U.S. patent application number 14/507492 was filed with the patent office on 2015-04-02 for volumetric induction phase shift detection system for determining tissue water content properties.
The applicant listed for this patent is The Regents of the University of California. Invention is credited to Cesar A. Gonzalez, Boris Rubinsky.
Application Number | 20150094549 14/507492 |
Document ID | / |
Family ID | 37532622 |
Filed Date | 2015-04-02 |
United States Patent
Application |
20150094549 |
Kind Code |
A1 |
Rubinsky; Boris ; et
al. |
April 2, 2015 |
Volumetric Induction Phase Shift Detection System for Determining
Tissue Water Content Properties
Abstract
A method and apparatus of determining the condition of a bulk
tissue sample, by: positioning a bulk tissue sample between a pair
of induction coils (or antennae); passing a spectrum of alternating
current (or voltage) through a first of the induction coils (or
antennae); measuring spectrum of alternating current (or voltage)
produced in the second of the induction coils (or antennae); and
comparing the phase shift between the spectrum of alternating
currents (or voltages) in the first and second induction coils (or
antennae), thereby determining the condition of the bulk tissue
sample.
Inventors: |
Rubinsky; Boris; (El
Cerrito, CA) ; Gonzalez; Cesar A.; (Anahuac,
MX) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
The Regents of the University of California |
Oakland |
CA |
US |
|
|
Family ID: |
37532622 |
Appl. No.: |
14/507492 |
Filed: |
October 6, 2014 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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14109647 |
Dec 17, 2013 |
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14507492 |
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13723696 |
Dec 21, 2012 |
8633033 |
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14109647 |
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13329080 |
Dec 16, 2011 |
8361391 |
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13723696 |
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13028082 |
Feb 15, 2011 |
8101421 |
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13329080 |
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12616102 |
Nov 10, 2009 |
7910374 |
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13028082 |
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11664755 |
Feb 25, 2008 |
7638341 |
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PCT/US06/18384 |
May 12, 2006 |
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12616102 |
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60689401 |
Jun 9, 2005 |
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Current U.S.
Class: |
600/306 ;
600/371; 600/547 |
Current CPC
Class: |
A61B 5/02042 20130101;
A61B 5/05 20130101; A61B 5/0205 20130101; A61B 5/443 20130101; A61B
5/0537 20130101; A61B 5/4244 20130101; A61B 5/725 20130101; A61B
5/7228 20130101; A61B 5/4064 20130101; G01N 27/026 20130101; G01R
33/34 20130101; A61B 2562/143 20130101; A61B 5/4869 20130101; A61B
5/4878 20130101; G01R 33/483 20130101; A61B 5/413 20130101; G01R
33/36 20130101; A61B 5/7225 20130101; A61B 5/053 20130101; G01R
33/4828 20130101; A61B 5/4519 20130101 |
Class at
Publication: |
600/306 ;
600/547; 600/371 |
International
Class: |
A61B 5/00 20060101
A61B005/00; G01R 33/36 20060101 G01R033/36; A61B 5/0205 20060101
A61B005/0205; G01R 33/48 20060101 G01R033/48; A61B 5/02 20060101
A61B005/02; G01R 33/34 20060101 G01R033/34; G01R 33/483 20060101
G01R033/483 |
Goverment Interests
GOVERNMENT SUPPORT
[0002] This invention was made with government support under Grant
No. RR018961 awarded by the National Institutes of Health. The
government has certain rights in the invention.
Claims
1. A method of determining the condition of a bulk tissue sample,
comprising: positioning a bulk tissue sample between a pair of
induction coils or antennae; passing a spectrum of alternating
current or voltage through a first of the induction coils or
antennae; measuring a spectrum of alternating current or voltage
produced in the second of the induction coils or antennae; and
comparing the phase shift between the spectrum of alternating
currents or voltages in the first and second induction coils or
antennae, thereby determining the condition of the bulk tissue
sample.
2. The method of claim 1, wherein the first and second induction
coils or antennae do not contact the bulk tissue sample.
3. The method of claim 1, wherein determining the condition of the
bulk tissue sample comprises: detecting at least one condition from
the group consisting of edema, ischemia, bleeding, dehydration,
water accumulation in the bulk tissue sample, extravasation, and
disease.
4. The method of claim 1, wherein the bulk tissue sample is
selected from the group consisting of brain tissue, lung tissue,
heart tissue, muscle tissue, skin tissue, kidney tissue, cornea
tissue, liver tissue, abdomen tissue, head tissue, leg tissue, arm
tissue, pelvis tissue, chest tissue or trunk tissue.
5. The method of claim 1, wherein the frequency of the spectrum of
alternating current is between 10 kHz and 10 GHz.
6. The method of claim 1, wherein the frequency of the spectrum of
alternating current is between 1 MHz and 10 GHz.
7. The method of claim 1, wherein determining the condition of the
bulk tissue sample comprises detecting edema, ischemia,
dehydration, extravasation, in the tissue sample, and wherein the
spectrum of frequency of the alternating current is between 100 kHz
to 10 GHz.
8. The method of claim 1, wherein determining the condition of the
bulk tissue sample comprises detecting interperitoneal bleeding in
the tissue sample, and wherein the spectrum of frequency of the
alternating current is between 100 kHz to 10 GHz
9. A method of determining changes in the condition of a bulk
tissue sample over time, comprising: positioning a bulk tissue
sample between a pair of induction coils or antennae; passing a
spectrum of alternating current or voltage through a first of the
induction coils or antennae; measuring a spectrum of alternating
current or voltage produced in the second of the induction coils or
antennae; and comparing the phase shift between the spectrum of
alternating currents or voltages in the first and second induction
coils or antennae over time, thereby determining a change in the
condition of the bulk tissue sample over time.
10. The method of claim 9, wherein the first and second induction
coils or antennae do not contact the bulk tissue sample.
11. The method of claim 9, wherein determining the change in the
condition of the bulk tissue sample over time comprises: detecting
a change over time in at least one condition from the group
consisting of edema, ischemia, bleeding, dehydration, water
accumulation in the bulk tissue sample, extravasation, and
disease.
12. The method of claim 9, wherein the bulk tissue sample is
selected from the group consisting of brain tissue, lung tissue,
heart tissue, muscle tissue, skin tissue, kidney tissue, cornea
tissue, liver tissue, abdomen tissue, head tissue, leg tissue, arm
tissue, pelvis tissue, chest tissue or trunk tissue.
13. An apparatus for determining the condition of a bulk tissue
sample, comprising: a first induction coil or antenna; a second
induction coil or antenna; an alternating current power supply
connected to the first induction coil or antenna, the alternating
current power supply configured to generate a spectrum of currents
or voltages in the first induction coil or antenna; and a
measurement system connected to the second induction coil or
antenna, wherein the measurement system is configured to measure a
phase shift difference in the spectrum of currents or voltages
between the first and second induction coils or antennae when the
first and second induction coils or antennae are positioned on
opposite sides of a tissue sample.
14. The apparatus of claim 13, further comprising: a system to
compare the phase shift between the alternating currents or
voltages in the first and second induction coils or antennae to
determine the condition of the bulk tissue sample.
15. The apparatus of claim 13, wherein the alternating current
power supply produces a spectrum of alternating currents with a
frequency between 10 kHz and 10 GHz.
16. The apparatus of claim 13, wherein the alternating current
power supply produces a spectrum of alternating currents with a
frequency between 1 MHz and 10 GHz.
17. The apparatus of claim 14, wherein the system to determine the
condition of the bulk tissue sample comprises: a system configured
to detect at least one of edema, ischemia, bleeding, dehydration,
water accumulation in the bulk tissue sample, extravasation, and
disease by analysis of the phase shift difference in the currents
between the pair of induction coils or antennae.
18. The apparatus of claim 13, wherein the alternating current
power supply comprises: a function generator configured to generate
an alternating current in the first induction coil or antenna
having a frequency that changes in pre-programmed steps.
19. The apparatus of claim 18, wherein the function generator
supplies an excitation signal of approximately 20 mA in the range
of 1 to 8.5 MHz at pre-programmed steps.
20. The apparatus of claim 13, further comprising: a first
differential receiving amplifier connected to the first induction
coil or antenna; and a second differential receiving amplifier
connected to the second induction coil or antenna.
21. The apparatus of claim 13, further comprising: a dual-channel
demodulator connected to the first and second induction coils or
antennae; and an analog-digital converter connected to the
dual-channel demodulator.
22. The apparatus of claim 21, wherein the dual-channel demodulator
comprises: a mixer; and a narrow band pass filter.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application is a Continuation and claims
priority to U.S. patent application Ser. No. 14/109,647, filed Dec.
17, 2013 (now abandoned); which is a continuation of U.S. patent
application Ser. No. 13/723,696, filed on Dec. 21, 2012 (now U.S.
Pat. No. 8,633,033); which is a continuation of U.S. patent
application Ser. No. 13/329,080, filed Dec. 16, 2011 (now U.S. Pat.
No. 8,361,391); which is a Continuation of U.S. patent application
Ser. No. 13/028,082, filed on Feb. 15, 2011 (now U.S. Pat. No.
8,101,421); which is a Continuation of U.S. patent application Ser.
No. 12/616,102, filed on Nov. 10, 2009 (now U.S. Pat. No.
7,910,374); which is a Continuation of U.S. patent application Ser.
No. 11/664,755, filed on Feb. 25, 2008 (now U.S. Pat. No.
7,638,341); which is a 371 National Phase patent application of PCT
application serial number PCT/US2006/18384, filed on May 12, 2006;
which claims the benefit of Provisional patent application Ser. No.
60/689,401, filed on Jun. 9, 2005, the disclosures of which are
hereby incorporated herein by reference in their entirety.
TECHNICAL FIELD
[0003] The present invention relates to non-contact systems for
assessing water content properties in bulk tissue, and identifying
medical conditions associated with abnormal tissue water content
properties.
BACKGROUND OF THE INVENTION
(a) Medical Conditions Caused by Abnormal Tissue Water Content:
[0004] A variety of different medical conditions are associated
with abnormal tissue water content. Examples of such medical
conditions include, but are not limited to: edema (including brain
edema), ischemia, internal bleeding (including intraperitoneal
bleeding), dehydration, and extravasation.
[0005] A change in water content occurring in an organ or a tissue
sample over time can be very indicative of a medical condition
developing. As will be explained below, different systems have been
developed to assess tissue water content properties (and changes in
such conditions over time). Such systems can be particularly useful
in diagnosing the onset of various medical conditions. However, as
will be shown, existing systems all suffer from various
disadvantages.
(b) Edema and Ischemia:
[0006] Tissue edema is a pathological condition involving an
increase in the amount of fluid in tissue. The accumulation of
fluid can be extracellular, intracellular or both. Extracellular
edema is caused either by increased ultrafiltration or decrease in
reabsorption. Intracellular edema can be caused by ischemia and the
resulting intracellular hyperosmolarity or as a consequence of
extracellular hypotonicity. Independent of the edema type, the
condition is one in which the amount of liquid in the tissue
increases and the balance is changed, usually as a function of time
after an event has occurred. Tissue edema is of substantial concern
when it occurs in the brain or in the lung. In the brain,
extracellular edema develops in a delayed fashion, over a period of
hours or days, after a large hemispheric stroke and is a cause of
substantial mortality. Ischemic brain edema begins with an increase
in tissue Na+ and water content and continues with blood brain
barrier breakdown and infarction of both the parenchyma and the
vasculature itself.
[0007] A study of the Center for Disease Control and Prevention for
the period from 1995 to 2001 indicates that at least 1.4 million
annual traumatic brain injuries occur in the USA alone. These
resulted in about 1.1 million emergency department visits, 235,000
hospitalizations and about 50,000 deaths. About 1,100 incidents per
100,000 in population occur in the age group from 0 to 4 years.
Head injury causes more deaths and disability than any other
neurological condition under the age of 50 and occurs in more than
70% of accidents. It is the leading cause of death in males under
35 yr old. Fatalities may not result from the immediate injury;
rather, progressive damage to brain tissue develops over time. In
response to trauma, changes occur in the brain that requires
monitoring to prevent further damage.
[0008] Brain swelling can be caused by an increase in the amount of
blood to the brain. Brain edema is one of the most important
factors leading to morbidity and mortality in brain tumors.
Cerebral edema, which is an increase in brain volume caused by an
absolute increase in tissue water content, ensues. The accumulation
of fluid can be extracellular, intracellular or both. Vasogenic
edema results from trans-vascular leakage often caused by the
mechanical failure of the tight endothelial junction of the
blood-brain barrier and increased ultrafiltration or decrease in
re-absorption. Vasogenic edema also results from extravasation of
protein rich filtrate in interstitial space and accumulation of
extracellular fluid. Cytotoxic edema is characterized by cell
swelling. Cytotoxic edema is an intracellular process resulting
from membrane ionic pump failure. It is very common after head
injury and it is often associated with post-traumatic ischemia and
tissue hypoxia. The primary mechanism is reduction of
sodium-potassium ATPase pump efficiency due to local hypoxia and
ischemia. This type of edema occurs in cancer with compression of
microcirculation. Interstitial or hydrocephalic edema occurs when
there is an accumulation of extracellular fluid in the setting of
hydrocephalus. Intraventricular tumors or tumors that constrict
ventricles can cause this type of edema.
[0009] Independent of the edema type, the condition is one in which
the amount of liquid in the tissue increases or the balance is
changed. Edema is of substantial concern when it occurs in the
brain. The characteristics of brain edema, is that it develops in a
delayed fashion, over a period of hours or days, after the brain
trauma has occurred and is a cause of substantial mortality.
Detection and continuous monitoring of edema in the brain is
essential for assessment of medical condition and treatment.
[0010] Pulmonary edema is often associated with lung injury and
also requires continuous monitoring and treatment. Detection and
continuous monitoring of edema in the brain and lung is useful for
assessment of medical condition and treatment.
[0011] Ischemia of tissues and organs is caused by a change in
normative physiological conditions such as deprivation of oxygen
and blood flow. It can occur inside the body, for instance as a
consequence of impediments in blood flow. Ischemia also can occur
outside the body when organs preserved for transplantation are
transported. Ischemia results in changes in the intracellular
composition which is accommodated by changes in the water content
properties of the intracellular and extracellular space and leads
to cell death.
[0012] Therefore, in medical applications it is important to be
able to detect changes in water content properties which are
indicative of the occurrence of edema and ischemia.
(c) Internal and Interperitoneal Bleeding:
[0013] Trauma is the third most common cause of death in all age
groups and the leading cause of death in the first three decades of
life. Of all traumatic injuries abdominal and pelvic injuries
contribute to about 20% of the fatalities. In addition, death from
abdominal hemorrhage is a common cause of preventable death in
trauma patients. Bleeding is the cause of one in four maternal
deaths worldwide. Death may occur in less than two hours after the
onset of bleeding associated with childbirth. In addition to
trauma, abdominal bleeding also occurs in several post-surgery
conditions. Unfortunately, early intraperitoneal bleeding cannot be
detected by vital signs (rate pulse or blood pressure) and it
becomes evident only after a critical amount of blood has found its
way into the abdominal cavity. Therefore, death from abdominal
hemorrhage is a common cause of preventable death in trauma
patients. However, early detection of intraperitoneal bleeding may
play a critical role in the patient survival.
(d)_Extravasation:
[0014] Extravasation is the unwanted passage or escape of blood,
serum, lymph or therapeutic drugs directly into body tissues. Signs
and symptoms may include the sudden onset of localized pain at an
injection site, sudden redness or extreme pallor at an injection
site, or loss of blood return in an intravenous needle.
Extravasation can lead to skin and tissue necrosis, and
"Compartment Syndrome" (a pathologic condition caused by the
progressive development of arterial compression and reduction of
blood supply).
[0015] Similar to the medical conditions described above,
extravasation results in a change in water content properties in
the tissue (typically at or near an injection site). Thus, it would
be desirable to detect extravasation, (preferably by a on-contact
system). Unfortunately, no such system currently exists.
(e) Existing Systems for Assessing Tissue Water Content
Properties--and their Limitations:
[0016] Accumulation of fluid in tissue changes the electrical
impedance of the tissue. This has suggested the use of
bioelectrical impedance measurements to detect water content in the
body since 1962. Edema and ischemia can be also detected with
bioelectric measurements. With edema or ischemia, the ratio between
extracellular and intracellular water changes. Since this should
cause a shift in the beta dispersion frequency, bioimpedance
spectroscopy based on measuring the changes in the overall
impedance has been viewed as a likely way to produce information on
edema and ischemia.
[0017] Another important method to evaluate and monitor edema is
Electrical Impedance Tomography (EIT). EIT uses an array of
electrodes (placed on the patient) to inject subsensory currents
and measure the resultant voltages. The data is used to reconstruct
a map of the electrical impedance of tissue. Unfortunately, a
problem with electrical impedance tomography (EIT) is that it
requires the placement of needles in contact with the tissue.
Furthermore, EIT produces an image of the area showing the location
of the change in water content properties. This is a time consuming
process. In addition the details produced by imaging may not be
needed in many applications of detection of water content
properties.
[0018] Another way to detect edema and ischemia is by performing
induction tomography. In this approach, induction currents rather
than injection currents are used to produce a map of the electrical
properties of tissue. The problem with this method is that the
induction coils need to be large, i.e. are much larger than
electrodes, and there are difficulties with using large number of
coils for good imaging resolution. Furthermore the imaging outcome
has the same overall attributes as EIT in regards to detection of
edema and ischemia. In general, imaging and tomography are
expensive and require many measurements. In the past, direct
impedance measurements of ischemia have been used to assess the
condition of organs preserved for transplantation. However as with
EIT, this requires the placement of needles on the organ or tissue.
This is cumbersome with organs and impossible in such tissues as
the brain and the lungs or large volumes of the abdomen.
[0019] Tumor associated edema is visible on both CT and MRI.
Unfortunately, the diagnostic is complicated by the fact that on CT
it produces low signal, which can be confused with low-signal
producing tumors. On MRI, the edematous brain produces a
hypersignal, which may be confused with hypersignal producing
tumors.
[0020] With regard to diagnosing abdominal injuries, there are two
methods for rapid detection of intraperitoneal bleeding, FAST
(focused assessment with sonography for trauma) ultrasound and
peritoneal lavage. Evaluations of the practice in the evaluation of
internal injuries show that physicians prefer to use FAST
ultrasound over diagnostic peritoneal lavage (DPL) because DPL is
invasive and most doctors have limited experience in DPL and
interpreting the results. However, rural hospitals rarely have
advanced imaging modalities such as CT scan or emergency
ultrasound. As a result, emergency physicians in such centers are
forced to rely on clinical examination and plain radiography alone.
The lack of advanced imaging may delay the identification of
patients who require transfer, or lead to inappropriate transfer of
patients who are later found not to require trauma centre
intervention.
[0021] In addition, most of the current bioelectronic techniques
for detection of abdominal bleedings try to produce an image or
information that will determine the site of bleeding. However,
currently in the medical emergency departments initial evaluation
and treatment is not geared towards identification of a specific
abdominal injury, but rather to determine if one exists.
SUMMARY OF THE INVENTION
[0022] The present invention provides an electrical measurement
system that conveniently produces bulk information on the
properties of organ or tissue. In preferred aspects, the present
invention uses bioimpedance analysis based on the conduction of an
applied electrical current in the tissue to detect a variety of
medical conditions.
[0023] In one aspect of the invention, the present system provides
a non-contact method for detecting tissue properties in a volume of
tissue by measuring change in electromagnetic induction
spectroscopic distribution of phase shift over time. Thus,
instantaneous bulk measurements of the electrical properties of an
organ or tissue sample can be made with induction currents. In
another aspect of the invention, the present system provides a
non-contact method for detecting changes in tissue properties in a
volume of tissue by measuring change in electromagnetic induction
spectroscopic distribution of phase shift over a period of
time.
[0024] In either of the above instantaneous "snapshot" aspect
approach, or the measurement of changes occurring over time
approach, measurements are made detecting phase shift between the
applied and measured currents. Specifically, a change is detected
in the phase angle between the AC currents in an emitting and a
sensing induction coil or antenna. This phase shift is caused by a
volume of tissue placed between the emitting and a sensing coil or
antenna through which AC currents are passed over a wide range
(i.e.: spectrum) of frequencies.
[0025] As will be shown below, the present invention provides a
spectroscopic measuring method that is simpler and more reliable
than overall impedance measurement. In addition, the present
invention provides a system of measuring the electromagnetic change
in water content properties in the bulk would suffice for many
applications.
[0026] The present invention can thus be use to evaluate the
medical condition of a volume of biological tissue by assessing the
bulk tissue electrical properties of the volume of tissue, and
determining how they change over time.
[0027] There are numerous advantages to the present invention,
including, but not limited to, the following:
[0028] First, the present invention does not require galvanic
coupling between the electrode and the skin or the tissue under
measurement. Instead, the present system is completely
non-invasive. As a result, it is easy to operate. Moreover, it is
inexpensive to build and to operate. Thus, the present invention
can be operated in locations and conditions such as remote
villages, traffic accidents or military engagement in which there
is no full medical service.
[0029] Second, measuring change in phase shift in the bulk of
tissue, body or organ with time is a simple measurement that
focuses only on the occurrence of changes in a particular frequency
or range of frequencies. Thus, the present system of bulk detection
has the advantage of low cost and ease of use while still providing
relevant data.
[0030] Third, a further advantage of the present system is that
instantaneous measurement of the phase shift can be made.
Alternately, however, time dependent measurements can also be made
to detect the progress of the phase shift in time to determine the
development of the medical condition
[0031] Fourth, the present invention is especially well suited to
detect edema in the brain since the skull does not represent a
barrier for the electro-magnetic field at certain frequencies.
[0032] Fifth, while imaging the body or the organ may be of
importance, very often in clinical practice it is sufficient simply
to know that there is a problem occurring (and to alert the
physician to the occurrence). I.E.: to determine that there is
edema (or bleeding, or other conditions) in a certain organ or
parts of the body; such as the brain the abdomen or the lung or
that extravasation or dehydration are taking place. Furthermore,
there are many applications in which it is sufficient to have a
general estimate of the occurrence of ischemia and not the precise
location of the ischemic tissue. For instance, in organ
transplantation it is important to know that the organ is
functional or not and not the degree of functionality of the
different parts of the organ. Accordingly, the present system of
bulk measurement indications of the occurrence of edema or ischemia
may be sufficient for many clinical many applications.
[0033] In one aspect, the present invention provides a method of
determining the condition of a bulk tissue sample, by: positioning
a bulk tissue sample between a pair of induction coils or antenna;
passing a spectrum of alternating current through a first of the
induction coils; measuring spectrum of alternating current produced
in the second of the induction coils; and comparing the phase shift
between the spectrum of alternating currents in the first and
second induction coils, thereby determining the condition of the
bulk tissue sample.
[0034] In another aspect of the method, the present invention
comparing the phase shift between the spectrum of alternating
currents in the first and second induction coils over time, thereby
determining a change in the condition of the bulk tissue sample
over time.
[0035] In another aspect, the present invention provides an
apparatus for determining the condition of a bulk tissue sample,
comprising: a first induction coil; a second induction coil; an
alternating current power supply connected to the first induction
coil, the alternating current power supply configured to generate a
spectrum of currents in the first induction coil; and a measurement
system connected to the second induction coil, wherein the
measurement system is configured to measure a phase shift
difference in the spectrum of currents or voltages between the
first and second induction coils when the first and second
induction coils are positioned in relation to each other and of a
tissue sample or organ or body parts.
[0036] In another aspect, the present invention provides an
apparatus for determining the condition of the bulk tissue sample,
comprising: a first antenna; a second antenna; a high frequency
electromagnetic waves supply to generate a spectrum of
electromagnetic waves in the first antenna; and a measurement
system connected to the second antenna, wherein the measurement
system is configured to measure a phase shift difference in the
spectrum of currents or voltages between the first and second
induction antennae when the first and second induction antenna are
positioned in relation to each other and of a tissue sample or
organ or body parts.
[0037] The present invention has been experimentally validated to
show that it can detect ischemia and/or edema and/or
intraperitoneal bleeding.
[0038] The present system can be used on a wide variety of tissues,
including, but not limited to brain tissue, lung tissue, heart
tissue, muscle tissue, skin tissue, kidney tissue, cornea tissue,
liver tissue, abdomen tissue, head tissue, leg tissue, arm tissue,
pelvis tissue, chest tissue or trunk tissue.
[0039] In some aspects of the invention, the frequency range of the
alternating current is from 10 kHz to 10 GHz. In one aspect, a,
more preferred range is from 1 MHz to 10 GHz. The present invention
can be used with coils or antenna. One preferred range for use with
coils is from 10 kHz to 1 GHz, with a more preferred range being
from 10 kHz to 300 MHz. One preferred range for use with antennae
is from 100 MHz to 10 GHz, with a more preferred range being from
300 MHz to 10 GHz.
BRIEF DESCRIPTION OF THE DRAWINGS
[0040] FIG. 1 is a simplified schematic of the present invention,
showing a tissue sample positioned between a pair of induction
coils.
[0041] FIGS. 2A, 2B and 2C show calculated bulk electrical
parameters as a function of frequency for various ratios of normal
tissue to edema.
[0042] FIG. 3 is a schematic of a device for electro-magnetic field
generation.
[0043] FIG. 4 is a multi-frequency inductive phase shift detection
spectrometer in accordance with the present invention.
[0044] FIG. 5 is a calculated graph of phase shift vs. frequency in
a simulation of intraperitoneal bleeding.
[0045] FIG. 6 is a magnified view of FIG. 5 in the frequency region
from 1 to 9 MHz.
[0046] FIG. 7 is experimentally measured homogenized absolute
values of the inductive phase shift as a function of frequency for
various tissue volumes of saline injected into a rat abdomen. The
percentage indicates the amount of saline injected relative to the
total body weight of the rat. The rats used in this experiment were
about 250 to 300 grin weight.
[0047] FIG. 8 is a calculated phase shift in brain tissue with
various degrees of edema.
[0048] FIGS. 9A and 9B are an experimentally measured phase shift
in brain tissue in vitro with various degrees of edema.
DETAILED DESCRIPTION OF THE DRAWINGS
(a) Theory:
[0049] As stated above, the present system assesses tissue
condition by determining volumetric bulk properties of the water
content of the tissue. Specifically, the sensing of an induction
phase shift is used to assess tissue condition.
[0050] Biological tissues contain compounds with measurable
electrical properties such as the intracellular and extracellular
ionic solutions, the capacitative cell membrane, charged
macromolecules and polar water. The combination of these compounds
in terms of composition and structure affect the overall
electromagnetic properties of the tissue. The particular effect of
each one of these components and combinations is affected in a
different way as a function of the electromagnetic field excitation
frequency and magnitude applied on the tissue. Typical
spectroscopic behavior of certain tissues is illustrated in the
100% blood, brain, muscle and lung curves in FIG. 2 (the other
curves in the figure will be discussed later). The overall effect
of excitation frequency on the electromagnetic properties is well
understood since the pioneering work of Schwan (Schwan, H. P.
(1957). "Electrical properties of tissue and cell suspensions."
Adv. Biol. Med. Phys. 5: 147-209.) Reviews can be can be found in
many texts on the topic: S. Grimnes and O. G. Martinsen,
Bioimpedance and Bioelectricity Basics. San Diego, Calif.: Academic
Press, 2000, pp. 87-124; K. R. Foster and H. P. Schwan, "Dielectric
properties of tissues" in Biological Effects of Electromagnetic
Fields. Boca Raton, Fla.: CRC Press, 1996, pp. 27-106. Briefly,
body tissues contain intra and extracellular fluids that behave as
electrical conductors and cell membranes that act as electrical
capacitors. At DC and low frequencies electrical current passes
mainly through the extracellular fluid; at higher frequencies,
however, current penetrates both intra and extracellular fluids.
Therefore, body fluids and electrolytes are responsible for
electrical resistance and cell membranes for reactance. At MHz
frequencies the impedance of proteins becomes important and at GHz
frequencies the behavior of water is sampled. In particular, up to
roughly about 100 MHz the behavior should be affected by Maxwell
Wagner relaxation of membranes, proteins in water and bound water
whereas above about 100 MHz it should depend on the relaxation of
free water, ionic conductivity and bound water. The increase in
conductivity in the tissue as a function of the GHz frequency
arises from the rotational relaxation of the water dipoles in
tissue. In this sense, at higher frequencies the observations
depend on the net water content in a volume rather than the
cellular structure.
[0051] The relation between water and tissue content and properties
and complex electromagnetic properties occurs throughout the
frequency domain. Accordingly, the present system can be used to
detect changes in tissue water properties with phase shift in a
broad range of frequencies from kHz to GHz. Since the measurement
of interest is phase shift in the bulk of tissue or organs there
are several considerations in choosing the appropriate frequency
and apparatus involving the significance of what is measured and
the dimensions that can be measured. Since the interest is in phase
shift DC type of measurements are not of interest for this type of
measurement. Theoretically it is anticipated that in the frequency
range from about 100 kHz to 1 GHz, depending on the type of tissue,
the phase shift measurement will be affected by both the relative
distribution between the intracellular water and the extracellular
water and the relative amount of water. Therefore this range would
be useful in detecting such conditions as ischemia, edema,
bleeding, extravasation, dehydration. The effects of change in
water content between the intracellular and extracellular would be
most pronounced between 1 MHz and 400 MHz, with the most sensitive
measurements between 1 and 100 MHz. Phase shift measured at the
higher frequency range from about 300 MHz to 10 GHz would be most
sensitive to water content and would be sensitive to detect edema,
bleeding and dehydration. In particular the range of 1 GHz to 10
MHz would be most sensitive to water content. However, in addition
to the sensitivity of various tissues to frequencies, which are
tissue and condition dependent, since the method involves
measurement in the bulk of tissue organs and the body the
penetration depth of the various electromagnetic wave frequencies
is of importance. For instance the penetration depth of microwave
frequency energy at between 1 GHz to 3 GHz is about 2 to 10 cm for
soft tissue. Therefore the particular application of the
measurement would relate the integration depth with the measurement
frequencies.
(b) Simplified Representation of the Invention:
[0052] The present invention deals with a method and an apparatus
for detecting phase shift due to tissue water properties in the
bulk of tissue. The method and the apparatus require an emitter of
electromagnetic waves and a receiver to be placed in relation to
the bulk tissue to be analyzed. When working in the frequency
domain electromagnetic coils are used for emitters and receivers in
the frequency range of up to 400 MHz. Beyond about 400 MHz to
several GHz range, antennae (such as microwave antennae) may be
used. In the range of frequencies from about 300 MHz to 1 GHz, both
coils and antennae could be used.
[0053] FIG. 1 is a simplified schematic of the present invention,
as follows.
[0054] System 10 consists of two induction coils 12 and 14 with the
organ or the part of the body (sample S) to be analyzed placed in a
determined relation to the coils. It is to be understood that coils
12 and 14 can be replaced with antennae when operating at higher
frequencies. Reference herein is made to coils, However, the
present invention is not so limited as antennae can be used
instead. Coil 12 is driven by an AC current power supply (not
shown) while the current in the other coil 14 is produced by
induction and measured. The properties of the material (sample S)
between coils 12 and 14 determine the currents in the induction
current coil 14. By comparing the voltages in first coil 12 to
those in second coil 14, a measure of the bulk electrical
properties of the tissue (sample S) there between can be made. In
preferred embodiments, the present invention measures the
difference in the phase between the two AC voltages, i.e. the
"phase shift". In alternate aspects of the invention, a spectrum of
voltages is passed through coil 12, and a current phase shift is
measured in coil 14.
(c) Mathematical Model:
[0055] Different mathematical models are used to describe the
system of this invention. The various mathematical models depend on
the frequency analyzed. In the frequency range of up to about 1
GHz, more rigorously up to 300 MHz a quasi-static assumption can be
made. In this range a solution such as that by (Griffiths, Steward
et. al., Magnetic Induction Tomography-A Measuring System for
Biological Materials" Ann. NY Acad. Sci. 873:335-345) can be used
for analyzing the phase shift due the water content properties of
tissue. In frequencies above that range the wave propagation
becomes important and the eddy currents are not constant and an
analysis of the type described in the same book but on page 327 is
applied.
(i) Theoretical Considerations:
[0056] The analysis here follows Griffiths and his colleagues (See:
Griffiths, Steward et. al., Magnetic Induction Tomography-A
Measuring System for Biological Materials" Ann. NY Acad. Sci.
873:335-345). We consider as a simple case study tissue sample S to
be a circular disk of tissue of radius Rand thickness t, placed
centrally and midway between a small excitation coil and a small
sensing coil spaced at a distance 2 a (See FIG. 1). The thickness
t, was considered to be much less than 2 a. A sinusoidal current,
of angular frequency .omega., flows in excitation coil 12 and
induces a magnetic field B. The circular non-magnetic tissue sample
S has conductivity .sigma. and relative permittivity
.epsilon..sub.r (it is assumed that the skin depth is greater than,
t, and therefore the attenuation produced by the disk is
neglected).
[0057] Our bulk model of edema assumes that the edema is uniformly
distributed in the tissue and that the occurrence of edema will
cause the bulk electrical parameters of the combined tissue to
change according to the formula:
? ( T , F ) = ( ? T ) + ( ? F ) 100 ? ( T , F ) = ( ? T ) + ( ? F )
100 ? indicates text missing or illegible when filed ( 1 )
##EQU00001##
[0058] where the subscripts c, t, and f stand for the composite
properties, the tissue properties and fluid properties,
respectively. The symbols, T, and, F, give the percentage volume of
the pure tissue or the pure fluid respectively. In accordance with
experiments performed by the Applicants in testing present
invention, the tissue and fluid data used were taken from Gabriel
and Lau (See: "The Dielectric Properties of Biological Tissues:
III. Parametric Models for the Dielectric Spectrum of Tissues"
Phys. Med. Biol. 41:2271-2293, 1996) and Duck (See: "Physical
Properties of Tissue", London, Academic press, 1990, Chapter 6, 167
223.) In accordance with experiments performed by the Applicants in
testing present invention, blood was considered as the edematous
fluid for brain and muscle tissues; and human serum was considered
for lung tissue.
[0059] FIGS. 2A, 2B and 2C show the bulk electrical parameters as a
function of frequency for various ratios of normal tissue to edema
calculated from Eqs. (1) and the data in Garbriel and Lau, and
Duck, supra. FIG. 2A shows brain tissues, FIG. 2B shows lung
tissues and FIG. 2C shows muscle tissues. As expected; three
typical major dispersion regions are observed for all the ratios
tissue/fluid. For the cases of brain and muscle tissues the bulk
electrical conductivity of all the ratios tissue/fluids have
similar values as the frequency approaches 1 GHz. It's evident that
at high frequencies the electrical properties of brain, muscle and
blood become essentially the same. This fact can be attributed to
the .gamma. dispersion region where the dielectric properties of
the tissue are dominated by the water content. In contrast; for the
case of lung tissue the bulk electrical parameters of all the
ratios tissue/fluids have different values in the whole bandwidth.
This behavior can be explained by the different electrical
properties of the human serum with respect to the lung tissue.
(ii) Phase Shift in Sensing Coil 14:
[0060] Considering the thin "tissue" disk model described above, a
sinusoidal current of angular frequency .omega., flows in
excitation coil 12 and induces a magnetic field B in sensing coil
14. According to Griffiths, supra, the current induced in the
"tissue" disk (sample S) placed between the excitation coil 12 and
the sensing coil 14 causes a perturbation .DELTA.B in the field of
the sensing coil given by:
.DELTA. B B = ( ? - j .sigma. ) ( ? .omega. ? 2 ) { 1 a 2 - a 2 + 2
R 2 ( a 2 + R 2 ) 2 } ? indicates text missing or illegible when
filed ( 2 ) ##EQU00002##
[0061] where .epsilon..sub.0 and .mu..sub.0 are the permittivity
and permeability of free space, respectively. The total magnetic
field B+.DELTA.B in sensing coil 14 is shifted relative to the
primary magnetic field B by an angle .theta.. The magnetic field
and its perturbation can be obtained from the voltages induced in
the sensing coil, V.sub.i and .DELTA.V.sub.i. .DELTA.B/B can be
defined in terms of the induced voltage in sensing coil 14, by:
.DELTA. B B = .DELTA. V i V i ( 3 ) ##EQU00003##
[0062] We define a constant k:
k = ( ? ? 2 ) { 1 a 2 - a 2 + 2 R 2 ( a 2 + R 2 ) 2 } ? indicates
text missing or illegible when filed ( 4 ) ##EQU00004##
[0063] Substituting (3) and (4) into (2), the phase of the total
induced voltage .theta.(V.sub.ind) in sensing coil 14 with respect
to the induced voltage by the primary magnetic field in coil 14
could be expressed as a function of frequency and electrical
parameters in the "tissue" disk between the coils [16], by:
.theta. ( V ind ) = arctg ( k .omega. .sigma. k .omega. 2 0 r + 1 )
( 5 ) ##EQU00005##
(ii) Phase Shift in Excitation Coil 12:
[0064] The magnetic field in the present invention can be generated
in the device as shown in FIG. 3. Specifically, an oscillator
supplies an excitation signal (V.sub.exc) through an output
impedance, Z.sub.out. The reference voltage (V.sub.ref) measured in
the excitation coil is given by expression (6) where Z.sub.L is the
impedance of a coil composite made of the resistance R.sub.L and
the inductance X.sub.L, in series.
V ref = V exc ( Z L Z out + Z L ) ( 6 ) ##EQU00006##
[0065] According to Hart L. et al. (See: A noninvasive
electromagnetic conductivity sensor for biomedical applications"
IEEE Trans Biomed Eng 32(12): 1011-1022, 1988), the presence of a
conductive sample (the "tissue" disk between the coils) causes a
change in the impedance of the excitation coil given by
.DELTA.Z.sub.L=.DELTA.R.sub.L+.DELTA.X.sub.L, where: .DELTA.R.sub.L
is the increase in the coil resistance and .DELTA.X.sub.L is the
increase in the coil inductance. The expressions for .DELTA.R.sub.L
and .DELTA.X.sub.L were derived in Hart et. al., supra as:
.DELTA.R=32.pi..sup.3*10.sup.-14N.sup.2f.sup.2R'.sup.3I'.DELTA..rho.
(7)
.DELTA.X=64.pi..sup.4*10.sup.-14N.sup.2f.sup.2R'.sup.3I'.epsilon..sub.0.-
DELTA..epsilon..sub.r (8)
[0066] where: f=.omega./2.pi. is the frequency of the excitation
signal, N is the number of coil turns, R' is the coil radius,
.epsilon..sub.0 is the permitivity of free space, and
.epsilon..sub.r and a are the relative permitivity and electrical
conductivity of the "tissue" disk sample respectively. The term I'
is a positive definite constant determined for a specific geometry
and several approximations are given in Hart et. al., supra. In
this study substitutions of .sigma..sub.c.fwdarw..DELTA..sigma. and
.epsilon..sub.r,c.fwdarw..DELTA..epsilon..sub.r were made for the
expressions (7) and (8) because changes in electrical conductivity
and relative permittivity of the "tissue" sample are
considered.
[0067] The phase of the reference voltage .theta.(V.sub.ref) with
respect to the excitation signal in the presence of a "tissue"
sample can be estimated from the following expression:
.theta. ( V ref ) = arctg [ Im [ Z L + .DELTA. Z L ? + Z L +
.DELTA. Z L ] / Re [ Z L + .DELTA. Z L ? + Z L + .DELTA. Z L ] ] ?
indicates text missing or illegible when filed ( 9 )
##EQU00007##
[0068] Later in this study, the analysis for estimation of phase
shift with edema was performed by using tissue properties from the
experimental data in Gabriel and Duck, supra, and from the solution
of equation (5) and (9) with the bulk properties from equation (1).
The total change in phase shift (.DELTA..theta.) between the
reference and induced voltages in the excitation and sensing coil
respectively is given by the expression:
.DELTA..theta.=.theta.(V.sub.ind)-.theta.(V.sub.ref) (10)
(d) Experimental System:
[0069] FIG. 4 illustrates a multi-frequency inductive spectrometer
system 10 as designed, constructed and operated by the Applicants.
This system is preferably used for a frequency of up to 400 MHz.
System 10 comprises four modules: function generator 20,
transceiver 30, dual-channel demodulator 40 and analog digital
converter 50. A personal computer 60 with a Pentium 2 GHz processor
(model 4400, Dell Inc. Round Rock, Tex.) controls the system and
processes the data.
[0070] Function generator 20 uses two identical programmable
synthesizers 22 and 24 (NI 5401, National Instruments Inc, Austin,
Tex.) as oscillators. Oscillator 22 supplies an excitation signal I
cos(.omega..sub.et) of approximately 20 mA in the range of 1 to 8
MHz at pre-programmed steps. A modulation signal I
cos(.omega..sub.mt) is generated by second oscillator 24. The
difference .omega..sub.e-.omega..sub.m=.omega..sub.o=100(2.pi.)
rad/sec is maintained constant in the whole bandwidth in order to
produce a narrow band measured voltage signal on a constant low
intermediate frequency for processing and demodulation, as proposed
by Ristic, B. et al. (See: "Development of an impredance
spectrometer for tissue monitoring: application of synchronous
sampling principle" Proc 21st IEEE Annual Northeast Conference,
22-23 May, 1995, pages 74-75).
[0071] The excitation and modulation signals are connected to
transceiver 30 and dual-channel demodulator 40 modules
respectively. Transceiver 30 consists of an excitation coil 12 and
a sensing coil 14 coaxially centered at a distance d=10 cm and two
differential receiver amplifiers 32 and 34 (AD8130, Analog Devices
Inc. Norwood, Mass.). Both coils 12 and 14 were built with magnet
wire AWG32 rolled on a cylindrical plastic former with radius r=2
cm, five turns. The coil inductance, as calculated on the basis of
Faraday's law, is approximately 40 .mu.H. The excitation coil 12
generates a primary oscillating magnetic field. The sensing coil 14
detects the primary magnetic field and its perturbation through a
proximal conductive tissue sample S. To avoid inductive pickup the
leads of the coils are twisted. The amplifiers 32 and 34 were
connected as conventional operational amplifiers and collect the
reference voltage (V.sub.ref) and the induced voltage (V.sub.ind)
in the excitation 12 and sensing 14 coils respectively. The gain of
amplifiers 32 and 34 was adjusted in order to obtain a dynamic
range of .+-.5V throughout the whole bandwidth.
[0072] Dual-channel demodulator 40 uses a pair of mixers 42 and
narrow band pass filters 44 to transfer the information of any
excitation and sensing signal of a variable frequency to a constant
low frequency (.omega..sub.o). A multiplier (AD835, Analog Devices
Inc. Norwood, Mass.) was used as mixer 42. Narrow band pass filter
44 was designed on the basis of operational amplifier 32 (AD844,
Analog Devices Inc. Norwood, Mass.). This module used two identical
channels for parallel demodulation.
[0073] To avoid additional inductance and stray capacitance in the
circuit, amplifiers 32 and 34 and dual channel-demodulator circuits
40 were shielded by a metallic box and connected to coils 12 and 14
with short coaxial cables (length less than 0.8 m). The current
passes through the shield to minimize any inductance mutual between
the circuit and the coils.
[0074] Analog-digital conversion module 50 digitized the reference
and induced voltage signals on the constant low frequency. A data
acquisition card NI 6071E (National Instruments Inc, Austin, Tex.)
with a sample rate of 1.25 MSamples/seg and a resolution of 12 bits
was used as analog-digital converter 50. The phase of the reference
and induced voltages were calculated in software over approximately
five cycles by an extract single tone function available in LAB
VIEW V 6.1 (National Instruments Inc, Austin, Tex.). This function
was programmed to find the highest amplitude at 100(2.pi.) rad/sec
and return the phase. The phase shift between the reference and
induced voltage was estimated as
.DELTA..theta.=.theta.(V.sub.ind)-.theta.(V.sub.ref). The ratio
signal to noise (SNR) for phase shift measurement was improved by
averaging over twenty spectra (39 dB at 1 MHz).
[0075] For use up to higher frequencies including GHz range the
present apparatus may comprise of a source of electromagnetic
energy such as an RF Signal generator (Agilent 8648D9 KHz-4 GHz.
The source is connected to an emitter which is a single frequency
commercial antenna for microwave or radiofrequency placed in
relation to the analyzed tissue and another similar receiving
antenna. The receiving antennae is connected to an amplifier such
as (Low Noise Amplifier, Agilent 11909A, 9 KHz-1 GHz), or
(Microwave system amplifier Agilent 83006A 10 MHz-26.5 GHz). The
signal and the phase shift can be detected with Agilent 4396B RF
Network/Spectrum/Impedance Analyzer, 100 kHz to 1.8 GHz).
(e) Experimental Results-Detection of Interperitoneal Bleeding in
Rats:
[0076] Intraperitoneal bleeding in the abdomen of a rat was
simulated by infusion of various volumes of physiological saline
into the abdominal cavity in rats. Specifically, experiments were
performed identically on each of five rats. The experiments started
with anesthetization of the animal via intraperitoneal injection of
Nembutal solution (50 mg/ml sodium pentobarbital, Abbot Labs, North
Chicago, Ill.) for a total of 100 mg sodium pentobarbital per kg of
rat. To simulate intraperitoneal bleeding and accumulation of
fluids in the abdomen we injected various volumes of physiological
saline (0.9% w/w NaCl) into the abdominal cavity through a short
intravenous catheter (Venflow). The catheter remained in place
throughout the experiment. We injected increasing volumes of saline
and the measurements were done for four volumes of: 1, 2.5, 5 and
7.5% of(weight of saline)/(weight of the tested rat). The
physiological saline was maintained at approximately 36.5.degree.
C. prior to injection. In all the experiments the baseline
reference measurement was for the experimental subject prior to the
intraperitoneal physiological saline injection. In all the
experiments the coils were placed around the abdomen of the rat in
such a way that the abdominal cavity was centered between the
excitation and sensing coils. The geometrical position was
carefully maintained as similar as possible for all the
subjects.
[0077] The Applicants studied the phase shift due to four different
volumes of saline in the frequency range from 1 MHz to 8.5 MHz with
an induction system for measuring bulk phase shift. As will be
shown below, the test results show that inductive bulk measurements
of phase shift are sensitive to the relative volume of saline at
frequencies higher than approximately 1 MHz, which is qualitatively
consistent with our theoretical predications. In addition, the
phase shift detected increases as a function of frequency and the
fluid volume also qualitatively consistent with the theoretical
predictions. As such, the results indicate that bulk induction
measurement of the phase shift has the potential for becoming a
robust means for non-contact detection of intraperitoneal
bleeding.
[0078] FIG. 5 is a calculated graph of phase shift vs. frequency.
FIG. 5 was obtained from our theoretical calculation for gut tissue
and shows the absolute homogenized values of the inductive phase
shift as a function of frequency for various volumes of
physiological saline into the abdominal cavity, simulating various
degrees of bleeding. The results are shown in a homogenized form
with respect to the values without saline. As can be seen, an
increase in the volume of injected saline causes an increase in
inductive phase shift. Specifically, the relative phase shift
caused by internal bleeding begins at about 1 MHz. The phase shift
difference due to internal bleeding has a characteristic inverse U
type shape with a maximal at about 1000 MHz. The behavior shown in
the figure beyond 1 GHz is highly approximate.
[0079] As can be seen, the values of the phase shift obtained from
the analytical calculations provide an excellent qualitative
indication of the effect of internal bleeding. Thus, the present
system operates even if the bulk properties of the tissue in the
abdomen are substantially different from the values that we used,
since we did not consider fat, muscle, food and many other
components in the abdomen. Nevertheless, the results suggest that
the resolution of the measurement is greater for certain optimal
values. In optional clinical applications, the phase shift can be
scanned over a wide range of values to determine the best frequency
for the highest signal to noise measurement.
[0080] The results in FIG. 5 indicate that the phase shift due to
internal bleeding should be detectable from about 1 MHz. FIG. 6 is
a magnified view of the phase shift in FIG. 5 in the frequency
region from 1 to 9 MHz, which confirms this. Here it is important
to notice that in this range the phase shift relative to baseline
increases with an increase in measurement frequency and amount of
simulated internal bleeding. We have chosen this range of
frequencies for our experimental studies because it is the onset of
the phenomenon of phase shift due to internal edema.
[0081] FIG. 7 shows the experimentally measured homogenized
absolute values of the inductive phase shift as a function of
frequency for various volumes of physiological saline into the
abdominal cavity, simulating various degrees of bleeding. The
results are shown in a homogenized form with respect to the control
values, the baseline measurements. In this mode of presentation,
the experimental subject without water produces zero phase shift at
all frequencies and the injection of the physiological saline
solution produces the departure from zero. Another advantage of
presenting the results homogenized with respect to the control
values is to overcome possible bias in the electronic circuitry.
The frequency is given in a logarithmic scale from 1 to 8.5 MHz.
The value of one standard error is also shown in the figure. The
beating of the heart, breathing as well as abdominal motion might
change the bulk electrical properties of the composite body under
measurement. These factors may affect the magnitude and phase of
the induced voltage at the sensing coil in the whole bandwidth. To
remove natural artifacts due to physiological activity, 20
measurements were taken at each frequency. Averaging over these
measurements has the effect of a robust filter to physiological
activity artifacts. The figure shows that the change in phase shift
due to simulated internal bleeding begins at about 1 MHz and
increases with frequency and amount of internal bleeding.
Qualitatively, the experimental results are very similar to the
theoretical calculations.
[0082] In summary: these experimental results confirm that
measuring the relative spectroscopic distribution of induction
phase shift in the bulk of the abdominal cavity can be used for
non-contact detection of intraperitoneal bleeding. Thus, in
clinical practice, induction phase shift can be measured as a
function of time and frequency in patients who are in danger of
internal bleeding.
(f) Experimental Results-Detection of Brain Edema:
[0083] As will be shown herein, our results verified that bulk
measurement of inductive phase shift can be used for non-contact
detection of the content of water in brain, lung and muscle tissue.
The analytical results of FIG. 2 showed an increase of the phase
shift proportional to the water content starting at frequencies as
low as 10 MHz. In addition, our results show that the phase shift
changes with frequency, in a rather complex manner.
[0084] The results show that the phase shift is sensitive to the
relative volume of edema at frequencies higher than approximately
10 MHz. The effect of edema on brain, lung and muscle tissues is
tissue type specific. Increasing the volume of tissue has the
effect of lowering the frequency at which the phase shift becomes
sensitive to the volume of edema. The results indicate that bulk
induction measurement of the phase shift has the potential for
becoming a simple means for non-contact detection of formation of
edema in brain, lung and muscle tissues.
[0085] As a first order model of edema in the brain, ex-vivo brain
tissue of pig (used approximately 8 hours after the animal
sacrifice) was processed through a mixer and combined with various
volumes of a physiological saline solution (0.9% w/w NaCl) to form
a homogeneous paste. In accordance with experiments performed by
the Applicants in testing present invention, the brain conductivity
data used in the relevant calculations were taken from Gabriel's
experimental report for excised bovine brain tissue supra. The data
for excised bovine brain tissue was obtained two hours postmortem
and at body temperature. The fluid was taken as a solution of 0.9%
w/w of NaCl, with a constant electrical conductivity .sigma.=1.3
S/m and a relative permittivity .epsilon..sub.r=80.
[0086] In our preparation, the changes in the electrical properties
of brain tissue with the increase in water content may be explained
as the dilution of a mixture of water and the proteins present in
dried tissue. In the analyzed frequency range the cellular
membranes have low impedance, and the tissue may be treated as a
suspension of proteins in water. The significance of this is that,
in the brain, at frequencies at the high end of the beta dispersion
and above our experimental model will be comparable to that in
viable tissue. At frequencies at the low end of the beta dispersion
a greater difference between live tissue and edematous fluid is
seen, and therefore, in that range, the effect of edema is more
pronounced than determined in our experiment. Therefore, the
present experimental model could be considered to provide a lower
limit in the sensitivity of edema detection with our techniques and
we can anticipate that the detection will be even better in a
living organism.
[0087] Three different volume ratios between the volume of brain
tissue and of saline were evaluated: 10, 20 and 30%. The paste was
placed in a cylindrical and nonmagnetic recipient made of Teflon
with a radius R=7.5 cm and height t=8 cm. This volume was chosen
because it is on the order of a typical adult brain volume. In
addition we studied samples of pure brain tissue that was also
homogenized and pure physiological saline.
[0088] A calculation of the penetration depth (.delta.) as a
function of frequency for saline and brain tissue was done
according to the expression:
.delta.=(2/.omega..mu..sub.0.sigma.).sup.1/2
[0089] where .mu..sub.0 is the permeability of free space. We used
the electrical conductivity data reported in Gabriel, supra for
excised bovine brain tissue. The data for excised bovine brain
tissue was obtained two hours post-mortem and at body temperature.
The fluid was taken as a solution of 0.9% w/w of NaCl, with a
constant electrical conductivity .sigma.=1.3 S/m and a relative
permittivity .epsilon..sub.r=80. The result shows that at 10 MHz;
the skin depth is around 14 and 30 cm for pure saline and brain
respectively. These values are larger than the thickness of the
sample (8 cm).
[0090] All the samples were geometrical and vertically centered
between excitation coil 12 and sensing coil 14. The geometrical
position was carefully maintained as similar as possible for all
the samples.
[0091] For every sample, twenty spectra of phase shift were
obtained in the range of from 1 to 8 MHz. The data were averaged
over twenty separate measurements, for each frequency. To overcome
the bias in the phase shift due to the system electronics, the data
were homogenized with respect to the values for brain 100%. In this
way the changes observed in phase will depend essentially only on
the electrical properties of the sample. The measurements were made
at the room temperature (approximately 24.degree. C.).
[0092] FIGS. 8 and 9 show the difference between the calculated
(FIG. 8) or measured (FIG. 9) phase shift in brain tissue with
various degrees of edema and the calculated or measured phase shift
in the case with 100% brain tissue, as a function of frequency. In
this mode of presentation brain tissue without edema produces zero
phase shift at all frequencies and the addition of saline produces
the departure from zero. FIG. 8 shows the calculated inductive
phase shift as a function of frequency for various ratios of normal
brain tissue to physiological saline, simulating various degrees of
edema. The calculations were made by solving Eq. (10) and inserting
in Eq. (1) brain tissue properties taken from Gabriel, supra. The
edematous fluid was taken as saline (NaCl, 0.9% w/w) with a
constant electrical conductivity .sigma.=1.3 S/m and a relative
permittivity .epsilon..sub.r=80. FIG. 8 shows the calculated phase
shift as a function of frequency in the range of from 1 MHz to 1000
MHz. The analytical study shows that the phase shift is changing
with frequency in a U shaped form and appears to have a maximum at
about 100 MHz. Evidently, the phase shift increases with saline
content, at any frequency. FIG. 8 shows that the phase shift can be
used to measure edema in a wide range of frequencies and that there
may be some optimal values of frequency that produce the highest
signal.
[0093] The outcome of our experiments is shown in FIG. 9A, which
shows the phase shift of various compositions of brain tissue and
saline as a function of frequency. Specifically, FIG. 9A shows the
phase shift from three different volume ratios between the volumes
of saline to brain tissue: 10, 20 and 30%. Data for 100% saline is
also shown. FIG. 9B shows the part of the curve developed in FIG. 8
in the range of the experimental measurements, to 8 MHz. A
comparison of FIGS. 9A and 9B shows that the experimental results
are quantitatively and qualitatively similar to the theoretical
predictions. The phase shift increases with frequency and with
water content. The frequency is given in a logarithmic scale from 1
to 8 MHz. The value of one standard error is also shown in the
figure. The error in our experimental apparatus increases with an
increase in frequency for all the volume ratios of saline to brain
tissue.
[0094] The data in FIGS. 8 and 9 are presented by homogenizing the
measured phase shift with respect to the phase shift in the case
with 100% brain tissue. Therefore, the difference between the
calculated or measured phase shift in brain tissue with various
degrees of edema and the calculated or measured phase shift in the
case with 100% brain tissue is shown as a function of
frequency.
[0095] In this mode of presentation, brain tissue without edema
produces zero phase shift at all frequencies and the addition of
saline produces the departure from zero. With this mode of
presentation, the sensitivity of our method for detecting edema by
measuring bulk phase shift becomes clear, as does the effect of
measurement frequency. Another advantage of presenting the results
homogenized with respect to 100% brain tissue phase shift is to
overcome possible bias in the electronic circuitry. Furthermore,
this homogenized mode of presentation removes any systemic errors
that could be caused by the electronics circuitry producing a bias
in the experimentally measured phase shift.
[0096] A further advantage of the present system is that in the
analyzed frequency domain phase shift is a measure that is strongly
dependent on water content in relation to organic molecular
cellular contents and not on cell structure.
[0097] It is clear from FIGS. 8 and 9 that phase shift due to
changes in water content is substantial and detectable. In FIGS. 8
and 9, the departure from zero is the indication for change in
water content. The change in phase shift increases with frequency
and with water content. The experimental results suggest that the
capability of the measurement system to detect water content
improves at high frequencies. For example, the phase shift value
detected at 8 MHz is clearly larger for all the tested samples.
[0098] Our results also show that measurable differences in phase
shift are noted between 3 MHz to 4 MHz with higher volumes of
saline producing measurable phase differences at lower frequencies.
Our results demonstrate that valuable information for detection of
phase shift with edema can be obtained at frequencies that are
three orders of magnitude lower than the microwave frequencies and
in a broad range of frequencies. The curve of saline alone provides
the upper limit of the expected phase shift measurement relative to
pure brain tissue.
[0099] The present invention can thus be used to continuously
monitor phase shift to detect worsening conditions of increase in
edematous fluid in the brain. Specifically, continuously measuring
the relative changes in phase shift with time would produce curves
as shown in FIG. 9 in the case of formation of edema. Thus,
detecting changes in phase shift could point to worsening
conditions of the patient.
[0100] Extending the present study over a wider range of
frequencies may also hold much information since our analytical
studies predicts a non-linear behavior throughout the range from
MHz to GHz.
[0101] In summary, the results of this theoretical and in vitro
study provide substantive preliminary information, which suggests
that measuring the relative spectroscopic distribution of induction
phase shift can produce a robust means for noncontact detection of
occurrence of edema in the brain.
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