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Publication numberUS20050085869 A1
Publication typeApplication
Application numberUS 10/966,484
Publication dateApr 21, 2005
Filing dateOct 15, 2004
Priority dateOct 15, 2003
Also published asDE112004001953T5, DE112004001954B4, DE112004001954T5, DE112004001957T5, US8116872, US8200336, US8255056, US8348941, US8412331, US8467876, US8509901, US20050085734, US20050085865, US20050085866, US20050085867, US20050085868, US20060030894, US20060036294, US20070021795, US20080183239, US20080183240, US20080188903, US20080208281, US20130296964, US20130296973, WO2005037077A2, WO2005037077A3, WO2005037172A2, WO2005037172A3, WO2005037173A2, WO2005037173A3, WO2005037174A2, WO2005037174A3, WO2005037220A2, WO2005037220A3, WO2005037366A1
Publication number10966484, 966484, US 2005/0085869 A1, US 2005/085869 A1, US 20050085869 A1, US 20050085869A1, US 2005085869 A1, US 2005085869A1, US-A1-20050085869, US-A1-2005085869, US2005/0085869A1, US2005/085869A1, US20050085869 A1, US20050085869A1, US2005085869 A1, US2005085869A1
InventorsAmir Tehrani, Chang Lee, David Ligon, Mark Meltzer, Anthony Mo
Original AssigneeTehrani Amir J., Chang Lee, David Ligon, Mark Meltzer, Anthony Mo
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
System and method for mapping diaphragm electrode sites
US 20050085869 A1
Abstract
A signal source coupled to one or more electrodes in the vicinity of the diaphragm for mapping therapeutic electrode sites. A stimulus signal from the signal source may be applied to the one or more electrodes to produce activation of the diaphragm. Activation of the diaphragm is sensed to provide information that may be correlated with the stimulus signal. The correlated information may be used to identify a therapeutic locus for a therapeutic electrode. An electrical stimulus comprising a series of pulses may be applied to the one or more electrodes to elicit a desired breathing response. The electrical stimulus may be applied between intrinsic breathing cycles, or between regulated breathing cycles. More than one electrode may be supported on a single substrate. The substrate may configured to be positioned on the diaphragm. A hierarchy of stimuli may be applied to a set of electrodes.
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Claims(54)
1. A system for mapping therapeutic electrode sites on a diaphragm comprising:
a signal source configured to provide a stimulus for eliciting a respiration response comprising an inspiration waveform having a morphology;
one or more implanted electrodes coupled to the signal source and configured to deliver the stimulus to body tissue within the body.
a sensor configured to sense a parameter corresponding to the respiration response; and,
a processor coupled to the sensor, configured to receive a signal from the sensor corresponding to the respiration response, and configured to determine a correlation between the morphology and a desired morphology.
2. The system for mapping therapeutic electrode sites of claim 1 wherein the desired morphology comprises a natural breathing pattern.
3. The system for mapping therapeutic electrode sites of claim 1 wherein the desired morphology is configured to elicit a desired physiological response.
4. The system for mapping therapeutic electrodes sites of claim 3 wherein the desired physiological response is to influence SaO2 levels.
5. The system for mapping therapeutic electrodes sites of claim 3 wherein the desired physiological response is to influence PCO2 levels.
6. The system for mapping therapeutic electrode sites on a diaphragm of claim 1 wherein the electrodes are coupled to a substrate.
7. The system for mapping therapeutic electrode sites on a diaphragm of claim 6 wherein the sensor is coupled to the substrate.
8. The system for mapping therapeutic electrode sites on a diaphragm of claim 1 wherein the waveform comprises information representative of inter-abdominal pressure over time.
9. The system for mapping therapeutic electrode sites on a diaphragm of claim 1 wherein the waveform comprises information representative of thoracic pressure over time.
10. The system for mapping therapeutic electrode sites on a diaphragm of claim 1 wherein the waveform comprises information representative of movement of the diaphragm over time.
11. The system for mapping therapeutic electrode sites on a diaphragm of claim 1 wherein the waveform comprises information representative of at least a portion of a diaphragm EMG over time.
12. The system for mapping therapeutic electrode sites on a diaphragm of claim 1 wherein the waveform comprises information representative of airway flow over time.
13. A system for mapping therapeutic electrode sites on a diaphragm comprising:
a signal source configured to provide a stimulus configured to elicit a respiration response;
one or more electrodes coupled to the signal source and configured to deliver the stimulus to tissue of a body;
a sensor configured to sense a response to the stimulus wherein the sensor is configured to sense at least one parameter corresponding the respiration response; and,
a processor coupled to the sensor and configured to receive a signal corresponding to the at least one parameter, wherein the processor is configured to determine from the at least one parameter, a ratio of a portion of peak volume over a portion of stimulation time.
14. The system of claim 13 wherein the processor is configured to determine whether the percentage of peak volume per percentage of and inspiration cycle corresponds to an acceptable respiration response.
15. The system of claim 14 wherein the acceptable response is a ratio of less than or equal to about 10.
16. The system of claim 15 wherein the acceptable response is a ratio of less than or equal to about 3.5.
17. A system for mapping therapeutic electrode sites on a diaphragm comprising:
a signal source configured to provide a stimulus configured to elicit a respiration response;
one or more electrodes coupled to the signal source and configured to deliver the stimulus to tissue of a body;
a sensor configured to sense a response to the stimulus wherein the sensor is configured to sense at least one parameter corresponding the respiration response; and,
a processor coupled to the sensor and configured to receive a signal corresponding to the at least one parameter, wherein the processor is configured to determine from the at least one parameter whether a sustained inspiration portion of a stimulation duration for a cycle is at an acceptable level.
18. The system of claim 17 wherein an acceptable level is about 0.5 of the stimulation duration or more.
19. The system of claim 17 wherein an acceptable level is about 0.75 of the stimulation duration or more.
20. A system for mapping therapeutic electrode sites on a diaphragm comprising:
a signal source configured to provide a stimulus configured to elicit a respiration response;
one or more electrodes coupled to the signal source and configured to deliver the stimulus to tissue of a body;
a sensor configured to sense a response to the stimulus wherein the sensor is configured to sense at least one parameter corresponding the respiration response; and,
a processor coupled to the sensor and configured to receive a signal corresponding to the at least one parameter, wherein the processor is configured to determine from the at least one parameter whether an instantaneous slope of peak flow over stimulation time is at an acceptable level.
21. The system of claim 20 wherein an acceptable level of instantaneous slope of peak flow over stimulation time is about 2 or less.
22. The system of claim 20 wherein an acceptable level of the instantaneous slope of peak flow over stimulation time is about 0.75 or less.
23. A system for mapping therapeutic electrode sites on a diaphragm comprising:
a signal source configured to provide a stimulus configured to elicit a respiration response;
one or more electrodes coupled to the signal source and configured to deliver the stimulus to tissue of a body;
a sensor configured to sense a response to the stimulus wherein the sensor is configured to sense at least one parameter corresponding the respiration response; and,
a processor coupled to the sensor and configured to receive a signal corresponding to the at least one parameter, wherein the processor is configured to determine from the at least one parameter whether an instantaneous slope of peak flow over stimulation time is at an acceptable level.
24. The system of claim 23 wherein an acceptable level of minimum time to reach peak flow between about 100 milliseconds and 300 milliseconds.
25. The system of claim 23 wherein an acceptable level of minimum time to reach peak flow is greater than or equal to about 300 milliseconds.
26. An electrode assembly comprising:
an inflatable member comprising a substrate and an inflation chamber configured to receive an inflation medium; and
one or more electrodes configured to deliver or sense an electrical signal, coupled to the substrate.
27. The electrode assembly of claim 26 wherein the assembly is configured to be positioned on a diaphragm.
28. The electrode assembly of claim 26 further comprising a manipulation member coupled to the inflatable member, wherein the manipulation member is configured to position the inflatable member in a desired location adjacent a portion of a body.
29. An electrode assembly for stimulating sites on a diaphragm comprising:
a member configured to be positioned on a diaphragm during electrical stimulation of the diaphragm; and,
a plurality of electrodes coupled to the member and configured to deliver electrical stimulation to the diaphragm.
30. The electrode assembly of claim 29 wherein the member comprises a keyed portion configured to be positioned adjacent an anatomical structure of the diaphragm to aid in positioning of the member.
31. The electrode assembly of claim 29 wherein the member comprises a flexible portion configured to accommodate movement of the diaphragm during electrical stimulation.
32. The electrode assembly of claim 29 wherein the member comprises a perimeter having a shape that conforms to a specific feature on a surface of a diaphragm.
33. The electrode assembly of claim 29 wherein the member comprises an active surface configured to interface with a diaphragm surface, wherein the plurality of electrodes is coupled to the active surface of the member, and wherein the active surface is curved.
34. The electrode assembly of claim 29 wherein at least one of the plurality of electrodes comprises a subsurface electrode.
35. The electrode assembly of claim 29 wherein at least one of the plurality of electrodes comprises a composite electrode.
36. The electrode assembly of claim 29 further comprising a switching network coupled to the plurality of electrodes.
37. The electrode assembly of claim 29 wherein the member comprises a mesh.
38. A method for delivering an electrode array to a diaphragm comprising the steps of:
providing an electrode array configured to be compressed to a first configuration and to expand to a second configuration;
compressing the electrode array to the first configuration;
positioning the electrode array adjacent a diaphragm within a subject's body; and
expanding the electrode array to the second configuration.
39. The method of claim 38 wherein the step of compressing the electrode array comprises folding the electrode array; and wherein the step of expanding the electrode array comprises unfolding the electrode array.
40. The method of claim 38 wherein the step of expanding the electrode array comprises inflating the electrode array.
40. A method for mapping electrode sites on a diaphragm, the method comprising:
placing a mapping electrode array on a surface of the diaphragm;
sensing and recording an intrinsic breathing pattern;
selecting an electrode of the mapping electrode array;
delivering a stimulus wave to the electrode; and,
sensing and recording a response to the stimulus wave.
41. The method of claim 40 further comprising calculating intrinsic breathing parameters and establishing a target response.
42. The method of claim 41 further comprising comparing the response to the target response.
43. The method of claim 42 further comprising the step of determining whether the response sufficiently correlates with the target response.
44. The method of claim 40 wherein the stimulus is applied asynchronously.
45. The method of claim 40 wherein the stimulus is applied synchronously.
46. The method of claim 40 wherein the stimulus is applied between intrinsic breathing cycles.
47. A method for mapping electrode sites on a diaphragm, the method comprising:
placing a mapping electrode array on a surface of the diaphragm;
selecting an electrode of the mapping electrode array;
delivering a stimulus to the selected electrode; and,
sensing and recording a response to the stimulus.
48. The method of claim 47 further comprising the step of:
defining an acceptable breathing response morphology.
49. The method of claim 48 further comprising the step of comparing the recorded response to the acceptable breathing response morphology.
50. The method of claim 49 further comprising the step of determining whether the response is sufficiently close to the desired breathing response morphology.
51. A system for electrically stimulating a diaphragm comprising:
an implantable electrode configured to be positioned on the diaphragm;
a signal source configured to provide a stimulation signal to the diaphragm through the electrodes, wherein the stimulation signal comprises a series of pulses that vary in amplitude.
52. The system of claim 51 wherein the pulses vary in frequency.
53. A system for electrically stimulating a diaphragm comprising:
an implantable electrode configured to be positioned on the diaphragm;
a signal source configured to provide a stimulation signal to the diaphragm through the electrodes, wherein the stimulation signal comprises a series of pulses that vary in frequency.
Description
    CROSS-REFERENCE TO RELATED APPLICATIONS
  • [0001]
    This application is a continuation-in-part to U.S. patent application Ser. No. 10/686,891, “BREATHING DISORDER DETECTION AND THERAPY DELIVERY DEVICE AND METHOD”, by Tehrani filed Oct. 15, 2003, and incorporated herein by reference.
  • FIELD OF THE INVENTION
  • [0002]
    The present invention relates to devices, systems, and methods useful for determining locations for therapeutic electrode placement on the diaphragm.
  • BACKGROUND
  • [0003]
    Electrical stimulation of the diaphragm has been performed by delivering a stimulus to the diaphragm through one or more electrodes. The location of the stimulation electrodes greatly affects the ability to obtain a desired response with a given stimulus and candidate electrode sites may be mapped in order to aid in selecting a location for electrode placement.
  • [0004]
    Diaphragm mapping is the process of correlating electrical stimuli applied at a set of points in the vicinity of the diaphragm muscle with the associated responses of the diaphragm muscle. When an electrical stimulus is applied, the diaphragm may respond directly or indirectly.
  • [0005]
    In a direct response, the diaphragm is activated by a signal that is received by muscle fibers without conduction along a nerve. In an indirect response, the muscle fibers respond to a signal that is conducted through a nerve. In general, activation of the diaphragm muscle involves both direct and indirect responses. The relative intensity of direct and indirect response will vary with electrode location.
  • [0006]
    The threshold for action potential initiation of nerves and muscle fibers is approximately the same. However, due to the signal attenuation of muscle tissue, direct stimulation is more localized with respect to an electrode than the response muscle tissue that is stimulated through nerve recruitment. Thus, changes in electrode location will typically affect the indirect and direct response differently.
  • [0007]
    A motor point mapping system is described in “Laparoscopic Placement of Electrodes for Diaphragm Pacing Using Stimulation to Locate the Phrenic Nerve Motor Points,” B. D. Schmit, T. A. Stellato, M. E. Miller, and J. T. Mortimer, IEEE Trans. Rehab. Eng., vol. 6, pp. 382-390, 1998. Mapping was done with the goal of finding a functional motor point on the surface of the diaphragm at which full hemidiaphragm activation could be achieved with a minimum stimulus current. Full activation of the diaphragm was correlated with a tidal volume or peak pressure value. Also, the anatomical motor point was determined to be substantially in the geometric center of a group of nerve branches.
  • [0008]
    Although electrode placement for obtaining full activation may be achieved by mapping a motor point, there are situations in which full activation may not be desirable, e.g., in the treatment of sleep apnea, because it may disturb the sleep of the subject.
  • [0009]
    U.S. Pat. No. 4,827,935 describes a demand electroventilator using a plurality of electrodes adapted for placement on the skin. It describes mapping locations on the skin for optimum electrode location. It also uses the tidal volume to determine the optimal placement. The optimum inspiratory points were located as the sites where the maximum volume of air was inspired per milliampere of current.
  • [0010]
    Since an activation level is characterized in each of these references by a peak or integrated value, a given activation level may be produced by many breathing patterns. Such peak or integrated value is not believed to be sufficient to determine proper placement of electrodes to achieve a desired breathing morphology because placement of electrodes influences the coordinated activation of various nerve and muscle fibers. Motor point mapping as performed in the prior art, for example, does not provide the information necessary for optimal placement of therapeutic electrodes intended to stimulate breathing patterns similar to those associated with certain activity levels such as, e.g., sleep. Such natural breathing patterns may be characterized by pressure or flow as a function of time. Also, tidal volume is not believed to provide sufficient information for optimal placement of electrodes to provide other desired inspiration morphologies that are characterized by flow properties.
  • [0011]
    Additionally, known mapping techniques have been done where the breathing of the subject is controlled by a ventilator, or by inducing a particular state (e.g., apnea induced by hyperventilation) and thus under artificial conditions. Threshold and full activation mapping have been done under these conditions, but it is not believed to be well suited for mapping that is directed to identifying optimal electrode placement for replicating intrinsic breathing patterns or for controlling or manipulating specific aspects of breathing morphology and related physiology.
  • [0012]
    Mapping has been done using a single electrode that is moved from one location to the next, with stimuli being applied and responses measured at each location. In this scheme there may be some placement error when the mapping electrode is removed and replaced with a permanent implanted electrode.
  • [0013]
    Thus, a need exists for a system and method of mapping sites on the diaphragm for therapeutic electrode placement that is more suitable to create intrinsic breathing or to control or manipulate specific aspects of breathing morphology and related physiology. A need also exists for a system and method that provides increased accuracy of electrode placement.
  • BRIEF SUMMARY OF THE INVENTION
  • [0014]
    The present invention provides a signal source for eliciting a desired respiration response that is coupled to one or more electrodes in the vicinity of the diaphragm. A stimulus signal from the source may be applied to the one or more electrodes to produce activation of the diaphragm. Respiration response is sensed to provide information that may be correlated with the stimulus signal. The correlated information may be used to identify a therapeutic locus for a therapeutic electrode.
  • [0015]
    Sensed respiration response may include, for example, parameters indicating diaphragm activation such as diaphragm movement or diaphragm EMG. Sensed respiration response may include parameters such as flow, tidal volume, intraabdominal, intrathoracic and airway pressure. Each of these parameters may be observed over time where they create a respiration or inspiration morphology.
  • [0016]
    In one embodiment of the invention an electrode is placed in the vicinity of the diaphragm and an electrical stimulus is applied between intrinsic breathing cycles, or regulated breathing cycles.
  • [0017]
    In a further embodiment an electrical stimulus comprising a series or burst of pulses is applied through one or more electrodes to the diaphragm to elicit a natural breathing response. The series of pulses may be varied in either or both amplitude and frequency.
  • [0018]
    In another embodiment a support structure supporting one or more electrodes is configured to be placed on the surface of the diaphragm. The support structure may be, e.g., a mesh or other flexible thin substrate. The support structure may comprise a variety of materials such as, e.g., silicone, PTFE, polyurethane, latex, polyester. The support structure may be a substrate with electrodes positioned on, attached to, or formed with the substrate. The substrate may be configured to be positioned on the diaphragm, e.g., by aiding proper locating, positioning and placement of the electrodes and/or by accommodating the movement of the diaphragm. The substrate may also be shaped to fit on the diaphragm and may also be keyed with anatomical structures to aid in ideal positioning. Electrical stimuli are applied sequentially and/or in combination through the electrodes to the diaphragm to elicit a natural breathing response from the diaphragm.
  • [0019]
    Another feature provides an array of electrodes configured to be laparoscopically delivered and to be positioned on the diaphragm. In addition to features that allow the device to be positioned on the diaphragm for stimulation, the substrate is foldable, deflatable and/or contractible so that it can be delivered through a small opening or cannula, and unfoldable, inflatable or expandable to be positioned on the diaphragm.
  • [0020]
    In yet another embodiment a hierarchy of stimuli are applied to a set of electrodes. At each level in the hierarchy the stimuli are more complex with a greater number of adjustable parameters. The set of electrodes may be reduced in number as each level in the hierarchy is reached.
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • [0021]
    FIG. 1 shows a diagram of a system for mapping electrode sites on a diaphragm in accordance with an embodiment of the present invention.
  • [0022]
    FIG. 2A shows a guide grid on a diaphragm in accordance with an embodiment of the present invention.
  • [0023]
    FIG. 2B shows electrode arrays placed with respect to an anatomical feature in accordance with an embodiment of the present invention.
  • [0024]
    FIG. 2C shows a template corresponding to each of electrode arrays of FIG. 2B
  • [0025]
    FIG. 3A shows a top view of an array of electrodes on a single substrate in accordance with an embodiment of the present invention.
  • [0026]
    FIG. 3B shows a cross-section view of the electrode array of FIG. 3A in accordance with an embodiment of the present invention.
  • [0027]
    FIG. 4A shows an electrode array arranged on an inflatable member in accordance with an embodiment of the present invention.
  • [0028]
    FIG. 4B shows a diagram of an in situ electrode substrate in accordance with an embodiment of the present invention.
  • [0029]
    FIG. 5 shows a perspective view of an electrode array with a suction field surrounding the electrodes in accordance with an embodiment of the present invention.
  • [0030]
    FIG. 6A shows a view of the active surface of an electrode array with an inflatable member in accordance with an embodiment of the present invention.
  • [0031]
    FIG. 6B shows a side view of the electrode array of FIG. 6A.
  • [0032]
    FIG. 6C shows the electrode array of FIG. 6A in a folded configuration in accordance with an embodiment of the present invention.
  • [0033]
    FIG. 7A shows a perspective view of an electrode array with an inflatable member and suction field in accordance with an embodiment of the present invention.
  • [0034]
    FIG. 7B shows a side view of the electrode array of FIG. 7A.
  • [0035]
    FIG. 7C shows the electrode array of FIG. 7A in a folded configuration in accordance with an embodiment of the present invention.
  • [0036]
    FIG. 8 shows a stimulus waveform in accordance with an embodiment of the present invention.
  • [0037]
    FIG. 9A shows a natural breathing response waveform in accordance with an embodiment of the present invention.
  • [0038]
    FIGS. 9B1-9B4 shows target, acceptable and unacceptable breathing response waveforms in response to stimulation in accordance with an embodiment of the present invention.
  • [0039]
    FIGS. 9C1-9C4 shows target, acceptable and unacceptable breathing response waveforms in response to stimulation in accordance with an embodiment of the present invention.
  • [0040]
    FIGS. 9D1-9D4 shows target, acceptable and unacceptable breathing response waveforms in response to stimulation in accordance with an embodiment of the present invention.
  • [0041]
    FIGS. 9E1-9E4 shows target, acceptable and unacceptable breathing response waveforms in response to stimulation in accordance with an embodiment of the present invention.
  • [0042]
    FIGS. 10A and 10B show timing diagrams for a stimulus applied during intrinsic breathing in accordance with embodiments of the present invention.
  • [0043]
    FIG. 11 shows an electrode array and sensors placed on the diaphragm in accordance with an embodiment of the present invention.
  • [0044]
    FIG. 12 shows a flow chart of a coarse mapping method in accordance with an embodiment of the present invention.
  • [0045]
    FIG. 13A shows a flow chart of a method for intrinsic breathing evaluation in accordance with an embodiment of the present invention.
  • [0046]
    FIG. 13B shows a flow chart of a method for baseline acquisition for mapping performed on a subject with regulated breathing in accordance with an embodiment of the present invention.
  • [0047]
    FIG. 14A shows a flow chart of a preliminary array mapping method in accordance with an embodiment of the present invention.
  • [0048]
    FIG. 14B shows a flow chart of a preliminary array mapping method in accordance with an embodiment of the present invention.
  • [0049]
    FIG. 15A shows a flow chart of a single parameter mapping method in accordance with an embodiment of the present invention.
  • [0050]
    FIG. 15B shows a flow chart of a single parameter mapping method in accordance with an embodiment of the present invention.
  • [0051]
    FIG. 16A shows a flow chart of a multi-parameter mapping method in accordance with an embodiment of the present invention.
  • [0052]
    FIG. 16B shows a flow chart of a multi-parameter mapping method in accordance with an embodiment of the present invention.
  • DETAILED DESCRIPTION OF THE INVENTION
  • [0053]
    FIG. 1 shows a system 100 for mapping electrode sites on a diaphragm 155 of a subject 135. A laparoscopic imaging unit 130 is coupled to a laparoscope 145 for observing the surface of the diaphragm 155. The imaging unit 130 is coupled to a diaphragm mapping control module 105. The imaging unit 130 may provide analog or digital images to the control module 105. The control module 105 includes a monitor 110, processing unit 115 and an I/O module 120.
  • [0054]
    The monitor 110 may be used displaying a graphical user interface and may also be used for displaying images. Displayed images may be either real-time images from the imaging unit 130 or stored images. Stored images may be overlaid with real-time images to provide visual references for electrode placement.
  • [0055]
    The processing unit 115 includes a data processor, memory, and program storage for data and image acquisition and manipulation. The processing unit 115 is coupled to an input/output (I/O) module 120, and may be used to control the timing of stimuli delivered to mapping electrodes.
  • [0056]
    The I/O module 120 is coupled to the imaging unit 130, and to one or more electrodes 151 on the mapping electrode substrate 150. The electrodes 151 on the mapping electrode substrate are configured for electrical stimulation and/or sensing of the diaphragm. The I/O module may also be coupled to other sensing devices coupled to the subject 135, such as a respiratory sensor 125 (e.g., pneumotachometer) or electrical/mechanical sensors 140 and/or 152. Sensor 152 is shown positioned for sensing abdominal movement, whereas sensor 140 is positioned for sensing movement in the thoracic region 160. Sensors 140, 152 may also be used to sense movement of the subject which can provide information, such as, activity level of the subject. Alternatively other sensors may positioned or coupled to the body and in communication with the I/O module. The I/O module may also have a keyboard, mouse, or other device for operator input.
  • [0057]
    Respiratory sensor 125 may be, e.g., a flow meter, pneumotachometer, or pressure sensor used to measure tidal volume, respiratory flow, and/or respiratory pressure. Sensor 140 may be, e.g., a piezo-film sensor, multi-axis accelerometer, strain gauge, pressure sensor, and may be used to measure abdominal movement, diaphragmatic movement, other subject movement or activity, intrathoracic pressure, or intraabdominal pressure.
  • [0058]
    The system 100 may be used to develop a coordinate system on a per subject basis by capturing an image of the surface of the diaphragm 155, upon which the mapping electrode substrate 150 is attached. The image obtained by the imaging unit 130 is transferred to the control module 105. Each time the mapping electrode substrate 150 is moved, a new coordinate system is created. Once a desired therapeutic locus is determined on the surface of the diaphragm 155 as described in more detail below, the control unit may use the images acquired during the mapping process to provide guidance for placement of a permanent electrode, e.g. through real-time visual aid (video feed, laser grid), audible proximity indicator beeps, or haptic feedback.
  • [0059]
    FIG. 2A shows an abdominal view of a diaphragm 205 with a reference grid 210 applied to the right hemidiaphragm 215 and a reference grid 220 applied to the left hemidiaphragm 225. The reference grid may be applied with an ink or dye, or it may be an optical projection. The grids 210 and 220 may be used as a reference for electrode placement.
  • [0060]
    FIG. 2B shows an abdominal view of a diaphragm 205 with attached electrode substrates 230 and 235. The electrode substrates are configured to be positioned on the diaphragm. The electrode substrates 230, 235 include electrodes 233 located on the substrates in a predetermined configuration. Electrode substrate 230 has a keyed or curved portion 231 on its perimeter that matches the depression 245 on the central tendon 240. Similarly, electrode substrate 235 has a keyed or curved portion 232 on its perimeter that matches the depression 250 on the central tendon 240. The keyed configuration of the electrode substrate 235 allows a more precise locating, positioning and placement of the substrates on the diaphragm. The substrates 230, 235 further include template openings 234 for marking the position of the substrates 230, 235 after electrode selection has been made.
  • [0061]
    The electrode substrates 230 and 235 may be attached to the diaphragm 205 in a number of ways with laparoscopic instruments, for example with sutures, staples or clips, temporary adhesive (bio-adhesive), and suction.
  • [0062]
    To identify the precise location of the selected mapping electrode after the substrates 230, 235 have been removed, a mark is made through each of the template openings 234. A template 236 as illustrated in FIG. 2C includes matching template openings 237 that match the orientation of the template openings 234 of the substrates 230, 235. Electrode openings 238 in the template 236 also match the orientation of the electrodes 233 on the substrates 230, 235. Thus, using the marks made through template openings 234 in the substrates 230, 235, the template is positioned with openings 237 over the marks. The electrode opening that corresponds to the selected electrode on the array may then be used to mark the correct location for a subsequently implanted electrode. Permanently implanted electrodes may then be placed in position of the selected optimal mapping electrode or electrodes as they were positioned with the mapping substrate.
  • [0063]
    The electrode substrate may also include an adhesive dye (which can be radio-opaque) in a pattern where once the substrate is removed, the adhesive sticks to the diaphragm indicating key locations so that mapped positions may be visually or radiographically identified. The locations of the mapping substrate and electrodes may also be identified with a photo taken of the substrate in position on the diaphragm.
  • [0064]
    This and other electrode assemblies and/or substrates described herein may be temporarily implanted or permanently implanted and used for stimulation once the assembly or substrate has been optimally positioned.
  • [0065]
    FIG. 3A shows a top view of an array of electrodes (310,315) on a single substrate 305 in accordance with an embodiment of the present invention. Electrode 310 is a subsurface electrode that is intended to penetrate the peritoneum on the diaphragm, whereas electrode 315 is a surface electrode that is intended for contact with the surface of the peritoneum on the diaphragm. A subsurface electrode 310 will generally provide a greater electrical efficiency, whereas a surface electrode 315 will more easily couple to a larger region. A surface electrode may 315 be combined with a subsurface electrode 310 to form a single composite electrode. These electrodes may also be selected to elicit a desired observed response.
  • [0066]
    The substrate 305 is preferably fabricated from a flexible material such as silicone, and may or may not be reinforced (e.g., with a mesh). The substrate is configured to fit on the diaphragm. The perimeter of the substrate 305 may be round, elliptical, or a more complex shape that conforms to a specific feature on the diaphragm surface. A complex perimeter shape may be used to facilitate placement of the substrate 305 at a particular location on the surface of the diaphragm, such as one of the depressions separating the three leaflets of the diaphragm, or characteristics of the central tendon.
  • [0067]
    The electrode array on the substrate 305 may contain only surface or subsurface electrodes or a combination of surface and subsurface electrodes. The electrodes may be arranged in a regular array using polar or rectangular coordinates, or they may be arranged as an irregularly spaced array, e.g., that is correlated with nerve structure that innervates the diaphragm. The electrodes may be attached to the substrate a number of ways, e.g., glued, welded, etched on, or encased with the substrate material.
  • [0068]
    FIG. 3B shows a cross-section view A-A of the electrode array of FIG. 3A. The substrate is thicker in the central region and tapers at the perimeter. A reinforcement 325 is also shown. The taper at the perimeter 321 reduces the dynamic interfacial forces that are produced between substrate and diaphragm during activation of the diaphragm. The enhanced peripheral flexibility reduces mechanical loading of the diaphragm and reduces the stress on the attachment (e.g., sutures or suction). The substrate surface 320 upon which the electrodes reside may be flat, or it may be curved to accommodate the surface of the diaphragm.
  • [0069]
    Electrodes 310 and 315 may be used individually as monopolar electrodes for sensing and/or stimulation, or any two electrodes may be select as a pair for bipolar sensing and/or stimulation.
  • [0070]
    The electrode assembly may also be in the form of a flexible wire member such as a flexible loop. The flexibility of the loops permits the ability to form the loops in the shape most ideally suited for a particular patient. Other shapes may be used as well, e.g. a loop with a branch that extends to the region adjacent the anterior branches of the phrenic nerve. The control unit may be programmed to activate the electrodes in a sequence that is determined to elicit the desired response from the diaphragm.
  • [0071]
    The electrodes of the electrode assemblies once implanted, may be selected to form bipolar or multipolar electrode pairs or groups that optimize the stimulation response.
  • [0072]
    FIG. 4A shows an electrode array 400 coupled to an inflatable member 405 defining an inflation chamber 406. In this embodiment, the inflatable member 405 may be inflated to contact a surface opposite the diaphragm to provide the force necessary to hold the electrode array 400 against the surface of the diaphragm. The electrodes may be coupled to an external I/O device with lead wires extending inside of, outside of or within the walls of the inflation tube. The inflation chamber 406 is coupled to a tube 420 that delivers an inflation medium to or from the chamber 407. The tube 420 may also serve to couple the pressure within the inflation chamber 407 to an external pressure transducer. Alternatively pressure within the inflation chamber 407 may be sensed by a local pressure transducer 425 which is coupled to an I/O port with a lead or in a similar manner as the electrodes. The inflation chamber 407 may be evacuated in order to reduce the volume of the inflation member 405 and electrode array 400 during an insertion or removal procedure.
  • [0073]
    FIG. 4B shows a diagram of an in situ electrode substrate 406. In this example, the electrode substrate 406 is coupled to a flexible tube 435 that penetrates the abdominal wall 440. A switching network 450 couples lines 441 and 442 from the control unit 430 to an array of nine electrodes. The switching network 450 allows any one or two of the nine electrodes to be selected, and reduces the number of leads that must be connected directly to the control unit 430. Electrode selection may be done either for monopolar/bipolar sensing, or stimulus delivery.
  • [0074]
    The electrode substrate 406 may support one or more sensors 445 for sensing electrical or mechanical activity of the diaphragm. Sensor 445 is coupled to the control unit 430 by lead 443. Examples of electrical sensors are monopolar and bipolar electrodes for electromyogram (EMG) sensing. Examples of mechanical activity sensors are: strain gauges, pressure sensors, piezo-electric devices, accelerometers, and position sensors.
  • [0075]
    FIG. 5 shows a perspective view of an electrode array structure 505 with a suction field surrounding the electrodes 515 in accordance with an embodiment of the present invention. The electrodes 515 are supported on a mesh 510 that is circumferentially enclosed by a seal surface 520 that interfaces with the diaphragm surface. A port 525 is used to connect a vacuum source to the electrode array structure 505. Vacuum is applied after the seal surface is placed on or mated to the surface of the diaphragm.
  • [0076]
    FIG. 6A shows a view of the active surface of an electrode array structure 605 with an inflation member 620 having an inflation chamber 621 in accordance with an embodiment of the present invention. Individual suction cups 615 are used to provide the attaching force to the diaphragm. Electrodes 610 are distributed on the surface between the suction cups 615. FIG. 6B shows a side view 601 of the electrode array structure of FIG. 6A. Vacuum ports 625 are shown connected to the suction cups 615, and a fill/evacuation port 630 is shown coupled to the inflation chamber 621.
  • [0077]
    FIG. 6C shows the electrode array of FIG. 6A in a folded configuration that is produced in conjunction with deflation of the inflation member 620. The deflation of the inflation chamber 621 of the inflation member 620 produces a reduction in volume and an elongated shape that facilitates the introduction and removal of the electrode array structure 605 through a cannula or a narrow opening.
  • [0078]
    FIG. 7A shows a perspective view of an electrode array 705 on an inflation member 740 with an inflation chamber 741 and a suction field mesh 710 in accordance with an embodiment of the present invention. Electrodes 715 are supported on the mesh 710. The mesh 710 is surrounded by a seal surface 720. The inflation chamber 741 is coupled to a fill/evacuation port 730. An evacuation port 725 is used provide to provide vacuum to the electrode array 705. Having the mesh 710 with electrodes 715 inside the suction field allows stabilization of the tissue via vacuum and provides intimate contact between the tissue and the electrodes 715 during contraction of the diaphragm. FIG. 7B shows a side view of the electrode array of FIG. 7A. The inflation member 740 has a radial symmetry (e.g., toroidal) with respect to the evacuation port 725.
  • [0079]
    FIG. 7C shows the electrode array of FIG. 7A in a folded configuration that is produced in conjunction with deflation of the inflation member 740. The deflation of the inflation member 740 produces a reduction in volume and an elongated shape that facilitates the introduction and removal of the electrode array structure 705 through a cannula or a narrow opening.
  • [0080]
    The electrode arrays described herein may be configured to be laparoscopically delivered to the diaphragm. They may be compressed to a smaller configuration and then expanded to be positioned on the diaphragm. They may also be delivered as individual components and assembled at the diaphragm. They may also be delivered as individual components and assembled at the diaphragm.
  • [0081]
    FIG. 8 shows an example of a stimulus waveform 800 that may be applied to the diaphragm through an electrode. Waveform 800 is a biphasic pulse train; however, in other embodiments a monophasic or other multiphasic pulse train may be used. The individual pulses within the pulse train 800 may have variable amplitudes. For example, pulse 805 has an amplitude A1 that is smaller than the amplitude A2 of pulse 810. The pulse train 800 may also have a variable frequency, with the period P1 between pulses 813 and 815 being greater than the period P2 between succeeding pulses 820 and 825. The first pulse amplitude A1 may be selected to on the basis of an observed or measured threshold value associated with the response of the diaphragm to an applied stimulus (e.g., an observed muscle twitch).
  • [0082]
    The stimulus waveform or pulse train 800 may incorporate a delay D between positive and negative pulses, as shown between positive pulse 810 and negative pulse 811.
  • [0083]
    FIG. 9A shows an example of a natural breathing flow response waveform 905 associated with a stimulation waveform 910 delivered to a therapeutic locus on the diaphragm. For purposes of this disclosure, “intrinsic breathing” refers to breathing that is not induced by an applied stimulus, and “natural breathing” refers to breathing that is similar or identical to intrinsic breathing, but is induced by an applied stimulus. The natural breathing flow response waveform 905 is similar to intrinsic respiration waveforms observed in humans. Flow increases gradually during most of the inspiration phase to a peak value, followed by a relatively sharp decline in flow to the onset of the expiration phase. In this example, the first pulse in the stimulation waveform 910 has an amplitude At, that is equal to a measured or observed threshold value for the therapeutic locus. FIG. 9A similarly illustrates a natural breathing EMG response waveform 906 and envelope 907 associated with the stimulation waveform 910.
  • [0084]
    FIG. 9B 1 illustrates a stimulation waveform 925 delivered to candidate therapeutic loci on the diaphragm. The various loci of stimulation correspond to resulting response waveforms 926, 927, 928 illustrated in FIGS. 9B2, 9B3, 9B4 respectively and each corresponding to a response resulting from stimulation at a different locus. Different waveforms may also result from variations in the stimulation pulses such as, e.g., in frequency pulse duration and amplitudes as well as by using different electrode firing sequences as described for example in parent application Ser. No. 10/686,891.
  • [0085]
    The waveform responses illustrated in FIGS. 9B1-9B2 are measured in airflow but may also be determined, from other respiration parameters, e.g. EMG or diaphragm movement. “Morphology” refers to the shape or form of the respiration waveform or waveform envelope and may include various aspects of the waveform including, e.g., length of various portions of the waveform, amplitude, frequency or slope. A desired response may be natural breathing as illustrated in FIG. 9A or another desired response.
  • [0086]
    FIG. 9B 2 illustrates a waveform response 926 in an ideal, preferred or target range. According to this target morphology, for a given portion of the inspiration cycle positive inhalation is sustained. A sustained inhalation period or portion of time is an inhalation period in which there is a positive airflow. The target range may be expressed as a portion, fraction or percentage of time of the inspiration cycle in which there is a positive or sustained inhalation. While this effect may be expressed in these terms, a percentage or fraction calculation is not required to achieve the effect of the invention or its equivalent. The target range is from about 75% to 100% sustained inhalation. The waveform illustrated in FIG. 9B 2 shows an inspiration cycle where 95% or 0.95 of the inspiration cycle is sustained positive inhalation.
  • [0087]
    FIG. 9B 3 illustrates a waveform response 927 in an acceptable range. The acceptable range is between about 50% and 100% sustained inhalation. The illustrated waveform is at 60% sustained positive inhalation.
  • [0088]
    FIG. 9B 4 illustrates a waveform 928 response in an unacceptable range. The unacceptable range is below about 50% sustained inhalation. The illustrated waveform is at 20% sustained positive inhalation. Less than about 50% suggests poor efficiency of the delivered stimulation pulse.
  • [0089]
    It is believed that long period of isometric diaphragm contraction can lead to diaphragm fatigue and patient discomfort. Staying within the target range suggests increased energy efficiency, likely responses similar to physiologic or natural conditions. Gradual contraction is also less likely to cause airway collapse or stretch receptor inhibition reflex and is likely to provide more comfortable breathing for patients.
  • [0090]
    FIG. 9C 1 illustrates a stimulation waveform 935 delivered to candidate therapeutic loci on the diaphragm. The various loci of stimulation correspond to resulting response waveforms 936, 937, 938 illustrated in FIGS. 9C2, 9C3, 9C4 respectively and each corresponding to a response resulting from stimulation at a different locus (or alternatively by varying stimulation parameters).
  • [0091]
    The waveform responses illustrated in FIGS. 9C1-9C2 are measured in airflow but may also be determined, from other respiration parameters, e.g. EMG or diaphragm movement.
  • [0092]
    FIG. 9C 2 illustrates a waveform response 936 in an ideal, preferred or target range. According to this target morphology, the ratio of peak flow over stimulation time for a given portion of the inspiration cycle is less than about 3.5. The ratio may also be expressed as a ratio of percentage of peak flow over a percentage of pacing time. While the effects herein may be expressed as a certain value, a specific calculation of the value is not required to achieve the invention or its equivalent.
  • [0093]
    FIG. 9C 3 illustrates a waveform response 937 in an acceptable range. The acceptable range ratio of peak flow over pacing time is about less than or equal to about 10.
  • [0094]
    FIG. 9C 4 illustrates a waveform response 938 in an unacceptable range. The unacceptable range ratio of peak flow over pacing time is above about 10. A ratio above 10 suggests an abrupt flow which may cause airway collapse, stretch receptor inhibition reflex, or pain for patients.
  • [0095]
    FIG. 9D 1 illustrates a stimulation waveform 945 delivered to candidate therapeutic loci on the diaphragm. The various loci of stimulation correspond to resulting response waveforms 946, 947, 948 illustrated in FIGS. 9D2, 9D3, 9D4 respectively and each corresponding to a response resulting from stimulation at a different locus (or alternatively by varying stimulation parameters).
  • [0096]
    The waveform responses illustrated in FIGS. 9D1-9D2 are measured in airflow but may also be determined, from other respiration parameters, e.g. EMG or diaphragm movement.
  • [0097]
    FIG. 9D 2 illustrates a waveform response 946 in an ideal, preferred or target range. According to this target morphology, the instantaneous slope of peak flow over stimulation time for a given portion of the inspiration cycle is less than about 0.75. The ratio may also be expressed as a ratio of percentage of peak flow per milliseconds. While the effects herein may be expressed as a certain value, a specific calculation of the value is not required to achieve the invention or its equivalent.
  • [0098]
    FIG. 9D 3 illustrates a waveform response 947 in an acceptable range. The acceptable range of instantaneous peak flow over time is about less than or equal to about 2.
  • [0099]
    FIG. 9D 4 illustrates a waveform response 948 in an unacceptable range. The unacceptable range of instantaneous peak flow over time is above about 2. A ratio above 2 suggests an abrupt flow which may cause airway collapse, stretch receptor inhibition reflex, or pain for patients.
  • [0100]
    FIG. 9E 1 illustrates a stimulation waveform 955 delivered to candidate therapeutic loci on the diaphragm. The various loci of stimulation correspond to resulting response waveforms 956, 957, 958 illustrated in FIGS. 9E2, 9E3, 9E4 respectively and each corresponding to a response resulting from stimulation at a different locus (or alternatively by varying stimulation parameters).
  • [0101]
    The waveform responses illustrated in FIGS. 9E1-9E2 are measured in airflow but may also be determined, from other respiration parameters, e.g. EMG or diaphragm movement.
  • [0102]
    FIG. 9E 2 illustrates a waveform response 956 in an ideal, preferred or target range. According to this target morphology, the minimum time elapsed before peak flow is achieved is greater than or equal to about 300 milliseconds or more.
  • [0103]
    FIG. 9E 3 illustrates a waveform response 957 in an acceptable range. The acceptable range of minimum time to reach peak flow is greater than or equal to about 100 milliseconds and more preferably between about 100 milliseconds and 300 milliseconds.
  • [0104]
    FIG. 9E 4 illustrates a waveform response 958 in an unacceptable range. The unacceptable range minimum time to reach peak flow is less than about 100 milliseconds. A time below about 100 ms suggests an abrupt flow which may cause airway collapse, stretch receptor inhibition reflex, or pain for patients.
  • [0105]
    Various desired responses may also include waveforms or morphologies that have a desired physiological outcome or effect such as desired blood oxygen saturation levels or PCO2 levels. Minute ventilation may be increased or decreased with respect to a baseline minute ventilation. This may be done by manipulation of one or more parameters affecting minute ventilation. Some of the parameters may include, for example, tidal volume, respiration rate, flow morphology, flow rate, inspiration duration, slope of the inspiration curve, and diaphragm created or intrathoracic pressure gradients. Increasing minute ventilation generally increases the partial pressure of O2 compared to a reference minute ventilation. Decreasing minute ventilation generally increases the partial pressure of CO2 compared to a reference minute ventilation.
  • [0106]
    As noted variations in stimulation parameters may be used to elicit different responses and therefore may also be used to determine optimal electrode location as well as optimal stimulus parameters. This stimulation may also be done with multiple electrodes simultaneously or in a sequence.
  • [0107]
    The system may adjust the pace, pulse, frequency and amplitude within a series of pulses to induce or control various portions of a respiratory cycle, inspiration, exhalation, tidal volume (area under waveform curve) slope of inspiration, fast exhalation and other parameters of the respiratory cycle. The system may also adjust the rate of the respiratory cycle.
  • [0108]
    The stimulation optimization may be used not only for mapping to identify electrode sites but may also be used to determine stimulation parameters for the ultimately implanted device. As such the ideal, preferred, target and acceptable waveform morphologies are not only for mapping but are also ideal, preferred, target and acceptable stimulation responses in the implanted device.
  • [0109]
    A breathing response depends upon both the electrode location and the applied stimulus waveform. Not all electrode locations may be capable of producing a desired response. Also, different stimulus waveforms may be required at those locations that are shown to be capable of producing a desired response.
  • [0110]
    FIG. 10A shows a timing diagram for a fixed stimulus 1000 applied during a rest period associated with intrinsic (or regulated) breathing. Regulated breathing refers to a predominantly regular breathing pattern that is produced by external assistance (e.g., a ventilator). Fixed stimulation may also be done during absence of breathing (e.g., in apnea) where stimulation is applied a certain period of time after apnea has begun. The fixed stimulus may be applied after a percentage (e.g., 30%) of the observed rest period has elapsed, or it may be applied after a fixed period of time has elapsed. The fixed period of time may be referenced to the beginning of inhalation 1005, end of inhalation 1010, or end of exhalation 1015. The fixed time period may also be referenced to a period of time after EMG waveform 1006 has stopped or after the EMG envelope 1007 has fallen off. Fixed stimulation is not necessarily in phase with intrinsic respiration, and rather, is offset from a previous cycle.
  • [0111]
    FIG. 10B shows a timing diagram for a dynamically synchronized stimulus 1020 applied during a rest period associated with intrinsic (or regulated) breathing. The dynamically synchronized stimulus is applied after a delay equal to the length of the inspiration phase, expiration phase, or the total respiratory cycle. The delay is indexed to the end of the respiration cycle 1035. In this example the delay at 1035 is approximately equal to or less than the total respiratory cycle. The delay may also be equal to the length of the EMG signal 1036 or to the length of the EGM envelope 1037. The delay may also be indexed to the end of the EMG envelope 1038. Dynamic synchronization may occur or be adjusted breath to breath.
  • [0112]
    While the stimulation may be fixed or dynamically synchronized, it may also switch between fixed and dynamically synchronized, for example depending on the rate of respiration. If a subject is hyperventilating, hypoventilating or apneaic, the stimulation may revert to a fixed stimulation mode.
  • [0113]
    FIG. 11 shows an abdominal view of a diaphragm 1105 with attached electrode substrates 1110 and 1120. Electrode substrates 1110, 1120 have keyed portions 1111, 1121 respectively for positioning the substrate 1110, 1120 on a conforming portions or surfaces of the central tendon 1106. Electrode substrate 1110 located on the right hemidiaphragm 1115 has a pair of extensions 1126 a-b. Electrode substrate 1120 located on the left hemidiaphragm 1125 has a single extension 1126 c. Each extension 1126 a-c supports a peripheral device 1130 that may be either an electrode (e.g., stimulation or sensing electrode) or a sensor (e.g., movement sensor). The extensions 1126 a-c are located adjacent specific portions of the diaphragm apart from the stimulation electrodes. The peripheral device or devices 1130 sense movement or EMG at a distal or radial location from the stimulation electrodes on the electrode substrates 1110, 1120. This sensed movement or EMG may be used to confirm activation or degree of activation of the diaphragm from stimulation by one or more electrodes on the substrates 1110, 1120.
  • [0114]
    FIGS. 12 through 16 show a series of flow charts for process sequences that may be combined to provide a hierarchical method for mapping diaphragm electrode sites. First, coarse mapping is done as described with reference to FIG. 12. Coarse mapping entails testing a wide area on the diaphragm which is typically greater than the are of the electrode assembly used in testing. Once an area for electrode array positioning is determined, specific electrode position testing is performed and then stimulation optimization as described in FIGS. 13A-16B. These process sequences may be performed using all or part of the system shown in FIG. 1.
  • [0115]
    FIGS. 13A, 14A, 15A and 16A are directed to patients who are breathing on their own. FIGS. 13B, 14B, 15B and 16B are directed to patients in artificial respiratory states (i.e.—ventilator dependent.
  • [0116]
    FIG. 12 shows a flow chart of a coarse mapping method in accordance with an embodiment of the present invention. This method may be used as a preliminary mapping process to determine the initial placement of an electrode array. Coarse mapping may be useful since physical land marks provided by the diaphragm might not be enough to identify an optimal positioning of the electrode array. In order to determine sections of the diaphragm that is more responsive to electrical stimulation course mapping may be performed. In step 1210 a coordinate system is established in a selected area. The selected area is typically larger than the foot print of the electrode array being placed. Selection of the area may be based upon visually observable features of the diaphragm, or may use information regarding the nerve structure of the diaphragm obtained by computer aided tomography (CAT), or other imaging technologies.
  • [0117]
    In step 1215 a single electrode probe is used to probe a series of points distributed across the area selected in step 1210. The locations may be marked, e.g. with ink, a laser grid, or on a monitor. The system depicted in FIG. 1 may be used, with the single electrode probe being substituted for the electrode substrate 150. A fixed waveform may be applied at each location and a response sensed, e.g., by one of the previously mentioned techniques.
  • [0118]
    In step 1220 the pattern of test locations obtained in step 1215 is evaluated to determine where within the selected area the electrode array should be placed. For example, the electrode array may be placed in the region of the selected area for which the underlying test points have the highest average response value. At step 1225 the process is done.
  • [0119]
    FIG. 13A shows a flow chart 1300 of a method for intrinsic breathing evaluation in accordance with an embodiment of the present invention. This process is typically used prior to applying mapping stimuli in order to establish a target response that may be subsequently updated during mapping.
  • [0120]
    In step 1310 the mapping electrode array is placed on the diaphragm. The mapping electrode array may be placed using the results of the coarse mapping procedure shown in FIG. 12, or may be placed using physical features of the diaphragm.
  • [0121]
    In step 1315 the intrinsic breathing pattern is sensed and recorded using respiratory flow sensors to determine time dependent characteristics such as flow rate, pressure and tidal volume.
  • [0122]
    In step 1320 the intrinsic breathing diaphragm movement and activity are sensed and recorded using electrical (e.g., EMG) and/or mechanical (e.g., accelerometer or strain gauge) sensors.
  • [0123]
    In step 1325 the intrinsic breathing parameters associated with the observed intrinsic breathing pattern are calculated to provide reference values for subsequent comparison to those calculated from observed responses to mapping stimuli. Examples of intrinsic (or desired) breathing parameters are inspiration length, exhalation length, rate, amplitude, rest length and cycle length, slope of the inspiration cycle, slope of the expiration cycle, peak flow per time, percent peak flow per percent of inspiration time, and sustaining positive flow as a time value or as a percent of inspiration cycle.
  • [0124]
    In step 1330 the optimum stimulation timing is determined. As previously discussed, the stimulation may be dynamically synchronized or fixed. At step 1335 the process is done.
  • [0125]
    FIG. 13B shows a flow chart of a method for baseline acquisition for mapping performed on a subject with regulated breathing in accordance with an embodiment of the present invention. Subjects with regulated breathing, such as those on a ventilator may lack the diaphragm activity associated with intrinsic breathing. In such cases, a baseline is developed during monitored intrinsic breathing prior to regulation. The baseline reference is a target response that is not updated during mapping.
  • [0126]
    In step 1340 a respiratory flow monitor (e.g., a pneumotachometer) is placed on the subject. In step 1345 the intrinsic breathing pattern is recorded.
  • [0127]
    In step 1350 the intrinsic breathing parameters are calculated. In contrast to the process of FIG. 13A, information regarding diaphragm activity is not used.
  • [0128]
    In step 1355 the baseline reference is stored. Since intrinsic breathing is absent during mapping performed on a subject with regulated breathing, the baseline reference will not change during mapping. At step 1360 the process is done.
  • [0129]
    FIG. 14A shows a flow chart of a preliminary array mapping method for intrinsic breathing (or desired breathing) in accordance with an embodiment of the present invention. In step 1410 an electrode is selected from the array. In step 1415 a locator wave is applied to the selected electrode (e.g., fixed or dynamically synchronized). A locator wave typically has fixed parameters and a low current and is a wave that will evoke an observable response for area close to the desired permanent electrode implantation site(or desired).
  • [0130]
    In step 1420 the response to the locator wave is sensed and stored. A desired or acceptable response may be with respect to any of the parameters set forth with respect to FIG. 13A. The response may be a particular parameter such as, e.g., the amplitude of the response.
  • [0131]
    In step 1425 the intrinsic breathing pattern is sensed and recorded. In step 1430 the intrinsic breathing parameters are recalculated. In step 1435 the stored response is compared to the intrinsic breathing parameters, and an accuracy score or figure of merit is determined for the response.
  • [0132]
    At step 1440 a check is made to see if all of the electrodes in the array have been evaluated. If not, steps 1410 through 1435 are repeated. If all electrodes have been evaluated, the process is done at step 1445.
  • [0133]
    FIG. 14B shows a flow chart of a preliminary array mapping method for regulated breathing in accordance with an embodiment of the present invention. In step 1450 an electrode is selected from the array. In step 1455 a locator wave is applied to the selected electrode (e.g., in a dynamic or fixed synchronized manner). A locator wave typically has fixed parameters and a low current.
  • [0134]
    In step 1460 the response to the locator wave is sensed and stored. In step 1465 the stored response is compared to a baseline reference (e.g., as obtained from the process of FIG. 13B), and an accuracy score or figure of merit is determined for the response.
  • [0135]
    At step 1470 a check is made to see if all of the electrodes in the array have been evaluated. If not, steps 1450 through 1465 are repeated. If all electrodes have been evaluated, the process is done at step 1475.
  • [0136]
    FIG. 15A shows a flow chart of a single parameter mapping method for intrinsic breathing in accordance with an embodiment of the present invention. In step 1510 a set of candidate electrodes is selected, i.e., electrodes that have given the best response. This set may be selected on the basis of accuracy scores determined by the process shown in FIG. 14A. In step 1515 a response parameter is selected for qualification. Examples of response parameters are: inspiration length, exhalation length, rate, amplitude, rest length and cycle length, slope of the inspiration cycle, slope of the expiration cycle, peak flow per time, percent peak flow per percent of inspiration time, and sustaining positive flow as a time value or as a percent of inspiration cycle.
  • [0137]
    In step 1520 a test wave is adjusted to match the intrinsic breath duration. Other parameters may subsequently be adjusted, for example: by lowering maximum current or lowering maximum frequency if peak flow/movement/EMG/volume/etc. are achieved too quickly; by increasing initial current amplitude or initial frequency if flow/EMG/pressure/etc initiation is delayed from delivery of initial pulse; or by changing (e.g., increasing) the ramp slope if flow/movement/EMG/volume/etc. has had more than one peak during an inspiration period. Other parameters that may also be adjusted are amplitude, frequency, shape, and timing. The test wave may also be adjusted to achieve a desired response, e.g., a percent of sustained positive airflow with respect to an inspiration cycle or other response.
  • [0138]
    In step 1525 an individual electrode is selected from the set of candidate electrodes selected in step 1510. In step 1530 the test wave constructed in step 1520 is delivered to the electrode (e.g., fixed or dynamically synchronized). In step 1535 the response to the test wave is sensed and stored.
  • [0139]
    In step 1540 the intrinsic breathing pattern is sensed and recorded. In step 1545 the intrinsic breathing parameters are recalculated. In step 1550 the stored response is compared to the intrinsic breathing parameters, and an accuracy score or figure of merit is determined for the response.
  • [0140]
    At step 1555 a check is made to see if all of the electrodes in the array have been evaluated. If not, steps 1510 through 1550 are repeated. If all electrodes have been evaluated, the process is done at step 1560.
  • [0141]
    FIG. 15B shows a flow chart of a single parameter mapping method for regulated breathing in accordance with an embodiment of the present invention. In step 1570 a set of candidate electrodes is selected. This set may be selected on the basis of accuracy scores determined by the process shown in FIG. 14B. In step 1572 a response parameter is selected for qualification. Examples of response parameters are: EMG, flow, tidal volume, movement and pressure.
  • [0142]
    In step 1574 a test wave is adjusted to match the intrinsic breath duration. Other parameters that may also be adjusted as well. In step 1576 an individual electrode is selected from the set of candidate electrodes selected in step 1570. In step 1578 the test wave constructed in step 1574 is delivered to the electrode (e.g., fixed or dynamically synchronized). In step 1580 the response to the test wave is sensed and stored.
  • [0143]
    In step 1582 the stored response is compared to a baseline reference, and an accuracy score or figure of merit is determined for the response.
  • [0144]
    At step 1584 a check is made to see if all of the electrodes in the array have been evaluated. If not, steps 1570 through 1582 are repeated. If all electrodes have been evaluated, the process is done at step 1586.
  • [0145]
    FIG. 16A shows a flow chart of a multi-parameter mapping method for intrinsic breathing in accordance with an embodiment of the present invention. In step 1610 an electrode is selected. The electrode may be selected on the basis of the accuracy score determined in the process shown in FIG. 14A or FIG. 15A.
  • [0146]
    In step 1615 a plurality of response parameters are selected for qualification. This may be done to refine the elelctorde choice or if a single parameter has not resulted in an electrode selection. Adjustments may be made where necessary in a manner similar as described with reference to FIG. 15A. Examples of response parameters are: EMG, flow, tidal volume, movement and pressure. An example of a pair of parameters are tidal volume and the measured parameter associated with diaphragm activation that shows the greatest dynamic range.
  • [0147]
    In step 1620 a therapy wave is adjusted to match the intrinsic breath duration. Other parameters may also be adjusted as described with reference to FIG. 15A. For example, the therapy wave may be adjusted to elicit an inspiration slope, a percentage peak value in a minimum percentage of the inspiration cycle, or a percentage of the peak inspiriaton in a minimum amount of time. In step 1625 the therapy wave constructed in step 1620 is delivered to the electrode (e.g., fixed or dynamically synchronized). In step 1630 the response to the therapy wave is sensed and stored.
  • [0148]
    In step 1635 the intrinsic breathing pattern is sensed and recorded. In step 1640 the intrinsic breathing parameters are recalculated. In step 1645 the stored response is compared to the intrinsic breathing parameters, and an accuracy score or figure of merit is determined for the response.
  • [0149]
    At step 1650 a check is made to see if the accuracy score or figure of merit determined in step 1645 is greater than a predetermined value. If not, steps 1610 through 1645 are repeated. If yes, the electrode location is qualified as a therapeutic locus and the process is done at step 1655.
  • [0150]
    FIG. 16B shows a flow chart of a multi-parameter mapping method for regulated breathing in accordance with an embodiment of the present invention. In step 1660 an electrode is selected. The electrode may be selected on the basis of the accuracy score determined in the process shown in FIG. 14B or FIG. 15B.
  • [0151]
    In step 1665 at least two response parameters are selected for qualification. Examples of response parameters are: EMG, flow, tidal volume, movement and pressure. An example of a pair of parameters are tidal volume and the measured parameter associated with diaphragm activation that shows the greatest dynamic range.
  • [0152]
    In step 1670 a therapy wave is adjusted to match the intrinsic breath duration. Other parameters may also be adjusted. In step 1675 the therapy wave constructed in step 1670 is delivered to the electrode (e.g., fixed or dynamically synchronized). In step 1680 the response to the therapy wave is sensed and stored.
  • [0153]
    In step 1685 the stored response is compared to a baseline reference, and an accuracy score or figure of merit is determined for the response.
  • [0154]
    At step 1690 a check is made to see if the accuracy score or figure of merit determined in step 1685 is greater than a predetermined value. If not, steps 1660 through 1685 are repeated. If yes, the electrode location is qualified as a therapeutic locus and the process is done at step 1695.
  • [0155]
    With respect to hierarchical optimization scheme described with reference to FIGS. 13-16, if one parameter does not give the user control over enough breathing parameters to match the intrinsic breathing characteristics, then another parameter is hierarchically added and adjusted that parameter until it provides sufficient control. If it does not, then again, another parameter is added until sufficient control over the breathing pattern or morphology is reached.
  • [0156]
    As an alternative, instead of using a natural breathing pattern as set for the with respect to FIGS. 12-16B, a desired breathing pattern, for example, to manipulate physiological responses or to treat disorders, may be selected or programmed into the device. The electrodes may the be selected as set forth with reference to FIGS. 14-16 using the desired breathing pattern instead of the natural breathing pattern for comparison.
  • [0157]
    The stimulation device may be used, for example in subjects with breathing disorders, heart failure patients and patients who cannot otherwise breathe on their own such as spinal cord injury patients.
  • [0158]
    Safety mechanisms may be incorporated into any stimulation device in accordance with the invention. The safety feature disables the device under certain conditions. Such safety features may include a patient or provider operated switch, e.g. a magnetic switch. In addition a safety mechanism may be included that determines when patient intervention is being provided. For example, the device will turn off if there is diaphragm movement sensed without an EMG as the case would be where a ventilator is being used.
  • [0159]
    While the invention has been described in detail with reference to preferred embodiments thereof, it will be apparent to one skilled in the art that various changes can be made, and equivalents employed, without departing from the scope of the invention.
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Classifications
U.S. Classification607/42, 600/529
International ClassificationA61B5/0488, A61N1/36, A61B5/08
Cooperative ClassificationA61B5/4818, A61B5/08, A61N1/36132, A61N1/3601, A61B5/7264, A61B5/0488
European ClassificationA61N1/36C
Legal Events
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Mar 14, 2005ASAssignment
Owner name: INSPIRATION MEDICAL, INC., CALIFORNIA
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:TEHRANI, AMIR J.;LEE, CHANG;LIGON, DAVID;AND OTHERS;REEL/FRAME:015899/0862;SIGNING DATES FROM 20050110 TO 20050201
Dec 14, 2007ASAssignment
Owner name: RMX, L.L.C., CALIFORNIA
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:INSPIRATION MEDICAL, INC.;REEL/FRAME:020266/0533
Effective date: 20070831