阅读说明：本技术 时间治疗疗法配置 (Chronotherapeutic treatment configuration ) 是由 E·麦克利恩 G·比尔 于 2019-06-17 设计创作，主要内容包括：一种电磁能量传输系统被配置为以特定时序安排传输能量以改善免疫反应。电磁能量传输系统可以包括受控电磁能量源和电磁能量施加器,其中受控电磁能量源被配置为根据由治疗配置文件限定的特定时序安排来发射电磁能量,治疗配置文件被配置为使得在所发射的电磁能量经由电磁能量施加器传输到宿主时,所发射的电磁能量刺激和/或抑制宿主中的免疫反应。一种电磁能量传输方法包括以特定时序安排传输能量以改善免疫反应。(An electromagnetic energy delivery system is configured to deliver energy with a particular timing schedule to improve an immune response. The electromagnetic energy delivery system may include a controlled electromagnetic energy source configured to emit electromagnetic energy according to a particular timing schedule defined by a treatment profile configured such that the emitted electromagnetic energy stimulates and/or suppresses an immune response in the host when the emitted electromagnetic energy is delivered to the host via the electromagnetic energy applicator. A method of electromagnetic energy delivery includes delivering energy with a particular timing schedule to improve an immune response.)

1. An electromagnetic energy delivery system delivers energy with a specific timing schedule to improve immune responses.

2. The electromagnetic energy transfer system of claim 1, comprising:

a controlled electromagnetic energy source; and

an electromagnetic energy applicator for applying an electromagnetic energy to the body,

wherein the controlled electromagnetic energy source is configured to emit electromagnetic energy according to the particular timing schedule defined by a treatment profile configured such that the emitted electromagnetic energy stimulates and/or suppresses an immune response in a host when the emitted electromagnetic energy is transmitted to the host via the electromagnetic energy applicator.

3. The electromagnetic energy delivery system of claim 2, wherein the controlled electromagnetic energy source is configured to emit electromagnetic energy in accordance with a treatment profile configured such that, when the emitted electromagnetic energy is delivered to the host via the electromagnetic energy applicator, the emitted electromagnetic energy stimulates and/or suppresses an immune response in the host without necrosis of cells or tissues of the host.

4. An electromagnetic energy delivery system according to claim 2 or 3, wherein the controlled electromagnetic energy source is configured to emit electromagnetic energy in accordance with a treatment profile configured such that, when the emitted electromagnetic energy is delivered to the host via the electromagnetic energy applicator, the emitted electromagnetic energy heats cells or tissue of the host.

5. The electromagnetic energy delivery system of any one of claims 2 to 4, wherein the controlled electromagnetic energy source is configured to emit electromagnetic energy in accordance with a treatment profile configured such that, when the emitted electromagnetic energy is delivered to the host via the electromagnetic energy applicator, the emitted electromagnetic energy heats cells or tissue of the host without ablating the cells or tissue of the host.

6. The electromagnetic energy transfer system of any one of claims 2 to 5, wherein:

the treatment profile defines one or more transmission periods, and the controlled electromagnetic energy source is configured to emit electromagnetic energy only during each transmission period, and optionally,

the treatment profile defines one or more series of pulses, each pulse having a duration equal to the transmission period, and optionally,

each transmission period is one thousandth of a second, one second, two seconds, two to three seconds, or up to twenty seconds or up to one or two minutes or ten minutes, and optionally,

the therapy profile defines one, five to ten, up to one hundred or one thousand transmission cycles, and optionally,

the therapy profile defines a plurality of transmission periods configured such that the emitted electromagnetic energy is pulsed at a rate of 5 Hz.

7. An electromagnetic energy delivery system according to any one of claims 2 to 6, wherein the controlled electromagnetic energy source is configured to emit electromagnetic energy in accordance with a treatment profile configured such that the emitted electromagnetic energy is emitted at a power in the range of 1-50W, such as in the range of 8W-10W, 2W-5W or 3W-8W.

8. An electromagnetic energy transfer system according to any one of claims 2 to 7 wherein the controlled electromagnetic energy source is configured to emit electromagnetic energy at microwave frequencies, for example wherein the controlled electromagnetic energy source is configured to emit electromagnetic energy at frequencies in the frequency range of 1-300 GHz.

9. An electromagnetic energy delivery system according to any one of claims 2 to 8, wherein the controlled electromagnetic energy source is configured to emit electromagnetic energy in accordance with a treatment profile configured such that the emitted electromagnetic energy is amplitude modulated, for example at a frequency in the range of 1-100 KHz.

10. The electromagnetic energy delivery system of claim 9, wherein the controlled electromagnetic energy source is configured to emit electromagnetic energy in accordance with a treatment profile configured such that the emitted electromagnetic energy is amplitude modulated in accordance with a Pulse Width Modulation (PWM) or on/off keying (OOK) modulation scheme.

11. An electromagnetic energy transfer system according to any one of claims 2 to 10 wherein the controlled electromagnetic energy source is configured to emit electromagnetic energy in accordance with a treatment profile configured such that the emitted electromagnetic energy is frequency modulated, for example at a frequency in the range of 1-100 KHz.

12. The electromagnetic energy delivery system of any one of claims 2 to 11, wherein the controlled electromagnetic energy source is configured to receive one or more signals from one of a plurality of physiological parameter sensors and adjust the treatment profile according to the one or more received signals.

13. The electromagnetic energy delivery system of claim 12, wherein the controlled electromagnetic energy source is configured to receive a PQRST heart rate signal from an ECG sensor and adjust the therapy profile according to the PQRST heart rate cycle signal, for example, by dynamically synchronizing the therapy profile to correspond to a particular point in the PQRST heart rate cycle signal.

14. The electromagnetic energy delivery system of claim 12 or 13, wherein the controlled electromagnetic energy source is configured to receive neural oscillation signals from an EEG sensor and to adjust the treatment profile in accordance with the neural oscillation signals, for example by dynamically synchronizing the treatment profile to correspond to the neural oscillation signals.

15. The electromagnetic energy delivery system of any of claims 12-14, wherein the controlled electromagnetic energy source is configured to receive a blood pressure signal from a blood pressure sensor and adjust the therapy profile as a function of the blood pressure signal, for example, by dynamically synchronizing the therapy profile to correspond to the blood pressure signal.

16. A method of electromagnetic energy delivery includes delivering energy in a specific timing schedule to improve an immune response.

17. The method of electromagnetic energy transfer of claim 16, comprising:

transmitting electromagnetic energy according to the particular schedule defined by the treatment profile; and

transmitting the emitted electromagnetic energy to the host,

wherein the treatment profile is configured such that, upon delivery of the emitted electromagnetic energy to the host, the emitted electromagnetic energy stimulates and/or suppresses the immune response in the host.

18. The method of claim 17, comprising emitting electromagnetic energy according to a treatment profile configured such that, upon transmission of the emitted electromagnetic energy to the host, the emitted electromagnetic energy stimulates and/or suppresses an immune response in the host without necrosis of cells or tissue of the host.

19. A method of electromagnetic energy transfer as in claim 17 or 18 comprising emitting electromagnetic energy in accordance with a treatment profile configured such that, upon transfer of the emitted electromagnetic energy to the host, the emitted electromagnetic energy heats cells or tissues of the host.

20. A method of electromagnetic energy delivery as claimed in any one of claims 17 to 19, including emitting electromagnetic energy in accordance with a treatment profile configured such that, upon delivery of the emitted electromagnetic energy to the host, the emitted electromagnetic energy heats cells or tissue of the host without ablating the cells or tissue of the host.

21. A method of electromagnetic energy transfer as claimed in any one of claims 17 to 20, wherein:

the treatment profile defines one or more transmission periods, and the method includes emitting electromagnetic energy only during each transmission period, and optionally,

the treatment profile defines one or more series of pulses, each pulse having a duration equal to the transmission period, and optionally,

each transmission period is one thousandth of a second, one second, two seconds, two to three seconds, or up to twenty seconds or up to one or two minutes or ten minutes, and optionally,

the therapy profile defines one, five to ten, up to one hundred or one thousand transmission cycles, and optionally,

the therapy profile defines a plurality of transmission periods configured such that the emitted electromagnetic energy is pulsed at a rate of 5Hz, and optionally,

the therapy profile defines a course of a plurality of therapies, each therapy comprising at least one transmission cycle, and each therapy being spaced at one or more week intervals, for example at four week intervals, and optionally,

the therapy profile defines one or more further transmission periods following a follow-up interval of at least 12 weeks.

22. A method of electromagnetic energy delivery as claimed in any one of claims 17 to 21, comprising emitting electromagnetic energy in accordance with a treatment profile configured such that the emitted electromagnetic energy is emitted at a power in the range 1-50W, for example in the range 8W-10W, 2W-5W or 3W-8W.

23. A method of electromagnetic energy transmission according to any one of claims 17 to 22 including transmitting electromagnetic energy at microwave frequencies, for example at frequencies in the range 1-300 GHz.

24. A method of electromagnetic energy delivery as claimed in any one of claims 17 to 23, including transmitting electromagnetic energy in accordance with a treatment profile configured such that the transmitted electromagnetic energy is amplitude modulated, for example at a frequency in the range of 1-100 KHz.

25. A method of electromagnetic energy transfer as claimed in any one of claims 17 to 24, comprising transmitting electromagnetic energy in accordance with a treatment profile configured such that the transmitted electromagnetic energy is frequency modulated, for example at a frequency in the range of 1-100 KHz.

26. A method of electromagnetic energy transfer as claimed in any one of claims 17 to 25, comprising:

receiving one or more signals from one of a plurality of physiological parameter sensors; and

adjusting the therapy profile according to the one or more received signals.

27. A method of electromagnetic energy transfer as claimed in claim 26, comprising:

receiving a PQRST heart rate signal from an ECG sensor; and

the therapy profile is adjusted based on the PQRST heart cycle signal, for example, by dynamically synchronizing the therapy profile to correspond to particular points in the PQRST heart cycle signal.

28. A method of electromagnetic energy transfer as claimed in claim 26 or 27, comprising:

receiving a neural oscillation signal from an EEG sensor; and

the therapy profile is adjusted according to the neuro-oscillatory signal, for example, by dynamically synchronizing the therapy profile to correspond to the neuro-oscillatory signal.

29. A method of electromagnetic energy transfer as claimed in any one of claims 26 to 28, comprising:

receiving a blood pressure signal from a blood pressure sensor; and

the therapy profile is adjusted according to the blood pressure signal, for example, by dynamically synchronizing the therapy profile to correspond to the blood pressure signal.

30. A method of electromagnetic energy delivery as claimed in any one of claims 17 to 29, including adjusting the treatment profile in accordance with measurements indicative of the immune cycle of the host.

31. A method of electromagnetic energy transfer as claimed in claim 30, wherein the measurements indicative of the immune cycle of the host include at least one of C-reactive protein (CRP) levels in blood, T regulatory cell (low-state) or T effector cell (high-state) measurements.

32. A method of electromagnetic energy transfer as claimed in any one of claims 17 to 31 and including administering one or more other therapies to the host before, during and/or after emission of electromagnetic energy according to the treatment profile and transfer of the electromagnetic energy to the host.

33. The method of electromagnetic energy transmission of claim 32 wherein the one or more other therapies include at least one of: radiotherapy, chemotherapy, immunotherapy, traditional drug therapy, Transcutaneous Electrical Nerve Stimulation (TENS) and frequency rhythm electrical modulation system (fresm).

34. A treatment profile for use with an electromagnetic energy transfer system according to any one of claims 2 to 15 or an electromagnetic energy transfer method according to any one of claims 17 to 33.

Technical Field

An electromagnetic energy transmission method is described that includes transmitting electromagnetic energy at specific timing arrangements (timing arrangements) to improve an immune response. The method may utilize multiple temporal therapeutic variables to facilitate an immune response by applying electromagnetic energy to the host.

An electromagnetic energy delivery system is described that delivers electromagnetic energy with a particular timing schedule to improve immune responses.

Background

Methods and systems for ablating host tissue using electromagnetic energy are known. Such systems typically transmit electromagnetic energy from an energy generator to a host via a connecting cable and then to a radiation applicator, which transmits the energy into the host's tissue. In these applicators, the radiating element is surrounded by or placed in contact with the tissue. For such systems, it is common standard practice to deliver energy for treatment, typically for 1-20 minutes, to bring the tissue temperature above 43-45 to 60, 70+ C and above, to cause necrosis within the desired ablation zone. This energy may be delivered at an amplitude or pulse width modulated duty cycle to ensure that the desired energy level is maintained or controlled for the duration of the energy release.

These standard types of electromagnetic generator systems are designed to destroy diseased or undesirable tissue.

Disclosure of Invention

It will be understood that one or more features of any of the following aspects may be provided in combination with one or more features of the other aspects.

According to one aspect of the present disclosure, an electromagnetic energy delivery system is provided that delivers energy with a particular timing schedule to improve an immune response.

Various advantageous methods and delivery profiles (profiles) are described herein with respect to the delivery of electromagnetic energy, such as microwave energy, that promotes and/or suppresses immune responses.

Various combinations of pulsing patterns, modulation schemes, treatment durations, treatment intervals, immunological measurements, and nervous system feedback methods are described with respect to the application of electromagnetic energy to affect an immune response.

The methods described herein are designed to treat in conjunction with the adaptive or innate biological immune system in a substantially immune response. Immune responses can be classified, for example, as: up-or down-regulation of the signal; inhibiting or promoting the growth of cell types, inducing apoptosis, regulating cell membranes.

One key aspect of immune response optimization therapy as compared to traditional ablation therapy is the synergistic control of energy application on a temporal micro-scale, temporal macro-scale, and other biological time scales associated with optimal immune response of diseased or abnormal tissue. Combinations of these requirements or elements thereof may be beneficial throughout the treatment profile to ensure such responses.

Without wishing to be bound by theory, on a microscopic scale (seconds), for a particular neurophysiologic event, unlike arterial pulsation, the rate of labor (1Hz or less) may be very close to the rate of rhythmic modulation of alpha wave power. Pulsed electromagnetic fields (e.g., 5Hz) may down-regulate inflammatory pathway markers in murine macrophages. The use of pulsed electromagnetic fields may activate mitogen-activated protein (MAP) kinases, thereby initiating cellular responses that lead to cell proliferation.

On a macroscopic scale (hours/days/weeks), it is assumed that the immune system acts in a periodic manner (e.g., one cycle may last 12 to 14 days depending on the individual) and that treatment for that cycle may optimize their efficacy. Acute exposure to microwave energy for a short duration of time may activate macrophages, which are more lethal and become activated 6 hours after exposure and remain activated for up to 12 days. In the wound healing cascade, the inflammation and macrophage phase may last 2 to 4 weeks as part of the healing phase.

Periodic discontinuation of the use of further therapeutic doses may activate protective responses, which may down-regulate immune activation. Also, a long delay between treatments may be detrimental to the overall healing or duration (if it corresponds to a period of low immune system activity), i.e. the response will not have as large an amplitude as in the optimal protocol.

Artificial stimulation of the vagus nerve may control the activation of the circulating immune cells and, conversely, attenuation of the vagal signaling provides an inhibitory effect on cytokine production.

Microwaves can interact directly with cell membranes, for example to mimic the effect of binding of a ligand to a specific receptor that produces a (non-thermal) effect associated with direct microwaves. The complete infection response may be important to maintain a normal immune defense mechanism. In some cases where the immune system is compromised (viral infection), it may be desirable to increase the infectious response. In some other cases, it may be desirable to reduce the infectious response, such as vascular occlusion.

Such a neural signaling system may be used, for example, for monitoring and influencing to promote or reduce immune effects as desired.

The electromagnetic energy delivery system may include a controlled electromagnetic energy source configured to emit electromagnetic energy according to a particular timing schedule defined by a treatment profile configured such that the emitted electromagnetic energy stimulates and/or suppresses an immune response in the host when the emitted electromagnetic energy is delivered to the host via the electromagnetic energy applicator, and an electromagnetic energy applicator.

The controlled electromagnetic energy source may be configured to emit electromagnetic energy in accordance with a treatment profile configured such that, when the emitted electromagnetic energy is transmitted to the host via the electromagnetic energy applicator, the emitted electromagnetic energy stimulates and/or suppresses an immune response in the host without necrosis of cells or tissue of the host.

The controlled electromagnetic energy source may be configured to emit electromagnetic energy in accordance with a treatment profile configured such that the emitted electromagnetic energy heats cells or tissue of the host as the emitted electromagnetic energy is transmitted to the host via the electromagnetic energy applicator.

The controlled electromagnetic energy source may be configured to emit electromagnetic energy in accordance with a treatment profile configured such that, when the emitted electromagnetic energy is transmitted to the host via the electromagnetic energy applicator, the emitted electromagnetic energy heats cells or tissue of the host without ablating the cells or tissue of the host.

The treatment profile may define one or more transmission periods, and the controlled electromagnetic energy source is configured to emit electromagnetic energy only during each transmission period.

The treatment profile may define one or more series of pulses, each pulse having a duration equal to the transmission period.

Each transmission period may be any duration of one thousandth of a second, one second, two seconds, two to three seconds, or up to twenty seconds, or up to one or two minutes, or ten minutes.

The treatment profile may define one, five to ten, up to one hundred, or up to one thousand transmission cycles.

The treatment profile may define a plurality of transmission cycles configured such that the emitted electromagnetic energy is pulsed at a rate of 5 Hz.

The controlled electromagnetic energy source may be configured to emit electromagnetic energy in accordance with a treatment profile configured such that the emitted electromagnetic energy is emitted at a power in a range of 1-50W (e.g., 8W-10W, 2W-5W, or 3W-8W).

The controlled electromagnetic energy source may be configured to emit electromagnetic energy in accordance with a treatment profile configured such that the emitted electromagnetic energy is emitted in a series of five pulses, each having a transmission period of two seconds.

The controlled electromagnetic energy source may be configured to emit electromagnetic energy at a microwave frequency.

The controlled electromagnetic energy source may be configured to transmit electromagnetic energy in the frequency range of 1-300 GHz.

The controlled electromagnetic energy source may be configured to emit electromagnetic energy in accordance with a therapy profile configured such that the emitted electromagnetic energy is amplitude modulated.

The controlled electromagnetic energy source may be configured to emit electromagnetic energy in accordance with a therapy profile configured such that the emitted electromagnetic energy is amplitude modulated at a frequency in the range of 1-100 KHz.

The controlled electromagnetic energy source may be configured to emit electromagnetic energy in accordance with a treatment profile configured such that the emitted electromagnetic energy is amplitude modulated in accordance with a Pulse Width Modulation (PWM) or on/off keying (OOK) modulation scheme.

The controlled electromagnetic energy source may be configured to emit electromagnetic energy according to a treatment profile configured such that the emitted electromagnetic energy is frequency modulated.

The controlled electromagnetic energy source may be configured to emit electromagnetic energy according to a treatment profile configured such that the emitted electromagnetic energy is frequency modulated at a frequency in the range of 1-100 KHz.

The controlled electromagnetic energy source may be configured to receive one or more signals from one of the plurality of physiological parameter sensors and adjust the therapy profile according to the one or more received signals.

The controlled electromagnetic energy source may be configured to receive a PQRST heart rate signal from an Electrocardiogram (ECG) sensor and adjust a therapy profile according to the PQRST heart rate cycle signal, such as by dynamically synchronizing the therapy profile to correspond to a particular point in the PQRST heart rate cycle signal.

The controlled electromagnetic energy source may be configured to receive a neural oscillation signal from an electroencephalography (EEG) sensor and adjust a therapy profile according to the neural oscillation signal, for example by dynamically synchronizing the therapy profile to correspond to the neural oscillation signal.

The controlled electromagnetic energy source may be configured to receive a blood pressure signal from the blood pressure sensor and adjust the therapy profile in accordance with the blood pressure signal, for example by dynamically synchronizing the therapy profile to correspond to the blood pressure signal.

The electromagnetic energy delivery system may be configured for use with a particular treatment regime (e.g., 10W, 2 seconds, five repetitions).

The electromagnetic energy delivery system may be configured for use with a particular ambient treatment.

The electromagnetic energy transfer system may be configured for use with a minimum of 12 weeks of follow-up.

According to one aspect of the present disclosure, an electromagnetic energy delivery system is provided that combines heating and biological stimulation, such as dielectrophoresis.

The electromagnetic energy delivery system may be configured for use with high frequency electromagnetic energy including 1-300GHZ at 1-100KHz amplitude.

The electromagnetic energy transfer system may be configured for use with high frequency electromagnetic energy including 1-300GHZ modulated with an amplitude and frequency of 1-100 KHz.

The electromagnetic energy delivery system may be dynamically synchronized to correspond to a particular point in the PQRST heart cycle.

The electromagnetic energy transfer system may be dynamically synchronized to correspond to the neural oscillation signal.

The electromagnetic energy delivery system may be configured to monitor a physiological parameter and dynamically adjust the delivered energy according to the physiological parameter.

The electromagnetic energy delivery system may be configured to adjust the delivered energy on a timescale of seconds (e.g., on a timescale of 5 seconds or less, 2 seconds or less, 1 second or less, or on a timescale of fractions of a second).

According to one aspect of the present disclosure, an electromagnetic energy delivery system is provided that delivers energy in a specific timing schedule in conjunction with a mapped immune cycle to optimize an immune response.

According to one aspect of the present disclosure, an electromagnetic energy delivery system is provided that forms a treatment method in conjunction with other therapies (radiation therapy, chemotherapy, immunotherapy and traditional pharmacologic therapies), wherein the temporal delivery is optimized by measurements from a host system.

According to one aspect of the present disclosure, a method of electromagnetic energy delivery is provided that includes delivering energy in a particular timing schedule to improve an immune response.

The electromagnetic energy delivery method may include emitting electromagnetic energy according to a particular timing schedule defined by a therapy profile, and delivering the emitted electromagnetic energy to a host, wherein the therapy profile is configured such that, when the emitted electromagnetic energy is delivered to the host, the emitted electromagnetic energy stimulates and/or suppresses an immune response in the host.

The electromagnetic energy delivery method may include emitting electromagnetic energy according to a treatment profile configured such that, when the emitted electromagnetic energy is delivered to a host, the emitted electromagnetic energy stimulates and/or suppresses an immune response in the host without necrosis of cells or tissue of the host.

The electromagnetic energy delivery method may include emitting electromagnetic energy according to a treatment profile configured such that, when the emitted electromagnetic energy is delivered to a host, the emitted electromagnetic energy heats cells or tissues of the host.

The electromagnetic energy delivery method may include emitting electromagnetic energy according to a treatment profile configured such that, when the emitted electromagnetic energy is delivered to the host, the emitted electromagnetic energy heats cells or tissue of the host without ablating the cells or tissue of the host.

The treatment profile may define one or more transmission periods, and the method includes emitting electromagnetic energy only during each transmission period.

The treatment profile may define one or more series of pulses, each pulse having a duration equal to the transmission period.

Each transmission period may be any duration of one thousandth of a second, one second, two seconds, two to three seconds, or up to twenty seconds, or up to one or two minutes, or ten minutes.

The treatment profile may define one, five to ten, up to one hundred, or up to one thousand transmission cycles.

The treatment profile may define a plurality of transmission cycles configured such that the emitted electromagnetic energy is pulsed at a rate of 5 Hz.

The therapy profile may define a course of a plurality of therapies, each therapy including at least one transmission cycle, and each therapy being spaced at intervals of one or more weeks (e.g., four weeks).

The therapy profile may define one or more further transmission periods following a follow-up interval of at least 12 weeks.

The method may include emitting electromagnetic energy according to a treatment profile configured such that the emitted electromagnetic energy is emitted at a power in a range of 1-50W (e.g., 8W-10W, 2W-5W, or 3W-8W).

The method may include emitting electromagnetic energy according to a treatment profile configured such that the emitted electromagnetic energy is emitted in a series of five pulses, each pulse having a transmission period of two seconds.

The method may include transmitting electromagnetic energy at a microwave frequency.

The method may include transmitting electromagnetic energy at a frequency in the range of 1-300 GHz.

The method may include transmitting electromagnetic energy according to a treatment profile, the treatment profile configured such that the transmitted electromagnetic energy is amplitude modulated.

The method may include transmitting electromagnetic energy according to a treatment profile configured such that the transmitted electromagnetic energy is amplitude modulated at a frequency pair in a range of 1-100 KHz.

The method may include transmitting electromagnetic energy according to a treatment profile, the transmitted electromagnetic energy the treatment profile is configured to be frequency modulated.

The method may include transmitting electromagnetic energy according to a treatment profile configured such that the transmitted electromagnetic energy is frequency modulated in a frequency range of 1-100 KHz.

The method may include receiving one or more signals from one of a plurality of physiological parameter sensors and adjusting a therapy profile based on the one or more received signals.

The method may include receiving a PQRST heart rate signal from an ECG sensor and adjusting a therapy profile based on the PQRST heart rate cycle signal, such as by dynamically synchronizing the therapy profile to correspond to a particular point in the PQRST heart rate cycle signal.

The method may include receiving a neural oscillation signal from an EEG sensor and adjusting a therapy profile in accordance with the neural oscillation signal, for example by dynamically synchronizing the therapy profile to correspond to the neural oscillation signal.

The method may include receiving a blood pressure signal from a blood pressure sensor and adjusting a therapy profile based on the blood pressure signal, such as by dynamically synchronizing the therapy profile to correspond to the blood pressure signal.

The method may include adjusting the therapy profile based on measurements indicative of the immune cycle of the host.

The measurements indicative of the immune cycle of the host may include at least one of a C-reactive protein (CRP) level in blood, T regulatory cell (low state), and T effector cell (high state) measurements.

The method may include administering one or more additional therapies to the host before, during, and/or after emitting and transmitting electromagnetic energy to the host according to the treatment profile.

The one or more other therapies may include at least one of: radiotherapy, chemotherapy, immunotherapy, traditional pharmacotherapy.

The one or more other therapies may include Transcutaneous Electrical Nerve Stimulation (TENS) and/or a Frequency Rhythm Electrical Modulation System (FREMS).

According to an aspect of the present disclosure, there is provided a treatment profile for use with any of the above systems or methods of electromagnetic energy transmission.

Electromagnetic energy can be delivered to a host in a specific temporal dosage profile or regimen to elicit and/or optimize various immune responses. These regimens include temporal doses for the initial treatment phase and the healing/immune cycle phase to induce the host immune system to produce an optimized immune response in the tissue.

Electromagnetic energy can be delivered to a host by delivering energy to biological tissue to elicit an immune response for ablative or non-ablative purposes.

The applied energy may be in the form of a fixed frequency or modulated (variable frequency) continuously oscillating electromagnetic wave (CW). The frequency range may be from 1MHz to 300GHz, but is preferably in the microwave range of 0.9GHz to 16 GHz.

The pulse states include amplitude control (AM pulses) and pulse width modulation control (PWM) of the signal energy and on/off keying (OOK).

The modulation scheme includes a pulse modulation rate (1-10kHz) or a frequency modulation rate (1-100 kHz).

The treatment duration may be a single injection or multiple injections or a continuous energy dose for a course of treatment. A single injection may be one thousandth of a second, one second, two seconds, or any duration up to twenty seconds or up to one minute or two minutes or ten minutes, and then the energy delivery is stopped. Preferably, the single injection may be 2 to 3 seconds and the power level does not result in an ablation temperature.

Multiple injections are a single injection as described above repeated in multiple doses from one to one hundred or one thousand doses over a course of treatment. Preferably, the multiple injections may be five to ten times during the treatment dose.

The continuous dose may be a fixed energy level or a modulated energy level during the course of treatment. This continuous energy delivery may be pulsed one or five or fifty times per second during an ongoing therapy session. Preferably, the continuous energy transfer may be pulsed five times per second (5 Hz).

The treatment interval describes the period between treatments, which may be twice weekly, biweekly, every four weeks, monthly, fourteen days, or other multi-day period. Preferably, a four week interval between treatments would be the best choice to address some viral diseases.

Immunological measurements describe the determination of immune system parameters to measure the effectiveness of the immune system (immune cycle map), e.g., C-reactive protein (CRP) levels, T regulatory cells (low state), or T effector cells (high state) in the blood for determining the optimal treatment time (immune cycle synchronization) to elicit the strongest immune response or to reduce the therapeutic dose to maintain an effective response.

The nervous system feedback method may include electrophysiological monitoring of the heartbeat, neural oscillation (Alpha 8-13Hz, Beta 16-31Hz, Delta 0.5-3Hz, Theta 4-7Hz, Mu 7.5-12.5Hz, SMR 12.5-15.5Hz, Gamma 32-100Hz) monitoring of afferent nerves (e.g., the vagus nerve), and/or stimulation of efferent nerves, monitoring and stimulation of the central or peripheral nervous system, or synchronous processing of the applied energy such that the applied energy corresponds to a particular natural oscillation, either synchronously with the Alpha wave or partially synchronously with any natural oscillation, for example, to be in phase or out of phase or to lead or lag between sinus rhythm of the heart. Preferably, synchronization with alpha oscillations would be desirable.

In one aspect, which may be separately provided, an electromagnetic energy delivery system or method is provided that combines heating and biological stimulation, such as dielectrophoresis.

The or each system may be configured to transmit high frequency electromagnetic energy, for example electromagnetic energy having a frequency in the range 1-300GHZ and/or having an amplitude modulation in the range 1-100 KHz.

The or each system may be configured to transmit high frequency electromagnetic energy, for example electromagnetic energy having a frequency in the range 1-300GHZ and/or having amplitude and frequency modulation, for example in the range 1-100 KHz.

The or each system may be configured to transmit a particular treatment profile, for example, applying electromagnetic energy at a selected energy level and/or for a selected duration and/or for a selected number of repetitions (e.g. 10W, 2 seconds, five repetitions).

Methods of using the system to provide specific 4-week treatments may be provided.

At least 12 weeks of follow-up may be provided.

In another aspect that may be separately provided, an electromagnetic energy delivery system or method is provided that is dynamically synchronized to correspond to a particular point in a cardiac cycle (e.g., a PQRST cardiac cycle).

In another aspect that may be separately provided, an electromagnetic energy delivery system or method is provided that is dynamically synchronized to correspond to neural oscillations.

In another aspect that may be separately provided, an electromagnetic energy delivery system or method is provided that monitors a physiological parameter and dynamically adjusts the energy delivery and/or energy delivery system in response to the monitoring.

The adjustment may be in seconds or fractions of seconds.

In another aspect that may be provided independently, an electromagnetic energy delivery system or method is provided that delivers energy in conjunction with a mapped immune cycle at a particular timing schedule to optimize an immune response.

In another aspect, which may be provided independently, an electromagnetic energy delivery system or method is provided that forms a treatment method in conjunction with other therapies (radiation therapy, chemotherapy, immunotherapy and traditional pharmacologic therapies) in which the temporal delivery is optimized by measurements from the host system.

Features of one aspect may be provided in combination with features of any other aspect. Any of the systems, methods, and devices may be provided as any other of the systems, methods, and devices.

Depending on the embodiment, one or more features of any one of the claims may be combined with one or more features of any other one or more of the claims, independently of the dependencies of the claims.

Drawings

Electromagnetic treatment systems and methods will now be described, by way of non-limiting example only, with reference to the accompanying drawings, in which:

FIG. 1 is a schematic illustration of an electromagnetic energy delivery system for stimulating and/or suppressing an immune response in a host;

figure 2 is a schematic illustration of a first electromagnetic energy treatment profile that may be used in accordance with the electromagnetic energy transmission system of figure 1, the electromagnetic energy treatment profile including periodic energy transmission intervals comprising continuous wave energy;

figure 3 is a schematic illustration of a second electromagnetic energy treatment profile usable in accordance with the electromagnetic energy delivery system of figure 1, the electromagnetic energy treatment profile including periodic energy delivery intervals comprising amplitude modulated energy;

figure 4 is a schematic illustration of a third electromagnetic energy treatment profile usable in accordance with the electromagnetic energy delivery system of figure 1, the electromagnetic energy treatment profile including periodic energy delivery intervals comprising amplitude modulation energy and frequency modulation energy;

figure 5 is a schematic illustration of a fourth electromagnetic energy treatment profile that may be used in accordance with the electromagnetic energy delivery system of figure 1 that includes periodic energy delivery intervals comprising continuous wave energy and/or amplitude modulated energy and/or frequency modulated energy;

fig. 6 is a schematic illustration of an additional electromagnetic energy treatment profile that may be used in accordance with the electromagnetic energy delivery system of fig. 1, the electromagnetic energy treatment profile being arranged to occur dynamically within a particular point corresponding to a measured sinus rhythm;

FIG. 7 is a schematic diagram of a typical neural oscillation;

fig. 8 is a schematic illustration of yet another treatment profile that may be used in accordance with the electromagnetic energy transmission system of fig. 1, the electromagnetic energy treatment profile including a plurality of treatment events (epicodes) and intervals that are spaced apart over a period of time; and

FIG. 9 is a schematic of a portion of the immune system cycle.

Detailed Description

Electromagnetic treatment systems and methods will now be described by way of example only. It will be appreciated by those skilled in the art that modifications may be made to the details of any of the electromagnetic treatment systems and methods described below without departing from the scope of the invention as defined by the appended claims.

Referring initially to fig. 1, there is shown an electromagnetic energy delivery system, generally designated 7, for stimulating and/or suppressing an immune response in a host or patient, generally designated 8.

The system 7 includes a controlled electromagnetic energy source, generally indicated at 10, an electromagnetic energy applicator 9, the electromagnetic energy applicator 9 including one or more antennas for radiating and/or applying electromagnetic energy to the host 8, and a cable 9a for transmitting electromagnetic energy from the controlled electromagnetic energy source 10 to the electromagnetic energy applicator 9.

Controlled electromagnetic energy source 10 includes an electromagnetic energy source 10a, a processing resource 10b, a memory 10c, and a user interface 10 d. Memory 10c contains instructions that, when executed by processing resource 10b, cause processing resource 10b to control electromagnetic energy source 10a to emit electromagnetic energy according to one or more treatment profiles. For example, one or more treatment profiles may be stored in memory 10 c. Additionally or alternatively, one or more therapy profiles may be manually entered via user interface 10 d.

The cable 9a includes or takes the form of a waveguide for transmitting electromagnetic energy emitted by the electromagnetic energy source 10a to one or more antennas of the electromagnetic energy applicator 9. The cable 9a may comprise or take the form of a coaxial cable. The cable 9a may be flexible or rigid.

In use, the electromagnetic energy applicator 9 remains adjacent to and/or in contact with the host 8, and the processing resource 10b controls the electromagnetic energy source 10a to emit electromagnetic energy in accordance with the one or more treatment profiles for providing electromagnetic energy to the host 8 via the cable 9a and the electromagnetic energy applicator 9 in accordance with the one or more treatment profiles. In one exemplary embodiment, the controlled electromagnetic energy source 10 may be configured for applying microwave energy to the host 8, and the electromagnetic energy applicator 9 may be a microwave applicator. In such embodiments, the electromagnetic energy source 10a may be configured to emit microwave energy, and the cable 9a may be configured to transmit the emitted microwave energy to one or more antennas of the microwave applicator 9.

Fig. 2 shows a first therapy profile. In this treatment profile, there is a duration 1, which represents the entire treatment time. This may be a few seconds, minutes or hours, and may in particular be one to thirty minutes. Within this duration 1, there are a plurality of energy transfer periods 2. These periods may be a proportion of one to five seconds, ten seconds, twenty seconds, or any other period proportional to duration 1.

These energy delivery cycles may be delivered in fixed or variable numbers and may include a treatment interval 3. The interval may be between each energy delivery cycle or may be a longer interval between a series of energy delivery cycles. An example of this may be a microwave therapy system that delivers ten watts of energy over a two second period, and each energy delivery period is repeated five times and such periods are repeated for up to fifteen minutes.

Fig. 3 shows a second therapy profile. The therapy profile represents a plurality of energy delivery cycles comprising modulated energy 4, which can advantageously be dynamically varied to meet therapy requirements. The modulation may be pulse width modulation or amplitude modulation, typically 1 to 10 kHz.

Fig. 4 shows a third therapy profile in which the signal is frequency modulated 5 and transmitted temporally (temporally) 6; in this case, the low frequency signal is superimposed on the high frequency signal. This can be achieved by amplitude or frequency modulation or a superposition of both, yielding the following result: -

a. The frequency of the carrier wave, e.g. 8GHz,

am PWM modulation, e.g. 1-10KHz,

frequency modulation of c.8GHz carriers, e.g., 100-200MHz/1-100 KHz.

Fig. 5 shows a fourth therapy profile in which the above modulation scheme is dynamically applied as frequency/amplitude modulation, frequency modulated continuous wave, fixed frequency/amplitude modulation, or fixed frequency. The advantage of the spaced pulse regime is that the temperature rise can be controlled within the therapeutic thermal window. Beyond this treatment window tissue may be damaged and necrosed by thermal injury. When energy transmission is dispersed, the heat dissipation created by natural perfusion allows excess heat to be transferred away from the treatment area. This is taken into account when finding the optimal immune response as a function of the time of exposure to the electromagnetic field. Furthermore, given the optimum frequency and amplitude, the rate of temperature rise may exceed the therapeutic thermal window, and thus control of the rate of energy delivery is also advantageous.

In addition to the heating process, this modulation can also be chosen to induce biological processes, for example modulated dielectrophoretic effects (ac-osmosis and dielectrophoresis), in which the inhomogeneous electromagnetic field generated by the modulation is used to disrupt the cell membrane (cell elution and ion transport through membrane proteins). The conductance of ion channels in cells undergoing dielectrophoresis in both directions is limited. Since this mechanism acts directionally, it can be used to effectively demodulate the carrier signal when the ions behave like an electron diode. Some ion channels have a directional effect in nature and act as diodes in the absence of field gradients. Frequency modulation can be used to selectively mask various ion channels and take advantage of resonance effects.

This disruption in cell signaling can be used to promote cell death by apoptosis (rather than necrosis). This is different from standard irreversible electroporation, which applies strong electric fields of more than 0.5V/nm at nanosecond intervals to promote the formation of pores in the cell membrane by water molecules. A disadvantage of such irreversible electroporation is that it can cause muscle contraction that requires neuromuscular blockade.

Furthermore, to avoid or utilize cardioelectric interventional electromagnetic therapy, the energy delivery cycle may be dynamically assigned 12 or synchronized to correspond 11 to specific points in the PQRST heart rate cycle, as shown in fig. 6. Further, the energy delivery cycle 13 may be incremented (ramped), delayed, attenuated, or modified to create a customized therapy profile.

Physiological knowledge can also be used to adjust the treatment to meet specific requirements. For example, referring again to fig. 1, the controlled microwave energy source 10 may selectively receive input from at least one of an Electrocardiogram (ECG) sensor 30, an electroencephalogram (EEG) sensor 32, a blood pressure sensor 34, and other physiological inputs (not shown) that may be relevant to the treatment. An example of a neural waveform that may be obtained from the electroencephalogram sensor 32 is described with reference to fig. 7. These waveforms represent different states of neural activity, and these measurements can be used to synchronize therapy delivery. For example, the transmission period may be synchronized with the alpha wave to excite pseudo-beating response. Such feedback responses may be used to stimulate the immune system in response to diseases that may be masked by the immune system, such as Human Papilloma Virus (HPV), melanoma, cancer, viral lesions, and the like.

The primary electromagnetic energy transmission may also be combined with secondary auxiliary energy transmission, such as Transcutaneous Electrical Nerve Stimulation (TENS) or frequency-rhythmic electrical modulation system (FREMS), etc., to advantageously stimulate the immune system. Another adjunctive combination approach includes radiation therapy, chemotherapy, immunotherapy and traditional drug therapy. The sequence of these other treatments with temporal electromagnetic treatment can also be derived from the patient's diagnostic physiological feedback.

Another advantageous aspect of the temporal delivery of treatment has been determined by post-marketing monitoring of efficacy data relating to viral lesions. Fig. 8 shows a therapy profile in which a plurality of therapy sessions 19 are transmitted at long time intervals. The optimal treatment delivery scheduling interval 21, 22 for each treatment #1, #2, #3 is one month (4 weeks) and the optimal review period 23 after cessation of treatment is 12 weeks. It will be appreciated that this protocol facilitates optimal immunological intervention. Reducing the scheduling interval interrupts the natural immune cycle and results in diminished efficacy. An optimal treatment profile with a 12-week review period may increase the reported 76% efficacy to over 90% (not reported).

Knowledge of the immune cycle can be used to further improve efficacy or alternatively reduce the number of treatments required. Fig. 9 shows an example of a measurement result representing an immune cycle. In this figure, measurements of C-reactive protein (CRP) levels, T regulatory cells (low state), or T effector cells (high state) in the blood can be used to determine the optimal treatment time (synchronization of the immune cycles) to elicit the strongest immune response or to reduce the therapeutic dose required to produce an effective response. In fig. 9, the maximum peak 25 in the measurement results representing the immune cycle appears every 2-3 weeks. The onset 24 of the increase in the measurement indicative of the immune cycle prior to this peak 25 (i.e., the time 24 when the rate of rise in the measurement indicative of the immune cycle increases toward the peak 25) may be utilized to generate a stronger immune response or alternatively to reduce the level of therapy required to achieve the same immune response. This may also be associated with other natural periods such as Resting Heart Rate (RHR). The window of best opportunity to deliver treatment occurs between the beginning 24, which represents an increase in the measurement of the immune cycle, and the peak 25, which represents the measurement of the immune cycle 25.

Those skilled in the art will appreciate that the periodicity for temporal electromagnetic treatment may be different from feedback derived from measurements obtained by sampling and/or tracking the level of markers, or real-time using EEG, ECG real-time measurements.