Directional deep brain stimulation closed-loop regulation and control system based on contact current multi-dimensional feedback

Abstract

The invention relates to a directional deep brain stimulation closed-loop regulation and control system based on contact current multi-dimensional feedback, and the system comprises a multi-point directional stimulation and transcranial focused ultrasound coupling module, a DBS contact current multi-dimensional real-time feedback module, and a DBS regulation and control module based on contact current real-time feedback, the multi-point directional stimulation and transcranial focused ultrasound coupling module is used for applying multi-point directional electrical stimulation to the stimulation target region and synchronously scanning the stimulation target region by adopting transcranial focused ultrasound in a multi-point cross-layer manner so as to couple and generate an acoustoelectric signal of the DBS; the DBS contact current multi-dimensional real-time feedback module is used for recording DBS acoustoelectric signals and feeding back characteristic information, including time history change, frequency characteristics, amplitude response and spatial distribution, of a stimulation target area; and the DBS regulation and control module based on the real-time feedback of the contact current is used for calculating and analyzing the position, the intensity, the frequency and the time domain deviation numerical value of the DBS contact current, and correcting the DBS contact, the waveform and the pulse width stimulation parameters in a targeted and self-adaptive manner according to the numerical value.

Description

Technical Field

[0001] The present invention relates to a deep brain stimulation closed-loop control system based on multi-dimensional real-time feedback of contact current. Background Art

[0002] Deep brain stimulation (DBS) is a surgical procedure that implants stimulation electrodes into specific areas of the brain. The stimulation electrodes are controlled by a pulse generator, and the high-frequency electrical pulses they generate can stimulate some nerve nuclei deep in the brain, regulate and correct abnormal neural circuits, and thus achieve therapeutic effects. DBS has the advantages of being non-destructive, reversible, individually adjusted for treatment, and having long-lasting efficacy. The therapeutic effect of DBS mainly depends on the current target location and the state of the stimulation current. Long-term implanted DBS electrodes may corrode, rotate, and migrate, etc., and stimulation parameters need to be adjusted scientifically and promptly after surgery to maintain the best therapeutic effect. Therefore, realizing closed-loop control of DBS based on real-time feedback of contact current is of great clinical significance for long-term and efficient treatment.

[0003] Electroacoustic imaging can spatially encode the biocurrent source by utilizing electroacoustic coupling, and obtain the electrical signal at the precise focal position in a targeted manner. It can directly depict the biocurrent density distribution and map its electrical characteristics, making the spatial distribution and dynamic evolution of the current source observable, quantifiable, and evaluable, providing a new idea for intuitive feedback on the spatial distribution and stimulation state of DBS contact current.

[0004] Current research mainly uses postoperative magnetic resonance imaging or computed tomography imaging data to reconstruct electrode positioning and predict the electric field distribution generated by the stimulating electrode in the brain tissue when the DBS contact is activated. However, this type of method is difficult to directly and in real time provide feedback on the spatial distribution and dynamic changes of the DBS contact current. At present, the DBS closed-loop control system still lacks intuitive electrical feedback on the contact current in the body, and it is impossible to adjust the stimulation parameters in real time according to the current state in clinical applications. In order to fill this gap, electroacoustic imaging, as a non-invasive bio-current source detection method with high temporal and spatial resolution, is expected to be used to feedback the spatial distribution and actual stimulation state of the DBS contact current, and realize DBS closed-loop control based on real-time feedback of the contact current. Therefore, the present invention proposes a directional DBS closed-loop control system based on multi-dimensional real-time feedback of the contact current, which provides technical support for adjusting the stimulation parameters after surgery and maintaining the optimal DBS therapeutic effect for a long time. Summary of the invention

[0005] The present invention aims to utilize the advantages of non-invasive and high-resolution electrical detection of acoustic and electrical imaging, provide multi-dimensional real-time feedback on the spatial distribution and stimulation state of DBS contact current, adaptively and targetedly adjust stimulation parameters according to feedback deviations, and achieve directional DBS closed-loop control. Compared with existing DBS closed-loop control technology, this system not only intuitively feedbacks the multi-dimensional information of DBS contact current in vivo in terms of time, frequency, amplitude and space, but also can adaptively and targetedly adjust contact current parameters according to feedback deviations. The technical solution is as follows:

[0006] A directional deep brain stimulation closed-loop control system based on multi-dimensional feedback of contact current, comprising a multi-point directional stimulation and transcranial focused ultrasound coupling module, a DBS contact current multi-dimensional real-time feedback module, and a DBS control module based on real-time feedback of contact current, wherein:

[0007] The multi-point directional stimulation and transcranial focused ultrasound coupling module is used to apply multi-point directional electrical stimulation to the stimulation target area, and simultaneously use transcranial focused ultrasound to scan the stimulation target area at multiple points across layers to couple and generate DBS acoustic and electrical signals;

[0008] DBS contact current multi-dimensional real-time feedback module is used to record DBS acoustic and electrical signals and feedback characteristic information of the stimulation target area including time course changes, frequency characteristics, amplitude response and spatial distribution;

[0009] The DBS control module based on real-time feedback of contact current is used to calculate and analyze the DBS contact current position, intensity, frequency, and time domain deviation values, and adaptively correct the DBS contact, waveform, and pulse width stimulation parameters accordingly, including:

[0010] Time domain deviation analysis unit: Pearson correlation analysis is used to evaluate the global and local synchronization between the feedback current and the preset current; the Pearson correlation coefficient between the long-term time domain waveform output by the time domain change feedback unit and the preset current waveform is calculated to evaluate their global synchronization; the Pearson correlation coefficient between the short-term time domain waveform output by the time domain change feedback unit and the preset current waveform is calculated to evaluate their local synchronization; the windowed time lag cross correlation is used to evaluate the directionality between the feedback current and the preset current; the time series of the feedback current and the preset current are divided into equal-length time periods, and the time lag cross correlation coefficients of each equal-length time window are calculated; the interaction between the feedback current and the preset current is compared according to each window or the sum of the windows;

[0011] Frequency deviation analysis unit: calculates the frequency deviation between the feedback current and the preset current;

[0012] Strength deviation analysis unit: calculate the error percentage between the feedback current and the preset current = (maximum output value - minimum output value) / (maximum output value + minimum output value) × 100%, the maximum output value and the minimum output value refer to the maximum and minimum values ​​of the feedback current when the preset current is the maximum and minimum;

[0013] Position deviation analysis unit: uses a three-dimensional coordinate system to calculate the deviation distance and offset direction between feedback currents and feedback contact positioning deviation;

[0014] Adaptive targeting correction unit.

[0015] Furthermore, the multi-point directional stimulation and transcranial focused ultrasound coupling module includes:

[0016] Multi-point directional DBS stimulation unit, which includes a multi-channel programmable pulse transmitter and DBS multi-contact electrodes, is used to apply electrical stimulation to the treatment target. The number, direction, and spacing of the stimulation contacts can be preset, and the waveform, frequency, amplitude, phase, pulse width, and polarity parameters of the initial stimulation current can be set to achieve directional, quantitative, and localized DBS stimulation.

[0017] The multi-point cross-layer synchronous scanning unit includes a multi-element phased array and a multi-element ultrasonic transducer, and is used to scan and stimulate the target area to generate DBS acoustic and electrical signals; by dividing the element area, multi-point cross-layer synchronous scanning can be selected.

[0018] Furthermore, the DBS acoustic and electrical signals after transcranial focused ultrasound scanning are collected, and the collected DBS acoustic and electrical signals are processed to obtain a signal s that can map the DBS contact current characteristics. DBS-AE (t), for s DBS-AE (t) Process and analyze the time domain changes, frequency characteristics, amplitude response and spatial distribution of the feedback contact current. The DBS contact current multi-dimensional real-time feedback module includes:

[0019] Time domain variation feedback unit: extract s DBS-AE (t) The long-term and short-term time domain waveforms are captured and saved according to a fixed time length;

[0020] Frequency characteristic feedback unit: Use Fourier transform of autocorrelation function to obtain power spectrum density of different durations and confirm the frequency corresponding to the peak value;

[0021] Amplitude response feedback unit: calculate different time lengths s DBS-AE The average amplitude of (t) reflects the steady-state stimulus intensity over a period of time, and s is calculated. DBS-AE (t) The amplitude at the peak and trough moments reflects the transient stimulus intensity;

[0022] Spatial distributed feedback unit: using the XY, XZ, YZ planes DBS-AE The (t) amplitude is used to establish its three-dimensional spatial distribution diagram, combined with the time-space dynamic changes of the contact current in three-dimensional space-time at different moments.

[0023] Further, the adaptive targeting correction unit includes: a preset time domain correlation coefficient threshold, when the time domain correlation coefficient is less than the preset threshold and the feedback current lags behind the preset current, the stimulation current phase is corrected forward, when the time domain correlation coefficient is less than the preset threshold and the preset current lags behind the feedback current, the stimulation current phase is corrected backward, otherwise the stimulation current phase is not corrected; a preset stimulation current frequency limit value, when (feedback current frequency-preset current frequency) ≥ frequency limit value, the stimulation current frequency is reduced, when (feedback current frequency-preset current frequency) ≤ the negative value of the limit value, the stimulation current frequency is increased, otherwise the stimulation frequency is not corrected; a preset stimulation intensity limit value, when the intensity error percentage is greater than the stimulation intensity limit value, the stimulation current amplitude is increased or decreased, otherwise the stimulation amplitude is not corrected; a preset deviation distance threshold and an offset angle threshold, when the deviation distance>deviation distance threshold or the offset angle>offset angle threshold, the current direction is changed in the following three ways: ①Reselect the stimulation contact position, including direction and spacing ②Use the anode and cathode to guide the current to a specific direction ③Modulate the DBS waveform by extending the stimulation pulse to change the stimulation current direction.

[0024] The present invention designs a directional DBS closed-loop control system based on multi-dimensional real-time feedback of contact current, which takes advantage of the non-invasive and high-resolution electrical detection of electroacoustic imaging, provides multi-dimensional real-time feedback of the spatial distribution and stimulation state of DBS contact current, and adaptively adjusts stimulation parameters according to feedback deviation to achieve directional DBS closed-loop control. Compared with the traditional DBS closed-loop control system, the directional deep brain stimulation closed-loop control system based on multi-dimensional real-time feedback of contact current has the following advantages:

[0025] (1) It can provide real-time feedback on the spatial position, time domain changes, frequency characteristics, and amplitude response of the contact current in the body from an intuitive electrical perspective.

[0026] (2) Based on the real-time multi-dimensional feedback of the contact current, the stimulation parameters can be adaptively and targetedly regulated to maintain the best therapeutic effect in the long term. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 It is a schematic diagram of the system structure of the present invention;

[0028] Figure 2 It is a work flow chart of the present invention;

[0029] Figure 3This is a working diagram of the DBS contact current multi-dimensional real-time feedback module of the present invention;

[0030] Figure 4 This is a working diagram of the DBS control module based on real-time feedback of contact current of the present invention. DETAILED DESCRIPTION

[0031] The present invention designs a directional DBS closed-loop control system based on multi-dimensional real-time feedback of contact current. This invention can be used in clinical medical diagnosis, neurological disease rehabilitation, neuroengineering and other fields. Further research can achieve efficient and stable DBS treatment effects, and is expected to obtain considerable social and economic benefits.

[0032] The structural block diagram of the directional DBS closed-loop control system based on multi-dimensional real-time feedback of contact current proposed in the present invention is as follows: Figure 1 As shown. The system is mainly composed of a multi-point directional stimulation and transcranial focused ultrasound coupling module, a DBS contact current multi-dimensional real-time feedback module, and a DBS control module based on contact current real-time feedback. Among them, the multi-point directional stimulation and transcranial focused ultrasound coupling module is used to apply multi-point directional electrical stimulation to the stimulation target area, and at the same time, transcranial focused ultrasound multi-point cross-layer synchronous scanning of the stimulation target area is used to couple and generate DBS acoustic and electrical signals; the DBS contact current multi-dimensional real-time feedback module is used to record DBS acoustic and electrical signals, and feedback characteristic information such as time course changes, frequency characteristics, amplitude response and spatial distribution of the stimulation target area; the DBS control module based on contact current real-time feedback is used to calculate and analyze the deviation values ​​of DBS contact current position, intensity, frequency, time domain, etc., and adaptively correct DBS contact, waveform, pulse width and other stimulation parameters accordingly.

[0033] The workflow diagram of the directional DBS closed-loop control system based on multi-dimensional real-time feedback of contact current is as follows: Figure 2 As shown, the whole process can be divided into the following three steps: ① multi-point directional DBS stimulation and multi-point cross-layer synchronous scanning; ② DBS acoustic and electrical signal acquisition and multi-dimensional real-time feedback of contact current; ③ feedback feature deviation analysis and adaptive targeted correction of stimulation parameters. The following is a detailed description of each module.

[0034] 1. Multi-point directional stimulation and transcranial focused ultrasound coupling module

[0035] (1) Multi-point directional DBS stimulation unit: The multi-point directional DBS stimulation unit consists of a multi-channel programmable pulse transmitter and a DBS multi-contact electrode, which is used to apply electrical stimulation to the treatment target. The number of stimulation contacts (1-6), direction (0-360°), spacing (1:0.5:5mm), and the waveform (pulse wave, square wave, sine wave), frequency (10-2000Hz), amplitude (0-300mA), phase (0-360°), pulse width (10-1000μs), polarity (monopolar / bipolar) and other parameters of the initial stimulation current can be preset to achieve directional, quantitative, and localized DBS stimulation.

[0036] (2) Multi-point cross-layer synchronous scanning unit: The multi-point cross-layer synchronous scanning unit consists of a 256-element phased array and a 256-element ultrasonic transducer, which is used to scan and stimulate the target area to generate DBS acoustic and electrical signals. By dividing the 256-element area, you can choose 1-4 multi-point cross-layer synchronous scanning, with a focusing accuracy of less than 1mm, to achieve high-efficiency and high-precision DBS-transcranial focused ultrasound coupling.

[0037] 2.DBS contact current multi-dimensional real-time feedback module

[0038] After transcranial focused ultrasound scanning, the DBS acoustic and electrical signals are collected by a conventional EEG amplifier, and the collected DBS acoustic and electrical signals are processed to obtain a signal that can map the DBS contact current characteristics. DBS-AE (t). The working process of DBS contact current multi-dimensional real-time feedback module is as follows Figure 3 As shown, for s DBS-AE (t) Process and analyze the time domain variation, frequency characteristics, amplitude response and spatial distribution of the feedback contact current.

[0039] (1) Time domain change feedback unit: extract s DBS-AE The long-term (1-10min) and short-term (0.01-1s) time domain waveforms of (t) are captured and saved at fixed time lengths.

[0040] (2) Frequency characteristic feedback unit: The Fourier transform of the autocorrelation function is used to obtain the frequency characteristics of different time lengths (5s, 30s, 60s, 300s) DBS-AE (t) to identify the frequency corresponding to the peak.

[0041] (3) Amplitude response feedback unit: calculate different time lengths s DBS-AE The average amplitude of (t) reflects the steady-state stimulus intensity over a period of time, and s is calculated. DBS-AE (t) The amplitude at typical moments (peaks and troughs) reflects the transient stimulus intensity.

[0042] (4) Spatially distributed feedback unit: using the sDBS-AE The (t) amplitude is used to establish its three-dimensional spatial distribution diagram, combined with the time-space dynamic changes of the contact current in three-dimensional space-time at different moments.

[0043] 3. DBS control module based on real-time feedback of contact current

[0044] The working process of DBS control module based on real-time feedback of contact current is as follows Figure 4 As shown, according to the output result of the above feedback unit, the deviation analysis is performed on the time domain, frequency, intensity and position between the feedback current and the preset current, and then the adaptive targeted correction of the corresponding stimulation parameters is implemented.

[0045] (1) Time domain deviation analysis unit: Pearson correlation analysis is used to evaluate the global and local synchronization between the feedback current and the preset current. The Pearson correlation coefficient between the long-term (1-10min) time domain waveform output by the time domain change feedback unit and the preset current waveform is calculated to evaluate their global synchronization; the Pearson correlation coefficient between the short-term (0.01-1s) time domain waveform output by the time domain change feedback unit and the preset current waveform is calculated to evaluate their local synchronization. The windowed time lag cross-correlation is used to evaluate the directionality between the feedback current and the preset current. The time series of the 1min feedback current and the preset current are divided into 60 equal-length time periods, and the time lag cross-correlation coefficients of 60 1s time windows are calculated. Then, the interaction between the feedback current and the preset current is compared based on each window or the sum of the windows. Compared with conventional time lag cross-correlation, this method can achieve a more fine-grained evaluation effect.

[0046] (2) Frequency deviation analysis unit: calculates the frequency deviation between the feedback current and the preset current, with a deviation range of ±0.5 Hz.

[0047] (3) Strength deviation analysis unit: Calculate the error percentage between the feedback current and the preset current = (maximum output value - minimum output value) / (maximum output value + minimum output value) × 100%, where the maximum output value and the minimum output value refer to the maximum and minimum values ​​of the feedback current when the preset current is maximum and minimum.

[0048] (4) Position deviation analysis unit: uses a three-dimensional coordinate system to calculate the deviation distance and offset direction between feedback currents and feedback contact positioning deviation.

[0049] (5) Adaptive targeted correction unit: When the time domain correlation coefficient is less than 0.6 and the feedback current lags behind the preset current, the stimulation current phase needs to be corrected forward; when the time domain correlation coefficient is less than 0.6 and the preset current lags behind the feedback current, the stimulation current phase needs to be corrected backward, otherwise the stimulation current phase will not be corrected; when (feedback current frequency - preset current frequency) ≥ 0.5 Hz, the stimulation current frequency is reduced; when (feedback current frequency - preset current frequency) ≤ -0.5 Hz, the stimulation current frequency is increased, otherwise the stimulation frequency will not be corrected; when the intensity error percentage is greater than 5%, the stimulation current amplitude is increased or decreased, otherwise the stimulation amplitude is not corrected; when the deviation distance is > 0.5 mm or the offset angle is > 5°, the current direction can be changed in the following three ways: ① Reselect the stimulation contact position, including direction (0-360°) and spacing (1:0.5:5 mm); ② Use the anode and cathode to guide the current to a specific direction; ③ Modulate the DBS waveform by extending the stimulation pulse to change the stimulation current direction.

Claims

1. A closed-loop control system for directional deep brain stimulation based on multi-dimensional feedback of contact current, comprising a multi-point directional stimulation and transcranial focused ultrasound coupling module, a DBS contact current multi-dimensional real-time feedback module, and a DBS control module based on contact current real-time feedback, wherein: The multi-point directional stimulation and transcranial focused ultrasound coupling module is used to apply multi-point directional electrical stimulation to the stimulation target area, and simultaneously use transcranial focused ultrasound to scan the stimulation target area at multiple points across layers to couple and generate DBS acoustic and electrical signals; DBS contact current multi-dimensional real-time feedback module is used to record DBS acoustic and electrical signals and feedback characteristic information of the stimulation target area including time course changes, frequency characteristics, amplitude response and spatial distribution; The DBS control module based on real-time feedback of contact current is used to calculate and analyze the DBS contact current position, intensity, frequency, and time domain deviation values, and adaptively correct the DBS contact, waveform, and pulse width stimulation parameters accordingly, including: Time domain deviation analysis unit: Pearson correlation analysis is used to evaluate the global and local synchronization between the feedback current and the preset current; the Pearson correlation coefficient between the long-term time domain waveform output by the time domain change feedback unit and the preset current waveform is calculated to evaluate their global synchronization; the Pearson correlation coefficient between the short-term time domain waveform output by the time domain change feedback unit and the preset current waveform is calculated to evaluate their local synchronization; the windowed time lag cross correlation is used to evaluate the directionality between the feedback current and the preset current; the time series of the feedback current and the preset current are divided into equal-length time periods, and the time lag cross correlation coefficients of each equal-length time window are calculated; the interaction between the feedback current and the preset current is compared according to each window or the sum of the windows; Frequency deviation analysis unit: calculates the frequency deviation between the feedback current and the preset current; Strength deviation analysis unit: calculate the error percentage between the feedback current and the preset current = (maximum output value - minimum output value) / (maximum output value + minimum output value) × 100%, the maximum output value and the minimum output value refer to the maximum and minimum values ​​of the feedback current when the preset current is the maximum and minimum; Position deviation analysis unit: uses a three-dimensional coordinate system to calculate the deviation distance and offset direction between feedback currents and feedback contact positioning deviation; Adaptive targeting correction unit.

2. The closed-loop control system for targeted deep brain stimulation according to claim 1, characterized in that: Multi-point directional stimulation and transcranial focused ultrasound coupling module, including: Multi-point directional DBS stimulation unit, which includes a multi-channel programmable pulse transmitter and DBS multi-contact electrodes, is used to apply electrical stimulation to the treatment target. The number, direction, and spacing of the stimulation contacts can be preset, and the waveform, frequency, amplitude, phase, pulse width, and polarity parameters of the initial stimulation current can be set to achieve directional, quantitative, and localized DBS stimulation. The multi-point cross-layer synchronous scanning unit includes a multi-element phased array and a multi-element ultrasonic transducer, and is used to scan and stimulate the target area to generate DBS acoustic and electrical signals; by dividing the element area, multi-point cross-layer synchronous scanning can be selected.

3. The closed-loop control system for targeted deep brain stimulation according to claim 1, characterized in that: The DBS acoustic and electrical signals after transcranial focused ultrasound scanning are collected, and the collected DBS acoustic and electrical signals are processed to obtain a signal s that can map the DBS contact current characteristics. DBS-AE (t), for s DBS-AE (t) Process and analyze the time domain changes, frequency characteristics, amplitude response and spatial distribution of the feedback contact current. The DBS contact current multi-dimensional real-time feedback module includes: Time domain variation feedback unit: extract s DBS-AE (t) The long-term and short-term time domain waveforms are captured and saved according to a fixed time length; Frequency characteristic feedback unit: Use Fourier transform of autocorrelation function to obtain power spectrum density of different durations and confirm the frequency corresponding to the peak value; Amplitude response feedback unit: calculate different time lengths s DBS-AE The average amplitude of (t) reflects the steady-state stimulus intensity over a period of time, and s is calculated. DBS-AE (t) The amplitude at the peak and trough moments reflects the transient stimulus intensity; Spatial distributed feedback unit: using the XY, XZ, YZ planes DBS-AE The (t) amplitude is used to establish its three-dimensional spatial distribution diagram, combined with the time-space dynamic changes of the contact current in three-dimensional space-time at different moments.

4. The closed-loop control system for targeted deep brain stimulation according to claim 3, characterized in that: The adaptive targeting correction unit includes: a preset time domain correlation coefficient threshold, when the time domain correlation coefficient is less than the preset threshold and the feedback current lags behind the preset current, the stimulation current phase is corrected forward, when the time domain correlation coefficient is less than the preset threshold and the preset current lags behind the feedback current, the stimulation current phase is corrected backward, otherwise the stimulation current phase is not corrected; a preset stimulation current frequency limit value, when (feedback current frequency-preset current frequency) ≥ frequency limit value, the stimulation current frequency is reduced, when (feedback current frequency-preset current frequency) ≤ the negative value of the limit value, the stimulation current frequency is increased, otherwise the stimulation frequency is not corrected; a preset stimulation intensity limit value, when the intensity error percentage is greater than the stimulation intensity limit value, the stimulation current amplitude is increased or decreased, otherwise the stimulation amplitude is not corrected; a preset deviation distance threshold and an offset angle threshold, when the deviation distance>deviation distance threshold or the offset angle>offset angle threshold, the current direction is changed in the following three ways: ① reselect the stimulation contact position, including direction and spacing ② use the anode and cathode to guide the current to a specific direction ③ modulate the DBS waveform by extending the stimulation pulse to change the stimulation current direction.

5. The closed-loop control system for targeted deep brain stimulation according to claim 4, characterized in that: The time domain correlation coefficient threshold is 0.

6.

6. The closed-loop control system for targeted deep brain stimulation according to claim 1, characterized in that: The stimulation current frequency limit value is 0.5 Hz.

7. The closed-loop control system for targeted deep brain stimulation according to claim 1, characterized in that: The stimulation intensity limit value is 5%.

8. The closed-loop control system for targeted deep brain stimulation according to claim 1, characterized in that: The deviation distance threshold is 0.5 mm, and the offset angle threshold is 5°.

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