NASA CASE NO.

PRINT FIG.

NOEICE

The invention disclosed in this document resulted from research in aeronautical

and space activities performed under programs of the National Aeronautics and Space

Administration. The invention is owned by NASA and is, therefore, available for

licensing in accordance with the patent licensing regulations applicable to U.S.

Government-owned inventions (37 CFR 404.1 at seq.).

To encourage commercial utilization of NASA-owned inventions, it is NASA

policy to grant licenses to commercial concerns. Although NASA encourages

nonexclusive licensing to promote competition and achieve the widest possible

utilization, NASA will provide the necessary incentive to the licensee to achieve early

practical application of the invention.

Address informational requests for this invention to the Technology

Applications Team, NASA Langley Research Center, Code 200, Hampton, Virginia

23681-0001.

Address applications for license to the Patent Counsel Office, Mail Stop 212,

3 Langley Boulevard, Hampton, Virginia 23681-0001.

Serial No." 08/297,474

Filed" 08/24/94 LaRC

(NASA-Case-LAR-13894-1)

NON-INVASIVE METHOD AND APPARATUS

FOR MONITORI_G INTRACRANIAL

PRESSURE AND PRESSURE VOLUME I_OEX

IN HUMANS Patent Application

(NASA. langley Research Center)

30 p

N95-26889

Unclas

G3/_2 0049677

i_,,  ̧ - ,.. /-_./J c

/ " ",/7
AWARDS ABSTRACT 

NON-INVASIVE METHOD AND APPARATUS FOR MONITORING 

INTRACRANIAL PRESSURE AND PRESSURE VOLUME INDEX IN HUMANS 

The present invention relates to the monitoring of intracranial pressure and 

pressure volume index in human patients in a non-invasive manner. 

Referring to FIGS. 1 A-1 6, the pressure volume index, a constant for any given 

patient, is determined by successive measurements of the patient's blood flow 

through a jugular vein. The blood flow is measured by a blood flow meter in contact 

with the patients neck which displays its results on an electronic display device. The 

first measurement is obtained while the patient is lying in the supine position, and a 

second measurement is obtained after tilting the patient's feet upward. By comparing 

the pressure and volume differences obtained as a result of the two measurements, 

an accurate value for the pressure volume index is obtained. 

Referring to FIG. 3, once the pressure volume index for a given patient has 

been obtained, the intracranial pressure can be continuously monitored with an 

ultrasonic transducer to measure the volume of the patient's cranium in conjunction 

with a blood flow monitor attached to the patient's neck to measure the blood flow 

through a jugular vein. 

Inventor: John H. Cantrell 

Home address: 101 Tuckahoe Trace 

Yorktown. VA 23693 

SS#: 

Employer: 

- NASA Langley Research Center, Hampton, VA 

Inventor: William T. Yost 

Home address: 797 Fawn Lane 

Newport News, VA 23602 

SS#: 

Employer: NASA Lanslev Research Center, Hampton, VA 

initial Evaluator: Joseph S'-. Heyman 

Serial No. 081297,474 

Filed 8/24/94 
LAR 13894-1 -1- PATENT APPLICATION

NON-INVASlVE METHOD FOR MEASURING AND MONITORING

INTRACRANIAL PRESSURE AND PRESSURE VOLUME INDEX

5

10

Origin nf the invention

The invention described herein was made in the performance of

work done by employees of the U.S. Government and may be

manufactured and used by or for the government for governmental

purposes without the payment of any royalties thereon or therefor.

Bankground of the invention

Field of the invention

15 This invention relates in general to measuring/monitoring of

intracranial pressure and pressure volume index in human patients, and

more specifically to a non-invasive method for monitoring intracranial

pressure and changes in intracranial pressure.

20 Description of the related art

Monitoring of intracranial pressure and pressure volume index is of

significant diagnostic and post-operative importance for patients with
LAR 13894-1 2 PATENT APPLICATION

cranial injuries, pathologies, or other conditions, that may affect the

pressure of the subarachnoidal fluid around the brain, and for patients

who have undergone brain surgery.

Intracranial pressure is regularly measured and monitored by

5 means of a pressure sensor inserted through the skull into the brain.

Usually a hole is drilled in the skull, and a catheter with a pressure sensor

is inserted into the brain fluid. To obtain a pressure volume index, the

change in intracranial pressure is monitored after a known bolus of saline

solution is inserted into the cerebrospinal fluid, or after a saline solution

10 is inserted at a known rate. This known procedure, while simple and

accurate, is not suitable for long term monitoring, because an open

wound must be maintained in the skull for the catheter with the pressure

sensor. Antibiotics are only partially effective in treating cranial

infections, so the pressure sensor can only be left in situ for two weeks

15 or less.

Long term monitoring of intracranial pressure, without the need for

maintaining an open wound in the skull, is possible if a pressure sensor

with a transmitter is implanted into the brain. The intracranial pressure is

thereafter monitored by means of a receiver located outside the skull.

20 Such a solution however, is unattractive because of risks involved in

implanting anything in the brain, and because of the problems of

providing power to an implanted transmitter. One such remote pressure
LAR 13894-1 -3- PATENT APPLICATION

sensor is described in U.S. Patent 4,124,023 to Fleischmann et al.

However, this device uses nuclear material as an energy source, making

it poorly suited for implantation into a human brain.

Other methods, claiming to be non-invasive methods suitable for

5 monitoring of intracranial pressure, are based on the measurement of

some quantity that depends on intracranial pressure, but which does not

have a fixed relationship to intracranial pressure.

One such method is described in U.S. Patent 4,204,547 to

Allecca. tMlocca occludes the blood flow in a jugular vein for a few

10 seconds, and measures the resulting rate of change of blood flow within

the jugular vein upstream of the occlusion as an indicator of the

intracranial pressure.

Another such method, proposed in U.S. Patent 4,564,022 to

Rosenfeld et al., directs a sensory stimulus towards the patient, e.g. a

15 flash of light into the eyes, and measures the latency of a resulting

negative-going wave of electrical brain activity as an indicator of

intracranial pressure.

These known indirect methods may be used, under very restricted

conditions, as possible indicators of variations of the intracranial pressure

20 in a patient. However, absolute values for the intracranial pressure

cannot be obtained directly as there is no predetermined fixed ratio

between the observed signals, obtained by these known non-invasive
5

LAR 13894-1 -4- PATENT APPLICATION

monitoring methods, and the absolute value of the intracranial pressure.

Such calibration is possible by inserting a pressure sensor into the brain

of the patient being monitored, however, this is a traumatic and

undesirable procedure.

_ummary of the Invention

Accordingly, it is the object of the present invention to provide a

non-invasive method for measurement of absolute values of intracranial

10 pressure and pressure volume index in a human patient.

It is another object of the present invention to provide a noninvasive method for long term monitoring of both intracranial pressure

and the pressure volume index in a human patient.

It is a further object of the present invention to provide a non15 invasive method for calibrating indirect measurements of intracranial

pressure to obtain absolute values for intracranial pressure.

It is a still further object of this invention to provide a means to

monitor changes in intracranial pressure in a human patient.

These and other objects of the invention are achieved by a method

20 for non-invasive measurement of intracranial pressure and pressure

volume index, which comprises the steps of: providing a non-invasive

measuring device responsive to intracranial pressure, calibrating said
LAR 13894-1 -5- PATENT APPLICATION

measuring device by introducing known changes in intracranial pressure

and recording the pressure changes by the measuring device, inducing

known changes in the volume of the cerebrospinal fluid while measuring

the corresponding changes in intracranial pressure by means of said

calibrated measuring device, obtaining two sets of corresponding values

for change in volume (AV) and change in intracranial pressure (Ap),

entering each of the two sets of values for AV and AP into equation

Av

PVI

Ap . PO (i0 -I)

io

to form a set of two equations with Po and PVI unknown, and

solving said set of two equations for PVI and Po to obtain accurate values

for the pressure volume index PVl and the intracranial pressure Po for the

patient.

15

20

Brief Description of the Drawings

These and other objects of the present invention will be

understood from the description herein, with reference to the

accompanying drawings, in which:

FIG. 1A is a side view of a patient with sensing devices attached

to forehead and neck lying in supine position on a horizontal hospital bed;
5

LAR 13894-1 -6- PATENT APPLICATION

FIG. 1B is a side view of a patient with sensing devices attached

to forehead and neck lying in supine position on a tilted hospital bed;

FIG. 2 is a perspective view of a seated patient with a sensing

device attached to the forehead and fitted with a pressurized skull cap;

FIG. 3 is a perspective view of a patient with a sensing device

attached to the forehead lying on the side;

FIG. 4 is a block diagram of a preferred measuring device for use

with the invention.

10 Detailed Description of a Preferred Embodiment

The human brain and the spinal cord are immersed in a fluid called

the cerebrospinal fluid. The cerebrospinal fluid (csf) is continuously

generated and reabsorbed by the body. The csf is contained in a

15 membrane covering the inside of the skull and the spinal cord, having a

sack at the sacrum. The brain and the membrane containing the csf also

contain blood vessels, which are in direct communication with the csf

and add to the total volume of the cerebrospinal system. The blood

volume varies rhythmically with the heart beat, causing corresponding

20 oscillations in the intracranial pressure (ICP). An accurate regulating

process in the brain normally controls the generation process, the

reabsorption process and the blood volume in the brain to maintain a
LAR 13894-1 -7-

constant ICP average value of about 40 mmH..

process can be disturbed, e.g. by tumors in the brain, or by trauma to

the brain, causing the ICP change. As little as 10 mmH= increase above

average value in the ICP may cause insidious damage to the brain.

When the ICP varies, the total volume of the csf also varies. As

an example a relationship between volume and ICP is expressed by

equation (1) for the cerebrospinal system for small values of (V-Vo).

v-v o

P.Poxl 0 PVI

PATENT APPLICATION

However, the regulating

(1)

10

15

where: P

V

Po

V o =

PVl

= peak ICP

= csf volume associated with P

= Steady state reference pressure for ICP

Steady state reference volume of csf

corresponding to Po

= Pressure-Volume Index

2O

PVl is a constant that depends on pathological conditions of a

given patient and varies from patient to patient, such that no fixed or

predetermined value for PVl can be used in equation (1). An accurate

value for PVl can, however, be calculated from known values for

changes in ICP (AP) and volume (AV) as follows:

Subtracting Po from each side of equation (1) gives equation (2):
LAR 13894-1 -8-

AP-P 0 (IoAV/PVI-I )

PATENT APPLICATION

(2)

5

where AV = V - V o = small variation in volume from V o

AP = P - Po = small variation in pressure from Po

If two pairs of AV and AP are measured, equations (3a) and (3b)

are obtained:

A pi.Po (10 Avl/PVI-I)

(3a)

AP2-P 0 (I oAV2/ PVI-I )

(3b)

10

15

Equations (3a) and (3b) are a set of two equations with only two

unknown variables, PVl and Po, so PVl and Po can be calculated by

solving the simultaneous equations (3a) and (3b) by known methods.

Examples of methods for solving this set of equations are given below.

By taking the ratio of equations (3a) and (3b), equation (4) is

obtained:

AP 1 IoAVJPVI_I

AP 2 IoAV2/PVI_I

(4)
LAR 13894-1 -9- PATENT APPLICATION

A quite accurate value for PVl is obtained by inserting into

equation (4) data from the measurement of two pairs of corresponding

values for AV and AP and fitting a computer generated algorithm of

equation (4) to the data by varying PVl, or by using the "SOLVE"

5 function in modern scientific calculators.

An approximate, but quite accurate, value for PVl may also be

obtained by expanding the exponential functions in the numerator and

the denominator of the right hand side of equation (4) in a truncated

power series, collecting terms, and solving the resulting equation for PVI.

10 If the first three terms in the power series is kept, equation (5) for PVl is

obtained:

PVI -

API _ 2

__ (AV2)2 (AVl)

AP 2

0. 868 [AV I- APIAvo]

AP2

(5)

If the first four terms in the power series is kept, the more

15 accurate, but still approximate, equation (6) for PVl is obtained:

A

PVI - --

B

(6a)
LAR 13894-1 -10- PATENT APPLICATION

Where:

AP 1

A - 4.61[_p-_2 (AV2)3-(AV1)3]

(6b)

and:

B- 3[(z_v 1)2 AP1

AP 2

---(AV2)2],[2 Ap 2 (AV1)3(AV2)'24- AP2 (AV2) 3 (AV1)

1

AP1 • AP1 4] -2

-18 AP2 (AVl)2-(AV2)2-15 (_2) (AV 2) 4-15 (AV 1)

(6c)

Once PVI is obtained, Pocan be calculated from either of equations

(3a) or (3b) by inserting the correct value for PVI.

Another way to calculate PVI from a single measured pair of Z_P

10 and AV when PVI has been determined may also be obtained by taking

the derivative of equation (1) to get equation (7)"

AV

dP P0 (7)

i0 PVI

dV 0. 434 (PVI)
LAR 13894-1 -11 - PATENT APPLICATION

For small variations in P and V, dP and dV can be replaced by Ap

and AV, respectively, and the resulting equation solved to get an

approximate, but quite accurate equation (8) for Po:

-AV

P0 " 0.434 (PVI) API0 PVI (8)

Av

5 Measurements of AP and AV can be obtained by non-invasive

methods. Two preferred methods, but by no means the only methods, to

measure AP and AV for the determination of intracranial pressure and

pressure-volume index will be described below.

It is commonly assumed that the skull of an adult is so rigid that

10 the skull volume is constant. It is therefore assumed that changes in csf

volume (AV) involve mainly compression of the spongy brain tissue.

Comprehensive tests have shown that this assumption is incorrect. The

skulls of adults actually expand and contract like balloons with changes

in ICP, and this expansion and contraction of the skull accounts for

15 almost all of the volume changes in the csf caused by variations in the

ICP.

Any measurement system or device sufficiently sensitive to

respond to appropriate anatomical configuration changes caused by

pressure changes can accordingly be used to measure changes in ICP. A

20 preferred device for measuring small variations in skull size in response to
LAR 13894-1 -12- PATENT APPLICATION

variations in ICP is the constant frequency pulsed phase-locked-loop

(CFPPLL) ultrasonic measurement device described by U.S. Patent

5,214,955 issued to Yost and Cantrell, and also described in a paper

entitled "Constant frequency pulsed phase-locked-loop instrument for

5 measurement of ultrasonic velocity" by Yost, Cantrell and Kushnick,

published in Rev. Sci. Instrum. 62 (10) October 1991. The CFPPLL

measurement device applied to measuring or monitoring intracranial

pressure will be described below with reference to FIG. 4.

The signal from the ultrasonic CFPPLL device depends on the

10 diameter of the cranium and is not a direct measure of the intracranial

pressure ICP. This is true for all measurement devices based on

mechanical deformation of the skull or related structures, as well as all

other known non-invasive measurement devices responsive to intracranial pressure variations. The signal from such non-invasive

15 measurement devices thus can not be used for measurements or

monitoring of absolute ICP variations unless a calibration as will be

described herein has first been performed.

2O

A. Methods to measure AP.

1. Tilt angle method.

FIGS. 1A and 1B show a patient 10 lying supine on a hospital bed

40. An ultrasonic transducer 20 mounted on the front of the skull above
LAR 13894-1 -13- PATENT APPLICATION

the nose and approximately 1 cm below the hairline is connected via a

cable 22 to an electronic apparatus 30. The measuring device 20, 30

provides an output proportional to changes in the travel time of an

ultrasonic toneburst emitted by the transducer 20 and reflected back to

5 the transducer 20 from the opposite side of the skull 12 or other

appropriate landmark.

In FIG. 1A the bed 40 is horizontal, and in FIG. 1B the bed 40 is

tilted by an angle (p from the horizontal 26, such that the patient's legs

19 are higher than the head 12. The cerebrospinal fluid is contained in

i0 membranes extending from the inside of the top of the skull 12 to the

sacrum, which lies approximately at "S" in FIGS. 1A and lB. When the

bed 40 is tilted as shown, the intracranial pressure will increase. If the

distance from the center of the skull 12 to the sacrum is L, as indicated

in FIGS. 1A and 1B, the increase in pressure will be as given in equation

iS (9):

Ap -pgLsin@ (9)

20

where:

Ap = Pressure change

p = Mass density of the spinal fluid

g = Gravitational constant

L = Distance
5

LAR 13894-1 -14- PATENT APPLICATION

q) = Tilt angle for patient

By using various tilt angles @, the various changes in intracranial

pressure (ICP) can be calculated from equation (9). These calculated

changes in ICP can be used to calibrate the output from the measuring

device 30, or any other appropriate measuring device sufficiently

sensitive to respond to appropriate anatomical configuration changes

caused by changes in intracranial pressure.

2. Pressurized skull cap method.

10 FIG. 2 illustrates another method of calibration, which uses a

helmet 40 containing an inflatable skull cap 45, in which a known

pressure is applied to the cranial vault 12 by means of a hose 57, a

pump 50, a valve 55, and a manometer 60. Calibration is accomplished

by correlating the output of a measuring device with a transducer 20

15 mounted on the front of the skull 12 with the applied pressure in the

skull cap 45. The accuracy of this method depends on the refinements

of the design of the skull cap 45 and may differ from the accuracy of the

tilt-angle method outlined above.

20 B. Methods to vary and measure AV:

1. Bolus Injection method.

FIG. 3 shows a patient 10, whose cerebrospinal axis is in the
LAR 13894-1 -15- PATENT APPLICATION

supine position, but where the patient is rotated onto the patient's side.

The patient has an ultrasonic transducer 20 placed against the skull

directly above the nose and approximately one centimeter below the hair

line. This transducer 20 is connected via cable 22 to an electronic

5 apparatus 30 for measurement of small variations in the diameter of the

skull 12.

Between appropriate vertebrae, or at an other appropriate access

point, a measured bolus of saline or other appropriate solution is injected

by a syringe 70 into the cerebrospinal system. Let the volume of a first

10 injection be AV 1. By assuming that the injection of this bolus is given at

the clinically recommended and appropriate injection rate, it will give rise

to a peak change in intracranial pressure API. This pressure change AP 1

is measured by readings from the measuring device 20, 30, which

previously has been calibrated by the tilt angle method or the pressurized

15 skull cap method, and is recorded along with the corresponding bolus

injection volume AV 1.

After allowing time for the intracranial pressure ICP to equilibrate

to its steady state value following the first bolus injection, a second bolus

injection of volume AV 2 is given, and the resulting peak change in

20 intracranial pressure AP 2 is measured.

The two measured pairs of values of AV and AP are then inserted

into equations (3a) and (3b), and the patient's pressure-volume index PVl
LAR 13894-1 -16- PATENT APPLICATION

and the intra-cranial pressure Po is calculated by solving the two

simultaneous equations by one of the methods described above in

connection with equations (4) - (8).

5 2. Blood Flow Method:

Another method for measurement of AV is based on measurement

of changes in blood flow to the brain, as indicated in FIG. 1A.

A patient 10 resting in supine position on a horizontal hospital bed

40 has an ultrasonic transducer 20 placed against the front of the skull

10 12. The transducer 20 is connected via a cable 22 to an electronic

apparatus 30 for accurate measurement of small variations in the

diameter of the skull 12. The measuring device 20, 30 has previously

been calibrated by the tilt angle method or the pressurized skull cap

method described above to provide accurate readings of variations in the

15 intracranial pressure.

The patient 10 also has an ultrasonic blood flow transducer 25

mounted on the neck. The blood flow transducer 25 is connected via a

cable 27 to an electronic apparatus 35. The blood flow transducer 25

with associated electronics 35 is arranged to measure the blood flow in

20 the patient's jugular vein. The diameter of the jugular vein can be

determined by using an ultrasonic A-scan instrument. By using the

determined vein diameter together with the velocity profile from the
LAR 13894-1 -17- PATENT APPLICATION

blood flow meter, an instantaneous blood volume change can be

determined. Devices for measurement of blood flow and blood vessel

diameter are well known in the art, and will not be discussed in detail

herein.

5 Theoretically, net blood flow into or out of the brain would require

measurement of the blood flow in all veins as well as in all arteries that

service blood flow out of and into the cerebral system. In most cases it

is, however, possible to model the total blood flow from measurement of

blood flow in one vein. With this in mind, we measure (1) the diameter

10 of the vein, and (2) the velocity profile of the venous flow. We calculate

a blood volume flow rate in a manner known to those skilled in the art.

The change in the blood volume flow rate is measured at a

temporary occlusion of an artery or a vein. One can then calculate a first

change in blood volume AV 1, which is recorded together with the

15 corresponding change AP1 in ICP, as measured by the previously

calibrated pressure responsive measuring device 20, 30.

A second pair of data, AV 2 and AP 2, is obtained by occluding a

different vein or artery. The two pairs of data are inserted into equations

(3a) and (3b), and PVl and Po are then calculated by solving the two

20 equations, e.g. as described above with reference to equations (4)-(8).

After the patient's pressure-volume index PVl and steady state

intracranial pressure Po has been determined, the calibrated measuring
LAR 13894-1 -18- PATENT APPLICATION

device 20, 30, or any other calibrated measurement device responsive to

changes in intracranial pressure, can be used to monitor changes in ICP

directly and continuously.

FIG. 4 is a block diagram for a Constant Frequency Pulsed Phase5 Locked-Loop (CFPPLL) ultrasonic measurement device, which is a

preferred measurement device for use as part of the invention.

The CFPPLL measurement system uses properties of an ultrasonic

wave propagating along a path defined by the ultrasonic beam and bound

by the skull-meninges-dura complex, or appropriate substructures within

10 this complex, and the measured change in the phase of the propagating

ultrasonic wave due to the change in the wave propagation path length

accompanying a change in ICP is used as a measure of variations in ICP.

The CFPPLL measuring device is preferred because it provides very high

sensitivity and excellent repeatability and long term stability.

15 The CFPPLL measuring device includes an ultrasonic transducer

20, which is shown mounted on the front of the skull 12 of a patient

under monitoring. The transducer 20 is via cable 22 supplied with

variable width acoustic tonebursts from an electronic apparatus 30,

which includes a constant frequency synthesizer 100 followed by a

20 power splitter 110, a gate 115, which determines the width of the

acoustic toneburst, a power amplifier 120, and a coupling/decoupling

network 125.
LAR 13894-1 -19- PATENT APPLICATION

Acoustic signals reflected from the far side of the skull 12 is

received by the transducer 20 and channelled via the cable 22, the

coupling/decoupling network 125, and a preamplifier 130 to a first input

(1) of a phase detector 140. A second input (2) of the phase detector

5 140 receives a second signal from the synthesizer 100 via a power

splitter 110, a buffer 112, a voltage controlled phase shift network 170,

a calibrated line stretcher 175, and another buffer 172.

The output signal from the phase detector 140 is fed via a sampleand-hold circuit 150 to an integrator 155, and from the integrator 155

10 via a normally closed phase shift control switch 168 to an adder circuit

160, which also receives a phase set point voltage from a phase set

point potentiometer 165. The output from the adder circuit 160 is fed as

a control voltage to input 180 of the phase shift network 170, and also

to a digital voltmeter 200 used as readout for the measuring device. The

15 digital voltmeter includes an IEEE interface connection 210 for external

data storage and processing.

A timing control unit 190 provides all sync and control signals for

the gate 115, the coupling/decoupling network 125, and the sample-andhold circuit 150. The coupling/decoupling network 125 protects the

20 preamplifier 130 from overload by decoupling the preamplifier 130 from

the transducer 20 when large voltage drive signals are coupled to the

transducer 20, and it improves system sensitivity by decoupling the
LAR 13894-1 -20- PATENT APPLICATION

output of the low-impedance drive amplifier 120 from the transducer 20

when a reflected signal is received by the transducer 20.

The apparatus 30 also provides outputs for supervision and setup,

including transducer output 133, phase comparison output 143, control

5 point monitor output 153, and sync signal output 193.

The function of the CFPPLL system outlined above is best

understood by considering that a constant frequency signal from an

oscillator 100 is split into two signal paths, 1 and 2, and that phase

differences between the two signal paths are measured.

10 Along path 1, which is a measurement path, an acoustic signal

generated in transducer 20 traverses the material enclosed by the skull

12 of the patient. The acoustic toneburst travels through the material

enclosed by the skull 12, is reflected at the far end of the skull 12, and

impinges on the transducer 20 as an echo of the original pulse. Any

15 changes in the propagation conditions, such as path length changes,

produce associated phase changes in path 1. These phase changes are

the information sought in measurement.

Path 2, which is a reference path, includes a voltage controlled

phase shift network 170, whose output is used for phase comparison

20 with the signal from the measurement path (1). The phase detector 140

detects the relative phase difference between the signals in the two

paths, and generates an output signal proportional to the cosine of the
LAR 13894-1 -21- PATENT APPLICATION

phase difference. The control voltage to the voltage controlled phase

shift network 170 is automatically changed until the output voltage of

the phase detector 140 is zero, which occurs when the two signals are in

quadrature.

5 The input to the voltage controlled phase shift network 170 comes

through a buffer 112 from the power splitter 110. The buffer 112

provides matching of the electrical input impedance to that of the phase

shift network 170. The phase shift is controlled by a dc voltage applied

to a control input 180 of the voltage controlled phase shift network 170.

10 The output of the voltage controlled phase shift network 170 passes

through a calibrated line stretcher 175, used for calibration of the

system, and a buffer 172 to the phase detector 140. During data

collection the setting of the calibrated line stretcher 175 is not changed.

Phase comparison of the two paths is performed by the phase

15 detector 140, which is a product detector combined with a low pass

filter. The phase detector 140 output voltage can be written as one-half

the product of the input voltage amplitudes times the cosine of the phase

difference between the two signals. The output of the phase detector

140 is passed both to the sample-and-hold circuit 150, which selects the

20 desired portion of the phase signal, and to an output port 143 through a

buffer 142 for observation on an oscilloscope (not shown). The portion

of the phase signal chosen for measurement is selected by an adjustable
LAR 13894-1 -22- PATENT APPLICATION

timing pulse to the sample and hold circuit 150, whose output is passed

to an integrator 155.

The loop control circuit, which is made up of the sample-and-hold

150, the integrator 155, the phase set point potentiometer 165, and the

5 adder 160, provides the control voltage 180 for the voltage controlled

phase shift network 170. The control voltage 180 is a sum of two

contributions, one coming from the integrator 155, and the other coming

from the phase set point potentiometer 165. The phase set point

potentiometer 165 sets the nominal phase shift about which the system

10 operates. The integrator 155 provides a voltage derived from the phase

detector 140. When the phase detector 140 output reaches null, the

integrator 155 output voltage stabilizes to a constant voltage, and

quadrature between paths 1 and 2 are established. The phase shift

control switch 168 is closed in the "locked" state when the system is

15 taking a measurement. For setup, it is moved to its open "unlocked"

state, so that the voltage controlled phase shift network 170 is under

manual control by the phase set point potentiometer 165.

The timing control unit 190 forms all of the necessary timing

signals needed by various sections for the measurement application. All

20 timing signals are referenced to the repetition rate, which is determined

by counting down from the synthesizer 100. The sync output marks the

beginning of the formation of a toneburst and is used for measurement
LAR 13894-1 -23- PATENT APPLICATION

setup and display. An adjustable width of the toneburst is also provided.

Signals to the coupling/decoupling network 125 and the sample-and-hold

circuit 150, used to measure the phase of the selected portion of the

received ultrasonic wave, are controlled by this unit. Timing sequences

5 are adjusted with the aid of an oscilloscope.

Adjustments for measurements are made in the following way:

With the outputs properly connected to an oscilloscope and the

phase shift control switch 168 in the open ("unlocked") position, the

received tonebursts and the phase comparison voltages are displayed.

10 The frequency of the synthesizer 100 is adjusted so that the amplitudes

of the reflected toneburst echoes at output 133 are far out of the noise,

and the phase comparison output voltage at output 143 is relatively "flat

topped" and stable at that portion of the tone burst echo chosen for

measurement. The phase set point potentiometer 165 is adjusted until

15 the phase comparison voltage 180 corresponding to the desired tone

burst is approximately 0 V. The control point is adjusted so that the

phase signal is sampled well into its latter half. Because of a time delay

in the low-pass filter in the phase detector 140 the phase signal is not

precisely synchronized with the tonebursts. The phase shift control

20 switch 168 is then placed in its closed ("locked") position for data taking.

A calibration procedure that uses a line stretcher 175 in the

reference path (2) permits the conversion of the change in control
LAR 13894-1 -24- PATENT APPLICATION

voltage, monitored by the voltmeter 200, to a change in phase shift

between the two paths. Calibration of the voltage controlled phase shift

network 170 in a CFPPLL system is normally accomplished by adjusting

the calibrated line stretcher 175 to introduce a known phase shift into

5 the calibration path while the system is locked in data taking mode. This

results in a change in the phase shift control voltage 180 to the voltage

controlled phase shift network 170. The change in phase shift control

voltage 180 is recorded, and a change of output voltage for a known

phase shift is thus determined. This result is used to calculate changes

10 to the measured phase shifts and, is particularly important information to

have in setups requiring measurements of small phase shifts of a few

hundred microradians.

When the CFPPLL system is used for measuring and/or monitoring

intracranial pressure ICP and pressure-volume index PVl according to the

15 present invention, such absolute calibration of output versus phase angle

is not required, but instead the change in output versus change in ICP is

calibrated by the tilt angle method or the pressurized skull cap method as

described above.

The method described above for non-invasive determination of PVl

20 and ICP according to a preferred embodiment of the invention is not only

useful for direct monitoring of ICP, but also for calibration of other

measuring devices using indirect methods for non-invasive monitoring of
LAR 13894-1 -25- PATENT APPLICATION

ICP. Such non-invasive measuring devices include, but are not limited to,

calipers, head bands, or other devices and measurement systems

possessing the sensitivity and accuracy to allow proper calibration, for

example, by using the measurement systems to monitor any dimensional

5 changes in the skull or other connected systems, such as the eyeball,

inner ear, or anatomical landmarks within or adjacent to the cranial cavity

and/or the spine or attached or adjacent structures, or configurational

changes of the spine or any other structures responding to increases in

intracranial pressure. The invention makes it possible to calibrate such

10 devices so accurate continuous recordings of absolute values of ICP can

be obtained without the need for invasive procedures.

Numerous modifications and adaptations of the present invention

will be apparent to those skilled in the art. Thus, the following claims

and their equivalents are intended to cover all such modifications and

15 adaptations which fall within the true spirit and scope of the present

invention.

What is claimed is:
LAR 13894-1 PATENT APPLICATION

NON-INVASIVE METHOD FOR MEASURING AND MONITORING

INTRACRANIAL PRESSUREAND PRESSUREVOLUME INDEX

5

Abstract of the DisclosurR

Non-invasive measuring devices responsive to changes in a

patient's intracranial pressure (ICP) can be accurately calibrated for

monitoring purposes by providing known changes in ICP by non-invasive

methods, such as placing the patient on a tilting bed and calculating a

10 change in ICP from the tilt angle and the length of the patient's

cerebrospinal column, or by placing a pressurized skull cap on the patient

and measuring the inflation pressure. Absolute values for the patient's

pressure-volume index (PVI) and the steady state ICP can then be

determined by inducing two known changes in the volume of

15 cerebrospinal fluid while recording the corresponding changes in ICP by

means of the calibrated measuring device. The two pairs of data for

pressure change and volume change are entered into an equation

developed from an equation describing the relationship between ICP and

cerebrospinal fluid volume. PVI and steady state ICP are then determined

20 by solving the equation. Methods for inducing known changes in

cerebrospinal fluid volume are described.
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