Intraoperative Cortical Function Visualization Fluorescent Labeling Methods, Devices and Systems

Abstract

This application relates to a method, device, and system for intraoperative cortical functional visualization and fluorescent labeling. The method, executed by a processor, includes: receiving electrophysiological response data from a multi-channel flexible electrode array; determining at least one target channel based on the electrophysiological response data; generating an electrical stimulation trigger signal corresponding to the target channel in response to a user-input target channel selection command, the electrical stimulation trigger signal being used to trigger the release of fluorescent dye loaded on the surface of the target channel; outputting the electrical stimulation trigger signal to the target channel and sending a fluorescence imaging trigger signal to an external fluorescence imaging device. This application achieves precise labeling of cortical functional response areas by immobilizing and electrically stimulating fluorescent dye on the surface of electrode contacts. Combined with intraoperative fluorescence imaging, it can provide high spatial accuracy visualization results of functional areas without additional instrument placement, improving the intuitiveness and accuracy of intraoperative localization.

Description

Technical Field

[0001] This application relates to the field of intraoperative neurosurgical auxiliary technology, and in particular to an intraoperative cortical function visualization fluorescent labeling method, device and system, flexible electrode, computing device and storage medium. Background Technology

[0002] In neurosurgery, accurate localization and spatial labeling of specific functional areas of the cerebral cortex are crucial for ensuring surgical safety and precision. Current intraoperative aids mainly include preoperative image navigation, electrophysiological localization, and fluorescence visualization, but these techniques still have significant limitations in providing real-time, intuitive, and stable labeling of functional areas.

[0003] 1. Technical limitations of preoperative functional imaging and neuronavigation techniques

[0004] By using preoperative fMRI, DTI, task-state / resting-state functional connectivity and other technologies to image specific brain regions, and integrating them with neuronavigation technology, surgical planning can be achieved through the fusion navigation system for guidance and localization.

[0005] This approach relies solely on preoperative images of the patient and cannot address the issue of brain tissue drift caused by factors such as cerebrospinal fluid release, tumor resection, and changes in posture during surgery. This leads to deviations between the intraoperative navigation position and the actual anatomical structure, reducing positioning accuracy. Furthermore, the navigation system only provides on-screen guidance and cannot generate physical markers or fluorescent indicators within the surgical field, lacking intuitive visual feedback.

[0006] 2. Limitations of intraoperative electrical stimulation and electrophysiological monitoring

[0007] Intraoperative motor evoked potentials (MEP), somatosensory evoked potentials (SEP), brainstem evoked potentials (BAEP), and direct cortical / subcortical electrical stimulation have become standard techniques in neurosurgery and standard means of locating functional areas in neurosurgery.

[0008] While the methods described above can identify functional areas, their output is typically in the form of stimulation results, potential waveforms, or numerical values ​​from monitoring instruments, failing to directly and visually mark the localization results on the brain surface. After functional area localization, surgeons often have to rely on memory, re-stimulation, or temporary marking with cotton pads. Such markings are easily covered or displaced due to bleeding, brain tissue movement, or obstruction by surgical instruments; they are difficult to maintain long-term effectiveness; and they are difficult to form a continuous and stable spatial representation.

[0009] 3. Limitations of intraoperative fluorescence imaging

[0010] Fluorescent agents such as 5-ALA and sodium fluorescein have been used for tumor boundary visualization; indocyanine green (ICG) is used to assess vascular blood flow.

[0011] However, existing fluorescence imaging technology is mainly aimed at tumor tissue or vascular structures, and cannot be used for selective labeling of functional areas, nor has it been integrated with electrical stimulation functional localization technology into a workflow.

[0012] 4. Although flexible electrodes and drug loading technologies exist, they have not been used for functional area visualization.

[0013] ECoG electrodes and microelectrode arrays can achieve multi-channel electrical stimulation and recording; studies on local sustained-release patches show that drugs can be loaded onto the implant surface and released locally.

[0014] However, these technologies have not yet been integrated with functional area localization, and the integrated mechanism of "electrical stimulation localization + fluorescence labeling + imaging synchronization" has not been achieved.

[0015] The main drawbacks of existing technologies include:

[0016] 1. It is impossible to directly and stably visualize the location of functional areas on the brain surface.

[0017] Navigation systems and electrophysiological monitoring rely on screen displays or surgeon memory, lacking physical, visual markers. Cotton pad markers are easily obscured or displaced by blood, leading to the "loss" of functional areas.

[0018] 2. Navigation schemes are ill-equipped to handle intraoperative brain tissue drift.

[0019] Preoperative image fusion navigation system can only represent the location of brain tissue before surgery. However, brain tissue drift caused by factors such as cerebrospinal fluid release, changes in body position, and empty cavities after tumor resection can cause deviations in the preoperative images relative to the actual location, making the navigation instructions inaccurate.

[0020] 3. Electrophysiological localization results are difficult to spatially integrate and maintain over a long period.

[0021] Intraoperative electrophysiological monitoring results are often limited to stimulation of a few discrete points. The significance of each point is very clear. However, once the cotton pad is moved, the electrode is moved, or bloodstains cover the brain surface, the original point is difficult to reproduce.

[0022] 4. Existing marking methods rely on manual and temporary physical marking.

[0023] Currently, the location of brain functional areas is mainly marked by tiny cotton pads or the surgeon's memory, but there are problems such as cotton pads obstructing the field of vision, affecting the operation, and memory bias.

[0024] In summary, existing intraoperative assistive technologies have significant gaps in the following aspects: real-time, direct, and visual labeling of functional areas; spatial integration and long-term maintenance of electrical stimulation localization results; dynamic labeling mechanisms capable of addressing brain tissue drift; and functional visualization schemes that can be synchronized with fluorescence imaging equipment. Therefore, there is an urgent need for a technology that can integrate "electrical stimulation identification of functional areas, targeted fluorescence release, and real-time imaging" intraoperatively to provide intuitive, objective, stable, and sustainable visualization results of cortical function. Summary of the Invention

[0025] In view of the problems existing in the background technology, such as the inability to visualize intraoperative functional localization, the inability to maintain it for a long time, the easy loss of markers, and the susceptibility of navigation to brain tissue drift, this application provides an intraoperative cortical functional visualization fluorescent marking method, device and system, flexible electrodes, computing device and storage medium. By loading controllably released fluorescent dye on the surface of electrode contacts, combined with electrophysiological response localization and intraoperative fluorescence imaging, real-time, stable and intuitive optical markers are generated on the surface of the cerebral cortex, providing the surgeon with accurate and repeatable spatial reference of functional areas.

[0026] To achieve the above objectives, the first aspect of this application provides a method for intraoperative cortical functional visualization fluorescent labeling, executed by a processor, comprising the following steps:

[0027] Receive electrophysiological response data from a multi-channel flexible electrode array, the electrophysiological response data corresponding to the bioelectrical signals recorded by each electrode channel under electrical stimulation;

[0028] Based on the electrophysiological response data, at least one target channel is identified;

[0029] In response to a user-inputted target channel selection command, an electrical stimulation trigger signal is generated that corresponds one-to-one with the target channel. The electrical stimulation trigger signal is used to trigger the release of fluorescent dye loaded on the surface of the target channel.

[0030] The electrical stimulation trigger signal is output to the target channel, and the fluorescence imaging trigger signal is sent to an external fluorescence imaging device.

[0031] As one possible implementation of the first aspect, the electrophysiological response data includes at least one of motor evoked potentials, somatosensory evoked potentials, or direct cortical electrical stimulation response signals.

[0032] As one possible implementation of the first aspect, determining at least one target channel includes: identifying electrode channels corresponding to functional regions based on the electrophysiological response data and marking them as target channels.

[0033] As one possible implementation of the first aspect, the fluorescent dye is loaded onto the electrode surface of the target channel by electrostatic adsorption, electrochemical deposition, or interfacial coordination.

[0034] The electrical stimulation trigger signal adopts an electrochemical release-driven waveform.

[0035] As one possible implementation of the first aspect, the electrochemical release driving waveform is a single-phase square wave, a two-phase balanced square wave, an exponentially decaying pulse, a constant potential step, or a constant current step signal.

[0036] As one possible implementation of the first aspect, the fluorescent dye is a near-infrared or visible light fluorescent agent.

[0037] As one possible implementation of the first aspect, sending a fluorescence imaging trigger signal to an external fluorescence imaging device includes:

[0038] Simultaneously send fluorescence imaging trigger signals to external fluorescence imaging equipment to achieve time synchronization between fluorescence release events and intraoperative fluorescence imaging.

[0039] As one possible implementation of the first aspect, the method can be repeated multiple times during the procedure; each time it is executed, electrophysiological response data is received again, and the target channel and the corresponding electrical stimulation trigger signal are updated.

[0040] A second aspect of this application provides an intraoperative cortical function visualization fluorescent labeling device, comprising:

[0041] An electrophysiological response data receiving module is used to receive electrophysiological response data from a multi-channel flexible electrode array, wherein the electrophysiological response data corresponds to the bioelectrical signals recorded by each electrode channel under electrical stimulation.

[0042] A target channel determination module is used to determine at least one target channel based on the electrophysiological response data;

[0043] An electrical stimulation trigger signal generation module is used to generate an electrical stimulation trigger signal corresponding to the target channel in response to a user-input target channel selection command. The electrical stimulation trigger signal is used to trigger the release of fluorescent dye loaded on the surface of the target channel.

[0044] The trigger signal output module is used to output the electrical stimulation trigger signal to the target channel and send the fluorescence imaging trigger signal to an external fluorescence imaging device.

[0045] A third aspect of this application provides a flexible electrode, comprising:

[0046] Flexible substrate;

[0047] A conductive layer encapsulated on a flexible substrate;

[0048] Electrode contacts integrated on a conductive layer, the contacts having both electrical stimulation and recording functions;

[0049] A fluorescent dye region is loaded on the surface of the contact point, and the fluorescent dye loaded region can release fluorescent dye under the stimulation of an electrical stimulation trigger signal.

[0050] As a possible implementation of the third aspect, the fluorescent dye can be fixed to the surface of the electrode contact by electrostatic adsorption, electrochemical deposition or other surface immobilization methods;

[0051] The electrical stimulation trigger signal adopts an electrochemical release-driven waveform.

[0052] As one possible implementation of the third aspect, the electrochemical release driving waveform is a single-phase square wave, a two-phase balanced square wave, an exponentially decaying pulse, a constant potential step, or a constant current step signal.

[0053] As one possible implementation of the third aspect, the fluorescent dye is a near-infrared or visible light fluorescent agent.

[0054] The fourth aspect of this application provides an intraoperative cortical function visualization fluorescent labeling system, comprising:

[0055] A flexible electrode array composed of the flexible electrodes described in the third aspect is attached to the surface of the cerebral cortex for applying electrical stimulation, recording electrophysiological response data and locally releasing fluorescent dyes.

[0056] An electrophysiological monitoring device, connected to the flexible electrode array, is used to collect and process electrophysiological response data from each channel;

[0057] The intraoperative cortical function visualization fluorescent labeling device described in the second aspect is communicatively connected to the electrophysiological monitoring device and is configured to perform the intraoperative cortical function visualization fluorescent labeling method described in the first aspect.

[0058] A fluorescence imaging device is signal-connected to the intraoperative cortical function visualization fluorescence labeling device, used to receive the fluorescence imaging trigger signal and perform real-time fluorescence imaging of the release area.

[0059] The fifth aspect of this application provides a computing device, comprising:

[0060] processor, and

[0061] A memory having stored program instructions that, when executed by the processor, cause the processor to perform any of the methods described in the first aspect above.

[0062] A sixth aspect of this application provides a computer-readable storage medium having program instructions stored thereon, which, when executed by a computer, cause the computer to perform any of the methods described in the first aspect above.

[0063] Compared with existing technologies, the intraoperative cortical function visualization fluorescent labeling method, device and system, and flexible electrode proposed in this application have the following advantages:

[0064] 1. Based on electrophysiological functional localization, achieve direct fluorescent visualization marking of specific brain regions in the surgical field, so that the surgeon can directly "see" the boundaries of functional areas or key connection points under fluorescence imaging equipment;

[0065] 2. Load the fluorescent dye onto the electrode surface and achieve controlled release, avoiding the need for additional dyeing carriers or repeated operations;

[0066] 3. To achieve controlled release of fluorescent dyes at specific electrode points, avoiding staining of non-target areas and ensuring the accuracy and safety of labeling;

[0067] 4. Achieve compatibility and integration with existing equipment without significantly altering the original intraoperative electrophysiological workflow, ensuring scalability. Attached Figure Description

[0068] Figure 1 This is a schematic diagram of the structure of a flexible electrode provided in an embodiment of this application;

[0069] Figure 2 This is a flowchart of a method for intraoperative cortical function visualization fluorescent labeling provided in an embodiment of this application;

[0070] Figure 3 This is an example of a fluorescent labeling effect provided in an embodiment of this application (left: no labeling in white light mode; right: region of interest displayed in fluorescent mode).

[0071] Figure 4 A schematic diagram of the structure of an intraoperative cortical function visualization fluorescent labeling device provided in this application embodiment;

[0072] Figure 5 A schematic diagram of the structure of an intraoperative cortical function visualization fluorescent labeling system provided in this application embodiment;

[0073] Figure 6 This is a schematic structural diagram of a computing device provided in an embodiment of this application.

[0074] It should be understood that the dimensions and shapes of the block diagrams in the above structural diagrams are for reference only and should not constitute an exclusive interpretation of the embodiments of this application. The relative positions and inclusion relationships between the block diagrams presented in the structural diagrams are only schematic representations of the structural relationships between the block diagrams, and are not intended to limit the physical connection methods of the embodiments of this application. Detailed Implementation

[0075] The technical solutions provided in this application will be further described below with reference to the accompanying drawings and embodiments. It should be understood that the system architecture and business scenarios provided in the embodiments of this application are mainly for illustrating possible implementations of the technical solutions of this application and should not be construed as the sole limitation on the technical solutions of this application. Those skilled in the art will recognize that the technical solutions provided in this application are equally applicable to similar technical problems as system architectures evolve and new business scenarios emerge.

[0076] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. In case of any inconsistency, the meaning set forth in this specification or derived from the content described herein shall prevail. Furthermore, the terminology used herein is for the purpose of describing embodiments of this application only and is not intended to limit the scope of this application.

[0077] Examples of flexible electrodes

[0078] In view of the limitations of existing technologies, whether navigation systems or cortical electrical stimulation, the results are only represented as electrical signals or coordinate information on the screen. These can only be temporarily marked by the surgeon based on memory or with cotton pads on the brain surface, and do not have the intuitive and stable visual effect of fluorescence imaging. This application proposes to load fluorescent dyes onto the surface of flexible electrodes through electrostatic modification, integrating electrical stimulation / recording functions and controllable release capabilities on the same electrode. This breaks through the limitation of existing electrodes being used only for signal acquisition, and realizes direct and visible fluorescent marking of specific brain regions in the surgical field.

[0079] Based on this, this application proposes as follows: Figure 1 The flexible electrode shown includes:

[0080] Flexible substrate;

[0081] A conductive layer encapsulated on a flexible substrate;

[0082] Electrode contacts integrated on a conductive layer, the contacts having both electrical stimulation and recording functions;

[0083] A fluorescent dye region is loaded on the surface of the contact point, and the fluorescent dye loaded region can release fluorescent dye under the stimulation of an electrical stimulation trigger signal.

[0084] The specific substrate and electrode types are determined according to actual needs.

[0085] In some embodiments, the flexible substrate may be selected from polyimide (PI), polydimethylsiloxane (PDMS), Parylene-C, or other biocompatible and flexible polymer materials, and a gold (Au), platinum (Pt), platinum-iridium alloy, or PEDOT conductive layer may be formed on its surface. The electrode contacts may be processed into circular, square, or micro-cylindrical structures with dimensions of 10–200 μm to balance spatial resolution and electrical stimulation and recording performance.

[0086] The fluorescent dye loading region is disposed on the electrode contact surface, and the fluorescent dye can be immobilized on the electrode surface through electrostatic adsorption, electrochemical deposition, or interfacial coordination. To obtain a stable dye immobilization effect, the electrode surface can be further modified with charged functional groups (such as... , Alternatively, by utilizing the inherent interfacial charge characteristics of the metal conductive layer, a controllable and reducible adsorption layer can be formed on the electrode surface by a charged small molecule fluorescent probe.

[0087] The electrostimulation trigger signal adopts an electrochemical release-driven waveform, which may include constant potential, pulse voltage, constant current, or pulse current modes. Its parameters (amplitude, frequency, duty cycle, duration, etc.) are optimized according to the charge characteristics of the fluorescent dye and the desired release rate to achieve quantitative and time-controllable in-situ release. Preferably, the polarity of the driving waveform is opposite to the charge of the fluorescent dye. By instantaneously adjusting the polarity or perturbing the electrode-electrolyte interface double layer, the electrostatic adsorption between the dye and the electrode is weakened or destroyed, thereby achieving rapid and localized in-situ electrochemical desorption.

[0088] The way to stimulate the release of fluorescent dyes is to apply potential pulses to regulate the double layer structure at the electrode / solution interface, reverse or shield the surface charge, thereby disrupting the electrostatic interaction between the fluorescent dye and the electrode, and achieving controllable desorption and release.

[0089] Specifically, when a voltage / current pulse of a specific polarity is applied to the electrode:

[0090] If the fluorescent dye is a cation, applying a positive potential → the electrode surface becomes positively charged → electrostatic repulsion → the fluorescent dye desorbs and is released;

[0091] If the fluorescent dye is an anion, applying a negative potential → the electrode surface becomes negatively charged → electrostatic repulsion → the fluorescent dye is released.

[0092] In some embodiments, the driving waveform may be a single-phase square wave, a two-phase balanced square wave, an exponentially decaying pulse, a constant potential step, or a constant current step signal. The electrochemical release driving waveform is preferably a single-phase or two-phase current pulse with a preset pulse width and amplitude, which creates an instantaneous electrochemical environment opposite in charge to the fluorescent dye through polarity changes, thereby triggering a locally controlled release based on an electrostatic repulsion mechanism. Typical parameters of the driving waveform range are: pulse width 0.1–5 ms, amplitude 0.1–5 mA, and frequency not exceeding 50 Hz. Specific values ​​can be adjusted according to the charge characteristics, adsorption strength, and desired release rate of the fluorescent dye.

[0093] Specifically, by applying a pulse polarity opposite to that of the fluorescent dye, a transient electrostatic repulsion field can be formed on the electrode surface, thereby triggering dye desorption. For example, when the fluorescent dye is a negative molecule (such as sodium fluorescein), a negative current pulse (such as -2 mA, 1 ms) can be applied to make the electrode surface negatively charged and achieve desorption through electrostatic repulsion; if the fluorescent dye is a positive molecule (such as methylene blue), a positive pulse can be applied. The above driving waveform can be generated by an external constant current stimulator or a digital-to-analog converter control circuit integrated into the device to ensure the localization, controllability, and tissue safety of the release process.

[0094] In some embodiments, the fluorescent dye is a near-infrared or visible light fluorescent agent. This includes, but is not limited to, fluorescein, rhodamine, methylene blue dyes, or near-infrared fluorescent agents such as ICG, IR-Dye800CW, Cy7, and their derivatives. The fluorescent probe may also be a small molecule probe with specific functional groups, an aggregation-induced emission (AIE) dye, or in the form of nanoparticles or polymer probes to obtain higher photostability, signal intensity, and tissue penetration.

[0095] Since the release results need to be observed by external fluorescence imaging equipment (such as microscopes or intraoperative imaging systems), it is preferable to use small molecule probes with strong fluorescence signals in the visible or near-infrared bands to ensure good microscopic imaging results.

[0096] The flexible electrode structure proposed in this application integrates fluorescent labeling and electrical stimulation positioning functions into the same electrode contact, enabling the same device to simultaneously possess the capabilities of stimulation, recording, and dye release. This avoids the need for additional dye carrier placement or repeated staining operations, thereby significantly simplifying the operation steps and improving positioning accuracy and spatial consistency.

[0097] Examples of intraoperative cortical function visualization fluorescent labeling methods

[0098] The method described in this application belongs to the field of intraoperative visualization technology in neurosurgery. It does not involve the determination or intervention of any pathological state, and its output is only physical spatial markings.

[0099] This application provides a method for intraoperative visual fluorescent labeling of cortical function. By loading controllably released fluorescent dyes onto electrode surfaces, combined with electrical stimulation of functional areas and intraoperative fluorescence imaging, a complete technical chain of "intraoperative functional area identification - precise labeling" is constructed. For example... Figure 2 As shown, this method is executed by a processor and includes:

[0100] S210: Receive electrophysiological response data from a multi-channel flexible electrode array, the electrophysiological response data corresponding to the bioelectrical signals recorded by each electrode channel under electrical stimulation.

[0101] In some embodiments, the flexible electrodes in the multi-channel flexible electrode array mentioned herein are the aforementioned flexible electrodes, and the multi-channel flexible electrode array is composed of them.

[0102] Specifically, the multi-channel flexible electrode array may contain no fewer than eight independently addressable electrode contacts, with typical channel numbers of 16, 32, 64, or 128. The array geometry may include a matrix (e.g., 4×4, 8×8), linear (1×N), or fan-shaped configurations, with a center-to-center spacing of 2–10 mm between adjacent contacts. Each channel is connected via an independent wire to an electrophysiological monitoring device and the intraoperative cortical function visualization fluorescent labeling device described below, supporting channel-by-channel stimulation, recording, and dye release control.

[0103] Before executing S210, the following two steps are required:

[0104] I. Surgical field preparation and electrode placement

[0105] Under a microscope, brain tissue surrounding a tumor / suspected functional area is exposed, and a multi-channel flexible electrode array is attached to the target area (such as the surface of the cerebral cortex), so that the electrodes cover the target functional area and its surrounding cortex.

[0106] II. Location of Electrical Stimulation Functional Areas

[0107] Then, using a standard electrophysiological protocol, signals were recorded / channel-by-channel stimulation was performed on the multi-channel flexible electrodes. Different electrophysiological modes were selected as needed: sensory area – peripheral stimulation to record cortical sensory evoked potentials; central sulcus – stimulation of the median nerve to observe phase inversion of cortical evoked potentials; motor area – cortical stimulation to monitor peripheral motor evoked potentials. Therefore, in some embodiments, the electrophysiological response data includes at least one of motor evoked potentials, somatosensory evoked potentials, or direct cortical electrical stimulation response signals.

[0108] Then, the electrophysiological monitoring device connected to the flexible electrode array collects the electrophysiological response data of the multi-channel flexible electrode array and inputs the electrophysiological response data of the multi-channel flexible electrode array into the processor, which then executes S210.

[0109] S220: Based on the electrophysiological response data, determine at least one target channel.

[0110] In some embodiments, determining at least one target channel includes: identifying electrode channels corresponding to functional regions based on the electrophysiological response data, and marking them as target channels.

[0111] Specifically, electrode channels corresponding to functional areas are identified based on multi-channel electrophysiological response data, and these electrode channels are marked as target channels. The determination of functional areas can be confirmed based on peripheral electromyographic activity, cortical evoked potential recordings, or behavioral responses of the patient in a conscious state.

[0112] Specifically, determining at least one target channel may include any of the following methods:

[0113] When the electrophysiological response data is motor evoked potential, if a compound muscle action potential (CMAP) with a peak value of not less than 50 μV is detected in the peripheral electromyography recording electrode after stimulation of a certain electrode channel, then the electrode channel is marked as the target channel.

[0114] When the electrophysiological response data is somatosensory evoked potential, if a certain channel records an N20 / P25 phase inverted waveform, then that electrode channel is marked as the target channel.

[0115] In awake surgery, if stimulation of a certain channel elicits a repeatable behavioral response (such as finger twitching or interruption of naming), then that electrode channel is marked as the target channel.

[0116] The aforementioned thresholds or criteria can be adjusted by the surgeon based on the intraoperative baseline electrophysiological level. The processor can automatically highlight candidate target channels based on the judgment results and provide them to the user for final confirmation, thereby improving the visualization of the judgment and operational efficiency.

[0117] S230: In response to a user-inputted target channel selection command, generate an electrical stimulation trigger signal corresponding to each target channel, wherein the electrical stimulation trigger signal is used to trigger the release of fluorescent dye loaded on the surface of the target channel.

[0118] In this process, after receiving the electrophysiological signal and identifying the target channel, the target channel to be fluorescently stained is selected through manual determination or user input.

[0119] Once the target channel is determined, the position information of each electrode is directly obtained because the position of each electrode is fixed. The transmission time of the electrical stimulation trigger signal can be set, allowing it to be sent at a specific time and location.

[0120] In this application, the multi-channel flexible electrode array used is the aforementioned flexible electrode. Therefore, in some embodiments, the flexible substrate can be selected from polyimide (PI), polydimethylsiloxane (PDMS), Parylene-C, or other polymer materials with good biocompatibility and flexibility, and a conductive layer such as gold (Au), platinum (Pt), platinum-iridium alloy, or PEDOT is formed on its surface. The aforementioned conductive materials can form a stable electric double layer structure at the electrode-electrolyte interface and have good surface modifiability. This can be achieved by constructing charged functional groups (such as...) on its surface. , By adjusting the resting interface potential (e.g., etc.), controllable adsorption sites can be provided for charged fluorescent molecules, thereby achieving stable immobilization.

[0121] The electrode contacts can be fabricated as microstructures such as circles, squares, or microcolumns, with typical sizes of 10–200 μm, to balance high spatial resolution with electrical stimulation and electrical signal recording performance. Fluorescent dyes can be loaded onto the electrode surface corresponding to the target channel through electrostatic adsorption, electrochemical deposition, or interfacial coordination.

[0122] The electrostimulation trigger signal adopts an electrochemical release-driven waveform. This waveform can be in constant potential, pulsed voltage, constant current, or pulsed current mode. Its parameters (amplitude, frequency, duty cycle, duration, etc.) are optimized based on the charge characteristics of the fluorescent dye and the desired release rate to achieve quantitative and time-controlled in-situ release. Typical parameters range from 0.1–5 ms for pulse width, 0.1–5 mA for amplitude, and no higher than 50 Hz for frequency. Preferably, the polarity of the driving waveform is opposite to the charge of the fluorescent dye, thereby triggering local desorption by instantaneously modulating the electrode-electrolyte interface double-layer structure to disrupt the electrostatic adsorption force between the dye and the electrode.

[0123] The waveforms described above can be generated by an external constant current stimulator or by a digital-to-analog converter integrated into the system to ensure the locality, controllability, and tissue safety of the release process.

[0124] In some embodiments, the fluorescent dye may be selected from small molecule probes in the visible or near-infrared bands, including fluorescein, rhodamine, methylene blue dyes, and near-infrared fluorescent probes such as ICG, IR Dye800CW, and Cy7. It may also be aggregation-induced emission (AIE) dyes or their nanoparticle or polymer probe forms to obtain higher photostability, signal intensity, and intraoperative visualization performance.

[0125] In practice, the operator inputs instructions to determine one or more target areas for fluorescent staining, then obtains the electrode position information corresponding to the target area, and generates the corresponding electrochemical release driving waveform. This electrochemical release driving waveform can be sent to the target channel (i.e., sent to the corresponding electrode position) at a preset time, or it can be sent to the target channel immediately after generation. This allows for the controllable release of fluorescent dye at a specific electrode point / at a specific time, avoiding staining of non-target areas and ensuring the accuracy and safety of the labeling.

[0126] S240: Output the electrical stimulation trigger signal to the target channel and send the fluorescence imaging trigger signal to the external fluorescence imaging device.

[0127] In some embodiments, sending a fluorescence imaging trigger signal to an external fluorescence imaging device includes:

[0128] Simultaneously send fluorescence imaging trigger signals to external fluorescence imaging equipment to achieve time synchronization between fluorescence release events and intraoperative fluorescence imaging, enabling external imaging devices to observe the spatial distribution of fluorescence release in real time.

[0129] The synchronous transmission of the fluorescence imaging trigger signal refers to: while outputting an electrical stimulation trigger signal to the target channel (with a time deviation of ≤10 ms), sending a frame trigger signal to the fluorescence imaging device via a TTL level signal or a USB communication command, so that the fluorescence imaging device can capture a fluorescence image for imaging within the first imaging cycle after dye release, thus avoiding motion artifact interference.

[0130] In practice, after exposing the target cortical region during surgery, a multi-channel flexible electrode array is attached to that region. Electrophysiological response data (such as motor evoked potentials, somatosensory evoked potentials, or direct cortical stimulation responses) is collected by electrically stimulating each channel to identify electrode channels associated with specific neural functions, and these channels are marked as target channels. Subsequently, an electrochemical release-driven waveform is applied to the target channels, triggering the release of local fluorescent dyes. The released dyes adhere to the corresponding cortical locations, appearing as bright areas under fluorescence imaging equipment, such as... Figure 3 The image shown illustrates the effect of fluorescent labeling. In the left image, the white light mode shows no labeling, while the right image shows the region of interest in fluorescent mode. Operators can switch between white light and fluorescent modes to directly observe the label's location within the anatomical field of view, serving as a spatial reference for subsequent procedures. Even with electrode displacement or visual field obstruction, fluorescent labeling provides continuous visual cues, reducing reliance on repetitive electrical stimulation or temporary manual labeling.

[0131] In some embodiments, the method can be repeated multiple times during the procedure; each time it is executed, electrophysiological response data is received again, and the target channel and the corresponding electrical stimulation trigger signal are updated.

[0132] The method can be operated in in vitro experiments, animal models, or clinical environments, and its technical essence is electro-chemical signal coordinated control logic.

[0133] Example of an intraoperative cortical function visualization fluorescent labeling device

[0134] like Figure 4 As shown, this application provides an intraoperative cortical function visualization fluorescent labeling device, which can be used to implement the intraoperative cortical function visualization fluorescent labeling method in the above embodiments, such as... Figure 4 As shown, the intraoperative cortical function visualization fluorescent labeling device has an electrophysiological response data receiving module 310, a target channel determination module 320, an electrical stimulation trigger signal generation module 330, and a trigger signal output module 340.

[0135] Among them, the electrophysiological response data receiving module 310 is used to receive electrophysiological response data from the multi-channel flexible electrode array, wherein the electrophysiological response data corresponds to the bioelectrical signals recorded by each electrode channel under electrical stimulation.

[0136] The target channel determination module 320 is used to determine at least one target channel based on the electrophysiological response data;

[0137] The electrical stimulation trigger signal generation module 330 is used to generate an electrical stimulation trigger signal corresponding to the target channel in response to the target channel selection command input by the user. The electrical stimulation trigger signal is used to trigger the release of fluorescent dye loaded on the surface of the target channel.

[0138] The trigger signal output module 340 is used to output the electrical stimulation trigger signal to the target channel and send the fluorescence imaging trigger signal to an external fluorescence imaging device.

[0139] For details, please refer to the detailed description in the method embodiments, which will not be repeated here.

[0140] Example of an intraoperative cortical function visualization fluorescent labeling system

[0141] The fourth aspect of this application provides an intraoperative cortical function visualization fluorescent labeling system, such as... Figure 5 As shown, it includes:

[0142] The flexible electrode array composed of the aforementioned flexible electrodes is attached to the surface of the cerebral cortex to apply electrical stimulation, record electrophysiological response data, and locally release fluorescent dyes.

[0143] An electrophysiological monitoring device, connected to the flexible electrode array, is used to collect and process electrophysiological response data from each channel;

[0144] The intraoperative cortical function visualization fluorescent labeling device proposed above is communicatively connected to the electrophysiological monitoring device and is configured to perform the intraoperative cortical function visualization fluorescent labeling method proposed above.

[0145] A fluorescence imaging device is signal-connected to the intraoperative cortical function visualization fluorescence labeling device, used to receive the fluorescence imaging trigger signal and perform real-time fluorescence imaging of the release area.

[0146] In summary, the intraoperative cortical functional visualization fluorescent labeling method, device, system, and flexible electrode proposed in this application can achieve the following beneficial effects:

[0147] 1. For the first time, fluorescent dyes are combined with flexible electrodes to achieve direct visualization of specific brain regions through controlled release.

[0148] In existing technologies, electrodes are only used for stimulating / recording signals and do not have dye release capabilities. This application loads fluorescent dyes onto the surface of flexible electrodes through electrostatic modification, integrating electrostimulation / recording functions and controllable release capabilities on the same electrode, achieving direct, visible fluorescent labeling of specific brain regions in the surgical field. This is the first time that "electrophysiological localization + fluorescent visualization labeling" has been integrated.

[0149] 2. The fusion of electrical stimulation localization and fluorescence imaging enables real-time and precise navigation of functional areas during surgery.

[0150] In existing technologies, functional channels only correspond to electrophysiological signals. This application, by triggering dye release through the target electrode channel, establishes a one-to-one correspondence between "electrical signals and fluorescent regions," allowing the location of functional areas to be directly reflected on the brain surface fluorescence image. This method is based on intraoperative real-time electrical stimulation localization, avoiding the localization errors caused by relying solely on preoperative image fusion navigation systems, and effectively overcoming the problem of inaccurate localization caused by brain tissue drift in preoperative image navigation.

[0151] 3. Establish a complete intraoperative workflow of "electrical stimulation localization - controlled release - fluorescence imaging".

[0152] In existing technologies, electrical stimulation and fluorescence imaging are not directly related. This application links electrical stimulation localization, channel selection, controlled dye release, fluorescence imaging, and surgical guidance into a complete, repeatable process, avoiding the disconnect between electrical stimulation and fluorescence imaging, and achieving precise, function-driven labeling.

[0153] 4. Compared to traditional intraoperative fluorescence imaging, it achieves "function-driven" fluorescent labeling, rather than structural or tumor staining.

[0154] Existing fluorescence methods are mostly targeted at tumor cells, blood vessels, etc., and are not coupled with electrophysiological localization; however, this application first determines the functional region through electrophysiology, and then realizes the controlled release of dye, achieving a "function-dependent" precise labeling, which is more targeted in terms of technology.

[0155] 5. Significantly reduces reliance on surgeon's memory / manual marking.

[0156] Fluorescent markers adhere persistently to the brain surface, unaffected by bleeding, rinsing, or cotton pad displacement. This application transforms abstract electrophysiological responses into intuitive spatial markers. Visualized markers ensure that functional areas remain present throughout the entire surgical process, significantly reducing the number of repetitive stimulations and improving surgical stability and safety.

[0157] 6. Compatible with existing equipment, possessing good scalability and expandability.

[0158] This application belongs to the interdisciplinary field of intraoperative multichannel signal processing, artificial intelligence-assisted analysis, and medical information visualization technology in neurosurgery. It does not require significant changes to the traditional intraoperative electrophysiological workflow. By simply modifying the electrode structure and adding a release control component, it can be integrated with existing electrophysiological systems and medical terminals such as fluorescence surgical microscopes to form an innovative technical solution for clinical needs. It supports the selection of different fluorescent dyes or electrode morphologies as needed and is suitable for neurosurgical scenarios involving cortical functional areas, with broad clinical translational potential.

[0159] It should be specifically noted that the method described in this application belongs to intraoperative visualization technology in neurosurgery and does not involve the determination of any pathological state, disease diagnosis, or treatment intervention. Its output is only physical spatial markings used to provide anatomical-functional location references; all clinical decisions are still made by the surgeon based on comprehensive information.

[0160] Examples of computing devices in this application

[0161] Figure 6 This is a schematic structural diagram of a computing device 900 provided in an embodiment of this application. This computing device can serve as an intraoperative cortical function visualization fluorescent labeling device, executing various optional embodiments of the above-described intraoperative cortical function visualization fluorescent labeling method. The computing device can be a terminal, or a chip or chip system within the terminal. Figure 6 As shown, the computing device 900 includes: a processor 910, a memory 920, and a communication interface 930.

[0162] It should be understood that Figure 6 The communication interface 930 in the computing device 900 shown can be used to communicate with other devices, and may specifically include one or more transceiver circuits or interface circuits.

[0163] The processor 910 can be connected to the memory 920. The memory 920 can be used to store the program code and data. Therefore, the memory 920 can be a storage unit inside the processor 910, an external storage unit independent of the processor 910, or a component that includes both the storage unit inside the processor 910 and the external storage unit independent of the processor 910.

[0164] Optionally, the computing device 900 may also include a bus. The memory 920 and communication interface 930 can be connected to the processor 910 via the bus. The bus can be a Peripheral Component Interconnect (PCI) bus or an Extended Industry Standard Architecture (EISA) bus, etc. The bus can be divided into an address bus, a data bus, a control bus, etc. For ease of representation, Figure 6 The symbol is represented by a line without an arrow, but this does not mean that there is only one bus or one type of bus.

[0165] It should be understood that in the embodiments of this application, the processor 910 may be a central processing unit (CPU). The processor may also be other general-purpose processors, digital signal processors (DSPs), application-specific integrated circuits (ASICs), field-programmable gate arrays (FPGAs), or other programmable logic devices, discrete gate or transistor logic devices, discrete hardware components, etc. The general-purpose processor may be a microprocessor or any conventional processor. Alternatively, the processor 910 may employ one or more integrated circuits to execute relevant programs to implement the technical solutions provided in the embodiments of this application.

[0166] The memory 920 may include read-only memory and random access memory, and provides instructions and data to the processor 910. A portion of the processor 910 may also include non-volatile random access memory. For example, the processor 910 may also store device type information.

[0167] When the computing device 900 is running, the processor 910 executes computer execution instructions stored in the memory 920 to perform any of the operational steps of the above method and any of the optional embodiments thereof.

[0168] It should be understood that the computing device 900 according to the embodiments of this application can correspond to the corresponding subject in executing the methods according to the various embodiments of this application, and the above and other operations and / or functions of each module in the computing device 900 are respectively for implementing the corresponding processes of the methods of this embodiment. For the sake of brevity, they will not be described in detail here.

[0169] Those skilled in the art will recognize that the units and algorithm steps of the various examples described in conjunction with the embodiments disclosed herein can be implemented in electronic hardware, or a combination of computer software and electronic hardware. Whether these functions are implemented in hardware or software depends on the specific application and design constraints of the technical solution. Those skilled in the art can use different methods to implement the described functions for each specific application, but such implementation should not be considered beyond the scope of this application.

[0170] Those skilled in the art will understand that, for the sake of convenience and brevity, the specific working processes of the systems, devices, and units described above can be referred to the corresponding processes in the foregoing method embodiments, and will not be repeated here.

[0171] In the several embodiments provided in this application, it should be understood that the disclosed systems, apparatuses, and methods can be implemented in other ways. For example, the apparatus embodiments described above are merely illustrative; for instance, the division of units is only a logical functional division, and in actual implementation, there may be other division methods. For example, multiple units or components may be combined or integrated into another system, or some features may be ignored or not executed. Furthermore, the coupling or direct coupling or communication connection shown or discussed may be through some interfaces; the indirect coupling or communication connection between apparatuses or units may be electrical, mechanical, or other forms.

[0172] The units described as separate components may or may not be physically separate. The components shown as units may or may not be physical units; that is, they may be located in one place or distributed across multiple network units. Some or all of the units can be selected to achieve the purpose of this embodiment according to actual needs.

[0173] In addition, the functional units in the various embodiments of this application can be integrated into one processing unit, or each unit can exist physically separately, or two or more units can be integrated into one unit.

[0174] If the aforementioned functions are implemented as software functional units and sold or used as independent products, they can be stored in a computer-readable storage medium. Based on this understanding, the technical solution of this application, in essence, or the part that contributes to the prior art, or a portion of the technical solution, can be embodied in the form of a software product. This computer software product is stored in a storage medium and includes several instructions to cause a computer device (which may be a personal computer, server, or network device, etc.) to execute all or part of the steps of the methods described in the various embodiments of this application. The aforementioned storage medium includes various media capable of storing program code, such as USB flash drives, portable hard drives, read-only memory (ROM), random access memory (RAM), magnetic disks, or optical disks.

[0175] This application also provides a computer-readable storage medium storing a computer program thereon, which, when executed by a processor, is used to perform the above-described method, which includes at least one of the schemes described in the above embodiments.

[0176] The computer storage medium in this application embodiment can be any combination of one or more computer-readable media. A computer-readable medium can be a computer-readable signal medium or a computer-readable storage medium. For example, a computer-readable storage medium can be, but is not limited to, an electrical, magnetic, optical, electromagnetic, infrared, or semiconductor system, apparatus, or device, or any combination thereof. More specific examples of computer-readable storage media (a non-exhaustive list) include: an electrical connection having one or more wires, a portable computer disk, a hard disk, random access memory (RAM), read-only memory (ROM), erasable programmable read-only memory (EPROM or flash memory), optical fiber, portable compact disk read-only memory (CD-ROM), optical storage device, magnetic storage device, or any suitable combination thereof. In this document, a computer-readable storage medium can be any tangible medium containing or storing a program that can be used by or in conjunction with an instruction execution system, apparatus, or device.

[0177] Computer-readable signal media may include data signals propagated in baseband or as part of a carrier wave, carrying computer-readable program code. Such propagated data signals may take various forms, including but not limited to electromagnetic signals, optical signals, or any suitable combination thereof. Computer-readable signal media may also be any computer-readable medium other than computer-readable storage media, capable of sending, propagating, or transmitting programs for use by or in connection with an instruction execution system, apparatus, or device.

[0178] The program code contained on a computer-readable medium may be transmitted using any suitable medium, including, but not limited to, wireless, wire, optical fiber, RF, etc., or any suitable combination thereof.

[0179] Computer program code for performing the operations of this application can be written in one or more programming languages ​​or a combination thereof, including object-oriented programming languages ​​such as Java, Smalltalk, and C++, and conventional procedural programming languages ​​such as "C" or similar programming languages. The program code can be executed entirely on the user's computer, partially on the user's computer, as a standalone software package, partially on the user's computer and partially on a remote computer, or entirely on a remote computer or server. In cases involving remote computers, the remote computer can be connected to the user's computer via any type of network, including a local area network (LAN) or a wide area network (WAN), or it can be connected to an external computer (e.g., via the Internet using an Internet service provider).

[0180] Furthermore, the terms "first, second, third, etc." or similar terms such as module A, module B, and module C used in the specification and claims are only used to distinguish similar objects and do not represent a specific ordering of objects. It is understood that, where permissible, a specific order or sequence may be interchanged so that the embodiments of this application described herein can be implemented in an order other than that illustrated or described herein.

[0181] In the above description, the labels of the steps involved, such as S110, S120, etc., do not mean that the steps will necessarily be executed. The order of the steps can be interchanged or executed simultaneously if permitted.

[0182] The term "comprising" as used in the specification and claims should not be construed as limiting itself to what follows; it does not exclude other elements or steps. Therefore, it should be interpreted as specifying the presence of the mentioned feature, integral, step, or component, but does not exclude the presence or addition of one or more other features, integrals, steps, or components, or groups thereof. Thus, the statement "device comprising means A and B" should not be limited to a device consisting solely of components A and B.

[0183] The terms "an embodiment" or "an embodiment" as used in this specification mean that a particular feature, structure, or characteristic described in conjunction with that embodiment is included in at least one embodiment of this application. Therefore, the terms "in one embodiment" or "in an embodiment" appearing throughout this specification do not necessarily refer to the same embodiment, but may refer to the same embodiment. Furthermore, in one or more embodiments, the particular features, structures, or characteristics can be combined in any suitable manner, as will be apparent to those skilled in the art from this disclosure.

[0184] Note that the above are merely preferred embodiments and the technical principles employed in this application. Those skilled in the art will understand that this application is not limited to the specific embodiments described herein, and various obvious changes, readjustments, and substitutions can be made without departing from the scope of protection of this application. Therefore, although this application has been described in detail through the above embodiments, this application is not limited to the above embodiments, and may include many other equivalent embodiments without departing from the concept of this application, all of which fall within the scope of protection of this application.

Claims

1. A fluorescent labeling device for intraoperative cortical function visualization, characterized in that, include: An electrophysiological response data receiving module is used to receive electrophysiological response data from a multi-channel flexible electrode array, wherein the electrophysiological response data corresponds to the bioelectrical signals recorded by each electrode channel under electrical stimulation. A target channel determination module is used to determine at least one target channel based on the electrophysiological response data; An electrical stimulation trigger signal generation module is used to generate an electrical stimulation trigger signal corresponding to the target channel in response to a user-input target channel selection command. The electrical stimulation trigger signal is used to trigger the release of fluorescent dye loaded on the surface of the target channel. The trigger signal output module is used to output the electrical stimulation trigger signal to the target channel and send the fluorescence imaging trigger signal to an external fluorescence imaging device.

2. The apparatus as claimed in claim 1, characterized in that, The electrophysiological response data includes at least one of motor evoked potentials, somatosensory evoked potentials, or direct cortical electrical stimulation response signals. And / or, The target channel determination module is specifically used to determine at least one target channel in the following manner: identifying electrode channels corresponding to functional areas based on the electrophysiological response data and marking them as target channels; And / or, The fluorescent dye is loaded onto the electrode surface of the target channel via electrostatic adsorption, electrochemical deposition, or interfacial coordination. The electrostimulation trigger signal adopts an electrochemical release driving waveform, which is used to change the interfacial charge state of the electrode surface and destroy the adsorption of fluorescent dye, thereby triggering the release of fluorescent dye.

3. The apparatus as described in claim 2, characterized in that, The electrochemical release driving waveform is a single-phase square wave, a two-phase balanced square wave, an exponentially decaying pulse, a constant potential step, or a constant current step signal. And / or, The fluorescent dye is a near-infrared or visible light fluorescent agent.

4. The apparatus as claimed in claim 1, characterized in that, The trigger signal output module is specifically used to send a fluorescence imaging trigger signal to an external fluorescence imaging device in the following manner: Simultaneously send fluorescence imaging trigger signals to external fluorescence imaging equipment to achieve time synchronization between fluorescence release events and intraoperative fluorescence imaging.

5. The apparatus as claimed in claim 1, characterized in that, The method applied in the device can be repeated multiple times during the procedure; each time it is executed, the electrophysiological response data is received again, and the target channel and the corresponding electrical stimulation trigger signal are updated.

6. A fluorescent labeling system for intraoperative cortical function visualization, characterized in that, include: A flexible electrode array, composed of flexible electrodes, is attached to the surface of the cerebral cortex to apply electrical stimulation, record electrophysiological response data, and locally release fluorescent dyes. An electrophysiological monitoring device, connected to the flexible electrode array, is used to collect and process electrophysiological response data from each channel; The intraoperative cortical function visualization fluorescent labeling device as described in any one of claims 1-5 is communicatively connected to the electrophysiological monitoring device; A fluorescence imaging device is signal-connected to the intraoperative cortical function visualization fluorescence labeling device, used to receive the fluorescence imaging trigger signal and perform real-time fluorescence imaging of the release area; The flexible electrode includes: Flexible substrate; A conductive layer encapsulated on a flexible substrate; Electrode contacts integrated on a conductive layer, the contacts having both electrical stimulation and recording functions; A fluorescent dye region is loaded on the surface of the contact point, and the fluorescent dye loaded region can release fluorescent dye under the stimulation of an electrical stimulation trigger signal.

7. The system as described in claim 6, characterized in that, The fluorescent dye is loaded onto the surface of the electrode contact via electrostatic adsorption, electrochemical deposition, or interfacial coordination. The electrical stimulation trigger signal adopts an electrochemical release-driven waveform.

8. The system as described in claim 7, characterized in that, The electrochemical release driving waveform is a single-phase square wave, a two-phase balanced square wave, an exponentially decaying pulse, a constant potential step, or a constant current step signal. And / or, The fluorescent dye is a near-infrared or visible light fluorescent agent.

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