WO2002000108A2

WO2002000108A2 - Method for determining a diagnostically relevant parameter from the electrocardiographical and magnetocardiographical data of a patient

Info

Publication number: WO2002000108A2
Application number: PCT/EP2001/006649
Authority: WO
Inventors: Fritz Steinberg; Mykola Budnyk; Volodymyr Sosnitzky
Original assignee: Squid International Ag
Priority date: 2000-06-12
Filing date: 2001-06-12
Publication date: 2002-01-03
Also published as: DE10128293A1; AU2001289601A1; EP1337181A2; WO2002000108A3

Abstract

The direction of the electromotive force vector (EMF vector) of the heart is determined for at least one selected point in the heart cycle, using electrocardiographical data. The direction of the electric current dipole vector (ECD vector) of the heart is determined for at least the same at least one selected point in the heart cycle, using magnetocardiographical data. The angle between the direction of the EMF vector and the ECD vector at the selected point in the heart cycle is then determined, the angle representing a measurement for the myocardial anisotropy of the heart of the examined patient. It has been shown that the angle determined for patients with coronary artery disease (CAD) lies in a completely different angle zone to the angle determined for healthy patients.

Description

Method for determining a diagnostically relevant parameter from electrocardiographic and magnetocardiographic data of a patient

Technical field of the invention

The invention relates to a method for determining a diagnostically relevant parameter from electrocardiographic and magnetocardiographic data of a patient. In particular, the application relates to a method by means of which a diagnostically relevant parameter can be determined, which is suitable as a measure for the deviation of the myocardial conductivity of the examined patient from the normal state and which makes it possible to identify heart diseases which are associated with conductivity disorders.

Background of the Invention

Many phenomena in human electrophysiology are accompanied by electrical currents. In particular, the electrical activity of the heart muscle is associated with a flow of charged ions. These ionic currents across the myocardial cells are caused by an impressed current density that generates both electrical and magnetic fields around the human thorax (see, e.g., J. Malmivuo and R. Plonsey, Bioelectromagenism: Principles and Application of Bioelectric and Biomagnetic Fields. - Oxford University Press: NY,

Oxford, 1994).

Today, electrocardiography (EGG), i.e. measurement of electrical potentials from the heart, an important role in clinical diagnosis and cardiac research. Clinical ECG procedures, such as B. the standard twelve-wire

System and the Frank Vector ECG use an equivalent electrical dipole as a model of the cardiac electrical source. This dipole is actually the vector of the electromotive force (EMF), ie the electrical potential caused by the current impressed. The EMF is also called the electrical heart vector (EHV) and generates ohmic volume flows throughout the body. This ohmic Currents into the heart depend on the myocardial conductivity (see, for example, J. Nenonen, J. Motonen, M. Makijarvi: Principles of Magnetocardiographic Mapping. In: Cardiac Mapping. Ed .: Shenasa et al.)

The first evidence of the heart's magnetic field, i.e. on

Magnetocardiogram (MCG) was reported in 1963 (see Baule G. McFee R., Detection of the Magnetic Field of the Heart. - Am. Heart J. - 55. - 1963 - p. 95 - 98). However, the precise determination of small biomagnetic signals only became possible after the development of the superconducting quantum interferometer in the early 1970s. Although the MCG procedure has not yet established itself as a routine clinical procedure, many successful results have been reported (Sutanen P .: Magnetocardiography. In: Comprehensive Electrocardiology - Ed .: MacFarlane P., Lawrie T. - Oxford: Pergamon Press, 1988, Ch 38).

The MCG process uses an equivalent magnetic dipole, which is also magnetic

Cardiac vector (MHV), and an equivalent current dipole (ECD) related, which is the vector of the said impressed current. If the ECD is embedded in an infinite homogeneous line medium, a magnetic field is missing. In the real case, MCG and ECG are not completely independent. The MCG has a complementary nature to the ECG, since the MCG is only sensitive to the tangential components of the ECD. On the other hand, the ECG is sensitive to both the radial and the tangential ECD components, and the latter component is delayed by a large electrical resistance of the surrounding lung tissue (Stroink G., Moshade W., Achenbach S .: Cardiomagnetism. In: Magnetism in Medicine - Andra W., Nowak H., Eds.- Berlin: Wiley VCH - 1998, p. 136 - 189).

The myocardium is known to have many types of anisotropy. The first reason is the difference between the transverse and longitudinal conductivity of the heart cell.

Another type of anisotropy is caused by the spiral nature of the heart muscle fibers. These types of anisotropy change from one normal subject to another. However, many types of anisotropy are determined by an anisotropy of conductivity.

The conductivity anisotropy changes in healthy people, but also changes to a sufficient extent due to cardiac disorders.

In any case, the aim of the ECG and MCG methods is to solve the so-called "inverse problem" (see, for example, B. Hailer et al .: The application of biomagnetism in cardiology. In: Praktische Kardiologie, Vol. 15, 1995 , Pp. 90 - 103, the content of which is hereby incorporated into the revelation by quoting). For this purpose one needs knowledge about the non-homogeneity and the anisotropy of the conductivity of the thorax, the human body parts and their forms. Realistic forms of each patient are usually obtained from magnetic resonance image data and numerically determined using the boundary element method. However, the procedures are complex and time consuming and the exact conductivity is unknown. Therefore, exactly solving the inverse problem is a very difficult question for both the ECG and MCG processes (see e.g. BM Makijarvi, J. Motonen, J. Nenonen: Clinical Application of Magnetocardiographic Mapping. In: Cardiac Mapping. Eds .: Shenasa et al.)

In order to verify the procedures for the inverse problem, solving the number of numerical simulations and model experiments were carried out with realistic phantoms. In this connection it was shown that the ECG signal is not sensitive to the anisotropy of the myocardial conductivity. In contrast, the MCG is influenced by the anisotropy mentioned.

The above results indicate that myocardial anisotropy cannot be recognized by an ECG alone.

In this sense, it is necessary to combine ECG data with MCG data. The angle between EHV and MHV in the QRS tip was shown to be very close to 90 °. It should be noted that if the angle was exactly 90 °, there would be no new information in the MCG compared to the ECG. However, it has been found that this angle varies markedly during the QRS complex, both from patient to patient (Nousiainen J., Lekkala J., Malmivuo J .: Comparative Study of the Normal Vector MCG and Vector ECG. J. Electrocardiol., 1986, 19 (3), 275 - 290) as well as in various cardiac disorders (Nousiainen J .: Behavior of the Vector MCG in Normal Subjects and in some Abnormal Cases. Tampere Univ. Tech., Tampere, Finland, Dr. Tech. Thesis, 1991, pp. 177).

Even more, the combination of ECG and MCG leads to an improvement in the sensitivity of both methods compared to their separate use. The classification of the five patient groups was shown to improve from 73.7% to 81.4%.

The above results show that the angle between MHV and EHV contains new information about myocardial conductivity. However, there were no significant improvements in the above approach. In other words, no longer testifies about conductivity, including the question of

Anisotropy. This is the reason why the MHV is not the correct index for the MCG, since only the multipole extension of the cardiac generator has a physiological sense (see e.g. Geselowitz D .: Multipol Representation for an Equivalent Cardiac Generator. Proc. IRE, 48, 75 - 79). According to this expansion, the cardiac generator is the sum of the equivalent current generators (dipole, quadrupole, octupol etc., where ECD is the equivalent generator of the lowest order).

A more complicated and therefore more realistic approach is to use a large number of individual ECDs (in a limited current level) instead of a single ECD. In addition, the equivalent magnetic dipole (EMD) should be included in the calculation. The reason for this is that each vector field can be broken down into a vortex and a flow part. The current generators mentioned in the previous paragraph reflect the "flow" currents, i.e. the currents which have thresholds and sinks. Closed or eddy currents are modeled by an equivalent magnetic multipole. The named EMD is the equivalent lowest order magnetic generator. The fundamental difference between ECG and MCG is that the former is insensitive to eddy currents, i.e. magnetic generators. It was shown that the ECG did not change after the stress test (the heart rate increased from 60 to 140 beats per minute) for the repolarization phase. In contrast, that shows MCG changes dramatically and the EMD changes its own value and direction.

Therefore, on the other hand, EMD is very sensitive to non-pathological changes in the human heart. This is the reason why it cannot be used to demonstrate myocardial conductivity, particularly the anisotropy caused by heart disease.

Therefore, there is a need for further research into diagnostically meaningful parameters ("heart indices") that allow the determination of anisotropies of the myocardial conductivity. This is the reason why the problem of developing a new method that has good sensitivity and specificity with regard to the various heart diseases accompanied by anisotropy changes is very topical today. The present invention fulfills the need for such a method and has corresponding advantages.

In this invention, a new method for determining the anisotropy of myocardial conductivity takes into account that the ECG cannot recognize the myocardial anisotropy - that the MCG is affected by the myocardial anisotropy, that the angle between ECG and MCG data is due to of

Heart disease varies that the combination of ECG and MCG the sensitivity of both procedures in the

Improved compared to their separate use, - that the ECD is preferred over the MHV as a model of the cardiac generator. The ECD vector is used as a model for the MCG and the EMF vector is used to interpret the ECG data. The combination of ECG and MCG should increase the sensitivity of the method mentioned.

The essence of the method offered is that the direction of the EMF

Vector is insensitive to additional changes in conductivity anisotropy caused by heart disease. In contrast, the ECD vector changes its direction significantly. That is why the degree of anisotropy is reflected by the angle between the ECD vector and the EMF vector. The present invention is devoted to developing a new method that has a number of advantages compared to conventional patterns. In particular, the proposed method distinguishes the group of normal subjects and the group of patients with coronary artery disease (CAD). This result allows the CAD patient identification procedure to be used.

Summary of the invention

The present invention provides a new method of processing human heart data obtained during clinical studies

Available. This processing enables the degree of anisotropy of the myocardium caused by the conductivity anisotropy to be determined. In the method offered, the degree of anisotropy is characterized by an angle γ between the direction (α) of a vector of the electromotive force (EMF) and the direction (β) of a simultaneous electrical current dipole vector (ECD) in the heart. In order to obtain the mentioned angle, the electrocardiographic (ECG) data are combined with the magnetocardiographic (MCG) data.

The method for obtaining an anisotropy angle is based on the following

Steps. First, a time sequence of the measured ECG signal of the human heart is measured. The time sequence of the electrical signals is filtered and then averaged with the time interval equivalent to a cardio cycle. In this way, both environmental external disturbances and non-correlated internal noise were greatly reduced. Then the direction of the EMF vector with

Calculated using the standard ECG procedure at every point in the cardio cycle.

Second, according to the present invention, a time sequence of the measured MCG signal of the human heart is measured. The magnetic signal is then filtered and also averaged. A time sequence of the two-dimensional magnetic field distribution maps is then formed (so-called magnetic field mapping - see, for example, the explanations in Wilfried Andrä, Hannes Nowak (ed.): Magnetism in Medicine. Berlin: WILEY-VCH, 1998, the content of which is hereby fully understood Quotation is used for revelation). The direction of the ECD vector at each point in time is determined using the method of magnetic Moments based solution of the inverse problem is calculated. The method of magnetic moments is described, for example, in WO 01/20477 A2, the content of which is hereby incorporated into the disclosure by citation, and in Romanovych: Supercurrents: Forward and Inverse Problems. In: Proc. 6th Conf. Superconductive electronics. Berlin, 1997, pages 344 - 346, the content of which is hereby quoted as

Revelation is consulted, as well as Romanovych: Reconconstruction of Three-Component Dipoles within Layer. In: Biomedical Technology, Volume 42, Supplement 1, 1997, pages 227 - 230, the content of which is hereby incorporated into the disclosure by quoting). Thirdly, the direction of the ECD vector is subtracted from the direction of the EMF vector for the same times in each case by one

Obtain anisotropy reflecting angles.

The presented method according to the invention is intended for the medical diagnosis of heart diseases. In particular, the method is intended to diagnose such heart diseases associated with various myocardial disorders

Conductivity occur.

The present invention provides a new method for identifying coronary artery disease (CAD) by detecting the following steps. First the R-tip and the T-tip of the cardio cycle are selected. Second, the anisotropy angles are determined at selected locations for CAD patients. Thirdly, the angles mentioned are compared with those of normal subjects at the same peaks.

According to the invention, the determination of the anisotropy angle for CAD

Patient the following three steps. The first step is to determine the EMF vector direction in the R and T peaks. The second step is to determine the ECD vector direction in the same peaks. The third step is to obtain the anisotropy angle in the selected peaks by subtracting the direction of the ECD vector from that of the EMF vector.

An important aspect of the invention is that the method is intended to process data measured by the single-channel magnetocardiograph installed in medical clinics and the vector electrocardiograph. In particular, the proposed method is aimed at diagnostic To use apparatus placed in an unshielded environment in the urban area.

Other features and advantages of the invention will be apparent from the following detailed description of the preferred embodiment, together with the accompanying drawings, the description of which exemplifies the principles of the invention.

Brief description of the drawings

The present invention will now be described with reference to a preferred embodiment of the invention, which is illustrated by way of non-limiting example and with reference to the figures of the accompanying drawings, in which:

1 shows the mean ± standard deviation values (SE) of the anisotropy angle γ in the R peak; and FIG. 2 shows the mean ± SE values of the anisotropy angle γ in the T-tip.

The angles for the group of CAD patients (CAD) and for the group of normal subjects (NORM) are each marked with gray or black color.

Detailed description of the preferred embodiment

In the currently preferred embodiment for measuring electrical cardiac signals, the vector ECG (company, model) and the standard method for determining the direction of the EMF vector in the frontal plane in the R and T tips are used (see, for example - .. the information on the above procedure). The single-channel magnetocardiograph (model MCG-1, manufacturer SQUID AG, Essen, Germany) is used to measure the magnetic heart signal in a non-shielded environment in medical clinics. The device mentioned allows

Registration of the vertical magnetic field gradient component d ² B / dz ² and a reference electrocardiogram. The signals are continuously sampled at a discretization frequency of 500 Hz for a period of 30 seconds. A software was developed to process the signals, which allows the scanning, filtering, artifact removal and averaging (for details see European patent - ... our patent). The software allows the reconstruction of magnetic field distribution maps and the determination of the ECD vector based on the solution of the inverse problem (Romanovich S., Sosnitsky V., Voytovich I .: Investigation of Biomagnetic Field Using 2D Model of Secondary Sources // Proc. 9 Int Conf.Biomagnetism, Vienna (Austria) - 1996. - p. 455 - 456).

In accordance with the invention, one method of demonstrating myocardial conductivity presented is based on the finding that the degree of manifestation of myocardial anisotropy is indicated by an angle γ between a direction (α) of an EMF vector and the direction (β) of a simultaneous ECD

Vector is characterized in the human heart. Then the isotropic l ₀ and anisotropic ^ components of the ECD vector J result

l ₀ = Jcos γ, lχ = Jsin γ, tan γ = S _x / S ₀ (1)

where SJ ^ S _{Q are} the transverse and axial components of myocardial conductivity. Therefore, the above angle reflecting the myocardial anisotropy is searched far from the expression

γ = α - ß (2).

In the present embodiment of the invention, the time sequences of the measured ECG and MCG signals from the human heart were measured. These time sequences were filtered and averaged to improve the signal-to-noise ratio. Then the directions of the EMF and ECD vectors were calculated.

After that, the value of an angle reflecting the myocardial anisotropy was obtained according to Expression (2). We examined 63 patients with coronary artery disease (CAD) with and without previous myocardial infarction and 35 healthy volunteers. In the ECG and MCG, the R and T peaks were selected in the cardio cycle.

The essence of the invention is clearly expressed with the aid of the figures. It can be seen from FIG. 1 that the anisotropy angle γ in the R peak is in a range of 20.8 ° ± 3.3 ° (mean ± standard error (SE)) for healthy volunteers and is within a range of 61.7 ° + 17.2 ° for CAD patients. Figure 2 shows that during the T-wave the angle is in the range of 18 ° + 5.3 ° for healthy people and in the range of 45.5 ° + 13.5 ° for CAD patients. Both figures clearly show that the anisotropy angles are significantly different for both groups. In addition, Student's t-test analysis shows that both groups differ with one

Significance level p <0.05 for the R peak with p <0.1 for the T wave.

To understand the method, it should be noted that the angle γ of anatomical peculiarities of the human heart depends on one person to another. It also varies due to myocardial disorders

Conductivity. This is the reason why the present invention offers a method for diagnosing heart diseases caused by pathological changes in the myocardial structure in the human heart.

In the preferred approach, the essential feature involves the use of a

Combination of ECG and MCG data. When considered individually, ECG or MCG data do not in principle give the quantity of information that is necessary to determine the degree of anisotropy in the human heart. Only ECG data combined with MCG data can solve the problem of anisotropy in myocardial conductivity. The reason for this is that the ECG and the MCG provide mutually complementary information about the electrical heart generator. This is the reason why the summarized data of the electric and magnetic fields generated by the human heart give the complete information about the electrophysiological process in the myocardium.

The most important advantageous result of the present invention is that the preferred approach can potentially be used to identify CAD. It is confirmed by the high level of specificity and sensitivity. In the present embodiment, the specificity and sensitivity are 85% and 93%, respectively. The results of the particular embodiment indicate that the angle of the

Anisotropy in CAD patients increases compared to healthy volunteers. The increase mentioned is greater for the R peak (approximately three times) than for the T wave (approximately twice). In accordance with the invention, the increase in CAD is explained by the decrease in the axial component of the myocardial conductivity due to the existence of ischemic zones with lower conductivity.

Another advantage of the approach presented is that it can be used in simple medical (cardiological) clinics that are only simple

ECG and MCG techniques are equipped. The ECG equipment must include a vector ECG apparatus with the standard software for determining the direction of the EMF vector. The above-mentioned MCG technique must include the least expensive one-channel magnetocardiograph that operates in the unshielded environment at the high level of urban magnetic interference and appropriate software that allows the direction of the ECD vector to be determined.

It can be seen that the method presented in this invention represents a significant advance in the field of non-invasive diagnosis of conductivity anisotropy in the human heart. The approach offered takes one into account

Change of anisotropy angle due to physiological variances as well as pathological disturbances of myocardial conductivity. The particular embodiment shows the possibility of using the anisotropy angle as a diagnostic criterion for identifying the CAD.

Although the R and T peaks of the cardio cycle are used in the particular embodiment of the invention, the invention is not so limited. The processing procedure for determining the degree of anisotropy can be complicated. For example, the calculation of the anisotropy angle can be carried out for every point in the cardio cycle.

Although in the preferred embodiment of the invention the method is used only to identify the CAD, the invention is not so limited. The heart disease to be diagnosed can be other than CAD. The necessary condition is essentially that the disease mentioned should have disorders of myocardial conductivity, which lead to a change in the degree of anisotropy.

While in the preferred embodiment the magnetocardiograph consists of low-temperature superconductors and is close to the absolute zero in liquid Helium works, the invention is not limited to this. The magnetocardiograph can be a high temperature magnetocardiograph and operated near or above 77 ° K. In addition, the magnetocardiograph can be a multi-channel magnetocardiograph with suppression of environmental noise, and can be located in a magnetic and / or radio frequency chamber. In the end, the magnetocardiograph need not necessarily be superconducting, but rather can work on the basis of some principles. The essential necessary condition is that the magnetocardiograph allows the measurement of the magnetic field in a grid that is placed in the frontal plane above the heart.

Specific embodiments of the invention have been described in detail for purposes of illustration. It is clear that in practice deviations and modifications in the arrangement and in details can be made by a person skilled in the art. In particular, the described invention implies a new one

Business processes, namely the economically interesting sale of automatically generated analyzes of electrocardiographic and magnetocardiographic data. This process is hereby expressly designated as part of the invention and is claimed to be protectable in those countries whose national law permits.

Industrial applicability

The method according to the invention makes it possible to create a working basis for the diagnostic activity of the doctor or

Claims

claims

1. A method for determining a diagnostically relevant parameter from electrocardiographic and magnetocardiographic data of a patient, with the following steps:

Acquisition of electrocardiographic data of the patient and determination of the direction of the electromotive force vector (EMF vector) of the heart of the patient from the acquired electrocardiographic data in at least one selected point in time of the cardio cycle, acquisition of magnetocardiographic data of the patient and determination of the

Direction of the electrical current dipole vector (ECD vector) of the heart of the patient from the acquired magnetocardiographic data at least in the same at least one selected point in time of the cardio cycle,

Determine the angle between the direction of the EMF vector and the ECD vector at the same selected point in time of the cardio cycle.

2. The method according to claim 1, characterized in that determining the direction of the EMF vector comprises the steps:

Collecting and averaging a time sequence of ECG data, - Calculating the direction of the EMF vector at selected times with

Using the standard vector ECG procedure.

3. The method according to claim 1 or 2, characterized in that determining the direction of the ECD vector comprises the following steps: collecting and averaging a time sequence of MCG data,

Calculate the direction of the ECD vector at selected times using the solution of the inverse problem.

4. The method according to any one of claims 1 to 3, characterized in that the direction of the EMF vector and the direction of the ECD vector at the time of

R peak and / or T peak of the cardio cycle are determined and the angle between the EMF and the ECD vectors is determined at the respective times.

5. The method according to any one of claims 1 to 4, characterized in that the determined angle between the compared EMF and ECD vectors compared automatically with reference angles stored in a database and is classified into one of at least two categories based on this comparison.

6. The method according to claim 5, characterized in that the result of the comparison is automatically stored in a self-learning database.

7. The method according to claim 5 or 6, characterized in that when classifying the angle in a corresponding to a non-normal state

An alarm marker is automatically set in the category and assigned to the data of the patient being examined so that when the patient's data is further processed or processed, a clear indication of the classification in the category mentioned is automatically triggered.

8. The method according to any one of claims 1 to 6, characterized in that the determined angle is displayed on a graphic output unit.

9. Computer-readable memory containing the commands required for the automatic implementation of a method according to one of claims 1 to 8.

10. A method for enabling the sale of analyzes of electrocardiographic and magnetocardiographic data comprising performing a method according to one of claims 1 to 8.