Method and apparatus for detecting a biomarker in the presence of electrical stimulation

• US 9,888,861 B2
• Filed: 08/20/2012
• Issued: 02/13/2018
• Est. Priority Date: 08/25/2011
• Status: Active Grant

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Carlson, David L., Afshar, Pedram, Denison, Timothy J., Giftakis, Jonathon E., Linde, David E., Stanslaski, Scott R.
• Primary Examiner(s): Hindenburg, Max
• Assistant Examiner(s): Foreman, Jonathan M
• Application Number:
  US13/589,270
• Publication Number:
  US 20130053722A1
• Time in Patent Office: 2,003 Days
• CPC Class Codes: A61B 5/24 Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
• CPC Class Codes: A61B 5/316 Modalities, i.e. specific diagnostic methods
• CPC Class Codes: A61B 5/369 Electroencephalography [EEG] devices for psychotechnics A61B5/16
• CPC Class Codes: A61B 5/389 Electromyography [EMG]
• CPC Class Codes: A61B 5/398 Electrooculography [EOG], e.g. detecting nystagmus; Electroretinography [ERG]
• CPC Class Codes: A61B 5/4082 Diagnosing or monitoring movement diseases, e.g. Parkinson, Huntington or Tourette
• CPC Class Codes: A61B 5/4094 Diagnosing or monitoring seizure diseases, e.g. epilepsy
• CPC Class Codes: A61B 5/7264 Classification of physiological signals or data, e.g. using neural networks, statistical classifiers, expert systems or fuzzy systems neural networks per se G06N3/00; expert systems per se G06N5/00
• CPC Class Codes: A61B 5/7282 Event detection, e.g. detecting unique waveforms indicative of a medical condition A61B5/4094, A61B5/4818, A61B5/349, A61B5/0823 take precedence
• CPC Class Codes: G16H 50/20 for computer-aided diagnosis, e.g. based on medical expert systems

Abstract

Various embodiments concern identifying a biomarker in the presence of electrical stimulation. Various embodiments concern delivering electrical stimulation to a patient and sensing one or more signals while the electrical stimulation is being delivered, the one or more signals including data indicative of physiological activity. Various embodiments further include determining an intensity of the electrical stimulation and determining whether the data indicates the presence of a biomarker based on a variable threshold, the variable threshold being variable based on the intensity of the electrical stimulation. Various embodiments concern determining a relationship between stimulation intensity and a biomarker parameter to determine the variability of the variable threshold.

Claims

1. A method of identifying a biomarker in the presence of electrical stimulation, the method comprising:

delivering electrical stimulation to a patient;

sensing one or more signals while the electrical stimulation is being delivered, the one or more signals including data indicative of physiological activity;

determining an intensity of the electrical stimulation; and

determining whether the data indicates the presence of a biomarker based on a variable threshold, the variable threshold being variable based on the determined intensity of the electrical stimulation, wherein at least one of sensing, determining the intensity, and determining whether the data indicates the presence of the biomarker are performed at least in part by control circuitry.

2. The method of claim 1, further comprising determining whether the patient is in a first state or a second state based on the presence or absence of the biomarker.

3. The method of claim 2, wherein the first state is a seizure state and the second state is a non-seizure state.

4. The method of claim 1, further comprising determining a relationship between the variability of the variable threshold and the intensity of the electrical stimulation.

5. The method of claim 4, wherein determining the relationship between the variability of the variable threshold and the intensity of the electrical stimulation comprises:

collecting a first set of signals indicative of physiological activity for a plurality of instances of a first patient state, wherein the electrical stimulation is delivered at a plurality of different intensity levels over the plurality of instances of the first patient state;

collecting a second set of signals indicative of physiological activity for a plurality of instances of a second patient state, wherein the electrical stimulation is delivered at the plurality of different intensity levels over the plurality of instances of the second patient state;

determining whether the biomarker is present in the first set of signals and the second set of signals, wherein the biomarker is indicative of the first patient state and the second patient state is associated with the absence of the biomarker; and

identifying a pattern of the biomarker, the pattern delineating whether the patient is in the first state or the second state over the plurality of different intensity levels based on the presence of the biomarker.

6. The method of claim 4, wherein determining the relationship between the variability of the variable threshold and the intensity of the electrical stimulation comprises:

mapping a plurality of electrical stimulation intensities and a plurality of sensed data samples as feature vectors to feature space for at least two different patient states; and

generating a boundary in the feature space delineating the at least two different patient states, wherein the variable threshold is based on the boundary.

7. The method of claim 1, wherein the intensity of the electrical stimulation is determined from the one or more signals.

8. The method of claim 1, wherein determining the intensity of the electrical stimulation comprises determining one or both of the voltage and the current of the electrical stimulation.

9. The method of claim 1, wherein sensing the one or more signals comprises tuning to a first signal frequency, the first signal frequency associated with the biomarker.

10. The method of claim 1, wherein sensing the one or more signals comprises tuning to a second signal frequency, the second signal frequency at or near the frequency at which the electrical stimulation is delivered.

11. The method of claim 1, further comprising generating an indication of one or both of the presence of the biomarker and a particular patient state based on the determined presence of the biomarker.

12. The method of claim 1, further comprising titrating the electrical stimulation based on the determined presence of the biomarker.

13. The method of claim 1, wherein determining whether the data indicates the presence of a biomarker based on a variable threshold comprises comparing the data to the variable threshold.

14. The method of claim 1, wherein determining whether the data indicates the presence of a biomarker comprises solving an equation, and wherein the determined intensity of electrical stimulation and a parameter indicative of the physiological activity are inputs to the equation.

15. A system comprising:

one or more electrodes;

stimulation circuitry configured to deliver electrical stimulation to a patient via at least one of the electrodes; and

control circuitry configured to;

sense one or more signals via at least one of the electrodes while the electrical stimulation is being delivered;

determine an intensity of the electrical stimulation;

determine whether the one or more sensed signals indicates the presence of a biomarker based on a variable threshold that is variable based on the determined intensity of the electrical stimulation; and

generate an output based on the presence of the biomarker.

16. The system of claim 15, wherein the control circuitry is configured to determine whether the patient is in a first state or a second state based on the presence or absence of the biomarker.

17. The system of claim 16, wherein the first state is a seizure state and the second state is a non-seizure state.

18. The system of claim 15, wherein the control circuitry is configured to determine a relationship between the variability of the variable threshold and the intensity of the electrical stimulation.

19. The system of claim 18, wherein the control circuitry is configured to determine the relationship between the variability of the variable threshold and the intensity of the electrical stimulation by:

receiving a first set of signals indicative of physiological activity for a plurality of instances of a first patient state, wherein the control circuitry is configured to control the stimulation circuitry to deliver the electrical stimulation at a plurality of different intensity levels over the plurality of instances of the first patient state;

receiving a second set of signals indicative of physiological activity for a plurality of instances of a second patient state, wherein the control circuitry is configured to control the stimulation circuitry to deliver the electrical stimulation at the plurality of different intensity levels over the plurality of instances of the second patient state;

determining the presence of the biomarker in the first set of signals and in the second set of signals, wherein the biomarker is indicative of the first patient state and the second patient state is associated with the absence of the biomarker; and

identifying a pattern of the biomarker, the pattern delineating whether the patient is in the first state or the second state over the plurality of different intensity levels based on the presence of the biomarker.

20. The system of claim 18, wherein the control circuitry is configured to determine the relationship between the variability of the variable threshold and the intensity of the electrical stimulation by:

mapping a plurality of electrical stimulation intensities and a plurality of sensed data samples indicative of a biomarker parameter as feature vectors to feature space for at least two different patient states; and

generating a boundary in the feature space delineating the at least two different patient states, wherein the variable threshold is based on the boundary.

21. The system of claim 15, wherein the control circuitry is configured to determine the intensity of the electrical stimulation from the one or more signals.

22. The system of claim 15, wherein the control circuitry is configured to determine the intensity of the electrical stimulation by determining one or both of the voltage and the current at which the stimulation circuitry is configured to deliver the electrical stimulation.

23. The system of claim 15, wherein the control circuitry is configured to tune to a first signal frequency, the first signal frequency associated with the biomarker, wherein tuning to the first signal frequency facilitates determining whether the one or more sensed signals indicates the presence of the biomarker by the control circuitry.

24. The system of claim 15, wherein the control circuitry is configured to tune to a second signal frequency, the second signal frequency at or near the frequency at which the stimulation circuitry is programmed to deliver the electrical stimulation, wherein tuning to the second signal frequency facilitates determining the intensity of the electrical stimulation by the control circuitry.

25. The system of claim 15, wherein the control circuitry is configured to titrate the electrical stimulation as the output generated based on the presence of the biomarker.

26. The system of claim 15, wherein the output generated by the control circuitry based on the presence of the biomarker comprises an indication of one or both of the presence of the biomarker and a particular patient state.

27. The system of claim 15, wherein the control circuit is configured to determine the intensity of electrical stimulation based on a measure of power of the electrical stimulation.

28. The system of claim 15, wherein the control circuit is configured to determine whether the one or more sensed signals indicates the presence of a biomarker based on a variable threshold by comparing data from the one or more sensed signals to the variable threshold.

29. A system comprising:

means for delivering electrical stimulation to a patient;

means for sensing one or more signals while the electrical stimulation is being delivered, the one or more signals including data indicative of physiological activity;

means for determining an intensity of the electrical stimulation; and

means for determining whether the data indicates the presence of a biomarker based on a variable threshold, the variable threshold being variable based on the determined intensity of the electrical stimulation.

30. A non-transitory computer-readable storage medium comprising instructions executable to cause control circuitry to:

deliver electrical stimulation to a patient via stimulation circuitry;

sense one or more signals via sensing circuitry while the electrical stimulation is being delivered, the one or more signals including data indicative of physiological activity;

determine an intensity of the electrical stimulation; and

determine whether the data indicates the presence of a biomarker based on a variable threshold that is variable based on the determined intensity of the electrical stimulation.

31. A method of identifying a biomarker in the presence of electrical stimulation, the method comprising:

delivering electrical stimulation to a patient;

sensing one or more signals while the electrical stimulation is being delivered, the one or more signals including data indicative of physiological activity;

determining an intensity of the electrical stimulation based on a measure of power of the electrical stimulation; and

determining whether the data indicates the presence of a biomarker based on a variable threshold, the variable threshold being variable based on the determined intensity of the electrical stimulation, wherein at least one of sensing, determining the intensity, and determining whether the data indicates the presence of the biomarker are performed at least in part by control circuitry.

32. A system comprising:

means for delivering electrical stimulation to a patient;

means for sensing one or more signals while the electrical stimulation is being delivered, the one or more signals including data indicative of physiological activity;

means for determining an intensity of the electrical stimulation based on a measure of power of the electrical stimulation; and

means for determining whether the data indicates the presence of a biomarker based on a variable threshold, the variable threshold being variable based on the determined intensity of the electrical stimulation.