SYSTEM AND METHOD FOR PREBALANCING ELECTRICAL PROPERTIES TO DIAGNOSE DISEASE

SYSTEME ET METHODE POUR PREEQUILIBRER LES PROPRIETES ELECTRIQUES DE L'ORGANISME EN VUE DE DIAGNOSTIQUER UNE MALADIE

English Abstract

A system and method for diagnosing the possibility of disease by
making electrical measurements in one of a first body part and a second
substantially similar body part are described. The present invention balances
out differences between homologous body parts that are due to natural
factors unrelated to disease, such as differences in size or symmetry between
left and right breasts. Once data are prebalanced, statistical analyses can be
performed on the data to diagnose disease. The system includes a
normalizing module for obtaining a normalizing factors database from a
screening population group to account for differences in spatial separation of
impedance measurements. Once a set of normalizing factors is obtained, a
prebalancing factor can be obtained that can further be used to adjust raw
electrical measurements. Normalizing factors are applied to a smaller subset
of measurements that are likely to better represent the body part as a whole.
This set of measurements is reduced further by eliminating a set of the
measurements that can be biased by a presence of a disease in a body part.
The remaining measurements for each body part are then averaged to obtain
an overall measure of a body part electrical property. The quotient between
these measures is then used to adjust raw measurements. The adjusted
measurements remove the imbalance that might exist due to natural
differences between body parts. Adjusted measurements are then used as
an input to other methods to obtain more accurate disease diagnostics.

Claims

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Claims:
What is claimed is:
1. A method for prebalancing an electrical property obtained from at least
one of a first body part and a second substantially similar body part, the
method comprising the steps of:
obtaining a prebalancing factor (PBF) from a population group to
account for variability between the first body part and the second body part;
measuring an electrical property of at least one of the first body part
and the second body part with an electrode array; and
utilizing the prebalancing factor to prebalance the electrical property.
2. The method of claim 1, wherein the first and second body parts are
breasts.
3. The method of claim 1, wherein the electrode array includes a plurality
of current injection electrodes and a plurality of voltage measurement
electrodes.
4. The method of claim 3, wherein the electrical property is electrical
impedance, and wherein the step of measuring includes

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injecting currents into the first body part with the plurality of current
injection electrodes;
measuring a set of impedances <IMG> with the plurality of voltage
measurement electrodes;
injecting currents into the second body part with the plurality of current
injection electrodes; and
measuring a set of impedances <IMG> with the plurality of voltage
measurement electrodes.
5. The method of claim 4, wherein the step of utilizing the prebalancing
factor includes
prebalancing <IMG> and <IMG> to yield the sets <IMG> and <IMG>,
where
<IMG>
6. The method of claim 5, further comprising comparing <IMG> to <IMG>
to diagnose the possibility of disease.

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7. The method of claim 1, wherein the step of obtaining a prebalancing
factor includes obtaining sets of normalizing factors <IMG> and <IMG> from the
population group to account for variability within the first and second body
parts.
8. The method of claim 7, wherein the step of obtaining a prebalancing
factor further includes
obtaining a set of impedances <IMG> from the first body part and a set
of impedances <IMG> from the second body part;
utilizing <IMG> and <IMG> to calculate a set of normalized impedances
<IMG>, and <IMG> and <IMG> to calculate a set of normalized impedances
<IMG>; and
averaging a subset of <IMG> and a subset of <IMG> to obtain
the prebalancing factor, the subsets formed by omitting normalized
impedances that could correspond to anomalous electrical pathways.
9. The method of claim 8, wherein the step of obtaining the set of
normalizing factors <IMG> includes
applying n e voltage measurement electrodes to the first body part of a
first member of the population group containing N g members, where n e and
N g are integers greater than one;

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measuring in the first member a set of voltages <IMG>, where <IMG> is
the voltage between an i th voltage measurement electrode and a j th voltage
measurement electrode, the i th and j th voltage measurement electrodes
chosen from among the n e voltage measurement electrodes; and
obtaining a reference specific impedance, <IMG>, associated with a pair
of reference electrodes chosen from among the n e voltage measurement
electrodes.
10. The method of claim 9, wherein the step of obtaining the set of
normalizing factors <IMG> further includes
calculating a set of impedances <IMG> obtained from <IMG>;
calculating a set of specific impedances <IMG> where
<IMG> = <IMG> and <IMG> is a distance related to the distance between the
i th and j th voltage measurement electrodes;
calculating a set of quotients <IMG> where <IMG> = <IMG>; and
calculating quotients for other members of the population group to
obtain all quotients, <IMG> where K runs from one to N g.
11. The method of claim 10, wherein the step of obtaining the set of
normalizing factors <IMG> further includes calculating the set according to
<IMG>

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12. The method of claim 8, wherein the step of obtaining the set of
impedances <IMG> includes
applying a plurality of current injection electrodes on the first body part;
and
applying a plurality of voltage measurement electrodes on the first body
part.
13. The method of claim 12, wherein the step of obtaining the set of
impedances <IMG> includes
injecting a first current between a first current injection electrode and a
second current injection electrode;
measuring a resultant voltage difference between a first voltage
measurement electrode and a second voltage measurement electrode;
obtaining an impedance <IMG> from the resultant voltage difference
between the first voltage measurement electrode and the second voltage
measurement electrode; and
repeating the above steps with other electrodes to obtain the set of
impedances <IMG>.
14. The method of claim 13, wherein the step of obtaining a set of
normalizing factors from the population group to account for variability
within

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the first and second body parts includes obtaining a normalizing factor <IMG>
for
each <IMG>.
15. The method of claim 14, wherein the step of utilizing <IMG> and <IMG>
includes calculating a set of normalized impedances <IMG> according to
<IMG>
16. The method of claim 1, further comprising utilizing the electrical
property after prebalancing to diagnose the possibility of disease in one of
the
first body part and the second body part
17. A system for prebalancing an electrical property obtained from at least
one of a first body part and a second substantially similar body, the system
comprising:
a prebalancing factor module for obtaining a prebalancing factor (PBS
from a population group to account for variability between the first body part
and the second body part;
an electrode array for measuring an electrical property of at least one
of the first body part and the second body part; and
a prebalancing module for utilizing the prebalancing factor to
prebalance the electrical property.

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18. The system of claim 17, wherein the first and second body parts are
breasts.
19. The system of claim 17, wherein the electrode array includes a plurality
of current injection electrodes and a plurality of voltage measurement
electrodes.
20. The system of claim 19, wherein the electrical property is electrical
impedance, and wherein
the plurality of current injection electrodes are used to inject currents
into the first and second body parts; and
the plurality of voltage measurement electrodes are used to measure a
set of impedances <IMG> and <IMG>.
21. The system of claim 20, wherein the prebalancing factor module
prebalances <IMG> and <IMG> to yield the sets <IMG> and <IMG>, where
<IMG>
22. The system of claim 21, further comprising a diagnosis module for
comparing <IMG> to <IMG> to diagnose the possibility of disease.

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23. The system of claim 17, further comprising a normalizing factor
calculation module for obtaining sets of normalizing fiactors <IMG> and <IMG>
to
account for variability within the first and second body parts.
24. The system of claim 23, wherein the electrode array is used to obtain a
set of impedances <IMG> from the first body part and a set of impedances
<IMG> from the second body part, which, together with the sets <IMG> and
<IMG>, yield a set of normalized impedances <IMG> for the first body part,
and a set of normalized impedances <IMG> for the second body part, the
system further comprising a prebalancing calculator module for obtaining the
prebalancing factor after averaging of a subset of <IMG> and a subset of
<IMG>, the subsets formed by omitting normalized impedances that could
correspond to anomalous electrical pathways.
25. The system of claim 24, further comprising n e voltage
measurement electrodes applied to the first body part of a first member of the
population group containing N g members, where n e and N g are integers
greater than one, to obtain a set of voltages <IMG>, where <IMG> is the
voltage between an i th voltage measurement electrode and a j th voltage

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measurement electrode, the i th and j th voltage measurement electrodes
chosen from among the n e voltage measurement electrodes.
26. The system of claim 25, further comprising a specific impedance
calculation module to calculate a set of specific impedances <IMG> from
<IMG> and to calculate a specific reference impedance <IMG> associated with
a pair of reference electrodes chosen from among the n e voltage
measurement electrodes, wherein <IMG> and <IMG> are used to calculate a
set of normalizing quotient <IMG> according to <IMG> = <IMG>, and
wherein other normalizing quotients for other members of the population
group are calculated to obtain all quotients, <IMG> where K runs from one to
N g.
27. The system of claim 26, wherein the normalizing factor calculation
module calculates a set of normalizing factors <IMG> according to
<IMG>
28. The system of claim 27, further comprising a diagnosis module for
utilizing the electrical property after prebalancing to diagnose disease.

Description

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System and Method for Prebalancing Electrical Properties to Diagnose
Disease
Field of the invention
This invention relates to a method for detecting and diagnosing disease
states in living organisms and specifically relates to diagnosis of disease by
measuring electrical properties of body parts.
Background of the invention
Several methods exist for diagnosing disease that involve measuring a
physical property of a part of the body. A change in such a physical property
can signal the presence of disease. For example, x-ray techniques measure
tissue physical density, ultrasound measures acoustic density, and thermal
sensing techniques measures differences in tissue heat generation and
conduction. Other properties are electrical, such as the impedance of a body
part that is related to the resistance that the body part offers to the flow
of
electrical current through it.
Values of electrical impedance of various body tissues are well known
through studies on intact humans or from excised tissue made available
following therapeutic surgical procedures. In addition, it is well documented
that a decrease in electrical impedance occurs in tissue as it undergoes

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cancerous changes. This finding is consistent over many animal species and
tissue types, including, for example human breast cancers.
A method for using electrical properties to diagnose disease involves
homologous body parts, i.e., body parts that are substantially similar, such
as
a left breast and a right breast. In this method, the impedance of a body part
of a patient is compared to the impedance of the homologous body part of the
same patient. One technique for screening and diagnosing diseased states
within the body using electrical impedance is disclosed in U.S. Pat. No.
6,122,544, which is incorporated herein by reference. In this patent, data are
obtained from two anatomically homologous bady regions, one of which may
be affected by disease. Differences in the electrical properties of the two
homologous body parts could signal disease.
To draw such a conclusion, it is assumed that, in the absence of
disease, the two homologous body parts are sufficiently similar, and, ideally,
identical. However, the difference may also arise because of natural
variability between body parts; such as variability due to size or structural
differences, or the effect of different surrounding tissues. If measured
impedances are used directly, the natural variability can skew the results and
a faulty diagnosis may result, such as showing disease in a body part.

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Summary of the invention
The present invention balances out differences between homologous
body parts that are due to natural factors unrelated to disease, such as
differences in size or symmetry between left and right breasts. Once data are
prebalanced, statistical analyses can be performed on the data to diagnose
disease.
In particular, a method for diagnosing the possibility of disease in one
of a first body part and a second substantially similar body part is described
herein. The system includes a normalizing module for obtaining a normalizing
factors database from a screening population group to account for differences
in spatial separation of impedance measurements. This module normalizes a
set of measurements within a body part. Once a set of normalizing factors is
obtained, a prebalancing factor can be obtained that can further be used to
adjust raw electrical measurements. Normalizing factors are applied to a
smaller subset of measurements that are likely to better represent the body
part as a whole. This set of measurements is reduced further by eliminating a
set of the measurements that can be biased by a presence of a disease in a
body part. The remaining measurements for each body part are then
averaged to obtain an overall measure of a body part electrical property. The
quotient between these measures is then used to adjust raw measurements.
The adjusted measurements remove the imbalance that might exist due to
natural differences between body parts. Adjusted measurements are then

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used as an input to other methods, such as HEDA (PCT/CA01101788) to
obtain more accurate disease diagnostics.
More particularly, a method and system for diagnosing the possibility of
disease in one of a first body part and a second substantially similar body
part
is described herein. The system includes a prebalancing factor module for
obtaining a prebalancing factor (PBF~ from a population group to account for
variability between the first body part and the second body part. The system
also includes an electrode array for measuring a first electrical property of
the
first body part and a second electrical property of the second body part. The
system further includes a prebalancing module for utilizing the prebalancing
factor to prebalance at least one of the first electrical property and the
second
electrical property. The prebalanced first electrical property and second
electrical property can be used to diagnose the possibility of disease in one
of
the first body part and the second body part.
Brief description of the drawincts
Figure 1 is a flow/system block diagram of the normalizing factor
module of the diagnostic system;
Figure 2 is a flowlsystem block diagram of the prebalancing factor
module of the diagnostic system; and

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Figure 3 is a filowchart illustrating the method steps performed by the
diagnostic system of Figure 1 and Figure 2 to diagnose disease in a body
part.
Detailed description of the invention
Normalizinc~Factors Module
Figure 1 shows a flow/system diagram for detecting and diagnosing
disease, such as a breast cancer. The system of Figure 1 includes a multi-
channel impedance-measuring instrument 11, an electrode array 12, a
normalizing module 14 and a normalizing factors database 18. In one
embodiment, the electrode array 12 includes ne current injection electrodes,
and ne voltage measurement electrodes. The electrodes are applied to the
body part, and each of the current injection electrodes is associated with the
adjacent voltage measurement electrode. Impedance is calculated by
measuring the voltage between two voltage electrodes when the current is
injected between the associated current electrodes. The total number of
independent current injections and related impedances is n~, = ne~(ne-1 )I2.
Normalization factors are calculated from a population of Ng subjects
who have no disease in a body part of interest (e.g. women with disease-free
breasts). For each subject, nc, impedance measurements, f Z~'K}, and nc,

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impedance measurements, {Z;~'~}, are acquired, where Z~~S'x is the
impedance of the first body part measured between voltage electrodes i and j
when current is injected between associated current electrodes, for the K'h
subject. For each measurement the specific impedance calculation module
22 calculates:
x
K Zt>>
Mt>J -'-
d;,~
where MK is a specific impedance(i.e., impedance per distance), Z,x is the
measured impedance between voltage electrodes i and j, d;,; is related to the
distance between the electrodes. (In the last equation and in the rest of this
section, the superscripts "first" and "sec" are omitted for clarity of
notation;
however, it should be understood that these are implied where quantities
pertain to the first or second body part.) In one embodiment the Euclidean
distance is measured between the voltage electrodes i and j on the electrode
array 12 while the electrode array is placed on a realistic model of a body
part. In other embodiments, a different metric can be employed that accounts
for the curvature of the electrode array, which duplicates the curvature of
the
breast.
Further, a pair of electrodes (refs, ref2) are selected, and its specific
impedance designated as a reference measurement (MYer). The reference
measurement electrodes are the same over the entire subject population.
The normalizing quotients for subject K can be calculated as:

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K
M. .
x =.,
qt>.i - Mre.!
for each pair of electrodes (ij). The normalizing quotients differ based on
the
position of electrodes on the body part (e.g. on a breast there is a
significant
difference between measurements in the inner lower region, as compared to
the outer upper region).
The normalizing factors calculation module 24 repeats the previous
steps in all members of the population group fio obtain the set of quotients,
~qi J,qi ~,...,C~Ng~, the superscripts denoting the various members of the
group.
The normalizing factor calculation module 24 calculates a set of
normalizing factors r,,~ given by:
N~ x
~,~ =1~ ~ ~m .
g K=I
The steps leading to the normalizing factors ~,~ are performed on a
population group with no disease. These values may then be stored in the
normalizing factors database 18.

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Prebalancing Factor Module
The prebalancing factor module 16 includes software andlor hardware
for obtaining a prebalancing factor P~F from a population group to account
for variability between the first body part and the second body part, as
described in more detail below. For example, if the first and the second body
part are right and left breasts, variability can arise because of size or
architectural differences. This variability can skew results when comparing
the right and left breasts, and cause faulty diagnosis. The present invention
attempts to eliminate such natural variability between the first and the
second
body part by prebalancing so that differences that do arise can be attributed
more confidently to the presence of disease.
Referring to Figure 2, the method uses impedance measurements
taken from the multi-channel impedance measuring instrument 11 with the
pair of electrode arrays 12 such as the one described in PCTlCA01/01788
which is incorporated herein by reference, plus the normalizing factors
database 18, and prebalancing module 16.
The electrodes of the electrode array 12 are applied on the patient, the
multi-channel impedance measurement instrument 11 measures electrical
properties (e.g, impedances) of two substantially similar body parts, such as
a
left and a right breast.

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A small subset of all measurements that characterize the body part is
taken. In the case where the first and the second body part are human
breasts, it is advantageous that 1) the distance between the electrode pairs
in
the subset is approximately the same; 2) the electrodes are disposed at the
outer area of the breast, and 3) the separation between electrodes in the
pairs
embraces about a quarter of the breast circumference.
Normalizing factors obtained from a normalizing factors database 18
are applied to the subset of first and second body part measurements 32, as
follows:
first first first sec sec sec
Znormi>~ - Zi,i bra J and Znormi,i - Zi>~ ~r>~
where Z~Stis the impedance measured between voltage electrodes i and j
when current is injected between associated current injection electrodes i and
j . In particular, the impedance may be obtained according to V;fi"t ~Ifi~ t,
where
V~f~st is the voltage difference between electrodes i and j when a current
1~tis
injected between associated current injection electrodes i and j.
This yields a normalized subset of impedances for both body parts.
These subsets are pared down further to yield a final (and smaller) normalized
subset by removing normalized impedances that could correspond to
anomalous electrical pathways. For example, these subsets can be formed
by removing approximately half of the smallest values of the normalized
impedances. These smaller values are removed because they could

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potentially correspond to electrical pathways encountering malignant tumors.
The highest value of the set, which could be an outlier, may also be removed.
(Alternatively, more than one, e.g., the two highest values can be removed).
The values in the final normalized subsets are averaged as follows:
Znormf"$' - ~ ~ZnormF S' and Zno~ns~ = n~~Znormp
p=1 y
where each Znormp S' is associated with a particular pair of electrodes, the
sum
running over the corresponding pairs that contribute to the subset. Thus,
n <_ nc, and n'<_ n~, . The prebalancing factor PBFis then calculated in the
prebalancing factor calculator module 34:
PBF _ Znorm 5e° .
Znorm ~"rs'
The prebalancing module 36 prebalances alf impedance
Z;,~ and Z; ~ Z. . Z. .
measurements ~' S~ to yield '~'* and ;;°* , where
Zfi'~'* = PBF ~ Z~~' and Z;S;°* - Z;;° , if PBF is greater
than one, and
Zfi~'* = Zf;~' and Z;;°* = Z; ~ l PBF , if PBF is less 'than one.
Once the raw impedance measurements have been prebalanced, the
prebalanced values can be processed to diagnose disease with a diagnosis
module 66. For example, statistical tests can be performed to determine if
significant differences exist between the right and left breast that could
signal
disease. Examples of such diagnostic procedures that can be performed are
described in U.S. Patent No. 6,122,544.

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Different computer systems can be used to implement the method for
diagnosing a disease in a body part. In one embodiment, the method can be
implemented on a 2 GHz PentiumT"~ system with 512 Mb RAM.
Figure 3 shows a flowchart which illustrates the steps performed for
diagnosing the possibility of disease in a body part. At the application step
(41 ), a plurality of electrodes is applied to a set of screening subjects,
and
impedance measurements are performed on each subject (42). Next, a set of
normalizing quotients is obtained for each subject (43). These quotients are
averaged to obtain a database of normalizing factors (44). The above steps
are performed only once to obtain the normalizing factors database.
For each subject to be diagnosed the following steps are performed. A
plurality of electrodes is applied to both body parts (46) and impedance
measurements are taken (47). A prebatancing factor is calculated based on a
subset of measurements and normalized factors database (48). All
impedance measurements are prebalanced using the calculated prebalancing
factor (49).
It should be understood that various modifications and adaptations
could be made to the embodiments described and illustrated herein, without
departing from the present invention, the scope of which is defined in the
appended claims. For example, although emphasis has been placed on
describing a system for diagnosing breast cancer, the principles of the
present

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invention can also be advantageously applied to other diseases of other body
parts. In addition, the same principles of the present invention used to
prebalance impedance measurements can be used to prebalance other
electrical or non-electrical measurements, such as acoustic impedance
measurements. Moreover, there are several reasons to prebalance electrical
properties besides the diagnosis of disease. For example, electrical data can
be prebalanced for the purpose of conducting research, to characterize
normal electrical differences between homologous body parts. The method
for prebalancing can be used as a predictor of homologous dififerences as
measured by tissue physical density or acoustic transmission properties. A
set of "normal or unaffected" values within a larger set may be sought that
may contain members that are likely to be outside the normal set. The
method and system described herein may then be used to prebalance the
appropriate values.
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Representative Drawing