Dynamic closed-loop nerve regulation and control method integrating ultrasonic array element and fNIRS probe

Abstract

The invention relates to the technical field of cranial nerve regulation and control, and discloses a dynamic closed-loop nerve regulation and control method integrating an ultrasonic array element and an fNIRS probe, which adopts a mode of combining a near-infrared light detector and the ultrasonic array element, can utilize the characteristics of transcranial focused ultrasound to stimulate deep nuclei of the brain, and utilizes near-infrared to observe the change of cerebral cortex in real time. Real-time observation of brain blood oxygen level change caused by cortical excitability of each brain region of a brain function network is realized, closed-loop feedback is formed, then dynamic parameter adjustment is performed on the phased array ultrasonic array, dynamic closed-loop nerve regulation and control of the integrated ultrasonic array element and the near-infrared brain function imaging probe are realized, and the brain blood oxygen level change is observed in real time. And the maximum change of the cortex excitability of the expected brain region or the brain network node is obtained through the focusing process, so that the precision of the stimulation target region is realized.

Description

Technical Field

[0001] The present invention relates to the field of brain nerve regulation technology, and specifically to a dynamic closed-loop nerve regulation method integrating an ultrasonic array element and an fNIRS probe. Background Art

[0002] Near-infrared brain functional imaging, also known as functional near-infrared spectroscopy (fNIRS), is a cutting-edge non-invasive brain functional neuroimaging technology with scientific research value: Near-infrared brain functional imaging has extensive scientific research value in many fields such as neuroscience, psychology, and physiology. It can help researchers gain a deeper understanding of the working principles of the brain and the mechanisms of diseases. In clinical practice, doctors can develop targeted treatment plans based on the results of near-infrared brain functional imaging and the patient's clinical manifestations. Near-infrared brain functional imaging requires an infrared laser or LED light source, which is guided into the head and into the skull through an optical fiber, absorbed and reflected by the brain, and then transmitted to the photosensitive device by the optical fiber.

[0003] Transcranial Low-Intensity Focused Ultrasound (TLIFU) is an emerging non-invasive brain stimulation technology that uses focused ultrasound beams to act on specific brain areas in a non-invasive manner to achieve neuromodulation. The main features of this technology are its high spatial focusing ability and deep penetration ability, which can accurately affect the deep structures of the brain. In order to effectively penetrate the skull, disperse the heat of the scalp, and electronically shift the focus, low-intensity transcranial focused ultrasound often uses a multi-element concave phased array probe. Depending on the size of the probe and the number of elements (generally 6~10mm in diameter and 8~128 transducers), there is a certain distance between each transducer.

[0004] The near-infrared light used in near-infrared brain functional imaging is transmitted to the scalp through optical fiber for near-infrared light injection, and also receives reflected and scattered near-infrared light to the photosensitive device avalanche photodiode through optical fiber. The transmitting probe and the receiving probe can be switched with each other, and there is a distance between them. In practice, it is found that the most sensitive spacing for detecting brain activity is about 3 to 4 cm. The size of the near-infrared transmitting and receiving optical fiber probes is 4 to 8 mm, and the number is 2 to 64. The transmitting and receiving are staggered and evenly or unevenly distributed on the surface of the head.

[0005] Currently, there is no integrated ultrasound and near-infrared brain imaging equipment on the market. The adjustment method is to adjust the patient's condition based on the results of cortical excitability detection by near-infrared brain functional imaging after treatment with ultrasound or other neuromodulatory equipment, guided by the theory of asymmetric balance of the cerebral hemispheres. This type of adjustment is not real-time, and it takes a while for the treatment to be completed before the test can be performed. The trial and error time and cost are high. Summary of the invention

[0006] In view of the above problems, the purpose of the present invention is to provide a dynamic closed-loop neural regulation method integrating ultrasound array elements and fNIRS probes, realize dynamic closed-loop neural regulation integrating ultrasound array elements and near-infrared brain functional imaging probes, and obtain the maximum change in cortical excitability of the desired brain area or brain network node through the focusing process, so as to achieve precise stimulation of the target area. The technical solution is as follows: A dynamic closed-loop neural control method integrating ultrasound array elements and fNIRS probes is provided, wherein a combined probe array including a plurality of near-infrared brain functional imaging probes and a plurality of ultrasound array elements is used, wherein the combined probe array is concave, and the curvature radius is set according to the radius of the human head; the control method is as follows: Step 1: Place the combined probe array in the brain area to be stimulated or the whole brain, and divide the brain area; Step 2: Collect near-infrared blood oxygen signals: The near-infrared brain functional imaging probe array collects near-infrared blood oxygen signals for 60 to 600 seconds to obtain the distribution of near-infrared blood oxygen signals in the brain; Step 3: Based on the obtained near-infrared blood oxygen signal, the functional connection calculation is performed with the correlation coefficient of each channel signal as an indicator to obtain the brain area corresponding to each detection node and the brain network state including the connection strength of each brain area, and determine the brain area with abnormal excitability; Step 4: Perform enhanced or inhibited ultrasound stimulation in the abnormally excitable brain area according to the disease type; Step 5: During the ultrasound stimulation process, the changes in near-infrared blood oxygen signals are monitored synchronously to measure the changes in cortical excitability of each node in the brain network; Step 6: At intervals of 20 to 60 seconds, the phased array ultrasonic array composed of multiple ultrasonic array elements changes the pulse timing to shift the focus. The focus shift strategy is determined according to the focal depth and the horizontal diameter D of the focal spot. The phase of each ultrasonic array element is controlled to move from the current focal spot center to a distance D, and then move clockwise along a hexagon with the current focal spot center as the center and a side length of D, for a total of six positions; Step 7: Measure the changes in the brain network, extract the near-infrared blood oxygen signal data at the target node, perform weighted smoothing on the data points with a time window of 20 to 200 milliseconds, and then take the derivative to obtain the maximum rate of change, which is used as the decision indicator; or use the change in the correlation coefficient of two groups of near-infrared blood oxygen signals in a specific functional area, that is, the maximum change rate of the connection strength as the decision indicator, and determine the focus position with the largest change in cortical excitability in step 5, which is the focal spot center for the next focus shift; Step 8: Repeat step 6. If the change of the near-infrared blood oxygen signal at the six surrounding positions is less than the set threshold, and the change of the functional connection strength is also less than the set threshold, it is judged that the correct target area is stimulated, otherwise proceed to the next step; Step 9: Go back to step 5 and iterate.

[0007] Furthermore, when dividing the brain regions in step 1, in the presence of a positioning device, MRI structural imaging is first scanned, and the functional regions of the individual brain are divided using software with functional partitioning; In the absence of positioning equipment, a near-infrared brain functional imaging probe cap with an electrode cap with coordinates equivalent to 10 to 20 of the EEG is used for positioning, and the corresponding area of ​​the small-area probe array is left vacant.

[0008] Furthermore, the specific process of step 3 is as follows: Step 3.1: Retrieve data from all near-infrared brain functional imaging probes in real time; Step 3.2: Correlation calculation: Calculate the Pearson correlation coefficient or Spearman correlation coefficient of the data of each two near-infrared brain functional imaging probes; Step 3.3: According to the calculated correlation coefficient, set a threshold, select the correlation coefficient greater than the threshold, or select the 20%~30% with the largest correlation coefficient as the valid functional connection point pairs; Step 3.4: Map the spatial positions of each effective connection point to the standard brain space to form a brain network; Step 3.5: Compare the normal excitability of the brain region with that established in the standard brain space, or compare with the excitability intensity distribution of the brain network established in step 3.4 to identify abnormal brain regions.

[0009] The beneficial effects of the present invention are as follows: the present invention adopts a method of combining near-infrared light detectors and ultrasonic array elements, which can utilize the characteristics of transcranial focused ultrasound to stimulate deep brain nuclei, utilize near-infrared real-time observation of changes in the cerebral cortex, and realize real-time observation of changes in cerebral blood oxygen levels caused by cortical excitability of various brain regions in the brain functional network, forming a closed-loop feedback, and then dynamically adjusting the parameters of the phased array ultrasonic array, realizing dynamic closed-loop neural regulation of the integrated ultrasonic array element and the near-infrared brain functional imaging probe, and obtaining the maximum change in cortical excitability of the desired brain region or brain network node through the focusing process, thereby realizing precise stimulation of the target area. BRIEF DESCRIPTION OF THE DRAWINGS

[0010] Figure 1 Schematic diagram of the spacing distribution between the near-infrared brain functional imaging probe and the ultrasound array elements.

[0011] Figure 2 Schematic diagram of the integrated concave surface for inserting the near-infrared brain functional imaging probe and the ultrasound array element.

[0012] Figure 3 Schematic diagram of the focus shifting sequence of the phased array ultrasonic array.

[0013] In the figure: 1-ultrasound array element; 2-near-infrared brain functional imaging probe. DETAILED DESCRIPTION

[0014] The present invention is further described in detail below with reference to the accompanying drawings and specific embodiments.

[0015] The present invention adopts a combination of near-infrared light detectors and ultrasonic array elements. It can utilize the characteristics of transcranial focused ultrasound to stimulate deep brain nuclei, and use near-infrared to observe changes in the cerebral cortex in real time, thereby realizing real-time observation of changes in cerebral blood oxygen levels caused by cortical excitability in various brain regions of the brain functional network, forming a closed-loop feedback, and then dynamically adjusting the parameters of the phased array ultrasonic array to achieve the purpose of optimal and precise neural regulation.

[0016] The structure of the combined probe array (cap) of the present invention is as follows: the combined probe array is concave, the radius of curvature is similar to the radius of the human head, the near-infrared brain function imaging probe 2 and the ultrasonic array element 1 are spaced apart, and the front side is Figure 1 shown.

[0017] To fit the head, the near-infrared brain function imaging probe and the ultrasound array element are cylindrical modules, which are inserted into the preset circular holes of the integrated concave surface. The depth is adjustable to ensure that each unit fits the scalp. Figure 2 shown.

[0018] The present invention has two working modes, the overall coverage mode and the combination mode. In the head coverage mode, the ultrasonic transducer and the infrared transceiver probe cover the whole brain. In the combination mode, the ultrasonic unit distribution area is small. For the area of ​​the head not covered by the combination transducer, the original near-infrared detector cap is used to cover it to obtain the near-infrared signal of other areas.

[0019] The combined probe array can be designed in different shapes and sizes according to treatment needs, including a concave array covering a small area of ​​about 6 cm in diameter and a hemispherical array covering the entire brain.

[0020] Due to the distortion of the sound field by the skull, the focal spot of the phased array ultrasound array will be seriously affected. This image can be corrected to a considerable extent by the working parameters of the phased array ultrasound array. After equipping the above-mentioned combined probe array or array cap, the corresponding brain area is stimulated by ultrasound, near-infrared imaging and signal acquisition are performed to achieve closed-loop adjustment of the phased array ultrasound array to achieve precise stimulation. The specific steps are as follows: Step 1: Place the combined probe array in the brain area to be stimulated or in the whole brain (for the whole brain, the ultrasound array element and nearby array elements in the corresponding brain area should be selected).

[0021] If there is a positioning device, MRI structural imaging can be scanned first, and software with functional partitioning (such as FREESURFER, etc.) can be used to divide the individual brain functional areas.

[0022] In the absence of positioning equipment, a near-infrared brain functional imaging probe cap with an electrode cap with the same coordinates as the EEG 10-20 is used for positioning. The small-area probe array needs to leave corresponding areas vacant to place other infrared detection units.

[0023] Step 2: Start collecting near-infrared blood oxygen signals. The near-infrared brain functional imaging probe array collects 60 to 600 seconds of near-infrared light signals and the distribution of near-infrared blood oxygen signals in the brain.

[0024] Step 3: Based on the obtained near-infrared blood oxygen signal, functional connectivity calculation is performed using the correlation coefficient of each channel signal (Pearson correlation coefficient or Spearman correlation coefficient) as an indicator to obtain the brain network status including whether the excitability of each node (brain area) is abnormal and the connection strength.

[0025] The calculation process is as follows: (1) Retrieve data from all near-infrared brain functional imaging probes in real time; (2) Perform pairwise correlation calculations. The correlation coefficient calculation method can be the Pearson correlation coefficient or the Spearman correlation coefficient; (3) According to the calculated correlation coefficient, a threshold is set, such as 0.5-0.6, and 20%-30% of the points with a correlation coefficient greater than the threshold or with a relatively large correlation coefficient are selected as valid functional connection point pairs; (4) Mapping the spatial locations of effective connection points to the standard brain space to form a brain network; (5) Compare the normal excitability of the brain region with that established in the standard brain space (relative intensity of the contralateral excitability of the norm), or compare with the excitability intensity distribution of the brain network established in step 4 to identify abnormal brain regions.

[0026] Step 4: Perform enhanced or inhibited ultrasound stimulation in the abnormally excitable brain area according to the disease type.

[0027] Step 5: During the ultrasound stimulation process, the changes in near-infrared light signals are synchronously monitored to measure the changes in cortical excitability of each node in the brain network.

[0028] Step 6: At intervals of 20 to 60 seconds, the phased array ultrasound array changes the pulse timing to shift the focus. The focus shift strategy is determined based on the focal depth and the focal spot horizontal diameter D (roughly about 1 cm in diameter). The phase of each ultrasound array element is controlled to move from the current focal spot center to a distance D, and then move clockwise along a hexagon with the current focal spot center as the center and a side length of D, for a total of six positions; the sequence is as follows: Figure 3 shown.

[0029] Due to the distortion of the sound field and the individual differences of the human brain, it is necessary to try this focus shift, and the effect is evaluated by near-infrared signals.

[0030] Step 7: Measure the changes in the brain network, extract the near-infrared light signal data at the target node, perform weighted smoothing on the data points with a time window of 20 to 200 milliseconds, and then take the derivative to obtain the maximum rate of change, which is used as the decision indicator; or use the change in the correlation coefficient of two groups of near-infrared light signals in a specific functional area, that is, the maximum change rate of the connection strength as the decision indicator, and determine the focus position with the largest change in cortical excitability in step 5, which is the focal spot center for the next focus shift.

[0031] Step 8: Repeat step 6. If the change in the near-infrared blood oxygen signal at the six surrounding positions is less than 5% and the change in the functional connection strength is less than 5%, it is determined that the correct target area is stimulated, otherwise proceed to the next step.

[0032] Step 9: Go back to step 5 and iterate.

[0033] The present invention proposes an adjustment method for real-time closed-loop neural regulation using a combination of ultrasound and near-infrared brain imaging. The focusing process is proposed for the first time and can achieve the maximum change in the cortical excitability of the desired brain area or brain network node, thereby achieving precise stimulation of the target area.

Claims

1. A dynamic closed-loop neural control method integrating ultrasound array elements and fNIRS probes, characterized in that: A combined probe array including multiple near-infrared brain function imaging probes and multiple ultrasonic array elements is used. The combined probe array is concave, and the curvature radius is set according to the radius of the human head. The control method is as follows: Step 1: Place the combined probe array in the brain area to be stimulated or the whole brain, and divide the brain area; Step 2: Collect near-infrared blood oxygen signals: The near-infrared brain functional imaging probe array collects near-infrared blood oxygen signals for 60 to 600 seconds to obtain the distribution of near-infrared blood oxygen signals in the brain; Step 3: Based on the obtained near-infrared blood oxygen signal, the functional connection calculation is performed with the correlation coefficient of each channel signal as an indicator to obtain the brain area corresponding to each detection node and the brain network state including the connection strength of each brain area, and determine the brain area with abnormal excitability; Step 4: Perform enhanced or inhibited ultrasound stimulation in the abnormally excitable brain area according to the disease type; Step 5: During the ultrasound stimulation process, the changes in near-infrared blood oxygen signals are monitored synchronously to measure the changes in cortical excitability of each node in the brain network; Step 6: At intervals of 20 to 60 seconds, the phased array ultrasonic array composed of multiple ultrasonic array elements changes the pulse timing to shift the focus. The focus shift strategy is determined according to the focal depth and the horizontal diameter D of the focal spot. The phase of each ultrasonic array element is controlled to move from the current focal spot center to a distance D, and then move clockwise along a hexagon with the current focal spot center as the center and a side length of D, for a total of six positions; Step 7: Measure the changes in the brain network, extract the near-infrared blood oxygen signal data at the target node, perform weighted smoothing on the data points with a time window of 20 to 200 milliseconds, and then take the derivative to obtain the maximum rate of change, which is used as the decision indicator; or use the change in the correlation coefficient of two groups of near-infrared blood oxygen signals in a specific functional area, that is, the maximum change rate of the connection strength as the decision indicator, and determine the focus position with the largest change in cortical excitability in step 5, which is the focal spot center for the next focus shift; Step 8: Repeat step 6. If the change of the near-infrared blood oxygen signal at the six surrounding positions is less than the set threshold, and the change of the functional connection strength is also less than the set threshold, it is judged that the correct target area is stimulated, otherwise proceed to the next step; Step 9: Go back to step 5 and iterate.

2. The dynamic closed-loop neural control method integrating ultrasound array elements and fNIRS probes according to claim 1, characterized in that: When dividing the brain regions in step 1, in the presence of a positioning device, MRI structural imaging is first scanned, and the functional regions of the individual brain are divided using software with functional partitioning; In the absence of positioning equipment, a near-infrared brain function imaging probe cap with an electrode cap with the same coordinates as the EEG 10-20 is used for positioning, and the corresponding area of ​​the small-area probe array is left vacant to place other near-infrared brain function imaging probes.

3. The dynamic closed-loop neural control method integrating ultrasound array elements and fNIRS probes according to claim 1, characterized in that: The specific process of step 3 is as follows: Step 3.1: Retrieve data from all near-infrared brain functional imaging probes in real time; Step 3.2: Correlation calculation: Calculate the Pearson correlation coefficient or Spearman correlation coefficient of the data of each two near-infrared brain functional imaging probes; Step 3.3: According to the calculated correlation coefficient, set a threshold, select the correlation coefficient greater than the threshold, or select the 20%~30% with the largest correlation coefficient as the valid functional connection point pairs; Step 3.4: Map the spatial positions of each effective connection point to the standard brain space to form a brain network; Step 3.5: Compare the normal excitability of the brain region with that established in the standard brain space, or compare with the excitability intensity distribution of the brain network established in step 3.4 to identify abnormal brain regions.

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