Abstract:
A non-invasive method and apparatus for monitoring changes in intracranial pressure which removes extracranial effects from the measurements. The method and apparatus can include the supplying of a fixed frequency electrical output to a transducer coupled to the patient&#39;s head, thereby generating an acoustical tone burst in the patient&#39;s head which generates a first echo and a second echo, the first echo reflecting from a first interface in the side of the patient&#39;s head coupled to the transducer, and the second echo reflecting from a second interface at the opposite side of the patient&#39;s head. The first and second echoes are received by the transducer which can generate a first electrical signal and a second electrical signal, wherein the first and second electrical signals vary in accordance with the corresponding first and second echoes. The counterbalancing phase shifts required to bring about quadrature between each of the first and second electrical signals and the fixed frequency electrical output can be measured, and values for the change in intracranial distance based on the changes in the counterbalancing phase shifts can be obtained.

Description:
ORIGIN OF INVENTION 
     The invention described herein was made by employees of the United States Government and may be manufactured and used by or for the Government for governmental purposes without payment of royalties thereon or therefor. 
    
    
     BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     This invention relates to measuring and monitoring of intracranial pressure changes in human patients, and more particularly to a non-invasive method and device for monitoring changes in intracranial pressure which removes extracranial effects from the measurements. 
     2. Background of the Invention 
     A prior method of measuring intracranial pressure included pulse phase-locked ultrasonic technology but this method did not include techniques nor refinements to remove extracranial effects from the measurements. 
     Another prior method includes an ultrasonic means to measure expansion of a pre-selected path through the cranial cavity by means of placement of a 500 KHz ultrasonic transducer at an appropriate location on the skull. In this technique, the measurement includes not only skull expansion, but also includes effects of edema and perfusion of tissues between the skin and the skull. This perfusion can result in measurements that are much larger than the path change due to cranial vault expansion alone. 
     Other measurement techniques such as strain sensor gauges located on a caliper can be placed across the cranial cavity for measurement. Such techniques, however, are also subject to the same problems associated with surface tissue edema and perfusion, similar to the ultrasonic technique. 
     Thus, although prior devices and methods are generally non-invasive, they are affected by surface tissue changes. These changes affect the accuracy of the determination of cranial vault expansion. In the above-mentioned techniques, the effects due to surface tissue could be eliminated, but that would require the excision of tissue around the connecting points (for the strain gauge caliper) or around the transducer point-of-contact (for the ultrasonic technique). This would make the techniques invasive, although not as invasive as drilling a hole through the cranium for insertion of a probe. 
     The present invention overcomes these and other disadvantages of the prior art by providing an improved method and device for measuring intracranial pressure changes and including the means to improve the accuracy of measurement of intracranial expansion. 
     BRIEF SUMMARY OF THE INVENTION 
     This invention is a method and device for measuring change in intracranial distances and includes calibration techniques necessary to convert these measurements to changes in intracranial pressure. It is an object of the invention to provide a non-invasive method and device for measuring change in intracranial distances which removes extracranial effects from the measurements, and to provide calibration techniques that enable that change in skull dimension to be related to the change in intracranial pressure. It is a further object to provide a non-invasive method for monitoring changes in intracranial pressure in human patients. 
     These and other objects of the invention are achieved by introducing known intracranial pressure changes using a non-invasive technique. The changes in skull dimension as a result of changes in intracranial pressure are then measured using a non-invasive device which removes extracranial effects (e.g., caused by changes in skin thickness and variation) from the measurement. The measured changes in skull dimension are then correlated to changes in intracranial pressure. 
    
    
     BRIEF DESCRIPTION OF DRAWINGS 
     FIG. 1 illustrates a pulsed phase-locked circuit for measurement of intracranial pressure (phase control). 
     FIG. 2 is a cross-section of a front view of a transducer positioned against the skin of a patient. 
     FIG. 3 illustrates a pulsed phase-locked circuit for measurement of intracranial pressure (frequency control) using multiple reflections. 
     FIG. 4 is an expanded view of a transducer positioned against the skin of a patient. 
     FIG. 5 is a front view of the head of a patient showing the transducer location. 
     FIG. 6 is a side view of the head of a patient showing the range of transcranial location of the transducer. 
     FIG. 7 is another embodiment of a pulsed phase-locked circuit for measurement of intracranial pressure according to the present invention. 
    
    
     DETAILED DESCRIPTION OF INVENTION 
     An acoustic waveform will partially reflect from and partially transmit through an interface in a propagation medium if there exists a difference in the acoustic impedance (mass density times wave velocity) on either side of the interface. For example, in considering the propagation of a wave through a medium with two interfaces, each interface having a difference in acoustic impedance on either side of the interface, the reflection of the wave at the second interface is delayed with respect to the reflection at the first interface by the propagation time associated with the distance between the first and second interfaces and the sound velocity associated with the propagation medium between the two interfaces. This means that for pulse phase-locked loop systems (PPLLs) the reflected wave profile associated with the propagation time between the two interfaces will have no contribution from the propagation lying beyond the second interface. 
     With regard to the present invention, as illustrated in FIG. 2, this means that contributions to the acoustic waveform from the extracranial tissue  74  lying on the reflection side of the cranium from the transducer  60  may be eliminated by positioning the sample-and-hold  102 ,  108  of the PPLL only in a position corresponding to reflections from cranial bone  72 . 
     Phase contributions to the PPLL phase-detector occur from various sources in the acoustic wave propagation path and from the PPLL instrument components. The principal wave propagation paths are those through extracranial tissue (skin  220 , subcutaneous fat, blood vessels, etc.)  74 , cranial bone  72 , and intracranial tissue (brain tissue, ventricles, CSF, etc.)  70 . The sound velocities of the various soft tissues are equal to within the overall measurement uncertainties of the present measurement configurations. Thus it is sufficiently accurate for present purposes to write the phase contributions from the extracranial tissue (ø ext )  74 , the cranial bone (ø bn )  72 , and intracranial tissue (ø int )  70  as:                ∅   ext     =     2                 π                 f                     l   ext       c   ext                 (   1   )                 ∅   bn     =     2                 π                 f                     l   bn       c   bn                 (   2   )                 ∅   int     =     2                 π                 f                     l   int       c   int                 (   3   )                                
     where ƒ is the acoustic wave frequency,  1   ext  is the path length and c ext  is the sound velocity in extracranial tissue,  1   bn  is the path length and c bn  is the sound velocity in bone, and  1   int  is the path length and c int  is the sound velocity in intracranial tissue. 
     Consider now the total phase contribution resulting from an acoustic pulse traversing a single transcranial round trip (i.e., the first acoustic echo). Denoting a single round trip by a subscripted 1, we write the total phase ø 1  as:                ∅   1     =       4                 π                   f              [         l   ext       c   ext       +       l   int       c   int       +       l   bn       c   bn         ]       +     γ                   (     f   1     )                 (   4   )                                
     where the phase term γ (ƒ 1 ) is the phase contribution from the instrument electronic components. 
     For the variable frequency PPLL system (VFPPLL), quadruture conditions between the reference oscillator signal and the received acoustic signal are maintained such that any variation in ø 1  is zero if c ext ≅c int  (i.e., assuming that the ultrasonic compressional velocity in brain tissue (c int ) is nearly equal to the ultrasonic compressional velocity in extracranial tissue (c ext )), i.e.,                Δ                   ∅   1       =             4                 π                   f   1       c          [       Δ                   l   ext       +     Δ                   l   int         ]       +         4                 π                 Δ                   f   1       c          [       l   ext     +     l   int     +       c     c   bn            l   b         ]       +     Δ                 γ                   (     f   1     )         =   0             (   5   )                                
     where Δø 1  is the variation in ø 1 , Δ 1   ext  is the variation in  1   ext , Δ 1   int  is the variation in  1   int , and Δγ(ƒ 1 ) is the variation in γ around ƒ 1 . 
     Similarly, the total phase contribution resulting from an acoustic pulse traversing two transcranial round trips (i.e., the second acoustic echo) is written as:                ∅   2     =       4                 π                   f   2       =       [         l   ext     c     +       l   bn       c   bn       +     2          l   nt     c         ]     +     γ                   (     f   2     )                   (   6   )                                
     where the subscripted 2 denotes second echo. We also have that:                Δ                   ∅   2       =             4                 π                   f   2       c          [       Δ                   l   ext       +     2                 Δ                   l   int         ]       +         4                 π                 Δ                   f   2       c          [       l   ext     +     2        l   int       +       c     c   bn            l   bn         ]       +     Δ                 γ                   (     f   2     )         =   0             (   7   )                                
     in order to maintain quadrature conditions in the VFPPL system. 
     Solving equations (5) and (7) simultaneously for Δ 1   int  we obtain:                Δ                   l   int       =         l   int          (         Δ                   f   1         f   1       -     2                     Δ                   f   2         f   2           )       +       l   int                     (         l   ext       l   int       +       c     c   bn                         l   bt       l   int           )                     (         Δ                   f   1         f   1       -       Δ                   f   2         f   2         )       +       c     4                 π                       (                γ                     (     f   1     )              f   1                           Δ                   f   1         f   1         -              γ                     (     f   2     )              f   2                           Δ                   f   2         f   2           )                 (   8   )                                
     where we have set          Δ                 γ                          γ        (     f   1     )                f   1                       Δ                   f   1       ,                  and                 Δ                 γ                   (     f   2     )       =              γ                     (     2   1     )              f   2                       Δ                     f   2     .                                
     In general,          c     c   bn       ,                  l   bn       l   int       ,                and                     l   ext       l   int                                
     are much smaller than unity. This means that the second term on the right-hand side of equation (8) is negligible compared to the first term on the right-hand side. The magnitude of the third term in the right-hand side of equation (8) is more difficult to estimate, since the functional dependence of γ on frequency ƒ is generally not known a priori. Clearly, if the first and second echo signals are measured at the same frequency and frequency variations, then this term vanishes. Using typical commercially available damped transducers and low Q transducer material then γ is small enough to be neglected. Otherwise, and for the general case, however, a procedure similar to that outlined in Appendix B of Yost, Cantrell, and Kuchnick (J. Acoust. Soc. Am. 91, 1456, 1992), which is incorporated herein by reference, must be followed to assess the magnitude of the third term on the right-hand side of equation (8). 
     For the constant frequency PPLL (CFPPLL) system, the problems associated with frequency variations disappear. For the CFPPLL, ƒ 1 =ƒ 2 =ƒ=constant, γ=constant and Δø 1 ≠0, Δø 2 ≠0.                Δ                   ∅   1       =         4                 π                 f     c                [       l   ext     +     Δ                   l   int         ]             (   9   )                 Δ                   ∅   2       =         4                 π                 f     c                [       Δ                   l   ext       +     2                 Δ                   l   int         ]             (   10   )                                
     solving equations (9) and (10) for Δ 1   int  we get:                Δ                   l   int       =       c     4                 π                 f            [       Δ                   ∅   2       -     Δ                   ∅   1         ]               (   11   )                                
     Thus, direct measurements of the phase shifts Δø 1  and Δø 2  with the CFPPLL system allow a direct determination of Δ 1   int . 
     FIG. 1 shows the preferred embodiment of the present invention. Using the illustrated specialized circuit  5  for the measurement of intracranial expansion by bone-to-bone multiple reflection, the operation is as follows. A continuous wave generator  10  (labeled “stable oscillator”) emits a continuous and stable voltage oscillation. This signal is sent through a power splitter  2  to the gate  20 , the timing control, which, in this embodiment uses count down electronics  30 , and through buffer  41  to the voltage-controlled phase shifter  40 . 
     The tone burst, a measured segment of the continuous wave (typically 3-20 cycles) is formed, amplified  45  and sent through the coupling/decoupling network  55 , and thus activates an ultrasonic mechanical oscillation of the transducer  60 . Upon reception by the transducer of the ultrasonic signals and their consequent conversion into electrical signals, the coupling/decoupling network  55  routes the electrical signals to the preamplifier  80 . 
     As shown in FIG. 4, to prepare the transducer  60  for positioning on a patient, the transducer  60  is coated with a suitable amount of an appropriate ultrasonic conducting gel  210 , cement, or similar material. The transducer  60  is then placed against the skin  220  on a patient&#39;s head, making certain that the gel  210  makes good contact between the skin  220  and the transducer. Although the above description applies to current ultrasonic measurement practices, it is understood that other methods of insertion and reception of acoustic or ultrasonic waves, including an air or other gas-filled gap, from patient&#39;s heads are permissible. 
     FIGS. 5 and 6 show front and side views of a patient&#39;s head illustrating the location of the transducer  60  for transcranial mounting. The transducer  60  (shown in FIG. 5) may be mounted on either the left side or the right side of the head. FIG. 6 shows some of the possible locations  60 A,  60 B for the transducer  60 . Although the operator preferably chooses the location to maximize the second echo, as indicated by the oscilloscope display  110 , the only limitation on location of the transducer is the ability to obtain a second echo. Once this has been achieved, the transducer  60  may be held in place by any conventional method, including the use of an ace bandage, tape, or similar strap. 
     As illustrated in FIG. 2, the ultrasonic mechanical wave traverses along Path  1   6  through the extracranial tissue  74  and bone  72 , and reflects off the proximate side of the patient&#39;s head at the interface of the bone  72  and the intracranial tissue  70 , and traverses back through the bone  72  and the extracranial tissue  74  to be received by the transducer  60 . Also, the ultrasonic mechanical wave traverses the extracranial tissue  74 , cranial bone  72 , and the intracranial tissue  70  in the cranial cavity along Path  2   7 , reflects off the cranial bone  72  on the distal side of the patient&#39;s head, and traverses the bone  72  and extracranial tissue  74  of the proximate side of the patient&#39;s head to be received by the transducer  60 . The transducer  60  converts the received ultrasonic waves traversing Paths  1  and  2   6 ,  7  into first and second electrical echo signals, respectively, which are routed by the coupling/decoupling network  55  through the preamp  80  and buffer  81  to the phase detector  90 , which phase detector, in at least one embodiment, could be in the form of a mixer. The output of the preamp  80  is also made available through a buffer  100  for echo display  110  used in set up of the system. 
     The phase detector  90  phase-compares the received signal with the output of the stable oscillator  10  after passing through a voltage-controlled phase shifter  40  and forms voltage outputs which are proportional to the cosine of the phase difference between these two signals. Selection of the appropriate portion of the phase signal (i.e., reflection  1  or reflection  2 ) is accomplished by sample/hold  1   102  and sample/hold  2   108 , respectively, under the control of the signals  34 ,  36  of the count down electronics  30 . The integration of these voltages are obtained by typical integrator circuits,  112  or  104 . These constitute the control voltages for the voltage controlled phase shifter  40 . Phase output from the phase detector  90  is filtered by the filter  95  and is sent along two paths. The first path is buffered by a buffer  97  and then sent to an output  98 . This output is displayed on an oscilloscope (not shown) for initial adjustments as described below. The second path goes through another buffer  99  to sample/hold  1   102 . The output from sample/hold  1   102  then passes through an integrator  104  to the analog switch  190  as input  1   106 . Similarly, the output from buffer  99  goes to sample/hold  2   108 . The output from sample/hold  2   108  then passes through an integrator  112  and a phase subtractor  114  (i.e. phase inversion), and then to the analog switch  190  as input  2   116 . The output of the analog switch  190  goes to the voltage controlled phase shifter  40  and to the voltmeter  160 . 
     As the bi-stable circuit  180  changes states, the state change is made available for adjustment purposes through buffers  122  and  124 , indicated on FIG. 1 by outputs A  126  and B  128 . Outputs A  126  and B  128  designate received echo  1  or received echo  2 , respectively. When output A  126  is high and output B  128  is low, the circuit  5  reads the phase shift of the first received echo. When output A  126  is low and output B  128  is high, the circuit  5  reads the phase shift of the second echo. 
     The count down electronics module  30  determines the pulse width  120  (the number of cycles in the tone burst); the repetition rate  130  (the number of tone bursts per second), Reflection  1   140 , and Δ  150 . 
     Reflection  1   140  generates the timing pulse  34  which selects a portion of the first echo. The phase comparison of this portion of the first echo is adjusted by a control voltage until quadrature is obtained. When quadrature is obtained, the control voltage is monitored by a voltmeter  160  connected to a data acquisition system (not shown) which includes a computer and appropriate software for data acquisition, processing, and display. 
     Similarly, Δ  150  generates the timing pulse  36  which selects a portion of the second echo. This adjustment permits location of the second reflection by entry of the number of oscillator cycles from the first reflection. The control voltage generated as for echo  1  controls the voltage control phase shifter  40 . As with the Reflection  1  case, the voltage controlled phase shifter  40  is monitored by a voltmeter  160  connected to the computer. Δ  150  also determines the number of waves between a round-trip of the ultrasonic wave across the cranium  70 . 
     Echo selection  240  aids in the appropriate alignment of the timing pulses to operate the sample/hold circuits  102 ,  108 . When echo  1  is received, timing pulse  1   34  emanates from the count down electronics  30  which causes sample/hold  1   102  to sample and hold the phase comparison of echo  1  with the oscillator  10 . Likewise, timing pulse  2   36  from the count down electronics  30  causes sample/hold  2   108  to sample and hold the phase comparison of echo  2  with the oscillator  10 . 
     The appropriate phase shifts of echo  1  and echo  2  are measured alternately with the ÷P circuit  170 , the bi-stable circuit  180  and the analog switch  190 . P is an integer that can be set and represents the number of repetitions used to give a stable measurement of the control voltage for quadrature of echo  1  with stable oscillator  10 . Then the circuit causes the measurement of the control voltage for quadrature of echo  2  with stable oscillator  10  to be stabilized and recorded. The process alternates as long as measurements are made. 
     The computer alternately records two sets of data. The first set is the control voltage associated with echo  1 . The second set is the control voltage associated with echo  2 . Each control voltage is related to its corresponding phase shift by the transfer function of the voltage controlled phase shifter  40 . These phase shifts can be used to calculate the path expansion, in its most general form, by the equation:                Δ                 x     =     x                     Δ                 ∅     ∅               (   12   )                                
     where Δx is the path expansion, x the path length is equal to Path  2 −Path  1 , Δø is the total phase shift (i.e., sum of the phase shifts), and ø is the initial phase of the wave across the cranium  70 . In the case where the velocity of compressional wave propagation in human brain tissue does not appreciably change with intracranial pressure, the above equation can be written as:                Δ                 x     =       C                   (   T   )         ω                 Δ                 ∅               (   13   )                                
     where C(T) is the velocity of compressional wave propagation in human brain tissue as a function of temperature, and ω=2πf, where f is the frequency in Hz. We assume that during the measurement period, temperature is stable. 
     By analysis of the ultrasonic waves we can write the path expansion by:                Δ                 x     =     x        [         Δ                 ∅       ∅     Echo   2         -       Δ                 ∅       ∅     Echo   1           ]               (   14   )                                
     A second embodiment of the present invention is shown in FIG.  3 . This embodiment works similarly to the first, except that a voltage controlled oscillator  200  generates oscillator frequency changes to bring about quadrature for each echo. As in the preferred embodiment, the ÷P circuit  170 , the bi-stable circuit  180  and the analog switch  190  work together to alternately select which signal ( 106  or  116 ) controls quadrature, in this case by controlling frequency. For this second embodiment, there is an inherent instrument error, due to electronics sensitivity to frequency changes. This error is typically no more than 15%. The equation for calculation of path expansion is, for the second embodiment:                Δ                 x     =     x        [         Δ                 f       f     Echo   1         -       Δ                 f       f     Echo   2           ]               (   15   )                                
     where f and Δf are measured by the frequency counter  162 . 
     A third embodiment of the present invention, as shown in FIG. 7, offers the advantages of near simultaneous measurement of both echoes, avoidance of switching transients, shorter response time, and requires a smaller dose of ultrasonic power. This embodiment is similar to the embodiment of FIG. 1, except for: sample and hold  1   102  captures the phase comparison of the echo  1  signal with the stable oscillator signal fed through the voltage controlled phase shifter  1   40  and holds its value. Sample and hold  2   108  captures the phase comparison of the echo  2  signal with the stable oscillator signal fed through voltage controlled phase shifter  2   43  and holds its value. These signals are then fed to their respective integrators  104 ,  112  so that: 
     a) a phase shifter control voltage is developed by integrator  1   104  that will produce quadrature with echo  1  signal, while, nearly simultaneously; 
     b) a phase shifter control voltage is developed by integrator  2   112  that will give quadrature with echo  2  signal; and 
     c) the control voltage applied to voltage controlled phase shift  1   40  is subtracted from the control voltage applied to voltage controlled phase shift network  2   43  by the difference circuit  129 ; this voltage then “follows” the path expansion (Δx). It is understood that the true change in intracranial distance is one-half of the path expansion. Adder  211  and adder  221  were incorporated to improve response time. 
     In constant frequency systems as shown in FIGS. 7 and 1, all of the functions can be performed with digital electronics. As an example, rather than detecting the phase differences between the echo signals and reference signal, and using the integrated phase difference to drive the signals to quadrature, the echo signals and the reference signal can be digitally recorded, and the phase difference determined by use of computer algorithms. As further example, timing control, gating, waveform generation (synthesizer), coupling/decoupling function, and even the preamp function, can be performed by digital electronics or an appropriately programmed digital computer. 
     Various methods may be used to establish a relationship between changes in intracranial distance with known changes in transcranial pressure (pressure gauge), as for example disclosed in U.S. Pat. No. 5,617,873 issued to Yost et al. at column 5, line 32 thru column 6, line 14, which is incorporated herein by reference. 
     It should be understood by those skilled in the art that the descriptions and illustrations herein are by way of examples and the invention is not limited to the exact details shown and described. For example, although the embodiment shown in FIG. 1 includes a voltage controlled phase shifter, it should be understood that any device that produces a controlled phase shift in response to a control signal may be used; for example, a current controlled phase shifter or an optically controlled phase shifter. And, although the invention is illustrated using a mixer, any means of phase detection may be used; for example, a synchronous detector, a homodyne detector, an analog mixer, or a digital mixer.