, is principally phase sensitivity or, in other words, temperature dependence of the SAW sensor  10  output signal phase shift relative to input signal at operation frequency.  
         [0065]     Measurements of phase sensitivity at operation frequency were carried out on test benches, equipped at BIOFIL, in the following order: A sinusoid signal was applied on the SAW sensor input for the resonant conditions for the given temperature frequency, f R . Input and output signals were recorded by conventional oscilloscopes TDS 3054 or TDS 5104. The temperature of the SAW sensor  10  was measured by a standard thermocouple temperature measuring device with accuracy ±3° C., or a diode measuring device, specially fabricated by BIOFIL, with an accuracy ±0.05° C. The SAW sensor body was heated up (by a thermal fan) or cooled off (such as by liquid nitrogen) to the given temperature. The input and output signal typical oscillograms are presented in  FIGS. 5A and 5B  for two different temperatures.  
         [0066]     The time shift of output signal relative to input signal was measured by an oscilloscope. Value Δ φ  was calculated from formula:  
         Δ   ⁢           ⁢   φ     =         360   ·   Δ     ⁢           ⁢   T     T         
 
         [0067]     ΔT is the output signal time shift (SAW-out) relative to Input signal (generator), and T is the input signal period (1/f R ). Computer processing of waveforms, obtained with the use of digital oscilloscope, allows one to carry out phase measurements with error ˜0.2°. At the sampled temperature ranges one can notice linear dependence between phase shift value and temperature for both types of the SAW sensors  10  (see  FIGS. 6A and 6B ) and phase sensitivity values in Table 5.  
                                 TABLE 5                           Phase sensitivity values, calculated on experimental data:                    Operation   Phase sensitivity,           Sensor   frequency   Phase degree of arc/° C.                       ANL (resonator type)   245 MHz   9.4 ± 0.9           “Etalon” (filter)   172 MHz   3.0 ± 0.2           “Etalon” (filter)   434 MHz   ″           “Etalon” (delay line)   434 MHz   144 ± 5                       
 
         [0068]     For the SAW sensor  10 , delay period is quite an important characteristic, as it determines intermediate frequency value.  
         [0069]     For measurement of delay period, t, at the SAW sensor  10 , an input pulsed signal filled by sinusoid at frequency f R , was applied. The SAW sensor  10  input and output values were recorded by oscilloscope. The time period between these two signals (see  FIGS. 7A and 7B  and Table 6) is equal to delay period, t, at the SAW sensor  10 .  
                               TABLE 6                                       Operation               sensor   frequency   Delay period t                           ANL (resonator type)   245 MHz   &lt;20 ns           “Etalon” (filter)   172 MHz   (250 ± 25) ns           “Etalon” (filter)   434 MHz   ″           “Etalon” (delay line)   434 MHz   10.4 ± 0.5                      
 
         [0070]     Error is connected with accuracy of determining the proper time interval duration with the help of oscilloscope, and such error can be explained by the fact that accuracy of determining the proper time interval duration with the help of oscilloscope is not high enough.  
         [0071]     An HF oscillator (HFO) with FM produces sinusoidal voltage in the frequency range 300 . . . to 900 MHz. Amplifying on the previous representation and as stated before, the basis of temperature measurement is most preferably the measurement of phase shift of the sensor signal response at an intermediate frequency. The signal from the similar SAW sensor  10 , in the case where the temperature is constant, is used as a reference signal.  FIGS. 8A and 8B  present typical oscillograms.  
         [0072]     The conditions, for which the oscillograms in  FIGS. 9A and 9B  are obtained, are presented in Table 7.  
                                         TABLE 7                                                                            Sensor type   Filter   Delay line       Manufacturer   “Etalon”   “Etalon”       operation frequency   172 MHz   434 MHz       frequency modulation range   172 . . . 177 MHz   420 . . . 440 MHz       frequency modulation frequency   1 kHz   0.66 kHz       oscillator output voltage   500 mV   200 mV       Intermediate frequency, of order   1 kHz   170 kHz                  
 
         [0073]      FIG. 10  presents the results of absolute calibration of the sensor, which oscillograms are shown in  FIGS. 9A and 9B . The variation in phase difference is therefore shown in relation to temperature differences.  
         [0074]     One can see that the dependence between phase shift and temperature is directly proportional. The achieved sensitivity is of the order of 0.1° C. and evidently is caused by operational non-stabilities of the temperature sensor electronic circuit. The “phase shift—temperature” converter is specially designed in BIOFIL for measurement of phase shift of two sinusoidal intermediate frequency signals and its proportional conversion into temperature. The converter block diagram is shown in  FIG. 11 .  
         [0075]     The proposed method readily enables the digital phase shift measurement. In such phase shift measurements one signal is taken as a reference one (input  1 ). As shown in  FIG. 11 , the second signal phase shift (input  2 ) is counted out relative to the first signal. The signals ({circle around ( 1 )} and {circle around ( 2 )}) fall at the null detectors input. At the detector output in the moment of changing signal signs, the pulses (({circle around ( 3 )} and {circle around ( 4 )}) appear, and they set and then release RS-trigger. At the same time the pulse, which is shaped at the RS trigger output ({circle around ( 5 )}) unlocks the switch and lets the HF oscillator ({circle around ( 6 )}) pulse sequence pass at the counter ({circle around ( 7 )}). The number of pulses, passing through the counter, is in the proportion to time difference between moments of passing the researched signals through null point, that is signal phase difference. The microcontroller reads from the counter a pulse number and outputs on a liquid crystal display the temperature value in degrees.  
         [0076]      FIG. 12  illustrates the converter basic circuit. Null detectors were assembled on the base of operation amplifier (OA) DA 1 , comparator DA 3  and operation amplifier (OA) DA 2 , comparator DA 4  correspondingly. RS trigger was made on the base of DD 5  chip. The switch is based on DD 3 . 2  element. HF oscillator is based on DD 4 . 1 , DD 4 . 2  and DD 4 . 3  elements.  12  digit cascade counter was fabricated using DD 6 , DD 7  and DD 8  chips. The microcontroller was fabricated using DD 12 . The liquid crystal display is a single line indicator, which consists of  16  cells and shows temperature.  
         [0077]     The intermediate frequency reference signal goes at (OA) DA 1 , which is switched on in accordance with the inverting Schmidt trigger circuit. The Schmidt trigger converts analog signal into pulse sequence of the same frequency and phase. Bipolar output signal of the Schmidt trigger goes at DA 3  comparator, which converts bipolar signal into single polar logical signal in the TTL levels, necessary for digital chips. The second signal of the same frequency, sent at DA 2  OA input, is converted in the same way. Digital signals, obtained from outputs of DA 3  and DA 4  comparators, commutate RS trigger DD 5 . On the RS trigger output a square pulse is generated. Its duration is equal to time difference between moments of passing the researched signals through null point, which is in proportion with signal phase difference. From the RS trigger output the pulse goes to the DD 3 . 2  electronic switch where controls passing through the switch of the crystal oscillator pulses. The crystal oscillator uses DD 4 . 1 , DD 4 . 2  and DD 4 . 3  elements. In such a way the null detector pulses are stuffed by the HF oscillator pulses, which are counted by 12 digit counter DD 6 , DD 7 , DD 8 . The DD 12  microcontroller reads in series on four digits the data from the counter through DD 9 , DD 10  and DD 11  multiplexers, by sampling them with the help of DD 13  decoder. Then the microcontroller converts the obtained data and outputs on a liquid crystal display the temperature value in degrees.  
         [0078]     The telemetry system  40  of  FIG. 2  was established according to the embodiment presented in  FIG. 13 . The operation frequency was preferably 434 MHz. Lines in  FIG. 13  represent galvanic coupling. All antennae were made in a similar way and they were dipoles of 17 cm length, which is about ¼ of the wavelength. The distance between the antennae was about several centimeters. A symmetric SAW filter with resonance frequency 434 MHz was used as the SAW sensor  10 . The oscillation phase shift at changing the SAW sensor temperature was registered by a Tektronix 3054 oscillograph with the pass bandwidth up to 500 MHz.  
         [0079]     Development of the antenna design  200  (see  FIG. 14 ) for 434 MHz was carried out with the help of a MMANA v.0.11 program (which is a freely distributed conventional program). For antenna development particular attention was given to fulfilling the requirements for the antenna input resistance, which must be close to the value of about 50 Ω. The matching elements (capacity and inductivity) shall have a small value. These features are related to the fact the SAW sensor  10  has input resistance of 50 Ω and capacity of about 5 pF.  
         [0080]     Two zig-zag antennas  210  and  220  were developed and investigated: 
    1. The dimensions were 130×65×1 mm 3  and the matching device to operate with coaxial cable; and     2. The dimensions were  130×65×1 mm   3 , without the matching device with purely active resistance in 50 Ω for direct connection to the SAW sensor  10 . 
 
 With the help of the second antenna  220  it was provided the length was no less than 3 meters. At a power of ≈20 mW on the transmitting antenna, the oscillograph signal was equal to ˜1 mV. 
   
 
         [0083]     Flagpole antennas operate with less efficiency than frame antennas in the absorbing media (brain substance falls in this category). That is why the variant of single-turn frame antenna was chosen for the preferred design. During the design, one goal was reducing the reactive component of the current because it does not take part in energy conversion.  
         [0084]     The antenna design  200  was developed with the help of MMANA v.0.11 program (which is freely distributed). The shape was given as a regular octagon with 24 mm equivalent diameter. Diameter of the wire (copper without surface insulation) was equal to 2.5 mm. The antenna parameters are the following: 
        Input resistance (0.102+0.004·)Ω    Current (9.78+0.35·i) A at the input voltage 1V     Standing wave ratio 489 (the cable wave resistance 50 Ω)     Gain factor 3.1 dB     Parameters of agreement (cable with wave resistance 50 Ω): capacity ≈160 pF in parallel, induction ≈0.001 μF—sequentially     Directional radiation pattern of this antenna is a toroid and practically does not contain “dead zones”.        
 
         [0091]     The measurements, conducted with this antenna  200  demonstrated that its characteristics allow obtaining an excess over the noise level of 10 dB at a distance between the antennas in the air of about ≈100 mm.  
         [0092]     Developing antennas of this type one should take into account the fact that the frame antenna efficiency usually is 0.001-0.0001, the antenna input resistance (about 0.1 Ω) is in rather poor agreement with wave resistance of receiving and transmitting devices (about 50 Ω).  
         [0093]     Since the SAW sensor  10  will be implanted into the brain, one of the telemetry system antennas described hereinbefore will be submerged in the brain, which dielectric properties significantly differ from the air properties. To estimate the influence of these factors a set of experiments was carried out. The experimental layout is presented in  FIG. 15 . The receiving antenna  230  of the SAW sensor  10  was covered with dielectric protecting coating. Than the antenna  230  was submerged in the brain medium simulator (I, table salt water solution, concentration from 0 to 3.3% per mass, the volume of liquid is 3 liters). The signal from the SAW sensor  10  is passed to the input of an oscillograph  240 , and the oscillograph start-up synchronizing was performed by the signal from the generator  245 . To reduce a level of parasite refraction a voltage divider  250  was used.  
         [0094]     The experimental results are tabulated at Table 8:  
                                     TABLE 8                       No   Experimental conditions   reduction                                1   Air medium   1.0       2   Distillated water   24.6       3   Dielectric protecting coating + air medium   15.0       4   Dielectric protecting coating + simulating   36.0           medium                  
 
         [0095]     One can see that reduction of the telemetry system efficiency takes place mainly as a result of negative effect of the protecting dielectric coating. If its parameters are optimized, a significant improving of the antenna characteristics can be achieved. In these experiments operation of the antennas  230 ,  245 , optimized for an air medium were investigated. It is much easier to optimize dipole antennas for media with various value of dielectric permittivity. That is why investigations on efficiency of dipole type antenna ( FIG. 16 ) and “flag pole” type antenna ( FIG. 17 ) within the medium, simulating the brain tissue properties, were carried out. An antenna  270  of ˜170 mm length is placed in the air, which corresponds to ¼ of wavelength. Within a simulating medium the wavelength reduces by more than 5 times and correspondingly the antenna length is equal to 30 mm. The antenna  270 , placed into the simulating medium, was enveloped by thin polyethylene film to avoid direct contact with conducting medium. Distance between the antennae is ˜50 cm, and thickness of the simulating liquid layer is several cm. The signal amplitude reduction, caused by insertion of the liquid layer, is no more than ˜3 times. This is accurate under the condition that the antennas were optimized for using them in the air and in the solution correspondingly.  
         [0096]     In view of the previous discussions and investigations, technical characteristics of the overall most preferred SAW temperature sensor  10  components are tabulated below in Table 9.  
                                                                   TABLE 9                                       SAW device                        Filter at               resonator   filter172 MHz   434 MHz   Delay line                        Resonance frequency, MHz   245   172   434   434       Phase sensitivity,   9.4   3.0       144       Phase degree of arc/° C.       Delay period   &lt;20 ns   0.25 μs       10.4 μs       Frequency modulation range,       172 . . . 177       420 . . . 440       MHz       Frequency modulation frequency,       1       0.66       kHz       Intermediate frequency (IF), kHz       ≈1       ≈170       Temperature dependence of       linear       phase difference at IF       Depletion at work within               ≈30       simulation liquid* )         Depletion at work within               ≈3       simulation liquid** )                   * ) antennas are optimized to operate in the air            ** ) antennas are optimized to operate within simulating medium             
 
         [0097]     All elements of the SAW sensor  10  have been achieved in order to carry out the monitoring of temperature conditions of a given patient. The technical characteristics show that the accepted concept, choice of circuit design and sensors perform as needed to achieve the desired advantageous results for an afflicted patient.  
         [0098]     The following non-limiting Examples illustrate various additional features and advantages of the invention.  
       EXAMPLE 1  
       [0099]     The SAW sensor is a crystal substrate with electrodes of comb shape, evaporated on it.  FIGS. 19A and 19B  present photos of two example sensors  10 , which can be used as a sensors in temperature measurement devices.  
         [0100]     In the table below dimensions of the SAW sensors  10  which can be used as temperature sensors are shown:  
                                       sensor   working frequency   dimensions                   ANL (resonator type)   245 MHz   Ø = 1 cm, h = 0.5 cm       “Etalon” (filter)   172 MHz   9 × 7 × 2 mm       “Etalon” (filter)   434 MHz   9 × 7 × 2 mm       “Etalon” (delay line)   434 MHz   14 × 8 × 2.5 mm                  
 
       EXAMPLE 2  
       [0101]     An HF oscillator with FM produces sinusoidal voltage in the frequency range 300 to 900 MHz. HFO block scheme is presented in  FIG. 20 .  
         [0102]     A saw-tooth voltage generator  300  generates a keying signal of saw-tooth shape, necessary for variation of current through transistors of an HF oscillator  310 . In this case parameters of their conductivity and diffusion capacities change, it allows to vary the oscillator frequency in the range 300 to 900 MHz. HF amplifier  320  amplifies the HF oscillator signal up to the required level (voltage amplification factor is ˜20 dB. We used the purchased device and the scheme, developed in BIOFIL, as a saw-tooth voltage generator  300 . A K174PS4 chip was used as a non-linear element (mixer) for operation frequency 434 MHz.  
         [0103]     Two signals are sent into the mixer inputs. They are: signal with HFO frequency 556 MHz and heterodyne oscillator signal with frequency 526.8 MHz. At the differential amplifier output we get the signal of intermediate frequency F intermed. =18,18 kHz, which oscillogram is presented in  FIG. 22 .  
       EXAMPLE 3  
       [0104]     Technical characteristics of the preferred SAW temperature sensor  10  components are tabulated below in Table 10.  
                                                                   TABLE                                       SAW device                    filter   Filter at   Delay           resonator   172 MHz   434 MHz   line                        Resonance frequency, MHz   245   172   434   434       Phase sensitivity,   9.4   3.0       144       Phase degree of arc/° C.       Delay period   &lt;20 ns   0.25 μs       10.4 μs       Frequency modulation range,       172 . . . 177       420 . . . 440       MHz       Frequency modulation frequency,       1       0.66       kHz       Intermediate frequency (IF), kHz       ≈1       ≈170       Temperature dependence of       linear       phase difference at IF       Depletion at work within       simulation liquid* )                 ≈30       Depletion at work within               ≈3       simulation liquid** )                   * ) antennas are optimized to operate in the air            ** ) antennas are optimized to operate within simulating             
 
         [0105]     The presented technical documentation demonstrates that in the project course all elements of the SAW remote temperature sensor have been well worked out unit by unit. The performed technical characteristics show that the accepted concept, choice of circuit design and sensors perform as needed.  
         [0106]     Application of delay line at 434 MHz, fabricated in “Etalon” pilot plant, Omsk, Russia, as a SAW sensor seems the most efficient.  
       EXAMPLE 4  
       [0107]     The following devices were used as a temperature sensors: 
        thermocouple measurement device with absolute measurement error ≈3° C., relative measurement error ≈0.3° C.     mercury thermometer with relative measurement error ≈0.05° C.     temperature sensor, fabricated in BIOFIL on the base of diode. Absolute measurement error ≈0.05° C., relative measurement error ≈0.005° C.        
 
         [0111]     Thermocouple measurement device and mercurial thermometer are purchased devices. Diode sensor is quite accurate and compact device in contrast to mercurial thermometer. That is why let us focus our attention on its construction, testing and efficiency in more details.  
         [0112]     The temperature measurement sensor was made on the base of semiconductor diode. It is well known that at passing continuous current through p-n transition, the p-n transition voltage drop depends on p-n transition temperature. We measured voltage drop at forward biased p-n transition at 1 mA continuous current passing. The temperature measurement sensors were calibrated with the help of mercurial thermometer with scale interval 0.1°C., which determines temperature measurement error. The calibration results are presented in  FIG. 21 .  
         [0113]     Ways of Temperature Stabilization and Variation  
         [0114]     To stabilize temperature of the object (SAW-sensor) and its specified variation several ways were used: 
    to provide significant temperature difference between two SAW-sensors.    
 
         [0116]     One sensor was placed into foam plastic cavity. Above it a metal vessel (cooler), containing water—ice mixture in proportion1:1, was located. All assembly was thermally insulated by foam rubber. In the process of the experiment water in the vessel was intermixed periodically. Temperature control in the cooler was carried out by mercurial thermometer.  
         [0117]     The second SAW sensor temperature was varied following to similar scheme. The sensor was placed into foam plastic cavity. Above it a metal vessel containing water, previously heated up to 55° C., was located. At time interval, equal to 20 minutes, the water was cooled down to 45° C. and since this moment the signal phase difference measurements started. Temperature control in the second SAW sensor also was carried out by mercurial thermometer. 
    to provide small temperature difference.    
 
         [0119]     The SAW sensor is placed into the previously cooled glass thermos. Temperature of the SAW element body was measured by mercurial thermometer. Initial temperature inside the thermos is ˜0° C. At this temperature the SAW element stays for about 1 hour. Then the thermos temperature starts to rise at the expense of natural heat exchange with ambient environment. The temperature rise velocity is ˜15 min/° C. The similar technique allows to carry out measurements at temperature variation 0.5° C. at temperature range 2-7° C. 
    to provide temperature difference with low accuracy requirements.    
 
         [0121]     Temperature of the SAW sensor body was measured by thermocouple temperature measuring device or diode measuring device, specially fabricated in BIOFIL. The SAW sensor body was heated up to the specified temperature by fan heater. The measurements were conducted at temperature range ≈20÷50° C.  
       EXAMPLE 5  
       [0122]     Media, Simulating the Human Body Tissues  
         [0123]     To develop telemetry system with implanted sensor one should know electric properties of the medium, into which antenna will be placed. One should know velocity of electric wave propagation in material (u), wavelength (λ), wave penetration depth (δ) and medium internal impedance (η). These characteristics are determined by radio wave frequency(ω) and the medium dielectric properties: dielectric permittivity(∈), magnetic conductivity(μ) and conductivity(σ). The ∈ and μ values of biological tissues are more than 1. That&#39;s why the radiation phase velocity and wave length within tissue is less than in the air. In the tissues with high water content the electromagnetic wave length reduces by a factor of 6.5-8.5 comparing with the air. In the tissues with low water content the wavelength reduces only by a factor of 2-2.5. So at the electromagnetic radiation frequency higher than 3·10 8  Hz, the electromagnetic radiation wave length is less than the human body sizes, it determines a local nature of the SHF electromagnetic radiation influence on the human organism. The EMR wavelength values for a number of tissues are presented in Table 11.  
                                                                                                     TABLE11                           SHF radiation wave length (in cm) within tissues       for a set of frequencies[3]                frequency, MHz            Tissue   100   200   400   1000   3000   10000   24000   35 000                    marrow   116.1   62.2   32.19   12.6   3.8   1.25   0.368   0.388       brain   31.7   19.4   11.16   4.97   1.74   0.595   0.200   0.201       fat   96.0   57.1   30.90   12.42   3.79   1.450   0.680   —       muscle   27.6   16.3   9.41   4.09   —   0.616   —   —       whole   25.1   15.3   8.89   3.87   1.36   0.449   0.214   0.167       blood       skin   28.1   17.9   10.12   4.41   1.49   0.506   0.250   —                  
 
         [0124]     Frequency dependences of the most important electric parameters of the medium (conductivity, permittivity and EMR penetration depth) for grey and white matter of the brain plus muscle tissue are presented in  FIGS. 23A-23C , respectively.  
       EXAMPLE 6  
       [0125]     The table below presents properties of the devices, used by BIOFIL on various ges of working out and testing the SAW temperature sensors  10 .  
                       TABLE                           1   Sinusoid signal generator:               Frequency variation range, Hz   from 10 kHz to 2 GHz           Signal amplitude, V   10 mV ÷ 5 V           Frequency resolution   &lt;1 kHz       2   Oscilloscope Tektronix           TDS 3054           Bandwidth   500 MHz           Number of channels   4           Maximal record size   10 000 points           Oscilloscope Tektronix           TDS 5104           Bandwidth, MHz   1000 MHz           Number of channels   4           Maximal record size   2 000 000 points       3   Temperature sensor   Relative measurements ±0.3° C.           thermocouple   Absolute measurements ±3° C.       4   Temperature sensor diode   absolute measurements ±0.05° C.           (fabricated by BIOFIL)   relative measurements ±0.005° C.       5   Fan heater   power 1.2 kW           Temperature variation range   25 ÷ 45° C.       6   Thermal electric battery   T         MO-7 (Peltie element)           Temperature variation range   25 ÷ 47° C.       7   high frequency modulator   Modulation frequency ≈100 kHz           (fabricated by BIOFIL)   Pulse duration ≈200 ns                  
 
       EXAMPLE 7  
       [0000]     SAW Sensor Test Data  
         [0126]     The following parameters were measured experimentally: 
    f—resonance frequency     t DL —delay time     τ—pulse rise time     K=U in /U out @f     S T   Δφ —temperature sensitivity    
 
         [0132]     δT=Δφ min /S T   Δφ —temperature resolution  
                                                                                                 f   t DL         τ   S T   Δφ     δT           MHz   μs   K   μs   angle degrees/° C.   ° C.                                    ANL   245.2 ± 0.1   &lt;0.02   0.1   &lt;0.005   9.4 ± 0.9   ±0.02       BIOFIL   172.2 ± 0.1   0.25 ± 0.025   0.3   0.1 ± 0.01   3.0 ± 0.2   ±0.07       BIOFIL     434 ± 0.1   ˜0.1   0.7   —   ˜1.5   0.14       BIOFIL     434 ± 0.1   10.2 ± 0.2    0.03   —   144 ± 5    ±0.0015                  
 
         [0133]     It should be understood that various changes and modifications referred to in the embodiment described herein would be apparent to those skilled in the art. Such changes and modifications can be made without departing from the spirit and scope of the present invention.