A brain glioma time sequence electric field treatment system and method

Abstract

This invention discloses a time-sequential electric field therapy system and method for glioma, relating to the fields of tumor electric field therapy and biomedical engineering technology. The system includes an electric field generation module, a CAR-T data input interface, a multimodal sensing electrode array, a central control unit, an image data processing module, a heat dissipation module, and an alarm module. The central control unit establishes a time sequence for immune pretreatment, proliferation protection, and homeostasis maintenance based on the CAR-T cell infusion day (D0), and switches the electric field output to intermittent or low-field-strength output according to changes in peripheral blood lymphocyte count or CAR-T copy number. The system also incorporates intracranial bioimpedance, temperature, EEG signals, metabolic indicators, and an intracranial implant model to regulate, interrupt, or lock the electric field output. This invention improves the time-sequential adaptability and safety control capabilities of electric field therapy and CAR-T therapy.

Description

Technical Field

[0001] This invention relates to the fields of biomedical engineering, tumor electric field therapy, and tumor immunotherapy, specifically to a sequential electric field therapy system and method for glioma. Background Technology

[0002] Gliomas, especially high-grade gliomas, are characterized by their high invasiveness, high recurrence rate, and difficulty in treatment. Tumor electric field therapy can interfere with the tumor cell division process through a mid-frequency alternating electric field, while CAR-T cell therapy can recognize and attack tumor-associated antigens through engineered immune cells. While the two treatments are complementary in their mechanisms, issues remain regarding timing coordination and safety control when used in combination.

[0003] Existing electric field therapy devices typically output electric fields continuously at preset frequencies and strengths, primarily focusing on electric field coverage, patch temperature, or device operational stability. When used in conjunction with CAR-T cell therapy, continuously applying a conventional electric field during the expansion phase after CAR-T cell infusion may affect the state of immune cells during the expansion period. Furthermore, the risks of CAR-T therapy-related fever, neurotoxicity, cerebral edema, and postoperative abnormalities in local electric field strength caused by intracranial metal implants all increase the complexity of control during electric field therapy.

[0004] Therefore, there is an urgent need for a sequential electric field therapy system and method for glioma, which can adjust the electric field output in stages according to the CAR-T infusion time and the state of immune cell expansion, and combine impedance, temperature, EEG, metabolic indicators and implant models for closed-loop safety control, thereby improving the compatibility and safety of electric field therapy combined with cell immunotherapy.

[0005] A search revealed that Chinese patent literature discloses a method for reducing the survival ability of cancer cells by applying an alternating electric field to cancer cells and administering checkpoint inhibitors [Application No.: 201980100236.3, Publication No.: CN114340667A]. This prior art patent discloses a technical solution for reducing the survival ability of cancer cells, especially glioblastoma cells, by applying an alternating electric field to cancer cells at a frequency between 100-500 kHz and administering checkpoint inhibitors. Its specification also describes that TTField can be used for GBM and involves the technical concept of combining alternating electric fields with immunotherapy drugs.

[0006] While the comparative patent achieves the goal of improving the treatment effect of glioma through alternating electric fields combined with immunotherapy, featuring the application of 100-500 kHz alternating electric fields to glioblastoma cells and the enhancement of immunotherapy response by combining checkpoint inhibitors, this invention does not simply combine electric field therapy with immunotherapies. Instead, it establishes immune pretreatment, CAR-T proliferation protection, and homeostasis maintenance phases based on the CAR-T cell infusion day (D0), and automatically switches to intermittent output or low field strength output during the CAR-T cell expansion phase. Furthermore, this invention incorporates multimodal closed-loop control using intracranial bioimpedance, scalp contact temperature, EEG signals, metabolic indicators, and a 3D conductivity model of the intracranial implant. Therefore, this invention possesses advantages in CAR-T treatment timing adaptation, immune cell protection during the expansion phase, and safety interlocking of combined treatments that the comparative patent lacks. Summary of the Invention

[0007] In view of the problems existing in the prior art, the purpose of the present invention is to provide a sequential electric field therapy system and method for glioma.

[0008] A control method for a time-series electric field therapy system for glioma, the system comprising an electric field generation module, a CAR-T data input interface, a multimodal sensing electrode array, and a central control unit, characterized by comprising the following steps: S1. Receive CAR-T infusion time, peripheral blood lymphocyte count or CAR-T copy number, and collect intracranial bioimpedance, scalp contact temperature, core body temperature input data or EEG signals. S2. Establish the sequence of immune pretreatment, proliferation protection and homeostasis maintenance on the day of reinfusion D0. During the pretreatment stage, output a 100-300kHz intermediate frequency alternating electric field and apply it to the head tumor target area. S3. When it is determined that CAR-T cells are in the expansion phase, switch the continuous output to intermittent output or low field strength output. S4. Adjust, interrupt, or lock the electric field output based on impedance, temperature, EEG signals, or metabolic indicators, and record the corresponding control status.

[0009] Preferably, in step S2, the immune pretreatment stage is from D-5 to D-1, during which the central control unit controls the electric field generating module to output a medium-frequency alternating electric field with a frequency of 200kHz and a field strength of 1.5V / cm; D0 is the CAR-T cell reinfusion day, during which the central control unit records CAR-T reinfusion data and uses the CAR-T reinfusion data as the benchmark information for subsequent proliferation protection timing judgment.

[0010] The above technical solution enables a correlation between electric field output and CAR-T cell reinfusion time. This treatment, which uses D0 as a time reference and sets an immune pretreatment phase between D-5 and D-1, allows electric field therapy to establish a pretreatment state before CAR-T cell reinfusion, thereby improving the clarity and continuity of subsequent proliferation protection timing determination.

[0011] Specifically, the central control unit distinguishes between the immunization pretreatment stage and the subsequent CAR-T proliferation protection stage by recording the CAR-T reinfusion day D0. A mid-frequency alternating electric field with a frequency of 200kHz and a field strength of 1.5V / cm is used as the output parameter for the pretreatment stage, providing a clear starting condition for the subsequent switching of the electric field output mode. Simultaneously, the CAR-T reinfusion data recorded on D0 can serve as benchmark information for subsequently determining the timing of proliferation protection, helping to reduce the problem of unclear time nodes in the control logic.

[0012] In practical applications, medical staff only need to enter the CAR-T cell infusion date into the system, and the central control unit can automatically establish the corresponding treatment sequence according to D0. This method enables the electric field output parameters to correspond to the CAR-T cell therapy process, thereby improving the operational stability and timing management effect of the glioma sequential electric field therapy system in combined treatment scenarios.

[0013] Preferably, in step S3, when the peripheral blood lymphocyte count increases by 50% from the baseline, the central control unit determines that the CAR-T cells are in the expansion phase and activates the proliferation protection mode; the proliferation protection mode includes switching the continuous output to intermittent output that is turned on for 1-2 hours and paused for 3-4 hours, and / or reducing the target area field strength to 0.7-1.0V / cm.

[0014] The above technical solution allows for adjustment of the electric field output mode when CAR-T cells enter the expansion phase. This method, which uses a 50% increase in peripheral blood lymphocyte count from baseline as a trigger condition and switches between intermittent and low-field-strength output, allows the electric field output to avoid the sensitive phase of CAR-T cell expansion, thereby improving the timing compatibility between electric field therapy and cellular immunotherapy.

[0015] Specifically, the central control unit compares the peripheral blood lymphocyte count with the baseline value. When the count reaches a preset increase, it determines that the CAR-T cells are in the amplification phase. At this time, the system can switch from continuous output to intermittent output, which is on for 1-2 hours and paused for 3-4 hours, or reduce the target field strength to 0.7-1.0 V / cm. These methods avoid maintaining a single continuous output during the amplification phase; simultaneously, both intermittent output and low field strength output provide executable control methods for the proliferation protection mode, facilitating the formation of a clear electric field avoidance logic.

[0016] In practical applications, the expansion status of CAR-T cells after reinfusion may vary due to individual patient differences. This method can automatically trigger a proliferation protection mode based on changes in peripheral blood lymphocyte counts, rather than relying solely on a fixed date, thereby improving the adaptability of electric field output control to changes in the expansion status of CAR-T cells.

[0017] Preferably, in step S4, the multimodal sensing electrode array collects intracranial bioimpedance data and scalp contact temperature data; when the intracranial bioimpedance decreases beyond a safety threshold within a set time, or when an abnormal preset impedance spectrum is detected, the central control unit interrupts the electric field output and triggers an alarm; when the scalp contact temperature, core body temperature input data, or CRS classification data meet the heat load control conditions, the central control unit reduces the electric field output power or increases the cooling fan speed.

[0018] The above technical solution enables the integration of intracranial bioimpedance and temperature information into the safety control of electric field output. This process, which triggers output interruption based on impedance anomalies and power adjustment based on temperature or CRS-related data, allows for feedback control of potential safety risks during electric field therapy, thereby improving the system's safety management capabilities during operation.

[0019] Specifically, the multimodal sensing electrode array can collect intracranial bioimpedance data and scalp contact temperature data. The central control unit determines whether to interrupt the electric field output based on the impedance change amplitude or a preset impedance spectrum. When the intracranial bioimpedance decreases beyond a safety threshold within a set time, or when an abnormal preset impedance spectrum is detected, the system can promptly interrupt the electric field output and trigger an alarm. Simultaneously, when the scalp contact temperature, core body temperature input data, or CRS classification data meet the thermal load control conditions, the system can reduce the output power or increase the cooling fan speed, which helps to reduce the continuous accumulation of local thermal load.

[0020] In practical applications, patients with gliomas receiving CAR-T therapy may experience fever, inflammatory responses, and changes in intracranial status. This approach allows electric field therapy devices to operate beyond fixed output parameters, incorporating impedance and temperature feedback for adjustments, thereby improving operational stability and safety under complex treatment conditions.

[0021] Preferably, in step S4, the central control unit periodically interrupts the output of the therapeutic electric field and enters a micro-silent window. The triggering period of the micro-silent window is 15-30 minutes, and the duration is 5-10 seconds. Within the micro-silent window, the multimodal sensing electrode array collects EEG signals. When spike-and-wave complexes or abnormal high-frequency discharges are detected, the central control unit locks the electric field output and triggers an alarm.

[0022] The above technical solution enables the creation of a low-interference time window for EEG acquisition during the operation of the therapeutic electric field. This periodic interruption of the therapeutic electric field and entry into a micro-silent window reduces the impact of the therapeutic electric field on EEG signal acquisition, thereby improving the feasibility of using abnormal EEG signals in safety interlock control.

[0023] Specifically, the central control unit pauses the therapeutic electric field for 5-10 seconds according to a trigger cycle of 15-30 minutes, and collects EEG signals through a multimodal sensing electrode array within this micro-silence window. Since EEG acquisition occurs during the pause of the therapeutic electric field, it reduces interference from continuous electric field output on EEG signal recognition. Simultaneously, when spike-and-wave complexes or abnormal high-frequency discharges are detected, the central control unit can lock the electric field output and trigger an alarm, facilitating the timely inclusion of abnormal EEG states into the electric field safety control process.

[0024] In practical applications, patients may exhibit abnormal brain electrical activity during treatment that is not easily observed externally. This method can coordinate treatment output and brain electrical monitoring through periodic micro-silence windows, thereby improving the system's responsiveness to abnormal brain electrical activity.

[0025] Preferably, in step S4, the central control unit receives one or more metabolic indicators among blood potassium, uric acid, and creatinine, and reduces the electric field strength when it determines that the metabolic load is close to a preset risk condition; the central control unit also imports the patient's head CT or MRI data through the image data processing module, constructs a 3D conductive model including the intracranial metal implant, and adjusts the voltage phase or switching state of each electrode unit in the multimodal sensing electrode array according to the 3D conductive model.

[0026] The above technical solution allows for the simultaneous incorporation of changes in metabolic load and intracranial implant status into the regulation of electric field output. This process, which reduces electric field strength based on metabolic indicators such as blood potassium, uric acid, and creatinine, and establishes a 3D conductivity model based on CT or MRI data, enables the electric field output to adapt to both the patient's overall metabolic state and intracranial structural differences, thereby improving the individualization of electric field control.

[0027] Specifically, the central control unit receives one or more metabolic indicators from serum potassium, uric acid, and creatinine to determine whether the metabolic load is approaching a preset risk condition. When the metabolic load is determined to be close to the preset risk condition, the system reduces the electric field strength to minimize the superposition of electric field output strength and metabolic load risk. Simultaneously, the central control unit imports the patient's head CT or MRI data through the image data processing module and constructs a 3D conductive model including the intracranial metal implant. Through this model, the system can identify the area affected by the electric field distribution related to the implant and adjust the voltage phase or switching state of the corresponding electrode unit, which helps to reduce abnormal concentration of local field strength.

[0028] In practical applications, postoperative intracranial structures and metabolic states vary among patients. This approach allows electric field therapy to be adjusted based on the patient's metabolic indicators and imaging structures, rather than simply following a uniform template, thereby improving the system's applicability in postoperative glioma patients.

[0029] Preferably, the system includes an electric field generation module, a CAR-T data input interface, a multimodal sensor electrode array, a central control unit, an image data processing module, a heat dissipation module, and an alarm module; the electric field generation module is used to output a 100-300kHz mid-frequency alternating electric field; the CAR-T data input interface is used to receive CAR-T infusion time, peripheral blood lymphocyte count, CAR-T copy number, CRS grade data, or metabolic indicators; the multimodal sensor electrode array is used to apply an electric field and collect intracranial bioimpedance, scalp contact temperature, or electroencephalogram (EEG) signals; and the central control unit is used to adjust the electric field output according to the staged treatment sequence and feedback signals.

[0030] The above technical solutions enable the formation of a complete system architecture for implementing a time-sequential electric field control method for gliomas. This design, which combines an electric field generation module, a CAR-T data input interface, a multimodal sensor electrode array, a central control unit, an image data processing module, a heat dissipation module, and an alarm module, allows data input, treatment output, signal feedback, and safety response to operate collaboratively within the same system, thereby improving the overall integrity of the system's functions.

[0031] Specifically, the electric field generation module outputs a 100-300kHz mid-frequency alternating electric field, the CAR-T data input interface receives CAR-T infusion time, peripheral blood lymphocyte count, CAR-T copy number, CRS grading data, or metabolic indicators, and the multimodal sensing electrode array applies the electric field and acquires intracranial bioimpedance, scalp contact temperature, or EEG signals. The central control unit processes these data and signals, adjusting the electric field output according to the phased treatment sequence and feedback signals. Simultaneously, the image data processing module, heat dissipation module, and alarm module respectively handle implant modeling, thermal load adjustment, and anomaly alerting, facilitating the formation of a closed-loop control structure.

[0032] In practical applications, this system can centrally manage CAR-T therapy-related data, electric field output parameters, and multimodal safety feedback. This approach reduces the fragmentation between functional modules, enabling the glioma sequential electric field therapy system to have better coordination and operability in combined treatment scenarios.

[0033] Preferably, the multimodal sensing electrode array includes a conductive unit, a thermistor, a microcurrent sensor, an EEG acquisition unit, and a functional conductive gel layer; the functional conductive gel layer is disposed between the conductive unit and the skin contact surface, the functional conductive gel layer contains phase change material microcapsules dispersed in it, and contains skin contact protective sustained-release components, the phase change temperature of the phase change material microcapsules is 38-40℃.

[0034] The above technical solution enables multimodal sensing electrode arrays to simultaneously perform electric field application, signal acquisition, and contact interface protection functions. This design, which incorporates conductive units, thermal sensors, microcurrent sensors, EEG acquisition units, and functional conductive gel layers within the electrode array, allows the same attachment structure to handle multiple types of feedback signal acquisition tasks, thereby improving the applicability of the electrode array in closed-loop control.

[0035] Specifically, the conductive unit applies a mid-frequency alternating electric field to the target area of ​​the head tumor, the thermistor collects scalp contact temperature, the microcurrent sensor collects intracranial bioimpedance data, and the EEG acquisition unit collects EEG signals within a micro-silent window. A functional conductive gel layer is disposed between the conductive unit and the skin contact surface, in which dispersed phase change material microcapsules participate in local thermal management when the temperature of the contact area rises; simultaneously, the skin contact protective sustained-release component reduces irritation to the skin contact surface during electrode attachment, which helps improve contact stability during the attachment process.

[0036] In practical applications, multimodal sensing electrode arrays need to maintain contact with the scalp for extended periods and perform both electric field output and feedback signal acquisition functions. This approach integrates electrical conduction, temperature monitoring, impedance monitoring, EEG acquisition, and contact interface protection into a single electrode array, thereby improving the system's feedback acquisition capability and adhesion adaptability during long-term operation.

[0037] Compared with the prior art, the present invention has the following advantages: 1. This invention uses the CAR-T infusion date as a timeline, dividing the electric field therapy process into stages such as immune pretreatment, proliferation protection, and homeostasis maintenance. The electric field output mode is adjusted based on changes in peripheral blood lymphocyte count or CAR-T copy number. By switching to intermittent or low-field-strength output during the CAR-T cell expansion phase, the electric field effect and the immune cell expansion process can be better coordinated in time, reducing the possibility of continuous electric field output adversely affecting the cell state during the expansion phase, thereby improving the coordination when electric field therapy and cellular immunotherapy are used in combination.

[0038] 2. This invention incorporates intracranial bioimpedance, scalp contact temperature, core body temperature, electroencephalogram (EEG) signals, metabolic indicators, and an intracranial implant model into a unified control process, enabling the system to adjust, interrupt, or lock the electric field output based on different feedback signals. Through impedance interlocking, temperature regulation, micro-silent window EEG monitoring, metabolic load control, and implant zoning avoidance, the electric field output can better match the patient's actual state during treatment, reducing the control deficiencies caused by a single fixed output mode, thereby improving the system's safety management capabilities during operation. Attached Figure Description

[0039] Figure 1 This is a schematic diagram of the module connections of the sequential electric field therapy system for glioma of the present invention; Figure 2 This is a flowchart of the phased treatment timing control of the glioma timing electric field therapy system of the present invention; Figure 3 This is the CAR-T proliferation protection mode state logic diagram of the sequential electric field therapy system for glioma of the present invention; Figure 4 This is a multimodal safety interlock control diagram of the sequential electric field therapy system for glioma of the present invention; Figure 5 This is a schematic diagram of the intracranial implant electrode avoidance zone control of the sequential electric field therapy system for glioma of the present invention; Figure 6 This is a schematic diagram of the multimodal sensing electrode array and the functional conductive gel layered structure of the sequential electric field therapy system for glioma of the present invention. Detailed Implementation

[0040] The present invention will be further described below with reference to the accompanying drawings and specific embodiments. It should be understood that the following embodiments are for illustrative purposes only and are not intended to limit the scope of protection of the present invention. All equivalent substitutions, improvements, and variations made within the spirit and principles of the present invention should fall within the scope of protection of the present invention.

[0041] The glioma timing electric field therapy system provided by this invention first establishes an electric field control timing sequence corresponding to the CAR-T infusion process during operation, and then adjusts the electric field output state by combining the impedance, temperature and EEG signals collected by the multimodal sensing electrode array, as well as the externally input metabolic indicators, CRS classification data and image data.

[0042] The specific process is as follows: First, data entry and baseline establishment are performed. The CAR-T infusion time is entered through the CAR-T data input interface, and the CAR-T infusion day is designated as D0. The central control unit uses D0 as the timeline to establish the patient's treatment timeline information. The CAR-T data input interface is also used to receive one or more data points, including peripheral blood lymphocyte count, CAR-T copy number, core body temperature, CRS classification, serum potassium, uric acid, and creatinine.

[0043] During initial system operation, the central control unit reads the baseline value of peripheral blood lymphocyte count or CAR-T copy number, and uses this baseline value as a reference for subsequent determination of whether CAR-T cells have entered the amplification phase. A multimodal sensor electrode array collects one or more data points from scalp contact temperature, intracranial bioimpedance, and electroencephalogram (EEG) signals, and transmits the collected data to the central control unit. This data is used to form the initial state record before electric field output.

[0044] Second, a phased treatment sequence is established. The central control unit uses the CAR-T infusion day D0 as a baseline to establish an immune preconditioning phase, a proliferation protection phase, and a homeostasis maintenance phase. The immune preconditioning phase is set before CAR-T infusion, preferably between D-5 and D-1; the proliferation protection phase is set after CAR-T infusion and is triggered based on peripheral blood lymphocyte count or CAR-T copy number; the homeostasis maintenance phase is set after the proliferation protection phase and is continuously controlled in a closed loop based on impedance, temperature, EEG, and metabolic indicators.

[0045] During the immune pretreatment phase, the central control unit controls the electric field generating module to output a 100-300kHz mid-frequency alternating electric field, which is then applied to the tumor target area in the patient's head via a multimodal sensing electrode array. Preferably, from D-5 to D-1, the electric field generating module outputs a mid-frequency alternating electric field with a frequency of 200kHz and a field strength of 1.5V / cm. On day D0, the central control unit records the CAR-T infusion data and uses this data as a time reference for subsequent assessment of the proliferation protection phase.

[0046] Third, the CAR-T proliferation protection mode is triggered. After D0, the central control unit continuously or at preset intervals receives peripheral blood lymphocyte counts or CAR-T copy numbers through the CAR-T data input interface. The central control unit compares the current peripheral blood lymphocyte count with the baseline value. When the peripheral blood lymphocyte count increases by 50% compared to the baseline, it determines that the CAR-T cells are in the expansion phase and activates the proliferation protection mode.

[0047] Upon entering the proliferation protection mode, the central control unit controls the electric field generating module to change its original continuous output state. The proliferation protection mode includes one or both of intermittent output and low field strength output. Intermittent output involves being on for 1-2 hours and then paused for 3-4 hours; low field strength output reduces the target area field strength to 0.7-1.0 V / cm. The central control unit can choose to execute one of the preset protection strategies, or it can alternate between them on different treatment days.

[0048] When the peripheral blood lymphocyte count or CAR-T copy number no longer meets the criteria for determining the amplification phase, the central control unit switches the electric field output to the output state corresponding to the steady-state maintenance phase based on the current treatment stage. Through this process, the system uses the CAR-T cell amplification state as the basis for adjusting the electric field output, transforming the electric field output from a fixed continuous mode to a time-series regulation mode associated with the CAR-T treatment process.

[0049] Fourth, implement multimodal safety interlock control. During the electric field output process, a multimodal sensing electrode array collects scalp contact temperature and intracranial bioimpedance data. The central control unit receives scalp contact temperature, core body temperature input data, or CRS classification data and determines whether the thermal load control conditions are met. When the thermal load control conditions are met, the central control unit reduces the electric field output power or increases the cooling fan speed. As a preferred method, when the core body temperature input data is 39°C, or when the temperature data and CRS classification data both indicate a risk of thermal load superposition, the central control unit controls the electric field output power to decrease by 20%.

[0050] The central control unit also monitors intracranial bioimpedance data. When the intracranial bioimpedance decreases by more than a safety threshold within a set time, or when an abnormal preset impedance spectrum is detected, the central control unit interrupts the electric field output and triggers an alarm. Preferably, when the intracranial bioimpedance decreases by 10% within 4 hours, the central control unit determines that the impedance safety interlock condition is met and executes the electric field output interruption.

[0051] Fifth, perform EEG monitoring within a micro-silent window. The central control unit interrupts the therapeutic electric field output according to a preset cycle and enters a micro-silent window. The trigger cycle of the micro-silent window is 15-30 minutes, and the duration is 5-10 seconds. Within the micro-silent window, the EEG acquisition unit in the multimodal sensing electrode array acquires EEG signals and sends the acquired EEG signals to the central control unit.

[0052] The central control unit identifies EEG signals. When spike-and-wave complexes or abnormal high-frequency discharges are detected, the electric field output is locked and an alarm is triggered. The locked state is released after manual verification or when preset reset conditions are met. Through this process, the system forms a periodic low-interference EEG acquisition window during the operation of the therapeutic electric field, allowing abnormal EEG signals to participate in the safe control of the electric field.

[0053] Sixth, metabolic load regulation is performed. The CAR-T data input interface receives one or more metabolic indicators from serum potassium, uric acid, and creatinine. The central control unit compares these metabolic indicators with preset metabolic load risk conditions. When the metabolic load is determined to be close to the preset risk conditions, the central control unit reduces the electric field strength and records the triggering basis for this regulation action.

[0054] When metabolic indicators return to within acceptable limits, the central control unit gradually restores the electric field output according to the current treatment stage. If the metabolic load control condition, impedance safety interlock condition, and EEG abnormality lockout condition are simultaneously met, the central control unit prioritizes executing the control actions corresponding to the impedance safety interlock or EEG abnormality lockout.

[0055] Seventh, implement intracranial implant avoidance control. Before the electric field output or during system initialization, import the patient's head CT or MRI data through the image data processing module. The central control unit identifies the location of intracranial metal implants such as titanium screws, titanium mesh, or shunt tubes based on the image data and constructs a 3D conductive model containing the intracranial metal implants.

[0056] The central control unit determines the electrode units corresponding to or adjacent to the intracranial metal implant based on the 3D conductivity model, and performs one or more control actions on the relevant electrode units, such as reducing output, shutting down output, or adjusting voltage phase. For electrode units far from the intracranial metal implant area, the central control unit maintains the corresponding electric field output according to the current treatment stage. If the system is also in the CAR-T proliferation protection stage, the central control unit continues to perform intermittent output or low field strength output while performing implant avoidance control.

[0057] Eighth, contact and feedback of the multimodal sensing electrode array are performed. The multimodal sensing electrode array includes a conductive unit, a thermistor, a microcurrent sensor, an EEG acquisition unit, and a functional conductive gel layer. The functional conductive gel layer is disposed between the conductive unit and the skin contact surface. Phase change material microcapsules are dispersed in the functional conductive gel layer, and it contains skin contact protective sustained-release components. The phase change temperature of the phase change material microcapsules is 38-40℃.

[0058] During system operation, conductive units apply a mid-frequency alternating electric field, thermistors acquire scalp contact temperature, microcurrent sensors acquire intracranial bioimpedance data, and EEG acquisition units acquire EEG signals within a micro-quiet window. A functional conductive gel layer forms the electrical conduction interface and, together with temperature feedback control, participates in local thermal management and skin contact protection.

[0059] Through the above process, the central control unit can take the CAR-T infusion day D0 as the core timing benchmark and combine immune pretreatment, CAR-T proliferation protection, homeostasis maintenance, multimodal safety interlock and implant avoidance control, so that the electric field output state can be adjusted according to the CAR-T treatment process and patient feedback data.

[0060] Example 1: Control of CAR-T reintegration timing and amplification protection electric field output Materials Preparation: A sequential electric field therapy system for glioma is prepared. The system includes an electric field generation module, a CAR-T data input interface, a multimodal sensor electrode array, and a central control unit. The central control unit has a pre-set phased treatment sequence program, which includes at least an immune pretreatment phase, a proliferation protection phase, and a homeostasis maintenance phase. The CAR-T data input interface receives CAR-T infusion time, peripheral blood lymphocyte count, or CAR-T copy number. The central control unit generates electric field output control commands based on the above data.

[0061] Process steps: First, the CAR-T infusion time is entered through the CAR-T data input interface, and the CAR-T infusion day is designated as D0. The central control unit establishes the treatment sequence based on D0, and enters the immune pretreatment stage from D-5 to D-1. During this stage, the central control unit controls the electric field generating module to output a mid-frequency alternating electric field. The frequency of the mid-frequency alternating electric field is 200kHz, and the field strength is 1.5V / cm. This field is applied to the head tumor target area through a multimodal sensing electrode array.

[0062] On day D0, the central control unit records CAR-T infusion data and uses this data as a time reference for determining the subsequent proliferation protection phase. After D0, the CAR-T data input interface continuously or at preset intervals receives peripheral blood lymphocyte counts or CAR-T copy numbers. The central control unit compares the current peripheral blood lymphocyte count with the baseline value. When the peripheral blood lymphocyte count increases by 50% from the baseline, it determines that the CAR-T cells are in the expansion phase and initiates the proliferation protection mode.

[0063] Upon entering the proliferation protection mode, the central control unit no longer maintains the original continuous electric field output, but instead switches the electric field output to intermittent output or low-field-strength output. The intermittent output involves being on for 1-2 hours and then paused for 3-4 hours; the low-field-strength output involves reducing the target area field strength to 0.7-1.0 V / cm. These two output modes can be selected according to the preset protection strategy in the central control unit, or they can be alternated across different treatment days. If the subsequent peripheral blood lymphocyte count or CAR-T copy number no longer meets the criteria for the amplification phase, the central control unit switches the electric field output to the output state corresponding to the steady-state maintenance phase based on the current treatment stage.

[0064] Results show that by reading the stage judgment records of the central control unit and the output records of the electric field generation module, it can be confirmed that the system can complete the continuous control process of "D0 timing establishment—preprocessing electric field output—amplification phase identification—protection mode switching—steady-state output recovery". The key to this embodiment is that the electric field output does not run continuously at a fixed frequency and duration, but rather uses the CAR-T infusion day and the CAR-T cell amplification status as control criteria, actively performing intermittent or low-field-strength output during the amplification phase. This embodiment specifically supports the technical features of S1, S2, and S3 in the claims and embodies the timing regulation characteristics of this invention, which distinguish it from ordinary continuous tumor electric field therapy.

[0065] Example 2: Electric Field Output Control under Multimodal Safety Interlocking Conditions Materials Preparation: Prepare a sequential electric field therapy system for glioma, comprising a CAR-T data input interface, a multimodal sensor electrode array, a central control unit, a heat dissipation module, and an alarm module. The multimodal sensor electrode array includes a thermal sensor, a microcurrent sensor, and an EEG acquisition unit. The thermal sensor is used to acquire scalp contact temperature, the microcurrent sensor is used to acquire intracranial bioimpedance data, and the EEG acquisition unit is used to acquire EEG signals during electric field pauses. The CAR-T data input interface is also used to receive core body temperature input data, CRS classification data, and one or more data points selected from serum potassium, uric acid, and creatinine.

[0066] The central control unit has preset thermal load control conditions, impedance safety interlock conditions, EEG abnormality recognition conditions, and metabolic load control conditions. These control conditions do not operate independently but work together according to preset control logic to affect the electric field output state. Among them, impedance safety interlock and EEG abnormality lockout take precedence over simple power reduction, while thermal load control and metabolic load control are used to adjust the output intensity when the emergency stop or lockout conditions are not met.

[0067] Process steps: During the electric field output process, a thermistor collects the scalp contact temperature, and the CAR-T data input interface receives core body temperature input data or CRS classification data. When the core body temperature input data is 39℃, or when the scalp contact temperature, core body temperature input data, or CRS classification data meet the heat load control conditions, the central control unit sends a power reduction command to the electric field generation module and a heat dissipation enhancement command to the heat dissipation module, reducing the electric field output power by 20% or increasing the cooling fan speed.

[0068] Simultaneously, a microcurrent sensor collects intracranial bioimpedance data. The central control unit analyzes changes in the intracranial bioimpedance data. When the intracranial bioimpedance decreases by 10% within 4 hours, or an abnormality in the preset impedance spectrum is detected, the central control unit determines that the impedance safety interlock condition is met, interrupts the electric field output, and triggers an alarm module. If both the thermal load control condition and the impedance safety interlock condition are met, the central control unit prioritizes executing the electric field interruption and alarm, rather than simply reducing the power.

[0069] During EEG monitoring, the central control unit interrupts the therapeutic electric field output according to a preset cycle, entering a micro-silent window. The trigger cycle of the micro-silent window is 15-30 minutes, and the duration is 5-10 seconds. Within the micro-silent window, the EEG acquisition unit collects EEG signals and sends the collected EEG signals to the central control unit. When the central control unit detects spike-and-wave complexes or abnormal high-frequency discharges, it locks the electric field output and triggers an alarm. The locked state requires manual verification or the release of preset reset conditions before the system can resume the corresponding treatment stage.

[0070] During metabolic load control, the CAR-T data input interface receives one or more metabolic indicators from serum potassium, uric acid, and creatinine. The central control unit compares these metabolic indicators with preset metabolic load control conditions. When the metabolic load is determined to be close to a preset risk condition, the electric field strength is reduced. If both the metabolic load control conditions and the impedance safety interlock conditions are met simultaneously, the central control unit prioritizes executing the interrupt output corresponding to the impedance safety interlock.

[0071] Results: By checking the control status of the central control unit, it can be confirmed that the system can perform different electric field control actions under different feedback signals. When the temperature or CRS-related data meet the heat load control conditions, the system reduces power or enhances heat dissipation; when the impedance data meets the safety interlock conditions, the system interrupts output and alarms; when the EEG signal meets the abnormal recognition conditions, the system locks output and alarms; when the metabolic indicators meet the control conditions, the system reduces the electric field strength.

[0072] The focus of this embodiment is not on detection by a single sensor, but on incorporating impedance, temperature, EEG, and metabolic indicators into the electric field output control, and establishing the execution relationship between different control actions. This approach avoids conflicting control actions when multiple abnormal states occur simultaneously, creating a unified control logic for the electric field output between proliferation protection and safety interlocking. This embodiment specifically supports the technical features of S4, impedance interlocking, temperature feedback, micro-silent window EEG acquisition, and metabolic load regulation as described in the claims.

[0073] Example 3: Control of Multimodal Electrode Arrays Based on Implant Modeling and Functional Conductive Gel Materials Preparation: A sequential electric field therapy system for glioma is prepared. This system includes an image data processing module, a central control unit, and a multimodal sensing electrode array. The image data processing module is used to import the patient's head CT or MRI data and identify intracranial metal implants such as titanium screws, titanium mesh, or shunts. The multimodal sensing electrode array includes multiple independently controllable electrode units, and includes conductive units, thermal sensors, microcurrent sensors, EEG acquisition units, and a functional conductive gel layer.

[0074] A functional conductive gel layer is disposed between the conductive unit and the skin contact surface. Phase change material microcapsules are dispersed within the functional conductive gel layer, which also contains skin-protective sustained-release components. The phase change temperature of the phase change material microcapsules is 38-40℃. A thermal sensor is positioned close to the skin contact surface, a microcurrent sensor is used to collect intracranial bioimpedance data, and an EEG acquisition unit is used to acquire EEG signals within a micro-silent window.

[0075] Process steps: Before treatment, the image data processing module imports the patient's head CT or MRI data and identifies any intracranial metal implants. The central control unit creates a 3D conductive model containing the intracranial metal implant based on the identification results and divides the multimodal sensing electrode array into multiple electrode control zones. The central control unit determines the electrode units corresponding to or adjacent to the intracranial metal implant based on the 3D conductive model and marks them as electrode units to be adjusted.

[0076] During electric field output, the central control unit performs one or more control actions on the electrode unit to be adjusted, such as reducing output, shutting down output, or adjusting voltage phase, to make it different from the electrode unit located far from the intracranial metal implant area. For electrode units located far from the intracranial metal implant area, the central control unit maintains the corresponding electric field output according to the current treatment stage. If the current treatment stage is also in the CAR-T proliferation protection stage, the central control unit, while performing implant avoidance control, still performs intermittent output or low field strength output according to the proliferation protection mode.

[0077] During electrode attachment, a functional conductive gel layer is positioned between the conductive unit and the skin contact surface to form an electrical conduction interface. Phase change material microcapsules within the functional conductive gel layer absorb localized heat when the contact area temperature rises, while skin-protective sustained-release components reduce irritation to the skin contact surface during electrode attachment. Temperature data collected by the thermal sensor, impedance data collected by the microcurrent sensor, and EEG signals collected by the EEG acquisition unit within the micro-silent window are all transmitted to the central control unit and participate in the safety interlock control described in Example 2.

[0078] Results: By reading the output status of each electrode control zone in the central control unit, it can be confirmed that the system can identify the intracranial metal implant area based on CT or MRI data, and perform control actions on the electrode units corresponding to or adjacent to the implant area that are different from other electrode units. By detecting the signal output of the multimodal sensing electrode array, it can be confirmed that the same electrode array can simultaneously perform the functions of electric field application, scalp contact temperature acquisition, intracranial bioimpedance acquisition, and micro-silent window EEG acquisition.

[0079] The key point of this embodiment is that the multimodal sensing electrode array is not a typical electric field output patch, but rather serves simultaneously as a treatment output end, a feedback acquisition end, and a local contact protection end. Through implant modeling and electrode zoning control, the system can adjust the output state of different electrode units according to the location of the intracranial metal implant; through a functional conductive gel layer, the system can integrate electric field conduction, local thermal management, and skin contact protection within the same patch structure. This embodiment specifically supports the technical features described in the claims regarding the image data processing module, 3D conductive model, electrode unit phase or on / off state adjustment, multimodal sensing electrode array, and functional conductive gel layer.

[0080] In the description of this invention, it should be understood that the terms "center," "longitudinal," "lateral," "length," "width," "thickness," "upper," "lower," "front," "rear," "left," "right," "vertical," "horizontal," "top," "bottom," "inner," "outer," "clockwise," and "counterclockwise," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are only for the convenience of describing this invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on this invention.

[0081] Furthermore, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. In the description of this invention, "a plurality of" means two or more, unless otherwise explicitly specified.

[0082] The above description is merely a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. A time-series electric field therapy system for glioma, the system comprising an electric field generation module, a CAR-T data input interface, a multimodal sensing electrode array, and a central control unit, characterized in that, Includes the following steps: S1. Receive CAR-T infusion time, peripheral blood lymphocyte count or CAR-T copy number, and collect intracranial bioimpedance, scalp contact temperature, core body temperature input data or EEG signals. S2. Establish the sequence of immune pretreatment, proliferation protection and homeostasis maintenance on the day of reinfusion D0. During the pretreatment stage, output a 100-300kHz intermediate frequency alternating electric field and apply it to the head tumor target area. S3. When it is determined that CAR-T cells are in the expansion phase, switch the continuous output to intermittent output or low field strength output. S4. Adjust, interrupt, or lock the electric field output based on impedance, temperature, EEG signals, or metabolic indicators, and record the corresponding control status.

2. The control method of the sequential electric field therapy system for glioma according to claim 1, characterized in that, In step S2, the immune pretreatment stage is from D-5 to D-1. During this period, the central control unit controls the electric field generating module to output a medium-frequency alternating electric field with a frequency of 200kHz and a field strength of 1.5V / cm. D0 is the CAR-T cell reinfusion day. The central control unit records the CAR-T reinfusion data on D0 and uses the CAR-T reinfusion data as the benchmark information for subsequent proliferation protection timing judgment.

3. The control method of the sequential electric field therapy system for glioma according to claim 1, characterized in that, In step S3, when the peripheral blood lymphocyte count increases by 50% from the baseline, the central control unit determines that the CAR-T cells are in the expansion phase and activates the proliferation protection mode; the proliferation protection mode includes switching the continuous output to intermittent output that is on for 1-2 hours and paused for 3-4 hours, and / or reducing the target area field strength to 0.7-1.0V / cm.

4. The control method of the sequential electric field therapy system for glioma according to claim 1, characterized in that, In step S4, the multimodal sensing electrode array collects intracranial bioimpedance data and scalp contact temperature data; when the intracranial bioimpedance decreases beyond a safety threshold within a set time, or when an abnormal preset impedance spectrum is detected, the central control unit interrupts the electric field output and triggers an alarm; when the scalp contact temperature, core body temperature input data, or CRS classification data meet the heat load control conditions, the central control unit reduces the electric field output power or increases the cooling fan speed.

5. The control method of the sequential electric field therapy system for glioma according to claim 1, characterized in that, In step S4, the central control unit periodically interrupts the output of the therapeutic electric field and enters a micro-silence window. The triggering period of the micro-silence window is 15-30 minutes, and the duration is 5-10 seconds. Within the micro-silence window, the multimodal sensing electrode array collects EEG signals. When spike-and-wave complexes or abnormal high-frequency discharges are detected, the central control unit locks the electric field output and triggers an alarm.

6. The control method of the sequential electric field therapy system for glioma according to claim 1, characterized in that, In step S4, the central control unit receives one or more metabolic indicators among blood potassium, uric acid and creatinine, and reduces the electric field strength when it determines that the metabolic load is close to the preset risk condition; the central control unit also imports the patient's head CT or MRI data through the image data processing module, constructs a 3D conductive model including the intracranial metal implant, and adjusts the voltage phase or switching state of each electrode unit in the multimodal sensing electrode array according to the 3D conductive model.

7. A sequential electric field therapy system for glioma, characterized in that, The system, used to execute the control method according to any one of claims 1-6, comprises an electric field generating module, a CAR-T data input interface, a multimodal sensor electrode array, a central control unit, an image data processing module, a heat dissipation module, and an alarm module; the electric field generating module is used to output a 100-300kHz mid-frequency alternating electric field; the CAR-T data input interface is used to receive CAR-T infusion time, peripheral blood lymphocyte count, CAR-T copy number, CRS grade data, or metabolic indicators; the multimodal sensor electrode array is used to apply an electric field and acquire intracranial bioimpedance, scalp contact temperature, or electroencephalogram (EEG) signals; and the central control unit is used to adjust the electric field output according to the phased treatment sequence and feedback signals.

8. The sequential electric field therapy system for glioma according to claim 7, characterized in that, The multimodal sensing electrode array includes a conductive unit, a thermistor, a microcurrent sensor, an EEG acquisition unit, and a functional conductive gel layer. The functional conductive gel layer is disposed between the conductive unit and the skin contact surface. The functional conductive gel layer contains phase change material microcapsules and skin contact protective sustained-release components. The phase change temperature of the phase change material microcapsules is 38-40℃.

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