U.S. patent application number 09/854369 was filed with the patent office on 2002-11-14 for system for quantifying edema.
Invention is credited to Bowman, Harry Frederick, Martin, Gregory T..
Application Number | 20020169388 09/854369 |
Document ID | / |
Family ID | 25318502 |
Filed Date | 2002-11-14 |
United States Patent
Application |
20020169388 |
Kind Code |
A1 |
Bowman, Harry Frederick ; et
al. |
November 14, 2002 |
System for quantifying edema
Abstract
A system is provided for monitoring edema in tissue. Thermal
energy is supplied to tissue at a site where tissue water content
is to be monitored to produce in the selected tissue a thermal
response as a function of an intrinsic thermal property of tissue
that varies with water content. Tissue water content is determined
from the thermal response, the energy supplied and the relationship
between tissue water content and the thermal property.
Inventors: |
Bowman, Harry Frederick;
(Needham, MA) ; Martin, Gregory T.; (Cambridge,
MA) |
Correspondence
Address: |
James L. Neal
Thermal Technologies, Inc.
Suite 0123
222 Third Street
Cambridge
MA
02142
US
|
Family ID: |
25318502 |
Appl. No.: |
09/854369 |
Filed: |
May 10, 2001 |
Current U.S.
Class: |
600/549 |
Current CPC
Class: |
A61B 2018/00797
20130101; A61B 5/4869 20130101; A61B 5/028 20130101; A61B 5/4878
20130101; A61B 2018/00815 20130101; G01N 25/18 20130101; A61B
5/4076 20130101; A61B 5/01 20130101 |
Class at
Publication: |
600/549 |
International
Class: |
A61B 005/00 |
Claims
What is claimed is:
1. A method for quantifying water content of living tissue
comprising the steps of: contacting tissue with a thermistor at a
site where tissue water content is to be quantified; energizing the
thermistor to cause the temperature of a volume of tissue to rise;
and calculating tissue water content of said volume of tissue as a
function of the power used to heat said thermistor and the
temperature rise of said thermistor, at least one of which is
controlled in a predetermined manner, and a value obtained from a
model relating tissue conductivity to tissue water content.
2. A method according to claim 1 wherein: said energizing step
comprises the step of energizing the thermistor cyclically to cause
the temperature of a volume of tissue to rise and fall cyclically;
and said calculating step comprises the step of calculating tissue
water content of said volume of tissue in each energizing cycle as
a function of the power used to heat said thermistor in each
energizing cycle and the temperature rise of said thermistor in
each energizing cycle, at least one of which is predetermined, and
a value obtained from a look-up reference relating tissue
conductivity to tissue water content.
3. A method for quantifying water content in living tissue
comprising the steps of: supplying thermal energy to tissue to
produce a thermal response therein functionally related to at least
one intrinsic thermal property of the tissue, which thermal
property varies as a function of tissue water content; producing a
signal functionally related to said thermal response and the
thermal energy supplied in said supplying step; and calculating the
water content of said tissue using said signal and a model that
relates tissue water content and said intrinsic thermal
property.
4. A method for quantifying water content in living tissue
comprising the steps of: heating a volume of tissue to produce
therein a thermal response functionally related to the thermal
conductivity of the tissue; producing a signal functionally related
to said thermal response and the thermal energy supplied in said
heating step; calculating the intrinsic thermal conductivity of the
volume of tissue in a first time interval during said heating step;
calculating the perfusion of the volume of tissue in a subsequent
time interval during said heating step using the calculated value
of intrinsic thermal conductivity; recalculating intrinsic thermal
conductivity in said first time interval using the calculated value
of perfusion; recalculating values for perfusion and intrinsic
thermal conductivity, in alternating fashion, until the
recalculated values of intrinsic thermal conductivity converge to a
substantially unchanging value, using in each recalculation of
perfusion the previously calculated value of intrinsic thermal
conductivity and in each recalculation of intrinsic thermal
conductivity the previously calculated value of perfusion; relating
intrinsic thermal conductivity values for tissue with corresponding
tissue water content values; and computing the water content of the
volume of tissue as a function of said substantially unchanging
value of intrinsic thermal conductivity and a substantially
equivalent value of intrinsic thermal conductivity taken from the
relationship of thermal conductivity values with tissue water
content values.
5. A method for quantifying the water content of living tissue
comprising the steps of: placing a thermistor in contact with
tissue at a site where water content is to be quantified;
energizing during a time interval the thermistor to elevate the
temperature of the thermistor and heat tissue at the site above the
baseline temperature of tissue at the site; relating the rate at
which heat is transferred in tissue with tissue water content; and
quantifying the water content of tissue at the site as a function
of the power supplied to the thermistor during the time interval,
the rate at which heat from the thermistor is transferred in tissue
at the site and the relationship established in said relating
step.
6. A method for monitoring the water content of living tissue at a
selected site comprising the steps of: causing the temperature of
tissue at the site to rise and fall cyclically; producing a signal
during each temperature cycle functionally related to the power
used in said causing step and a thermal property of the tissue at
the site, which thermal property varies as a function of tissue
water content; and using a model of the relationship of the thermal
property of tissue to tissue water content, computing the water
content of tissue at the site during each temperature cycle as a
function of the signal resulting from said signal producing step
and the modeled relationship.
7. A method for monitoring the water content of living tissue
comprising the steps of: introducing into tissue an energizable
thermistor adapted for thermal contact with tissue surrounding said
thermistor; energizing and deenergizing said thermistor cyclically
to cause the temperature of the surrounding tissue to rise and fall
cyclically; producing a signal during each energizing and
deenergizing cycle functionally related to the power used to
energize said thermistor and the thermal conductivity of the
surrounding tissue; modeling the relationship of tissue water
content and the thermal conductivity of tissue; calculating the
value of the intrinsic thermal conductivity of the surrounding
tissue in a first time interval during each energizing and
deenergizing cycle; calculating perfusion in a subsequent time
interval during each energizing and deenergizing cycle using the
calculated value of intrinsic thermal conductivity; recalculating
intrinsic thermal conductivity in said first time interval using
the calculated value of perfusion; recalculating values for
perfusion and intrinsic thermal conductivity, in alternating
fashion, until the recalculated values of intrinsic thermal
conductivity converge to a substantially unchanging value, using in
each recalculation of perfusion the previously calculated value of
intrinsic thermal conductivity and in each recalculation of
intrinsic thermal conductivity the previously calculated value of
perfusion; and computing the water content of the surrounding
tissue during each energizing and deenergizing cycle as a function
of said substantially unchanging value of intrinsic thermal
conductivity and the relationship resulting from said modeling
step.
8. A method for assessing water content of living tissue comprising
the steps of: supplying thermal energy to tissue to cause the
temperature of tissue at a selected site to rise; and calculating a
value indicative of tissue water content of tissue at the selected
site as a function of the power used in said heating step and the
temperature rise of tissue at the selected site, at least one of
which is predetermined, and a value provided by a model relating
tissue conductivity or tissue diffusivity to tissue water
content.
9. A method for assessing the water content in living tissue at a
site in the body comprising the steps of: introducing a thermistor
into contact with tissue at a site where water content is to be
assessed; energizing the thermistor to elevate the temperature of
the thermistor above the baseline temperature of tissue at the
site; producing a signal as a function of the energy supplied to
the thermistor in said energizing step and the rate at which heat
from the thermistor is transferred in tissue at the site; and using
a known relationship which correlates the rate at which heat is
transferred in tissue with tissue water content and the signal
resulting from said producing step, producing a signal indicative
of the water content of tissue at the site.
10. A system for quantifying water content of living tissue
comprising: a thermistor for heating a volume of tissue; means for
energizing said thermistor to cause the temperature of the volume
of tissue to rise; means for relating tissue conductivity to tissue
water content; and means communicating with said energizing means
and said relating means for calculating tissue water content of
said volume of tissue as a function of the power used to heat said
thermistor and the temperature rise of said thermistor, at least
one of which is controlled in a predetermined manner, and a water
content value obtained from said relating means.
11. A system according to claim 10 wherein: said energizing means
comprises means for energizing said thermistor cyclically to cause
the temperature of the volume of tissue to rise and fall
cyclically; said relating means comprises a look-up reference; and
said calculating means comprises means for calculating the tissue
water content of said volume of tissue in each energizing cycle as
a function of the power used to heat said thermistor in each
energizing cycle and the temperature rise of said thermistor in
each energizing cycle, at least one of which is predetermined, and
a water content value obtained from said look-up reference relating
tissue conductivity to tissue water content.
12. A system for assessing water content in living tissue
comprising: thermistor means for thermally contacting tissue at a
site where tissue water content is to be assessed; means for
energizing and deenergizing said thermistor means to cause the
temperature of tissue at the site to rise and fall; means for
producing a signal during the energizing and deenergizing cycle as
a function of the power used to energize said thermistor means and
at least one thermal property of tissue at the site, which thermal
property varies as a function of tissue water content; means for
modeling the relationship of tissue water content to the at least
one thermal property of tissue; and means for assessing the water
content of tissue at the site during the energizing and
deenergizing cycle as a function of the signal resulting from said
signal producing means and the relationship modeled by said
modeling means.
13. A system according to claim 12 wherein: said energizing means
comprises means for cyclically energizing and deenergizing said
thermistor means to cause the temperature of tissue at the site to
rise and fall cyclically; said signal producing means comprises
means for producing during each energizing and deenergizing cycle a
signal as a function of the power used to energize said thermistor
means during each energizing and deenergizing cycle and at least
one thermal property of tissue at the site; and said means for
assessing tissue water content comprises means for assessing the
water content of tissue at the site in each energizing and
deenergizing cycle as a function of the signal resulting from said
signal producing means in each energizing and deenergizing cycle
and the relationship modeled by said modeling means.
14. A system according to claim 12 or 13 wherein said signal
producing means comprises means for producing a signal as a
function of the thermal conductivity of tissue at the site and the
power used to energize said thermistor means.
15. A system according to claim 12 or 13 wherein said signal
producing means comprises means for producing a signal as a
function of the thermal diffusivity of tissue at the site and the
power used to energize said thermistor
16. A system according to claim 12 or 13 wherein said thermistor
means comprises a probe adapted to be introduced invasively into
tissue at a site where tissue water content is to be assessed and
at least one thermistor mounted on said probe for contact with
tissue at the site.
17. A system according to claim 12 or 13 wherein said thermistor
means comprises a noninvasive probe adapted for thermal contact
with the surface of tissue at a site where tissue water content is
to be assessed and at least one thermistor mounted on said probe
for contact with tissue at the site.
18. A system for monitoring water content in living tissue
comprising: a probe adapted for contact with the surface of tissue
at a site where tissue water content is to be quantified; a
thermistor on said probe adapted for thermal contact with the
tissue surface; means for energizing and deenergizing said
thermistor cyclically when said thermistor is in contact with the
tissue surface to cause the temperature of tissue at the site to
rise and fall cyclically; means for producing a signal during each
energizing and deenergizing cycle as a function of the power used
to energize said thermistor; means for correlating water content of
tissue to tissue conductivity; and means for quantifying the water
content of tissue at the site in each energizing and deenergizing
cycle as a function of the signal produced by said producing means
in each energizing and deenergizing cycle and the correlation
established by said correlating means.
19. A system for assessing the water content of tissue comprising:
means for thermally energizing tissue at a selected site; means for
relating tissue water content to a thermal property of tissue,
which thermal property of tissue varies as a function of tissue
water content; means indicative of the thermal response produced in
tissue at the site, which thermal response is a function of said
thermal property of tissue at the site; and means for indicating
the water content of tissue at the site as a function of the
relationship established by said relating means, the energy used to
energize tissue at the site and the thermal response produced in
the tissue at the site.
20. A system for assessing the water content of tissue comprising:
means for heating tissue to be assessed; modeling means for
relating tissue water content to an intrinsic thermal property of
tissue which varies as a function of tissue water content; means
for producing a signal as a function of the power used by said
heating means to heat the tissue to be assessed and the thermal
response produced in the tissue to be assessed, which thermal
response is a function of said intrinsic thermal property of the
tissue to be assessed; and means communicating with said producing
means and said modeling means for producing a signal indicative of
the tissue water content of tissue to be assessed as a function of
the signal produced by said producing means and the relationship
established in said modeling means.
21. A system for assessing the water content of tissue comprising:
a thermistor adapted for thermal communication with tissue to be
assessed; control means for heating said thermistor and producing a
signal functionally related to the power used to heat said
thermistor and the temperature rise of said thermistor; means for
relating tissue thermal conductivity to tissue water content; and
means communicating with said control means and said relating means
for producing a signal indicative of the water content of tissue to
be assessed as a function of the signal produced by said control
means and the relationship established by said relating means.
22. A system for assessing the water content of tissue comprising:
a thermistor adapted for thermal communication with tissue to be
assessed; energizing means for heating said thermistor; means for
relating tissue thermal conductivity to tissue water content; and
means for indicating of the water content of tissue to be assessed
as a function of the relationship established by said relating
means, the energy used to heat said thermistor and the temperature
rise of said thermistor
Description
BACKGROUND OF THE INVENTION
[0001] Edema, the abnormal or excessive retention of fluid at a
site in the body, can produce damaging stress on the body and
inhibit proper functioning of organs. Edema inhibits blood flow in
tissue, raises systemic blood pressure and otherwise impairs
healthy body function.
[0002] Edema produces swelling which often results in a
constriction of blood flow to the affected area. This can place
stress on the heart, kidneys, brain, muscle tissue and other
organs. Causes of edema include trauma, burns, hypersensitive
reactions, thrombophlebitis and disease. Edema can even result from
malnutrition, obesity and lack of exercise. In the heart, edema can
produce heart failure. Cardiac edema increases the volume of the
heart wall; the wall thickens and reduces the volume of the
chambers of the heart. Cardiac output is reduced and the workload
of the heart is increased. Head trauma often results in edema.
Serious head injury is almost always associated with excessive
fluid retention in brain tissue and brain swelling. As the brain
swells the increase in tissue volume is confined by the rigid
cranial cavity. The resulting pressure increase restricts blood
supply and, if not relieved, produces brain damage. In muscle
tissue edema can produce compartment syndrome. Injury can cause a
volume of tissue to retain excess fluid and swell. The volume of
the swelling tissue is constrained by surrounding tissue so that
blood supply to the tissue is restricted.
[0003] When excessive fluid collects in tissue there is a need to
mitigate the condition to avoid related adverse physiological
effects and as an aid to treatment. Edema is often associated with
low blood flow and its attendant problems and can affect any
location or organ of the body. As water content of tissue can
change from time-to-time, and sometimes rapidly, there is a need
for an edema monitor which can detect tissue water content in any
tissue or organ of the body and monitor it continuously.
[0004] Prior devices for measuring edema, such as those for
measuring pulmonary edema, involve injection of indicator directly
into the bloodstream. Catheters introduced into the circulatory
system deliver the indicator and detect the response. One such
device is described in U.S. Pat. No. 4,676,252 issued to Trautman
et al. U.S. Pat. No. 4,819,648 to Ko discloses a device for
electromagnetically sensing impedance changes in the brain to
monitor brain fluid levels.
SUMMARY OF THE INVENTION
[0005] It is a purpose of this invention to provide a system to
quantify the water content or condition of edema in any selected
tissue or organ of the body and continuously monitor changes
therein.
[0006] It is a further purpose of this invention to quantify tissue
water content by modeling the relationship between tissue water
content and a thermal property of tissue that varies as a function
of tissue water content.
[0007] It is a purpose of this invention to provide an edema
monitor in which a thermal probe is introduced into thermal
communication with live tissue at a selected site and energized to
transfer thermal energy to the tissue and tissue water content is
determined from a thermal property of tissue which varies as a
function of tissue water content.
[0008] It is an objective of this invention to assess tissue water
content as a function of the power used to heat tissue at a
selected site and a thermal property of tissue which varies as a
function of tissue water content.
[0009] It is also an object of this invention to quantify edema in
tissue as a function of the power used to heat tissue at a selected
site and the thermal conductivity of tissue.
[0010] In the present invention, the monitoring of water content
(edema) in live tissue is provided by detecting the thermal
response of the subject tissue to the application of thermal energy
and computing water content as a function of the thermal response
and thermal energy or power used. Certain thermal properties of
tissue vary as a function of tissue water content. For example,
thermal diffusivity and thermal conductivity of the tissue increase
as the water content of the tissue increases. Accordingly, the
thermal response to the introduction of heat in a selected tissue
sample or organ is a function of these properties. Herein, the
terms tissue water content and edema are essentially synonymous,
edema being a condition of abnormally high tissue water
content.
[0011] A preferred embodiment, the invention includes a thermal
probe which thermally communicates with tissue in contact with it
and which electrically communicates with a monitor. The probe
incorporates an embedded thermistor. In a minimally invasive probe,
a distal thermistor is embedded in the tip of a narrow gage
catheter (1-mm diameter). The catheter is inserted into tissue at a
site to be examined and effects thermal contact with surrounding
tissue. The thermistor, adapted for thermal contact with the
tissue, is heated to a small increment above the tissue temperature
baseline. (For example the temperature of the thermistor surface
may be elevated to a predetermined temperature approximately
2.degree. C. above the tissue temperature baseline.) A second or
proximal thermistor may be embedded in the probe for monitoring
tissue baseline temperature and compensating for baseline
temperature fluctuations. The distal thermistor is heated at
intervals by power source within a control circuit. The power used
to elevate the temperature in an interval is indicative of a value
of the selected thermal characteristic, for example, thermal
conductivity and/or thermal diffusivity, in tissue at the location
of the thermistor. The sensed temperature results in a signal from
the power source functionally related to the thermal response in
the tissue to the application of heat, which signal is used to
calculate a value indicative of tissue water content. The following
example is based on thermal conductivity.
[0012] When the thermistor is in thermal contact with live tissue
at a site where water content is to be assessed, the power
dissipated by the heated thermistor (typically within the range of
0.005-0.01 W) provides a measure of the ability of the tissue to
carry heat by both conduction in the tissue and convection due to
tissue blood flow. In operation, the thermistor is energized and a
thermal field propagates into tissue contacting and surrounding the
thermistor. The initial propagation of the field is due
substantially to inherent tissue conductivity (thermal
conductance). Subsequent propagation of the field is affected more
by tissue convection (blood flow or perfusion). A monitor or data
processor controls the probe, records the data and distinguishes
between the effect of the inherent thermal conductivity
characteristic of the tissue and convective heat transfer due to
tissue blood flow. The inherent or intrinsic thermal conductivity
of the tissue at the site of the thermistor is determined from the
initial rate of propagation of the thermal field in the tissue,
separated from the effects of convective heat transfer.
[0013] A data processing technique by which the thermal conductive
and convective effects of the heated thermistor are distinguished
and separated will now be discussed. Measurements are made under
effectively transient conditions, i.e., at times which are short
relative to the time required for the system to reach steady state.
Accordingly, the temperature change produced in the tissue is
permitted to vary in any arbitrarily selected manner with time. The
power required to heat the tissue and the resulting temperature
change are recorded. An intrinsic thermal conductivity value is
calculated using data obtained at an initial time period. The
conductivity value is used to assess the fluid content (or edema)
of tissue at the site of the probe. The water content of the tissue
is computed as a function of the intrinsic thermal conductivity of
the tissue and data derived by using a model of the relationship of
intrinsic tissue conductivity values to tissue water content
values.
[0014] As is often the case in monitoring procedures, there is some
margin of error that must be held within a range deemed appropriate
for acceptable or optimum operation. When direct computation of
conductivity (or other thermal property) does not lead to an
acceptably accurate calculation of water content, an iterative
process may be used to optimize the accuracy of the water content
calculation. For example, computation can be based on a thermal
model requiring a series of heating cycles with measurements at two
or more selected times within each cycle. These measurements occur
during a temperature change cycle in which the temperature of
tissue at the selected site is raised from a first unperturbed
value to a second value and relaxed back to an unperturbed value. A
thermal model and related mathematical equations are described in
U.S. Pat. No. 4,852,027 to Bowman et al. When data used to assess
the thermal conductivity of tissue includes measurements made at
least two selected time periods in an overall temperature changing
cycle, data processing occurs in an interactive or iterative
operation so as to converge relatively rapidly to a final solution
for conductivity of tissue at the site of the probe. In one
embodiment, the thermistor is energized to heat the tissue at the
selected site from an unperturbed temperature value to a second
higher temperature value and then permitted to decay, i.e. to cool,
to an unperturbed value. Power is applied to energize the
thermistor in any appropriate manner that produces an arbitrarily
selected change as a function of time in the volume mean
temperature of the tissue surrounding the thermistor. Measurements
are made in at least two selected time periods during the heating
and cooling cycle. The effects of the flow in the tissue
(perfusion) on the measurements involved are least (substantially
negligible) during the initial stage of the heating cycle and
greater during the later portion of the cycle. Particularly, the
effects of flow are greater during the cooling portion of the cycle
than during the heating portion.
[0015] In the iterative computation, the temperature of the
thermistor is caused to rise to initiate each heating cycle and
relax at the end of each cycle. An initial determination of a value
for intrinsic thermal conductivity (or thermal diffusivity), is
calculated during a first time period in the initial and each
subsequent heating cycle. This first time period calculation is
made at the initial stage of each heating cycle. A calculation of
the convective heat transfer effect in the tissue due to perfusion
of the tissue is separately calculated at a second time period,
later in the heating cycle, using the conductivity value obtained
in the initial time period and perfusion data obtained at the
second time period, the effects of convective heat transfer during
the second time period being greater than the convective heat
transfer effects during the first time period. The perfusion value
obtained at the second time period is used to recompute a second,
more accurate value of thermal conductivity in the first time
period. The process can be repeated as many times as necessary. In
each calculation of perfusion the value of conductivity obtained in
the prior calculation is used. Similarly, in each successive
computation of thermal conductivity the prior value of perfusion is
used. The iterative process will lead to convergence wherein the
same value of thermal conductivity is obtained in successive
calculations. This value of conductivity can be used to compute the
fluid content of tissue at the location of the probe.
[0016] The calculation of edema in the above described embodiment
thus takes into account the effective thermal conductivity of the
subject tissue, that being the convective heat transfer effect
produced by tissue perfusion plus the intrinsic thermal conduction
of the tissue, and separates the convective heat transfer effect
(perfusion) from the intrinsic thermal conductivity. (Similarly,
effective thermal diffusivity is the intrinsic thermal diffusivity
of the tissue plus the perfusion related diffusivity effects.)
BRIEF DESCRIPTION OF THE DRAWINGS
[0017] FIG. 1 is a block diagram of a system according to one
embodiment of the invention;
[0018] FIG. 2A illustrates one example of a probe useful in
connection with an embodiment of this invention diagrammed in FIG.
1;
[0019] FIG. 2B illustrates a typical pattern of heat distribution
in tissue produced by the heated probe of FIG. 2A;
[0020] FIG. 3 is a schematic view of the invention as applied in
monitoring brain tissue;
[0021] FIG. 4 illustrates an empirical water content model as a
curve of conductivity versus percent mass water content;
[0022] FIG. 5 illustrates a theoretical water content model;
[0023] FIG. 6 illustrates an empirical water content model as a
curve of thermal diffusivity versus percent mass water content;
[0024] FIG. 7 depicts curves of thermistor temperature and power as
a function of time in accordance with an embodiment of the
invention;
[0025] FIG. 8 shows curves of thermistor temperature as a function
of time in accordance with another embodiment of the invention;
[0026] FIG. 9A is an extrapolated curve of thermal conductivity
with reference to the embodiment of the invention referred to in
connection with FIG. 8;
[0027] FIG. 9B is an extrapolated curve of thermal diffusivity with
reference to the embodiment of the invention referred to in
connection with FIG. 8; and
[0028] FIG. 10 is a flow chart illustrating an exemplary embodiment
of the invention.
[0029] FIG. 11 is a flow chart illustrating another exemplary
embodiment of the invention.
DETAILED DESCRIPTION OF THE DRAWINGS
[0030] A system such as that shown in FIG. 1 and, for example, a
probe of the type shown in FIG. 2A can specifically implement the
techniques of the invention. As shown, a probe 10 is immersed in
tissue 12. A self-heating distal thermistor 14 mounted on a
catheter 11 is heated by power from an electrical power source and
control circuit 16. In FIG. 1 the heater voltage supplied via the
power source and control circuit 16 is indicated as V.sub.h(t). The
thermistor 14 is energized to heat a surrounding volume of tissue
12. The mean temperature of the thermistor 14 is rapidly raised to
a predetermined level above its initial equilibrium temperature, or
above the baseline temperature of tissue 12, by the power source
and control circuit 16. A typical heat distribution pattern in
tissue 12 is illustrated in FIG. 2B. The maximum temperature occurs
at the center of the thermistor bead and decreases in all
directions therefrom to the reference temperature; that is, it
decreases to the baseline temperature of the unperturbed tissue
surrounding the site of the thermistor. The volume of tissue
surrounding the thermistor 14 in which the temperature of the
tissue is elevated to any substantial extent by the heated
thermistor is referred to as the measurement field.
[0031] The rate at which heat is transferred from the thermistor 14
is a function of the effective thermal conductivity of the tissue
12. The power used or dissipated in the thermistor to maintain a
predetermined elevated temperature level thus is also a function of
the effective thermal conductivity of the surrounding tissue. The
effective thermal conductivity of living tissue has two principal
components, intrinsic thermal conductivity of the tissue and tissue
perfusion (i.e.: the effect of convection in the tissue). Intrinsic
thermal conductivity of tissue is a function of tissue water
content. Therefore the rate of heat transfer from the thermistor 14
and in tissue 12 is also a function of tissue water content. The
voltage V.sub.h(t) across the thermistor 14 (an electrically
resistive thermistor bead which is heated in an active mode and
unheated in a sense mode) provides a parameter from which a
determination of the effective thermal conductivity is made. In the
data processor 20 the thermal effect of intrinsic thermal
conductivity and the thermal effect of perfusion are separated and
the intrinsic thermal conductivity value is used in the calculation
of tissue water content
[0032] The signal V.sub.h(t) from the power source and control
circuit 16 is indicative of the power or thermal energy supplied by
the control circuit 16 to the thermistor 14, the value of which is
also a function of the thermal response in the tissue resulting
from the application of heat. The signal V.sub.h(t), functionally
related to effective thermal conductivity of tissue 12, is supplied
in digital form via a suitable analog-to-digital converter 15 to a
digital data processor 20 which computes the intrinsic thermal
conductivity. A proximal thermistor 18, located on probe 10 to be
outside the thermal range or measurement field of thermistor 14,
monitors the baseline temperature and provides a signal V.sub.s(t)
which adjusts for baseline temperature shifts. The proximal
thermistor 18 is an option used where baseline temperature shifts
are (or are expected to be) substantial enough to interfere with
effective monitoring. In stable thermal environments the
compensation provided by thermistor 18 is not required.
[0033] The data processor 20 processes power related signals from
the control circuit 16 and baseline signals from the thermistor 18
(if used) and provides to a display device 22 a signal the value of
which is indicative of tissue water content. A display device then
displays the assessment of tissue water content. More particularly,
the thermal property model 24 (which may be an algorithm forming
part of data processor 20) communicates with power source 16, water
content model 26 (which also may be an algorithm forming part of
data processor 20) and probe 10. The thermal property model 24
determines the intrinsic thermal conductivity (k) as a function of
the power supplied to the thermistor 14 (via the signal V.sub.h(t)
provided by control circuit 16) and, in an embodiment where
baseline adjustment is required, a baseline signal from thermistor
18. Drawing on the water content model 26 and the thermal property
model 24, the data processor 20 computes the water content of
tissue 12.
[0034] In the embodiment shown in FIG. 1, an intrinsic thermal
conductivity data signal is provided to the water content model 26
from the thermal property model 24. The water content model 26
relates the conductivity value to a corresponding value for tissue
water content. The tissue water content or edema value provided by
the model 26 is communicated to the display device 22 for
appropriate display. Tissue water content or edema is determined by
water content model 26 which correlates the conductivity signal
provided by the thermal property model 24 with a corresponding
tissue water content value. The thermal property model 24 and the
water content model 26 will be discussed further below.
[0035] The example given is directed to the use of an invasive
probe 10 having thereon a thermistor 14 to which power is applied
to heat the thermistor and, accordingly, to heat the tissue
surrounding it. However, the invention is not so limited. For
example, rather than applying heat to the tissue in an internal or
invasive sense by applying power to a probe immersed in the tissue,
heat can be applied non-invasively to the tissue from an external
heat source. Examples of probes that are adapted for non-invasive
use are shown in U.S. Pat. No. 4,859,078 to Bowman et al. and U.S.
Pat. No. 4,841,543 to Dittmar et al. Probes such as these can be
used on the skin surface or, during surgery, on the surface of an
internal organ without penetrating the skin or organ with a probe.
The volume of tissue within the measurement field is that volume of
tissue which is heated above the tissue baseline temperature.
[0036] A representation of the system of this invention for
monitoring edema in the brain is illustrated schematically in FIG.
3. In some cases of head trauma and some surgeries, one or more
openings or burr holes 32 are formed in the skull 30 and fitted
with hollow bolts 34 to provide access to the brain cavity. The
hollow bolts can serve as an access to the brain for introduction
of the probe 10. The probe 10 is passed through the hollow bolt 34
to imbed the distal thermistor 14 in brain tissue. In embodiments
with a baseline monitoring proximal thermistor 18, the probe 10 is
positioned so the thermistor 18 is also imbedded in brain tissue.
Brain edema is monitored during surgery and can be monitored
following surgery. One use for the tissue water content data is to
identify a condition of edema associated with swelling of the brain
sufficient to cause constriction of blood flow, so appropriate
treatments or surgical interventions can be made. In other
surgeries, such as heart surgery, the probe 10 or a non-invasive
probe may be applied to the heart or to surrounding tissue to
assess tissue fluid retention at those locations.
[0037] The tissue water content model 26 will now be described. The
tissue water content model may be formulated to model a thermal
property of tissue that varies in a known way with tissue water
content. For example, values for rates at which heat may be
transferred in tissue can be related by the model with
corresponding tissue water content values. The relationship
established by the model and the power supplied to heat a volume of
tissue at a selected site can be used to quantify water content of
tissue at the site. One such model based on the thermal
conductivity of tissue is an empirical model that correlates
possible or probable intrinsic thermal conductivity values with
corresponding values of tissue water content. This model is based
upon the conductivity of the three major components constituting
tissue, water, fat and protein. The thermal conductivity of water
is 6.23 mW/cm-.degree. C. and the thermal conductivity of both fat
and protein approximate 2.00 mW/cm-.degree. C. The values for fat
and protein are sufficiently close to each other and sufficiently
distinct from that of water that an effective model can be based
either on an assumed approximate value (for example 2.0) for both
fat and protein or on individual values for fat and protein. An
empirical model of tissue conductivity at various percentages of
water content can be formulated using a water-glycerol mixture with
the glycerol (having a thermal conductivity of 2.85 mW/cm-.degree.
C. at 37.degree. C.) being the model for fat and protein.
Measurements taken using a water-glycerol mixture yielded the curve
illustrated by FIG. 4. In the range of 60% to 100% water content,
which is the range in which most applications of the invention
fall, the data points fall substantially in a straight line
indicating water content to have substantially a linear
relationship with conductivity. A line that fits the data points
can be expressed as:
y=3.802x+2.445 (1)
[0038] where "y" represents thermal conductivity and "x" represents
percent mass water content. Below 60% water content, the data
points measured in the water-glycerol mixture were not linear. A
curve that fits the data over the full 0%-100% range of water
content can be expressed as:
y=-0.852x.sup.3+1.993x.sup.2+2.2436x+2.854 (2)
[0039] where "y" represents thermal conductivity and "x" represents
percent mass water content.
[0040] An empirical model can also be based on actual tissue
measurements when there is independent confirmation of the water,
fat and protein content of the tissue samples in which thermal
conductivity data are taken.
[0041] Additionally, the model can be based on theoretical values
for thermal conductivity of fat, protein and water. An example is
shown by FIG. 5, where there is essentially a straight-line
relationship between thermal conductivity and percent mass water
content. The relationship can be expressed as:
y=ax.sup.3+bx.sup.2+cx+d; (3)
[0042] where "y" represents thermal conductivity, "x" represents
percent mass water content and a, b, c, and d are constants. This
expression is similar in form to Expression No. 2, above.
[0043] The above referenced models for intrinsic thermal
conductivity of tissue are based on the principle that the
conductivity of a volume of tissue is a function of the
conductivity of each constituent component, weighted by its mass
fraction. That is:
m.sub.t=m.sub.h+m.sub.f+m.sub.p. (4)
[0044] Where: m.sub.t is the mass of the tissue; m.sub.h is the
mass of the water component; m.sub.f is the mass of the fat
component and m.sub.p is the mass of the protein component.
[0045] Dividing Equation (4) by the mass of tissue (m.sub.t) to
obtain the mass fraction, the result is:
1=.gamma.+.beta.+.theta. (5)
[0046] Where: .gamma.=m.sub.h/m.sub.t=the mass fraction of water in
the tissue;
[0047] .beta.=m.sub.f/m.sub.t=the mass fraction of fat in the
tissue; and
[0048] .theta.=m.sub.p/m.sub.t=the mass fraction of protein in the
tissue.
[0049] Therefore the conductivity of tissue can be expressed in
terms of mass fractions as:
k.sub.t=.gamma.k.sub.h+.beta.k.sub.f+.theta.k.sub.p (6)
[0050] Where: k.sub.t is the conductivity of tissue; k.sub.h is the
conductivity of water in the tissue, k.sub.f is the conductivity of
fat in the tissue and k.sub.p is the conductivity of protein in the
tissue.
[0051] Similarly, other thermal properties of tissue (such as
diffusivity) can be expressed in terms of mass fractions as:
.alpha..sub.t=.gamma..alpha..sub.h+.beta..alpha..sub.f+.theta..alpha..sub.-
p (7)
[0052] Where .alpha.t is the thermal property (such as diffusivity)
of tissue, .alpha..sub.h is the thermal property of water in the
tissue, .alpha..sub.f is the thermal property of fat in the tissue
and .alpha..sub.p is the thermal property of protein in the
tissue.
[0053] In addition, one tissue water content model may be
formulated from another when the relationship between them is
known. For example, in the case of thermal diffusivity, the
relationship between conductivity (k) and diffusivity (.alpha.) is
expressed as:
.alpha.=k/.rho.c (8)
[0054] Where .rho. and c are, respectively, density and heat
capacity. Accordingly a water content model for diffusivity can be
calculated readily from the conductivity model.
[0055] A model for diffusivity can also be empirically derived, for
example, with the same water-glycerol mixture described in
connection with empirical development of the conductivity model.
One such model is illustrated by FIG. 6. A curve that fits the data
points of FIG. 6 can be expressed as:
y=-0.131x.sup.3+0.229x.sup.2-0.068x+0.099. (9)
[0056] where "y" represents thermal conductivity and "x" represents
percent mass water content.
[0057] Since the water content of tissue changes, this change is
reflected in a corresponding change in the intrinsic value of the
thermal property such as conductivity and diffusivity. During
injury to tissue, for example, water content will typically
increase resulting in the condition of edema. According to this
invention, a measure of at least one of the water-dependent thermal
properties of tissue, for example, intrinsic thermal conductivity,
in an area of injury is made and used to quantify the tissue water
content (i.e.: to quantify edema). The data processor 20 is
programmed with a model of the relationship of conductivity and
tissue water content, such as one of those referenced above. The
system processes thermal conductivity data in accordance with a
tissue water content model as described above to quantify the
percent mass water content of tissue (or edema) and provide an
appropriate display.
[0058] The water content model 26 may function as a look-up
reference wherein for any known value of a tissue thermal property
such as conductivity or diffusivity, a corresponding or related
value for tissue water content is provided.
[0059] It will be appreciated that, in alternate data processing
techniques, tissue water content can be computed directly from the
primary data, without actually computing a value signal for
conductivity. For example, the data processor 20 can be caused to
compute water content in response to data supplied via circuit 16,
input from a model of tissue water content (as illustrated by
alternate water content model 26' in FIG. 1) and data from the
probe 10. Alternate model 26' acts as a look-up reference that
correlates tissue thermal property values, such as conductivity and
diffusivity, to water content. The alternate model 26' provides to
the data processor 20 an input of the correlated water content
values and the data processor calculates the water content of the
subject tissue as a function of the three inputs: correlated data
input from the alternate model 26'; the signal from the control
circuit 16 functionally related to the power required to heat the
thermistor 14; and the baseline signal from probe 10.
[0060] The above-described techniques calculate tissue water
content based on measurements of a thermal property variable with
water content (e.g.: thermal conductivity or thermal diffusivity)
in the selected tissue. To monitor continuously, the values for
edema calculated as described are recalculated in rapid succession.
The thermistor 14 is cyclically energized and deenergized to
produce repetitive heating cycles and edema is recalculated in each
energizing cycle, during each rise and fall of the temperature of
the thermistor. By the described techniques of this invention, an
updated edema value can be obtained, for example, every three to
six minutes.
[0061] A description of thermal property model 24 and mathematics
for a method for determining effective thermal conductivity,
thermal diffusivity and intrinsic thermal conductivity are
described in the above referenced U.S. Pat. Nos. to Bowman et al.
4,059,982 and 4,852,027. As taught there, various heating protocols
can be used to heat the thermistor. The thermistor 14 can be heated
to a constant or predetermined temperature or thermistor
temperature can be measured during heating at a constant or
predetermined power or other heating protocols can be used. In all
protocols, procedures using the same principles are used to analyze
data. Power used to heat the thermistor and the temperature rise of
the thermistor are functional inputs to the calculation of tissue
water content and, in calculating water content, one of the values
is predetermined. Two heating protocols will be described, one in
connection with FIG. 7 and a second in connection with FIGS. 8, 9A
and 9B.
[0062] In FIG. 7, graphical representations are presented of the
mean bead temperature V.sub.b and of the heating power P, both as
functions of time. In the particular procedure illustrated, power P
is applied at to in a manner such that the thermistor bead
temperature V.sub.b rapidly rises to a selected level V.sub.b2 to
heat a volume of tissue and is maintained at that level for a
selected time period (until time t.sub.i, for example) at which
time the power is reduced to zero (shut-off) and the temperature
V.sub.b falls to baseline temperature in a general manner as shown,
completing one energizing and deenergizing cycle.
[0063] Approximation algorithms, as discussed below, can be used
with data derived from measurements taken at different times during
the overall heating/cooling cycle as, for example, early in the
heating portion thereof at the time range or time window,
illustrated by "A" in FIG. 7 and later in the heating portion at
"B".
[0064] Data taken during time window "A" are dominated by tissue
conduction (i.e.: conductivity) and the effects of the flow
(perfusion) in the tissue are relatively low. Data taken during the
time window "B", occurring later in time as heating continues, are
influenced to a greater extent by perfusion, (i.e.; the effects of
flow in the tissue are greater than at time window "A".)
[0065] One exemplary data analysis algorithm usable at time windows
"A" and "B" is illustrated by the flow chart of FIG. 10. As stated,
the effects of the flow of the medium during the time window "B"
are greater than during time window "A" (FIG. 7). Calculations with
respect to time windows "A", and "B" can be made as follows: (1)
Cause the temperature of the thermistor to change from a first
temperature (T.sub.1) to a second temperature (T.sub.2) to initiate
a thermal cycle while controlling in a predetermined manner either
the temperature or the power required to effect the temperature
change; (2) cause the temperature to relax from the second
temperature to a final temperature (T.sub.f) at the end of a
heating cycle; (3) measure temperature and power; (4) calculate a
value of the intrinsic thermal conductivity and/or diffusivity
during time window "A"; (5) assuming a value of zero for perfusion;
calculate a tissue water content (edema) using the values(s) from
step (4) and the water content model; and (6) display the
calculated tissue water content value.
[0066] Alternately, if a smaller margin of error is required than
that obtained above in step (5), iterative calculations are
performed following step (4) as follows: (7) using the calculated
values of intrinsic thermal conductivity and/or diffusivity from
step (4), calculate a value for perfusion during time window "B";
(8) using the calculations of the thermal conductivity and/or
diffusivity as calculated during time window "A" and the perfusion
value as calculated during time window "B" recalculate the thermal
conductivity and/or diffusivity during time window "A" (9) using
such recalculations for intrinsic thermal conductivity and/or
diffusivity, recalculate the value for perfusion during time window
"B"; (10) using such recalculated perfusion and recalculated values
for intrinsic thermal conductivity and/or diffusivity recalculate
again thermal conductivity and/or diffusivity; (11) repeat steps
(9) and (10) until convergence to substantially non-changing
thermal conductivity and/or diffusivity value(s) is achieved; (12)
calculate to quantify tissue water content (edema) using the
values(s) from step (11) and the water content model; and (13)
display the calculated tissue water content.
[0067] FIG. 11 illustrates a further embodiment in which water
content is determined from various parameters affected by the
conductivity or other thermal property of tissue without a
calculation of the thermal property value. Temperature, power and a
model that relates them both (P/.DELTA.T) to tissue water content
(% H2O) are used in the direct calculation of water content. The
model may be empirically or theoretically based. The steps are: (1)
cause the temperature of the thermistor to change from a first
temperature (T.sub.1) to a second temperature (T.sub.2) to initiate
a thermal cycle while controlling either the temperature or the
power required to effect the temperature change; (2) cause the
temperature to relax from the second temperature to a final
temperature (T.sub.f) at the end of a heating cycle; (3) measure
temperature (T) and power (P); (4) Determine the ratio of power to
the change in temperature (P/.DELTA.T); (5) using the combined
model determine a water content value corresponding to the value of
P/.DELTA.T resulting from step (4); and (6) display the water
content value.
[0068] Another exemplary alternative algorithm will be described in
connection with FIGS. 8, 9A and 9B. FIG. 8 illustrates an
energizing cycle similar to that shown in FIG. 7. FIGS. 9A and 9B
illustrate, respectively, data extrapolations for thermal
conductivity and thermal diffusivity. The calculation of edema
consists of the following steps: (1) calculate a plurality of
effective thermal conductivity and/or thermal diffusivity values
during a plurality of time windows X.sub.l where X.sub.l is X,
X.sub.l, X.sub.ll, etc, with an assumed perfusion value of zero;
and (2) extrapolate the thermal conductivity and diffusivity values
obtained in step (1), above to time to, i.e., to the instant of
time at which heating begins, to obtain values for intrinsic
thermal conductivity and/or intrinsic thermal diffusivity. (See
FIGS. 9A and 9B.) (The points X, X.sub.l, X.sub.ll, etc. are
selected at the same normalized position within each window, e.g.
the middle or the end of each window). The extrapolated values will
be the nonperfused, intrinsic thermal conductivity (k) value and
the nonperfused, intrinsic thermal diffusivity (.alpha.) value; (3)
calculate a tissue water content (edema) using the values(s) from
step (2); and (4) display the calculated tissue water content
value. A value for tissue water content (edema) with no substantial
margin of error can be obtained by continuing the calculation
process according to the following steps: (5) use extrapolated
values of intrinsic thermal conductivity and diffusivity from step
(2) above to calculate the perfusion at a selected time during
which a perfusion effect occurs, e.g. time window "Y" (FIG. 8); (6)
recalculate the intrinsic thermal conductivity and diffusivity at
said plurality of time windows X.sub.l using the calculated
perfusion value for the selected time window "Y"; (7) extrapolate
the thermal conductivity and diffusivity values obtained in step
(6) to time to; and (8) repeat steps (6) and (7) until intrinsic
thermal conductivity and thermal diffusivity values converge to
substantially non-changing values; (9) calculate tissue water
content (edema) using the values(s) from step (8); and (10) display
the calculated tissue water content value.
[0069] While the above illustrative embodiments discuss procedures
in which the temperature is raised to and maintained at a higher
level for a finite time period, this analysis technique may also be
applied to measurements obtained when the temperature is raised to
an appropriate level and immediately allowed to relax to an
unperturbed value, the most crucial time for the thermal property
measurements being the time or instant when the heating cycle is
begun.
[0070] The invention is not to be deemed as limited to the
particular embodiments described above, except as defined by the
appended claims.
* * * * *