U.S. patent application number 11/992430 was filed with the patent office on 2010-11-18 for electrical impedance myography.
This patent application is currently assigned to Beth Israel Deaconess Medical Center, Inc.. Invention is credited to Ronald Aaron, Seward B. Rutkove, Carl A. Shiffman.
Application Number | 20100292603 11/992430 |
Document ID | / |
Family ID | 37889545 |
Filed Date | 2010-11-18 |
United States Patent
Application |
20100292603 |
Kind Code |
A1 |
Shiffman; Carl A. ; et
al. |
November 18, 2010 |
Electrical Impedance Myography
Abstract
Electrical impedance myography (EIM) can be used for the
assessment and diagnosis of muscular disorders. EIM includes
applying an electrical signal to a region of tissue and measuring a
resulting signal. A characteristic of the region of tissue is
determined based on the measurement. Performing EIM at different
frequencies and/or different angular orientations with respect to a
muscle can aid in the assessment and diagnosis. Devices are
described that facilitate assessment and diagnosis using EIM.
Inventors: |
Shiffman; Carl A.; (Waban,
MA) ; Aaron; Ronald; (Newton Centre, MA) ;
Rutkove; Seward B.; (Brookline, MA) |
Correspondence
Address: |
WOLF GREENFIELD & SACKS, P.C.
600 ATLANTIC AVENUE
BOSTON
MA
02210-2206
US
|
Assignee: |
Beth Israel Deaconess Medical
Center, Inc.
Boston
MA
Northeastern University
Boston
MA
|
Family ID: |
37889545 |
Appl. No.: |
11/992430 |
Filed: |
September 21, 2006 |
PCT Filed: |
September 21, 2006 |
PCT NO: |
PCT/US2006/036863 |
371 Date: |
August 3, 2010 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
60719426 |
Sep 21, 2005 |
|
|
|
Current U.S.
Class: |
600/547 |
Current CPC
Class: |
A61B 5/0536 20130101;
A61B 2562/164 20130101; A61B 5/389 20210101; A61B 5/053 20130101;
A61B 2562/046 20130101; A61B 5/0531 20130101; A61B 5/296
20210101 |
Class at
Publication: |
600/547 |
International
Class: |
A61B 5/053 20060101
A61B005/053 |
Goverment Interests
FEDERALLY SPONSORED RESEARCH
[0002] This invention was made with Government support under Center
for Integration of Medicine and Innovative Technology (CIMIT) grant
number O7-33. The Government may have certain rights in this
invention.
Claims
1. A method of determining at least one characteristic of a region
of tissue, the method comprising acts of: applying a plurality of
first electrical signals to the region of tissue, each of the
plurality of first electrical signals being applied at a respective
one of a plurality of orientations so as to propagate through at
least a portion of the region of tissue in a respectively different
direction with respect to a first axis of the region of tissue;
obtaining a plurality of measurements from the region of tissue,
each of the plurality of measurements indicative of a respective
one of a plurality of second electrical signals, each of the
plurality of second electrical signals resulting from applying a
respective one of the plurality of first electrical signals; and
determining the at least one characteristic based, at least in
part, on the plurality of measurements.
2. The method of claim 1, wherein the act of applying the plurality
of first electrical signals to the region of tissue includes an act
of applying at least one first electrical signal in a direction
substantially parallel to the first axis and applying at least one
first electrical signal in a direction substantially perpendicular
to the first axis.
3. The method of claim 2, wherein the act of applying the plurality
of electrical signals to the region of tissue includes an act of
applying at least one first electrical signal in a direction
substantially parallel to the first axis and applying at least one
electrical signal at least every approximately 30.degree. rotation
from the first axis over a range of approximately 180.degree..
4. The method of claim 2, wherein the first axis is substantially
aligned in a direction of muscle fibers of the region of
tissue.
5. The method of claim 1, wherein the plurality of first electrical
signals include a plurality of current signals, and wherein the
plurality of second electrical signals include a plurality of
voltage signals, each resulting from a respective one of the
plurality of current signals.
6. The method of claim 1, wherein the act of determining the at
least one characteristic includes an act of determining at least
one property of the region of tissue at each of the plurality of
orientations, based on the plurality of measurements.
7. The method of claim 6, further comprising an act of generating a
first signature of the region of tissue, the first signature
comprising the at least one property as a function of
orientation.
8. The method of claim 7, wherein the at least one property
includes a resistance of the region of tissue at the respective
orientation.
9. The method of claim 7, wherein the at least one property
includes a reactance of the region of tissue at the respective
orientation.
10. The method of claim 7, wherein the at least one property
includes a phase derived from a resistance and a reactance of the
region of tissue at the respective orientation.
11. The method of claim 7, wherein the act of determining the at
least one characteristic includes an act of determining a degree of
anisotropy of the first signature.
12. The method of claim 7, wherein the act of determining the at
least one characteristic includes an act of comparing the first
signature with a second signature obtained from a reference region
of tissue.
13. The method of claim 12, wherein the second signature is
obtained from healthy tissue.
14. The method of claim 1, wherein the act of applying a plurality
of first electrical signals includes an act of applying a plurality
of first electrical signals, each at a respective one of a
plurality of frequencies at each of the plurality of
orientations.
15. The method of claim 14, wherein the act of obtaining the
plurality of measurements includes an act of obtaining a plurality
of measurements from the region of tissue, the plurality of
measurements including at least one measurement at each of the
plurality of frequencies at each of the plurality of
orientations.
16. The method of claim 15, wherein the act of determining the at
least one characteristic includes an act of determining at least
one property of the region of tissue at each of the plurality of
frequencies at each of the plurality of orientations, based on the
plurality of measurements.
17. The method of claim 16, further comprising an act of generating
a first signature of the region of tissue, the first signature
comprising the at least one property as a function of orientation
and frequency.
18. The method of claim 17, wherein the act of determining the at
least one characteristic includes an act of determining a degree of
anisotropy of the first signature.
19. The method of claim 18, wherein the act of determining the
muscle characteristic includes an act of comparing the first
signature with a second signature obtained from a reference region
of tissue.
20. A method of determining at least one characteristic of a region
of tissue, the method comprising acts of: applying a plurality of
first electrical signals to the region of tissue, each of the
plurality of first electrical signals being applied at a respective
one of a plurality of frequencies; obtaining a plurality of
measurements from the region of tissue, each of the plurality of
measurements indicative of a respective one of a plurality of
second electrical signals, each of the plurality of second
electrical signals resulting from applying a respective one of the
plurality of first electrical signals; and determining the at least
one characteristic based, at least in part, on the plurality of
measurements.
21. The method of claim 20, wherein the plurality of first
electrical signals include a plurality of current signals and the
plurality of second electrical signals includes a plurality of
voltage signals, each resulting from the application of a
respective one of the plurality of current signals.
22. The method of claim 20, wherein the act of determining the at
least one characteristic includes an act of determining at least
one property of the region of tissue at each of the plurality of
frequencies, based on the plurality of measurements.
23. The method of claim 22, further comprising an act of generating
a first signature of the region of tissue, the first signature
comprising the at least one property as a function of
frequency.
24. The method of claim 22, wherein the at least one property
includes a resistance of the region of tissue at the respective
frequency.
25. The method of claim 22, wherein the at least one property
includes a reactance of the region of tissue at the respective
frequency.
26. The method of claim 22, wherein the at least one property
includes a phase derived from a resistance and a reactance of the
region of tissue at the respective frequency.
27. The method of claim 23, wherein the act of determining the at
least one characteristic includes an act of determining a degree of
anisotropy of the first signature.
28. The method of claim 23, wherein the act of determining the at
least one characteristic includes an act of comparing the first
signature with a second signature obtained from a reference region
of tissue.
29. The method of claim 28, wherein the second signature is
obtained from healthy tissue.
30. The method of claim 20, wherein the act of applying a plurality
of first electrical signals includes an act of applying the
plurality of first electrical signals at the plurality of
frequencies at each of a plurality of orientations.
31. The method of claim 30, wherein the act of obtaining the
plurality of measurements includes an act of obtaining a plurality
of measurements from the region of tissue, the plurality of
measurements including at least one measurement at each of the
plurality of frequencies at each of the plurality of
orientations.
32. The method of claim 31, wherein the act of determining the at
least one characteristic includes an act of determining at least
one property of the region of tissue at each of the plurality of
frequencies at each of the plurality of orientations, based on the
plurality of measurements.
33. The method of claim 32, further comprising an act of generating
a first signature of the region of tissue, the first signature
comprising the at least one property as a function of orientation
and frequency.
34. The method of claim 33, wherein the act of determining the at
least one characteristic includes an act of determining a degree of
anisotropy of the first signature.
35. The method of claim 34, wherein the act of determining the
muscle characteristic includes an act of comparing the first
signature with a second signature obtained from a reference region
of tissue.
36. A device adapted for application to a surface of skin to
determine at least one characteristic of a region of tissue, the
device comprising: a first electrode adapted to apply a first
electrical signal to the region of tissue; a second electrode
adapted to detect a second electrical signal at the region of
tissue resulting from the application of the first electrical
signal; a rotatable base on which the first electrode and the
second electrode are mounted and arranged such that, when the
rotatable base is rotated, the first electrode and the second
electrode are rotated with respect to the region of tissue to apply
the first electrical signal to the region of tissue at a plurality
of orientations so as to propagate through at least a portion of
the region of tissue in a respectively different direction with
respect to a first axis of the region of tissue, and to detect the
second electrical signal resulting from the application of the
first electrical signal at the plurality of orientations; and a
measurement component coupled to the second electrode to obtain at
least one measurement indicative of the second electrical signal at
each of the plurality of orientations.
37. The device of claim 36, wherein the first electrode and the
second electrode are spaced apart in a first direction such that
the first electrical signal applied to the region of tissue
propagates essentially in the first direction through the region of
tissue toward the second electrode.
38. The device claim 37, wherein, when the rotatable base is
rotated, the first electrical signal propagates in a different
direction through the region of tissue with respect to a first axis
of the region of tissue at each of the plurality of
orientations.
39. The device of claim 38, wherein the rotatable base is capable
of being rotated through a range of at least 90.degree..
40. The device of claim 38, wherein the rotatable base is capable
of being rotated through a range of at least 180.degree..
41. The device of claim 38, wherein the rotatable base is capable
of being rotated through a range of at least 360.degree..
42. The device of claim 38, wherein the measurement component is
adapted to determine at least one property based on the at least
one measurement to generate a first signature, the first signature
comprising the at least one property as a function of
orientation.
43. The device of claim 36, wherein the first electrode is adapted
to apply a plurality of first electrical signals to the region of
tissue, each of the plurality of first electrical signals having a
respective one of a plurality of frequencies, and wherein the
second electrode is adapted to detect a plurality of second
electrical signals, each of the plurality of second signals
resulting from a respective one of the plurality of first
electrical signals.
44. The device of claim 43, wherein the measurement component is
adapted to obtain a plurality of measurements, each of the
plurality of measurements indicative of a respective one of the
plurality of the second electrical signals.
45. The device of claim 44, wherein the measurement component is
adapted to determine at least one property based on each of the
plurality of measurements to generate a first signature, the first
signature comprising the at least one property as a function of
orientation and frequency.
46. The device of claim 45, wherein the at least one property
includes a resistance of the region of tissue at the respective
orientation and frequency.
47. The device of claim 45, wherein the at least one property
includes a reactance of the region of tissue at the respective
orientation and frequency.
48. The device of claim 45, wherein the at least one property
includes a phase derived from a resistance and a reactance of the
region of tissue at the respective orientation and frequency.
49. The device of claim 42, further comprising an analysis
component to determine a degree of anisotropy of the first
signature.
50. The device of claim 45, further comprising a comparison
component coupled to receive the first signature, the comparison
component adapted to compare the first signature with a second
signature obtained from a reference region of tissue.
51. The device of claim 12, further comprising a display coupled to
the measurement component, the display adapted to present the first
signature in a human perceptible format.
52. A device adapted for application to a surface of skin to
determine at least one characteristic of a region of tissue, the
device comprising: a plurality of first electrodes each adapted to
apply a respective one of a plurality of first electrical signals
to the region of tissue; a plurality of second electrodes
respectively associated with the plurality of first electrodes to
form a plurality of electrode pairs, each of the plurality of
second electrodes adapted to detect a respective one of a plurality
of second electrical signals at the region of tissue, each of the
plurality of second electrical signals resulting from the
application of a respective one of the plurality of first
electrical signals; a base on which the plurality of electrode
pairs are mounted, the plurality of electrode pairs each arranged
at a respective one of a plurality of orientations such that when
the base is applied to the region of tissue, the plurality of first
electrical signals may be selectively provided to the region of
tissue at the plurality of orientations; and a measurement
component capable of being selectively coupled to each of the
plurality of second electrodes, the measurement component adapted
to obtain at least one measurement indicative of one of the
plurality of second electrical signals corresponding to one of the
plurality of second electrodes to which the measurement component
is coupled.
53. The device of claim 52, wherein the plurality of orientations
are spaced apart by at least 30 degrees.
Description
RELATED APPLICATIONS
[0001] This application claims priority under 35 U.S.C.
.sctn.119(e) to U.S. Provisional Application Ser. No. 60/719,426,
entitled "Method and Apparatus for Electrical Impedance Myography,"
filed on Sep. 21, 2005, which is hereby incorporated by reference
in its entirety.
BACKGROUND OF INVENTION
[0003] Neuromuscular diseases encompass a large collection of
disorders, ranging from relatively mild conditions such as focal
compression neuropathies and nerve root injuries, to severe and
life-threatening syndromes, including amyotrophic lateral sclerosis
(ALS) and muscular dystrophies. These disorders may lead to muscle
atrophy and weakness, caused either by injury to or disease of the
neuron (neurogenic disorders), the neuromuscular junction, or the
muscle cell itself (myopathic disorders). Another disorder, disuse
atrophy, may occur when a limb is immobilized or a patient is
bed-bound for a prolonged period of time, although not classically
considered a neuromuscular disorder, also produces substantial
morbidity.
[0004] Neuromuscular diseases have been assessed and diagnosed
using various techniques, including nerve condition studies, needle
electromyography, muscle imaging, muscle biopsy and genetic
testing. However, the initial assessment of the neuromuscular
diseases has advanced relatively little beyond conventional needle
electromyography and nerve conduction techniques. Similarly, there
have been few good approaches to the assessment of disuse atrophy
and dysfunction.
[0005] Nerve conduction studies (NCSs) and needle electromyography
(EMG) are often the first tests obtained when evaluating a patient
for neuromuscular causes of atrophy. NCSs involve stimulation of a
nerve with one set of electrodes and recording the resulting muscle
or nerve potential with a second set of electrodes. Although useful
for evaluating nerve pathology, NCSs are of limited use for
evaluating muscle disease or disuse states. The stimuli can be
uncomfortable and only a relatively limited set of distal muscles
in the arms and legs can be evaluated.
[0006] Needle electromyography is geared more specifically to
muscle evaluation. Needle electromyography can provide a quick
survey of muscles to determine whether they are being affected by
neurogenic injury or myopathic injury. However, the test has
considerable limitations. First, needle electromyography is very
subjective because physicians qualitatively assess the attributes
of motor unit action potentials (MUAPs) as they rapidly pass across
an oscilloscopic display. Second, there are substantial limitations
with respect to the sensitivity of needle electromyography. It is a
common experience amongst electromyographers that only with
extensive probing are one or two questionably abnormal MUAPs
identified. Third, the lack of quantifiable results makes EMG an
unsuitable modality for following disease progression/remission.
Finally, needle EMG remains a somewhat painful, invasive procedure
and can thus only be used in a very limited fashion in
children.
[0007] Imaging techniques such as magnetic resonance imaging (MRI)
and ultrasound have found some use in muscle atrophy assessment.
For example, MRI can be used to identify muscles with active
inflammation to assist with biopsy site choice in patients with
myositis. However, MRI has otherwise remained of limited use since
it is difficult to evaluate different areas of the body, is costly,
cannot easily assess dynamic muscle states during muscle
contraction, and may not be used in patients with pacemakers and
implanted defibrillators. Ultrasound has found limited use in
neuromuscular disease and disuse atrophy assessment, and remains
very qualitative.
[0008] Muscle biopsy is another test for evaluation of muscle
disease and can be helpful in arriving at a specific diagnosis.
Muscle biopsy frequently yields limited or contradictory
information and may be unsuitable for monitoring progression of
atrophy because of its inherent invasiveness. Given that many
diseases are patchy (i.e., regions of diseased muscle tissue is
interspersed throughout ostensibly healthy muscle tissue), a
negative biopsy does not exclude disease, and repeat biopsies
sometimes need to be performed.
[0009] Genetic tests can be very useful for assisting in the
evaluation of a number of mostly rare conditions (such as the
muscular dystrophies), but is expensive and not relevant to a
variety of the most common, acquired conditions.
SUMMARY OF INVENTION
[0010] Existing techniques for assessing and diagnosing
neuromuscular diseases can be unreliable, subjective and sometimes
painful to the patient. Embodiments of the invention relate to
methods and devices that can provide a reliable, quantitative and
relatively painless assessment and diagnoses of neuromuscular
diseases, and for assessment of disuse atrophy. Applicant has
developed generally non-invasive techniques for characterizing
muscle tissue, facilitating the assessment, diagnosis, monitoring
and/or treatment of characteristics and/or conditions of muscle
tissue that may be indicative of one or more neuromuscular
disorders, including disuse atrophy.
[0011] One embodiment according to the present invention includes a
method of determining at least one characteristic of a region of
tissue, the method comprising acts of applying a plurality of first
electrical signals to the region of tissue, each of the plurality
of first electrical signals being applied at a respective one of a
plurality of orientations, obtaining a plurality of measurements
from the region of tissue, each of the plurality of measurements
indicative of a respective one of a plurality of second electrical
signals, each of the plurality of second electrical signals
resulting from applying a respective one of the plurality of first
electrical signals, and determining the at least one characteristic
based, at least in part, on the plurality of measurements.
[0012] Another embodiment according to the present invention
includes a method of determining at least one characteristic of a
region of tissue, the method comprising acts of applying a
plurality of first electrical signals to the region of tissue, each
of the plurality of first electrical signals being applied at a
respective one of a plurality of frequencies, obtaining a plurality
of measurements from the region of tissue, each of the plurality of
measurements indicative of a respective one of a plurality of
second electrical signals, each of the plurality of second
electrical signals resulting from applying a respective one of the
plurality of first electrical signals, and determining the at least
one characteristic based, at least in part, on the plurality of
measurements.
[0013] Another embodiment according to the present invention
includes a device adapted for application to a surface of skin to
determine at least one characteristic of a region of tissue, the
device comprising a first electrode adapted to apply a first
electrical signal to the region of tissue, a second electrode
adapted to detect a second electrical signal at the region of
tissue resulting from the application of the first electrical
signal, a rotatable base on which the first electrode and the
second electrode are mounted and arranged such that, when the
rotatable base is rotated, the first electrode and the second
electrode are rotated with respect to the region of tissue to apply
the first electrical signal to the region of tissue at a plurality
of orientations and to detect the second electrical signal
resulting from the application of the first electrical signal at
the plurality of orientations, and a measurement component coupled
to the second electrode to obtain at least one measurement
indicative of the second electrical signal at each of the plurality
of orientations.
BRIEF DESCRIPTION OF DRAWINGS
[0014] The accompanying drawings are not intended to be drawn to
scale. In the drawings, each identical or nearly identical
component that is illustrated in various figures is represented by
a like numeral. For purposes of clarity, not every component may be
labeled in every drawing. In the drawings:
[0015] FIG. 1 is a diagram illustrating an example of a device that
performs electrical impedance myography, according to one
embodiment of the invention;
[0016] FIG. 2 is a flow chart illustrating a multi-frequency method
of determining a characteristic of a tissue region of an organism,
according to one embodiment of the invention;
[0017] FIGS. 3A-C show plots of measured electrical parameters
versus frequency, using multi-frequency electrical impedance
myography obtained in accordance with various aspects of the
invention;
[0018] FIGS. 4A-B are diagrams illustrating an example of a device
that performs rotational electrical impedance myography, according
to one embodiment of the invention;
[0019] FIG. 5 is a diagram illustrating an example of a device that
performs electrical impedance myography at a plurality of angles,
according to one embodiment of the invention; and
[0020] FIG. 6 is a diagram illustrating an example of a hand-held
device that performs electrical impedance myography, according to
one embodiment of the invention;
[0021] FIG. 7 is a flow chard illustrating a method of performing
rotational electrical impedance myography, according to one
embodiment of the invention;
[0022] FIGS. 8A-C show plots of measured electrical parameters
versus angular orientation of the measurement obtained in
accordance with various aspects of the invention; and
[0023] FIG. 9 is a three-dimensional plot of measured electrical
parameters versus frequency and angular orientation obtained in
accordance with various aspects of the invention.
DETAILED DESCRIPTION
[0024] Embodiments of the invention relate to methods and devices
for determining a characteristic of a region of tissue by applying
an electrical signal to the region and, in response to applying the
electrical signal, obtaining an electrical measurement of the
region of tissue. Such a technique may be referred to as electrical
impedance myography (EIM). Neuromuscular disorders can be assessed
and diagnosed based on the measured electrical signals. In some
embodiments, the quantitative nature of the techniques described
herein can facilitate the evaluation of the progress of a
neuromuscular disorder. For example, the effectiveness of
treatments for neuromuscular disorders, such as newly-developed
drugs, may be evaluated using the techniques described herein.
[0025] To perform an EIM technique, an electrical signal (e.g.,
electric current) may be applied to the region of tissue using
electrodes applied to the skin. Various characteristics can be
determined based on the electrical parameters that are measured for
the region, such as the impedance, reactance, resistance and/or
phase shift. In contrast to existing techniques for assessing and
diagnosing neuromuscular disease, EIM may be more rapid, more
quantitative, less invasive and more repeatable. EIM can be used
for the assessment of muscle conditions, and more specifically,
neuromuscular disease. However, it should be appreciated that EIM
is not limited to the assessment of neuromuscular disease, as any
other suitable tissue characteristic(s) may be measured using EIM,
such as the amount of muscle atrophy that has occurred through
disuse of a muscle (or more rarely, hypertrophy), as the aspects of
the invention are not limited in this respect.
[0026] Some embodiments of the invention relate to methods and
devices for performing multi-frequency EIM, which involves
performing EIM using at least two different frequencies of
electrical signals. Because the electrical parameters of a muscle
can be dependent on the frequency of an alternating current applied
to a muscle, measurements of the muscle impedance for a plurality
of frequencies can be utilized to facilitate diagnosis of muscle
condition, and to differentiate between normal and abnormal muscle
tissue. Multi-frequency EIM can be performed by varying the
frequency of the alternating current applied to the muscle or group
of muscles. For example, the frequency that is applied may be in
the range between about 2 kHz and about 2 MHz, but the invention is
not limited to this particular frequency range, as any other
suitable frequency range can be used.
[0027] The alternating current can be injected via one set of
surface electrodes (referred to as current-injecting electrodes),
and the resulting voltage patterns can be recorded via a second set
of surface electrodes (referred to as voltage-recording
electrodes). Based on the measurement of the injected current's
magnitude, an impedance instrument can convert the voltage signals
into a resistance (R) and reactance (X), for each applied
frequency. From these parameters, a phase (.theta.) may be
computed, for each applied frequency. However, any suitable
electrical parameters may be measured and/or calculated for
evaluation of muscle tissue, as the invention is not limited in
this respect.
[0028] Some embodiments of the invention relate to a method and
apparatus for performing multidirectional EIM (also referred to as
rotational EIM). Because the measured electrical parameters of a
muscle can be anisotropic, and therefore dependent on the
orientation of the measurement electrodes relative to the muscle
fibers, electrical parameter measurements in a plurality of
different directions can be utilized to facilitate diagnosis of
muscle condition, and to differentiate between normal and abnormal
muscle tissue.
[0029] In some embodiments of the invention, a method and apparatus
is provided for both multi-frequency and multidirectional EIM. Such
combined measurements can provide more diagnostic information than
multi-frequency or multidirectional EIM alone. In some embodiments,
a method and apparatus is provided for performing EIM during
contraction of a muscle, referred to as dynamic EIM. The
contraction can be voluntary or electrically induced. In yet other
embodiments, a combination of multi-frequency, multidirectional,
and/or dynamic EIM measurements can also be used to differentiate
between different types of abnormal muscle conditions, including
neuromuscular conditions (e.g., amyotrophic lateral sclerosis
(ALS), inflammatory myopathy) and neurogenic conditions. It should
be appreciated that any of the aforementioned embodiments can be
performed on one or more muscles including quadriceps, biceps,
tibialis anterior, etc., as the invention is not limited to any
specific muscle or muscle group.
[0030] FIG. 1 illustrates an example of an apparatus 100 that may
be used to perform multi-frequency EIM, according to one embodiment
of the invention. Apparatus 100 includes electrodes 112-115, and
also circuit 102 that measures and generates electrical signals
using signal measurement circuit 104 and signal generation circuit
106. Apparatus 100 may include any components in any arrangement
capable of delivering electrical signals and measuring electrical
signals resulting from the electrical signals delivered, as the
aspects of the invention are not limited in this respect.
[0031] In this embodiment, signal generating circuit 106 is coupled
to two spaced-apart current-injecting electrodes 112 and 113, which
may be applied to region of tissue 108. Using electrodes 112 and
113, an electrical signal is applied to region of tissue 108, for
example, by passing an electrical current through the skin and into
the region of tissue. The electrical signal that is applied may be
any suitable signal, such as a predetermined voltage potential or a
predetermined current. The electrodes may be isolated from a supply
voltage using a transformer or any suitable device, such that a
"floating" signal, and applied to the patient, thus enhancing the
safety of the procedure.
[0032] In one example, the signal that is applied to
current-injecting electrodes 112 and 113 may be a sinusoidally
varying voltage having a magnitude of approximately 1 volt
(peak-to-peak) and a frequency between 2 kilohertz and 2 megahertz.
As a consequence of applying this signal, electric current is
injected into region of tissue 108. However, it should be
appreciated that these values of voltage, shape and frequency are
provided merely by way of illustration, as the invention is not
limited in these respects. Furthermore, any suitable circuit and/or
technique may be used to generate the electrical signal applied to
the region of tissue, as the aspects of the invention are not
limited for use with any particular method of electrical signal
generation and/or application.
[0033] Signal measuring circuit 104 is coupled to two spaced-apart
voltage-measuring electrodes 114 and 115. While the generated
signal is applied to tissue region 108 by signal generation circuit
106, signal measurement circuit 104 measures a signal at the tissue
region using voltage-measuring electrodes 114 and 115. The signal
that is measured may be a voltage difference between the two
electrodes that results from the generated signal. Any suitable
circuit and/or technique may be used to measure the signal, as the
aspects of the invention are not limited in this respect.
[0034] Circuit 102 may analyze the measured signal and determine a
characteristic of the region of tissue based on the measured
signal. Any suitable property of the signal may be measured, such
as the magnitude, phase, impedance, resistance and reactance or any
suitable combination thereof. In some embodiments of the invention,
the measured voltage difference at electrodes 114 and 115 may be
divided by the current applied through electrodes 112 and 113 to
obtain an impedance measurement. Circuit 102 may determine an
impedance, resistance, reactance, phase and/or any other suitable
property of the region. Based on the measured signal, any of
suitable electrical parameters, and/or electrical properties of the
region of tissue, circuit 102 may determine a muscle
characteristic. For example, circuit 102 may diagnose and/or assess
a neuromuscular disease based on any suitable criteria, as
discussed in further detail below.
[0035] In some circumstances, circuit 102 may display one or more
of the determined electrical parameters to facilitate diagnosis
and/or assessment by a physician or technician. Circuit 102 may
include any suitable components for performing such measurements,
calculations, determinations and presentation functions. As one
example, circuit 102 may include a lock-in amplifier for impedance
measurement, a computer for performing calculations and a display
for displaying the results to a human (e.g., a technician or a
physician). However, it should be appreciated that any suitable
components or combination of components may be used, as the
invention is not limited for use with any particular components or
configuration of the components.
[0036] FIG. 2 is a flowchart of a method 200 for performing
multi-frequency EIM, according to one embodiment of the invention.
As described above, a first signal of a first frequency is applied
to a tissue region in step 202, and a first signal measurement is
made in step 204, such that the measured signal is a result of
applying the first signal of the first frequency. Next, a second
signal of a second frequency is applied to the tissue region in
step 202, and a second signal measurement is made for the second
frequency in step 204. Further signals at different frequencies may
also be applied, and corresponding measurements may be taken. Any
suitable number of frequencies may be used in the multi-frequency
EIM procedure, as the invention is not limited as to the number of
frequencies measured or the exact frequencies at which measurements
are taken. Preferably, if multi-frequency EIM is performed, the
frequencies used should be of a number and value such that the
measurements are sufficient to provide information useful in
assessment or diagnosis of the tissue region, e.g., the assessment
or diagnosis of a muscle condition.
[0037] In step 206, a characteristic of the region of tissue is
determined based on the measurements. The characteristic that is
determined may be a muscle characteristic, and may be determined
based on one or more electrical properties obtained from the
measurements, such as the impedance, phase, resistance and/or
reactance of the muscle. As another example, a frequency-averaged
impedance, phase, resistance and or reactance may be determined for
at least a portion of the range of frequency measurement. The
frequency-averaged parameter may be a useful parameter for
comparing healthy vs. unhealthy tissue, and evaluating changes in
the tissue over time. For example, a diagnosis of a neuromuscular
condition may be made based on a frequency-averaged parameter being
above or below a threshold value.
[0038] One or more electrical properties obtained from measurements
taken from the region of tissue as a function of frequency may be
used as a signature for the region of tissue. The term signature
refers herein to any collection of information obtained from a
region of tissue that is characteristic of the tissue. The
signature of the tissue, once obtained, may be analyzed to assess,
diagnose or otherwise determine a characteristic and/or condition
of the region of tissue.
[0039] The signature of the tissue may be computationally processed
and/or analyzed or presented to a physician or technician for
analysis. As one example, a plot of an electrical parameter vs.
frequency (e.g., resistance, reactance or phase of the tissue vs.
frequency) may be displayed on a computer monitor, and a physician
may make a diagnosis based on the plot displayed. Multiple plots
displaying any of various electrical properties of the tissue with
respect to frequency may be displayed, as the aspects of the
invention are not limited in this respect.
[0040] FIGS. 3A-C show plots of resistance, reactance and phase vs.
the logarithm of frequency, respectively, measured for two
different ALS patients (C and J) at two different visits, 3-4
months apart each. The solid line shows the measurements taken at
the first visits and the dashed lines shows the measurements taken
at the follow-up visits. Patient C had relatively mild ALS, while
patient J had a more severe form of the disease. As can be readily
appreciated from FIGS. 3B-C, the patient (J) with the more severe
muscle disorder had lower phase and reactance values than the
patient (C) with the less severe disorder. At the follow-up visit,
both patients exhibited primarily a decrease in both phase and
reactance measured, which illustrates the progression of the
disease over time.
[0041] Additionally, the patient with less severe ALS had a much
more pronounced frequency peak in both reactance and phase than the
patient with the more severe form of ALS. These results are
provided to illustrate various criteria that may be used in
determining characteristics of a region of tissue using EIM, and
which may displayed for use by a suitable medical practitioner.
However, it should be appreciated that any suitable measured and/or
calculated criteria may be used for characterization, as the
invention is not limited as to the particular criteria used. In
some circumstances, a diagnoses or assessment may be made by
circuit 102. For example, circuit 102 may be configured to analyze
the signature (e.g., one or more electrical properties as a
function of frequency) to determine a characteristic of the region
of tissue and/or to assess a condition of the region of tissue.
[0042] As discussed above, multidirectional (or rotational) EIM may
be used for the assessment and characterization of a region of
tissue. Multidirectional EIM can be performed by measuring the
voltage difference between voltage-measuring electrodes that are
arranged with a desired orientation with respect to an axis of the
muscle fibers. Both the current-injecting electrodes and the
voltage-recording electrodes may have the same orientation with
respect to the muscle fibers. The electrical properties of the
region of tissue at various orientations may be used to
characterize the region of tissue, e.g., to assess a condition of
the muscle and/or to perform a diagnosis of the muscle.
[0043] FIGS. 4A-B are diagrams illustrating performing EIM at
different orientations with respect to a region of tissue 108.
FIGS. 4A-B show electrodes 112-115, as described above with respect
to FIG. 1. Electrodes 112-115 may be mounted on a base 402. FIG. 4A
illustrates performing EIM along a direction A-A aligned with an
axis of the region of tissue 108, e.g., substantially aligned with
fibers of the muscle. FIG. 4B illustrates performing EIM along a
direction at an angle .theta. with respect to the axis.
Measurements obtained at the different orientations may be used to
characterize and/or otherwise assess a condition of the region of
tissue 108. Measurements may be obtained at multiple orientations
to obtain information about how properties of the tissue vary with
orientation (e.g., to determine a degree of anisotropy of the
tissue), as discussed in further detail below.
[0044] In one embodiment, electrodes 112-115 are mounted on
rotatable base 402, which is made of electrically insulating
material. When a measurement is to be taken, electrodes 112-115 are
brought into contact with the skin at the region of tissue, and are
aligned in a first direction with respect to an axis of the region.
When a second measurement is to be taken, base 402 is rotated by
the desired angle .theta., and electrodes 112-115 are again brought
into contact with the skin at the new orientation.
[0045] Multiple different measurements may be made at different
angles. As one example, measurements may be made at six different
angles, each 30.degree. apart (0.degree., 30.degree., 60.degree.,
90.degree., 120.degree. and 150.degree.). However, it should be
appreciated that any suitable angle increments or number of
measurements at different angles may be used, as the invention is
not limited in this respect. Preferably, if rotational EIM is
performed, the angles used should be of a number and increment such
that the measurements are sufficient to provide information useful
in assessment or diagnosis of the tissue region, e.g., the
assessment or diagnosis of a muscle condition.
[0046] In another embodiment, electrodes 112-115 may be mounted on
rotatable base 402 made of an electrically conductive material. In
this embodiment, the electrically conductive base 402 may be
brought into contact with the skin at the region of measurement,
and the electrodes themselves may not contact the region directly.
In one example, electrically conductive base 402 may be
anisotropically conductive such that it preferentially conducts
current in a direction perpendicular to the base (e.g., into the
patient's body). The anisotropy of the conductive base can prevent
undesirable cross-talk between the electrodes, and may allow
current to penetrate a greater depth into the tissue region.
[0047] FIG. 5 illustrates another embodiment using rotational EIM,
in which a plurality of current-injecting electrodes 502 and
voltage-measuring electrodes 504 are mounted on base 402 at
different orientations. Since the electrodes are mounted at a
plurality of different orientations, it may not be necessary to
rotate the electrodes or base 402 to make measurements at different
angles. When a first measurement is to be made, an appropriate pair
of current-injecting electrodes can be selected and coupled to
signal-generating circuit 106 using any suitable switches. That is,
the plurality of electrodes may be configured such that the
combination of electrodes 502 and 504 at any desired orientation
may be selectively activated.
[0048] For example, the current-injecting electrodes that lie along
line 506 may be selected first. Additionally, the appropriate pair
of voltage measuring electrodes 504 that lie along line 506 may be
selected, and may be coupled to signal-measuring circuit 104 using
any suitable switches. A first measurement may then be taken along
direction 506. When a measurement is to be made along a different
direction, the switches may be reconfigured to couple different
electrodes 502 and 504 to the appropriate circuits, and measurement
may be taken at a different orientation.
[0049] FIG. 6 illustrates an example of a hand-held apparatus 600
that may be used for performing ELM, including rotational and/or
multi-frequency EIM. Providing a hand-held ELM device may
facilitate making EIM measurements, and thus may reduce the amount
of time needed to make the measurements. Hand-held apparatus 600
may include a handle 602, a user interface 604, a body 606, base
608 and electrodes 112-115. The electrodes may be coupled to
circuit 102 in any suitable way, such as through a cord attached at
the bottom of handle 602, for example. FIG. 6 illustrates direction
A-A corresponding to direction A-A illustrated in FIG. 4A.
[0050] In one embodiment, base 608 may be rotatable, as discussed
above, for performing rotational EIM. In another embodiment, base
608 may not be rotatable, but may have a plurality of electrodes
502 and 504 positioned at different orientations, as described in
connection with FIG. 5. Apparatus 600 may be configured such that
either technique may be used, depending on the type of
base/electrode combination that is mounted to the apparatus. In
some circumstances, it may be desirable to provide multiple
different base/electrode combinations of different sizes that may
be easily interchangeable for measuring different types of muscles,
or muscles of different sizes. When a different size is needed, the
base 608 may be detached from apparatus 600 and another base may be
attached.
[0051] FIG. 7 is a flow chart of a method 700 of performing
rotational EIM, according to one embodiment of the invention. In
step 702, a first signal is applied to a tissue region at a first
orientation, and in step 704 a second signal, resulting from the
first applied signal, is measured at the region. Next, a third
signal is applied to the tissue region at a different orientation.
For example, a linear electrode array may be rotated, and another
measurement may be made, as illustrated in FIGS. 4A-B. As another
example, if a quasi-circular electrode array is used (FIG. 5), a
different set of electrodes may be selected that correspond to a
different orientation, and a corresponding measurement may be made.
It is preferred that at least one measurement be made along a
muscle axis, and that at least one measurement be made
perpendicular to the muscle axis. Finally, in step 706, a tissue
characteristic is determined based on the measurements, using any
suitable criteria as discussed above.
[0052] The one or more electrical properties obtained as a function
of orientation may be used as a signature of the region of tissue.
As discussed above, this signature may be analyzed to determine a
characteristic of the tissue and/or to assess a condition of the
muscle. For example, how the one or more electrical properties vary
with orientation (e.g., a degree of anisotropy) may be used to
assess the health of the tissue and/or diagnose a condition such as
a specific neuromuscular disorder. The signature may be analyzed
quantitatively, or compared to a reference signature obtained from
known healthy or diseased tissue to assist in the analysis and/or
diagnosis of the tissue.
[0053] FIGS. 8A-C show plots of resistance, reactance and phase vs.
angular orientation, respectively, for both control patients and an
ALS patient. As shown in the figures, the measured electrical
parameters depend on the orientation of the measurement with
respect to an axis of the muscle fibers, with 0.degree. being
aligned with the axis. The reactance and phase were lower for the
patient with ALS than for the control patients. Additionally, the
control measurements exhibited more significant peaks at 90.degree.
in both reactance and phase for the control patients than for the
patient with ALS. These and/or any other suitable criteria may be
used in determining a characteristic of a region of tissue, as
these examples are described merely by way of illustration.
[0054] In one embodiment, the frequency dependence and orientation
dependence of one or more electrical properties of a region of
tissue are both exploited to obtain a signature of the region of
tissue. For example, at each of a plurality of orientations, an
electrical signal may be applied at a plurality of frequencies.
Measurements of the tissue may be taken for each frequency at each
orientation to determine one or more electrical properties of the
tissue at the various frequencies and orientations. By obtaining
information about both frequency and orientation dependence, a
richer set of indicators are available to facilitate determining a
muscle characteristic and/or assessing a condition of the
tissue.
[0055] FIG. 9 shows a three-dimensional plot 900 illustrating the
results of performing both multi-frequency and rotational EIM.
Overall, the control patient exhibited higher phase measurements
and more pronounced phase peaks with respect to both frequency and
orientation, as compared to a patient with ALS. Thus,
multi-frequency and rotational EIM can be useful, either alone and
in combination, for assessing and detecting neuromuscular
disorders. In particular, the quantitative nature of the
measurements may allow for more accurate assessment and diagnoses
of neuromuscular disorders, and also the evaluation of therapies
for muscle disorders.
[0056] Having thus described several aspects of at least one
embodiment of this invention, it is to be appreciated various
alterations, modifications, and improvements will readily occur to
those skilled in the art. Such alterations, modifications, and
improvements are intended to be part of this disclosure, and are
intended to be within the spirit and scope of the invention.
Accordingly, the foregoing description and drawings are by way of
example only.
[0057] Various aspects of the present invention may be used alone,
in combination, or in a variety of arrangements not specifically
discussed in the embodiments described in the foregoing and is
therefore not limited in its application to the details and
arrangement of components set forth in the foregoing description or
illustrated in the drawings. The invention is capable of other
embodiments and of being practiced or of being carried out in
various ways. In particular, various EIM techniques described
herein may be used alone or in any combination.
[0058] Use of ordinal terms such as "first", "second", "third",
etc., in the claims to modify a claim element does not by itself
connote any priority, precedence, or order of one claim element
over another or the temporal order in which acts of a method are
performed, but are used merely as labels to distinguish one claim
element having a certain name from another element having a same
name (but for use of the ordinal term) to distinguish the claim
elements.
[0059] Also, the phraseology and terminology used herein is for the
purpose of description and should not be regarded as limiting. The
use of "including," "comprising," or "having," "containing",
"involving", and variations thereof herein, is meant to encompass
the items listed thereafter and equivalents thereof as well as
additional items.
[0060] What is claimed is:
* * * * *