U.S. patent application number 10/579174 was filed with the patent office on 2009-03-05 for method and device for treating osteoarthritis and cartilage disease, defects, and injuries in the human hip.
Invention is credited to Carl T. Brighton, Solomon R. Pollack.
Application Number | 20090062885 10/579174 |
Document ID | / |
Family ID | 34623117 |
Filed Date | 2009-03-05 |
United States Patent
Application |
20090062885 |
Kind Code |
A1 |
Brighton; Carl T. ; et
al. |
March 5, 2009 |
Method and device for treating osteoarthritis and cartilage
disease, defects, and injuries in the human hip
Abstract
A method of determining the voltage and current required for the
application of specific and selective electric and electromagnetic
signals to diseased articular cartilage in the treatment of
osteoarthritis, cartilage defects due to trauma or sports injury,
or used as an adjunct with other therapies (cell transplantation,
tissue-engineered scaffold, growth factors, etc.) for treating
cartilage defects in the human hip joint and a device for
delivering such signals to a patient's hip. Anatomic, analytical,
and planar circuit models are developed to determining the
impedances, conductivities, and current flows in the human hip
joint and its surrounding soft tissues and skin that are required
to produce a 20 mV/cm electric field in the synovium and articular
cartilage of the human hip. The voltage of the signal applied to
the surface electrodes or to a coil(s) or solenoid is varied based
on the size of the hip joint; larger hip joints require larger
voltages to generate the effective electric field.
Inventors: |
Brighton; Carl T.; (Malvern,
PA) ; Pollack; Solomon R.; (North Wales, PA) |
Correspondence
Address: |
WOODCOCK WASHBURN LLP
CIRA CENTRE, 12TH FLOOR, 2929 ARCH STREET
PHILADELPHIA
PA
19104-2891
US
|
Family ID: |
34623117 |
Appl. No.: |
10/579174 |
Filed: |
November 12, 2004 |
PCT Filed: |
November 12, 2004 |
PCT NO: |
PCT/US04/37926 |
371 Date: |
November 12, 2008 |
Current U.S.
Class: |
607/50 ;
128/898 |
Current CPC
Class: |
A61N 1/326 20130101;
A61N 1/40 20130101 |
Class at
Publication: |
607/50 ;
128/898 |
International
Class: |
A61N 1/00 20060101
A61N001/00; A61B 19/00 20060101 A61B019/00 |
Claims
1. A method of treating disease tissue in a human through the
application of a specific and selective electric or electromagnetic
field to the disease tissue in the human, comprising the steps of:
a. Determining the voltage and current output that produces a 20
mV/cm electric field in the diseased tissue of the human; b.
Constructing an anatomic model of human diseased tissue showing all
the pertinent tissues and structures through which the current
passes between the skin overlying one side of the diseased tissue
through the skin on the opposite side of the diseased tissue; c.
Constructing an analytic model of the diseased tissue from which
size parameters are determined for each of the tissues and
structures through which the current passes between the anterior
and posterior skin surfaces enclosing the diseased tissue; d.
Constructing a planar circuit model of the diseased tissue giving
the impedance and current flow in detail of all the structures and
tissues through which the current must flow to achieve a 20 mV/cm
electric field in the diseased tissue; e. Computing the electric
field amplitude (20 mV/cm) in the diseased tissue as equal to the
targeted diseased tissue current density divided by the targeted
diseased tissue conductivity; and f. Applying the computed voltage
and current to the diseased tissue of the human.
2. The method of claim 1 wherein the computed voltage and current
applying step comprises the step of applying the computed voltage
and current to the human using two electrodes in the case of
capacitive coupling.
3. The method of claim 1 wherein the computed voltage and current
applying step comprises the step of applying the computed voltage
and current to the human using a solenoid or coil(s) in the case of
inductive coupling.
4. The method of claim 1 wherein the voltage and current output
determining step comprises the step of determining the voltage and
current output that produces a 20 mV/cm electric field in the
tissues of the diseased human hip.
5. The method of claim 4 wherein the anatomic model constructing
step comprises the step of constructing an anatomic model of the
human hip.
6. The method of claim 5 wherein the step of constructing an
anatomic model of the diseased tissue comprises the step of
constructing an analytic model of the diseased human hip from which
size parameters are determined for each of the tissues and
structures through which the current passes between anterior and
posterior skin surfaces enclosing the human hip.
7. The method of claim 6 wherein the step of constructing the
planar circuit model comprises the step of constructing a planar
circuit model of the human hip in order to determine the
circumferential flow of current through a fat layer, a leakage flow
of current through muscle and other soft tissue, and current flow
across and through the human hip.
8. The method of claim 7 wherein the step of constructing the
planar circuit model comprises the step of constructing a planar
circuit model of the human hip giving the impedance and current
flow of all the tissues and structures through which the current
must flow to achieve a 20 mV/cm electric field in the human
hip.
9. The method of claim 8 wherein the step of computing the electric
field amplitude comprises the set of computing the desired electric
field amplitude (20 mV/cm) in the diseased human hip as equal to
the current density in the tissues of the hip divided by the
conductivity of the tissues in the hip.
10. The method of claim 1 wherein the computed voltage and current
are applied to a diseased human hip.
11. A device for treating diseased tissue in the human hip joint
through the application of a specific and selective electric or
electromagnetic field to the diseased or injured tissue in the
human hip joint comprising: a. one of (a) at least two electrodes,
in the case of capacitive coupling, adapted for application in the
proximity of a patient's hip joint; and (b) a solenoid or at least
one coil, in the case of inductive coupling, adapted for
application in the proximity of a patient's hip joint; and b. a
signal generator that generates electric signals for application to
the electrodes, the solenoid, or at least one coil so as to produce
an electric field of approximately 20 mV/cm.+-.15% and a current
density range of approximately 120 .mu.A/cm.sup.2.+-.15% within the
synovium and articular cartilage of the patient's hip joint.
12. A device for treating osteoarthritis, cartilage defects due to
trauma or sports injury, or used as an adjunct with other therapies
for treating cartilage defects in a human hip joint through the
application of specific and selective electric or electromagnetic
field to the afflicted tissue in the human hip joint, comprising:
a. one of (a) at least two electrodes on the surface of the skin
and (b) a solenoid or at least one coil located external to the
skin adapted for application in the proximity of a patient's hip
joint; and b. a signal generator that generates electric signals
for application to the electrodes, the solenoid, or at least one
coil so as to produce an electric field of approximately 20
mV/cm.+-.15% and a current density range of approximately 120
.mu.A/cm.sup.2.+-.15% within the synovium and articular cartilage
of the patient's hip joint.
13. A device as in claim 12, wherein the signal generator provides
one of the plurality of output electric signals in accordance with
a size of the human hip joint and its surrounding soft tissue and
skin.
14. A device as in claim 13, wherein one of the plurality of output
electrical signals of the signal generator for a 60 kHz frequency
has a voltage of approximately 4.3 V.sub.p-p.+-.10% for a small
size hip joint.
15. A device as in claim 13, wherein one of the plurality of output
electrical signals of the signal generator for a 60 kHz frequency
has a voltage of approximately 4.5 V.sub.p-p.+-.10% for a medium
sized hip joint.
16. A device as in claim 13, wherein one of the plurality of output
electrical signals of the signal generator for a 60 kHz frequency
has a voltage of approximately 5.7 V.sub.p-p.+-.10% for a large
sized hip joint.
17. A device as in claim 13, wherein one of the plurality of output
electrical signals of the signal generator for a 60 kHz frequency
has a voltage of approximately 10.2 V.sub.p-p.+-.10% for a extra
large sized hip joint.
18. A method of treating osteoarthritis in a human knee joint
through the application of a specific and selective electric or
electromagnetic field to the diseased tissue in the human knee
joint, comprising the steps of: converting electric potential into
an electric signal that when applied to one of (a) at least two
electrodes on the surface of the skin and (b) a solenoid or at
least one coil located external to the skin adapted for application
in the proximity of a patient's hip joint, an electric field of not
less than approximately 20 mV/cm.+-.15% is produced and a current
density of not less than approximately 120 .mu.A/cm.sup.2.+-.15% is
produced within the synovium and articular cartilage of the
patient's hip joint; and applying the electric signal to the at
least two electrodes, solenoid or coil so as to produce the
electric field within the synovium and articular cartilage of the
patient's hip joint.
19. A method as in claim 18, comprising the additional step of
selecting one of a plurality of output electric signals with a
voltage in accordance with a size of the human hip joint.
20. A method as in claim 19, wherein the selecting step comprises
the step of selecting an electrical signal having a voltage of
approximately 4.3 V.sub.p-p.+-.10% for a small size hip joint.
21. A method as in claim 19, wherein the selecting step comprises
the step of selecting an electrical signal having a voltage of
approximately 4.5 V.sub.p-p.+-.10% for a medium sized hip
joint.
22. A method as in claim 19, wherein the selecting step comprises
the step of selecting an electrical signal having a voltage of
approximately 5.7 V.sub.p-p.+-.10% for a large sized hip joint.
23. A method as in claim 19, wherein the selecting step comprises
the step of selecting an electrical signal having a voltage of
approximately 10.2 V.sub.p-p.+-.10% for a extra large sized hip
joint.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present patent application claims priority to U.S.
Provisional Patent Application Nos. 60/520,088 filed Nov. 14, 2003
and 60/535,734 filed Jan. 9, 2004. The present patent application
also claims priority to U.S. patent application Ser. No.
10/257,126, filed Oct. 8, 2002, entitled "Regulation of Genes Via
Application of Specific and Selective Electrical and
Electromagnetic Signals", which claims priority to PCT/US01/05991
filed Feb. 23, 2001, and U.S. Provisional Application No.
60/184,491 filed Feb. 23, 2000, and U.S. patent application Ser.
No. 10/255,241, filed Sep. 26, 2002, entitled "Regulation of
Aggrecan Gene Expression with a Specific and Selective Electrical
Signal", Ser. No. 10/267,708, filed Oct. 9, 2002, entitled
"Regulation of Type II Collagen Gene Expression with a Specific and
Selective Electrical Signal", Ser. No. 10/457,167, filed Jun. 9,
2003, entitled "Method and Apparatus for Treating Osteoarthritis,
Cartilage Disease, Defects and Injuries in the Human Knee Joint,"
Ser. No. 10/461,188, filed Jun. 13, 2003, entitled "Regulation of
Matrix Metalloproteinase Gene Expression Using Specific and
Selective Electrical and Electromagnetic Signals," and Ser. No.
10/603,226, filed Jun. 25, 2003, entitled "Portable Electrotherapy
Device for Treating Osteoarthritis and Other Diseases, Defects and
Injuries of the Knee Joint." The contents of all of these
applications are hereby incorporated by reference in their
entireties.
FIELD OF THE INVENTION
[0002] The present invention is directed to a method of determining
the voltage and current output required for the application of
specific and selective electric and electromagnetic signals to
diseased articular cartilage the treatment of osteoarthritis,
cartilage defects due to trauma or sports injuries, or as an
adjunct with other therapies (e.g., cell transplantation,
tissue-engineered scaffolds, growth factors, etc.) for treating
cartilage defects in the human hip joint and a device for
delivering such signals to a patient's hip.
BACKGROUND OF THE INVENTION
[0003] The bioelectrical interactions and activity believed to be
present in a variety of biological tissues and cells are one of the
least understood of the physiological processes. However, there has
recently been much research into these interactions and activities
related to the growth and repair of certain tissues and cells. In
particular, there has been considerable interest in stimulation by
electric and electromagnetic fields and their effect on the growth
and repair of bone and cartilage. Scientists believe that such
research might be useful in the development of new treatments for a
variety of medical problems.
[0004] Osteoarthritis, also known as degenerative joint disease, is
characterized by degeneration of articular cartilage as well as
proliferation and remodeling of subchondral bone. The usual
symptoms are stiffness, limitation of motion, and pain.
Osteoarthritis is the most common form of arthritis, and prevalence
rates increase markedly with age. It has been shown that elderly
patients with self-reported osteoarthritis visit doctors twice as
frequently as their unaffected peers. Such patients also experience
more days of restricted activity and bed confinement compared to
others in their age group. In one study, the majority of
symptomatic patients became significantly disabled during an 8-year
follow-up period (Massardo et al., Ann Rheum Dis 48:893-897,
1989).
[0005] Nonsteroidal anti-inflammatory drugs (NSAIDs) remain the
primary treatment modality for osteoarthritis. It is unknown
whether the efficacy of NSAIDs is dependent upon their analgesic or
anti-inflammatory properties or the slowing of degenerative
processes in the cartilage. There is also a concern that NSAIDs may
be deleterious to patients. For example, NSAIDs display well-known
toxic effects in the stomach, gastrointestinal tract, liver and
kidney. Moreover, aspirin inhibits proteoglycan synthesis and
normal cartilaginous repair processes in animals. One study in
humans also suggested that indomethacin might accelerate breakdown
of hip cartilage. All adverse effects appear more commonly in the
elderly--the very population most susceptible to
osteoarthritis.
[0006] In the disease commonly known as osteoporosis, bone
demineralizes and becomes abnormally rarefied. Bone comprises an
organic component of cells and matrix as well as an inorganic or
mineral component. The cells and matrix comprise a framework of
collagenous fibers that is impregnated with the mineral component
of calcium phosphate (85%) and calcium carbonate (10%) that imparts
rigidity to bone. While osteoporosis is generally thought to
afflict the elderly, certain types of osteoporosis may affect
persons of all ages whose bones are not subject to functional
stress. In such cases, patients may experience a significant loss
of cortical and cancellous bone during prolonged periods of
immobilization. Elderly patients are known to experience bone loss
due to disuse when immobilized after fracture of a bone; this may
ultimately lead to a secondary fracture in an already osteoporotic
skeleton. Diminished bone density may lead to collapse of
vertebrae, fractures of hips, lower arms, wrists and ankles, as
well as incapacitating pains. Alternative non-surgical therapies
for such diseases are needed.
[0007] Pulsed electromagnetic fields (PEMFs) and capacitive
coupling (CC) have been used widely to treat non-healing fractures
and related problems in bone healing since approval by the Food and
Drug Administration in 1979. The original basis for the trial of
this form of therapy was the observation that physical stress on
bone causes the appearance of tiny electric currents that, along
with mechanical strain, were thought to be the mechanisms
underlying transduction of the physical stress into a signal that
promotes bone formation. Along with direct electric field
stimulation that was successful in the treatment of nonunion bone
fractures, noninvasive technologies using PEMF and CC (where the
electrodes are placed on the skin in the treatment zone) were also
found to be effective. PEMFs generate small, induced currents
(Faraday currents) in the highly conductive extracellular fluid,
while CC directly causes currents in the tissues; both PEMFs and CC
thereby mimic endogenous electrical currents.
[0008] The endogenous electrical currents, originally thought to be
due to phenomena occurring at the surface of crystals in the bone,
have been shown to be due primarily to movement of fluid containing
electrolytes in channels of the bone containing organic
constituents with fixed negative charges, generating what are
called "streaming potentials." Studies of electrical phenomena in
cartilage have demonstrated a mechanical-electrical transduction
mechanism that resembles those described in bone, appearing when
cartilage is mechanically compressed, causing movement of fluid and
electrolytes over the surface of fixed negative charges in the
proteoglycans and collagen in the cartilage matrix. These streaming
potentials apparently serve a purpose in cartilage similar to that
in bone, and, along with mechanical strain, lead to signal
transduction that is capable of stimulating chondrocyte synthesis
of matrix components.
[0009] The main application of direct current, CC, and PEMFs has
been in orthopaedics in the healing of nonunion bone fractures
(Brighton et al. J Bone Joint Surg 1981; 63:2-13; Brighton and
Pollack J Bone Joint Surg 1985; 67:577-585; Bassett et al. Crit Rev
Biomed Eng 1989; 17:451-529; Bassett et al. J Am Med Assoc 1982;
247:623-628). Clinical responses have been reported in avascular
necrosis of hips in adults and Legg-Perthe's disease in children
(Bassett et al. Clin Orthop 1989; 246:172-176; Aaron et al. Clin
Orthop 1989; 249:209-218; Harrison et al. J Pediatr Orthop 1984;
4:579-584, 1984). It has also been shown that PEMFs (Mooney. Spine
1990; 15:708-712) and CC (Goodwin et al. Spine 1999; 24:1349-135)
can significantly increase the success rate of lumbar fusions.
There are also reports of augmentation of peripheral nerve
regeneration and function and promotions of angiogenesis (Bassett.
Bioessays 1987; 6:36-42). Patients with persistent rotator cuff
tendonitis refractory to steroid injection and other conventional
measures showed significant benefit compared with placebo treated
patients (Binder et al. Lancet 1984; 695-698). Finally, Brighton et
al., have shown in rats the ability of an appropriate CC electric
field to both prevent and reverse vertebral osteoporosis in the
lumbar spine (Brighton et al. J Orthop Res 1988; 6:676-684;
Brighton et al. J Bone Joint Surg 1989; 71:228-236).
[0010] More recently, research in this area has focused on the
effects that stimulation has on tissues and cells. For example, it
has been conjectured that direct currents do not penetrate cellular
membranes and that control is achieved via extracellular matrix
differentiation (Grodzinsky Crit Rev Biomed Eng 1983; 9:133). In
contrast to direct currents, it has been reported that PEMFs can
penetrate cell membranes and either stimulate them or directly
affect intracellular organelles. An examination of the effect of
PEMFs on extracellular matrices and in vivo endochondral
ossification found increased synthesis of cartilage molecules and
maturation of bone trabeculae (Aaron et al. J Bone Miner Res 1998;
4:227-233). More recently, it was reported (Lorich et al. Clin
Orthop Related Res 1998; 350:246-256) that signal transduction of a
capacitively coupled electric signal is via voltage-gated calcium
channels, leading to an increase in cytosolic calcium with a
subsequent increase in activated (cytoskeletal) calmodulin.
[0011] Much research has been performed using tissue culture
techniques in order to understand the mechanisms of response. In
one study, it was found that electric fields increased
[.sup.3H]thymidine incorporation into the DNA of chondrocytes,
supporting the notion that Na.sup.+ and Ca.sup.+2 fluxes generated
by electrical stimulation trigger DNA synthesis (Rodan et al.
Science 1978; 199:690-692). Studies have found changes in the
second messenger, cAMP, and cytoskeletal rearrangements due to
electrical perturbations (Ryaby et al. Trans BRAGS 1986; 6; Jones
et al. Trans. BRAGS 6:51, 1986; Brighton and Townsend J Orthop Res
1988; 6:552-558). Other studies have found effects on
glycosaminoglycan, sulfation, hyaluronic acid, lysozyme activity
and polypeptide sequences (Norton et al. J Orthop Res 1988;
6:685-689; Goodman et al. Proc Natl Acad Sci 1988;
85:3928-3932).
[0012] It was reported in 1996 by one of the present inventors that
a cyclic, biaxial 0.17% mechanical strain produces a significant
increase in TGF-.beta..sub.1 mRNA in cultured MC3T3-E1 bone cells
(Zhuang et al. Biochem Biophys Res Commun 1996; 229:449-453).
Several significant studies followed in 1997. In one study it was
reported that the same cyclic, biaxial 0.17% mechanical strain
produced a significant increase in PDGF-A mRNA in similar bone
cells (Wang et al. Biochem Mol Biol Int 1997; 43:339-346). It was
also reported that a 60 kHz capacitively coupled electric field of
20 mV/cm produced a significant increase in TGF-.beta..sub.1 mRNA
in similar bone cells (Zhuang et al. Biochem Biophys Res Commun
1997; 237:225-229). However, the effect such a field would have on
other genes has not been reported in the literature.
[0013] In the above-referenced parent patent application, entitled
"Regulation of Genes Via Application of Specific and Selective
Electrical and Electromagnetic Signals," methods were disclosed for
determining the specific and selective electrical and
electromagnetic signals for use in creating specific and selective
fields for regulating target genes of diseased or injured tissues.
The present invention builds upon the technique described therein
by describing the method of determining the voltage and current
output required, and the corresponding apparatus for delivering
specific and selective electrical and electromagnetic signals to
the human hip joints in patients afflicted with osteoarthritis and
other cartilage defects, diseases and injuries.
SUMMARY OF THE INVENTION
[0014] The present invention related to treating osteoarthritis and
other cartilage diseases, defects, and injuries in human hip joints
via the application of specific and selective fields generated by
specific and selective electric and/or electromagnetic signals. The
invention includes a method of determining the voltage and current
of the signal to apply to electrodes or to a solenoid or to at
least one coil applied to the hip for treatment.
[0015] More particularly, the invention relates to a method of
treating diseased tissue in a human through the application of a
specific and selective electric or electromagnetic field to
diseased tissue in a human, including osteoarthritis and other
cartilage diseases, defects and injuries in the hip, or used as an
adjunct with other therapies (cell transplantation,
tissue-engineered scaffolds, growth factors, etc.) in treating
cartilage defects in the human hip. The method includes the steps
of determining the voltage and current output that produces the
desired 20 mV/cm electric field in the articular cartilage of the
human hip joint, and other voltage and current values for other
effective electric field amplitudes thought or known to be
effective. The method includes constructing an anatomic model of
the human hip joint and translating the anatomic model to an
analytical model of the hip in which the dimensions for the tissues
encountered from skin (anterior) through fat and skin (posterior)
are determined. Planar circuits were then constructed in which the
various tissue conductivities, impedances and current flow were
used in calculating the voltage and current required to be applied
to surface electrodes placed anteriorly and posteriorly on the skin
covering the hip in order to produce an electric field at 20 mV/cm
in articular cartilage of the hip joint at a frequency of 60 kHz.
One knowledgeable in the field could perform the same analysis at
other frequencies, adjust the tissue impedances to their values at
the new frequency and obtain different values for the ranges of the
electrical field and current density at any chosen frequency or set
of frequencies.
[0016] The invention also includes a method and a device for
treating diseased tissue (such as osteoarthritis), defective or
injured tissue in a human hip joint through the application of a
specific and selective electric or electromagnetic field to the
afflicted tissue in the human hip joint. Such a device in
accordance with a capacitive coupling embodiment of the invention
includes at least two electrodes adapted for application in the
proximity of a patient's hip joint and a signal generator that
generates electric signals for application to the electrodes so as
to produce an electric field of amplitude of 20 mV/cm.+-.15% and a
current density of 120 .mu.A/cm.sup.2.+-.15% within the synovium
and articular cartilage of the patient's hip joint. An inductive
coupling embodiment of the invention includes a coil(s) or solenoid
adapted and configured to receive the electric signals to produce
these electric fields. Preferably, the signal generator provides
one of a plurality of output electric signals with a voltage
selected by a user in accordance with a size of the human hip
joint. Larger hip joints receive signals of larger voltages.
[0017] These and other aspects of the present invention will be
elucidated in the following detailed description of the
invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0018] The present invention will be apparent from the following
detailed description of the invention in conjunction with the
accompanying drawings, of which:
[0019] FIG. 1 illustrates an anatomic model of the human hip joint
showing all the important tissues and structures through which the
current passes between the anterior and posterior surface
electrodes placed on skin.
[0020] FIG. 2 illustrates an analytical model of the human hip
joint from which size parameters are determined for each of the
tissues and structures indicated.
[0021] FIG. 3A illustrates a planar circuit model of the human hip
joint showing circumferential flow of current through the fat
layers (I.sub.3) plus leakage flow of current through the muscle
and other soft tissue (I.sub.4), plus current flow across the hip
joint (I.sub.2) and the impedance (Z) compartments.
[0022] FIG. 3B illustrates a planar circuit showing in detail the
current flow and impedances across the hip joint (Z.sub.T1).
[0023] FIG. 4 illustrates schematically the three currents that
were calculated in determining the output current and voltage
required to produce a 20 mV/cm field in the articular cartilage of
the hip joint. The three currents are the circumferential current,
the leakage current, and the current flowing through the hip
joint.
[0024] FIG. 5 illustrates electrode placement on the skin that is
required to produce the desired electric field in the hip
joint.
DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS
[0025] The invention will be described with reference to FIGS. 1-5
and Tables 1-3. Those skilled in the art will appreciate that the
description given herein with respect to these figures is for
exemplary purposes only and is not intended in any way to limit the
scope of the invention. All questions regarding the scope of the
invention may be resolved by referring to the appended claims.
[0026] Definitions:
[0027] As used herein, the term "signal" is used to refer to a
variety of signals including mechanical signals, ultrasound
signals, electromagnetic signals, and electric signals outputted by
a device.
[0028] As used herein, the term "field" refers to an electric field
within a targeted tissue, whether it is a combined field or a
pulsed electromagnetic field, or generated by direct current,
capacitive coupling, or inductive coupling.
[0029] Determination of Voltage and Current:
[0030] Previous studies by the present inventors have shown that a
capacitively coupled field significantly increased the
proliferation of bone cells grown in culture (Brighton, Pollack, et
al, V. Orthop. Research, 3:331-340, 1985) and significantly
increased the rate of healing in a rat fractured fibula model
(Brighton, Pollack, et al, Clin. Orthop. And Related Research,
285:255-262, 1992). Also, the field distributions in the vertebral
bodies of rats during capacitively coupled electrical stimulation
have been determined (Carter, Vresilovic, Pollack, and Brighton,
IEEE transactions on Biomedical Engineering, 36(-3): 333-3345,
1989). In order to determine the required output voltage and
current required to produce an equivalent electric field and
current density in a human hip joint, the analytical model depicted
in FIG. 2 was developed in accordance with the invention for
representing the typical human hip joint illustrated in FIG. 1.
[0031] As shown in FIG. 1, the typical human hip joint includes
layers of cartilage and synovial fluid that is bounded by the
acetabulum and the femoral head. In accordance with the invention,
osteoarthritis, cartilage disease, defects and injuries in the hip
joint is treated by the application of specific and selective
electric fields via electrodes 10, 20 attached relative to the hip
joint substantially as shown in FIG. 1. A signal generator 30
provides the appropriate signals to the electrodes for generating
the specific and selective electric fields. The specific and
selective electric field needed to treat osteoarthritis, cartilage
disease, defects and injuries in the hip joint is calculated in
accordance with the invention using the analytical model of the hip
joint depicted in FIG. 2.
[0032] FIG. 1 illustrates an anatomical model for use in
determining the electric field amplitude and current density
obtained in the cartilage space in a hip joint when electrodes 10,
20 are placed anteriorly and posteriorly, respectively, and a
voltage is applied causing a current to flow through the body. In
the analytical model of FIG. 2, the following elements are
identified as indicated: electrodes 10, 20, skin 40, fat 50, muscle
60, bone (acetabulum) 70, cartilage and synovial fluid 80, and
femoral head 90. In an exemplary embodiment, the frequency of a
sine wave voltage is taken to be 60 kHz; however, the methodology
described herein can be applied to any frequency as long as the
electrical properties of the tissues are chosen for those
frequencies. It is desired to determine the voltage and the current
to be applied to the electrodes 10, 20 in order to obtain in the
cartilage of the hip joint a therapeutic electric field amplitude
of 20 mV/cm in a preferred embodiment, and voltage and current
values for other effective electric field amplitudes known to be
effective.
[0033] It is clear from FIGS. 1 and 2 that patients of different
sizes may require different applied voltages and currents to
achieve the therapeutic electric field amplitudes. Accordingly, the
calculation in accordance with the invention will model the patient
for four (4) different size classifications. The essential
geometric model parameters for these four sizes along with the
relevant electrical properties of all tissue types are shown below
in Tables 1A and 1B with reference to the distances illustrated in
FIG. 2. The electrodes 10, 20 are assumed to be 2''.times.2''
square and the currents are calculated by considering the current
flow through the patient's body for a 2''.times.2'' rectangle from
one electrode to the other plus the circumferential flow of current
through the fat layer plus the leakage current that flows through
the muscle and other soft tissues outside of the 2''.times.2''
rectangle but excluding the circumferential current in the fat
layer. These currents are shown in FIGS. 3 and 4. The impedances of
the tissue compartments through which the current I.sub.2 (FIG. 3)
flows are shown in FIG. 3B. A line drawing showing patient
electrode placement is presented in FIG. 5. In FIG. 5, the region
in broken lines is modeled as a 2''.times.2'' rectangle 100 in
which the body current is assumed to flow. Leakage currents as
shown in FIGS. 3A and 4 include circumferential flow in the fat
layer and body currents outside of the 2''.times.2'' rectangle 100.
The current flow and impedance through region 100 are those shown
in FIG. 3B.
TABLE-US-00001 TABLE 1A Size Parameters for Four Patient
Classifications Patient Classification Small Medium Large
Extra-Large Measurement (m) (m) (m) (m) Electrode-to electrode
0.1524 0.18 0.21 0.305 distance (D*) Fat layer thickness (F*)
0.00635 0.00762 0.0222 0.699 Fat layer width 0.051 0.051 0.051
0.051 Muscle (M.sub.3*) length 0.051 0.0635 0.0635 0.0635 Muscle
(M.sub.3*) width 0.051 0.051 0.051 0.051 Muscle (M.sub.4*) length
0.0635 0.0762 0.0762 0.0762 Muscle (M.sub.4*) width 0.0254 0.0254
0.0254 0.0254 Muscle (M.sub.8*) length 0.0254 0.0254 0.0254 0.0254
Muscle (M.sub.8*) width 0.051 0.051 0.051 0.051 Cartilage junction
length 0.08 0.08 0.08 0.08 Cartilage junction width 0.0127 0.0127
0.0127 0.0127 Femoral head radius (R*) 0.0254 0.0254 0.0254 0.0254
Acetabular thickness (B*) 0.015 0.015 0.015 0.015 Acetabular width
0.04 0.04 0.04 0.04 *See FIG. 2
TABLE-US-00002 TABLE 1B Electrical Conductivities TISSUE
CONDUCTIVITY Fat 0.02 S/m Muscle 0.45 S/m Bone 0.01 S/m Cartilage
0.6 S/m Skin Admittance 3 .times. 10.sup.-3 S/cm.sup.2
[0034] The definitions of terms in FIGS. 2, 3A, 3B and 4 are shown
below in Table 2. Each impedance labeled in FIGS. 3 and 4 was
calculated using the relationship:
Z = 1 .sigma. Length Area ( Equation 1 ) ##EQU00001##
Where Length is the dimension of the tissue in the direction of the
current flow, Area is the cross-sectional area of the tissue
perpendicular to the direction of current flow, and a is the
electrical conductivity.
TABLE-US-00003 TABLE 2 Definitions of dimensions and symbols shown
in FIGS. 2 and 3 D = electrode to electrode distance F = fat layer
thickness M = muscle: M.sub.3 = distance (thickness) of muscle from
posterior fat layer to posterior acetabulum M.sub.4 = distance
(thickness) of muscle from posterior acetabulum to anterior
acetabulum M.sub.8 = distance (thickness) of muscle from anterior
acetabulum to anterior fat layer Z = impedance: Z.sub.1 = impedance
of skin Z.sub.2 = impedance of fat Z.sub.3 = impedance of muscle
posterior to the acetabulum Z.sub.4 = impedance of the muscle
around the hip joint Z.sub.5 = impedance of bone (acetabulum)
Z.sub.FH {open oversize brace} Z.sub.6 = impedance of bone (femoral
head) Z.sub.7 = impedance of articular cartilage- synovium Z.sub.8
= impedance of muscle anterior to the acetabulum Z.sub.T1 =
impedance across the hip joint; i.e., the combined impedance from
Point A to Point B in FIG. 3B I = current: I.sub.total = total
current flowing from electrode to electrode I.sub.FH = current
flowing through hip joint I.sub.4 = current flowing through muscle
I.sub.6 = current flowing through femoral head I.sub.7 = current
flowing through articular cartilage B = Bone (acetabulum) thickness
C = cartilage-synovium thickness R = radius of femoral head J =
current density (A/cm.sup.2) E = electric field (V/cm)
[0035] The impedances were then calculated using Equation 1, the
dimensions in Table 1A and the conductivities in Table 1B. Using
standard lump circuit analysis for series/parallel impedances, the
total current, I.sub.1 (FIG. 3A) that must flow from the electrodes
was calculated for each patient classification for a voltage
applied to the electrodes. In addition, I.sub.2, the current flow
through the muscle-femur-cartilage-muscle layers; the current
I.sub.3, the current flowing circumferentially through the fat
layer and I.sub.4, the leakage currents, were also calculated. This
enabled the calculation of the current through the cartilage,
I.sub.cartilage, and the current density, J.sub.cartilage, from
which the electric field amplitude in the cartilage,
E.sub.cartilage, could be computed from the equation:
J.sub.cartilage=.sigma..sub.cartilageE.sub.cartilage (Equation
2)
where J.sub.cartilage and E.sub.cartilage are described above and
.sigma..sub.cartilage is the electrical conductivity of the
cartilage as shown in Table 1B. These results are summarized in
Table 3A. From Table 3A, it is apparent that for an applied voltage
of approximately 5 V peak-to-peak sine wave at 60 kHz, one obtains
electric fields of 20 mV/cm.+-.3.5 mV/cm for the small, medium and
large patient, but not for the extra-large patient. The extra-large
patient requires a voltage that is approximately twice that
required for the other three patient sizes.
TABLE-US-00004 TABLE 3A Device Voltage and Current Required to
Apply 20 mV/cm Electric Field to Cartilage in the Human Hip Device
Current Electrode Current Patient Size Device Voltage (2'' .times.
2'' electrode) Density Small 4.3 V.sub.p-p 26.8 mA 1.04 mA/cm.sup.2
Medium 4.5 V.sub.p-p 31.6 mA 1.23 mA/cm.sup.2 Large 5.7 V.sub.p-p
32.0 mA 1.24 mA/cm.sup.2 Extra Large 10.2 V.sub.p-p 52.1 mA 2.02
mA/cm.sup.2
[0036] It is now possible to calculate the device current to the
2''.times.2'' electrodes 10, 20 in order to achieve a 20 mV/cm
electric field amplitude in the cartilage. These values, and the
approximate device voltages that achieve these device currents are
shown below in Table 3B along with the current and current density
in the cartilage when the applied voltage is as shown for each
patient size:
TABLE-US-00005 TABLE 3B Cartilage Current and Current Density When
a 20 mV/cm Electric Field is Applied to the Cartilage of the Human
Hip Patient Size Cartilage Current Cartilage Current Density Small
0.15 mA 120 .mu.A/cm.sup.2 Medium 0.15 mA 120 .mu.A/cm.sup.2 Large
0.15 mA 120 .mu.A/cm.sup.2 Extra Large 0.15 mA 127
.mu.A/cm.sup.2
[0037] It is noted that for extra-large patients, the current
density value at the electrodes, 2.02 mA/cm.sup.2, is at the
maximum value and should not be exceeded.
[0038] It is understood that patients with a specific size, i.e.,
electrode-to-electrode dimension, may have tissue compartment sizes
and/or skin impedance values that differ from those modeled here.
Therefore, devices that power the electrodes should have output
variability to increase the peak-to-peak voltage to achieve the
desired electrode current (density).
[0039] The current (or electric field) that flows through the
cartilage of the hip when a voltage is applied to the electrodes on
the skin is determined by the impedances shown in FIGS. 3A and 3B.
For a given patient size, the dimensions of various tissue
compartments (and therefore their impedances) can vary so that the
current that actually flows through the cartilage could be higher
or lower than the values shown for an applied device voltage as
shown above. Taking reasonable variations in dimensions of the
tissue compartments for each patient size, it may be determined
that for a given device voltage, the cartilage current (and
therefore the cartilage electric field) could differ by .+-.15%.
Therefore, in order to account for this variation, and to account
for the variation of skin electrical impedance from patient to
patient, the device should be designed to apply the device current
value plus or minus 15% to the pair of 2''.times.2'' electrodes 10,
20.
[0040] Thus, in accordance with the invention, the approximate size
of the patient's hip is determined, and a signal is generated and
applied to the electrodes that will generate the desired electric
field with a voltage of 20 mV/cm.+-.15% and a current density of
120 .mu.A/cm.sup.2.+-.15% within the synovium and articular
cartilage for treatment of osteoarthritis in the hip, for example.
Preferably, the signal generator includes a select control (FIG. 1)
that allows the operator to select the proper output based on the
size of the patient's hip.
[0041] Although implementations of the invention have been
described in detail above, those skilled in the art will readily
appreciate that many additional modifications are possible without
materially departing from the novel teachings and advantages of the
invention. For example, those skilled in the art will appreciate
that the techniques of the invention may be applied to capacitive
and inductive coupling systems. In the case of capacitive coupling,
the scaled voltage and current are applied to the hip region using
two electrodes as illustrated in FIGS. 1 and 2. On the other hand,
in the case of inductive coupling, the scaled voltage and current
are applied to the hip region using a solenoid or coil(s). Any such
modifications are intended to be included within the scope of the
invention as defined in the following claims.
* * * * *