Method and apparatus for determining conditions of a biological tissue

• US 20050283091A1
• Filed: 06/20/2005
• Published: 12/22/2005
• Est. Priority Date: 06/18/2004
• Status: Active Grant

• Current Assignee: Tallinn University Of Technology
• Original Assignee: Smartimplant Ou, Tallinn University Of Technology
• Inventors: Ratsep, Indrek, Kink, Andres, Parve, Toomas, Min, Mart
• Granted Patent: US 7,970,461 B2
• Time in Patent Office: Days
• US Class Current: 600/547
• CPC Class Codes: A61B 5/0537 Measuring body composition by impedance, e.g. tissue hydration or fat content
• CPC Class Codes: A61B 5/413 Monitoring transplanted tissue or organ, e.g. for possible rejection reactions after a transplant

Abstract

In one method, one or more excitation signals with the same or different frequencies are applied to a biological object such as a tissue, simultaneously or consequently. Response signals are then cross-correlated with delayed excitation signals. Cross-correlation products are then auto-correlated. Cross-correlation products correspond to conditions of the tissue and auto-correlation product corresponds to changes in the conditions. Measuring electrical characteristics at low, intermediate and high frequency is also disclosed. At low frequency, the current flows mostly through the extracellular liquid of tissue. At high frequency, the current passes through the cell membranes freely enough to dominate the overall impedance. At both frequencies, the delay is less than 1/30 of the period of the respective signal. The intermediate frequency between the low frequency and the high frequency carries information about quick changes in the condition of the tissue. The delay in one example is from about 1/30 to ¼ of the period of the intermediate signal.

Claims

1. A method for determining conditions of a bio-object, comprising a biological tissue by measuring its electrical characteristics, the method comprising:

generating a first excitation signal and a first reference signal, whereas said first reference signal is delayed compared to said first excitation signal by a first delay time;

introducing said first excitation signal into the bio-object and receiving a first response signal from the bio-object;

cross-correlating said first response signal and said first reference signal, thereby producing a first cross-correlation product; and

calculating a first set of indices characterizing conditions of the bio-object, based on said cross-correlation product and said first delay time.

2. A method as in claim 1, wherein said first excitation signal is a periodic sine wave having a first predetermined frequency that is selected low enough so that a current caused by said first excitation signal flows mostly through an extracellular liquid of the tissue and said first cross-correlation product corresponding to said first excitation signal reflects the amount of extracellular liquid in the tissue.

3. A method according to claim 2, wherein the first predetermined frequency is between about approximately 10 to about approximately 1000 Hz and is chosen so that the maximal value of said cross-correlation product is obtained at said first delay time being less than about approximately 1/30 of the period of said first excitation signal.

4. A method as in claim 1, wherein said first excitation signal is a sine wave having a first predetermined frequency that is selected so that a current caused by said first excitation signal is capable to flow through cell membranes of the tissue so that said first cross-correlation product corresponding to said first excitation signal reflects the total amount of liquid in intracellular and extracellular region of the tissue.

5. A method according to claim 4, wherein the first predetermined frequency is between about approximately 10 kHz to about approximately 10 MHz and is chosen so that the maximal value of said cross-correlation product is obtained at said first delay time being less than about approximately 1/30 of the period of said first excitation signal.

6. A method as in claim 1, additionally comprising generating a second excitation signal and a second reference signal, wherein said second reference signal is delayed compared to said second excitation signal by a second delay time, and introducing said second excitation signal into the tissue and receiving a second response signal from the tissue, cross-correlating said second response signal and said second reference signal, thereby producing a second cross-correlation product, and calculating a second set of indices to describe the condition of the tissue, based on said second cross-correlation product and said second delay time.

7. A method as in claim 6, wherein said first excitation signal is a first periodic sine wave with a first predetermined frequency and said second excitation signal is a periodic sine wave with a second predetermined frequency, wherein said first predetermined frequency is selected so that said first excitation signal flows mostly through an extracellular liquid of the tissue and said first cross-correlation product corresponding to said first excitation signal reflects the amount of extracellular liquid in the tissue and said second predetermined frequency is selected so that said second excitation signal is capable to flow through cell membranes of the tissue so that said second cross-correlation product corresponding to said second excitation signal reflects the total amount of liquid in the intracellular and the extracellular region of the tissue.

8. A method as in claim 7, wherein said first predetermined frequency is between about approximately 10 to about approximately 1000 Hz and said second predetermined frequency is about approximately 10 kHz to about approximately 10 MHz, whereas both said first predetermined frequency and said second predetermined frequency are selected so as to maximize said first cross-correlation product and said second cross-correlation product respectively at said first delay time and said second delay time being less than about approximately 1/30 of a period of said first excitation signal and said second excitation signal respectively.

9. A method as in claim 7, additionally comprising generating a third excitation signal and a third reference signal, whereas said third reference signal is delayed compared to said third excitation signal by a third delay time, and introducing said third excitation signal into the tissue and receiving a third response signal from the tissue, cross-correlating said third response signal and said third reference signal, thereby producing a third cross-correlation product, and calculating a third set of indices to describe the condition of the tissue, based on said third cross-correlation product and said third delay time, and wherein said third reference signal is a third sine wave with a third predetermined frequency, said third predetermined frequency being higher than said first predetermined frequency and lower than said second predetermined frequency, and wherein said third delay time between said third excitation signal and said third reference signal is adjusted to a value between about approximately 1/30 and ¼

of a period of said third excitation signal to maximize the value of the third cross-correlation product.

10. A method as in claim 6, wherein said first excitation signal is a first periodic sine wave and said second excitation signal is a second periodic sine wave with a second predetermined frequency, whereas both said first excitation signal and said second excitation signal are introduced simultaneously into the tissue.

11. A method as in claim 9, wherein said first excitation signal, said second excitation signal and said third excitation signal are introduced simultaneously into the tissue.

12. A method as in claim 6, wherein said first excitation signal is a first periodic sine wave and said second excitation signal is a second periodic sine wave with a second predetermined frequency, whereas said first excitation signal and said second excitation signal are introduced into the tissue in turns at different time intervals and corresponding said first cross-correlation products and said second cross-correlation products are produced for different moments of time which correspond to said different time intervals.

13. A method as in claim 9, wherein said first excitation signal, said second excitation signal and said third excitation signal are introduced into the tissue in turns at different time intervals and corresponding said first cross-correlation products, said second cross-correlation products and said third cross-correlation products are produced for different moments of time which correspond to said different time intervals.

14. A method according to claim 1, wherein said first excitation signal consists of pulse waves.

15. A method according to claim 14, wherein the said pulse waves are trains of rectangular pulses with predetermined duty-cycle and pulse widths.

16. A method according to claim 6, wherein at least one of said first excitation signal and said second excitation signal consists of pulse waves.

17. A method for determining conditions of a bio-object, comprising a biological tissue, by measuring its electrical characteristics, the method comprising:

generating an excitation signal and a reference signal corresponding to said excitation signal, whereas said reference signal is delayed compared to said excitation signal by a delay time;

introducing said excitation signal into the bio-object and receiving a response signal from the bio-object;

cross-correlating said response signal and said reference signal at different moments of time, thereby producing cross-correlation products, characterizing the state of the bio-object at different moments of time;

auto-correlating said cross-correlation products at different lag intervals to produce an auto-correlation products; and

calculating a set of indices from said auto-correlation products corresponding to the changes in a state of the bio-object.

18. A method according to claim 17, wherein said set of indices is selected from the group consisting of liquid amount and balance of the tissue, revivability of a transplanted tissue, and reperfusion and resuscitation processes in a transplanted tissue.

19. An apparatus for monitoring condition of a bio-object, comprising a biological tissue by measuring its electrical characteristics, the apparatus comprising:

a generator, capable of generating at least one type of excitation signal, and having at least one output for said excitation signal and coupled with the bio-object; and

a measuring device for receiving a response signal to said excitation signal from the bio-object, said measuring device comprising a cross-correlator, having a first input for said response signal, a second input for a reference signal generated from said excitation signal, a delay circuit for delaying said reference signal compared to said excitation signal, and a multiplier for multiplying said delayed reference signal with said response signal.

20. An apparatus as in claim 19, wherein said cross-correlator comprises an averager and said device comprises a calculator device for calculating a set of indices, characterizing the bio-object and changes in conditions of the bio-object.