Multi-contact electrode and integrated circuit for s-eeg

Abstract

A multi-contact electrode device includes an elongate body (10) having a plurality of pick-up contacts (20) and a narrow long ASIC (50) into a hollow interior cavity (18). The ASIC is configured to read out, process, and digitize EEG signals present at the contacts, and selectively apply a high RF current to any selected contact pair for thermal coagulation. The ASIC also includes a microcontroller having a digital communication interface (85).

Description

Technical Field

[0001] The present invention relates to a multi-contact electrode for medical use. Embodiments of the present invention relate to intracerebral electrodes intended to be placed in a patient's brain for diagnostic and therapeutic procedures such as stereotactic electroencephalography (S-EEG), but the present invention may also be applied to other instrumented medical procedures. Background Art

[0002] Multi-contact electrodes are used for electrophysiological exploration of several structures in the body, especially in the central nervous system. For example, stereotactic electroencephalography (S-EEG) relies on electrodes that penetrate the brain, which measure electrophysiological activity in deep structures that are not easily accessible by surface measurement techniques such as transcranial electroencephalography (EEG) and electrocorticography (ECoG). Stereotactic EEG is considered less invasive than electrocorticography because it only requires a small diameter burr hole in the skull, rather than a more extensive craniotomy.

[0003] Existing S-EEG readouts employ thin passive S-EEG electrodes (about 1.5 mm in diameter) connected by thin wires to a processing and visualization station typically at a distance of several meters. The number of conductors is proportional to the number of recording sites within the patient's brain, in other words the number of electrical contacts, and can be in the range of 4-20 wires per electrode.

[0004] Document US 2012 / 0296404 A1 discloses a multi-electrode intracerebral electrode for placement in a patient's brain. The electrode has a plurality of contact pads in the form of metal rings on the side of an elongated catheter.

[0005] In addition to recording electrical activity of living tissue, the elongated electrodes are also used in thermal coagulation procedures, in which the electrodes are used to inject radiofrequency current that destroys or inactivates a target area of ​​tissue. These procedures have been proposed and used in the treatment of drug-resistant epilepsy (as disclosed in IN2002011001043), in the control of spinal cord-derived pain, and in the management of other conditions.

[0006] These known devices present a common disadvantage: the weak electrical signals collected by the electrodes are transmitted to an external electronic processor via thin conductors. The wires may pick up unwanted signals, such as the main line signal at 50 / 60 Hz and signals caused by the inevitable movement of the patient and the cable, which can interfere with the interpretation of the true electrophysiological signals. In addition, the thin wires are not suitable for transmitting RF at the current levels required in thermal coagulation procedures, and there is a limit to the number of conductors that can find a place in the lumen of a catheter of reasonable size.

[0007] US 9381063 B2 discloses a magnetically guided flexible catheter for renal nerve ablation. This device has a transistor circuit at its proximal end for processing electrophysiological signals. Summary of the invention

[0008] It is an object of the present invention to provide an apparatus that overcomes the disadvantages and limitations of the prior art.

[0009] According to the invention, these objects are achieved by the objects of the appended claims, in particular by a multi-contact electrode device, comprising an elongated body having a distal end placed in a target area of ​​a patient's body, the device comprising a plurality of pick-up contacts on an active part of the elongated body adjacent the distal end for recording the electrical activity of the target area and for delivering radiofrequency current into the target area, the elongated body containing in the active part an integrated circuit, the integrated circuit comprising: a read-out unit with a plurality of input channels, which is configured for amplifying and digitizing electrical signals applied to at least some of the pick-up contacts by the electrical activity of the target area; a thermocoagulation unit receiving radiofrequency signals, which is selectively connectable to at least one contact selected from the pick-up contacts for injecting local radiofrequency current into the target area; a digital communication interface, and by means of a specially configured integrated circuit as detailed above, the integrated circuit having two linear dimensions below 2 mm, preferably below 1 mm, more preferably equal to or below 0.75 mm.

[0010] The dependent claims relate to important and advantageous optional features, such as the fact that the thermocoagulation unit is configured to handle a current of at least 50 mA rms, preferably more than 120 mA rms, and a voltage of at least 15 V rms, preferably more than 20 V rms, at selected contacts, that there is a readout channel for the temperature sensor, the pick-up contacts being made of conductive areas on a flexible printed circuit wrapped around the active part, that the integrated circuit is placed in the hollow inner cavity of the elongated body, possibly through identical, ten or more readout channels, preferably through longitudinal slots in a differential high-pass filter with a cut-off frequency lower than 0.2 Hz.

[0011] Other optional features of the invention include: wireless digital communication interface, generation of electrocoagulation RF signal in the electrode by DC / AC converter, or generation of voltage supply required by integrated circuit in the electrode by AC / DC converter, automatic classification of S-EEG signal based on algorithm implemented in integrated circuit. These features are intended to reduce the number of wires to each electrode and simplify and reduce the complexity of external equipment.

[0012] The present invention provides several advantages over what is known in the art. On the one hand, the weak electrical signals picked up by the contacts are amplified and converted into a robust digital format in the distal end of the electrode, rather than being carried by thin wires to external processing components. In addition, the number of wires is no longer proportional to the number of readout sites, because the data can be carried on the digital bus in a serial format. This reduces the number of cables extending to the electrodes, eliminating most of the electronic pickup noise and power losses that occur in the wires during the thermocoagulation procedure.

[0013] Electronic processing of the data is simplified, since the data is pre-processed in the electrode itself.

[0014] The electrodes of the present invention are suitable for use in a variety of medical procedures in the central nervous system, in the spine or other regions.For the sake of brevity, this disclosure will only refer to S-EEG procedures, with the intention that this is not a limitation of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Exemplary embodiments of the present invention are disclosed in the specification and are illustrated by the accompanying drawings, in which:

[0016] Figure 1 The active area of ​​the electrode is schematically illustrated.

[0017] Figure 2 and Figure 3 An application specific integrated circuit (ASIC) is shown.

[0018] Figure 4 A possible structure of an ASIC is schematically shown.

[0019] Figure 5 An apparatus for S-EEG studies and thermocoagulation using the electrodes of the present invention is illustrated in a conceptual manner.

[0020] Figure 6 and 7 A cross section of the active area of ​​the electrode is shown in two implementation examples. DETAILED DESCRIPTION

[0021] Figure 1 The active distal portion of an S-EEG depth electrode according to the invention is shown. The electrode has a tip 11 corresponding to the distal end and an elongated body 10. It is generally cylindrical in shape, but other cross-sections are not excluded, such as flat or prismatic.

[0022] Several electrical contacts 20 are provided along the side of the elongated body 10. Their number is not a necessary limitation of the present invention. In one possible example, the electrode has eighteen contacts, but the number can be lower or higher as required. The diameter of the body 10 can be 3 mm or less.

[0023] The elongated body 10 is drawn partially transparent to show that it contains a flexible printed circuit board 23 with an application specific integrated circuit 50, which will be further described later. Importantly, the circuit is manufactured on a semiconductor die having at least two linear dimensions (e.g., width and thickness) that are smaller than the lateral dimensions of the electrode. In one possible embodiment, the electrode is hollow and has an internal cavity containing the integrated circuit. In other implementations, the cavity can be filled with a suitable material after the integrated circuit is inserted. In an example, the thickness and width of the die are less than 2 mm, preferably less than 1 mm, and more preferably equal to or less than 0.75 mm. In one embodiment, the dimensions of the die are 0.75 mm×0.75 mm×14 mm, resulting in an aspect ratio of approximately 1÷18.

[0024] The limited space available in the inner cavity requires a particularly compact packaging, preferably a lead-free packaging, for the integrated circuit 50. To further save space, the integrated circuit 50 may be a bare die soldered directly onto the flexible printed circuit 23, such as a flip chip circuit.

[0025] Figure 2 and Figure 3 A possible implementation of an integrated circuit 50 in a flip chip package is shown. The circuit has a very narrow and long form factor and a plurality of contact pads 53, 54 on one surface which are connectable to a printed circuit via solder bumps. The contact pads 53 are dimensioned to carry higher currents and can withstand higher potentials. They are used in radio frequency thermocoagulation procedures. Near the thermocoagulation contacts 53 is an array 73 of high current switches which are used to select a pair of contacts in the thermocoagulation procedure.

[0026] The aspect ratio (length to width) of the chip of the integrated circuit 50 is preferably higher than 10, more preferably higher than 15. The chip in the example has a width of 750 μm and a length of 14 mm. The thickness is 750 μm, which is a standard value proposed by many semiconductor foundries and is quite easy to handle. Surprisingly, this thickness is the same as the width of the chip in this example. The thickness can be reduced, for example to 300 μm or 100 μm, although this will require more careful handling and may require the use of a carrier. The chip can also be thinned by a grinding step before or after its welding.

[0027] Figure 4is a conceptual representation of the subunits that make up the integrated circuit 50 in one embodiment. The readout unit 60 receives the weak bioelectric signal present at the contact 20, which is electrically connected to the input terminal 165 of the IC, and converts the bioelectric signal into a suitable digital representation. As mentioned, the number of contacts is not determined in the present invention, but for example, the electrode of the present invention can have eighteen pickup contacts 20, organized in nine pairs along the electrode, and the integrated circuit 50 can have eighteen input terminals 165 for reading 18 signals from the same contacts 20. For simplicity, Figure 4 Only four readout channels are shown.

[0028] The readout unit comprises an analog to digital converter 69 which reads a plurality of input channels in a time multiplexed manner determined by the sequential commutation of the switch 66. The sampling frequency will be chosen according to the bandwidth of the signal of interest and may be programmable.

[0029] ADC 69 may be implemented as a successive approximation converter, a monotonically switching successive approximation converter, a sigma-delta ADC, or in any other suitable manner. Much of the important information of the EEG signal is contained in the lower portion of the spectrum at or below 10 Hz, but the higher frequency components are also of clinical importance, and it is advantageous to oversample the signal to extract its fine features and filter out noise. In a practical embodiment, assuming a multiplexing factor of 20÷1, the ADC may be run at 2Ms / s, and the sampling rate on each channel will be 100kHz.

[0030] The analog processing front end 68 exists between each input terminal 65 and the corresponding port in the multiplexer 68. For simplicity, Figure 4 Only four front-end channels are shown, but the integrated circuit 50 may comprise several more, possibly identical channels as required, in order to obtain the signals of all contacts 20 .

[0031] In the example presented, the analog front end is differential and all refer to a common reference terminal 164. Multiplexer switch 66 is also differential, as is the analog input to converter 69. This differential topology improves the rejection of common mode noise, but is not a necessary feature of the invention.

[0032] Each processing channel includes a low noise amplifier 62, which in this example is followed by a programmable gain amplifier 64 (the gain factor of which can be set by a control unit 80), a low pass filter 67, which can be, for example, an anti-aliasing low pass filter or a more complex filter, and a buffer 65 in front of a multiplexing switch 66. In one embodiment, the bandwidth of the analog processing channel can be 5 kHz, and the corner frequency of the low pass filter can be programmable to 5 kHz, 1 kHz or other desired values ​​by the control unit 80 as needed. Although the low pass filter 67 is represented by a separate block in the figure, the desired transfer function can be inherently provided by the programmable amplifier 64 or another element.

[0033] The overall gain of each analog front end is preferably programmable by the control unit 80 and can be up to 57 dB or higher. Preferably, the gains of the individual front ends are equalized to a common nominal value by trimmable elements in the integrated circuit 50.

[0034] Assuming a sampling rate of 100 kHz, the EEG signals are heavily oversampled, which helps extracting their fine features. The buffer 65 is useful to drive the input of the ADC 69 and the parasitic impedance of the passive channels, which appears as a capacitive load of a few pF.

[0035] In clinical reality, the EEG signal is usually superimposed on a slowly drifting DC voltage. The analog channel 68 preferably also includes a high-pass filter 63 to suppress this DC component. This high-pass filter should have a very low cut-off frequency to retain the slow component of the EEG signal, for example, a cut-off frequency below 0.2 Hz or between 0.1 Hz and 0.2 Hz. The high-pass filter can be implemented in any suitable manner, for example as a passive CR filter, in which the resistor element is obtained in an integrated circuit with a MOS pseudo-resistor. The low noise amplifier 62 should have a high input impedance to avoid loading the high-pass filter. An additional interstage high-pass filter (not shown) can be used to remove the DC offset from the amplifier.

[0036] In another implementation not shown in the figure, the analog front end 68 can be DC coupled, and in a feedback configuration, the DC offset is mitigated or compensated by subtracting a suitable correction signal. The feedback loop can include a hybrid analog / digital circuit or a switched capacitor circuit. This approach can provide a transfer function similar to that of a very low frequency high pass filter, thereby avoiding the large decoupling capacitors and some pseudo resistors required for passive filters.

[0037] The readout unit 60 may have additional input channels that acquire other analog signals at the same time as the EEG signal appears at the terminal 165. These additional channels will be designed to process the dynamics of the corresponding signals. For example, the integrated circuit 50 may have a terminal 66 for an electrical thermometer (such as a thermistor, a bandgap semiconductor temperature sensor, or any other suitable transducer) to read body temperature. The dedicated processing circuit 61 is configured to provide an analog temperature signal compatible with the A / D converter 69.

[0038] Thermal coagulation is achieved by applying a radio frequency high voltage signal across two intended electrodes. The thermal coagulation unit 70 receives a high voltage radio frequency signal from a suitable source, which may be an approved medical device for RF thermal coagulation and connected to terminal 175. Typically, the signal appearing at terminal 175 may be a sine wave having a frequency of 480 kHz and a differential amplitude of 64 Vpp or approximately 22 Vrms. The thermal coagulation unit 70 is configured as a switch matrix that can selectively connect the high voltage source to one or more selected terminals 65 via switches 73a and 73b.

[0039] Importantly, the analog front end 68 is connected to the corresponding input terminal through an isolation switch 72, which can be operated by the onboard controller 80 during the thermocoagulation procedure. In this way, the analog front end 68 is protected from the high voltages used during thermocoagulation. To increase attenuation, the isolation switch 72 is configured to open the connection between the input of the analog channel and the terminal 165, and simultaneously short the input of the analog channel to ground.

[0040] Switches 73a and 73b are open during EEG readout and can be selectively closed by controller 80 to apply an RF voltage to a selected pair of contacts. It is possible that a pair of consecutive switches are closed to apply an RF voltage to a pair of adjacent contacts, but other schemes are possible. Because the currents involved are quite large, the switches should present a low resistance in the "on" state. The inventors have determined that a resistance of about or less than 20Ω is a favorable compromise. This value is much lower than the combined resistance of the supply conductor and the neural tissue being treated. Even lower resistance will result in lower losses, but will occupy more silicon area. The RF current injected into the tissue will be at least 50mA, preferably more than 120mA rms, and the voltage drop between the selected contacts will be at least 15V rms, for example 22V rms. The switches included in the thermal coagulation unit 70 are configured and sized to handle such voltage and current levels.

[0041] The control signals required to operate the isolation switch 72 and the selection switches 73a, 73b are generated by the logic unit 80 following a predefined program and / or command received through the data bus interface 85. The logic circuit 80 operates at a much lower voltage level than the high voltage selection matrix 70, and the integrated circuit 50 may include a level shifter (not shown) for raising the control signal from the voltage domain of the logic circuit to the voltage domain of the thermocoagulation unit. Typically, the logic level of the control signal may be 0V and 1.8V, which is shifted to ±16V or more.

[0042] In another variant, not represented, the high voltage radio frequency signal may be generated by a suitable RF generator in the multi-contact electrode, or possibly on the same integrated circuit 50 instead of by an external unit.

[0043] The integrated circuit 50 also includes a power management unit 90, which receives electrical power from the terminal 195 and provides the DC voltage required to power the other elements of the integrated circuit. Possibly, the power management unit will receive an external DC power supply, such as +3.3 VDC, from which the stable voltage and current required by the logic unit 80 and the readout unit 60 are obtained. The power management unit may include a bandgap reference or another stable voltage reference to ensure that the generated voltage corresponds to the desired level. The power supply is bypassed by an external capacitor connected to a dedicated terminal (not shown in the figure).

[0044] In a variant, the power management unit 90 may include an AC / DC converter which provides the required DC voltage using the RF AC signal present at the terminal 175. In this case, the number of wires per electrode is reduced.

[0045] The control and communication unit 80 has a logic circuit 84, by which all functions of the integrated circuit 50 can be remotely controlled, and an interface 85 for a communication bus 185 (e.g., an SPI bus). The logic circuit 84 can be a finite state machine, a microcontroller, or any other suitable logic circuit. The control and communication unit may also include a digital memory to store the value generated by the ADC 69 before transmission via the data bus 185.

[0046] Even though the functionality of the integrated circuit 50 has been described using separate blocks, this is a conceptual analogy that may or may not be followed in a specific hardware implementation of the invention. The integrated circuit 50 may include separate circuit areas corresponding to the readout unit 60, the radio frequency unit 70, the power management unit 90, and the control and communication unit 80. However, in other embodiments of the invention, the circuit 50 may be organized differently.

[0047] Figure 5A possible setup for an S-EEG procedure is shown, in which a certain number of electrodes 10 are implanted in a target area 100, such as a selected structure in the patient's brain. The electrodes are connected to an interface unit 120 via a digital bus 185, and the EEG signals picked up by the contacts 20 are transmitted to the interface 120 as robust digital signals, unaffected by electromagnetic interference 200 (e.g. induced signals from the main network at 50 / 60 Hz). Furthermore, even though the number of active channels may be large, the data is transmitted over a limited number of conductors. It is then possible to employ thinner electrodes and / or increase the gauge of the conductors.

[0048] Figure 5 An RF source 75 for thermal coagulation procedures is shown connected to the electrode 10 by a separate line 274. The electrode may also receive a low voltage power source via another line not shown.

[0049] In a possible variation of the present invention, the wired bus 85 may be replaced by a wireless data communication channel (eg ) instead, and the number of wires can be further reduced. In a particularly advantageous variant, the communication is wireless, and the power management unit is powered by the RF signal itself, so that the only wired connection required will be the line 274 carrying the RF signal. Alternatively, if the chip 50 is capable of generating the high voltage RF signal required for thermal coagulation, the external generator 75 and the corresponding line 274 will no longer be required.

[0050] The integrated circuit may include additional functionality including automatic classification of the S-EEG signal based on an algorithm preferably implemented in the integrated circuit 50. This may include a machine learning system, a neural network, or any suitable automatic classification procedure. Possibly, the multi-contact electrode 10 may implement a pre-classification that may be improved and completed in the external processor 120.

[0051] The interface 120 is greatly simplified when compared to what is required in conventional S-EEG programs because much of the processing is performed in the integrated circuit 50 in the electrode 10. The interface 120 can perform digital signal processing of the signal, such as using advanced digital filters to make the desired signal stand out from the noise or to classify the EEG signal. However, in its simplest implementation, the processing is performed entirely in the ASICS 50 of the electrode 10, and the interface 120 acts primarily as a storage device and concentrator. The analysis workstation 150 (which can be a personal computer running a specialized program) interacts with the interface via a suitable network link 185 (e.g., an IP link).

[0052] Figure 6The cross section of the electrode of the present invention in the active area is shown, where the tubular body surrounds the hollow lumen 18. The flexible circuit 23 enters the lumen 18 through the slit 17 and is wrapped around the tubular mandrel 15. The pick-up contacts 20 on the surface of the circuit 23 are exposed on the side of the electrode, while the integrated circuit 50 is in the internal lumen. The flexible circuit 23 can be implemented with a polyimide film or any other suitable material. The flexible circuit can be adhesively bonded to the surface of the mandrel 15. If desired, once the flexible circuit 23 is in place, the slit 17 can be closed to seal the internal lumen 18.

[0053] Figure 7 An alternative implementation is shown in which the flex circuit 23 is wrapped more than one turn upon itself, providing a hole-free uninterrupted cylindrical surface 26. A hollow mandrel 15 may be used, but may be omitted if the wrapped flex circuit provides sufficient rigidity.

[0054] Reference symbols in the drawings

[0055] 10 Slender body

[0056] 11 Distal end, tip

[0057] 15 Tubular body

[0058] 17 Slit

[0059] 18 Lumen

[0060] 20 Pick up contact

[0061] 23 Flexible Printed Circuit

[0062] 26 Side

[0063] 50 ASIC

[0064] 53 Contact pads, high voltage and current

[0065] 54 Contact pads, low voltage and current

[0066] 60 Readout unit

[0067] 61 Temperature front end

[0068] 62 Low Noise Amplifier

[0069] 63 High pass filter

[0070] 64 Programmable Gain Amplifier

[0071] 65 Buffer, Class AB Driver

[0072] 66 Multiplexer switch

[0073] 67 Low pass filter

[0074] 68 readout channels

[0075] 69 A / D converter

[0076] 70 Thermal Coagulation Unit

[0077] 72 Isolating switch

[0078] 73a / b Selector switch, odd / even channels

[0079] 75 High Voltage RF Generator

[0080] 80 Logic and Communication Unit

[0081] 84 Logic units, microcontrollers, finite state machines, data buffers

[0082] 85 Digital Communication Interface

[0083] 90 Power Management Unit

[0084] 100 Target Area

[0085] 120 Interface

[0086] 122 Digital Signal Processing

[0087] 124 Storage Devices

[0088] 150 Analysis Stations

[0089] 165 input channels

[0090] 166 Temperature transducer terminal

[0091] 175 High voltage input terminal

[0092] 185 Data bus terminal

[0093] 274 High Voltage Cable

[0094] 285 Network

Claims

1. A multi-contact electrode device comprising an elongated body (10) having a distal end (18) for placement into a target area (100) of a patient's body, the device comprising a plurality of pick-off contacts (20) on an active portion of the elongated body (10) adjacent the distal end (18) for recording electrical activity of the target area (100) and for delivering radiofrequency current into the target area, the elongated body (10) containing an integrated circuit (50) in the active portion, the integrated circuit (50) comprising: a readout unit (60) having a plurality of input channels (65) configured to amplify and digitize electrical signals imposed on at least some of said pick-off contacts (20) by the electrical activity of said target area, a thermocoagulation unit (70) receiving a radiofrequency signal (75), selectively connectable to at least one contact selected from said pick-up contacts (20) for injecting a local radiofrequency current into said target area (100), - A digital communication interface (85).

2. The device according to the preceding claim, wherein: The integrated circuit (50) has two linear dimensions lower than 2 mm, preferably lower than 1 mm, more preferably equal to or lower than 0.75 mm.

3. The device according to any one of the preceding claims, wherein: The thermocoagulation unit (70) is configured to handle a current of at least 50 mA rms, preferably more than 120 mA rms, and a voltage of at least 15 V rms, preferably more than 20 V rms, at selected contacts.

4. A device according to any of the preceding claims, comprising a readout channel for a temperature sensor (61).

5. The device according to any one of the preceding claims, wherein: The pickup contacts (20) are conductive areas on a flexible printed circuit (26) wrapped around the active portion (15).

6. Apparatus according to any one of the preceding claims, wherein: The integrated circuit (50) is within the hollow interior cavity (18) of the elongated body (10).

7. Device according to claims 5 and 6, said elongated body having a longitudinal slit in said active portion so as to allow a portion of said printed circuit to enter said inner cavity (18).

8. An integrated circuit comprising: a readout unit (60) having a plurality of terminals (65) connectable to the pick-up contacts, configured to process and digitize the bioelectric signals picked up by the pick-up contacts, - an input for a radio frequency signal (75), selectively connectable to at least one terminal selected from said terminals (65), for injecting a local radio frequency current into a target area near the pickup contact, - a digital communication interface (85), Therein, the integrated circuit has two linear dimensions lower than 2 mm, preferably lower than 1 mm, more preferably equal to or lower than 0.75 mm.

9. An integrated circuit according to the preceding claim, configured to handle at selected pick-up contacts a radio frequency signal having a current of at least 50 mA rms, preferably more than 120 mA rms, and a voltage of at least 15 V rms, preferably more than 20 V rms.

10. An integrated circuit according to any one of claims 8 to 9, comprising a readout channel for a temperature sensor (61).

11. The integrated circuit according to any one of claims 8 to 10, the readout unit comprising ten or more readout channels configured to process a plurality of bioelectric signals from different pick-off contacts.

12. The integrated circuit according to any one of claims 8 to 11, the readout unit comprising a differential readout channel configured to process the bioelectric voltage signal relative to a reference potential.

13. The integrated circuit according to any of claims 8 to 12, the readout unit comprising one or more high pass filters having a cut-off frequency below 0.2 Hz.

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