WO2006111497A2

WO2006111497A2 - Method and device for the non-invasive analysis of a biological tissue of a mammal, especially a human

Info

Publication number: WO2006111497A2
Application number: PCT/EP2006/061573
Authority: WO
Inventors: Martin Hoheisel; Bernhard Scholz; Christoph BÖHME; Klaus Lips
Original assignee: Siemens Aktiengesellschaft; Hahn-Meitner-Institut Berlin
Priority date: 2005-04-18
Filing date: 2006-04-13
Publication date: 2006-10-26
Also published as: DE102005017818A1; WO2006111497A3

Abstract

The invention relates to a method and a device for the non-invasive analysis of a biological tissue (1, 2, 12, 14, 15) of a mammal, especially a human, whereby the conductivity of the tissue (1, 2, 12, 14, 15) is determined. The aim of the invention is to increase the precision and reliability of the analysis. To this end, a permutation symmetry imbalance is generated in the tissue (1, 2, 12, 14, 15) by a magnetic field (4), the permutation symmetry imbalance is locally modified by irradiating a magnetic alternating field (10), and the consequent modifications in the conductivity are determined.

Description

description

Method and device for the non-invasive examination of a biological tissue of a mammal, in particular of a human

The invention relates to a method and a device for the non-invasive examination of a biological tissue of a mammal, in particular of a human.

From mamma diagnostics, a method is known in which, based on measurements of the conductivity, lesions in a tissue can be detected. In the known method, z. Measured as a Trans Scan TS2000 speed values of the Trans Scan Medical, Ltd., Migdal Ha'emek, Israel, Conductive ^¬. Based on the conductivity values is with a, z. B. Bernhard Scholz, "Towards Virtual Electrical Breast Biopsy: Space-Frequency MUSIC for Trans-Admittance ^Data ", IEEE Transactions on Medical Imaging, 21, pp. 588-595, 2002, discloses an algorithm that determines whether the tissue lesions having. A disadvantage of this method is that the lesions can not be reliably and reliably detected. The method is not suitable as an independent diagnostic method.

As by Sato et. al. In "Imaging of Electromagnetic Detection (EDMR) of a Silicon Wafer" in Journal of Magnetic Resonance 153, pages 113 to 116, 2001, defects in silicon materials can be detected electrically with conventional electron spin resonance devices. However, conventional electron spin resonance devices are not suited to the internal structure of biological tissue, in particular ^¬ sondere of parts or organs of the human body to investigate.

DE 101 47 460 A1 discloses a method and a device for measuring time-resolved spin-dependent recombination processes in organic and inorganic semiconductor processes. known samples. In the known method, a transit is siente the Leitfähigeit, photoconductivity or Photolumi ^¬ neszenz the semiconductor sample by EDMR determined. The ^method is carried out in a cryostat at temperatures in the range between 5 K and 100 K.

The object of the invention is to eliminate the disadvantages of the prior art. In particular, a method and a device are to be specified with which the internal structure of a biological tissue of a mammal, in particular of a human, can be examined accurately and reliably. Furthermore, a method and a device for non-invasive examination of the tissue are to be specified, with which the most reliable diagnoses can be created.

This object is solved by the features of claims 1, 11, 12 and 21. Advantageous embodiments of the invention will become apparent from the claims 2 to 10 and 13 to 20.

According to the invention, a method is provided with the following steps:

a) generating a permutation symmetry imbalance in the tissue by means of a magnetic field,

b) determining the conductivity of the tissue or a corresponding physical quantity by means of electrodes attached to the tissue,

c) irradiation of an alternating magnetic field for changing the permutation ^symmetry imbalance in a given location in the tissue and

d) spatially resolved determination of a magnetic

Alternating field caused change in the conductivity or the corresponding physical size. The term "irradiation" is understood in particular to mean continuous and / or pulsed irradiation.

As described by Böhme and Lips in "Theory of the time-domain measurement of spin-dependent recombination with pulsed electrically detected magnetic resonance" in Physical Review B 65, 245105, 2003, there is a population asymmetry of coupled spin pairs, such as As nuclear spin / electron spin or electron spin / electron spin pairs, an imbalance between groups of spin pairs with different permutation symmetries. This imbalance is referred to herein by the term "permutation symmetry imbalance".

The magnetic field can act on the spins from the outside as well as be caused by the local fields of the spins themselves or of the tissue.

The corresponding to the conductivity physical quantity, for example, the current, the resistance of the specifi ^¬ specific resistance, the specific conductivity, impedance, or the like. be. The conductivity and the corresponding physical quantities are also referred to below as measured variables. The measured variables are characteristic for the tissue and depend in particular on the internal structure of the tissue. Both the measured quantities, z. As the current, as well as their changes can be determined particularly easily and with high accuracy with the electrodes attached to the tissue. In particular, small changes can be determined reliably and safely. By the Permutationssymmetrie- is imbalance changed in a predetermined location in the tissue, it is possible that changes in a spatially resolved to ermit ^¬ stuffs. With the proposed method, the internal structure of the tissue can be examined accurately and reliably and a reliable diagnosis can be made.

For the purposes of the present invention, the term "biological tissue" is understood to mean such biological tissue, in which changes of a permutation symmetry imbalance are electronically detectable. These may be tissue, in particular biological, in particular of mammals, in particular of humans. It is also possible that the tissue is a part or organ of an organism, in particular of a mammal, in particular of man. In the Un ^¬ tersuchung a portion or the entire fabric may, in particular ^¬ sondere a surface layer or the interior of the tissue to be examined.

According to one embodiment of the invention, a gradient field is used as the magnetic field. A change of the permutation symmetry imbalance occurs when one of the Resonanzbe ^¬ is irradiated dingung sufficient alternating field. The resonance condition is z. B. fulfilled when the frequency of the alternating field corresponds to the Larmor frequency of the electrons in the magnetic field. For a gradient field, the resonance condition is a function of the location in the tissue. By knowing the strength of the gradient field and the gradient strength, an alternating field satisfying the known resonance condition at a predetermined location can be radiated. The spatially resolved ^¬ He mediation of the change of the measured variable can be simplified.

To generate the magnetic field or the gradient field and the alternating field, magnetic coils and / or permanent ^magazines can be used. The alternating field is preferably generated with ^¬ means of solenoids. The alternating field may be ^¬ be irradiated such that it acts on the whole tissue. But it is also possible to irradiate the alternating field only to a predetermined area located in the tissue. The location of the area can be used as additional location information to improve the spatial resolution of the method.

According to one embodiment of the invention in step lit. b) ER- conductivity or corresponding thereto physika ^¬ metallic size with a plurality of electrodes and at least one counter electrode having electrode array averages. The electrode and the counter electrode may be mounted on un ^¬ terschiedlichen sides of the fabric. It is also possible to surround the counterelectrode circumferentially around the tissue or on a body connected to the tissue. By using an electrode array is to determine mög ^¬ Lich the measured variable depending on the position of the tissue be ^¬ attached electrodes. The position can be used as additional location information for the tissue-generated changes detected with an electrode. All electrodes can be used simultaneously, a given group of electrodes or individual electrodes.

According to one embodiment of the invention, the conductivity or corresponding thereto physi ^¬'s size is used to determine lit in step. b) measured at the electrodes anlie ^¬ ing DC voltage or flowing in the tissue direct current. With a DC or DC can caused by the alternating field changes of static electrical variables such. B. the conductivity or the ohmic resistance can be determined.

According to a further embodiment of the invention, to determine the conductivity or the corresponding size in step lit. b) measured an alternating voltage applied to the electrodes or an alternating current flowing in the tissue. With the AC voltage or AC, changes in dynamic electrical variables, such. As the impedance can be detected. The changes in the dynamic electrical quantities may depend on capacitive and / or inductive properties of the tissue and / or on the frequency of the AC voltage or AC current. The capacitive and / or inductive properties or the dependence on the frequency can be used to investigate the internal structure of the tissue. Preferably, two distinct AC ^¬ or alternating current frequencies are used at least. It is also possible to use DC or DC and AC To use voltage or an alternating current. For the examination of the tissue, the changes of the static and / or the dynamic quantities and / or the frequency dependence can be combined. The inner structure of the tissue can be examined very carefully.

According to a further embodiment of the invention, a spatially resolved representation of the changes or a value derived therefrom can be automatically generated from the determined changes. The spatially resolved representation can be a one- or three-dimensional representation. The representation may be a grayscale or false color representation. The two-dimensional representation can contain one or more cut or projection images. The spatially resolved representation can be used to create a diagnosis. The derived value may be a diagnostic parameter selected from the following group: density, electrolyte content, homogeneity, concentration and / or composition of the electrolytes, composition of the tissue.

According to a further embodiment of the invention is for performing at least one of the steps lit. a) to d) and / or used to generate the representation of a computer. By using a computer, the performance of the method can be automated and simplified for the user. Furthermore, the reliability and accuracy of the method z. By avoiding mistakes of the user.

According to another aspect of the invention, a device for non-invasive examination of a biological tissue of a mammal, in particular a human, provided with

a) a first magnetic field means for generating a permutation imbalance imbalance in the tissue by means of a magnetic field, b) a an electrode array having a plurality of electric ^¬ and at least one counter electrode having measuring ^¬ means for determining the conductivity of the tissue or corresponding thereto physical quantity by means of the mounted on the tissue electrode and counter electrode ^¬ de,

c) a second magnetic field means for generating a Än ^¬ for the Permutationssymmetrieungleichgewichts countries appropriate alternating magnetic field, and

d) an evaluation unit for the spatially resolved determination of at least the tissue change caused ness by the alternating magnetic field in a portion ^¬ range of conductivity or corresponding thereto large physical ^¬ SSE.

The advantages of the device according to the invention result from the advantages of the method according to the invention.

The method according to the invention and the invention Before ^¬ direction in greater detail below with reference to examples he explained ^¬. Show it:

1 shows schematically an arrangement for carrying out the method,

Fig. 2 shows schematically the position of magnetic coils in the An ^¬ order of Fig. 1 and

Fig. 3 shows schematically another arrangement for carrying out the method in a mammal examination on the human body.

In FIGS. 1 to 3, unless otherwise stated, the same or similar features are designated by the same reference numerals. Fig. 1 shows schematically an arrangement for carrying out the method. An object 1 with an internal inhomogeneity 2, z. B. a density inhomogeneity is between two first Mag ^¬ netspulen 3 for generating a magnetic field 4 is arranged. On the object 1 is an electrode array 5 with a plurality of

Electrodes 6 attached. Opposite the electrode array 5, a counter electrode array 7 with a plurality of Ge ^¬ gene electrodes 8 is attached. Between the electrodes 6 and the counter electrode 8, an electric current flows 9. A perpendicular to the magnetic field 4 on the object 1 irradiated magne ^¬ diagram alternating field is denoted by the reference numeral 10 degrees. A predetermined location in the object 1 is designated by the reference symbol X.

Fig. 2 shows schematically the position of magnetic coils in the

Arrangement of FIG. 1. The object 1 with an internal inhomogeneity 2 is arranged between the two first magnetic coils 3. A second magnetic coil for generating the alternating magnetic field 10 is designated by the reference numeral 11.

The procedure is carried out as follows:

In a first step, a permutation symmetry imbalance is generated in the object 1 with the magnetic field 4 generated by the first magnetic coils 3.

In a second step, the conductivity of the object 1 is determined by means of the electrodes 6 and counterelectrodes 8 with a measuring means, not shown. The object 1 is z. B. to a biological tissue, ^{insbesonde ¬} re human tissue such. B. an organ. In the Elek ^¬ trodenarray 5 and counter electrode array 7 may be z. B. an elastic material with embedded gleichmä ^¬ larly spaced apart electrodes 6 and Gegenelektro- the 8 act. To determine the conductivity is at the

Electrodes 6 and counter electrodes 8, a voltage applied and a flowing through the object 1 current 9 measured. Instead of the electrode array 5 and / or counter electrode arrays 7 can Also, a single electrode 6 and / or counter electrode 8 ver ^¬ applies.

In a third step, an alternating magnetic field 10 is irradiated onto the object 1. The alternating magnetic field 10 influences the orientation of the spins. The orientation as ^¬ derum affects the probability of transition of electrons between different states, and thus the conductivity of the object 1. The alternating magnetic field 10 is irradiated on the object 1, that the alternating field

10 or at least a component thereof perpendicular to the magnetic ^¬ field 4. Further, the frequency of the alternating field 10 satisfies the resonance condition at the predetermined location X. The resonance condition is satisfied when the frequency of the alternating field 10 corresponds to the Larmor frequency of the electrons.

In a fourth step, a change in conductivity caused by the alternating field 10 is shown with a non-ge ^¬ detected with the electrodes 6 and counter electrode 8 verbunde- NEN evaluation. As location information for the change ^¬ tion, the location X, where the resonance condition is met and the position of the attached to the object 1 electrodes 6 and counter electrodes 8, used. To determine the changes, all the electrodes 6 or counterelectrodes 8 can be used simultaneously. However, it is also possible to use individual electrodes 6 or counterelectrodes 8. In order to further improve the accuracy of the examination, the changes for different arrangements of the Elektrodenar- rays 5, counter electrode arrays 7, the first magnetic coils 3 and the second magnetic coil 11 can be determined. This is special then to ^¬ advantageous if the object 1 or its nere in ^¬ structure is anisotropic. Finally, from the determined changes, a spatially resolved representation of a diagnostic parameter associated with the change can be created. The diagnostic parameter can be, for example, the

Density, the electrolyte content, the homogeneity, the Konzentra ^¬ tion and / or composition of the electrolyte, the composition of the fabric or the like. be. The voltage may be a DC voltage and / or an AC voltage. The current 9 may be a direct current and / or an alternating current. With a DC voltage or a direct current can be detected by the alternating field 10 caused Ände ^¬ approximations of static electrical values. The static electrical variables can z. As the current 9, the ohmic resistance, the conductivity, the corresponding specific sizes or the like. be. With an alternating voltage or an alternating current, changes in dynamic electrical variables caused by the alternating field 10 can be taken into account. The dynamic electrical variables, such. As the impedance, may be dependent on the capacitive and inductive properties of the object 1. It is possible to determine both the changes in static and dynamic electrical quantities. Thus, the internal structure of the object 1 associated with the changes can be examined even more precisely. The accuracy of the investi ^¬ investigations may be determined to further increase the changes for different voltage values. Furthermore, it is possible to determine the changes for different AC voltage or AC frequencies.

The position of the second magnetic coil 11 can be used as location information for spatially resolved determination of the changes. It is also possible that a Gra ^¬ dientenfeld is used as the magnetic field 4. By using a gradient ^¬ field, the resonance condition changed in the direction of the gradient. The resonance condition is consequently dependent on the location X in the object 1. By irradiating an alternating field 10 with a frequency corresponding to the resonance condition at the predetermined location X, the permutation symmetry imbalance at location X can be changed. The gradient field itself therefore indirectly contains location information that can be used to determine the changes in a spatially resolved manner.

The strength of the magnetic field 4 can be constant. To satisfy the resonance condition, the frequency of the alternating field 10 becomes changed. But it is also possible that the frequency of the alternating field 10 is changed constantly and the strength of the magnetic field 4.

Fig. 3 shows schematically the implementation of the method in a mammal examination on the human body. For examining a female breast 12, a magnetic field 4 is generated with first magnetic coils 3. Perpendicular to the magnetic field 4, an alternating field 10 is irradiated. The alternating field 10 causes a change in the permutation symmetry imbalance in a predetermined location X in the breast 12. With a hand-held scanner 13, a current 9 flowing through the breast 12 is measured by means of a plurality of electrodes 6 resting against the breast 12. A mammary carcinoma surrounded by healthy tissue 14 in the breast 12 is indicated by the reference numeral

15 denotes. 3 for reasons of clarity only a second coil 3 and only the electrodes 6, but not depending ^¬ counter electrode 8 shown in Fig.. A predetermined location lying in the chest 12 is designated by the reference symbol X.

The investigation is carried out as follows:

In a first step, a magnetic field 4 acting in the region of the breast 12 is generated with the first magnetic coils 3.

The magnetic field 4 generates a permutation symmetry imbalance.

In a second step, a current 9 flowing through the breast 12 is determined with the hand-held scanner 13 as a function of the position of the electrodes 6 on the breast 12.

In a third step, the alternating field 10 fulfilling the resonance condition in the location X is radiated onto the breast 12. This changes the permutation symmetry imbalance in location X. In a fourth step, the change in the current 9 caused by the change in the permutation symmetry imbalance is measured with the hand-held scanner 13 and the change in the conductivity is determined. To further determine the location X, the location of the electrodes 6 on the breast 12, at which a change in the current 9 is detected, may be used as additional location information. In order for the amendments ^¬ stakes in X as possible can be accurately detected, as described above, an alternating current used. Furthermore kön- nen different voltage values and Wechselstromfrequen ^¬ zen be used.

The tissue structure of mammary carcinoma 15 differs from that of healthy tissue 14. Because of the different tissue structures, the changes detected in mammary carcinoma 15 differ from those of healthy tissue 14. Based on these differences, mammary carcinoma 15 can be safely and reliably identified in healthy tissue 14 and localized.

In a fifth step, a spatially resolved representation of a diagnostic parameter of the breast 12 can be determined automatically.

The counter electrode 8 may be disposed 6 of the hand scanner 13 similar to FIG. 1 gegenüberlie ^¬ quietly the electrodes. It is also possible that a counter-electrode 8 is attached to a belie ^¬ bigen site on the human body. For example, an annular counter electrode surrounding the breast 12 or a counter electrode to be held in the patient's hand can be used.

Instead of the electrodes 6 attached to the hand-held scanner 13, it is also possible to use a single electrode 6. As an additional information about the location X changes while the position of the electrode 6 can be applied to the breast 12 ^¬ used to. Information about the place X can also be taken from the place X dependent resonance condition when using a gradient field are determined.

In carrying out the method described with reference to FIGS. 1 to 3, steps lit. a) to d) carried out in succession. However, it is also possible to change the order. For example, the steps lit. a) and b) are reversed. Further, in performing the method, a computer may be used in all steps. The computer can on the one hand, the setting of the voltage, the AC voltage, the field strength of the magnetic field 4, the gradient strength of the gradient field, the frequency of the alternating field 10 or the like. take. On the other hand, the computer can be used to determine the changes and automatically generate the display of the diagnostic parameter. With a computer, the process can be carried out particularly quickly and efficiently. In particular, the through ^¬ out the method for a user to facilitate, and are largely however, avoids the user error caused.

A device suitable for carrying out the method may comprise the components shown in FIGS. 1 to 3. Accordingly, the device may comprise first coils 3, a second coil 11, at least one electrode 6 and a counterelectrode 8, a measuring means and an evaluation means. With the device biological tissues can be examined. Due to the advantages of the method, the device can be used as a stand-alone, non-invasive diagnostic means for examining a biological tissue.

Claims

claims

1. A method for the non-invasive examination of a biological tissue (1, 2, 12, 14, 15) of a mammal, in particular of a human, with the following steps:

a) generating a permutation symmetry imbalance in the tissue (1, 2, 12, 14, 15) by means of a magnetic field (4),

b) determining the conductivity of the tissue (1, 2, 12, 14, 15) or a physical quantity corresponding thereto by means of electrodes (1, 2, 12, 14, 15) attached to the ^electrode (6, 8),

c) irradiation of an alternating magnetic field (10) for changing the permutation symmetry imbalance in a predetermined location (X) in the tissue (1, 2, 12, 14, 15) and

d) spatially resolved determination of a change in the conductivity or the physical quantity corresponding thereto caused by the alternating magnetic field (10)

2. The method of claim 1, wherein a gradient field is used as the magnetic field (4).

3. The method according to any one of the preceding claims, wherein the magnetic field (4) and the alternating field (10) by means of Mag ^¬ net coils (3, 11) and / or permanent magnets are generated.

4. The method according to any one of the preceding claims, wherein in step lit. b) the conductivity or the corres ^¬ corresponding physical size with a plurality of electrodes (6) and at least one counter electrode (8) aufwei ^¬ send electrode array (5, 7) is determined.

5. The method according to any one of the preceding claims, wherein the determination of the conductivity or the corresponding korrespondie ^¬ ing physical size in step lit. b) one to Electrodes (6, 8) applied DC voltage or in the tissue (1, 2, 12, 14, 15) flowing DC current (9) is measured.

6. The method according to any one of the preceding claims, wherein for determining the conductivity or the corresponding korrespondie ^¬ ing physical size in step lit. b) an alternating voltage applied to the electrodes (6, 8) or an alternating current (9) flowing in the tissue (1, 2, 12, 14, 15) is measured.

7. The method of claim 6, wherein the conductivity or the corresponding physical quantity is determined for at least two mutually different AC or AC current frequencies.

8. The method according to any one of the preceding claims, wherein from the determined changes automatically a spatially resolved representation of the changes or a value derived therefrom is generated.

The method of claim 8, wherein the derived value is a diagnostic parameter selected from the following group: density, electrolyte content, homogeneity, concentration and / or composition of the electrolytes, composition of the tissue.

10. The method according to any one of the preceding claims, wherein for carrying out at least one of the steps lit. a) to d) and / or to generate the representation of a computer is used.

11. Use of a method according to one of claims 1 to 10 for the non-invasive examination of a biological tissue (1, 2, 12, 14, 15) of a mammal, in particular of a human, for the presence of a carcinoma, in particular a breast carcinoma. 12. An apparatus for non-invasive examination of a biolo gical ^¬ fabric (1, 2, 12, 14, 15) of a mammal, insbesonde re ^¬ a person, with

a) a first magnetic field means (3) for generating a mutation imbalance imbalance in the tissue (1, 2, 12, 14, 15) by means of a magnetic field (4),

b) a an electrode array (5, 7) having a plurality of electrodes (6) and at least one counter electrode (8) on ^¬ facing measuring means (13) for determining the conductivity of the fabric (1, 2, 12, 14, 15) or a to corres ^¬ exploding physical quantity by means of the fabric (1, 2, 12, 14, 15) to be attached electrodes (6) and counter electrode (8),

c) a second magnetic field means (11) for generating an alternating magnetic field (10) for changing the permutation imbalance imbalance in a predetermined location (X) in the tissue (1, 2,

12, 14, 15) and

d) an evaluation means (13) for spatially resolved determination by the magnetic alternating field (10) caused change ^¬ tion of the conductivity or the physical quantity corresponding thereto.

13. The apparatus of claim 12, wherein the magnetic field (4) is a gradient field.

14. Device according to one of claims 12 and 13, wherein the first and the second magnetic field means comprise magnetic coils (3, 11) and / or permanent magnets.

15. Device according to one of claims 12 to 14, wherein the measuring means (13) having a with the electrodes (6) and counterelectro ^¬ the (8) connected DC or DC power source.

16. Device according to one of claims 12 to 15, wherein the measuring means (13) having a with the electrodes (6) and counterelectro ^¬ the (8) connected AC or AC source.

17. Device according to one of claims 12 to 16, wherein the measuring means (13) connected to the electrodes (6) and Gegenelektro ^¬ den (8) AC or AC source for generating AC voltages or AC currents (9) with at least two mutually different Has frequencies.

18. Device according to one of claims 12 to 17, comprising an image generating means for automatically generating a spatially resolved representation of the changes or a value derived therefrom.

19. The apparatus of claim 18, wherein the derived value is a selected from the group consisting of diagnostic patent is parameters: density, electrolyte content, homogeneity, concent ration ^¬ and / or composition of the electrolyte, the composition of the tissue.

20. Device according to one of claims 12 to 19, with a computer for computer-aided execution of at least one of the steps lit. a) to d) and / or for generating the representation.

21. Use of a device according to one of claims 12 to 20 for the non-invasive examination of a biological

Tissue (1, 2, 12, 14, 15) of a mammal, in particular of a human, for the presence of a carcinoma, in particular a breast carcinoma.