Patent Description:
Many organs and nerves, including the brain, are concentrated in the head of a human, and measuring biological information in this site is very significant in terms of health control and disease prevention. In particular, intracranial pressure (ICP) is always maintained constant due to biological homeostasis, and it is known that the increased or decreased intracranial pressure may cause a fatal severe disease in some cases. Moreover, the intracranial pressure is used as an index for therapy and diagnosis of brain damage, stroke, and intracranial hemorrhage. Thus, it is particularly significant to find the establishment of an intracranial pressure measuring method.

As conventional intracranial pressure measuring methods, a method of placing a piezoelectric sensor directly under the cranium bones (PTL <NUM>, NPL <NUM> and <NUM>) and a method of directly inserting a tube into the lateral ventricle and measuring pressure of a water column rising therefrom (PTL <NUM>, NPL <NUM>) have been generally known. In each of the methods, however, a hole needs to be drilled in the cranium bone or a sensor or a tube needs to be placed inside the cranium bone, which is highly invasive for subjects and requires subjects to take a complete rest during measurement. It is difficult to measure and evaluate the intracranial pressure by only one momentary value, and it is a common practice to measure continuous values for a certain period of time. There is a risk that subjects may be infected with fungus during the measurement, and the countermeasures need to be taken into consideration. Thus, studies have been made on many intracranial pressure measuring technologies that put less burden on subjects, that is, low-invasive.

Examples of the intracranial pressure measuring methods reported so far include a technology of injecting a contrast medium in the cranium bone of a subject and measuring the intracranial pressure by NMR measurement (PTL <NUM>). Another report is a technology of injecting a contrast medium in the cranium bone of a subject, generating fine bubbles in this site, acquiring low frequency response, and analyzing resonant frequency (PTL <NUM>). Another report is a technology of irradiating the eyeball of a subject with infrared rays and performing FT-IR analysis of reflected light to measure the intracranial pressure (PTL <NUM> to <NUM>). Another report as a technology of non-invasively detecting biological information from a site near the brain is a technology of measuring pulse waves in the ear canal (PTL <NUM> to <NUM>). It has been reported to measure acoustic data on the artery blood pressure and the blood flow of middle cerebral artery and take a non-linear correlation therebetween to calculate the intracranial pressure (PTL <NUM>). In medical animal testing, it has been known from simultaneous recording of ear canal pressure waves, artery pressure waves, and intracranial pressure waves of cats, the amplitude of the ear canal pressure increases when the blood pressure rises, and the propagation time from the artery pressure waves to the ear canal pressure waves is shortened when the intracranial pressure rises (NPL <NUM>), and it has been known from the measurement of artery pressure waves (which is main component of pressure waves in ear canal) and intracranial pressure waves of dogs that a notch appears on a transfer function and is affected by change in pressure in the brain (cerebrospinal pressure) (NPL <NUM>).

To deal with the technical problems inherent to the above-mentioned technologies, the inventors of the invention have proposed a method of measuring carotid pulse waves and external ear canal pressure pulse waves to estimate the intracranial pressure based on amplitude information and waveform information on both the pulse waves (PTL <NUM>).

<CIT> relates to a method of estimating an intracranial pressure, comprising the steps of providing a predetermined acoustic signal to the head of a subject and measuring an amplitude of a received signal at a location on the head different from where the signal was provided to the head of the subject. The intracranial pressure is determined based on the amplitude of the received signal.

<CIT> relates to a method of measuring changes in an intracranial pressure from a normal intracranial pressure, comprising the steps of applying a predetermined input vibration signal at first location on the skull and detecting an output vibration signal from a second location on the skull. The method further comprises measuring the thickness and radius of the skull and storing data characteristic of the thickness and the radius and the input and output signals into a database.

<CIT> relates to a method for measuring intracranial pressure, comprising the steps of transmitting a first acoustic signal through a first cranial point and receiving a second acoustic from signal a second cranial point. The determination of the intracranial pressure is based on an analysis of sets of frequency components extracted from the received second acoustic signal.

The importance of intracranial pressure measurement with a non-invasive and simple configuration is particularly recognized in emergency medical care and control of critically ill patients, such as patients with disturbance of consciousness due to brain disorder. For intracranial pressure measurement in such medical cares, a device used for the measurement needs to be able to measure the intracranial pressure non-invasively with as simple a configuration as possible.

The invention has been made in view of the above-mentioned problems. The invention can provide an intracranial pressure estimating method and the like capable of estimating intracranial pressure in real time without putting burden on subjects by using a non-invasive and simple device.

According to the invention, there is provided an intracranial pressure estimating method for estimating an intracranial pressure from time-series data on external ear canal pressure pulse waves according to claim <NUM>. This method performed by an arithmetic unit comprises:.

According to the invention, the intracranial pressure can be estimated based on external ear canal pressure pulse waves that can be measured by a non-invasive and simple device, and hence the intracranial pressure estimating method capable of estimating the intracranial pressure in real time without putting burden on subjects can be implemented. Further, the first formant frequency of the external ear canal pressure pulse wave data is corrected based on the personal information on the subject, and the obtained corrected value is used to calculate the estimated value of the intracranial pressure. Thus, an intracranial pressure estimating method capable of accurately estimating the intracranial pressure can be implemented.

In the above-mentioned intracranial pressure estimating method, the external ear canal pressure pulse wave data are subjected to high-pass filter processing.

Consequently, influence of breathing and heartbeat of subjects can be reduced, and hence an intracranial pressure estimating method capable of accurately estimating the intracranial pressure can be implemented.

In the above-mentioned intracranial pressure estimating method, the estimation step may include calculating an estimated value PICP of the intracranial pressure based on the following equation: <MAT> where A and B are constants, and Xf1 is the corrected value.

Consequently, an intracranial pressure estimating method capable of accurately estimating the intracranial pressure can be implemented.

In the above-mentioned intracranial pressure estimating method, the correction step may include calculating the corrected value Xf1 based on the following equation: <MAT> where f1 is the first formant frequency, β1, K, and β2 are constants, Age is the age of the subject, and FM is the sex of the subject (<NUM> for male and <NUM> for female).

According to the invention, there is further provided an intracranial pressure estimating device according to claim <NUM>.

With this, the intracranial pressure can be estimated based on external ear canal pressure pulse waves that can be measured by a non-invasive and simple device, and hence the intracranial pressure estimating device capable of estimating the intracranial pressure in real time without putting burden on subjects can be implemented. Further, the first formant frequency of the external ear canal pressure pulse wave data is corrected based on the personal information on the subject, and the obtained corrected value is used to calculate the estimated value of the intracranial pressure. Thus, an intracranial pressure estimating device capable of accurately estimating the intracranial pressure can be implemented.

Preferred embodiments of the invention are described in detail below with reference to the drawings. The drawings to be referred to are illustrative. Note that the following embodiments do not unduly limit the scope of the invention as stated in the claims. In addition, all of the elements described in connection with the following embodiments should not necessarily be taken as essential requirements of the invention.

<FIG> is a functional block diagram illustrating a configuration example of an intracranial pressure estimating device according to an embodiment of the invention. An intracranial pressure estimating device <NUM> includes an external ear canal pressure pulse wave sensor <NUM>, an amplifier <NUM> (AC amplifier), an AD converter <NUM>, an arithmetic unit <NUM> having an arithmetic processing unit (processor) and a storage unit, and a display unit <NUM>.

The external ear canal pressure pulse wave sensor <NUM> detects external ear canal pressure pulse waves. The external ear canal pressure pulse waves (ear canal pulse wave sound pressure) detected by the external ear canal pressure pulse wave sensor <NUM> are amplified by the amplifier <NUM>, converted into digital data by the AD converter <NUM>, and output to the arithmetic unit <NUM>. As the external ear canal pressure pulse wave sensor <NUM>, a sound sensor or a pressure sensor can be used.

<FIG> is a diagram illustrating a configuration example of the external ear canal pressure pulse wave sensor <NUM>. The external ear canal pressure pulse wave sensor <NUM> includes a sealed portion <NUM> that seals the ear canal to form a sealed space, and a microphone <NUM> that detects sound pressure in the sealed space as ear canal pulse wave sound pressure. The sealed portion <NUM> has a substantially hemispherical shape and is provided with a sound hole <NUM> communicating to a sound hole <NUM> in the microphone <NUM>. When detecting the external ear canal pressure pulse waves, the sound hole <NUM> is mounted to communicate to the ear canal. The sealed portion <NUM> and the microphone <NUM> are coupled such that the distal end of the sound hole <NUM> in the microphone <NUM> communicates to the sound hole <NUM> in the sealed portion <NUM>. As the sealed portion <NUM>, for example, an ear tip made of resin or an ear tip combined with plastic material may be employed. An air hole may be provided in the sealed portion <NUM> and may be sealed when the insertion to the ear canal is completed. As the microphone <NUM>, for example, a condenser electret microphone may be employed.

Referring back to <FIG>, the arithmetic unit <NUM> analyzes external ear canal pressure pulse wave data (output signal of AD converter <NUM>) obtained by digitalizing time-series data on the external ear canal pressure pulse waves detected by the external ear canal pressure pulse wave sensor <NUM>, calculates a first formant frequency of the external ear canal pressure pulse wave data, corrects the calculated first formant frequency based on the age and the sex of the subject (personal information on subject) to calculate a corrected value, and calculates an estimated value of the intracranial pressure based on the calculated corrected value. The arithmetic unit <NUM> analyses data obtained by subjecting the external ear canal pressure pulse wave data to high-pass filter processing to calculate the first formant frequency.

The display unit <NUM> (display) displays the external ear canal pressure pulse wave data and arithmetic results of the arithmetic unit <NUM> (estimated value of intracranial pressure). As the display unit <NUM>, for example, a liquid crystal display or a CRT display can be employed.

<FIG> is a diagram illustrating an equivalent circuit model that simulates pulse wave propagation from the carotid to the ear canal. <FIG> is a diagram schematically illustrating the heart, the inside of the cranium, the inner ear, and the ear canal. In the equivalent circuit model illustrated in <FIG>, blood flow source pulse waves (artery) l1(t) and blood flow source pulse waves (vein) l2(t) are input as current, and the flow of media (blood, bone-marrow fluid, air) is simulated by current and pressure is simulated by voltage. The compliance is represented by a capacitor, the channel resistance is represented by a resistor, and the mass is represented by a coil. The blood inside the cranium and the bone-marrow fluid are insulated by a transformer and the inner ear and the ear canal (eardrum) are insulated by a transformer. ECP(t) in <FIG> represents the external ear canal pressure pulse wave sensor <NUM>.

When it is supposed from the equivalent circuit model illustrated in <FIG> that an intracerebral substance minutely vibrates in the cranium due to the volume change in blood caused by heartbeat, a natural resonant frequency fo due to the compliance Cx in the cranium and the inertial mass L1 in the cranium is present.

When the natural resonant frequency fo is supposed to be a single resonant system as illustrated in <FIG>, fo is given by the following Equation (<NUM>).

From Equation (<NUM>), the compliance Cx in the cranium is expressed by the following Equation (<NUM>).

The intracranial pressure ICP is given by the following Equation (<NUM>) based on the known relational expression between the intracranial pressure ICP and the compliance Cx inside the cranium. <MAT> where α1 is a proportionality constant.

<FIG> is a table illustrating the relation among a measured value MICP (unit: cmH<NUM>O) of the intracranial pressure, a first formant frequency f1 (unit: Hz), and age and sex (male = <NUM>, female = <NUM>) of nineteen subjects. <FIG> is a graph illustrating the measured value MICP of the intracranial pressure of each subject, <FIG> is a graph illustrating the first formant frequency f1 of each subject, <FIG> is a graph illustrating the age of each subject, and <FIG> is a graph illustrating the sex of each subject. The measured value MICP of the intracranial pressure was measured by using an intracranial pressure sensor (drainage pressure sensor or indwelling subdural space sensor). The first formant frequency f1 was determined by subjecting external ear canal pressure pulse wave data to high-pass filter processing for cutting signal components of <NUM> or lower and performing linear predictive analysis (LPC analysis: <NUM>,<NUM> points (<NUM> seconds), 20th order). f1 illustrated in <FIG> is an average value in a measurement period (about <NUM> minutes).

The first formant frequency f1 illustrated in <FIG> was substituted into Equation (<NUM>) as fo to calculate an estimated value PICP of the intracranial pressure, and the estimated value PICP of the intracranial pressure was compared with the measured value MICP of the intracranial pressure illustrated in <FIG>. L1 in Equation (<NUM>) was a constant value. <FIG> illustrates the comparison results. The coefficient of determination R<NUM> (square of correlation coefficient) representing how well the estimated value PICP fits the measured value MICP when L1 is constant is <NUM>, which indicates that the correlation is low. The conceivable reason is that L1 differs depending on the age and the sex.

Thus, in the intracranial pressure estimating method in an embodiment of the invention, the first formant frequency f1 is corrected based on the age and the sex of the subject. Specifically, the first formant frequency f1 is corrected by the following Equation (<NUM>) to calculate a corrected value Xf1. <MAT> where β1, K, and β2 are constants, and Age is the age. FM is the sex, which is <NUM> for male and <NUM> for female.

The corrected value Xf1 in Equation (<NUM>) is used to rewrite Equation (<NUM>), and the estimated value PICP of the intracranial pressure is given by the following Equation (<NUM>). <MAT> where A and B are constants. For example, the constants in Equation (<NUM>) are set such that β1 = <NUM>, β2 = -<NUM>, and K = <NUM>, and the data (first formant frequency f1, age, and sex) illustrated in <FIG> are used to determine a corrected value Xf1 by Equation (<NUM>). The determined corrected value Xf1 and the measured value MICP of the intracranial pressure illustrated in <FIG> are used to perform linear regression analysis to determine optimal values of the constants in Equation (<NUM>). The determined optimal values are A = <NUM> and B = -<NUM>. For Age, the upper limit value and the lower limit value were provided, and Age was <NUM> for <NUM>-year-old or younger subjects and <NUM> for <NUM>-year-old or older subjects.

The optimal values of the constants and the corrected value Xf1 obtained from the data illustrated in <FIG> were used to calculate the estimated value PICP of the intracranial pressure by Equation (<NUM>), and the calculated estimated value PICP of the intracranial pressure was compared with the measured value MICP of the intracranial pressure illustrated in <FIG>. <FIG> illustrates the comparison results. By calculating the estimated value PICP by using the corrected value Xf1 obtained by correcting the first formant frequency based on the age and the sex, the coefficient of determination R<NUM> representing how well the estimated value PICP fits the measured value MICP was improved to <NUM>. In this manner, it was confirmed that the estimation accuracy of the intracranial pressure could be improved by the intracranial pressure estimating method in an embodiment of the invention.

<FIG> is a flowchart illustrating the flow of processing of the intracranial pressure estimating device <NUM>.

First, the arithmetic unit <NUM> acquires external ear canal pressure pulse wave data obtained by digitalizing time-series data on external ear canal pressure pulse waves detected by the external ear canal pressure pulse wave sensor <NUM> (Step S10). Further, the arithmetic unit <NUM> acquires age Age and sex FM of a subject input from an input unit (not shown).

Next, the arithmetic unit <NUM> executes high-pass filter processing on the acquired external ear canal pressure pulse wave data (Step S11). For example, a high-pass filter for cutting frequencies of <NUM> or lower can be applied to remove disturbance elements, such as breathing and heartbeat of the subject. Next, the arithmetic unit <NUM> analyzes the external ear canal pressure pulse wave data subjected to the high-pass filter processing (such as LPC analysis) to calculate a first formant frequency f1 (Step S12).

Next, the arithmetic unit <NUM> corrects the calculated first formant frequency f1 by Equation (<NUM>) based on the age Age and the sex FM of the subject to calculate a corrected value Xf1 (Step S13). Next, the arithmetic unit <NUM> calculates an estimated value PICP of the intracranial pressure by Equation (<NUM>) based on the calculated corrected value Xf1 (Step S14).

According to an embodiment of the invention, the intracranial pressure can be estimated based on external ear canal pressure pulse waves that can be measured by a non-invasive and simple device, and hence the intracranial pressure can be estimated in real time without purring burden on subjects. Further, the first formant frequency f1 of the external ear canal pressure pulse wave data is corrected based on the age and the sex of the subject, and the obtained corrected value Xf1 is used to calculate the estimated value PICP of the intracranial pressure. Thus, the intracranial pressure can be accurately estimated in consideration of the difference in inertial mass L1 in the cranium depending on the age and the sex of subjects.

Claim 1:
An intracranial pressure estimating method for estimating an intracranial pressure (ICP) from time-series data on external ear canal pressure pulse waves performed by an arithmetic unit (<NUM>), the method comprising:
an acquisition step (S10) of acquiring external ear canal pressure pulse wave data obtained by digitalizing time-series data on external ear canal pressure pulse waves of a subject caused by blood flow pulse wave propagation from the carotid to the ear canal;
a filtering step (S11) of subjecting the external ear canal pressure pulse wave data to high-pass filter processing;
an analysis step (S12) of analyzing said external ear canal pressure pulse wave data to calculate the first formant frequency (f1) in the external ear canal pressure pulse wave data by performing linear predictive analysison high-pass filtered data obtained in the filtering step (S11), the first formant frequency (f1) relating to a natural resonant frequency of vibrating intracerebral substance inside the cranium;
a correction step (S13) of correcting the first formant frequency (f1) based on personal information on the subject to calculate a corrected value (Xf1); and
an estimation step (S14) of calculating an estimated value (PICP) of an intracranial pressure based on the corrected value (Xf1).