Tissue resistance measurement

The disclosure describes tissue resistance measurement techniques. To avoid errors caused by bandwidth limitations of the amplifier that amplifies a signal used to determine the tissue resistance, the disclosure describes determining values at different frequencies, where the values include respective error values. The respective error values are proportional to the respective frequencies, and based on this relationship the error value can be removed from the tissue resistance measurement.

TECHNICAL FIELD

The disclosure relates to tissue resistance measurement.

BACKGROUND

Implantable medical devices, such as electrical stimulators or therapeutic agent delivery devices, have been proposed for use in different therapeutic applications, such as deep brain stimulation (DBS), spinal cord stimulation (SCS), pelvic stimulation, gastric stimulation, peripheral nerve stimulation, functional electrical stimulation. In some therapy systems, an implantable electrical stimulator delivers electrical therapy to a target tissue site within a patient with the aid of one or more electrodes, which may be deployed by medical leads, on a housing of the electrical stimulator, or both.

During a programming session, which may occur during implant of the medical device, during a trial session, or during an in-clinic or remote follow-up session after the medical device is implanted in a patient, a clinician may generate one or more therapy programs (also referred to as therapy parameter sets) that provide efficacious therapy to the patient, where each therapy program may define values for a set of therapy parameters. A medical device may deliver therapy to the patient according to one or more stored therapy programs. In the case of electrical stimulation, the therapy parameters may define characteristics of the electrical stimulation waveform to be delivered.

SUMMARY

The disclosure describes example techniques for resistance measurement. For instance, the techniques may reduce, or otherwise remove, an error value in a resistance measurement, where the error is caused due to circuit bandwidth limitations. For example, for tissue resistance measurement, a medical device includes an amplifier that receives an input signal that includes a real-part and an imaginary-part, and outputs a signal that includes a real-part and an imaginary-part. The amplitude of the real-part of the input signal is a function of the tissue resistance, and the imaginary-part of the input signal is a function of reactance in a signal path to the tissue. The input and output signals may be modulated signals with a certain frequency. The medical device determines the tissue resistance based on the real-part of the output signal (e.g., after further processing of the output signal to remove the imaginary-part).

In this disclosure, the terms “real-part” and “imaginary-part” are used to differentiate between signals generated from resistive and reactive components. The real-part is from resistance, and the imaginary-part is generated form reactive components like capacitors and inductors. The term “imaginary” should not be interpreted to mean that this so-called imaginary-part does not exist, but rather as a way to differentiate the signal types.

Ideally, the real-part of the output signal is a rectangular wave. However, due to bandwidth limitations of the amplifier, the real-part of the output signal is not a rectangular wave, resulting in errors in the tissue resistance determination. In the techniques described in this disclosure, the medical device may generate the output signal at different frequencies (e.g., a plurality of signals outputted by the amplifier). In each of the output signals, there is a portion related to the actual tissue resistance, and a portion related to the respective error values. The actual tissue resistance is not a function of the signal frequency, but the respective error values may be a function of the signal frequency (e.g., in instances where the further processing of the output of the amplifier is performed at the same frequency as the frequency of the input or output signal). Because the error value is a function of the signal frequency and the actual tissue resistance is not, the medical device may be able to remove the error value based on the different frequencies of the different output signals.

In one example, the disclosure describes a method for tissue resistance measurement, the method comprising generating, at an electrode, a first electrical signal of a first type through outputting, via the electrode, a first electrical signal of a second type at a first frequency, processing the first electrical signal of the first type at the first frequency to generate a first output signal, generating, at the electrode, a second electrical signal of the first type through outputting, via the electrode, a second electrical signal of the second type at a second, different frequency, processing the second electrical signal of the first type at the second frequency to generate a second output signal, and determining a tissue resistance at the electrode based on the first output signal, the second output signal, and a ratio between the first frequency and the second frequency.

In another example, the disclosure describes a system for tissue resistance measurement, the system comprising at least one electrical signal source configured to generate, at an electrode, a first electrical signal of a first type through outputting, via the electrode, a first electrical signal of a second type at a first frequency, and generate, at the electrode, a second electrical signal of the first type through outputting, via the electrode, a second electrical signal of the second type at a second, different frequency. The system also includes resistance measurement circuitry configured to process the first electrical signal of the first type at the first frequency to generate a first output signal, and process the second electrical signal of the first type at the second frequency to generate a second output signal. The system also includes a processor configured to determine a tissue resistance at the electrode based on the first output signal, the second output signal, and a ratio between the first frequency and the second frequency.

In another example, the disclosure describes a system for tissue resistance measurement, the system comprising means for generating, at an electrode, a first electrical signal of a first type through outputting, via the electrode, a first electrical signal of a second type at a first frequency, means for processing the first electrical signal of the first type at the first frequency to generate a first output signal, means for generating, at the electrode, a second electrical signal of the first type through outputting, via the electrode, a second electrical signal of the second type at a second, different frequency, means for processing the second electrical signal of the first type at the second frequency to generate a second output signal, and means for determining a tissue resistance at the electrode based on the first output signal, the second output signal, and a ratio between the first frequency and the second frequency.

DETAILED DESCRIPTION

A medical device, such as an implantable medical device (IMD), may be configured to determine the resistance of tissue such as, e.g., human tissue. By determining the resistance of tissue, the IMD or a clinician can determine therapy parameters (e.g., amplitude) of electrical neurostimulation (e.g., voltage or current) outputted by the IMD to provide proper neurostimulation therapy.

One example way in which to determine the tissue resistance is for the IMD to output a current via electrodes coupled to the tissue, determine a voltage caused by the flow of current through the tissue, and divide the voltage by the current to determine the tissue resistance. Conversely, the IMD may output a voltage via electrodes coupled to the tissue, determine a current caused by the voltage applied to the tissue, and divide the voltage by the current to determine the tissue resistance. For ease of description, the techniques are described with respect to a flow of current.

However, the flow of direct current (DC) current through tissue may not be advisable, and the IMD may instead output a modulated current or modulated voltage (e.g., such as one that forms a rectangular wave with a particular frequency) via electrodes. This modulated current or modulated voltage is referred to as an excitation signal. The excitation signal may be DC free using push-pull voltage and current sources to create a voltage or current that swings around zero volts. However, due to device error or if the duty cycle between the pus-pull voltage and current sources is not exactly 50%, there may be a slight DC voltage or current. To further ensure that DC current does not flow through tissue, the IMD includes a capacitor in the signal path of the electrode to block the DC current.

The inclusion of the capacitor in the signal path of the electrode adds a reactive component in the signal path, which adds reactance. For example, if there was no capacitor in the signal path, then the voltage caused by the flow of current would only be a function of the resistance of the tissue (i.e., V=I*Rtissue). However, because there is a capacitor in the signal path, the voltage caused by the flow of current is a function of the resistance of the tissue and the reactance of the capacitor (i.e., V=I*(Rtissue+jXcapacitor)). In addition to the capacitor in the signal path, there may other sources of capacitance as well such as capacitance from tissue interface, capacitance in the return path with the housing of the medical device, as well as other possible capacitance sources.

In other words, the voltage caused by the flow of the modulated current includes a real-part (e.g., I*Rtissue) and an imaginary-part (e.g., I*jXcapacitor, where j is square-root of −1). Again, this so-called imaginary-part refers to the contribution to the signal from the reactive components such as capacitors, and should not be interpreted to mean that the signal does not exist. By removing the imaginary-part of the voltage signal, the IMD may determine the tissue resistance. One example technique to remove the imaginary-part of the voltage signal is to use a chopper circuit and an averager circuit. For instance, an amplifier may receive input voltage signal that includes the real-part and the imaginary-part. The amplifier outputs a voltage signal (e.g., in examples where the amplifier is a voltage amplifier) or a current signal (e.g., in examples where the amplifier is a transconductance amplifier). In either case, the output signal includes a real-part and an imaginary-part.

As described above, the modulated current may be a rectangular wave with a certain frequency. Because the tissue is predominantly resistive, the real-part of the output signal is still a rectangular wave (assuming a very high bandwidth amplifier), but because the capacitor is reactive and the reactance is a function of frequency, the imaginary-part of the output signal is not a rectangular wave, and is instead a triangular wave.

The chopper circuit receives the output signal, and performs chopping at the same frequency as the frequency of the modulated current. The chopping function can be considered as multiplying the signal by one for half a period, and multiplying the signal by negative one for the other half of the period. Because the chopping frequency is the same as the frequency of the rectangular wave, the chopper circuit results in multiplying the real-part of the output signal by one for the portion of the real-part of the output signal that is positive, and multiplying the imaginary-part of the output signal by negative one for the portion of the real-part of the output signal that is negative, thereby converting the negative portion to a positive value. In this example, in addition to the chopping frequency being the same as the frequency of the rectangular wave, the chopping may be phase aligned with the rectangular-wave (e.g., the chopper circuit multiplies the rectangular wave by one for half a period and switches to multiplying the rectangular wave by negative one for half a period and approximately at the time when the rectangular wave switches from a high to a low).

This way, the chopper circuit converts the real-part of the output signal into a constant value (e.g., constant voltage or current, or DC voltage or DC current). Based on the same principles, the chopper circuit converts the imaginary-part of the output signal into a saw-tooth waveform. An averager circuit (e.g., an averaging analog-to-digital converter) averages the output of the chopper circuit. Because the saw-tooth waveform includes as many positive values as negative values, the averaging of the saw-tooth waveform results in approximately zero (or as described above results in a value that can be compensated for based on measurements during manufacturing). However, the averaging of the constant value results in no change (i.e., the average of the constant values is the constant value).

As described above, the constant value is determined from the real-part of the output signal, which is a function of the tissue resistance, and the saw-tooth waveform is determined from the imaginary-part of the output signal which is a function of the reactance of the capacitor. The averager circuit removes the contribution of the saw-tooth waveform from the output of the chopper circuit, leaving only the constant value. A processor (e.g., of the IMD or of an external device) determines the tissue resistance based on the resulting constant value.

While the chopper circuit and averager circuit may be well suited for determining the tissue resistance, there may be certain drawbacks. For instance, as noted above, the amplifier may need to be very high bandwidth amplifier to ensure that the real-part of the output signal is a rectangular wave. A rectangular wave includes very fast rising and falling edges (i.e., very fast slew rates), and the amplifier would need very high bandwidth to be able to output such a rectangular wave with fast slew rates. However, amplifiers with such high bandwidth tend to be expensive and require high amounts of power for operation.

This disclosure provides example ways in which to utilize amplifiers, without needing the amplifiers to operate at extremely high bandwidth, while still providing accurate tissue resistance measurements. For example, if the amplifier does not provide relatively high bandwidth, the real-part of the output signal is not a rectangular wave, but more of a trapezoidal wave. This trapezoidal wave is referred to as an intermediate electrical signal, as it is between the amplifier and the chopper circuit. In this case, the trapezoidal wave is an input to the chopper circuit, and the output of the chopper circuit is not a constant value for the real-part, but instead a signal that for a portion is approximately equal to the constant value that the chopper circuit would have outputted had the input been a rectangular wave, and for the other portion equal to a value that is not the constant value.

The averager circuit receives the output of the chopper circuit and outputs an average value. In the case of a rectangular output signal to the chopper circuit, the average value that the averager circuit outputs is proportional to the tissue resistance. In the case of a trapezoidal output signal to the chopper circuit, the average value that the averager circuit outputs is a first value, which is proportional to the tissue resistance, plus a second value, which is an error value. If the IMD were to determine the tissue resistance based on this output of the averager circuit, the determined tissue resistance would be the actual tissue resistance plus a resistance error value.

In accordance with the techniques described in this disclosure, the IMD is configured to remove the error value from the output of the averager circuit. One example way in which the IMD may remove the error value from the output of the averager circuit is by applying a plurality (e.g., at least two) of input signals to the electrodes at different modulation frequencies. As described in more detail below, the actual tissue resistance is not a function of the modulation frequency, but the error value is. For instance, if the IMD applies an input signal at a first modulation frequency, the output of the averager circuit would be a first value plus a first error value, where the first error value is a function of the first modulation frequency. If the IMD applies an input signal at a second modulation frequency, the output of the averager circuit would be the same first value plus a second error value, where the second error value is a function of the second modulation frequency. The IMD may then remove the error value based on the two outputs of the averager circuit.

As an example, assume that the output of the averager circuit for a first modulation frequency is a first average value equal to A+B, where A is proportional to the actual tissue resistance and B is an error value and a function of the first modulation frequency. Assume that the output of the averager circuit for a second modulation frequency is a second average value equal to A+C, where A is still proportional to the actual tissue resistance and C is an error value and a function of the second modulation frequency. If the second modulation frequency is N times the first modulation frequency, then the second average value can be rewritten as A+N*B (i.e., because C will equal N*B). In this example, the IMD may multiply the first average value by N, resulting in the value of N*A+N*B, and multiply the second average value by −1, resulting in the value of −A−NB. The IMD may add the two resulting values together, for a value of (N−1)*A, and divide the resulting value by (N−1), resulting in the final value of A. As described above, the value of A is proportional to the actual tissue resistance, and in this way, the IMD removes the error caused by the limited bandwidth of the amplifier. The IMD may then determine the tissue resistance based on the value of A. Also, if the value of N is two, then division by (N−1) may not be needed since two minus one is one.

While the foregoing describes steps and processes as being implemented by an IMD, it will be understood this is for illustration only. Described processes and steps may be performed in whole, or in part, by some other device or system, such as one or more processors that reside outside the body. Such processor(s) could be provided, for instance, by a clinician or patient programmer or by a separate server, workstation, and so on.

FIG. 1is a conceptual diagram illustrating an example therapy system10that is configured to deliver therapy to patient12to manage a disorder of patient12. Patient12ordinarily will be a human patient. In some cases, however, therapy system10may be applied to other mammalian or non-mammalian non-human patients. In the example shown inFIG. 1, therapy system10includes medical device programmer14, implantable medical device (IMD)16, lead extension18, and one or more leads20A and20B (collectively “leads20”) with respective sets of electrodes24,26. IMD16includes a stimulation generator configured to generate and deliver electrical stimulation therapy to one or more regions of brain28of patient12via one or more electrodes24,26of leads20A and20B, respectively, alone or in combination with an electrode provided by outer housing34of IMD16.

In the example shown inFIG. 1, therapy system10may be referred to as a DBS system because IMD16is configured to deliver electrical stimulation therapy directly to tissue within brain28, e.g., a tissue site under the dura mater of brain28or one or more branches or nodes, or a confluence of fiber tracks. Frequency bands of therapeutic interest in DBS therapy may include the delta band (less than 4 Hz), the theta band (4-8 Hz), the alpha band (8-13 Hz), the beta band (13-35 Hz), the gamma band (35-100 Hz) and the high gamma band (100-400 Hz). In other examples, leads20may be positioned to deliver therapy to a surface of brain28(e.g., the cortical surface of brain28). For example, in some examples, IMD16may provide cortical stimulation therapy to patient12, e.g., by delivering electrical stimulation to one or more tissue sites in the cortex of brain28. Frequency bands of therapeutic interest in cortical stimulation therapy may include the theta band, and the gamma band.

DBS may be used to treat or manage various patient conditions, such as, but not limited to, seizure disorders (e.g., epilepsy), pain, migraine headaches, psychiatric disorders (e.g., major depressive disorder (MDD), bipolar disorder, anxiety disorders, post traumatic stress disorder, dysthymic disorder, and obsessive compulsive disorder (OCD), behavior disorders, mood disorders, memory disorders, mentation disorders, movement disorders (e.g., essential tremor or Parkinson's disease), Huntington's disease, Alzheimer's disease, or other neurological or psychiatric disorders and impairment of patient12. Therapy systems configured for treatment of other patient conditions via delivery of therapy to brain28can also be used in accordance with the techniques for determining one or more therapeutic windows disclosed herein.

In the example shown inFIG. 1, IMD16may be implanted within a subcutaneous pocket in the pectoral region of patient12. In other examples, IMD16may be implanted within other regions of patient12, such as a subcutaneous pocket in the abdomen or buttocks of patient12or proximate to the cranium of patient12. Implanted lead extension18is coupled to IMD16via connector block30(also referred to as a header), which may include, for example, electrical contacts that electrically couple to respective electrical contacts on lead extension18. The electrical contacts electrically couple the electrodes24,26carried by leads20to IMD16. Lead extension18traverses from the implant site of IMD16, along the neck of patient12and through the cranium of patient12to access brain28. IMD16can be constructed of a biocompatible material that resists corrosion and degradation from bodily fluids. IMD16may comprise a hermetic outer housing34to substantially enclose components, such as a processor, a therapy module, and memory.

In the example shown inFIG. 1, leads20are implanted within the right and left hemispheres, respectively, of brain28in order to deliver electrical stimulation to one or more regions of brain28, which may be selected based on many factors, such as the type of patient condition for which therapy system10is implemented to manage. Other implant sites for leads20and IMD16are contemplated. For example, IMD16may be implanted on or within cranium32or leads20may be implanted within the same hemisphere at multiple target tissue sites or IMD16may be coupled to a single lead that is implanted in one or both hemispheres of brain28.

During implantation of lead16within patient12, a clinician may attempt to position electrodes24,26of leads20such that electrodes24,26are able to deliver electrical stimulation to one or more target tissue sites within brain28to manage patient symptoms associated with a disorder of patient12. Leads20may be implanted to position electrodes24,26at desired locations of brain28via any suitable technique, such as through respective burr holes in the skull of patient12or through a common burr hole in the cranium32. Leads20may be placed at any location within brain28such that electrodes24,26are capable of providing electrical stimulation to target therapy delivery sites within brain28during treatment.

The anatomical region within patient12that serves as the target tissue site for stimulation delivered by IMD14may be selected based on the patient condition. Different neurological or psychiatric disorders may be associated with activity in one or more of regions of brain28, which may differ between patients. Accordingly, the target therapy delivery site for electrical stimulation therapy delivered by leads20may be selected based on the patient condition. For example, a suitable target therapy delivery site within brain28for controlling a movement disorder of patient12may include one or more of the pedunculopontine nucleus (PPN), thalamus, basal ganglia structures (e.g., globus pallidus, substantia nigra or subthalamic nucleus), zona inserta, fiber tracts, lenticular fasciculus (and branches thereof), ansa lenticularis, or the Field of Forel (thalamic fasciculus). The PPN may also be referred to as the pedunculopontine tegmental nucleus.

As another example, in the case of MDD, bipolar disorder, OCD, or other anxiety disorders, leads20may be implanted to deliver electrical stimulation to the anterior limb of the internal capsule of brain28, and only the ventral portion of the anterior limb of the internal capsule (also referred to as a VC/VS), the subgenual component of the cingulate cortex (which may be referred to as CG25), anterior cingulate cortex Brodmann areas 32 and 24, various parts of the prefrontal cortex, including the dorsal lateral and medial pre-frontal cortex (PFC) (e.g., Brodmann area 9), ventromedial prefrontal cortex (e.g., Brodmann area 10), the lateral and medial orbitofrontal cortex (e.g., Brodmann area 11), the medial or nucleus accumbens, thalamus, intralaminar thalamic nuclei, amygdala, hippocampus, the lateral hypothalamus, the Locus ceruleus, the dorsal raphe nucleus, ventral tegmentum, the substantia nigra, subthalamic nucleus, the inferior thalamic peduncle, the dorsal medial nucleus of the thalamus, the habenula, the bed nucleus of the stria terminalis, or any combination thereof.

As another example, in the case of a seizure disorder or Alzheimer's disease, for example, leads20may be implanted to deliver electrical stimulation to regions within the Circuit of Papez, such as, e.g., one or more of the anterior thalamic nucleus, the internal capsule, the cingulate, the fornix, the mammillary bodies, the mammillothalamic tract (mammillothalamic fasciculus), or the hippocampus. Target therapy delivery sites not located in brain28of patient12are also contemplated.

Although leads20are shown inFIG. 1as being coupled to a common lead extension18, in other examples, leads20may be coupled to IMD16via separate lead extensions or directly coupled to IMD16. Moreover, althoughFIG. 1illustrates system10as including two leads20A and20B coupled to IMD16via lead extension18, in some examples, system10may include one lead or more than two leads.

In the examples shown inFIG. 1, electrodes24,26of leads20are shown as ring electrodes. Ring electrodes may be relatively easy to program and may be capable of delivering an electrical field to any tissue adjacent to leads20. In other examples, electrodes24,26of leads20may have different configurations. For example, one or more of the electrodes24,26of leads20may have a complex electrode array geometry that is capable of producing shaped electrical fields, including interleaved stimulation. An example of a complex electrode array geometry may include an array of electrodes positioned at different axial positions along the length of a lead, as well as at different angular positions about the periphery, e.g., circumference, of the lead. The complex electrode array geometry may include multiple electrodes (e.g., partial ring or segmented electrodes) around the perimeter of each lead20, in addition to, or instead of, a ring electrode. In this manner, electrical stimulation may be directed to a specific direction from leads20to enhance therapy efficacy and reduce possible adverse side effects from stimulating a large volume of tissue.

In some examples, outer housing34of IMD16may include one or more stimulation and/or sensing electrodes. For example, housing34can comprise an electrically conductive material, which forms a capacitive interface with the surrounding tissue, that is exposed to tissue of patient12when IMD16is implanted in patient12. In other examples, leads20may have shapes other than elongated cylinders as shown inFIG. 1with active or passive tip configurations. For example, leads20may be paddle leads, spherical leads, bendable leads, or any other type of shape effective in treating patient12.

IMD16may deliver electrical stimulation therapy to brain28of patient12according to one or more therapy programs. A therapy program may define one or more electrical stimulation parameter values for therapy generated by a stimulation generator of IMD16and delivered from IMD16to a target therapy delivery site within patient12via one or more electrodes24,26. The electrical stimulation parameters may define an aspect of the electrical stimulation therapy, and may include, for example, voltage or current amplitude of an electrical stimulation signal, such as a voltage or current pulse amplitude, a frequency of the electrical stimulation signal, and, in the case of electrical stimulation pulses, a pulse rate, a pulse width, a waveform shape, and other appropriate parameters such as duration or duty cycle. In addition, if different electrodes are available for delivery of stimulation, a therapy parameter of a therapy program may be further characterized by an electrode combination, which may define electrodes24,26selected for delivery of electrical stimulation and their respective polarities. In some examples, stimulation may be delivered using a continuous waveform and the stimulation parameters may define this waveform.

In addition to being configured to deliver therapy to manage a disorder of patient12, therapy system10may be configured to sense bioelectrical brain signals of patient12. For example, IMD16may include a sensing module that is configured to sense bioelectrical brain signals within one or more regions of brain28via a subset of electrodes24,26, another set of electrodes, or both. Accordingly, in some examples, electrodes24,26may be used to deliver electrical stimulation from the therapy module to target sites within brain28as well as sense brain signals within brain28. However, IMD16can also use a separate set of sensing electrodes to sense the bioelectrical brain signals. In some examples, the sensing module of IMD16may sense bioelectrical brain signals via one or more of the electrodes24,26that are also used to deliver electrical stimulation to brain28. In other examples, one or more of electrodes24,26may be used to sense bioelectrical brain signals while one or more different electrodes24,26may be used to deliver electrical stimulation.

Examples of bioelectrical brain signals include, but are not limited to, electrical signals generated from local field potentials (LFP's) within one or more regions of brain28, such as, but not limited to, an electroencephalogram (EEG) signal or an electrocorticogram (ECoG) signal. In some examples, the electrical signals within brain28may reflect changes in electrical current produced by the sum of electrical potential differences across brain tissue.

External medical device programmer14is configured to wirelessly communicate with IMD16as needed to provide or retrieve therapy information. Programmer14is an external computing device that the user, e.g., the clinician and/or patient12, may use to communicate with IMD16. For example, programmer14may be a clinician programmer that the clinician uses to communicate with IMD16and program one or more therapy programs for IMD16. In addition, or instead, programmer14may be a patient programmer that allows patient12to select programs and/or view and modify therapy parameter values. The clinician programmer may include more programming features than the patient programmer. In other words, more complex or sensitive tasks may only be allowed by the clinician programmer to prevent an untrained patient from making undesired changes to IMD16.

Programmer14may be a hand-held computing device with a display viewable by the user and an interface for providing input to programmer14(i.e., a user input mechanism). For example, programmer14may include a small display screen (e.g., a liquid crystal display (LCD) or a light emitting diode (LED) display) that presents information to the user. In addition, programmer14may include a touch screen display, keypad, buttons, a peripheral pointing device or another input mechanism that allows the user to navigate though the user interface of programmer14and provide input. If programmer14includes buttons and a keypad, then the buttons may be dedicated to performing a certain function, e.g., a power button, the buttons and the keypad may be soft keys that change in function depending upon the section of the user interface currently viewed by the user, or any combination thereof.

In other examples, programmer14may be a larger workstation or a separate application within another multi-function device, rather than a dedicated computing device. For example, the multi-function device may be a notebook computer, tablet computer, workstation, cellular phone, personal digital assistant or another computing device that may run an application that enables the computing device to operate as a secure medical device programmer14. A wireless adapter coupled to the computing device may enable secure communication between the computing device and IMD16.

When programmer14is configured for use by the clinician, programmer14may be used to transmit programming information to IMD16. Programming information may include, for example, hardware information, such as the type of leads20, the arrangement of electrodes24,26on leads20, the position of leads20within brain28, one or more therapy programs defining therapy parameter values, and any other information that may be useful for programming into IMD16. Programmer14may also be capable of completing functional tests (e.g., measuring the impedance of electrodes24,26of leads20).

With the aid of programmer14or another computing device, a clinician may select one or more therapy programs for therapy system10and, in some examples, store the therapy programs within IMD16. Programmer14may assist the clinician in the creation/identification of therapy programs by providing physiologically relevant information specific to patient12.

Programmer14may also be configured for use by patient12. When configured as a patient programmer, programmer14may have limited functionality (compared to a clinician programmer) in order to prevent patient12from altering critical functions of IMD16or applications that may be detrimental to patient12.

Whether programmer14is configured for clinician or patient use, programmer14is configured to communicate to IMD16and, optionally, another computing device, via wireless communication. Programmer14, for example, may communicate via wireless communication with IMD16using radio frequency (RF) telemetry techniques known in the art. Programmer14may also communicate with another programmer or computing device via a wired or wireless connection using any of a variety of local wireless communication techniques, such as RF communication according to the 802.11 or BLUETOOTH® specification sets, infrared (IR) communication according to the IRDA specification set, or other standard or proprietary telemetry protocols. Programmer14may also communicate with other programming or computing devices via exchange of removable media, such as magnetic or optical disks, memory cards or memory sticks. Further, programmer14may communicate with IMD16and another programmer via remote telemetry techniques known in the art, communicating via a local area network (LAN), wide area network (WAN), public switched telephone network (PSTN), or cellular telephone network, for example.

Therapy system10may be implemented to provide chronic stimulation therapy to patient12over the course of several months or years. However, system10may also be employed on a trial basis to evaluate therapy before committing to full implantation. If implemented temporarily, some components of system10may not be implanted within patient12. For example, patient12may be fitted with an external medical device, such as a trial stimulator, rather than IMD16. The external medical device may be coupled to percutaneous leads or to implanted leads via a percutaneous extension. If the trial stimulator indicates DBS system10provides effective treatment to patient12, the clinician may implant a chronic stimulator within patient12for relatively long-term treatment.

System10shown inFIG. 1is merely one example of a therapy system for which therapeutic electrical stimulation parameters may be determined. The techniques described herein can be used to evaluate therapy programs for other therapy systems, such as therapy systems with other configurations of leads and electrodes, therapy systems with more than one IMD, and therapy systems including one or more leadless electrical stimulators (e.g., microstimulators having a smaller form factor than IMD16and which may not be coupled to any separate leads). The leadless electrical stimulators can be configured to generate and deliver electrical stimulation therapy to patient12via one or more electrodes on an outer housing of the electrical stimulator.

In some examples, IMD16, programmer14, or a user of programmer14determines the therapy parameters for the stimulation based on the tissue resistance at electrodes24,26. Tissue resistance at an electrode refers to the (spreading) resistance of the tissue from the electrode to ground. The ground node may be another electrode through which the current passes such as an electrode on lead20A or20B or an electrode on housing34. In some examples, housing34may itself form the ground.

There may be various reasons for tissue resistance determination, such as for therapy programming. For instance, if the tissue resistance at one of electrodes24,26is determined to be relatively high, then IMD16, programmer14, or the user may determine that a relatively high amplitude stimulation pulse is needed to reach the target stimulation area. As another example, IMD16, programmer14, or the user may control the amount of voltage or current delivered to each of electrodes24,26for therapy field steering. To achieve the intended therapy field, IMD16, programmer14, or the user may determine the amount of voltage or current delivered to each of electrodes24,26based on the determined tissue resistance at electrodes24,26.

In accordance with the techniques described in this disclosure, IMD16includes circuitry for determining the tissue resistance. For example, IMD16outputs a current via an electrode and determines the amount of voltage generated at the electrode due to the output of the current. IMD16or programmer14determines the tissue resistance by dividing the determined amount of voltage by the current. Although the above example describes IMD16outputting a current, in some examples, IMD16outputs a voltage via an electrode and determines the amount of current generated at the electrodes (e.g., the amount of current that flows through the electrode) due to the output of the voltage, and IMD16or programmer14determines the tissue resistance by dividing the voltage by the determined amount of current.

For ease of description, the techniques are described with IMD16outputting a current and determining a voltage. However, in general, IMD16may be considered as generating, at an electrode, an electrical signal of a first type (e.g., a voltage signal or a current signal) by outputting an electrical signal of a second type (e.g., a current signal if the generated signal is a voltage signal or a voltage signal if the generated signal is a current signal).

As described above, it may be undesirable for a DC current to flow through patient12, and therefore the electrical signal that IMD16outputs should be a modulated signal that is modulated at a particular frequency. As one example, the electrical signal that IMD16outputs is a rectangular wave current signal with a certain frequency (e.g., 3.125 kHz).

An electrical signal having a rectangular waveform applied to the tissue coupled to the electrode would result in another electrical signal having a rectangular waveform (e.g., a current signal with a rectangular waveform applied to the tissue results in a generated voltage signal with a rectangular waveform, and vice-versa). This is because the tissue is mainly resistive and not reactive.

However, to ensure that DC current does not flow into patient12, the signal path to one or more of electrodes24,26each include a reactive component that blocks the DC current. For example, each signal path to electrodes24,26includes a DC blocking capacitor. In this case, the capacitor adds reactance. Therefore, the signal that is generated from IMD16outputting the electrical signal is not a rectangular wave, but is a combination of a rectangular waveform and a triangular waveform.

For example, a current signal having a rectangular waveform flowing through the resistance of the tissue results in a voltage signal having a rectangular waveform, and the current signal having a rectangular waveform flowing through a capacitor results in a voltage signal having a triangular waveform. The rectangular waveform of the generated electrical signal is a function of the tissue resistance, and the triangular waveform of the generated electrical signal is a function of the reactance. In this disclosure, because the rectangular waveform of the generated electrical signal is a function of the resistivity of the tissue, the rectangular waveform may be referred to as the real-part of the generated electrical signal, and because the triangular waveform of the generated electrical signal is a function of the reactance of the reactive component, the triangular waveform may be referred to as the imaginary-part of the generated electrical signal.

To determine the tissue resistance, IMD16may remove the contribution of the imaginary-part from the generated signal, leaving the contribution of the real-part. One way in which to remove the contribution of the imaginary-part is to output the generated signal to a chopper circuit. In the techniques described in this disclosure, the chopper circuit operates at the same frequency as the frequency of the electrical signal that IMD16outputs.

A chopper circuit functions by multiplying an input signal by one for half a period, and negative one for the other half of the period. If the input to the chopper circuit is a rectangular wave, and the frequency of the chopper circuit is the same as that of the rectangular wave, then during the period where the rectangular wave is positive, the chopper circuit multiplies the rectangular wave by one. During the period where the rectangular wave is negative, the chopper circuit multiplies the rectangular wave by negative one, due to the frequency of the rectangular wave and frequency of the chopper circuit being the same.

By multiplying the rectangular wave by one when the rectangular wave is positive, and multiplying the rectangular wave by negative one when the rectangular wave is negative, the chopper circuit, in essence, keeps the positive portion of the rectangular wave the same and flips the negative portion of the rectangular wave into the positive portion. If the amplitude of the positive portion of the rectangular wave is the same as the negative portion of the rectangular wave, the output of the chopper circuit is a constant value.

For a triangular wave, the chopper circuit performs functions similar to those described for the rectangular wave. However, the output of the chopper circuit for an input triangular wave is not a constant value, and instead is a saw-tooth wave. The saw-tooth wave is positive for the same amount of time that it is negative (i.e., the saw-tooth wave includes no DC component).

The output of the chopper circuit may then be averaged by an averager circuit, which may be an analog circuit or a circuit including an A/D converter followed by a processor executing firmware to perform the averaging function. Averaging may include an integration operation and a division of the resulting integration by the amount of time used for the integration. For example, the A/D may be an integrator whose integration value is divided by the time over integration to determine an average value.

Because the saw-tooth wave is positive for the same amount of time that it is negative, the average of the saw-tooth wave is zero. However, in some cases, due to phase delay the average of the saw-tooth wave may not be zero. As described below, the error can be accounted for during manufacturing. The average of the constant value is the constant value. In this way, the averager circuit can be considered as removing the saw-tooth wave portion of the output from the chopper circuit, and maintains the constant value portion of the output from the chopper circuit. As described above, the constant value that the chopper circuit outputs is based on the real-part (i.e., rectangular wave) of the input to the chopper circuit, and the saw-tooth wave that the chopper circuit outputs is based on the imaginary-part (i.e., triangular wave) of the input to the chopper circuit. By averaging the output of the chopper circuit, the imaginary-part is removed (i.e., the saw-tooth wave is zeroed by the averaging or can be compensated for if not precisely zero) and the real-part is present (i.e., the average of the constant value is the constant value).

As also described above, the real-part of the input to the chopper circuit is proportional to the tissue resistance, and the imaginary-part of the input to the chopper circuit is proportional to the reactance. By averaging the output of the chopper circuit, the remaining constant value is proportional only to the tissue resistance, and IMD16or programmer14may determine the tissue resistance based on the constant value.

However, if the input to the chopper circuit is not a combination of a square wave and a triangular wave, then the output of the chopper circuit is not a combination of a constant value and a saw-tooth. For instance, the input of the chopper circuit is from the output of an amplifier, where the input to the amplifier is an electrical signal generated by the application of the voltage signal or current signal to electrodes24,26for tissue resistance measurement.

Accordingly, the input to the amplifier is a combination of a rectangular wave (e.g., the portion of the electrical signal that is proportional to the tissue resistance, also referred to as the real-part of the electrical signal) and a triangular wave (e.g., the portion of the electrical signal that is proportional to the reactance, also referred to as the imaginary-part of the electrical signal). Due to limited bandwidth of the amplifier, the amplifier may not output a combination of a rectangular wave and a triangular wave. Rather, the amplifier may output a combination of a trapezoidal wave and a triangular-like wave with sinusoidal transitions from a negative slope to a positive slope, and vice-versa.

For instance, a rectangular wave includes a very high slew rate (i.e., very fast rising and falling edges), and the amplifier may not be capable of outputting signals with such a high slew rate. Therefore, rather than a transition from a high to a low or vice-versa being virtually instantaneous, as would be the case in a rectangular wave, the transition from high to low or vice-versa in the output of the amplifier takes longer, resulting in a more trapezoidal wave. For similar reasons, the triangular wave portion of the electrical signal that the amplifier receives results in a triangular-like wave with sinusoid transitions from a negative slope to a positive slope, and vice-versa, because of the inability of the amplifier to perform immediate transitions from a negative slope to a positive slope, and vice-versa, due to the bandwidth limitations. The trapezoidal wave and triangular-like wave together form an intermediate electrical signal that is then processed to determine the tissue resistance.

In this case, the output of the chopper circuit for the trapezoidal wave portion may not be a constant value, and the output of the chopper circuit for the triangular-like wave portion may not be a saw-tooth. Although the result of chopping the triangular-like wave portion is not a saw-tooth, but saw-tooth-like, the resulting wave may still be positive for the same amount of time that it is negative (or approximately the same amount of time). Therefore, the averager circuit may still average this saw-tooth-like wave to zero, or approximately zero. Some calibration may be needed because the average may not be zero.

For the resulting wave from the chopping of the trapezoidal wave portion, the averager circuit may output an average value. However, this average value may be different than the constant value that the averager circuit would output if the output of the amplifier had been a more ideal rectangular wave. For example, assume that the output of the averager circuit for the case where the input to the chopper circuit is a combination of the rectangular wave and the triangular wave is a first average value, and the output of the averager circuit for the case where the input to the chopper circuit is a combination of a trapezoidal wave and a triangular-like wave is a second average value. In this example, the second average value equals the first average value plus an error value, where the error value is due to the input to the chopper circuit including a trapezoidal wave, rather than a rectangular wave. There may be little to no effect of the input to the chopper circuit including a triangular-like wave, rather than a triangular wave.

In the above example, the “first average value” would be the result had the input to the chopper circuit included a rectangular wave, rather than a trapezoidal wave, where the trapezoidal wave exists due to the bandwidth limitations of the amplifier. Therefore, the “first average value” is proportional to the tissue resistance, whereas the “second average value” includes an error value. The techniques described in this disclosure describe ways to reduce or eliminate the “error value.”

For instance, the error value is proportional to the frequency of the electrical signal. The greater the frequency of the electrical signal, the greater the error value in the output of the averager circuit will be, and the lower the frequency of the electrical signal, the lower the error value in the output of the averager circuit will be. As described in more detail below, the techniques described in this disclosure may exploit the relationship between the frequency of the electrical signal and the error value to remove or reduce the error value from the output of the averager circuit.

In some examples, the trapezoidal wave does not have the same rise and fall time as the rectangular wave, but rather slowly rises to a settling high voltage or slowly falls to a settling low voltage. The period of the electrical signal should be long enough to allow the trapezoidal wave to reach the settling high voltage or to fall to the settling low voltage. In this disclosure, the error value of the impedance measurement is proportional to the area difference between the rectangular wave and the trapezoidal wave that reaches its settling high or low voltages. The difference between the rectangular wave and the trapezoidal wave that reaches its settling high or low voltages (e.g., the error value in the tissue resistance) is a function of the frequency. By determining the impedance at different frequencies, IMD16or programmer14may subtract out the error value to determine a more accurate tissue resistance.

For example, IMD16or programmer14may determine multiple output values from the averager circuit for different electrical signals generated at different frequencies. Because the error value in each output of the averager circuit is proportional to the frequencies of the respective electrical signals, the ratio between the frequencies and the ratio between the error values may be approximately equal. IMD16or programmer14may utilize the ratio between the frequencies to determine by how much to add to or subtract from one of the values outputted by the averager circuit to remove the error value. After the error value from the output of the averager circuit is removed, the resulting value is proportional to the tissue resistance. In this manner, IMD16and/or programmer14may determine the value proportional to the tissue resistance, and then determine the tissue resistance based on the value proportional to the tissue resistance.

FIG. 2is functional block diagram illustrating components of an example IMD16. In the example shown inFIG. 2, IMD16includes processor60, memory62, stimulation generator64, sensing module66, switch module68, telemetry module70, and power source72. Memory62, as well as other memories described herein, may include any volatile or non-volatile media, such as a random access memory (RAM), read only memory (ROM), non-volatile RAM (NVRAM), electrically erasable programmable ROM (EEPROM), flash memory, and the like. Memory62may store computer-readable instructions that, when executed by processor60, cause IMD16to perform various functions described herein.

In the example shown inFIG. 2, memory62stores therapy programs74and operating instructions76, e.g., in separate memories within memory62or separate areas within memory62. Each stored therapy program74defines a particular program of therapy in terms of respective values for electrical stimulation parameters, such as an electrode combination, current or voltage amplitude, and, if stimulation generator64generates and delivers stimulation pulses, the therapy programs may define values for a pulse width and pulse rate of a stimulation signal. The stimulation signals delivered by IMD16may be of any form, such as stimulation pulses, continuous-wave signals (e.g., sine waves), or the like. Operating instructions76guide general operation of IMD16under control of processor60, and may include instructions for monitoring brain signals within one or more brain regions via electrodes24,26and delivering electrical stimulation therapy to patient12.

Stimulation generator64, under the control of processor60, generates stimulation signals for delivery to patient12via selected combinations of electrodes24,26. In some examples, stimulation generator64generates and delivers stimulation signals to one or more target regions of brain28(FIG. 1), via a select combination of electrodes24,26, based on one or more stored therapy programs74. The target tissue sites within brain28for stimulation signals or other types of therapy and stimulation parameter values may depend on the patient condition for which therapy system10is implemented to manage.

The processors described in this disclosure, including processor60, may include one or more digital signal processors (DSPs), general purpose microprocessors, application specific integrated circuits (ASICs), field programmable logic arrays (FPGAs), or other equivalent integrated or discrete logic circuitry, or combinations thereof. The functions attributed to processors described herein may be provided by a hardware device and embodied as software, firmware, hardware, or any combination thereof. Processor60is configured to control stimulation generator64according to therapy programs74stored by memory62to apply particular stimulation parameter values specified by one or more therapy programs.

In the example shown inFIG. 2, the set of electrodes24of lead20A includes electrodes24A,24B,24C, and24D, and the set of electrodes26of lead20B includes electrodes26A,26B,26C, and26D. Processor60may control switch module68to apply the stimulation signals generated by stimulation generator64to selected combinations of electrodes24,26. In particular, switch module68may couple stimulation signals to selected conductors within leads20, which, in turn, deliver the stimulation signals across selected electrodes24,26. Switch module68may be a switch array, switch matrix, multiplexer, or any other type of switching module configured to selectively couple stimulation energy to selected electrodes24,26and to selectively sense bioelectrical brain signals with selected electrodes24,26. Hence, stimulation generator64is coupled to electrodes24,26via switch module68and conductors within leads20. In some examples, however, IMD16does not include switch module68. For example, IMD16may include multiple sources of stimulation energy (e.g., current sources).

Stimulation generator64may be a single channel or multi-channel stimulation generator. In particular, stimulation generator64may be capable of delivering a single stimulation pulse, multiple stimulation pulses or continuous signal at a given time via a single electrode combination or multiple stimulation pulses or waveforms at a given time via multiple electrode combinations. In some examples, however, stimulation generator64and switch module68may be configured to deliver multiple channels on a time-interleaved basis. For example, switch module68may serve to time divide the output of stimulation generator64across different electrode combinations at different times to deliver multiple programs or channels of stimulation energy to patient12.

Sensing module66, under the control of processor60, is configured to sense bioelectrical brain signals of patient12via a selected subset of electrodes24,26or with one or more electrodes24,26and at least a portion of a conductive outer housing34of IMD16, an electrode on outer housing34of IMD16or another reference. Processor60may control switch module68to electrically connect sensing module66to selected electrodes24,26. In this way, sensing module66may selectively sense bioelectrical brain signals with different combinations of electrodes24,26(and/or a reference other than an electrode24,26). Although sensing module66is incorporated into a common housing34with stimulation generator64and processor60inFIG. 2, in other examples, sensing module66is in a separate outer housing from outer housing34of IMD16and communicates with processor60via wired or wireless communication techniques.

Telemetry module70is configured to support wireless communication between IMD16and an external programmer14or another computing device under the control of processor60. Processor60of IMD16may receive, as updates to programs, values for various stimulation parameters from programmer14via telemetry module70. The updates to the therapy programs may be stored within therapy programs74portion of memory62. Telemetry module70in IMD16, as well as telemetry modules in other devices and systems described herein, such as programmer14, may accomplish communication by RF communication techniques. In addition, telemetry module70may communicate with external medical device programmer14via proximal inductive interaction of IMD16with programmer14. Accordingly, telemetry module70may send information to external programmer14on a continuous basis, at periodic intervals, or upon request from IMD16or programmer14.

Power source72delivers operating power to various components of IMD16. Power source72may include a small rechargeable or non-rechargeable battery and a power generation circuit to produce the operating power. Recharging may be accomplished through proximal inductive interaction between an external charger and an inductive charging coil within IMD16. In some examples, power requirements may be small enough to allow IMD16to utilize patient motion and implement a kinetic energy-scavenging device to trickle charge a rechargeable battery. In other examples, traditional batteries may be used for a limited period of time.

In some example, the therapy parameters stored as part of therapy programs74are based on the tissue resistance at electrodes24,26. The tissue resistance is the resistance from the tissue coupled to one of electrodes24,26to ground, where one example of the ground is the case of IMD16(i.e., outer housing34). The tissue may not include any reactive components; hence, the term tissue “resistance,” rather than “impedance.”

The tissue resistance may affect the amplitude of the therapy parameters, as one example. For instance, if the target area to be stimulated is located in a relatively high resistance area of patient12, the amplitude of the therapy parameters may be selected to be higher than if the target area to be stimulated were located in a relatively low resistance area of patient12. For instance, in a current based stimulation system, the actual stimulation field, or V-field, is determined mostly by the resistive properties of the tissue, with the tissue resistance of the target area determining the shape of the realized stimulation V-field. Accordingly, in some examples, processor60may be configured to determine the tissue resistance of the tissue coupled to electrodes24,26.

As one example, switch module68may include tissue resistance circuitry needed for determining values that processor60uses to determine the tissue resistance. It should be understood that, in some examples, rather than or in addition to processor60determining the tissue resistance, programmer14may determine the tissue resistance based on the values determined by circuitry within switch module68. Also, the tissue resistance circuitry used to determine the tissue resistance need not necessarily reside within switch module68, and may be external or otherwise separate from switch module68.

Processor60may determine one impedance matrix Z, where the impedance matrix Z is a two dimensional matrix of tissue resistance values for each of electrodes24of lead20A, and another impedance matrix Z, where this matrix is a two dimensional matrix of tissue resistance values for each of electrodes26on lead20B. To generate the impedance matrix Z, processor60may cause switch module68to output an electrical signal (e.g., excitation signal) via one of electrodes24(e.g., electrode24A), and determine the tissue resistance at electrode24A and determine the tissue resistance values at electrodes24B-24D when the electrical signal is outputted by electrode24A. The resulting values form the first column in the impedance matrix Z. Next, processor60causes switch module68to output an electrical signal via electrode24B, and determines the tissue resistance at electrode24B and determines the tissue resistance values at electrodes24C-24D (and optionally24A) when the electrical signal is outputted by electrode24B. The resulting values form the second column in the impedance matrix Z. Processor60may repeat these steps to determine the resistance values at electrode24C, and24A,24B and24D when the electrical signal is outputted at electrode24C, and determine the resistance value at electrodes24D and at electrodes24A-24C, when the electrical signal is outputted via electrode24D.

At the conclusion of this process, processor60may have determined half of the values of impedance matrix Z for lead20A. For example, for a two-dimensional matrix, assume there is a diagonal line from the left-top of the matrix to the bottom-right of the matrix. Using the above techniques, processor60may have determined the tissue resistance values for the bottom portion of this hypothetical diagonal bisecting line. The tissue resistance values for the top portion of this hypothetical diagonal bisecting line may be the mirror of the bottom portion. In this manner, processor60may determine the impedance matrix Z for lead20A, and implement similar techniques to determine the impedance matrix Z for lead20B.

For example, the resistance measurement on the electrode on which the excitation signal is outputted makes the diagonal resistance measurement in the impedance matrix Z. The resistance measurement on the other electrodes based on the excitation signal is referred to as a transresistance and fills in the rest of the resistance Z matrix.

One way for the resistance measurement circuitry to determine the impedance matrix Z is to inject a small-signal sinusoidal AC current (e.g., AC current with relatively low amplitude) into each of lead electrode24, and measure the resulting voltage magnitude on all electrodes of interest (e.g., electrodes24). The division of the measured voltage with the current equals the magnitude of the resistance. However, due to parasitic capacitance and any DC blocking capacitors in the signal path to electrodes24,26B, the values in the impedance matrix Z include a real-part (Re(Z)) and an imaginary-part (Im(Z)). The magnitude of the values in the impedance matrix Z may be substantially equal to only the real-part if the value of the imaginary-part is minimized. In other words, by minimizing the affect of the parasitic capacitance and any DC blocking capacitors, the determined impedance matrix Z may be substantially equal to the tissue resistance.

To minimize the affect of the parasitic capacitance and any DC blocking capacitors, the resistance measurement circuitry may output the current at a frequency that is sufficiently high so that the real-part Re(Z) dominates the measured magnitude, but not so high because, otherwise, parasitic capacitance increases the contribution of the imaginary-part Im(Z). However, there may be drawbacks to such a technique for determining tissue resistance. For example, the optimal frequency range for determining the impedance matrix Z depends on the resistivity of the tissue itself. If lead20A is placed in a low-ohmic region (e.g., relatively low resistive area), the resistance measurement circuitry may need to output an AC current at a high frequency, and outputting current at such a high frequency may be impractical (i.e., the frequency region where resistance dominates the measured impedance shifts to high frequencies for the low-ohmic region). Conversely, if lead20A is placed in a high-ohmic region (e.g., relatively high resistive area), parasitic capacitors may dominate the magnitude of the values of the impedance matrix Z, reducing the accuracy of the estimation of the real-part of the value.

Furthermore, relying on the magnitude of determined values of the impedance matrix Z may at best be an estimation of the actual tissue resistance. For cases where a more precise tissue resistance measurement is appropriate, it may be possible that no frequency range of the AC current exists to provide a sufficiently precise tissue resistance determination.

In accordance with the techniques described in this disclosure, the resistance measurement circuitry may not rely on the magnitude of the determined impedance to estimate the tissue resistance. Rather, the resistance measurement circuitry may remove the imaginary-part, so that only the real-part is left. In this manner, the techniques described in this disclosure provide for a way to measure the real matrix (Re(Z)) directly without the drawbacks of the estimating tissue resistance from the magnitude of the Z values. The techniques may be used robustly and independently of the actual measured tissue resistance with low-frequency current or voltage injection sources. In other words, the techniques described in this disclosure can be utilized for any tissue location, and at a relatively low frequency that the resistance measurement circuitry can generate.

In the above examples, the bandwidth limitation of the amplifier causes an error value in the resistance measurement. However, one additional cause of the error value could be the input range of the amplifier. Therefore, if the techniques described in this disclosure are not used, the amplifier would need to be a high bandwidth amplifier with a wide input range that the amplifier can amplify without overloading. With the techniques described in this disclosure, the error value can be removed without needing an amplifier having a high bandwidth and wide input range.

As described in more detail, the frequency of a current signal or voltage signal that the resistance measurement circuitry outputs (i.e., the injection source frequency of the excitation signal) is compatible with the power-efficient and low-noise instrumentation amplifiers typically used in neural recording front-ends (i.e., the techniques described in this disclosure may utilize amplifiers already in an existing system, rather than needing additional amplifiers, for the tissue resistance measurement). Accordingly, the resistance measurement circuitry may be integrated into switch module68without much additional power or hardware overhead. The resistance measurement circuitry may be coupled to the lines that connect to electrodes24,26for the tissue resistance measurement, and may be used to determine the tissue resistance without requiring too much additional power or additional components.

As described in more detail below, the resistance measurement circuit includes at least one electrical signal source, an amplifier, a chopper circuit, and an averager circuit. The output of an electrical signal of a first type (e.g., a current signal), via one of electrodes24,26(e.g., electrode24A) by the at least one electrical signal source, generates an electrical signal of a second type (e.g., a voltage signal) at the input of the amplifier. For instance, the at least one electrical signal source may output a current signal having a rectangular waveform (i.e., a rectangular wave current signal). The reactance of the parasitic capacitance and the DC blocking capacitor, and the tissue resistance coupled to electrode24A result in a voltage signal forming at the input of the amplifier. This voltage signal includes a real-part from the tissue resistance, and an imaginary-part from the reactance component. The real-part of the input voltage signal provided to the amplifier may be a rectangular wave (i.e., a rectangular wave input voltage signal), and the imaginary-part of the input voltage signal to the amplifier may be triangular wave (i.e., a triangular wave input voltage signal).

The output of the amplifier is an electrical signal having a real-part and an imaginary-part, and referred to as an intermediate electrical signal. Assuming the bandwidth of the amplifier is extremely high, the real-part of the amplifier output would be a rectangular wave, and the imaginary-part of the amplifier output would be a triangular wave. The chopper circuit, functioning at the same frequency as the frequency of the electrical signal outputted by the at least one electrical signal source, converts the rectangular wave portion outputted by the amplifier to a constant value, and converts the triangular wave portion outputted by the amplifier to a saw-tooth wave, where the average of the saw-tooth wave is zero (i.e., the saw-tooth wave includes no DC component). The averager circuit averages the output of the chopper circuit. The result is that the constant value portion of the output of the chopper circuit remains, and the saw-tooth portion of the output of the chopper circuit averages out to close to zero (the difference if not zero can be determined during manufacturing). In this way, the final resulting value is proportional only to the tissue resistance, and the contribution from the parasitic and DC blocking capacitance is removed.

In other words, utilizing a chopper circuit and an averager circuit for tissue resistance may be based on the observation that the response of resistors (e.g., tissue resistance) and capacitors (e.g., parasitic, tissue interface, or DC blocking) is different when an AC current excitation is applied. This difference can be used to remove the capacitor response (i.e., the imaginary-part) from the measurement signal (i.e., the voltage signal) so that only the resistive response of interest remains.

However, the amplifier may not have sufficient bandwidth to output an electrical signal having a rectangular wave or a triangular wave. For such cases, the amplifier may output an electrical signal that includes a trapezoidal wave and a triangular-like wave (e.g., intermediate electrical signal). The chopper circuit may output a first jagged waveform for the trapezoidal wave input, and a second jagged waveform for the triangular-like wave input. The averager circuit may output an average value that is different than the value the averager circuit would have outputted had the output of the amplifier included a rectangular wave and a triangular wave. In other words, the average value outputted by the averager circuit equals the value outputted by the averager circuit for the rectangular wave scenario plus an error value.

In the techniques described in this disclosure, by determining average values with different frequencies for the electrical signal that the at least one electrical signal source outputs, processor60may be able to determine a value that is proportional to the tissue resistance, and remove the error value and the contribution from the parasitic and DC blocking capacitance. For example, the error value is proportional to the frequency of the electrical signal outputted by the at least one electrical source. In this case, the difference in the average values at the different frequencies may be proportional to the ratio of the different frequencies used to generate the average values. Utilizing techniques described in more detail herein, processor60may utilize the ratio between the different frequencies to remove the error value from one of the average values, resulting in a value that is proportional only to the tissue resistance. Processor60may then determine the tissue resistance from the resulting value.

In other words, utilizing multiple average values for tissue resistance measurement relates to power-efficient improvements to the accuracy of the tissue resistance measurement. Each measurement (e.g., average value) includes an error caused by the finite settling speed of the amplifier (e.g., the bandwidth limitations). If two subsequent measurements are performed, at two different current excitation frequencies (i.e., the frequency of the rectangular wave of the current signal), the dominant settling error in both measurements can be removed to improve the tissue resistance measurement accuracy without needing a fast-settling and power hungry front-end (e.g., without needing a high bandwidth, high power amplifier). As noted above, this error may be removed if the trapezoidal wave has enough time to settle (e.g., the frequency is not too fast and the trapezoidal wave has enough time to reach its final value).

The example illustrated inFIG. 2is one example way in which the techniques described in this disclosure may be implemented. However, the techniques described in this disclosure are not so limited.

FIG. 3is a functional block diagram illustrating components of an example medical device system. For example,FIG. 3shows schematically and in greater detail an example of a system for brain applications, here for neurostimulation and/or neurorecording as a deep brain stimulation system. As illustrated, probe system100comprises at least one probe130for brain applications with stimulation and/or recording electrodes132(e.g., 40 electrodes132can be provided on outer body surface at the distal end of the probe130). By means of the extension wire120, pulses P supplied by controller110(e.g., stimulation pulses) can be transmitted to the active lead can (ALC)111. The controller110can be an implantable pulse generator (IPG)110. In other words, IPG110, illustrated inFIG. 3, is another example of IMD16.

FIG. 4is a functional block diagram illustrating components of another example medical device system. For example,FIG. 4shows a schematic drawing of a system for brain applications according to one example of an electronic module500. The electronic module500is in this example integrated into the active lead can111.

System100ofFIG. 4having a DBS probe130as defined above comprises an IPG110and an active lead can111with an array of electronic switches that connects electrodes132arranged at the distal end of the lead300with the pulse generator lines of the IPG110either directly or indirectly through logic in the active lead can111and/or in the IPG110. In addition, IPG110includes neural recording facilities. IPG110and active lead can111may be connected through an interface cable120which may include for example, five lines. Accordingly, the IPG110has a 5-pin connector115which is connected to active lead can111via the interface cable120.

In one example, interface cable120comprises multiple cables including a lead extension that couples at a proximal end to the LCFX connector115of IPG110, and which terminates in a distal end connector (not shown inFIG. 4). This distal end connector couples to a corresponding proximal end connector carried by a cable that extends from, but is not selectively connectable/disconnectable to/from active lead can111. In an alternative example, interface cable120may comprise a single cable having a proximal end connector that couples to connector115of IPG110and a distal end connector that couples to 5-pin LCFX connector510of the active lead can111.

The active lead can111comprises a multi-pin connector with a 5-pin LCFX connector510for the interface cable120and a 40-pin connector520for the lead300. It is mechanically possible to design these two feed-through connectors510,520with a high pin density to reduce the area of the active lead can111significantly. However, this area advantage may only materialize if the electrical components of the active lead can111are shrunk in similar proportions as the feed-through connectors510,520. Moreover, a very thin active lead can111, most desirable to reduce its impact on skin erosion, may need a high pin density, but also a reduction in the height of both feedthrough pins511,521and interior electrical components. Thus, both the electronics volume and area of the active lead can111are miniaturized to realize a small active lead can111. Note that techniques to shrink the active lead can111can also be applied to the implantable pulse generator110, or any other implant module, for example, to trade for an increase in battery life time and/or increased functionality.

In accordance with the techniques described in this disclosure, active lead can111ofFIGS. 4 and 5may be configured to implement the tissue resistance techniques described in this disclosure. For example, active lead can111may include the resistance measurement circuitry of at least one electrical signal source, an amplifier, a chopper circuit, and an averager circuit as described above, and IPG110or active lead can111may include a processor, like processor60ofFIG. 2, for the tissue resistance determination.

As described above, the parasitic capacitance affects the tissue resistance measurement. This parasitic capacitance, formed by the electrode-tissue interface, as well as the DC blocking capacitor, may impact the tissue resistance measurement more when small electrodes, such as electrodes132, are formed on probe130. Moreover, active lead can111may be a relatively miniaturized module, and therefore, there may be limited space for DC blocking capacitors. This may result in needing low capacitance DC blocking capacitors, leading to relatively low block capacitance per electrode. In the techniques described in the disclosure, the effects of the parasitic capacitance and the DC blocking capacitors are removed, leading to an accurate tissue resistance measurement, which may otherwise have been impacted by the parasitic capacitance and the capacitance from the DC blocking capacitors.

Furthermore, leads20A and20B are one example of leads that can be utilized for therapy delivery and sensing. However, the techniques described in this disclosure are not so limited.

FIGS. 5A-5Cillustrate examples of probes for stimulation and/or sensing. Relative toFIGS. 5A and 5B,FIG. 5Cfurther illustrates a typical architecture for a Deep Brain Stimulation probe130that comprises a DBS lead300and an active lead can111comprising electronic means to address electrodes132on the distal end304of the thin film301, which is arranged at the distal end313and next to the distal tip315of the DBS lead300, as illustrated inFIG. 5B. The lead300comprises a carrier302for a thin film301, the carrier302providing the mechanical configuration of the DBS lead300and the thin film301. The thin film301may include at least one electrically conductive layer, such as one made of a biocompatible material. The thin film301is assembled to the carrier302and further processed to constitute the lead300. The thin film301for a lead may be formed by a thin film product having a distal end304, a cable303with metal tracks and a proximal end310, as illustrated inFIG. 5A. The proximal end310of the thin film301arranged at the proximal end311of the lead300is electrically connected to the active lead can111. The active lead can111comprises the switch matrix of the DBS steering electronics. In some examples, active lead can111may further comprise a signal generator that is in addition to, or instead of, a pulse/signal generator provided by IPG110. This signal generator of active lead can111may provide a signal to control stimulation delivered via electrodes132.

The distal end304of thin film301comprises the electrodes132for the brain stimulation. The proximal end310comprises the interconnect contacts305for each metal line in the cable303. The cable303comprises metal lines (not shown) to connect each distal electrodes132to a designated proximal contact305.

FIG. 6is a functional block diagram illustrating components of a resistance measurement circuitry. The resistance measurement circuitry includes electrical signal source1000and1010, switches S2and S3, inverter INV, resistor R2, amplifier1020, chopper circuit1040, and averager circuit1060. The components of the resistance measurement circuitry may be formed as an integrated circuit, and may be an ASIC that is part of switching module68. However, the techniques described in this disclosure are not so limited, and this logic may be separate components, combined in different ways, and need not necessarily be part of switching module68. For instance, in the example ofFIG. 4, some or all of these components may reside within active lead can.

InFIG. 6, the signal path SPX refers to the way in which stimulation therapy flows out of electrode24A, and the way in which sensed electrical signals enter via electrode24A. For ease of illustration, the connection to switch module68and the way in which the output from stimulation generator64flows to electrode24A or the way in which the sensed electrical signals are received by sensing module66is not illustrated. The signal path SPX includes a simplified model of one of a plurality of signal paths that can be coupled to stimulation generator64or sensing module66through a switch matrix (e.g., switch module68) or ALC. When switch S1is closed, stimulation is outputted or sensed electrical signals are provided.

Each signal path SPX relates to one electrode (e.g., electrode24A is illustrated inFIG. 6). Accordingly, there are for example, forty signal paths SPX, in examples where there are forty electrodes on a probe (e.g., as inFIG. 4) or four signal paths SPX (e.g., one for each of electrodes24A-24D). For ease of illustration, the circuitry for only electrode24A is illustrated, with the understanding that similar techniques may be used for tissue resistance determination for the other electrodes. It should be understood that the techniques described in this disclosure are applicable to other types of electrodes as well. As one example, the electrode that is part of the housing of IMD16may also be used as an electrode for implementing the example techniques. In general, any conductive component on IMD16may be used for performing the example techniques described in this disclosure.

The resistance R1represents all the resistance between switch module68(e.g., switch matrix resistance of switch module68, lead track resistance, which is resistance of the wire or bus within lead that connects to the electrode, and the tissue resistance itself) and a chosen return terminal (e.g., ground via housing34and/or housing of ALC111). The capacitor C is formed by the total series capacitance (e.g., DC blocking capacitor and electrode-tissue interface capacitance) in the loop.

The resistance measurement circuitry includes two electrical signal sources (e.g., electrical signal source1000and electrical signal source1010), supplying respective constant currents I1and I2. In some examples, electrical signal source1000and1010may supply constant voltages. The example is illustrated with respect to electrical signal sources1000and1010supplying constant currents. The amplitude of the output of electrical signal source1000and1010may be approximately the same, but it may be possible for the amplitudes to differ. Although not illustrated, a control loop, such as a DC servo loop, may control the amplitudes of electrical signal source1000and1010so that the amplitudes are kept to be the same.

Electrical signal source1000is coupled in series with switch S2to node RSV (response signal voltage). Electrical signal source1010is coupled in series with switch S3to node RSV. In this example, electrical signal sources1000and1010together implement a push-pull current source mutually supplying currents I1and I2to the signal path SPX if switch S1is closed. Switches S2and S3are controlled by control signal ΦCH (referred to as CLCK) which is a clock signal that alternately opens and closes switches S2and S3(i.e., switch S3receives the inverse of the signal to switch S2via inverter INV). Accordingly, either current I1or current I2flow through signal path SPX and out of electrode24A, when current I1is flowing, and into electrode24B, when current I2is flowing. The magnitudes of currents I1and I2may be equal (I1=I2=I0).

The stimulus or excitation signal (e.g., the electrical signal generated by electrical signal sources1000and1010) is a rectangular wave current signal alternating around a ground level (for example analog ground, system ground or virtual ground) with a positive amplitude and a negative amplitude of I0. The excitation signal may not include any DC content. In other words, the push-pull excitation generates a DC neutral periodic rectangular-wave current. For example, current I1flows out of electrode24A, and current I2flows in through electrode24A. Therefore, equal amounts of current flows out of electrode24A in one direction and into electrode24A in the other direction. In this case, current I1can be considered as a positive current and current I2can be considered as a negative current, meaning that there is no DC component in the current flowing through patient tissue.

The alternating frequency may be an order of magnitude larger than the typical stimulation frequencies for the neural application. For example, the frequency of the CLCK signal may be much larger than the frequency of neural application (e.g., 3.125 kHz or greater as merely one non-limiting example). In some examples, processor60may provide the CLCK signal; however, a component other than processor60may provide the CLCK signal. The amplitude I0(e.g., the amplitude of the current signals outputted by electrical signal sources1000and1010) is advantageously far below the currents typically used to stimulate neural tissue. As described above, this excitation current is injected via the switch module68or a switch matrix in ALC111of which only a single switch S1is shown. This switch S1connects to a series combination of a resistance R1and a capacitor C including all the resistance and capacitance of the signal path SPX.

If the signal path SPX is excited with an alternating current excitation signal (e.g., electrical signal sources1000and1010output an electrical signal of a second type), the response signal on node RSV is a voltage signal (e.g., an electrical signal of a first type). Node RSV is coupled to an input of amplifier1020. In some examples, amplifier1020is an instrumentation amplifier, such as an operational transconductance amplifier (OTA). In examples where amplifier1020is an OTA, amplifier1020converts the voltage signal at its input into a current signal.

It should be understood that amplifier1020is described as an OTA, as merely on example. In some examples, amplifier1020may be an amplifier that does not convert the voltage signal into a current signal, and is a voltage amplifier that outputs an amplified voltage signal. As another example, in examples where electrical signal sources1000and1010generate a rectangular wave voltage signal, amplifier1020may receive as input a current signal. In such cases, amplifier1020may covert the current signal into a voltage signal, or keep the current signal, and output an amplified current signal.

Amplifier1020may be a high resistance input so that the output of electrical signal sources1000and1010does not flow into amplifier1020, but instead through the tissue. Amplifier1020may convert the RSV voltage and covert it into a differential output current (however, a differential system is not needed and provided as one example). Amplifier1020may provide gain to the current or voltage input to amplifier1020, may be a unity gain amplifier (e.g., gain of 1), or may reduce the amplitude (e.g., provide less than 1 gain so that the output is smaller than the input).

In a possible configuration, input resistor R2is coupled to the positive input of amplifier1020. In the example illustrated inFIG. 6, amplifier1020amplifies (or unity gain or less than unity gain) the voltage signal generated on node RSV and, in case of an OTA, converts the signals into output currents IO1− and IO1+. Amplifier1020may convert the generated voltage signal into a current signal because it can be advantageous to process currents in the following stages (e.g., in chopper circuit1040) because the averager is used as integrator and it is easier to implement the integrator as an on-chip capacitor. If voltages were used, an inductor would be needed for integration, and forming an inductor on chip may not be possible requiring the inductor to be off chip.

As illustrated inFIG. 6, amplifier1040can have a symmetrical architecture (e.g., fully differential). In other words, the rectangular-wave current flowing through the resistance R1of the signal path SPX introduces a rectangular-wave voltage component, as illustrated inFIG. 7and described in more detail below, in the signal measured by amplifier1020. This same excitation current is integrated by the series capacitance C and this adds a triangular waveform component, illustrated inFIG. 8and explained in more detail below, to the signal measured by amplifier1020. The voltage signal at the input of amplifier1020(e.g., the voltage signal that includes the rectangular waveform component and the triangular waveform component) has no DC component.

Chopper circuit1040is coupled to the output(s) of amplifier1020. The frequency at which chopper circuit1040operates may be the same as the frequency of the excitation current. For example, as illustrated, the clock signal CLCK that controls switches S2and S3is the same clock signal that controls the operation of chopper circuit1040. In this way, the same frequency that is used for the alternating signal supplied by electrical signal sources1000and1010is used for chopper circuit1040.

The output signals of chopper circuit1040are signals IO2−, IO2+, which may be currents, and in some examples, symmetric currents. Averager circuit1060is coupled to the output of chopper circuit1040for receiving the output signal(s) IO2−, IO2+ of chopper circuit1040at input terminals IN1ADC, IN2ADC, respectively. Output signal(s) IO2−, IO2+ form intermediate electrical signal that outputs to chopper circuit1040. An example of the intermediate signal having the trapezoidal wave and triangular like wave is illustrated inFIGS. 13 and 14, respectively.

Averager circuit1060may be an analog-to-digital converter (ADC), and is an averaging and/or integrating ADC. However, averager circuit1060need not necessarily be an ADC in every example. Averaging generally increases the signal-to-noise ratio (SNR) of the ADC. In the techniques described in this disclosure, the averaging configuration of averager circuit1060positively affects the errors and noise produced by the previous stages (amplifier1020and chopper circuit1040) as some of these errors and/or artifacts are eliminated by averager circuit1060. Averager circuit1060may perform the averaging in an analog or in a digital manner. In general, averager circuit1060may average by summing up several samples and dividing the sum by the amount of samples. For example, averager circuit1060may perform an integration operation over a known time (e.g., a set number of periods) and dividing by the time over which the integration was performed.

In general, the amplifier1020amplifies its input voltage into a current (OTA) which is subsequently chopped, by chopper circuit1040, at the same frequency as the excitation source changes from current source I1to current source I2. To chop the output of amplifier1020, chopper circuit1040multiplies the current signal received from amplifier1020by one for half a period of the CLCK clock signal, and multiplies the current signal received from amplifier1020by negative one for the other half period of the CLCK clock signal.

The result of chopper circuit1040multiplying the rectangular wave of the current signal by one for half period, and by negative one for the other half period, results in a DC current component because one multiplied by the amplitude of positive part of the rectangular wave, which is half the period, results in the amplitude of the rectangular wave, and negative one multiplied by the amplitude of the negative part of the rectangular wave, which is the other half of the period, results in the same amplitude of the rectangular wave (i.e., negative one multiplied by a negative value is a positive value).

Therefore, the ADC of averager circuit1060digitizes a DC current component (illustrated inFIG. 9), which is the result of the chopped instrumentation amplifier rectangular-wave output current, and a superimposed saw-tooth component (illustrated inFIG. 10), which is the result of the chopped amplified triangular current wave. The averaging by averager circuit1060results in only the DC current at the input giving rise to a digital code DOUT at the output of averager circuit1060, while the saw tooth, whose DC content is zero, is effectively eliminated by the averaging (e.g., integrating action) of averager circuit1060. Thus the digital output code is representative of the measured resistance, and therefore, the real parts Re(Z) of the impedance matrix Z of all the signal paths can directly be measured by the techniques described in this disclosure when all electrodes132,24, or26of interest are scanned one after another.

It should be noted that if chopper circuit1040and electrical signal sources1000and1010are disabled, the same architecture can be used as neural recording channel. In other words, amplifier1020may be the same amplifier as that used for sensing signals, and a new, separate amplifier is not needed. Moreover, when the bandwidth of the amplifier1020in neural recording mode is too low for the excitation current frequency (typically in the kHz range), amplifier1020can be programmed to have a larger, but still relatively small, bandwidth during resistance measurement. In this manner, the architecture illustrated inFIG. 6together with the automatic programming of the ALC switch matrix via built-in state machines enables the direct measurement of the real part Re(Z) of the impedance matrix Z.

However, if the bandwidth of amplifier1020is limited (e.g., for a low-cost, low-power option), the output of amplifier1020may not be a combination of a rectangular wave current and a triangular wave current. Rather, the output of amplifier1020may be a combination of a trapezoidal wave current and a triangular-like wave current.

Moreover, the impact of the small-bandwidth, but power-efficient amplifier1020on the achievable measurement accuracy can largely be eliminated by the measurements of the resistance at two different frequencies f1(e.g., 1 kHz to 100 kHz) and f2(e.g., 10 kHz to 100 kHz). However, f1and f2should not be considered limited to these example frequency ranges. Processor60may then be configured to vary the control signal ΦCH between a first frequency f1and a second frequency f2. In some examples, these two frequencies f1and f2may be relatively close together. In this way, the errors due to insufficient settling (limited bandwidth) of amplifier1020and/or other stages can be eliminated.

To eliminate the errors from the limited bandwidth of amplifier1020, processor60may be configured to determine multiple average values (e.g., two average values) by generating multiple electrical signals (e.g., two electrical signals) at different frequencies (e.g., f1and f2). For example, electronic signal sources1000and1010may output, via electrode24A, a first current signal at a first frequency, causing a first voltage signal to be generated at the input of amplifier1020. Again, it should be noted that rather than outputting a current, it may be possible to output a voltage, which causes a current to be generated at the input of amplifier1020. For purposes of example, the techniques are described with respect to a current being outputted, with the understanding that the techniques function the same with a voltage being outputted.

The resistance measurement circuitry may process this first voltage signal. For example, processing this first voltage signal includes amplifier1020amplifying the first voltage signal, chopper circuit1040chopping the output of amplifier1020(e.g., the chopping the intermediate electrical signal), and averager circuit1060averaging the output of chopper circuit1040to generate a first output signal (e.g., a first average value). In this example, the first average value equals a value proportional to the tissue resistance plus a first error value that is proportional to the first frequency.

Then, electronic signal sources1000and1010may output, via electrode24A, a second current signal at a second frequency, causing a second voltage signal to be generated at the input of amplifier1020. Amplifier1020, chopper circuit1040, and averager circuit1060may process this second voltage signal to generate a second output signal (e.g., second average value). In this example, the second average value equals a value proportional to the tissue resistance plus a second error value that is proportional to the second frequency.

Because the first error value is proportional to the first frequency, and the second error value is proportional to the second frequency, the ratio of the first frequency to the second frequency equals the ratio of the first error value to the second error value (i.e., second frequency divided by first frequency equals second error value divided by first error value). For example, assume that the second frequency divided by the first frequency equals N (i.e., f2/f1=N). Accordingly, the second error value divided by the first error value also equals N (i.e., second error value/first error value=N). The second error value therefore equals N multiplied by the first error value (i.e., second error value=N*first error value).

As described above, the equations for the first average value and second average value are:
first average value=value proportional to tissue resistance+first error value;
second average value=value proportional to tissue resistance+second error value.

By substituting N*first error value for the second error value, the equation for the second average value can be rewritten as:
second average value=value proportional to tissue resistance+N*first error value.

In this case, there are now two equations and two unknowns (e.g., first average value and second average value are known from the output of averager circuit1060, the value of N is known because processor60sets the first frequency and second frequency, and the value proportional to tissue resistance and the first error value are unknown). By multiplying the equation for the first average value by N, the resulting equation is:
N*first average value=N*value proportional to tissue resistance+N*first error value.

Processor60may subtract the equation for the second average value from the above equation for N*first average value. In equation form, processor60may determine:
N*first average value−second average value=(N*value proportional to tissue resistance+N*first error value)−(value proportional to tissue resistance+N*first error value).

The above equation can be rewritten as:
N*first average value−second average value=(N*value proportional to tissue resistance−value proportional to tissue resistance)+(N*first error value−N*first error value).

The result of the above equation is:
N*first average value−second average value=(N−1)*value proportional to tissue resistance.

The above equation can then be rewritten as:
(N*first average value−second average value)/(N−1)=value proportional to tissue resistance.

Because N, the first average value, and the second average value are known, by multiplying the first average value by the ratio between the first excitation frequency and the second excitation frequency, subtracting the second average value from the result of the multiplication, and dividing the result of the subtract by (N−1), processor60may determine a value that is proportional to the tissue resistance, and the error value is removed from the measurement. Processor60may then determine the tissue resistance at electrode20A based on the value that is proportional to the tissue resistance. For example, if a current is applied, and the measured signal is a voltage (e.g., the value proportional to tissue resistance), the tissue resistance is equal to the voltage divided by the current. In some examples, if the ratio between the first and second frequencies is 2 (i.e., N=2), then processor60may multiply the first average value by 2 and subtract the second average value to determine the value proportional to the tissue resistance.

FIG. 7is a graphical diagram illustrating the rectangular wave portion of the electrical signal formed at an input of an amplifier used for tissue resistance measurement. For example,FIG. 7is a simplified representation of the waveform of the real part of a response signal received in the example illustrated inFIG. 6. The shown response signal is received on node RSV if the signal path SPX is excited by electronic signal sources1000and1010, in particular a push-pull current source as previously described. The real part is generated by the resistance RX of signal path SPX which is mainly due to the resistance of the tissue. The real part is a rectangular wave voltage signal alternating between the positive voltage V0=RX*I0(for I1=I0) and −V0=−RX*IO (for I2=I0) around ground level (0V), where RX is the tissue resistance.

For example, the rectangular-wave current flowing through the resistance R of the tissue introduces a rectangular-wave voltage component, as shown inFIG. 7, in the signal measured by amplifier1020. In this manner, a push-pull excitation source (e.g., electronic signal sources1000and1010) generates a DC neutral periodic rectangular-wave current whose frequency is an order of magnitude larger than the typical stimulation frequencies and whose amplitude is far below the currents typically used to stimulate neural tissue. This excitation current is injected via a switch matrix (which may reside within switch module68in the example ofFIG. 2or may reside within active lead can111in the example ofFIG. 4) of which only a single switch is shown inFIG. 6. This switch connects to a series combination of a resistance R and a capacitor C. The resistance R represents all the resistance between the excitation current source (e.g. switch matrix resistance, lead track resistance and the tissue resistance itself and in some cases resistance of extension wire120) and a chosen return terminal (e.g. IPG and/or ALC housing), while the capacitor C is formed by the total series capacitance (mainly DC blocking capacitor and electrode-tissue interface capacitance) in the loop.

FIG. 8is a graphical diagram illustrating the triangular wave portion of the electrical signal formed at an input of an amplifier used for tissue resistance measurement. For example,FIG. 8is a simplified representation of the waveform of the imaginary part of a response signal received in the example inFIG. 6. As described above, the same excitation current used to generate the rectangular wave portion illustrated inFIG. 7is integrated by the series capacitance C and this adds a triangular waveform component, illustrated inFIG. 8, to the signal measured by amplifier1020. The triangular wave includes no DC component. For example, due to the push/pull configuration of electrical signal source1000and electrical signal source1010, there is no DC in the triangular wave.

As described above, amplifier1020amplifies its input voltage into a current (OTA) which is subsequently chopped by chopper circuit1040at exactly the same frequency as the excitation current source. Therefore, the analog-to-digital converter (ADC) of averager circuit1060digitizes a DC current component, which is the result of the chopped instrumentation amplifier rectangular-wave output current and a superimposed saw tooth component, which is the result of the chopped amplified triangular current wave.

FIG. 9is a graphical diagram illustrating a DC current component that is proportional to the tissue resistance generated from chopping the rectangular wave illustrated inFIG. 7.FIG. 9is a simplified representation of the waveform of the real part after chopping of a response signal received in the example ofFIG. 7.FIG. 10is a graphical diagram illustrating a saw-tooth wave that is proportional to the reactance in the signal path.FIG. 10is a simplified representation of the waveform of the imaginary part after chopping of a response signal received in the example ofFIG. 8.

Averager circuit1060is an averaging analog-to-digital converter (ADC), which implies that only the DC current at the ADC's input gives rise to a digital code at its output, while the saw tooth, whose DC content is zero, is effectively eliminated by the integrating action of the averaging ADC of averager circuit1060. Thus the digital output code is representative of the measured tissue resistance, and therefore, the real part Re(Z) of the complete impedance matrix Z can directly be measured by this architecture when all electrodes of interest are scanned one after another (e.g., apply excitation signal on one electrode, determine resistance on that electrode and transresistance on all other electrodes, then apply excitation signal on another electrode, determine resistance on that electrode and transresistance on all other electrodes, and so forth for each electrode). Also, if chopper circuit1040and excitation current sources (e.g., electrical signal sources1000and1010) are disabled, the same architecture can be used as a neural recording channel. Moreover, when bandwidth of amplifier1020in neural recording mode is too low for the excitation current frequency (typically in the kHz range), it can be programmed to have a larger, but still relatively small, bandwidth during resistance measurement.

FIG. 11is a graphical diagram illustrating the electrical signal at the input of the amplifier. For instance,FIG. 11is the combined signal ofFIGS. 7 and 8, whereFIGS. 7 and 8illustrated the real and imaginary-parts of the signal at the input of amplifier1020.FIG. 12is a graphical diagram illustrating the output of a chopper circuit when the input is the wave illustrated inFIG. 11. For instance,FIG. 12is the combined signal ofFIGS. 9 and 10, whereFIGS. 9 and 10illustrated the real and imaginary-parts of the signal at the output of chopper circuit1040.

As described above, although real-part and the imaginary part of the input signal to amplifier1020may be as illustrated inFIGS. 7 and 8, the output of amplifier1020may not be an ideal rectangular wave and triangular wave due to the bandwidth of amplifier1020. Rather, the real-part of the output signal (e.g., real-part of intermediate electrical signal) from amplifier1020may be trapezoidal and the imaginary-part of the output signal (e.g., imaginary-part of intermediate electrical signal) from amplifier1020may be triangular.

FIG. 13is a graphical diagram illustrating the trapezoidal wave portion of the electrical signal formed at an output of an amplifier used for tissue resistance measurement. As illustrated, the real-part of the output of amplifier1020does not have fast rise and fall times, as compared to the rectangular wave. Rather, the signal rises slowly or falls slowly to a settling level (e.g., the same as the level of the rectangular wave). InFIG. 13, the difference between the rectangular wave and the trapezoidal wave is illustrated with the dark shading. This dark shading represents the error in the tissue resistance measurement that is caused by the bandwidth limitations of amplifier1020(e.g., the difference between the ideal rectangular wave and the actual trapezoidal wave that amplifier1020outputs). This error is a function of the frequency of the electrical signal that electrical signal source1000and1010output and chopping frequency of chopper circuit1040.

For example, if the frequency of the electrical signal that electrical signal source1000and1010output and chopping frequency of chopper circuit1040is increased relative to the example illustrated inFIG. 13, then the area of the dark shaded area will increase. If the frequency of the electrical signal that electrical signal source1000and1010output and chopping frequency of chopper circuit1040is decreased relative to the example illustrated inFIG. 13, then the area of the dark shaded area will decrease. Also, in the illustrated example inFIG. 13, the period of the electrical signal is sufficiently large to allow the electrical signal to settle to its peak value or to its trough value. In some examples, the frequency of the electrical signal that electrical signal source1000and1010output and chopping frequency of chopper circuit1040should be low enough that the electrical signal that amplifier1020outputs settles before another rising or falling edge.

For instance, as described above, to determine the error in the tissue resistance measurement, processor60may determine the tissue resistance measurement at two different frequencies of the electrical signal that electrical signal source1000and1010output and of chopper circuit1040, and perform the example computations to remove the error caused by the bandwidth limitation of amplifier1020. The frequency of both of these tissue resistance measurements should be low enough to allow the electrical signal that amplifier1020outputs to settle.

FIG. 14is a graphical diagram illustrating the triangular wave portion of the electrical signal formed at an output of an amplifier used for tissue resistance measurement. The bandwidth limitations of amplifier1020may also affect the imaginary-part (e.g., triangular wave portion) of the electrical signal that amplifier1020amplifies. For instance, inFIG. 14, the triangular wave that amplifier1020receives is illustrated in dashed line, and the actual triangular wave that amplifier1020outputs is illustrated in solid line. As can be seen, the bandwidth limitations of amplifier1020cause rounding on the peaks of the triangular wave.

In addition, amplifier1020also causes a phase delay in the output of the triangular wave as illustrated by the output of amplifier1020not lining up with the input of amplifier1020. In some cases, the phase delay may be relatively small and the phase delay may not affect the tissue resistance measurement. However, in some cases, the phase delay may be relatively large, which may be another cause of error in the tissue resistance measurement.

For example, the imaginary-part output of amplifier1020is chopped with chopper circuit1040to generate the saw-tooth wave (e.g., as illustrated inFIG. 10). To generate the saw-tooth wave, chopping performed by chopper circuit1060should be phase aligned with the output of amplifier1020. However, the phase delay caused by amplifier1020results in the chopping performed by chopper circuit1060to be phase misaligned with the output of amplifier1020. This phase misalignment results in a wave that is not like a saw-tooth, but of a different shape. This different shape waveform is then integrated by averager circuit1060.

For the saw-tooth waveform, the integration by averager circuit1060results in approximately zero. However, the integration by averager circuit1060of this non-saw-tooth shaped waveform results in a value that is not approximately zero.

In some cases, the value may be close to zero and therefore, have minimal effect, but in other cases, the value may cause additional error in the tissue resistance measurement. However, the amount of error caused by this phase delay may be determinable during manufacturing and processor60may then subtract this determined amount of error cause by the phase delay to more accurately determine the tissue resistance.

Also, in the example above, electrical signal sources1000and1010output an electrical signal via electrode24A, and processor60determines the tissue resistance at electrode24A. However, the output of the electrical signal via electrode24A also causes a voltage signal to generate on other electrodes (e.g., electrodes24B-24D). In some examples, this voltage signal generated on electrode24B may be processed by an amplifier, a chopper circuit, and an averager circuit, like amplifier1020, chopper circuit1040, and averager circuit1060coupled to electrode24A. Processor60may determine the tissue resistance at the other electrodes24B-24D, when the current is outputted via electrode24A, based on the output of the averager circuit for these respective electrodes24B-24D. Processor60may then repeat these steps by outputting the electrical signal via electrode24B and determining the resistance of respective electrodes24A,24C, and24D, and so forth for each one of electrodes24to determine the tissue resistance matrix.

In the tissue resistance measurements at electrodes from which the excitation current is not being outputted, there may be no imaginary part. This is because the tissue includes no reactance components, and no current flows through the signal paths of these other electrodes, meaning there is no effect from the capacitance in the signal paths of these other electrodes. However, there may be some capacitance in the return path (e.g., capacitance between tissue and electrode on IMD16). In some examples, the tissue resistance measurements for the other electrodes (e.g., the electrodes through which there is not an excitation current being outputted) may be more accurate than for the electrode that is outputting the excitation current because there is no imaginary part to remove. However, the error due to the limited bandwidth of their respective amplifiers would need to be removed using the example techniques described in this disclosure.

Also, in some examples, during manufacturing, a DC blocking capacitor and a capacitor to emulate the parasitic capacitance caused by tissue-electrode coupling may be connected to switch module68and a resistance measurement of a resistor in series to emulate the tissue resistance may be performed. The resulting error in the resistance measurement is measured, and stored into a memory (e.g., an One Time Programmable (OTP)) memory) of IMD16. In some examples, when IMD16performs the resistance measurement, processor60corrects for the error.

For example, during manufacturing of processor60, a resistor having a known resistance may be added to electrode24A, and processor60may determine the resistance of this resistor using the techniques described in this disclosure. During manufacturing, the gain of amplifier1020and the amplitude of electrical signal source1000and1010can be set and the efficacy of the techniques described in this disclosure may be checked until confirmed that processor60determines the resistance of the resistor to equal the known resistance.

During manufacturing of processor60, the resistor may then be replaced with a capacitor having a known capacitance (e.g., one that is approximately equal to the capacitance experienced after IMD16is implanted such as approximately 10 nF). In this case, processor60should determine the resistance to be zero. However, as described with respect toFIG. 14, the phase delay caused by amplifier1020may result averager circuit1060outputting a non-zero value. Again, under ideal case, where a 10 nF capacitor is coupled to electrode24A, the output of chopper circuit1040should be a saw-tooth with average value of zero, and averager circuit1060would output zero. However, due to the phase delay, where a 10 nF capacitor is coupled to electrode24A, the output of chopper circuit1040is not an ideal saw-tooth with average value of zero, resulting in averager circuit1060outputting a non-zero value.

In some examples, processor60may use the non-zero value to more accurately determine the tissue resistance. For example, during operation when processor60is determining the tissue resistance, processor60may account for the error in the tissue resistance cause by bandwidth limitations of amplifier1020by determining the tissue resistance at two different frequencies as described above. During operation when processor60is determining the tissue resistance, processor60may account for the error in the tissue resistance caused by phase delay by amplifier1020by subtracting this non-zero value determined during manufacturing from the tissue resistance measurement because this non-zero value was determined based on an approximation of the actual capacitance in the system.

When a few electrodes are connected in parallel, rather than in the case of a single electrode, processor60may not be able to compensate for this error. For example, the error will be the difference between the actual error and the amount of error correction that processor60applies based on stored error values. For normal resistance measurement, only a single electrode is excited at a time, and therefore, the resistance measurement may be fairly accurate by applying the compensation tested during manufacturing, as compared to attempting to compensate with many electrodes at one time. It should be understood that even in a patient-to-patient spread, the capacitance may be sufficiently close that the error is minimal.

FIG. 15is a functional block diagram illustrating components of an example medical device programmer14. Programmer14includes processor80, memory82, telemetry module84, user interface86, and power source88. Processor80controls user interface86and telemetry module84, and stores and retrieves information and instructions to and from memory82. Programmer14may be configured for use as a clinician programmer or a patient programmer. Processor80may comprise any combination of one or more processors including one or more microprocessors, DSPs, ASICs, FPGAs, or other equivalent integrated or discrete logic circuitry. Accordingly, processor80may include any suitable structure, whether in hardware, software, firmware, or any combination thereof, to perform the functions ascribed herein to processor80and programmer14.

A user, such as a clinician or patient12, may interact with programmer14through user interface86. User interface86includes a display (not shown), such as a LCD or LED display or other type of screen, with which processor80may present information related to the therapy (e.g., therapy programs,). In addition, user interface86may include an input mechanism to receive input from the user. The input mechanisms may include, for example, any one or more of buttons, a keypad (e.g., an alphanumeric keypad), a peripheral pointing device, a touch screen, or another input mechanism that allows the user to navigate though user interfaces presented by processor80of programmer14and provide input. In other examples, user interface86also includes audio circuitry for providing audible notifications, instructions or other sounds to patient12, receiving voice commands from patient12, or both.

Memory82may include instructions for operating user interface86and telemetry module84, and for managing power source88. Processor80may store the therapy programs and associated scores in memory82as stored therapy programs94. A clinician may review the stored therapy programs94and associated scores (e.g., during programming of IMD16) to select one or more therapy programs with which IMD16may deliver efficacious electrical stimulation to patient12. For example, the clinician may interact with user interface86to retrieve the stored therapy programs94and respective scores.

In some examples, processor80is configured to generate and present, via a display of user interface86, a graphical user interface (GUI) that presents a list of therapy programs and the respective scores. A user (e.g., a clinician) may interact with the GUI to manipulate the list of therapy programs. For example, in response to receiving user input requesting the list of therapy programs be ordered by score, processor80may reorganize the list of therapy programs based on the respective scores (e.g., from highest to lowest scores or vice versa).

In some examples, a user may also interact with the graphical user interface to select a particular therapy program, and, in response to receiving the user input, programmer14may provide additional details about the therapy program. For example, the additional details presented by programmer14may include details about the individual parameter settings of the therapy program, such as the electrical stimulation parameter values, electrode combination, or both.

In addition, in some examples, processor80may be configured to implement example techniques described in this disclosure. As one example, in addition to or instead of processor60determining a value proportional to the tissue resistance, processor60may output the two average values determined at the different frequencies to programmer14. Processor80may determine the value proportional to the tissue resistance based on the two average values, as described above. Processor80may then determine the tissue resistance, and in some examples, output the tissue resistance value for user review. In some examples, processor80may determine therapy parameters for therapy programs94based on the determined tissue resistance.

In some examples, patient12, a clinician or another user may interact with user interface86of programmer14in other ways to manually select therapy programs from the stored therapy programs94for programming IMD16, generate new therapy programs, modify stored therapy programs94, transmit the selected, modified, or new therapy programs to IMD16, or any combination thereof.

Memory82may include any volatile or nonvolatile memory, such as RAM, ROM, EEPROM or flash memory. Memory82may also include a removable memory portion that may be used to provide memory updates or increases in memory capacities. A removable memory may also allow sensitive patient data to be removed before programmer14is used by a different patient.

Wireless telemetry in programmer14may be accomplished by RF communication or proximal inductive interaction of external programmer14with IMD16. This wireless communication is possible through the use of telemetry module84. Accordingly, telemetry module84may be similar to the telemetry module contained within IMD16. In other examples, programmer14may be capable of infrared communication or direct communication through a wired connection. In this manner, other external devices may be capable of communicating with programmer14without needing to establish a secure wireless connection.

Power source88is configured to deliver operating power to the components of programmer14. Power source88may include a battery and a power generation circuit to produce the operating power. In some examples, the battery may be rechargeable to allow extended operation. In other examples, traditional batteries (e.g., nickel cadmium or lithium ion batteries) may be used. In addition, programmer14may be directly coupled to an alternating current outlet to operate.

FIG. 16is a flowchart illustrating an example technique of tissue resistance measurement. As illustrated inFIG. 16, IMD16may generate, at an electrode, a first electrical signal of a first type by outputting, via the electrode, a first electrical signal of a second type at a first frequency (1400). For instance, electronic signal sources1000and1010may output, via electrode24A, a first current signal at a first frequency to generate, at electrode24A, a first voltage signal.

IMD16may process the first electrical signal of the first type at the first frequency to generate a first output signal (1410). For example, amplifier1020, chopper circuit1040, and averager circuit1060may process the first voltage signal. In this example, chopper circuit1040operates at the same frequency as the first frequency (e.g., 3.125 kHz). For instance, amplifier1020may amplify the first electrical signal of the first type to generate a first intermediate electrical signal. Chopper circuit1040may chop the first intermediate electrical signal at the first frequency to generate a first chopped signal. Averager circuit1060may average the first chopped signal to generate the first output signal, where the first output signal is a first value.

IMD16may generate, at the electrode, a second electrical signal of the first type by outputting, via the electrode, a second electrical signal of the second type at a second frequency (1420). For instance, electronic signal sources1000and1010may output, via electrode24A, a second current signal at a second frequency (e.g., 6.250 kHz) to generate, at electrode24A, a second voltage signal. IMD16may process the second electrical signal of the first type at the second frequency to generate a second output signal (1430). For example, amplifier1020, chopper circuit1040, and averager circuit1060may process the voltage signal. In this example, chopper circuit1040operates at the same frequency as the second frequency.

For instance, amplifier1020may amplify the second electrical signal of the first type to generate a second intermediate electrical signal. Chopper circuit1040may chop the second intermediate electrical signal at the second frequency to generate a second chopped signal. Averager circuit1060may average the second chopped signal to generate the second output signal, where the second output signal is a second value. The first value equals a value proportional to the tissue resistance plus a first error value, the second value equals the value proportional to the tissue resistance plus a second error value, and the second error value approximately equals the first error value multiplied by a ratio between the first frequency and the second frequency.

IMD16or programmer14may determine a tissue resistance at the electrode based on the first output signal, the second output signal, and a ratio between the first frequency and the second frequency (1440). For example, processor60or processor80may multiply the first output signal with the ratio between the first frequency and the second frequency, subtract the second output signal from a result of the multiplication, and determine the tissue resistance based on a result of the subtraction.

FIG. 17shows an X-ray picture of the electronic module500.FIG. 18shows a schematical cross-sectional view of the electronic module500according to one example. In the following description,FIGS. 17 and 18are described together.

In particular,FIG. 17shows the top feedthrough and the underlying feed through capacitor of the integrated passive device. InFIG. 17, both the connector510and the connector520on the outside as well as the top of the substrate568(FIG. 18) of the capacitor array on the inside, underneath the feedthrough, are shown. The ground plane of the capacitor array is electrically connected via the top part585aof the ground plane to the housing530of the active lead can element111via a ring of conductive epoxy glue710.

In particular, a ground ring of the connector510can be directly and/or indirectly electrically (galvanically, ohmically) connected to the housing530of the active lead can111via a ring of conductive epoxy glue712and/or a ground ring of the connector520can be directly and/or indirectly electrically (galvanically, ohmically) connected to the housing of the active lead can111via a ring of conductive epoxy glue714. It is also possible to apply a single ring of conductive epoxy glue surrounding both connectors to electrically connect the housing530to the top ground plane585a. If required, the feed through pins can be grouped into other combinations, in multiple sections or combined into just one single feed through.

The electronic module500may comprise connection pins521and connection pins511. The connection pins521are connected to the DC blocking capacitors of integrated passive device568and also to the feed-through filter capacitors564a. Although not explicitly shown, the connection pins511are also connected to integrated passive device568to realize the same DC blocking and EMI filtering.

Each feed-through pin511,521contacts to a capacitor top contact, which can be a gold top contact, on the substrate top of thick film integrated passive device567. The pins521are contacted to capacitors564aand the pins511are contacted to capacitors564c. The top contacts are simultaneously the top plates of capacitors564aand capacitors564c. Thus a thick film substrate with screen printed capacitors564aand capacitors564cforms a (single) feed-through filter substrate567(see e.g.,FIG. 18) that is directly put on top of and connected with the feedthrough pins511,521.

The connector510has a titanium flange515forming a border of the connector510and the connector520has a titanium flange525forming a border of the connector520. The titanium flanges are integrated in the titanium active lead can housing530.

The electronic module500comprises a filtering element, wherein the filtering element is a feed-through filter567, and a blocking element, wherein the blocking element is a DC blocking element and an ASIC600, wherein the integrated passive device comprises the at least one filtering element, wherein the filtering element is exemplarily a feed-through filter, and/or the at least one blocking element, wherein the blocking element is exemplarily a DC blocking element. The filtering can be provided by any means which is/are capable to provide a filtering. In particular, a filtering can be provided by any passive means or passive network.

The filtering element may be configured such that interferences, in particular unwanted interferences e.g. caused by mobile phones or the like, can be removed before they may enter, e.g., a part of the housing for the electronics of the system for neural applications100. Thereby, the advantage is achieved that a protection of the interior electronics against electromagnetic interference (EMI) is provided, for example, against mobile phone induced fields while the patient is using its mobile phone. The other way around, (high-frequency) interference generated inside the active lead can111is prevented from radiating outside.

The filtering element may be or may comprise e.g. an RF feed-through filter567. The filter may comprise, e.g., a capacitor, a coil, an inductor, a resistor or any other suitable passive component. The blocking element may be configured such that in the event of a leakage current such leakage current, in particular DC leakage current flow is prevented. No DC current should flow through the patient carrying an implant such as a deep brain stimulator, even when a (single) failure occurs of, for example, the implant's electronics. This DC leakage design problem is solved by the application of DC blocking capacitors. Again, with a high number of feed-through pins511it may be beneficial to integrate those blocking capacitors to achieve a minimum volume and area claim as opposed to the application of discrete components.

The ASIC600may comprise a part or e.g. all active electronics with some external passives, for example, power supply decoupling capacitors. A substrate with integrated passives, here the integrated passive device560, with e.g. resistors, capacitors and inductors may be used as substrate for off-chip (rerouting to) an ASIC600. By the use of one or more application specific integrated circuits600the active electronic components of at least a part of the system for neural application100may be miniaturized.

Both for the novel feed-through filter and the DC blocking capacitor technology a substrate is used for their realization, which opens up another unique opportunity to combine all electrical and electronics components into a single stack mounted on top of the feed-through pins511of the connector510and the feed-through pins521of the connector520directly as shown inFIG. 18. This 3-layer stack with the ASIC600on the DC blocking element568achieves a very high integration density.

Electrical connections are provided via stud bumps505, which are embedded into epoxy underfill700. All active components of the implantable electronic device111(e.g., the ASIC600) and passive (e.g. feed-through filters567and DC blocking capacitors) components of the active lead can111can be combined into a single stack and the stack can be mounted directly on top of the pins521of the connector520and the 5-pin511connector510(drawing is not true to scale).

While the techniques described above are primarily described as being performed by processor60of IMD16or processor80of programmer14, in other examples, one or more other processors may perform any part of the techniques described herein alone or in addition to processor60or processor80. Thus, reference to “a processor” may refer to “one or more processors.” Likewise, “one or more processors” may refer to a single processor or multiple processors in different examples.

In this manner, the disclosure describes techniques related to an electronic circuit, an electronic module, an active lead can, a system and methods for determining the real part of an impedance of a first signal path for a neural application. In general, implantable neurostimulation devices have been used for the past ten years to treat acute or chronic neurological conditions. Deep brain stimulation (DBS), the mild electrical stimulation of sub-cortical structures, belongs to this category of implantable devices, and has been shown to be therapeutically effective for Parkinson's disease, Dystonia, Essential Tremor, Obsessive Compulsive Disorder, and Epilepsy. New applications of DBS in the domain of psychiatric disorders (clinical depression, anorexia nervosa, schizophrenia) are being researched. In existing systems, a lead carrying four ring electrodes at its tip is connected to an implantable pulse generator.

Currently, systems are under development with more, smaller electrodes using a technology based on thin film manufacturing. These systems include a lead made from a thin film based on thin film technology, as, e.g., described in WO 2010/055453 A1, to Koninklijke Philips Electronics, entitled “SPIRALED WIRES IN A DEEP-BRAIN STIMULATOR PROBE.” The thin film carries multiple electrodes to cover the distal tip with an array of electrodes, and is assembled into a lead. Such leads will enhance the precision to address the appropriate target in the brain and relax the specification of positioning. Meanwhile, undesired side effects due to undesired stimulation of neighboring areas can be minimized. Leads that are based on thin film manufacturing are e.g. described by U.S. Pat. No. 7,941,202 by Hetke et al. and entitled “MODULAR MULTICHANNEL MICROELECTRODE ARRAY AND METHODS OF MAKING SAME” and have been used in research products in animal studies.

In existing systems, the DBS lead has e.g. four 1.5 mm-wide cylindrical electrodes at the distal end spaced by 0.5 mm or 1.5 mm. The diameter of the lead is 1.27 mm and the metal used for the electrodes and the interconnect wires is an alloy of platinum and iridium. The coiled interconnect wires are insulated individually by fluoropolymer coating and protected in a urethane tubing of a few tens of micron thick. With such electrode design, the current distribution emanates uniformly around the circumference of the electrode, which leads to stimulation of all areas surrounding the electrode.

The lack of fine spatial control over current and electric field distributions implies that stimulation easily spreads into adjacent structures inducing adverse side-effects in as much as 30% of the patients. To overcome this problem, systems with high density electrode arrays are being developed, hence providing the ability to steer the stimulation field to the appropriate target (hence the term steering brain stimulation).

The clinical benefit of DBS is largely dependent on the spatial distribution of the stimulation field in relation to brain anatomy. To maximize therapeutic benefits while avoiding unwanted side-effects, control over the stimulation field is desirable. During stimulation with existing DBS leads there is an option to use monopolar, bipolar, or even multipolar stimulation. Neurostimulator devices with steering brain stimulation capabilities can have a large number of electrode contacts (n>10) that can be connected to electrical circuits such as current sources and/or (system) ground. Stimulation may be considered monopolar when the distance between the anode and cathode is several times larger than the distance of the cathode to the stimulation target. During monopolar stimulation in homogeneous tissue the electric field is distributed roughly spherical similar to the field from a point source. When the anode is located close to the cathode the distribution of the field becomes more directed in the anode-cathode direction. As a result the field gets stronger and neurons are more likely to be activated in this area due to a higher field gradient.

Although the exact mechanisms of DBS are unknown, it is hypothesized that polarization (de- and/or hyperpolarization) of neural tissue is likely to play a prominent role both for suppression of clinical symptoms, and for induction of stimulation-induced side-effects. In order to activate a neuron it has to be depolarized. Neurons are depolarized more easily close to the cathode than by the anode (about 3-7 times more depending on type of neuron, etc.).

According to an aspect of the disclosure, electronic circuitry for determining the real part of an impedance of a first signal path of a system for neural stimulation and/or sensing applications is provided. The electronic circuit comprises a signal source. The signal source is a current source, in one example. The signal source can be configured to feed an alternating periodic stimulus signal (e.g., an alternating current) having a first frequency into the signal path. The signal can be fed into the signal path from the first end of the signal path and/or a connecting line.

The real part of the impedance of the signal path comprises all of the resistance between the signal source excitation current source (e.g. switch matrix resistance, lead track resistance and the tissue resistance itself) and a chosen return terminal (e.g. IPG and/or ALC housing), while the total capacitance comprises the total series capacitance (mainly DC blocking capacitor and electrode-tissue interface capacitance plus capacitance of the return terminal) in the loop.

The electronic circuit can further be configured to determine a magnitude of a response signal to the alternating signal (at the first end of the connecting line) and to derive the real part of the impedance from the determined magnitude. In an aspect, the electronic circuitry comprises a modulation (or de-modulation) stage, as for example a chopper stage to which the response signal is supplied. The chopper stage can then be configured to operate synchronously with the alternating signal source, i.e., at the same (first) frequency. The chopper stage can be coupled to the first end of the signal path at least somewhere between the electrode and the signal source. The chopper stage demodulates the alternating signal with the first frequency.

An instrumentation amplifier such as, for example, an operational transconductance amplifier, can be coupled between the signal path and the chopper stage. The response signal on the signal path that is an alternating voltage if the stimulus signal from the signal source is an alternating current can then be amplified and/or converted by the amplifier into a corresponding current.

The amplifier can have a settling time that is less than or equal to half the period (period relating to the first frequency) of the alternating signal. This provides that the amplifier can have reduced power consumption. These instrumentation amplifiers are often used for neural applications, in particular for neural recording. Accordingly, in an aspect of the techniques described in this disclosure, an instrumentation amplifier that is used for neural recording is used for amplifying the response of the response signal of a signal path.

In a further aspect, the amplifier may be made configurable to have a first bandwidth for a neural application, as for example neural recording and a second bandwidth if it is used for amplifying the response signal on the signal path. This allows reusing most of the components, if not all, of the amplifier and avoids implementation of several amplifiers for the measurement of the real part of the impedance of the signal paths.

The output signal of the chopper stage can be fed to an analog-to-digital converter. This way the output signal can be converted into a digital signal. The output signal is a representation of the real part of the impedance within certain limits of accuracy. Accordingly, an analog-to-digital converter (ADC) can be provided and be coupled to the output of the chopper stage. The ADC may be an averaging ADC. This means that the signal undergoes an integration/low pass function, thereby suppressing noise and/or eliminating artifacts, errors and/or other deficiencies of the electronic stages preceding the ADC.

In an example, the electronic circuit can further be configured to consecutively feed the alternating signal to the first signal path and to a second signal path comprising a second connecting line, a second electrode and human tissue to which the second electrode is coupled for individually determining the real part of the impedance of the first signal path and the real part of the impedance of the second signal path, respectively. In general, the electronic circuit can be figured to supply the alternating signal into any number of signal paths, each signal path having an electrode being in contact with human tissue. The electronic circuit is then configured to consecutively supply at least one signal path with the alternating (current) signal and to measure the response for each signal path (i.e. each channel) thereby determining the respect real parts of each signal path. Each real part substantially represents the resistance of the human tissue to which the electrode is coupled.

If a plurality of signal paths is measured in accordance with the aspects and techniques described in this disclosure, the electronic circuitry may comprise a matrix of switches for feeding the alternating signal to the different signal paths. This switch matrix may, for example be a switch matrix that is already provided for coupling different signal paths to the same pulse generating source.

The alternating signal can be configured to symmetrically alternate around a ground level with the first frequency, such that the a full period of the alternating signal substantially has no DC content with respect to the ground level. The alternating signal can be a square wave signal that is symmetric around ground. If this kind of signal is processed by the chopper stage, the signal components relating to capacitances in the signal path can be eliminated.

The signal source can be a push-pull current source alternately supplying a first current having a first magnitude and a second current having the same (first) magnitude but flowing in opposite direction than the first current. The push-pull current source can comprise two complementary current sources being alternately switched to supply the first and second current to the signal path. Such a push-pull current source is suitable to be integrated in an integrated circuit and generally constitutes a robust and simple implementation of the signal source.

In an aspect, the signal source can be configured to alternate the alternating signal at the first frequency and at a second frequency that is different from the first frequency. The frequency of the alternating may repeatedly and/or periodically be changed. This aspect provides that errors due to limited settling behavior and bandwidth of the components can be reduced.

The first frequency can be between 1 kHz and 100 kHz; however, other ranges are possible, and the techniques described in this disclosure should not be considered limited to the example frequency range. The second frequency can be different from the first frequency by 1 kHz to 10 kHz; however, other ranges are possible, and the techniques described in this disclosure should not be considered limited to the example frequency range.

The magnitude of the currents supplied by the signal source can be substantially smaller than any stimulation signals for the neural applications. The amplitude of the alternating signal can be approximately 8 micro-amps, but other current amplitudes are possible. Any signal path can comprise the at least one connecting line coupled to the signal source at a first end, and an electrode coupled to a second end of the connecting line opposite to the first end and human tissue to which the electrode is coupled. The connecting line and/or the signal path can comprise cables, wires, interconnects, switches, resistors, integrated components and wires as well as bond pads, bonding wires etc.

Any connecting line of a signal path can comprise at least one or more of a blocking capacitor, a switch, a connector, a bond pad, etc. This provides a comparably small size and still sufficient DC decoupling.

The present technique may also provide an electronic module comprising the electronic circuitry according to the aspects and examples described in this disclosure. The present techniques may also provide an active lead can that comprises the electronic circuitry and/or the electronic module according to the aspects and/or examples described in this disclosure. The present techniques may also provide a system for neural applications comprising an electronic circuit and/or an electronic module and/or an active lead can and/or a pulse generating device according to the aspects and examples described in this disclosure. The system also includes the signal path at least up to the electrode.

The present techniques may further provide methods of operating an electronic circuitry, an electronic module, an ALC and/or a system in accordance with the aspects and/or examples described in this disclosure. The techniques may also provide a method of determining a real part of an impedance of a signal path for a neural application. Accordingly, an alternating signal can be injected into a first signal path comprising a first electrode coupled to human tissue. The response signal (of the signal path) to the alternating signal can then be chopped synchronously to the alternating signal and the real part of the impedance of the first signal path can be determined based on the chopped response signal. Other aspects of this method can be derived from the aspects and examples of the electronic circuit, system etc. as described herein.

In one or more examples, the functions described in this disclosure may be implemented in hardware, software, firmware, or any combination thereof. If implemented in software, the functions may be stored on, as one or more instructions or code, a computer-readable medium and executed by a hardware-based processing unit. Computer-readable media may include computer-readable storage media forming a tangible, non-transitory medium. Instructions may be executed by one or more processors, such as one or more DSPs, ASICs, FPGAs, general purpose microprocessors, or other equivalent integrated or discrete logic circuitry. Accordingly, the term “processor,” as used herein may refer to one or more of any of the foregoing structure or any other structure suitable for implementation of the techniques described herein.

In addition, in some aspects, the functionality described herein may be provided within dedicated hardware and/or software modules. Depiction of different features as modules or units is intended to highlight different functional aspects and does not necessarily imply that such modules or units must be realized by separate hardware or software components. Rather, functionality associated with one or more modules or units may be performed by separate hardware or software components, or integrated within common or separate hardware or software components. Also, the techniques could be fully implemented in one or more circuits or logic elements. The techniques of this disclosure may be implemented in a wide variety of devices or apparatuses, including an IMD, an external programmer, a combination of an IMD and external programmer, an integrated circuit (IC) or a set of ICs, and/or discrete electrical circuitry, residing in an IMD and/or external programmer.