RU2815286C2 - Method and device for non-invasive determination and/or control of intracranial compliance - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: group of inventions relates to a method and device for non-invasive determination and/or control of intracranial compliance of biological material. When performing the method, acoustic spectroscopy of the biological material is carried out using the first means. The biological material is a human or animal skull. Several acoustic transmission signals of varying frequencies and/or amplitudes are emitted into the biological material using an acoustic signal transmission device. After their passage through the biological material, the corresponding transmitted and reflected acoustic received signals of various frequencies and/or amplitudes are received using an acoustic signal receiving device. The acoustic transmitted signals are compared with the corresponding received acoustic signals using a comparative analytical device. The characteristic n-dimensional function and signal transit time values are determined for the biological material. The elongation of the biological material is determined using a second means. The linear and/or volumetric stretch of the biological material is measured using a measuring device. The intracranial compliance of the biological material is determined based on the comparisons and measurements performed using a data processing unit. Acoustic spectroscopy and/or determination of the stretch of biological material is performed in the direction of the frontal plane of the skull directly above the external auditory canal. The device contains a first means, a comparative analytical device, a second means, and a data processing unit. The first means includes an acoustic signal transmitting device and an acoustic signal receiving device. The second means includes a measuring device for measuring linear and/or volumetric stretch of the biological material.

EFFECT: use of a measuring segment with the highest possible amount of cerebrospinal fluid is ensured, the result of a physically measured change in the stretch of biological material is taken into account, which makes it possible to maximize the intensity of sound characterizing the areas of the intracranial system due to minimal suppression of acoustic waves in it, and thereby to increase the accuracy of determining intracranial compliance.

12 cl, 6 dwg

Description

The invention relates to a method and device for non-invasive determination and/or control of intracranial compliance of biological material in accordance with the generic concept according to independent claims.

The dynamics of varying intracranial pressure (ICP) in the human or animal skull is a significant complication for numerous cerebral diseases and has a significant impact on mobility and mortality, as well as other prognoses. For example, it has been found that 18% of patients with severe brain damage, such as, for example, after a traumatic brain injury and/or stroke, have persistent functional impairments that require many years of professional and/or social rehabilitation. Moreover, the scale of severity of these disorders is not only determined by the primary severity of the corresponding injury, but is also significantly affected by the developed secondary brain damage. Consequently, significant parthenogenetic significance is attached to changing intracranial pressure that is not detected in a timely manner and not properly treated. Therefore, measuring intracranial pressure is an important starting point for making therapeutic decisions in the treatment of patients with severe brain damage. Therefore, it is not surprising that, as is currently known from the prior art, it is proposed to carry out, whenever possible, continuous determination of intracranial pressure, the results of which have not only therapeutic, but also prognostic significance.

Various methods and devices for measuring intracranial pressure are known from the prior art. Until today, intracranial pressure has been measured exclusively by neurosurgically implanted pressure probes into the skull, the measurement being carried out by means of a pressure probe inserted into the intraventricular or epidural region, which ensures continuous monitoring of intracranial pressure, also over long periods of time. However, the methods and devices known from the prior art have the disadvantage that they are invasive and necessitate neurosurgical intervention, including the attendant risk of infection.

Therefore, as is known from the prior art, further attempts have been made to develop non-invasive methods and devices for monitoring intracranial pressure. In this regard, one can mention, for example, transcranial Doppler sonography (TCD), which provides direct, non-invasive analysis of cerebral hemodynamics in the large basal arteries of the brain. The disadvantage with this method, however, is that only rough estimates of the intracranial pressure in a person or animal are possible. However, the disadvantage is that transcranial Doppler sonography is difficult to carry out and therefore it is performed only by specially trained medical personnel.

In addition, other direct, non-invasive methods and/or devices for monitoring intracranial pressure are known in the art. In this regard, for example, the following references should be mentioned, but by no means limited to them: “The pulsating brain. A review of experimental and clinical studies of intracranial pulse pressure”, “Phase-locked frequency control device for monitoring intracranial pressure during spaceflight", "Non-invasive assessment of intracranial pressure waveforms using sound transmission technology using phase-locked frequency control. Technical note", "Determination of increased cranial volume by increased intracranial pressure", "Investigation of a model of ultrasound monitoring of intracranial cerebral media", "Dynamics intracranial pressure as determined by non-invasive ultrasound during 30 days of bed rest", "Intracranial pressure control - invasive versus non-invasive methods. Review" and "Non-invasive measurements of intracranial volume and pressure using ultrasound (for examination of the brain and spinal cord )". However, a disadvantage with these prior art methods and/or devices is that it is not possible to accurately determine and/or monitor intracranial pressure and associated brain damage.

Along with this, the duplex method of ultrasound examination of arteries is currently known from the state of the art as a recognized diagnostic tool for monitoring the condition of vessels in the extracranial region, in the neck, especially arteries a. carotis (carotid artery) and a. vertebral (vertebral artery). Due to this, duplex ultrasound of the arteries provides valuable information about vascular calcification and, therefore, about the associated blood flow turbulence and/or blood flow deficits. At the same time, it was found that the thickness of the skull and the associated sound attenuation prevented similarly detailed, visualization of intracranial vessels. Thus, although the ultrasound imaging technique, on the one hand, is an important and proven tool for diagnosis and therapy in medicine, however, these systems, unfortunately, only provide information about the internal structure of the target object in the form of two - or a three-dimensional image, but not information about the composition of the object.

Therefore, there is a great need for such a method and device for non-invasive determination and/or control of intracranial compliance of biological material, which provides a simple, fast, reliable and sufficiently accurate determination and/or control of the state of biological material so that changing intracranial pressure and/or can be timely detected. or treat it appropriately. In addition, the method and device must be the least expensive in terms of implementation/manufacturing, reliable in operation and suitable for short-term or long-term determination and/or monitoring of the state of biological material. Another aspect is that the determination and/or control of intracranial compliance should be carried out in such a way that it is not subject to interference, does not cause interference, does not require labor-intensive maintenance, does not create noise, does not cause side effects and does not cause harm to the patient concerned. Therefore, the invention was faced with the task of preparing a method and device for non-invasive determination and/or control of intracranial compliance of biological material in order to overcome the above-mentioned difficulties and, above all, to timely detect changing intracranial pressure and/or secondary brain damage that develops from it.

This problem is solved in a surprisingly simple but effective manner thanks to a method for non-invasive determination and/or control of intracranial compliance of biological material, as well as a corresponding device according to the technical solution in the independent main claims.

According to the invention, a method is proposed for non-invasive determination and/or control of intracranial compliance of biological material, which includes the following steps:

a) performing acoustic spectroscopy of a biological material, which is a human or animal skull, wherein several acoustic transmitted signals of various frequencies and/or amplitudes are emitted into the biological material and, after their passage through the biological material, the corresponding transmitted and reflected acoustic received signals of various frequencies and/or are received amplitudes,

b) comparison of the acoustic transmitted signals with the corresponding received acoustic signals, and for the biological material the characteristic n-dimensional function and signal travel time values are determined,

c) determining the stretch of the biological material, wherein the linear and/or volumetric stretch of the biological material is measured, and

d) determination of intracranial compliance of biological material based on comparisons made in step b), and measurements made in step c),

wherein acoustic spectroscopy and/or determination of the stretch of biological material is performed in the direction of the frontal plane of the skull immediately above the external auditory canal.

The method according to the invention is based on the basic idea that for a sufficiently accurate determination and accompanying appropriate treatment of changing intracranial pressure, a procedure for determining and/or monitoring the intracranial compliance of the human or animal skull will be sufficient. At the same time, it was determined that on the basis of acoustic spectroscopy of the skull of a person or animal, the travel time of the acoustic signal is measured, as well as, at the same time, its change along the measured segment and the speed of sound. Based on these data, it is possible to reliably determine the intracranial compliance in the appropriate measuring range and, based on this, first of all, based on the division of the measured values into categories, a conclusion can be drawn about the intracranial pressure, cerebral blood flow and/or pathological state. This is justified by the fact that in the context of the present invention it has been found that the concept corresponding to the invention, namely acoustocerebrography (ACG), which pursues another possible method of applying acoustic waves, can be used in relation to biological material. Accordingly, it was found that the use of multiple frequencies reflects the dispersive nature of brain tissue and allows signal changes to be interpreted in a specific way. Dispersion is an effect in which the nonlinear, frequency-dependent bulk modulus of a medium results in different sound propagation velocities at different frequencies. In nonlinear material, such as, for example, biological tissue, especially human or animal brain tissue, the dispersion effect of sound waves can be clearly observed and measured. We are talking about an effect in which the volumetric compression modulus of a nonlinear, frequency-dependent medium leads to different speeds of sound propagation at different frequencies. Since the properties of the bulk modulus depend on specific characteristics of the medium, such as composition, mixture concentration, content distribution and/or - in some situations - also on the chemical composition, a pattern of frequency-dependent sound velocities can be used to identify the state of the medium.

In other words, from the following equations (Eq. 1) and (Eq. 2), it can be seen that the propagation speed c(f) is a function of frequency and/or wavelength. It depends on the bulk modulus or Young's modulus Kv for liquid media and on the bulk modulus K _B for solid media.

From the equations (Eq. 1 and Eq. 2) it is clear that the bulk modulus K can be decomposed into volume V, volume change dV and the corresponding pressure change dp. By analogy, a given density ρ can be decomposed into mass m and volume V.

Further, in the context of the invention, it was found that the above equations (Eq. 1) and (Eq. 2) can be applied to a human or animal skull only when the structure of the corresponding biological material is taken into account. Consequently, it has been found that acoustic spectroscopy of biological material alone is not sufficient to accurately determine the intracranial compliance of biological material. In addition, it is necessary to take into account in parallel the expansion of the human or animal skull due to intracranial pressure during the systolic phase. It is highly dependent on various factors, such as, for example, age, intracranial pressure and/or the presence of at least one pathological condition and has been confirmed in volunteers during bed rest studies to be on the order of 20 µm. Moreover, in the context of the invention, it was established that expansion and contraction of the skull occur as a result of changes in intracranial pressure and are compensated by the rigidity of the surrounding parts of the skull. In doing so, measuring the expansion of the human or animal skull during the systolic phase can provide valuable data on changing intracranial pressure, cerebral blood flow and/or at least one pathological condition.

The expression "method for non-invasive determination and/or control" refers to a method for determining the intracranial compliance of a biological material, with which a sufficiently accurate and reliable determination of the intracranial compliance in the corresponding measuring range is possible. In this case, as one can imagine, the method is based on determining intracranial compliance, as well as its changes, which can be improvement or deterioration. Preferably, this change is determined over time. Even more preferably, the determination of the change is performed once or repeated at regular or irregular intervals, and is carried out short-term or long-term so that the trend of changes in intracranial compliance can be captured. This is especially important since in the case of the biological material being studied we are not talking about a static system. In addition, it is possible to track under what conditions and/or influencing factors the change in intracranial compliance progresses or slows down. In addition, the occurrence and/or cause of this change can be identified. It is therefore possible that the method according to the invention may include additional steps after or between the specifically identified essential steps a) to d). Preferably, the method is carried out in an automated manner.

The expression "biological material" refers to the skull of a person or animal, as known to those skilled in the art. Also, specialists are aware of the general and special distinctive features of the anatomical and/or physiological environment of the skull and/or brain and the cerebral vascular system.

The expression "determination of intracranial compliance" refers to the determination of the actual indicator of intracranial compliance. Preferably, the determination is carried out by semi-quantitative analysis, quantitative analysis, direct and/or indirect way. For example, by determining intracranial compliance, it seems possible to indirectly obtain additional information about the material being studied.

The expression "monitoring intracranial compliance" refers to monitoring and/or predicting a measured indicator of intracranial compliance. The control results can be presented, for example, in digital format and/or graphically, but in no case only in this way. Therefore, to improve the accuracy of monitoring, it is preferably carried out at regular or irregular intervals or on an ongoing basis. The advantage of long-term monitoring on an ongoing basis is that prediction, prediction and/or modification of intracranial compliance can be performed.

It will be appreciated by those skilled in the art that determination and/or monitoring generally may not be 100 percent accurate. Therefore, with regard to detection or tracking accuracy and/or prediction, the expression refers to a statistically significant probability. Whether such a determination and/or control is statistically significant can be determined by specialists, even those not involved in the field of invention, using methods known in the expert community. For example, statistical evaluation tools can be mentioned, such as, for example, the assessment of the coincidence interval, the assessment of the p-statistic, the Student's t test, the Mann-Whitney test, etc. The corresponding intervals are at least 90% accurate, at least 95% accurate, at least 97% accurate, at least 98% accurate, or at least 99% accurate. The p values are preferably 0.1, 0.05, 0.01, 0.005 or 0.0001. Preferably, the determination and/or control of intracranial compliance in the context of the present invention is at least 80%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6% accurate. 99.7%, 99.8%, 99.9%, 99.95%, 99.99% or 100%.

The expression "intracranial compliance" is used interchangeably with the expression "intracranial pressure-volume ratio", which are both known to those skilled in the art and describe the relationship between intracranial volume and intracranial pressure in the skull of a human or animal. Thus, increases in intracranial pressure are usually buffered by the displacement of venous blood and cerebrospinal fluid from the skull when intracranial volume (ICV) increases. However, those skilled in the art know that intracranial compliance depends on various factors, such as, for example, changes in intracranial pressure, elastic stiffness (the inverse of compliance), hydraulic compliance (the relationship between the instantaneous change in intracranial volume and/or the corresponding change in intracranial pressure), and /or movement of the skull bones at their sutures. In addition, it is known that the increase in intracranial pressure with an increase in intracranial volume has a non-linear characteristic, as described by the pressure-volume ratio. In addition, specialists know the standard indicators.

The method according to the invention includes the step of performing acoustic spectroscopy of a biological material, wherein several acoustic transmitted signals of different frequencies and/or amplitudes are emitted into the biological material and, after their passage through the biological material, corresponding transmitted and reflected acoustic received signals of different frequencies and/or amplitudes are received. In the next step, the transmitted acoustic signals are compared with the corresponding received acoustic signals, whereby a characteristic function in n-dimensions is specified for the biological material and the signal travel times and/or, equivalently, the phase shift are determined. It seems possible that for each pair of transmitted and received signals, along with the values of the signal travel time, the frequency shift of the associated acoustic signal is also determined. In other words, this means that with the method according to the invention, for each pair of transmitted and received signals at one corresponding or specific frequency, the result is a pair of data consisting of the corresponding signal travel time and in this case the frequency offset.

According to the invention, using the method according to the invention, for each pair of transmitted and received signals at one corresponding or defined frequency, the result is a pair of data consisting of the corresponding values of the signal travel time and - in this case, frequency offset and, if necessary, stored in the corresponding a properly tuned device set to the appropriate frequency. When implementing the method, very large arrays of output data are obtained, since for each frequency and the pair of transmitted and received signals associated with it, an array of output data with the corresponding transit time and, in this case, the frequency shift is determined, stored and/or graphically represented.

Therefore, it is preferably provided that data compression is performed, for example in the data compression device, a derived compressed data array is made from a certain output data array, wherein the compressed output data array reflects the specificity of the particular output data array and has a smaller data volume. How data compression is carried out is, in principle, all the same, and this is determined by professional skill.

The expression "acoustic spectroscopy" refers to the acoustic study of a medium based on inferences about changes in acoustic waves and/or acoustic vibrations in the audio frequency range (from 20 kHz to 1 GHz), primarily in the range of ultrasonic and/or longitudinal waves, the basis of the changes being interaction of structures contained in biological material with acoustic waves and/or vibrations. Thus, using acoustic spectroscopy, it is possible to non-invasively examine biological material, thereby determining changes in the structure of the environment. Preferably, acoustic spectroscopy is carried out using a suitable device, which is partially or completely located on the biological material and which is configured to emit vibrations, transmit vibrations, amplify vibrations and/or receive vibrations in the material, such as, for example, a device for transmitting and/or receiving acoustic signals.

In addition, according to the invention, it is provided that, based on a comparison of the corresponding pairs of transmitted and received signals, preferably on the basis of the obtained corresponding arrays of output data, it is possible to set a characteristic function for the biological material in n-dimensions, as well as determine the values of the signal transit time and/or - as an equivalent - phase shift. Those skilled in the art will recognize that the expressions "n-dimensional function" and "function in n-dimensions" are used interchangeably as synonyms. In addition, those skilled in the art know appropriate methods and apparatus for determining travel time values of signals, such as, but by no means limited to, travel time measurement. The expressions "time-of-flight measurement" and "time-of-flight measurement" are used interchangeably to refer to a method for indirectly measuring distance and/or speed by measuring the time it takes a signal to travel along a measured distance. Preferably, essentially only time differences are determined, so that the travel time measurement is a relative time system without a specifically defined zero point.

In the context of the invention, it was found that the speed of wave propagation directly depends on the properties of the biological material and, therefore, indirectly reflects its characteristic state. For example, it can be assumed that the density of biological material changes when venous blood is displaced from the brain of a person or animal. Further, it can be assumed that the speed of wave propagation changes under the influence of cerebral blood flow (diastolic/systolic flow) and/or perfusion of cerebral tissues.

Then, in step c), the elongation of the biological material is determined, and the linear and/or volumetric elongation of the biological material is measured. This step is particularly important since, in the context of the invention, it has been found that due to the stretching of the skull during acoustic spectroscopy, a phase change and/or time dilation or equivalently a reduction in travel time must occur in the transmitted signal. The stretching of the examined skull during acoustic spectroscopy is in the range of up to 20 µm and depends on various conditions such as age, intracranial pressure and/or possible pre-existing diseases. Preferably, the stretch is determined during the systolic phase. The determination of stretch is preferably carried out by semi-quantitative analysis, quantitative analysis, direct and/or indirect. Further, it seems possible that to determine the stretch of a biological material, an appropriate device is used, with which the linear and/or volumetric stretch of the biological material can be measured quite accurately. It is therefore possible that this respective device will directly or indirectly measure the stretch using devices and/or methods known from the prior art.

The functional relationship can be represented, for example, but by no means limited to, as a two-dimensional function as a trend of parameters over time, for example, as linear, logarithmic, exponential, logistic, polygonal functions and/or a combination thereof .

The expression "comparison" refers to the comparison of relative parameters with each other, especially the comparison of acoustic transmitted signals with corresponding received acoustic signals. It is understood that the comparison used in this context is related to the comparison of the corresponding parameters and/or values.

In the context of the invention, the comparison, determination and/or identification is carried out preferably using computer technology. To perform these steps, for example steps b), c) and/or d), using computer technology, you can use all means known to those skilled in the art, such as, for example, a computer and/or a computer program. The computer program may further analyze the corresponding result, for example, may automatically provide a score for the value. It is also possible, for example, that a data processing unit, an analysis device and/or a comparative analysis device are used to assist in performing steps b) and/or d) to evaluate the results. Advantageously, it is also possible to take into account in the comparison procedure successive transmitted and/or acoustic received signals in such a way that, based on this comparison, a prediction can be made as to how the state of the material will change as a function of time.

In the context of the invention, it is considered quite clear that the result of the method, that is, the determination of intracranial compliance, directly or indirectly depends on the biological material being studied. Therefore, it can be assumed that a small and insignificant, large and significant and/or no change in the intracranial compliance of biological material in a time dependence is an indicative indicator of a change in intracranial compliance. A change in intracranial compliance may preferably be an improvement and/or a deterioration thereof. In this regard, it is possible that the result of the method can be output as time-related data as an absolute and/or relative value.

In the last step, the intracranial compliance of the biological material is determined based on the comparisons made in step b) and the measurements made in step c). It is clear to those skilled in the art that the determination can be made through calculation, countdown, derivation and/or through cause-and-effect inferences, primarily based on the adoption of one or more assumptions. In addition, it is possible that an evaluation of the results obtained is carried out.

Thus, using the method according to the invention, it is possible to simply, quickly, reliably and sufficiently accurately determine and/or control the intracranial compliance in the human or animal skull in order to determine the intracranial compliance, for example, over time or over a long period of time. It is also possible to carry out this determination and/or control interactively. Due to the simplicity of the method according to the invention, it is therefore possible that not only specially trained medical personnel can implement the invention, but also any person for self-monitoring, be it in a private household, or emergency service paramedics, nurses and/or auxiliary workers .

Preferably, in the context of the invention, it has been found that the method provides a measurement range of several microseconds with a resolution of single picoseconds and, thus, represents an adequately suitable tool for non-invasive determination and/or monitoring of intracranial compliance in the human or animal skull, which (method , tool) while significantly contributing to the medical diagnosis of intracranial pressure, cerebral blood flow and/or at least one pathological condition. Due to this, it is possible to promptly detect changing intracranial pressure and properly treat it, which has a particularly positive effect on predicting mobility and mortality and/or the condition of patients.

Preferred improved embodiments of the invention, which can be implemented individually or in combination, are presented in the dependent claims.

In one improved embodiment of the invention, it is possible that the method further includes:

e) determination of intracranial pressure, cerebral blood flow and/or pathological state of biological material based on the intracranial compliance determined in step d).

With this option, based on the established intracranial compliance, information about other important factors can be obtained through calculation, countdown, derivation and/or through causal inference (making assumptions).

The expression "intracranial pressure (ICP)" refers to the pressure that occurs inside the skull and therefore in the brain tissue and cerebrospinal fluid. Experts know that intracranial pressure is critical to blood flow, and therefore to brain function, because it counters the pressure at which blood is pumped to the brain. In addition, specialists know the interdependent relationship between the volumes of cerebrospinal fluid and blood; the Monroe-Kelly doctrine, according to which, with an intact skull, the volume of the brain, blood and cerebrospinal fluid in it is constant. Therefore, an increase in pressure in one component results in a decrease in pressure in one or both of the other components. In addition, specialists know the standard indicators. Preferably, intracranial pressure is derived from equations (Eq. 1) and (Eq. 2) given elsewhere and depends on the linear and/or volumetric distension of the skull.

The expressions "cerebrospinal fluid (CSF)", "liquor cerebrospinal" and "CSF" are known to those skilled in the art and are used in the context of the invention as interchangeable synonyms for cerebrospinal fluid, colloquially referred to as cerebral fluid. In addition, specialists know the standard indicators.

The expression “cerebral blood flow (CBF)” is known to specialists and refers to the amount of blood supplied to the brain in a certain unit of time.

In addition, specialists know the standard indicators. It is known from the prior art that cerebral blood flow accounts for about 15 percent of cardiac output and is approximately 750 ml/min. However, in the context of the invention, the total cerebral blood flow may differ from the actual cerebral blood flow. Preferably, cerebral blood flow is calculated from equations (Eq. 1) and (Eq. 2) given elsewhere.

The expression "pathological condition" refers to any injury to the skull of a person or animal and therefore has a special meaning. For example, the pathological condition refers to traumatic brain injury, skull damage, apoplexy, congestion, cerebral edema, insufficient blood supply, cerebral ischemia, cerebral hemorrhage, especially intracranial, intracerebral, parenchymal and/or extracerebral cerebral hemorrhage, subarachnoid hemorrhage , thrombosis, irritation and/or changes in blood vessels, insufficient perfusion and/or perfusion of brain tissue. Preferably, the pathological condition is derived from equations (Eq. 1) and (Eq. 2) given elsewhere. In addition, it is advantageous to determine the location of the pathological condition in the human or animal skull.

With this additional step, therefore, based on the previously determined intracranial compliance, other important parameters can be obtained for timely detection (pathology) and proper treatment of the patient.

In another embodiment of the invention, it is possible that the method further includes:

f) presentation of the results of the determination made in step d) and/or step e).

With this option, the identified parameters can be presented in digital format and/or graphically, thereby making it easier to understand what was identified in step d) and/or step e). Those skilled in the art will know appropriate means for presenting the output parametric data. An additional output device may be used to assist in step e).

In yet another embodiment of the invention, it is possible that acoustic transmitted signals are emitted at a first point of the biological material and acoustic received signals are received at a second point of the biological material and that the first and second points are located identically or opposite to each other. With this option, the means necessary for implementing the method can be arranged in a space-saving and comfortable manner for the patient being examined, while at the same time reliably identifying the above parameters.

In addition, it is possible that acoustic spectroscopy and/or determination of the stretch of biological material is performed essentially in the region of the left and right hemispheres of the cerebrum and the longitudinally extending cerebral fold. In the context of the invention, it has been found that the equations given elsewhere (eq. 1) and (eq. 2) provide the best possible determination of the above parameters, taking into account the structure of the human or animal skull. It was found that the skin, muscles, skull bones and/or brain fluid can be neglected in terms of their effect on sound, and therefore can be considered as constants. At the same time, the areas of the left and right hemispheres of the cerebrum and the longitudinally running cerebral fold, including part of the cerebrospinal fluid, are very dependent on the cardiovascular system and blood supply to the brain tissue. Therefore, these areas of biological material are suitable for carrying out the method according to the invention.

The expression "substantially" means that there is only a minor, primarily not significant, change, adjustment and/or deviation from the specified parameter or range/area. Thus, for example, it is possible that acoustic spectroscopy and/or strain detection of biological material is carried out with some deviation from the preferred region of the left and right cerebral hemispheres and the longitudinal cerebral fold, which means that the impact on the detection performed is zero or not significant.

As stated above, acoustic spectroscopy and/or determination of the stretch of biological material is performed essentially in the direction of the frontal (coronal) plane of the skull slightly above the external auditory canal. In the context of the invention, it has been found in this regard that the best suitable areas for performing this measurement method are surfaces that lie in the direction of the frontal plane of the skull immediately above the external auditory canal. With this embodiment, it is ensured that the intensity and/or strength of the sound can be maximized, since this region of the cranial system is characterized by the least suppression of acoustic waves. Therefore, with the greatest probability, a complete echo can be obtained from the opposing bones of the skull, so that based on the above analyzes a simplified layered structure of the cranial system can be tentatively accepted.

The definitions and/or interpretations of the above expressions are intended to apply to all aspects set forth below in this specification unless otherwise noted.

In addition, according to the invention, a device is provided for non-invasive determination and/or control of intracranial compliance of biological material in the manner described above. A device according to the invention includes first means for performing acoustic spectroscopy of a biological material that is a human or animal skull, the first means including an acoustic signal transmission device for emitting multiple acoustic transmission signals of different frequencies and/or amplitudes into the biological material and a receiving device acoustic signals for receiving corresponding transmitted and reflected acoustic received signals of various frequencies and/or amplitudes after they have passed through the biological material. In addition, the device includes a comparative-analytical device for comparing acoustic transmitted signals with corresponding received acoustic signals, configured to determine for biological material a characteristic n-dimensional function and signal travel time values and/or equivalently, a phase shift. In addition, the device includes second means for determining the elongation of the biological material, the second means including a measuring device such as, for example, but by no means limited to: a film strain gauge, a pressure sensor, a capacitive sensor, or others sensors for measuring linear and/or volumetric stretching of biological material. Finally, the device also includes a data processing unit for determining the intracranial compliance of the biological material based on the comparisons made and the measurements taken.

Preferably, the device according to the invention is a self-adjusting and/or self-calibrating device in order to achieve the optimal possible determination and/or control of intracranial compliance. Also, preferably, the device can be used as part of acoustocerebrography (ACG). Also, preferably, the device is suitable for short-term or long-term determination and/or monitoring of the condition of biological material.

The expression “first means” refers to any means known to those skilled in the art, which in the range of sound frequencies, especially in the range of ultrasonic frequencies and in the range of longitudinal waves, is designed to emit vibrations, transmit vibrations, amplify vibrations and/or receive vibrations in biological material. Preferably, the agent is partially or completely located on the biological material. Preferably, the first means is an acoustic signal transmission device for emitting multiple acoustic transmission signals of different frequencies and/or amplitudes into the biological material and/or an acoustic signal receiving device for receiving corresponding transmitted and reflected acoustic reception signals of different frequencies and/or amplitudes after they have passed through biological material.

The expression “second means” refers to any means known to the person skilled in the art that is designed to measure the stretch of a biological material, especially the linear and/or volumetric stretch of the biological material. The measurement can be carried out directly or indirectly using means/devices and/or methods known from the prior art.

The expression "comparative-analytical device" refers to a device that is configured to compare acoustic transmitted signals with corresponding received acoustic signals. Suitable comparative analytical devices are known to those skilled in the art: for example, a computer and/or a computer program. The computer can additionally evaluate the results of comparisons.

The expression "data processing unit" refers to a unit that is configured to process data or detect intracranial compliance of biological material. For example, the data processing unit is a computer and/or a computer program.

The device according to the invention has the advantage that it is designed with sufficiently precise sensitivity to provide a simple, fast, reliable and sufficiently accurate determination and/or control of intracranial compliance of biological material, which can be carried out in a short-term or long-term mode. It is also possible to carry out this determination and/or control interactively. Moreover, preferably, the device has a measurement range of several microseconds with a resolution of single picoseconds and, thus, represents an adequately suitable tool for non-invasive determination and/or monitoring of intracranial compliance of biological material, which (instrument) significantly contributes to the establishment of a medical diagnosis when intracranial pressure, cerebral blood flow and/or pathological condition. In addition, the device is rigid enough to withstand the stress of everyday handling over a long period of time.

Preferred improved embodiments of the invention, which can be implemented individually or in combination, are presented in the dependent claims.

In one improved embodiment of the invention, it is possible that the data processing unit is configured to determine intracranial pressure, cerebral blood flow and/or pathological state of biological material based on the determined intracranial compliance, as described in detail elsewhere in the text.

In addition, it is possible that the device of the invention includes a data output device for presenting the results of the determination made by the data processing unit.

The expression "data output device" refers to a device that is configured to represent the detected parameters. With this option, intracranial compliance and its derived parameters, i.e. intracranial pressure, cerebral blood flow and/or pathological condition, can be represented digitally and/or graphically, thereby making it easier to understand what has been detected. Those skilled in the art will know suitable output devices for presentation.

It is further possible that the acoustic signal transmitting device is located at a first point of the biological material and the acoustic signal receiving device is located at a second point of the biological material and that the first and second points are located identically or opposite to each other, as has been described in detail elsewhere .

It is also still possible that acoustic spectroscopy and/or determination of the stretch of biological material is performed essentially in the region of the left and right cerebral hemispheres and the longitudinally extending cerebral fold, as has already been described in detail elsewhere.

In another embodiment of the invention, it is possible that the first means, the second means, the comparative analysis device, the data processing unit and/or the data output device are located in one structural unit. Preferably, the assembly is a hybrid acoustic sensor, a hairband, a hairband, and/or an earpiece. This embodiment of the invention provides the advantage that the device is compact and easy to handle, and is also well suited for transport.

In yet another embodiment of the invention, it is possible that the device is rotatable and/or movable, thereby changing its position and providing an improved determination of intracranial compliance and its derived parameters, i.e. intracranial pressure, cerebral blood flow and/or pathological condition and so that, First of all, determine the localization of the pathological condition.

Other features, features and advantages of the invention follow from the following description of preferred embodiments in connection with the dependent claims. In this case, the corresponding features can be implemented either individually or in multiples in combination with each other.

The invention is not limited to the examples provided. Examples of implementation are shown schematically in the figures. Identical reference numerals in individual figures designate elements that are identical or identical in purpose and design or functionally corresponding to each other.

The individual figures show:

Fig. 1: schematic representation of a device according to the invention, FIG. 2: schematic representation of the structure of the human skull (Fig. 2A) and, accordingly, a layer-by-layer model of the human skull according to Fig. 2A (Fig. 2B),

Fig. 3: first (Fig. 3A) and second (Fig. 3B) schematic representation of the area of the human skull most suitable for carrying out the method according to the invention or for positioning the device according to the invention,

Fig. 4: Overview of signal attenuation along the measurement path in the human skull.

Fig. 5: graphical representation of data from measurements on a 72-year-old patient,

Fig. 6: Graphical representation of the propagation of the cardiac pulse pressure signal, primarily the intracranial pressure measurement captured by the intracranial pressure probe.

In fig. 1 schematically shows a device 01 located on biological material 02 - a human skull - according to the invention. As well as can be recognized in Fig. 1, the device 01 includes a first means 10, which includes an acoustic signal transmitting device 11 located at a first point X1 and an acoustic signal receiving device 12 located at a second point X2. In this case, it can be clearly recognized that the first and second points X1, X2 lie opposite to each other and that acoustic spectroscopy is carried out in the direction of the frontal (coronal) plane of the skull 02 slightly above the external auditory canal.

In addition, the device 01 includes a second means 30 with a measuring device 31 such as a film strain gauge, a pressure sensor, a capacitive sensor or other sensors. In fig. 1 also shows the built-in comparative-analytical device 20 and the data processing unit 40. It is also possible that such could be provided as non-built-in components. The parameters recorded by device 01 can then be transmitted further to a data output device, not shown here.

The following exemplary embodiments serve merely to illustrate the invention. They should in no way limit the subject matter of the invention set forth in the claims.

Example 1: Basic principles of the concept according to the invention - acoustocerebrography (ACG)

As has been previously described in detail elsewhere in the text, in the context of the present invention it has been found that the concept according to the invention, namely, acoustocerebrography (ACG), can be used in relation to biological material. Accordingly, it was found that the use of multiple frequencies reflects the dispersive nature of brain tissue and allows signal changes to be interpreted in a specific way. Dispersion is an effect in which the nonlinear, frequency-dependent bulk modulus of a medium results in different sound propagation velocities at different frequencies. In nonlinear material, such as, for example, biological tissue, especially human or animal brain tissue, the dispersion effect of sound waves can be clearly observed and measured. We are talking about an effect in which the volumetric compression modulus of a nonlinear, frequency-dependent medium leads to different speeds of sound propagation at different frequencies. As has been described in detail elsewhere in the text, the properties of the bulk modulus depend on specific characteristics of the medium, such as composition, mixture concentration, content distribution and/or - in some situations - also on chemical composition, so that the frequency pattern dependent sound propagation velocities can be used to identify the state of the medium.

To use the equations (eq. 1) and (eq. 2) given elsewhere in the text in relation to the human or animal skull, it is necessary to take into account the structure of the corresponding biological material. In fig. 2A provides an overview of the structure of the human skull, and FIG. 2B is a corresponding layer-by-layer model of the human skull according to FIG. 2A. The following Table 1 provides explanations for those shown in FIGS. 2A and 2B tissue structures 1a, 1b, 2, 3 (with ventricles), 4 and 5 of the human skull:

As can be clearly understood from Table 1, presented in Fig. 2A and 2B structures: skin (1a), muscles (1b), skull bones (2) and brain fluid (3) in the human skull do not have any effect on the performed acoustic spectroscopy and therefore can be considered as constants. In this case, the left and right hemispheres of the cerebrum (4), the longitudinally extending cerebral cleft (fold) (5), including part of the cerebrospinal fluid (3), have an effect on the conducted acoustic spectroscopy, which is very dependent on the cardiac cycle and blood supply to the brain tissue. These areas are of particular interest for further research.

The data must be obtained by measuring the time of travel of the signals (time of flight method) according to the following equation (Eq. 3). If we have a sample of T tissue layers, then the total propagation time will be obtained by summing the propagation time values for each tissue in the sample.

The concept according to the invention and the underlying model can be conveniently reformatted or modified, for example by adding additional layers of fabrics. If accurate and detailed dispersion data is available, tissue-specific dispersion can also be modeled as a nonlinear function of frequency. In relation to a specific tissue i, the propagation time t _i (f) in relation to the frequency f can be determined according to the equation below (eq. 4).

In the above equation (Eq. 4), d _i is the depth of tissue crossed by the acoustic wave, c _oi is a certain base speed at the fundamental frequency f _oi , and Δi is the tendency of tissue dispersion, which characterizes the dependence of frequency on propagation speed. The signal is transmitted from one ultrasonic head and received either by another head (transmission mode) or by the same head (reflection mode). The speed of the transmitted signal, as already described, depends on the medium. Based on an anatomical analysis of the human skull-brain system, it can be shown in this regard that, depending on the area of the system, there are very different conditions for the propagation of acoustic waves. As a result of reflection, we came to the conclusion that it was necessary to optimize the direction of research in tissue. Due to this, it was found that for measurements in transmission and/or reflection mode, the one shown in FIG. 3A direction of the frontal (coronal) plane.

Restrictive conditions in terms of minimum intensity of ultrasonic waves prompted a search for areas in the skull that would be characterized by the least suppression of acoustic waves. The analysis shows that the most suitable areas to perform this measurement method in this context are surfaces, which, as shown in FIG. 3B, are located slightly above the external auditory canal. The choice of such (localization) for the measuring device ensures that with the greatest probability a complete echo can be obtained from the opposing skull bones. Based on the above analyzes with reference to FIG. 2A and FIG. 2B, as well as Table 1, a simplified layer-by-layer structure of the cranial system can be conventionally accepted.

Taking the above shown in FIG. 2A and FIG. 2B, as well as in Table 1, a layer-by-layer model of the human skull as an input value and using the physical parameters of various tissues of the skull presented in Table 2 below, it is therefore possible to determine the values of the travel time of the acoustic signal, as well as the signal attenuation caused by these structures along the path measurements.

Signal attenuation along the measurement path in the human skull in the case of those shown in FIGS. 2A and 2B structures, namely skin (1a), muscles (1b), skull bones (2), cerebrospinal fluid (3), left cerebral hemisphere (4a), right cerebral hemisphere (4b) and longitudinally running cerebral cleft ( fold) (5) is shown in Fig. 4. In addition, Table 3 below shows a human head model to determine the ultrasonic signal attenuation and the predicted time of flight of the signal along the measurement path.

Considered in signal transmission mode, the measurement process of the invention involves "injecting" an acoustic wave into the central brain system at a selected point X1 shown in FIG. 3A and 3B and its subsequent reception at the opposite point X2, depending on the direction of propagation of the acoustic beam. Therefore, this method preferably requires the use of two ultrasonic probes, one for emitting and one for receiving the acoustic signal.

The cerebrovascular system is a very complex system and therefore the state of the blood supply to the brain has a great influence on its physical and chemical parameters. Intracranial pressure depends on the volumes of intracranial fluid and tissue and on the pulsatile volumes caused by the pulsation of arterial blood within the skull. Based on the known normal blood supply to the brain or normal cerebral blood flow (CBF), for example, 50 ml/100 g/min for an average brain weight of 1.375 g, the average CBF was found to be approximately 690 ml per minute. This gives a blood flow rate of approximately 11.6 ml per second (estimated as the volume per heartbeat). With this in mind, it is possible to measure the travel time of signals (time of flight measurement) and the speed of sound and/or change in sound based on the standard cranial blood supply (CBF) of tissues. The bone movement confirmed in volunteers during bed rest is of the order of up to 20 microns and can be calculated using the equation below (UR-5).

Let's take a very simplified model as shown in the equation below (Eq. 6). A standard cerebral blood flow (CBF) of 50 ml/100 g/min means that for each heart rate per minute, for example, 60 beats per minute (bpm), 8% to 10% are exchanged between diastole and systole. masses.

Next, according to the above equation (Eq. 5), you can try to estimate the change in the speed of acoustic waves. If we assume that approximately 10% of the cerebrospinal fluid (CSF), in accordance with normal perfusion rates, is periodically replaced by blood, then we can try to calculate changes in the speed of passage of the acoustic wave. The corresponding K-values for cerebrospinal fluid and blood can be calculated from the known c and ρ according to the equations below (Eq. 7) to (Eq. 10).

If we take the area of the cerebrospinal fluid, that is, the area in which the brain tissue is stretched due to pulsation, as a whole equal to 1 cm, then using the equation below (Eq. 11) the diastolic transit time can be calculated:

Using the result from equation (Eq. 10) and assuming a maximum skull distension of 20 µm, the predicted systolic transit time (within the faster environment since 10% of the CSF has been replaced) can be calculated using the equation below (Eq. 12). blood):

From the above equations (Eq. 11) and (Eq. 12) it turns out that during the diastolic phase we have a travel time of the acoustic signal with _csf = 1498 m/s. During the systolic phase (at x = 10% = 0.1) By calculation, we obtain the travel time of the acoustic signal c _sys - 1506.76 m/s. Even though sound travels faster during the systolic phase by 1506.76 - 1498 = 8.76 m/s, we see an increasing time-of-flight waveform between the diastolic and systolic phases. This is because the skull expands during the systolic phase due to intracranial pressure.

This shows that even with an increase in the speed of sound - as a result of the replacement of cerebrospinal fluid with blood in the corresponding area of interest to us - by more than 8.75 m/s, the total travel time of a packet of acoustic signals increases either due to a longer path, or due to longer distance. If we now subtract t _sys from t _DiA , then in this case we obtain the maximum difference of 94 ns shown in the equation below (eq. 13). The transit time measurements are performed with appropriate resolution, which is more than ten times better than the predicted difference limit of approximately 94 ns (better than 90 ps).

The maximum difference of 94 shown in equation (Eq. 13) is not the criterion that is achieved with the method and apparatus of the invention. Thus, as an adequately suitable medical diagnostic tool, they are suitable for providing support in making a medical diagnosis for intracranial pressure and other pathologies. Time with ±45 tolerances should not be measured at the appropriate resolution, i.e. better than 100x resolution (approx. 400 ps per step) and faster than 30 measurements per second. At the same time, we must note that the signal transit time difference (increase/decrease) may decrease if the expansion of the skull decreases or may even turn into a negative value if the skull no longer expands due to increased intracranial pressure. This can be very useful information in terms of emergency medical care.

Example 2: Dispersive ultrasound as a non-invasive diagnostic system

Acoustocerebrography (ACG) uses quasi-persistent packets of ultrasonic waves at different frequencies to scan the environment to obtain transit times at each transmission frequency. This method provides an assessment of the sample dispersion sf in relation to a specific contained (in the skull) environment. Observed changes in propagation speed are typically very small and require very precise measurements of propagation speed. Instead of measuring the speed of sound in media, it would be easier to accurately measure the propagation time of ultrasound.

Using the equation (Eq. 4) given elsewhere in the text, one can very accurately estimate the propagation speed c(f) based on the propagation time f(f), assuming that the constant size d is known.

A very high scan rate is required for the received signal to accurately measure the travel time t(f). To achieve the required accuracy, the scanning frequency must be in the gigahertz range (specifically 2.5 GHz with a resolution of 400 ps). Determining the signal path from transmitter to receiver therefore requires time resolution to be in the subnanosecond range. Such a system would be very expensive and would have unacceptable power consumption for a portable device. Alternatively, it is known that an ultrasonic signal can be described not only by its frequency, but also by its phase information, as shown in the following equation (Eq. 14).

To meet the requirement for a high scanning frequency, the phase information of the ultrasonic wave must therefore be used together with its amplitude to obtain accurate travel time estimates. It is common knowledge that phase information only covers the range from -π to +π. Therefore, it can only be used to obtain additional information about the period of the signal. In addition, this information is repeated all the time. In this case, a phenomenon from wave theory is used - the tone of the beats. In acoustics, beat is the effect of interference between two tones with easily distinguishable frequencies, which is perceived as a fluctuation in the volume of a sound, the intensity of which is equal to the difference between both frequencies. From the phenomenon of beat tone it follows that there is a combination of two long wave signals, which are close in pitch to each other, but are not identical. The difference in frequency causes beats. The frequency of the beat tone is given by the following equation (Eq. 15).

The closer to each other they lie the lower the resulting frequency beat and the longer the period of the resulting beat phase Using this beat tone substitution provides unambiguous identification of a specific point in the signal. Once this unambiguous point is found, the phase information of the individual frequency can be used in certain situations to calculate accurate travel times. In addition to the observed changes in propagation speed, different extinction profiles can also be observed. The mutual relationship between wave speed and damping is consistent with the Kramers-Kronig relation, which, in particular, reflects the relationship shown in the equation below (eq. 16).

In equation (Eq. 16), c1, c2 are the propagation velocities (speed of sound) for waves with circular oscillation frequency ω1 or ω2, and α(ω) is the damping for waves with circular oscillation frequency ω. Moreover, after the introduction And The following equation is valid in the formula (eq. 17):

Such patterns of frequency-dependent extinctions and corresponding propagation velocities can be used to identify the state of the environment and monitor in real time possible changes in brain tissue. In order to achieve the required time resolution to obtain a realistic medical diagnostic picture, as shown in FIG. 5, some essential requirements must be put forward for determining the phase. In fig. Figure 5 shows the heart waveform of a 72-year-old patient during transit time measurements using the Acoustocerebrum o Graffine (ACG) system as part of an approved clinical trial. The X-axis is the time [t] in seconds (s), and the Y-axis is the travel time measurement in microseconds (μs).

Assuming that the acoustic measurement band of interest for acoustocerebrography (ACG) falls in the range from 0.7 MHz to 2.7 MHz, this will give the following prediction of signal phase resolution. We need better than 400 ps phase resolution at 0.7 MHz. Each higher frequency gives higher time resolution - as the wavelength becomes shorter, this means that time resolution will be greater. If we assume that the average speed of a quasi-constant packet of acoustic waves in the skull is 1540 m/s, we can get an explanation according to the equations given elsewhere in the text and the equation below (eq. 18).

As follows from equation (Eq. 18), this 2.2 mm is the length of exactly one period (360° or 2π phase) with a duration of 1.4285714 μs. Therefore, the required phase resolution must be within 0.1° or better.

Example 3: Evaluation of transit time measurements on a patient

When resorting to monitoring intracranial pressure (ICP monitoring), in clinical practice it is very important to determine the validity of the obtained pressure value. Access to a high-resolution visualized representation of the intracranial pressure waveform in this regard allows for more accurate analysis of the identified intracranial pressure indicators. When carrying out the method according to the invention, it is therefore important to check whether the resulting ICP signal is indeed an indicator of intracranial pressure. Thus, it is necessary to make sure that in fact there is an oscillating pressure curve known to specialists with a progressive decrease in the P1, P2 and P3 waves, which show the propagation of the pulse cardiac pressure signal. Such an oscillating pressure curve is shown as an example in FIG. 6, which shows the propagation of the cardiac pulse pressure signal, primarily (during) the measurement of intracranial pressure captured by the intracranial pressure probe. The X-axis shows time [t] in milliseconds (ms), and the Y-axis shows intracranial pressure (ICP).

It is clear that deviations from the pressure curve shown as an example in FIG. 6 may indicate altered intracranial compliance, altered intracranial pressure, impaired cerebral blood flow and/or pathological condition. For example, the P1 and P2 waves interchanged indicate a state of impaired autoregulation.

Taking a closer look at the waveform in FIG. 5 confirms the conclusion from Application Example 1 above in that it shows a difference of approximately 50 in the transit time measurement between the diastolic and systolic phases. It also shows that the patient has impaired autoregulation because there is a reversal of the P1 and P2 waves, as can be seen at seconds 6, 7, 8, 9, 14, 15 and 16.

Claims (23)

1. A method for non-invasive determination and/or control of intracranial compliance of biological material (02), including: a) performing acoustic spectroscopy of a biological material (02), which is a human or animal skull, wherein several acoustic transmitted signals of different frequencies and/or amplitudes are emitted into the biological material (02) and, after they pass through the biological material (02), the corresponding transmitted signals are received and reflected acoustic received signals of various frequencies and/or amplitudes, b) comparison of the acoustic transmitted signals with the corresponding received acoustic signals, and for the biological material (02) the characteristic n-dimensional function and the signal travel time values are determined, c) determining the stretch of the biological material (02), wherein the linear and/or volumetric stretch of the biological material (02) is measured, and d) determination of intracranial compliance of biological material (02) based on comparisons made in step b) and measurements made in step c). wherein acoustic spectroscopy and/or determination of the stretch of biological material (02) is performed in the direction of the frontal plane of the skull immediately above the external auditory canal. 2. The method according to claim 1, additionally including: e) determination of intracranial pressure, cerebral blood flow and/or pathological state of biological material (02) based on the intracranial compliance determined in step d). 3. The method according to claim 1 or 2, additionally including: f) presentation of the results of the determination made in step d) and/or step e). 4. Method according to one of paragraphs. 1-3, in which the acoustic transmitted signals are emitted at the first point (X1) of the biological material (02), the acoustic received signals are received at the second point (X2) of the biological material (02), and the first and second points (X1, X2) are located identically . 5. Method according to one of paragraphs. 1-4, in which acoustic spectroscopy and/or determination of the stretch of biological material (02) is performed in the region of the left and right hemispheres of the cerebrum and the longitudinally extending cerebral fold. 6. Device (01) for non-invasive determination and/or control of intracranial compliance of biological material (02) by the method according to one of the previous paragraphs, containing: - first means (10) for performing acoustic spectroscopy of biological material (02) representing a human or animal skull, wherein the first means (10) includes an acoustic signal transmission device (11) for emitting several acoustic transmission signals of different frequencies and/or amplitudes into the biological material (02) and an acoustic signal receiving device (12) for receiving corresponding transmitted and reflected acoustic received signals of various frequencies and/or amplitudes after they have passed through the biological material (02), - a comparative analytical device (20) for comparing acoustic transmitted signals with the corresponding received acoustic signals, configured to determine for biological material (02) a characteristic n-dimensional function and signal travel time values, - second means (30) for determining the stretch of the biological material (02), wherein the second means (30) includes a measuring device (31) for measuring the linear and/or volumetric stretch of the biological material (02), and - a data processing unit (40) to determine the intracranial compliance of the biological material (02) based on the comparisons made and the measurements taken, whereby acoustic spectroscopy and/or determination of the stretch of the biological material (02) is carried out in the direction of the frontal plane of the skull directly above the external auditory canal. 7. Device (01) according to claim 6, in which the data processing unit (40) is configured to determine intracranial pressure, cerebral blood flow and/or pathological state of the biological material (02) based on the determined intracranial compliance. 8. The device (01) according to claim 6 or 7, including a data output device for presenting the results of the determination made by the data processing unit (40). 9. Device (01) according to one of paragraphs. 6-8, in which the device (11) for transmitting acoustic signals is located at the first point (X1) of the biological material (02), and the device (12) for receiving acoustic signals is located at the second point (X2) of the biological material (02), the first and the second points (X1, X2) are located identically. 10. Device (01) according to one of paragraphs. 6-9, in which acoustic spectroscopy and/or determination of the stretch of biological material (02) is carried out in the region of the left and right hemispheres of the cerebrum and the longitudinally extending cerebral fold. 11. Device (01) according to one of paragraphs. 6-10, in which the first means (10), the second means (30), the comparative analytical device (20), the data processing unit (40) and/or the data output device (50) are configured to be located in one structural unit. 12. Device (01) according to one of paragraphs. 6-11, made with the possibility of rotation and/or movement.