METHOD OF USING MAGNETIC FIELDS TO UNIFORMLY INDUCE ELECTRIC FIELDS FOR THERAPEUTIC PURPOSES

BACKGROUND

Field of the Invention

[0001] The present invention relates generally to the use of magnetic fields, and more particularly, to methods of using magnetic fields to uniformly induce electric fields for therapeutic purposes.

Related Art

[0002] Exposure to electromagnetic fields (EMFs) has become an increasingly useful tool in the treatment of many medical conditions. For example, exposure to time-varying magnetic fields is an accepted method of accelerating bone and wound healing. For example, EMFs may be used to limit damage to a heart during a heart attack and to protect bone marrow during chemotherapy and x-ray therapy for destruction of tumors.

[0003] When an EMF is applied to a cell, the electric field acting on the cell is the main mechanism by which the EMF affects the cell. For most purposes, the use of a low frequency time-varying magnetic field is the most convenient and controllable method of causing an electric field to appear across the tissue to be treated. A time-varying magnetic field may be created external to the body (for example with a pair of coils and a time-varying current source). When this field enters a body, it induces (by Faraday's Law) a time- varying electric field. It is fairly straightforward to create a uniform magnetic field in a body because the body's magnetic properties are quite uniform. However, the induced electric field is very non-uniform because the body's electrical conductivity may vary enormously from organ to organ {e.g., lung to heart) and within an organ (e.g., heart muscle to heart blood).

[0004] This lack of uniformity represents a serious limitation in the therapeutic application of time- varying magnetic fields. A good example of this limitation is in the use of magnetic fields to limit damage to the heart after an ischemic event (e.g., heart attack). Application of the magnetic field for a period of 30 minutes or more induces activation of heat shock proteins (hsps) in the cells of the heart muscle. These hsps act to protect the heart from cell death (necrosis) during the period in which the stoppage of blood flow (ischemia) causes cell

stress. The problem that exists with this technique is that the induced electric fields vary so greatly that in many regions of the heart the induced electric field is not great enough to cause the cells to produce hsps. For example, the lung is a high resistance region adjacent to the heart. As a result, if the induced electric field passes through both the lung and heart, most of the field will appear across the lung and very little in the heart. Even if the induced electric field is applied in a direction that does not cross the lung, there will be regions in the heart that do not experience a significant electric field because the blood has such a low conductivity relative to the heart muscle.

[0005] Which regions of an organ do not experience a significant electric field depends critically upon the direction of the applied magnetic field, and thus the direction of the induced EMF. One proposed solution may be to simply apply fields in the x, y and z directions simultaneously. This however does not work since the vector sum of these fields would be simply a new magnetic field in a single direction.

SUMMARY

[0006] According to a first broad aspect of the present invention, there is provided a method of delivering an electric field to a body, comprising delivering a polarized magnetic field in a first direction to a body and directed at a desired target within the body; and changing the delivery direction of the magnetic field to a second direction directed at the desired target to induce an electric field across the desired target.

[0007] According to a second broad aspect of the present invention, there is provided a method of delivering an electric field to a body, comprising delivering a first magnetic field from a first coil in a first orientation to a body and directed at a desired target within the body; and delivering a second magnetic field from a second coil in a second orientation directed at the desired target within the body to induce an electric field across the desired target, wherein only one magnetic field is delivered to the body at any one time.

[0008] According to a third broad aspect of the present invention, there is provided a method of delivering an electric field to a body, comprising delivering a first magnetic field from a first coil in a first orientation to a body and directed at a desired target within the body; delivering a second magnetic field from a second coil in a second orientation directed at the desired target within the body; and delivering a third magnetic field from a third coil in

a third orientation directed at the desired target within the body to induce an electric field across the desired target.

[0009] According to a fourth broad aspect of the present invention, there is provided an apparatus for delivering an electric field to a body, comprising a means for delivering a first magnetic field from a first coil in a first orientation to a body and directed at a desired target within the body; a means for delivering a second magnetic field from a second coil in a second orientation directed at the desired target within the body to induce an electric field across the desired target; and a means for alternating a current between the first coil and the second coil.

BRIEF DESCRIPTION OF THE DRAWINGS

[0010] The invention will be described in conjunction with the accompanying drawings, in which:

[0011] FIG. 1 is a schematic representation of a coil arrangement in accordance with an embodiment of the present invention in which 2 pairs of coils are oriented perpendicular to each other;

[0012] FIG. 2 is a schematic representation of a coil arrangement in accordance with an embodiment of the present invention in which 2 pairs of coils are oriented perpendicular to each other;

[0013] FIG. 3 is a schematic representation of a coil arrangement in accordance with an embodiment of the present invention using 3 pairs of coils;

[0014] FIG. 4 is a graph of on/off intervals and percentage of maximum response for different models of EMF-induced effects, including hypoxia protection (circles) and changes in enzyme activity (squares);

[0015] FIG. 5 is a table showing the effect of EMFs on damage after a heart attack using vertical and horizontal linear EMF exposure polarization; and

[0016] FIG. 6 is a table showing the effect of EMFs on damage after a heart attack using vertical circular, horizontal circular and alternating vertical and horizontal linear EMF exposure polarization.

DETAILED DESCRIPTION

[0017] It is advantageous to define several terms before describing the invention. It should be appreciated that the following definitions are used throughout this application.

Definitions

[0018] Where the definition of terms departs from the commonly used meaning of the term, applicant intends to utilize the definitions provided below, unless specifically indicated.

[0019] For the purposes of the present invention, the term "linearly polarized magnetic field" refers to a magnetic field that varies in time but whose direction is always directed along a given fixed line.

[0020] For the purposes of the present invention, the term "circularly polarized magnetic field" refers to a magnetic field whose field vector rotates about a fixed axis and appears to go around in a circle.

[0021] For the purposes of the present invention, the term "linear vertical field" refers to a linearly polarized field whose field vector is oriented in the vertical direction.

[0022] For the purposes of the present invention, the term "linear horizontal field" refers to a linearly polarized field whose field vector is oriented in the horizontal direction.

[0023] For the purposes of the present invention, the term "circular vertical field" refers to a circularly polarized field in which the field vector rotates about the vertical axis.

[0024] For the purposes of the present invention, the term "circular horizontal field" refers to a circularly polarized field in which the field vector rotates about the horizontal axis.

[0025] For the purposes of the present invention, the term "uniform electric field" refers to an induced electric field which is essentially constant in all of the tissues to be treated.

[0026] For the purposes of the present invention, the term "orientation" refers to the arrangement, configuration, direction, etc. of the element identified, such as the orientation of the magnetic field.

Description

[0027] The present invention provides a method and apparatus for delivering an electric field to a body by delivering a first magnetic field from a first coil in a first orientation to a body and directed at a desired target within the body, and delivering a second magnetic field from a second coil in a second orientation directed at the desired target within the body to induce an electric field across the desired target, wherein only one magnetic field is delivered to the body at any one time. The present invention provides an increase in the uniformity of the induced electric field. Increased uniformity is beneficial because, if the induced electric field is not uniform, its value may (in some regions of the tissue to be treated) fall below the threshold value necessary to induce beneficial biological effects, and thus the treatment may be only partially effective.

[0028] Under certain conditions, the effectiveness of a magnetic field treatment (whose duration may be, for example, from approximately 30 minutes to approximately 60 minutes duration) may be significantly enhanced if the direction of the magnetic field direction is changed in time during the treatment.

[0029] A linearly polarized magnetic field may be used that alternately switches back and forth from one direction {e.g., vertical) to a perpendicular direction {e.g., horizontal). In other embodiments of the present invention, the delivery direction of the field may be switched approximately 90 degrees +/- 30 degrees with respect to the original direction of the field.

[0030] In some embodiments of the present invention, the timing of the exposure is an important element of an effective treatment. In some embodiments of the present invention, the magnetic field remains in any given direction for at least 5 seconds before switching the delivery direction to a new direction. A change in the delivery direction of the magnetic field may induce an electric field across the desired target. In some embodiments of the present invention, the minimum time of exposure in any direction is greater than 10 seconds before switching the delivery direction. In some embodiments of the present invention, the

maximum time of exposure in any direction is 300 seconds or more before switching the delivery direction. Thus, a suitable duration for exposure in any one direction may be from approximately 5 seconds to approximately 300 seconds or more, preferably from approximately 10 to approximately 30 seconds. The timeframes for exposure may be modified depending on the tissues or cells being treated, the frequency of exposure, and depending on the length of time between treatments.

[0031] A magnetic field for use in the present invention may be generated with, for example, 2 pairs of coils that are oriented perpendicular to each other and in which an AC current alternately flows in one pair and then in the perpendicular pair. Such an arrangement provides a field in two perpendicular directions i.e. the planar orientation of one of the magnetic fields is substantially perpendicular to the planar orientation of the other magnetic field. FIGS. 1 and 2 provide schematic representations of coil arrangements in accordance with embodiments of the present invention in which 2 pairs of coils are oriented perpendicular to each other.

[0032] One goal of the present invention is to obtain a uniform induced electric field. Thus, according to an embodiment of the present invention, it is preferable to start with a reasonably uniform magnetic field. Current flowing in a single coil may be used in the present invention, although such an arrangement creates a relatively non-uniform magnetic field, thus introducing some of the problems mentioned above. A pair of coils which lie in planes that are perpendicular to each other yields much more uniform magnetic fields when current flows in them in such a way that the fields of the two coils are additive in the region between the coils.

[0033] In another arrangement of the present invention, two pairs of coils are arranged perpendicular to each other and the AC current in one pair is 90 degrees out of phase with the other pair of coils so that a circular polarized magnetic field is created. According to embodiments of the present invention, the currents may be other than 90 degrees out of phase, such as 90 degrees +/- 30 degrees. If the currents are out of phase, but not 90 degrees out of phase, then the resultant field may be considered to be composed of a circular polarized field (caused by that component of the currents which are 90 degrees out of phase) and a linearly polarized magnetic field (caused by the component of the currents which are in phase with each other). This is generally less effective than the 90 degree out of phase condition. However, such an arrangement is encompassed within the scope of the present

invention. Thus, for example, a magnetic field is created which rotates from, for example, the vertical direction to the horizontal direction continuously. Such an arrangement provides a field in two perpendicular directions.

[0034] Another embodiment of the present invention provides for a circular polarized magnetic field in which the circular field has a plane with a direction that is switched in time to a perpendicular direction. This may be accomplished with three pairs of coils oriented perpendicular to each other. Such an arrangement may be seen in FIG. 3. These coils may be designated coil pair 302, coil pair 304 and coil pair 306, respectively. In an exemplary embodiment of the present invention, AC current flows first in coil pairs 302 and 304. The currents in these coils may be 90 degrees out of phase. After a period of time, which may be, for example, at least approximately 5 seconds, preferably greater than approximately 10 seconds, but typically not greater than approximately 300 seconds, the current is switched so that coil pair 302 and coil pair 306 are energized with or without 90 degree out of phase currents. In an embodiment of the present invention, coil pair 304 and coil pair 306 are also 90 degrees out of phase. Such an arrangement provides a field in three perpendicular directions.

[0035] Magnetic fields as used in embodiments of the present invention include such fields ranging in frequency from approximately 10 Hz to 5 GHz. The type of magnetic field used in a given embodiment may be determined by cost of equipment and ease of application. According to embodiments of the present invention, the frequency of the applied magnetic field is at least approximately 20 Hz. In other embodiments of the present invention, the frequency of the applied magnetic field may be approximately 20 Hz to approximately 60 Hz, or greater. The current in the coils should be great enough to create a magnetic field in the tissue being treated which is sufficient to induce an electric field at 60 Hz which is greater than about 10 microvolts/meter. At frequencies above 60 Hz, the magnetic field may remain the same as that calculated above for the 60 Hz condition. At frequencies below 60 Hz, the magnetic field should increase inversely with the decrease in frequency. Thus, for example, at 20 Hz the magnetic field should be 3 times more than needed at 60 Hz.

[0036] For use in the present invention, any suitable magnetic field generating coils may be used, including, Helmholtz coils, etc. FIGS. 1, 2 and 3 show schematic representations of coil arrangements, and should not be construed to limit the application of the present

invention to such arrangements. Coils of the present invention may be of various shapes and arrangements now known or later developed.

[0037] Embodiments of the present invention may use an athermal EMF, i.e. a field which causes no increase in tissue temperature. An athermal EMF can create the desired biological effect, such as a modification of the hsp concentrations, when field parameters, e.g. amplitude, frequency, and waveform, are constant for periods or intervals of at least several seconds. Athermal EMF applied to tissue having on-off cycles ranging from approximately 0.1 second to approximately 1 to 2 seconds will have no biological effect. In one embodiment, athermal EMF applied to tissue having on-off cycles greater than 10 seconds yield a desired biological effect.

[0038] The present invention may be used in various treatment protocols including single treatments or multiple treatments on one day, in one week, or over several weeks or months, depending on the particular application. A single treatment may be provided for a period of seconds, minutes or hours depending on the particular application.

[0039] EMF exposures according to the present invention may be used to target and enhance therapeutic or palliative treatments including, without limitation, physical, chemical, radiative or gene therapies applied for the treatment and prevention of diseases. The present invention improves the effectiveness of magnetic field therapy when treating various organs in the body for conditions including cancer, arthritis, psoriasis, diabetes mellitus, autoimmune diseases, heart attacks, etc.

[0040] Application of EMFs activate cell signaling pathways resulting in the production of stress proteins. These stress proteins protect the cell against deleterious stimuli. However, prolonged or repetitive stimulation causes the cells to diminish or down-regulate this stress response. This leaves the cells in a more sensitive state after EMF exposure. Therefore, any therapeutic agent applied to damage these cells will be more effective. Thus, the present invention may be used in combination methods which relate the use of EMFs and temporal constancy requirements to the ability to focus the biological effect of an EMF. Such methods have the ability to selectively either protect or de-protect a volume of tissue depending on the parameters of the EMF exposure applied. Embodiments of the present invention may further the targeting of specific volumes of tissue to focus the effect of the chosen EMF exposure.

[0041] For cancer, the present invention may also be used in combination with anti-cancer agents or chemotherapy drugs or in combination with radiation therapy. The application of long-term EMF exposure according to embodiments of the present invention to tumor cells may make the tumor cells more susceptible to subsequent treatments using toxic chemicals, such as taxol. In one embodiment, the cells are exposed to the EMF prior to the administration of taxol, which leads to a very significant increase in the toxic effect of taxol. For example, chick embryos exposed an EMF for 48 continuous hours prior to injection of taxol and 48 continuous hours after injection, showed an increase in the toxic effect of taxol.

[0042] It will be obvious to a person skilled in the art upon reading this application that embodiments could be applied to other medical procedures using deleterious stimuli which are intended to destroy or modify a chosen volume of tissue or biological cells for a reason other than cancer therapy. Some examples of this are benign growths, keloids, arterio- venous malformations, benign prostatic hyperplasia, splenomegaly, etc. Further, the adjuvant application of embodiments is not only for treatment intended to cure, but could also be to aid in palliative measures, for example, with ionizing radiation used for reducing the mass or growth of a tumor to temporarily relieve symptoms caused by that mass.

[0043] In addition, when time varying magnetic fields are used as a prophylactic to protect against hypoxic, UV light,x-ray stresses or other adverse stresses, the present invention makes the time varying magnetic fields more effective. The protection that is induced, however, is highly dependent on the dose of the EMF used. Short-term field exposures (ranging from 20 minutes to several hours) are protective against stress and can also reduce cytokine expression which leads to swelling and inflammation. Long-term prior exposures (greater than 12 hours) can cause cells, tissues and organs to be more susceptible to subsequent damage from stress. The degree of protection or increased susceptibility depends upon the time duration of exposure and the strength of the applied EMF.

[0044] The following data show the impact of the present invention. Studies were conducted to investigate the ability of induced electric fields in a rat heart to protect against a simulated heart attack. In this study, magnetic fields were applied in only one of 2 directions (vertical or horizontal linear, relative to the rat). As may be seen in the data presented in Table 1 of FIG. 5, no statistically significant reduction in necrotic heart tissue was observed. This was because large regions of the heart muscle were not being exposed to an electric field capable of inducing a biological effect (in this case, ischemic protection).

[0045] In further studies, however, it was discovered that by changing in time the direction of the applied magnetic field, such that more than one plane of magnetic field application was used during the exposure, a three-fold improvement in salvage of the myocardial tissue could be obtained. In this second study, rats were exposed either to a circularly polarized field (in the vertical or horizontal plane), or a field in which the direction of the applied magnetic field switched from vertical to horizontal every 30 seconds. In these experiments, shown in Table 2 of FIG. 6, a reduction of -15% in necrotic tissue was observed compared to the reduction of ~5% in Table 1 of FIG. 5.

[0046] As is summarized in Table 1 of FIG. 5 and Table 2 of FIG. 6, all of the linear, one- directional EMFs (vertical or horizontal) were only marginally effective in reducing the infarct size following simulated heart attack. This is to be expected given the non-uniform nature of the electric fields induced by these one-directional exposures. However, as summarized in Table 2 of FIG. 6 the other EMF exposures tested (vertical circular, horizontal circular or alternating) resulted in significant improvements in reduction of heart damage. These findings support the notion that multi-direction EMF exposures are capable of inducing more uniform electric fields, and thus, significant biological effects in the tissue.

[0047] According to an embodiment of the present invention, a multi-directional, magnetic field exposure approach may be coupled with specific timing protocols in order to increase its effectiveness. Specific time scales for exposure induce a more robust biological effect. It has previously been described that if a magnetic field exposure is temporally constant for some minimal period of time, for example, greater than approximately 10 seconds, a full biological effect may be achieved. FIG. 4 shows this phenomenon for a number of different models of EMF-induced effects, including hypoxia protection (circles) and changes in enzyme activity (squares). As may be seen in FIG. 4, according to an embodiment of the present invention, a minimum on/off time interval of approximately 10 seconds achieves a maximum induced biological effect. Thus, in an embodiment of the present invention, the direction of the field is not switched on time scales less than about 10 seconds. Ih other embodiments, however, the time scales may be more or less than 10 seconds between switching field direction.

[0048] Furthermore, whereas all uniaxial exposures create inhomogeneous induced electric fields in the tissue, most multi-axial exposures do this as well. This is because, when tissues are exposed to multi-directional fields simultaneously, the actual applied field is a sum

of all the different-direction applied fields, resulting in a one-directional magnetic field exposure vector. In order to avoid this scenario, the multi-directional exposures may be applied other than simultaneously. One way to achieve this is through the use of a circularly- polarized magnetic field, whose direction continually changes {e.g., vertical or horizontal circular shown in Table 2 above). However, this method yields induced electric fields that are more difficult to quantify and is not always the most effective means of inducing electric fields in tissue, since there may still be regions with sub-threshold induced electric fields. Instead, according to an embodiment of the present invention, the use of applied magnetic fields (linear or circular), whose direction/orientation changes at certain time intervals to a second plane of exposure (as evidenced by the alternating linear data given in Table 2) is provided. If a magnetic field exposure is temporally constant for some minimal period of time (for example, greater than approximately 10 seconds), a full biological effect may be achieved.

[0049] Although the present invention has been fully described in conjunction with several embodiments thereof with reference to the accompanying drawings, it is to be understood that various changes and modifications may be apparent to those skilled in the art. Such changes and modifications are to be understood as included within the scope of the present invention as defined by the appended claims, unless they depart therefrom.