CHRONOTHERAPEUTIC TREATMENT PROFILING

Abstract

An electromagnetic energy delivery system is configured to deliver energy in specific timing arrangements to improve an immune response. The electromagnetic energy delivery system may comprise a controlled electromagnetic energy source and an electromagnetic energy applicator, wherein the controlled electromagnetic energy source is configured to emit electromagnetic energy according to the specific timing arrangements as defined by a treatment profile which is configured so that the emitted electromagnetic energy stimulates and/or inhibits an immune response in a host when the emitted electromagnetic energy is delivered to the host via the electromagnetic energy applicator. A method of electromagnetic energy delivery,comprises delivering energy in specific timing arrangements to improve an immune response.

Claims

1. An electromagnetic energy delivery system that delivers energy in specific timing arrangements to improve an immune response.

2. The electromagnetic energy delivery system as claimed in claim 1, comprising: a controlled electromagnetic energy source; and an electromagnetic energy applicator, wherein the controlled electromagnetic energy source is configured to emit electromagnetic energy according to the specific timing arrangements as defined by a treatment profile which is configured so that the emitted electromagnetic energy stimulates and/or inhibits an immune response in a host when the emitted electromagnetic energy is delivered to the host via the electromagnetic energy applicator.

3. The electromagnetic energy delivery system as claimed in claim 2, wherein at least one of: the controlled electromagnetic energy source is configured to emit electromagnetic energy according to a treatment profile which is configured so that the emitted electromagnetic energy stimulates and/or inhibits an immune response in the host without causing necrosis of cells or tissue of the host when the emitted electromagnetic energy is delivered to the host via the electromagnetic energy applicator; wherein the controlled electromagnetic energy source is configured to emit electromagnetic energy according to a treatment profile which is configured so that the emitted electromagnetic energy heats cells or tissue of the host when the emitted electromagnetic energy is delivered to the host via the electromagnetic energy applicator; wherein the controlled electromagnetic energy source is configured to emit electromagnetic energy according to a treatment profile which is configured so that the emitted electromagnetic energy heats cells or tissue of the host without ablating the cells or tissue of the host when the emitted electromagnetic energy is delivered to the host via the electromagnetic energy applicator.

4. (canceled)

5. (canceled)

6. The electromagnetic energy delivery system as claimed in claim 2, wherein: the treatment profile defines one or more delivery periods and the controlled electromagnetic energy source is configured to only emit electromagnetic energy only during each delivery period, and optionally the treatment profile defines one or more series of pulses, each pulse having a duration equal to the delivery period, and optionally each delivery period is one thousandth of a second, one second, two seconds, two to three seconds, or any time duration up to twenty seconds or up to one or two or ten minutes, and optionally the treatment profile defines one, five to ten, up to one hundred or one thousand delivery periods, and optionally the treatment profile defines a plurality of delivery periods configured so that the emitted electromagnetic energy is pulsed at a rate of 5 Hz.

7. The electromagnetic energy delivery system as claimed in claim 2, wherein at least one of: the controlled electromagnetic energy source is configured to emit electromagnetic energy according to a treatment profile which is configured so that the emitted electromagnetic energy is emitted with a power in the range 1-50 W, such as 8 W-10 W, 2 W-5 W or 3 W-8 W; the controlled electromagnetic energy source is configured to emit electromagnetic energy at a microwave frequency, for example wherein the controlled electromagnetic energy source is configured to emit electromagnetic energy at a frequency in a frequency range of 1-300 GHz; the controlled electromagnetic energy source is configured to emit electromagnetic energy according to a treatment profile which is configured so that the emitted electromagnetic energy is amplitude modulated, for example at a frequency in the range 1-100 KHz; the controlled electromagnetic energy source is configured to emit electromagnetic energy according to a treatment profile which is configured so that the emitted electromagnetic energy is modulated according to a pulse width modulation (PWM) or an on/off keying (OOK) modulation scheme; the controlled electromagnetic energy source is configured to emit electromagnetic energy according to a treatment profile which is configured so that the emitted electromagnetic energy is frequency modulated, for example at a frequency in the range 1-100 KHz.

8. (canceled)

9. (canceled)

10. (canceled)

11. (canceled)

12. An electromagnetic energy delivery system as claimed in claim 2, wherein the controlled electromagnetic energy source is configured to receive one or more signals from one of more physiological parameter sensors and to adapt the treatment profile according to the one or more received signals and, optionally, wherein the controlled electromagnetic energy source is configured to receive a PQRST heart rhythm signal from an ECG sensor and to adapt the treatment profile according to the PQRST heart rhythm cycle signal, for example by dynamically synchronising the treatment profile to correspond with a particular point in the PQRST heart rhythm cycle and, optionally, wherein the controlled electromagnetic energy source is configured to receive a neural oscillation signal from an EEG sensor and to adapt the treatment profile according to the neural oscillation signal, for example by dynamically synchronising the treatment profile to correspond with the neural oscillation signal and, optionally, wherein the controlled electromagnetic energy source is configured to receive a blood pressure signal from a blood pressure sensor and to adapt the treatment profile according to the blood pressure signal, for example by dynamically synchronising the treatment profile to correspond with the blood pressure signal.

13. (canceled)

14. (canceled)

15. (canceled)

16. A method of electromagnetic energy delivery, comprising delivering energy in specific timing arrangements to improve an immune response.

17. The method of electromagnetic energy delivery as claimed in claim 16, comprising: emitting electromagnetic energy according to the specific timing arrangements as defined by a treatment profile; and delivering the emitted electromagnetic energy to the host, wherein the treatment profile is configured so that the emitted electromagnetic energy stimulates and/or inhibits the immune response in the host when the emitted electromagnetic energy is delivered to the host.

18. The method of electromagnetic energy delivery as claimed in claim 17, comprising at least one of: emitting electromagnetic energy according to a treatment profile which is configured so that the emitted electromagnetic energy stimulates and/or inhibits an immune response in the host without causing necrosis of cells or tissue of the host when the emitted electromagnetic energy is delivered to the host; emitting electromagnetic energy according to a treatment profile which is configured so that the emitted electromagnetic energy heats cells or tissue of the host when the emitted electromagnetic energy is delivered to the host; emitting electromagnetic energy according to a treatment profile which is configured so that the emitted electromagnetic energy heats cells or tissue of the host without ablating the cells or tissue of the host when the emitted electromagnetic energy is delivered to the host.

19. (canceled)

20. (canceled)

21. The method of electromagnetic energy delivery as claimed in claim 17, wherein: the treatment profile defines one or more delivery periods and the method comprises only emitting electromagnetic energy during each delivery period, and optionally the treatment profile defines one or more series of pulses, each pulse having a duration equal to the delivery period, and optionally each delivery period is one thousandth of a second, one second, two seconds, two to three seconds, or any time duration up to twenty seconds or up to one or two or ten minutes, and optionally the treatment profile defines one, five to ten, up to one hundred or one thousand delivery periods, and optionally the treatment profile defines a plurality of delivery periods configured so that the emitted electromagnetic energy is pulsed at a rate of 5 Hz, and optionally the treatment profile defines a schedule of treatments, each treatment comprising at least one delivery period, and each treatment being separated by an interval of one or more weeks, for example four weeks, and optionally the treatment profile defines one or more further delivery periods after a follow-up interval of at least 12 weeks.

22. The method of electromagnetic energy delivery as claimed in claim 17, comprising at least one of: emitting electromagnetic energy according to a treatment profile which is configured so that the emitted electromagnetic energy is emitted with a power in the range 1-50 W, such as 8 W-10 W, 2 W-5 W or 3 W-8 W; emitting electromagnetic energy at a microwave frequency, for example at a frequency in the range 1-300 GHz; emitting electromagnetic energy according to a treatment profile which is configured so that the emitted electromagnetic energy is amplitude modulated for example at a frequency in the range 1-100 KHz; emitting electromagnetic energy according to a treatment profile which is configured so that the emitted electromagnetic energy is frequency modulated for example at a frequency in the range 1-100 KHz.

23. (canceled)

24. (canceled)

25. (canceled)

26. The method of electromagnetic energy delivery as claimed in claim 17, comprising: receiving one or more signals from one of more physiological parameter sensors; and adapting the treatment profile according to the one or more received signals.

27. The method of electromagnetic energy delivery as claimed in claim 26, comprising: receiving a PQRST heart rhythm signal from an ECG sensor; and adapting the treatment profile according to the PQRST heart rhythm cycle signal, for example by dynamically synchronising the treatment profile to correspond with a particular point in the PQRST heart rhythm cycle.

28. The method of electromagnetic energy delivery as claimed in claim 26, comprising: receiving a neural oscillation signal from an EEG sensor; and adapting the treatment profile according to the neural oscillation signal, for example by dynamically synchronising the treatment profile to correspond with the neural oscillation signal.

29. The method of electromagnetic energy delivery as claimed in claim 26, comprising: receiving a blood pressure signal from a blood pressure sensor; and adapting the treatment profile according to the blood pressure signal, for example by dynamically synchronising the treatment profile to correspond with the blood pressure signal.

30. The method of electromagnetic energy delivery as claimed in claim 17, comprising adapting the treatment profile according to a measurement representative of an immune cycle of the host.

31. The method of electromagnetic energy delivery as claimed in claim 30, wherein the measurement representative of the immune cycle of the host comprises at least one of measurement of C-reactive protein (CRP) levels in the blood, T-regulatory cells (low state) and T-effector cells (high states).

32. The method of electromagnetic energy delivery as claimed in claim 17, comprising administering one or more other therapies to the host, before, during and/or after emitting electromagnetic energy according to the treatment profile and delivering the electromagnetic energy to the host.

33. The method of electromagnetic energy delivery as claimed in claim 32, wherein the one or more other therapies comprise at least one of: radiotherapy, chemotherapy, immunotherapy, traditional pharmacological therapies, transcutaneous electrical nerve stimulation (TENS) and frequency rhythmic electrical modulation systems (FREMS).

34. A treatment profile for use with the electromagnetic energy delivery system as claimed in claim 2 or the method of electromagnetic energy delivery as claimed in claim 17.

Description

BRIEF DESCRIPTION OF DRAWINGS

[0106] Electromagnetic treatment systems and methods will now be described by way of non-limiting example only with reference to the accompanying drawings of which:

[0107] FIG. 1 is a diagrammatic illustration of an electromagnetic energy delivery system for stimulating and/or inhibiting an immune response in a host;

[0108] FIG. 2 is a diagrammatic illustration of a first electromagnetic energy treatment profile according to which the electromagnetic energy delivery system of FIG. 1 may be used, the electromagnetic energy treatment profile including periodic energy delivery intervals containing continuous-wave energy;

[0109] FIG. 3 is a diagrammatic illustration of a second electromagnetic energy treatment profile according to which the electromagnetic energy delivery system of FIG. 1 may be used, the electromagnetic energy treatment profile including periodic energy delivery intervals containing amplitude modulated energy;

[0110] FIG. 4 is a diagrammatic illustration of a third electromagnetic energy treatment profile according to which the electromagnetic energy delivery system of FIG. 1 may be used, the electromagnetic energy treatment profile including periodic energy delivery intervals of amplitude modulated energy and frequency modulated energy;

[0111] FIG. 5 is a diagrammatic illustration of a fourth electromagnetic energy treatment profile according to which the electromagnetic energy delivery system of FIG. 1 may be used, the electromagnetic energy treatment profile including periodic energy delivery intervals of continuous-wave energy and/or amplitude modulated energy and/or frequency modulated energy;

[0112] FIG. 6 is a diagrammatic illustration of additional electromagnetic energy treatment profiles according to which the electromagnetic energy delivery system of FIG. 1 may be used, the electromagnetic energy treatment profiles being arranged to dynamically occur within specific points corresponding with a measured sinus rhythm;

[0113] FIG. 7 is a diagrammatic illustration of typical neural oscillations;

[0114] FIG. 8 is a diagrammatic illustration of a yet further treatment profile according to which the electromagnetic energy delivery system of FIG. 1 may be used, the electromagnetic energy treatment profile including multiple treatment episodes and intervals spaced across a period of time; and

[0115] FIG. 9 is a diagrammatic illustration of part of an immune system cycle.

DETAILED DESCRIPTION OF THE DRAWINGS

[0116] Electromagnetic treatment systems and methods will now be described purely by way of example. One of ordinary skill in the art will understand that modifications of the details of any of the electromagnetic treatment systems and methods described below may be made without departing from the scope of the invention as defined by the appended claims.

[0117] Referring initially to FIG. 1 there is shown an electromagnetic energy delivery system generally designated 7 for stimulating and/or inhibiting an immune response in a host or patient generally designated 8.

[0118] The system 7 includes a controlled electromagnetic energy source generally designated 10, an 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.

[0119] The controlled electromagnetic energy source 10 includes an electromagnetic energy source 10a, a processing resource 10b, a memory 10c, and a user interface 10d. The memory 10c contains instructions which, when executed by the processing resource 10b, cause the processing resource 10b to control the electromagnetic energy source 10a to emit electromagnetic energy according to one or more treatment profiles. The one or more treatment profiles may, for example, be stored in the memory 10c. Additionally or alternatively, the one or more treatment profiles may be manually input via the user interface 10d.

[0120] The cable 9a includes, or takes the form of, a waveguide for transmitting the electromagnetic energy emitted by the electromagnetic energy source 10a to the one or more antennas of the electromagnetic energy applicator 9. The cable 9a may include, or take the form of, a co-axial cable. The cable 9a may be flexible or rigid.

[0121] In use, the electromagnetic energy applicator 9 is held 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 according to one or more of the treatment profiles for delivery of electromagnetic energy to the host 8 according to the one or more of the treatment profiles via the cable 9a and the electromagnetic energy applicator 9. In an 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 an embodiment, 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 the one or more antennas of the microwave applicator 9.

[0122] A first treatment profile is illustrated in FIG. 2. In this treatment profile there is a time duration 1 which represents the overall treatment time. This may be in seconds, minutes or hours and specifically may be one to thirty minutes. Within this time duration 1 a number of energy delivery periods 2 exist. These periods may be proportions of one second to five seconds, ten seconds, twenty seconds or any other period that is a proportion of the time duration 1.

[0123] A fixed or variable number of these energy delivery periods may be delivered and may include a treatment interval 3. The interval can be between each energy delivery period or could be a longer interval between a series of energy delivery periods. An example of this would be a microwave treatment system that delivers ten Watts of energy for a period of two seconds and each energy delivery period is repeated five times, with this cycle being repeated for up to fifteen minutes.

[0124] A second treatment profile is illustrated in FIG. 3. This treatment profile represents a number of energy delivery periods containing modulated energy 4, advantageously the energy delivery period can be dynamically altered to suit treatment requirements. The modulation may be pulse width modulation or amplitude modulation typically from 1 to 10 kHz.

[0125] A third treatment profile is illustrated in FIG. 4 in which the signals are frequency modulated 5 and delivered temporally 6; in this case a lower frequency signal is superimposed on a high frequency signal. This can be achieved as amplitude or frequency modulation or superposition of both resulting in the following: [0126] a. Carrier, e.g. 8 GHz, [0127] b. AM PWM modulation, e.g. 1-10 KHz, [0128] c. Frequency modulation of 8 GHz carrier, e.g. 100-200 MHz/1-100 KHz

[0129] A fourth treatment profile is illustrated in FIG. 5 in which the foregoing modulation schemes are dynamically applied to be frequency modulated/amplitude modulated, frequency modulated continuous wave, fixed frequency/amplitude modulated or fixed frequency. Advantages of an interval pulsing scheme are that the temperature rise can be controlled to be within a therapeutic thermal window. Exceeding the therapeutic window can be detrimental to the tissues and cause necrosis though heat damage. When interspersing the energy delivery, the heat dissipation through natural perfusion allows excess heat to be transported away from the treatment zone. This is of consideration when optimal immune responses are found to be a function of exposure time to the electromagnetic field. Additionally, the rate of temperature rise at given optimal frequencies and amplitudes may exceed the therapeutic thermal window thus control over the rate of energy delivery is also an advantage.

[0130] This modulation may be chosen to effect a biological process in addition to a heating process, e.g. a modulated dielectrophoretic effect (AC electro-osmosis and dielectrophoresis) where non-uniform electromagnetic fields as a result of modulation are used to disrupt cellular membranes (cellular elution and ionic transportation via membrane proteins). The ion channels in cells experiencing dielectrophoresis are limited in their ability to conduct in both directions. As this mechanism can act directionally it can be utilised to effectively demodulate carrier signals as the ions behave akin to an electronic diode. Some ion channels intrinsically act directionally and behave as diodes in the absence of field gradients. The modulation of frequency can be utilised to selectively cover a variety of ion channels and to take advantage of resonant effects.

[0131] This disruption in cellular signalling can be utilised to promote cell death via apoptosis as opposed to necrosis. This differs from standard irreversible electroporation where a very strong electrical field of more than 0.5 V/nm is applied in nanosecond intervals to motate water molecules forming pores in the cellular membrane. Irreversible electroporation has the disadvantage of inducing muscle contractions requiring neuromuscular blockade.

[0132] In addition, to avoid or utilise electrocardial involvement in electromagnetic treatments, energy delivery periods can be dynamically allocated 12 or synchronised to correspond with a particular point in a PQRST heart rhythm cycle 11 as illustrated in FIG. 6. In addition, the energy delivery periods 13 can be ramped, delayed, decayed or modified to create bespoke treatment profiles.

[0133] Knowledge of the physiology can also be used to tailor the treatment to meet particular requirements. For example, referring back to FIG. 1, the controlled microwave energy source 10may optionally receive an 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) which may be relevant to a treatment. An example of neural waveforms available from an electroencephalogram sensor 32 is described with reference to FIG. 7. These waveforms represent different states of neural activity and use of these measurements may be made to synchronise treatment delivery. For example, the delivery period could synchronise with Alpha waves to stimulate a pseudo-throbbing response. This feedback response can be used to stimulate the immune system in dealing with conditions that may be masked from the immune system, e.g., HPV, Melanoma, carcinoma, viral lesions.

[0134] Primary electromagnetic energy delivery could also be combined with a secondary adjunctive energy delivery such as transcutaneous electrical nerve stimulation (TENS) or Frequency rhythmic electrical modulation systems (FREMS) to advantageously stimulate the immune system. Another adjunctive combination method include radiotherapy, chemotherapy, immunotherapy and traditional pharmacological therapies. The sequencing of these other therapies with the temporal electromagnetic treatment may also be derived from diagnostic physiological feedback from the patient.

[0135] A further advantageous aspect to the temporal delivery of treatments has been determined via post market surveillance of treatment efficacy data relating to viral lesions. FIG. 8 shows a treatment profile in which a number of treatment sessions 19 are delivered spaced apart by long time intervals. The optimal treatment delivery schedule spacing 21, 22 for each treatment #1, #2, #3 is one month (4 weeks) and the optimum review period 23 after cessation of treatment is 12 weeks. It is understood that this regimen promotes the optimum immune involvement. Reducing the schedule spacing interrupts the natural immune cycle and results in a less efficacious outcome. This optimum treatment profile with 12 week review cycle can raise the 76% efficacy reported to over 90% (unreported).

[0136] Knowledge of the immune cycle can be used to further boost the efficacy or alternatively reduce the number of treatments required. An example of a measure representative of the immune cycle is illustrated in FIG. 9. In this illustration, a measurement of C-reactive protein (CRP) levels in the blood, T-regulatory cells (low state) or T-effector cells (high states) can be used to determine the optimal time for treatment (immune cycle synchronisation) to elicit either the strongest immune response or to reduce the treatment dose required to produce an effective response. In FIG. 9, the largest peak 25 in the measure representative of the immune cycle occurs once every 2-3 weeks. The onset 24 of the growth in the measure representative of the immune cycle which precedes this peak 25 (i.e. the time 24 when the rise rate in the measure representative of the immune cycle increases towards the peak 25) can be utilised to create a stronger immune response, or alternatively to reduce the treatment levels required to achieve the same immune response. This may also correlate with other natural cycles such as resting heart rate (RHR). The optimal window of opportunity for administering a treatment occurs between the onset 24 of the growth in the measure representative of the immune cycle and the largest peak 25 in the measure representative of the immune cycle 25.

[0137] One of ordinary skill in the art will understand that the periodicity used for the temporal electromagnetic treatment may vary from the feedback derived from measurements taken by sampling and or tracking the levels of a marker, or in realtime with the use of EEG, ECG realtime measurements.