Impedance spectroscopy system and catheter for ischemic mucosal damage monitoring in hollow viscous organs

Abstract

An impedance spectroscopy system for monitoring ischemic mucosal damage in hollow viscous organs comprises a sensor catheter and an impedance spectrometer for electrically driving the catheter to obtain a complex tissue impedance spectrum. Once the catheter is in place in one of a patient's hollow viscous organs, the impedance spectrometer obtains the complex impedance spectrum by causing two electrodes in the tip of the catheter to inject a current into the mucosal tissue at different frequencies, while two other electrodes measure the resulting voltages. A pattern recognition system is then used to analyze the complex impedance spectrum and to quantify the severity of the mucosal injury. Alternatively, the complex impedance spectrum can be appropriately plotted against the spectrum of normal tissue, allowing for a visual comparison by trained personnel.

Description

X=Z sin  Eq. 2.
Analysis of these plots shows that normal tissue spectra have a characteristic shape or pattern. According to the Cole-Cole electric model of biological tissues, this shape is the arc of a circle when plotted in the complex plane. However, if tissue is damaged after an extended period of ischemia, the spectra of the damaged tissue loses this characteristic shape. In fact, when plotted in the complex plane, the spectra of the damaged tissue become sigmoid- or S-shaped, deviating significantly from the normal tissue spectra.

FIGS. 8A-11C show averaged experimental data obtained in the small intestine of a group of test subjects subjected to a period of intestinal ischemia followed by a period of reperfusion (restored blood flow), in comparison to a group of test subjects in which normal perfusion and oxygenation was maintained. The data is presented in both the frequency plots and in the complex plane. For the Nyquist plots (complex plane), the data has been normalized so that the shapes of the curves can be more easily compared, e.g., the point at the highest measurement frequency (300 KHz) has an adimensional impedance of 1 and a phase angle of 0.

FIGS. 8A-8C show the impedance spectra of intestine with less than ten minutes of reduced blood flow, wherein the intestine is already ischemic, with associated rising acidity. In particular, FIGS. 8A and 8B show the average amplitude and phase impedance spectra, respectively, of both normal intestine and the intestine subjected to reduced blood flow, while FIG. 8C shows the normalized Nyquist plot of the normal and ischemic intestinal tissue. As can be seen, although the intestine with reduced blood flow is ischemic, the tissue is not yet damaged, and the spectra are not easily distinguishable from the spectra of the normally perfused intestines. Note that the spectra contain some noise, but resemble the circular arc predicted by the Cole-Cole model.

FIGS. 9A and 9B show the average amplitude and phase impedance spectra, respectively, of both normal intestine and intestine after 1.5 hours of severe ischemia, while FIG. 9C shows the normalized Nyquist plot of the normal and ischemic intestinal tissue. Here, the ischemic tissue has suffered moderate damage, and the spectra have become clearly distinguishable B the ischemic tissue spectra have lost their circular shape and have taken on a sigmoidal shape with several inflection points.

FIGS. 10A-10C show similar plots for normal intestines and intestines after two hours of severe ischemia. By now, the damage is even more severe, and the spectra have become even more distorted.

FIGS. 11A-11C show the spectra of normal intestines and intestines after an hour of ischemia followed by 1.5 hours of reperfusion. After an hour of ischemia, the tissue has suffered some damage. However, after being reperfused, most of this damage has been reversed, and the spectra of the damaged tissue have largely regained their characteristic shape, although they are still somewhat abnormal and are still moderately distinguishable from the spectra of the normal tissue.

As should be appreciated, a plot or graph of the complex impedance spectrum of potentially damaged tissue versus the spectrum of normal tissue, e.g., as shown in FIGS. 8A-11C, can be used by appropriately-trained personnel to determine the level of damage due to ischemia, by way of a visual comparison. Accordingly, the signal processing device 22 may be configured to graph or plot the spectrum for visual analysis, accordingly the general guidelines given above, on a screen or monitor, or by way of a print-out.

Alternatively, the signal processing device 22 can be configured to automatically determine tissue damage, by way of the pattern recognition system or other standard signal processing techniques, such as filtering, or smoothing and extracting inflection points by analysis of derivatives. Another alternative is the use of principal component decomposition or any other method of extracting a characteristic vector describing the shape of the spectrum. Such a characteristic vector can then be analyzed by a classifying or pattern recognition algorithm to provide a score in a predetermined tissue damage scale. Such an algorithm can use one of many standard techniques for classification and/or pattern recognition, such as Bayesian statistics, neural networks, fuzzy logic, statistical classifiers, expert systems, or any combination of these. Further detail regarding a pattern recognition system suitable for use or adaptation for use in the present invention can be found in U.S. Pat. No. 5,807,272 to Kun et al., previously incorporated by reference.

Although the catheters of the present invention have been illustrated as having Ag/AgCl electrodes, one of ordinary skill in the art will appreciate that other types of electrodes could be used instead without departing from the spirit and scope of the invention.

Although the electrodes and spacers of the fourth embodiment of the catheter have been illustrated as having separate passageways and through-bores, one of ordinary skill in the art will appreciate that the passageways and through-bores could be connected, i.e., they do not have to be separate openings, as long as there is a space for the leads.

Since certain changes may be made in the above described impedance spectroscopy system and catheter for ischemic mucosal damage monitoring in hollow viscous organs, without departing from the spirit and scope of the invention herein involved, it is intended that all of the subject matter of the above description or shown in the accompanying drawings shall be interpreted merely as examples illustrating the inventive concept herein and shall not be construed as limiting the invention.

Claims

1. A catheter for use in a system for monitoring mucosal damage in hollow viscous organs, said catheter comprising:

a. a length of tubing suitable for insertion into hollow viscous organs;

b. a plurality of electrodes disposed proximate a distal end of the tubing; and

c. a plurality of electrical leads respectively electrically connected to the plurality of electrodes and extending through the tubing to a proximal end thereof;

2. The catheter of claim 1 further comprising a fill extending through the spacers and axial bores of the electrodes.

3. A catheter for use in a system for monitoring mucosal damage in hollow viscous organs, said catheter comprising:

a. a length of tubing suitable for insertion into hollow viscous organs;

b. a plurality of electrodes disposed proximate a distal end of the tubing; and

c. a plurality of electrical leads respectively electrically connected to the plurality of electrodes and extending through the tubing to a proximal end thereof;

4. The catheter of claim 3 further comprising a fill extending through the spacers and axial bores of the electrodes.

5. A catheter for use in a system for monitoring mucosal damage in hollow viscous organs, said catheter comprising:

a. a tip having a rounded fore portion and a projection extending back from the fore portion;

b. a plurality of electrodes each having: an annular side surface; and a through-bore extending through the electrode and complementary in shape to the projection;

c. at least one spacer having: an annular side surface; and a through-bore extending through the spacer and complementary in shape to the projection;

d. a length of tubing suitable for insertion into hollow viscous organs; and

e. a plurality of electrical leads respectively electrically connected to the plurality of electrodes; wherein:

f. the electrodes are positioned over the projection with the projection extending through the electrode through-bores, said electrodes being spaced apart from one another by the at least one spacer being positioned therebetween and over the projection with the projection extending through the spacer through-bore; and

g. a rear portion of the projection lies inserted within the tubing, with the electrodes and at least one spacer being positioned between the rounded fore portion of the tip and an end of the tubing.

6. The catheter of claim 5 wherein the through-bores and the projection are both V-shaped.

7. The catheter of claim 5 wherein the through-bores and the projection both have a rounded trough shape.

8. The catheter of claim 5 wherein:

a. each electrode further comprises a passageway extending through the electrode;

b. the at least one spacer further comprises a passageway extending through the spacer; and

c. the electrical leads extend through the electrode and spacer passageways.

9. The catheter of claim 5 wherein there are four electrodes and three spacers.

10. In a catheter for use in a system for monitoring mucosal damage in hollow viscous organs, wherein the catheter includes a length of tubing suitable for insertion into hollow viscous organs, a plurality of electrodes disposed proximate a distal end of the tubing, the improvement comprising:

a. a plurality of electrical leads respectively electrically connected to the plurality of electrodes and extending through the tubing to a proximal end thereof;

b. a plurality of annular spacers adapted in size and shape to be mounted on the catheter, and,

c. means for interconnecting adjacent spaced apart pairs of the spacers with electrodes snap locking into the pairs, wherein:

i. the interconnecting electrodes each have cylindrical central portions with two annular side walls and a diameter generally equal to an outer diameter of the tubing sections: first and second cylindrical extensions attached to a top and a bottom of the cylindrical central portion, respectively, and coaxial therewith, said first and second cylindrical extensions having a diameter smaller than the diameter of the cylindrical central portion; and an axial bore extending through the cylindrical central portion and first and second cylindrical extensions; and

ii. the extensions fit into through-bores of the spacers.

11. A catheter for use in a system for monitoring mucosal damage in hollow viscous organs, the catheter comprising:

a. a tip having a rounded fore portion and a projection extending back from the fore portion;

b. a plurality of electrodes each having: an annular side surface; and a through-bore extending through the electrode and complementary in shape to the projection;

c. a plurality of spacers, made of a relative non-conductor of electricity, each having: an annular side surface; and a through-bore extending through the spacer and complementary in shape to the projection;

d. a length of tubing suitable for insertion into hollow viscous organs;

e. a plurality of electrical leads respectively electrically connected to the plurality of electrodes; wherein:

i. the electrodes are positioned over the projection with the projection extending through the electrode through-bores, the said electrodes being spaced apart from one another by respective spacers being positioned therebetween and over the projection with the projection extending through the spacer through-bores; and

ii. a rear portion of the projection lies inside within the tubing, with the electrodes and at least one spacer being positioned between the rounded fore portion of the tip and an end of the tubing; and

f. a plurality of discrete passageways in the electrodes;

g. a plurality of discrete passageways in the spacers; and

h. the electrical leads extend separately through connecting electrode passageways and spacer passageways, whereby the leads are insulated and isolated form one another.

12. A catheter for use in a system for monitoring mucosal damage in hollow viscous organs, the catheter comprising:

a. a tip having a rounded fore portion and a projection extending back from the fore portion;

b. a plurality of electrodes, each having an annular side surface;

c. at least one spacer, made of a relative non-conductor of electricity, having an annular side surface; and a through-bore extending through the spacer, which is complementary in shape to the projection, and mounted onto the projection;

d. a length of tubing suitable for insertion into hollow viscous organs;

e. a plurality of electrical leads respectively electrically connected to the plurality of electrodes; wherein:

i. the electrodes are spaced apart from one another by the at least one spacer being positioned therebetween; and

ii. the electrodes are connected to the at least one spacer; and

f. discrete passageways in the electrodes;

g. a passageway in the at least one spacer, wherein the spacer passageway connects with one of the passageways of the electrodes; and

h. an electrical lead extends separately through the connecting electrode and spacer passageways, whereby the lead is insulated and isolated.

13. The catheter of claim 12 wherein each electrode has a through-bore.

14. A catheter for use in a system for monitoring mucosal damage in hollow viscous organs, the catheter comprising:

a. a tip having a rounded fore portion and a projection extending back from the fore portion;

b. a plurality of electrodes, each having an annular side surface;

c. at least one of the electrodes has a through-bore, which is complementary in shape to the projection, and mounted onto the projection;

d. at least one space, made of a relative non-conductor of electricity, having an annular side surface;

e. a length of tubing suitable for insertion into hollow viscous organs;

f. a plurality of electrical leads respectively electrically connected to the plurality of electrodes; wherein:

i. the electrodes are spaced apart from one another by the at least one spacer being positioned therebetween; and

ii. the electrodes are connected to the at least one spacer; and

g. discrete passageways in the electrodes;

h. a passageway in the at least one spacer, wherein the spacer passageway connects with one of the passageways of the electrodes; and

i. an electrical lead extends separately through the connecting electrode and spacer passageways, whereby the lead is insulated and isolated.

15. The catheter of claim 14 wherein the at least one spacer has a through-bore.

16. A catheter comprising:

a. a tip having a rounded fore portion and a projection extending back from the fore portion;

b. a plurality of electrodes each having: an annular side surface; and a through-bore extending through the electrode and complementary in shape to the projection;

c. a plurality of spacers, made of a relative non-conductor of electricity, each having: an annular side surface; and a through-bore extending through the spacer and complementary in shape to the projection;

d. a length of tubing suitable for insertion into hollow viscous organs;

e. a plurality of electrical leads respectively electrically connected to the plurality of electrodes; wherein:

i. the electrodes are positioned over the projection with the projection extending through the electrode through-bores, the electrodes being spaced apart from one another by respective spacers being positioned therebetween and over the projection with the projection extending through the spacer through-bores; and

ii. a rear portion of the projection lies inserted within the tubing, with the electrodes and at least one spacer being positioned between the rounded fore portion of the tip and an end of the tubing; and

f. a plurality of discrete passageways in the electrodes;

g. a plurality of discrete passageways in the spacers; and

h. the electrical leads extend separately through the connecting electrode passageways and spacer passageways, whereby the leads are insulated and isolated from one another.

17. A catheter comprising:

a. a tip having a rounded fore portion and a projection extending back from the fore portion;

b. a plurality of electrodes, each having an annular side surface;

c. at least one spacer, made of a relative non-conductor of electricity, having: an annular side surface; and a through-bore extending through the spacer, which is complementary in shape to the projection and mounted onto the projection;

d. a plurality of electrical leads respectively electrically connected to the plurality of electrodes; wherein:

i. the electrodes are spaced apart form one another by the at least one spacer being positioned therebetween; and

ii. the electrodes are connected to the at least one spacer; and

e. discrete passageways in the electrodes;

f. a passageway in the at least one spacer, wherein the spacer passageway connects with one of the passageways of the electrodes; and

g. an electrical lead extends separately through the connecting electrode and spacer passageways, whereby the lead is insulated and isolate.

18. A catheter comprising:

a. a tip having a rounded fore portion and a projection extending back from the fore portion;

b. a plurality of electrodes, each having an annular side surface;

c. at least one of the electrodes has a through-bore, which is complementary in shape to the projection, and mounted onto the projection;

d. at least one spacer, made of a relative non-conductor of electricity, having an annular side surface;

e. a plurality of electrical leads respectively electrically connected to the plurality of electrodes; wherein:

i. the electrodes are spaced apart from one another by the at least one spacer being positioned therebetween; and

ii. the electrodes are connected to the at least one spacer; and

f. discrete passageways in the electrodes;

g. a passageway in the at least one spacer, wherein the spacer passageway connects with one of the passageways of the electrodes; and

h. an electrical lead extends separately through the connecting electrode and spacer passageways, whereby the lead is insulated and isolated.

19. The catheter of claim 18 wherein the at least one spacer has a through-bore.

20. A catheter comprising:

a. a plurality of electrodes separated by spacers, made of a relative non-conductor of electricity, wherein the spacers and electrodes are interconnected;

b. each electrode has at least one electrode through-bore and at least one passageway extending through the electrode;

c. the spacers have at least one spacer though-bore aligned with at least one electrode through-bore, and have passageways which are connected to passageways in the electrodes to form discrete channels through which leads attached to respective electrodes pass; and

d. whereby the leads are insulated and isolated from one another.

21. A catheter comprising:

a plurality of electrodes each having an annular side surface, at least one electrode through-bore and at least one passageway extending through the electrodes;

at least one spacer made of a relative non-conductor of electricity, the at least one spacer connected to the electrodes and disposed to electrically isolate the electrodes from one another;

the at least one spacer including at least one spacer through-bore aligned with at least one electrode through-bore, and including at least one passageway connected to the at least one passageway in the electrodes; and

leads extending through the electrode and spacer passageways, the leads connected to corresponding electrodes.

22. The catheter of claim 21 further comprising a projection extending through the electrode and spacer though-bores.

23. The catheter of claim 22 where the electrode and spacer through-bore have a shape complementary to the shape of the projection.

24. The catheter of claim 22 further comprising a tip extending from the projection to a rounded fore portion.

25. A catheter comprising:

a plurality of electrodes each having an annular side surface and at least one passageway extending through the electrodes;

at least one spacer made of a relative non-conductor of electricity, the at least one spacer connected to the electrodes and disposed to electrically isolate the electrodes from one another;

the at least one spacer including at least one passageway connected to the at least one passageway in the electrodes; and

leads extending through the electrode and spacer passageways, the leads connected to corresponding electrodes,

wherein each electrode includes a cylindrical central portion having an annular side surface and first and second cylindrical extensions extending from opposite ends of the cylindrical central portion, the first and second cylindrical extensions having a diameter smaller than the diameter of the cylindrical central portion, and

wherein each spacer includes a through-bore to connect to the electrode by fitting the cylindrical extensions of the electrode in the spacer through-bore such that the spacer abuts to the cylindrical central portions.

26. The catheter of claim 25 where:

the spacers each include at least on annular, inwardly-facing shoulders spaced back from the ends of the spacers; and

the cylindrical extensions of the electrodes each include an annular lip facing the cylindrical central portions, the cylindrical extensions dimensioned to fit within the spacers such that the lips abut the shoulders to lock the electrodes to the spacers.

27. The catheter of claim 25 where the electrodes and spacers include aligned through-bores, the catheter further comprising:

a projection extending through the electrode and spacer through-bores along a length of the catheter; and

a length of tubing enclosing the projection through the length of the catheter and extending to cover the cylindrical extension of the first of the plurality of electrodes, the diameter of the tubing being substantially the same as tote diameter of the cylindrical central portion.

28. The catheter of claim 21 where the leads are insulated and isolated from one another.

29. A catheter comprising:

a plurality of electrodes each having an annular sidewall, a through-bore and at least one passageway extending through the electrodes;

at least one spacer made of a relative non-conductor of electricity, the at least one spacer disposed to electrically isolate the electrodes from one another, the at least one spacer including a spacer through-bore connected to the electrode through-bore, and at least one passageway connected to the at least one passageway in the electrodes;

a projection extending though the electrode and spacer through-bores along a length of the catheter; and

leads extending along the length of the catheter through the electrode and spacer passageways, the leads connected to corresponding electrodes.

30. The catheter of claim 29 further comprising:

a length of tubing enclosing the projection and the leads along the length of the catheter and extending to an end of the tubing abutting the first of the plurality of electrodes.

31. The catheter of claim 29 further comprising a tip extending from the projection to a rounded fore portion.

32. The catheter of claim 29 where the leads are insulated and isolated from one another.