Note: Descriptions are shown in the official language in which they were submitted.
CA 02671117 2009-05-27
WO 2008/066509 PCT/US2006/045491
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
1
CA 02671117 2009-05-27
WO 2008/066509 PCT/US2006/045491
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
2
CA 02671117 2009-05-27
WO 2008/066509 PCT/US2006/045491
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
3
CA 02671117 2009-05-27
WO 2008/066509 PCT/US2006/045491
[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.
4
CA 02671117 2009-05-27
WO 2008/066509 PCT/US2006/045491
[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
CA 02671117 2009-05-27
WO 2008/066509 PCT/US2006/045491
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
6
CA 02671117 2009-05-27
WO 2008/066509 PCT/US2006/045491
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 deterniined 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
7
CA 02671117 2009-05-27
WO 2008/066509 PCT/US2006/045491
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, auto-
immune 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.
8
CA 02671117 2009-05-27
WO 2008/066509 PCT/US2006/045491
[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).
9
CA 02671117 2009-05-27
WO 2008/066509 PCT/US2006/045491
[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. In 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
CA 02671117 2009-05-27
WO 2008/066509 PCT/US2006/045491
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.
11
