U.S. patent application number 12/627068 was filed with the patent office on 2011-06-02 for aspiration methods and devices for assessment of viscoelastic properties of soft tissues.
This patent application is currently assigned to Artann Laboratories, Inc.. Invention is credited to Armen P. Sarvazyan.
Application Number | 20110130683 12/627068 |
Document ID | / |
Family ID | 44069406 |
Filed Date | 2011-06-02 |
United States Patent
Application |
20110130683 |
Kind Code |
A1 |
Sarvazyan; Armen P. |
June 2, 2011 |
ASPIRATION METHODS AND DEVICES FOR ASSESSMENT OF VISCOELASTIC
PROPERTIES OF SOFT TISSUES
Abstract
Methods for assessing viscoelastic properties of soft tissues
are based on detecting an inflection point on a pressure-time plot
when air is aspirated from a cavity placed over the tissue sample.
A small diameter tube through which air aspiration is conducted is
ultimately closed off by tissue being drawn into the cavity causing
an abrupt change in pressure slope. First or second derivatives of
the pressure-time plot can be used to detect the inflection point.
Repeating the test with a different aspiration rates or after a
predetermined relaxation time allows determining tissue viscosity
and tissue creep in addition to tissue elasticity expressed as
Young's modulus.
Inventors: |
Sarvazyan; Armen P.;
(Lambertville, NJ) |
Assignee: |
Artann Laboratories, Inc.
Lambertville
NJ
|
Family ID: |
44069406 |
Appl. No.: |
12/627068 |
Filed: |
November 30, 2009 |
Current U.S.
Class: |
600/587 |
Current CPC
Class: |
A61B 5/441 20130101;
A61B 5/6834 20130101; G01N 2203/0071 20130101; G01N 3/00 20130101;
A61B 5/442 20130101; G01N 2203/0094 20130101; A61B 5/0055 20130101;
G01N 2203/0089 20130101 |
Class at
Publication: |
600/587 |
International
Class: |
A61B 5/103 20060101
A61B005/103 |
Claims
1. An aspiration method for assessing viscoelastic properties of
soft tissue, the method comprising the steps of: a) providing a
test cavity in a sealed contact with said tissue, said test cavity
includes an opening connected to an aspiration system, said opening
located on a path of expected deformation of said tissue, b)
activating said aspiration system to evacuate air through said
opening from said cavity at a first rate of aspiration to draw said
tissue into said cavity, c) conducting pressure measurements in
said aspiration system and said test cavity as a function of time
as said tissue is being drawn into said cavity, continue to draw
said tissue into said cavity to cause closure of said opening by
said tissue and separation of said test cavity from said aspiration
system, d) detecting a first slope of said pressure measurements in
said test cavity, e) detecting a first inflection point in said
pressure measurements, said first inflection point defining a first
pressure level and a first time point at which said pressure
measurements deviate from said first slope indicating closure of
said opening by said tissue and cessation of said tissue being
drawn into said test cavity, said first inflection point is
detected using a method selected from a group consisting of: i.
detecting deviation of said first slope above a predetermined slope
deviation threshold, ii. detecting a first derivative of said first
slope exceeding a predetermined first derivative threshold, and
iii. detecting a second derivative of said first slope exceeding a
predetermined second derivative threshold, f) determining
elasticity of said tissue using said first slope of said pressure
measurements and said first pressure level at said first inflection
point.
2. The method as in claim 1, wherein said step (d) further
including constructing a first best-fit straight line through said
measurements located prior to said inflection point and a second
best-fit straight line through said measurements located after said
inflection point, said method further including defining a
corrected inflection point located at an intersection of said first
best-fit straight line and said second best-fit straight line.
3. The method as in claim 1, wherein said test is stopped once said
inflection point is determined and said cavity is immediately
vented to release said tissue.
4. The method as in claim 1 further comprising venting said cavity
to release said tissue, waiting during a first predetermined time
to allow said tissue to relax, and repeating steps (b) through (f)
wherein step (b) includes evacuating air from said cavity at a
second rate of aspiration, said step (d) includes detecting a
second slope of pressure measurements in said cavity, said step (e)
includes detecting a second inflection point defining a second
pressure level and a second time point at which said tissue is
drawn into said test cavity, said step (f) further including
determining tissue viscosity using said first pressure level and
said second pressure level.
5. The method as in claim 1, further comprising the steps of: g.
venting said cavity to release said tissue, h. waiting during a
second predetermined time to allow said tissue to partially relax,
and i. repeating steps (b) through (g) to detect a third inflection
point defining a third pressure level, wherein said step (f)
further including determining tissue creep using said first
pressure level and said third pressure level.
6. A device for assessing viscoelastic properties of soft tissues
by aspiration, said device comprising: a probe having a cavity
adapted to be sealingly placed against said tissue, a tube
extending from said cavity to a vacuum pump, a pressure sensor in
fluid communication with said tube, and an electronic unit adapted
to activate said vacuum pump and conduct pressure measurements in
said tube as a function of time, said electronic unit further
adapted to detect at least one inflection point in said pressure
measurements, said unit further adapted to determine at least one
viscoelastic property of said tissue.
7. The device as in claim 6, wherein a ratio of a volume of said
cavity to a volume of said tube is selected between 2 and 10.
8. The device as in claim 6, wherein said tube protrudes inside
said cavity to end at a predetermined distance from a plane defined
by an outer edge of said cavity.
9. The device as in claim 6 further including a vent valve in fluid
communication with said tube, said electronic unit adapted to vent
said tube once said inflection point is detected.
10. The device as in claim 6 adapted to aspirate air from said
cavity at different rates of aspiration.
11. The device as in claim 10, wherein said electronic unit is
adapted to cause operation of said vacuum pump at more than one
speed so as to provide for more than one aspiration rate from said
cavity.
12. The device as in claim 10, wherein said tube further including
a first restrictor.
13. The device as in claim 10, wherein said tube further including
a plurality of parallel restrictors, each restrictor having a
corresponding shut-off valve, said electronic unit adapted to open
one or more of said shut-off valves to route the flow from said
tube to said vacuum pump therethrough, whereby the aspiration rate
from said cavity is defined by a combined flow resistance through
all restrictors with opened shut-off valves.
14. The device as in claim 13, wherein said restrictors have
different diameters defining different individual flow
resistance.
15. The device as in claim 6 wherein said probe including a
disposable replaceable tip defining said cavity.
16. The method as in claim 1, wherein in step (e) said first slope
increases in value after said first pressure level and said first
time point.
Description
BACKGROUND OF INVENTION
[0001] The invention relates to methods and devices for assessing
viscoelastic properties of soft tissues. In particular, the
invention relates to using aspiration methods to detect elasticity,
viscosity, creep and other properties of accessible living tissues
such as skin, cervix, vaginal wall, etc.
[0002] Mechanical properties of skin (e.g., elasticity of skin) may
change due to disease, stress, or dehydration. When the body
becomes dehydrated as a result of diseases such as those that cause
diarrhea or reduced liquid intake such as famine or marathon
running, the skin becomes "doughy" and does not snap back when
pinched. In a test for dehydration called the "pinch test" or
"turgor test," the skin is grasped and pulled up in a pinch-like
manner and then released. Healthy skin will quickly snap back to
its undeformed state, whereas dehydrated skin returns to its
undeformed state slowly. Such conventional test is subjective and
inaccurate. Objective determination of skin elasticity is important
for detecting a state of dehydration as well as diagnosis of other
pathological conditions.
[0003] Characterizing viscoelastic properties of other human soft
tissues is clinically important as well. One such tissue is female
uterine cervix. The occurrence of cervical ripening before 34 weeks
of gestation leading to preterm delivery represents a serious
medical problem. Preterm delivery is a major cause of perinatal
morbidity and mortality. About 12.5 percent of babies (more than
half a million a year) in the United States are born prematurely.
For reasons that doctors do not fully understand, the rate of
premature birth has increased by more than 30 percent since 1981.
Premature babies are at increased risk for newborn health
complications, as well as lasting disabilities, such as mental
retardation, cerebral palsy, lung and gastrointestinal problems,
vision and hearing loss, and even death.
[0004] The uterine cervix has to provide mechanical resistance to
ensure a normal development of the fetus. Cervical softening occurs
progressively in the last one-third of pregnancy. The process of
cervical ripening, consisting of softening of the connective tissue
components, is not easily identifiable with present methods.
Objective quantitative assessment of cervical ripening will allow
dispensing of therapy for preterm labor. Specific defects in
cervical ripening will then be diagnosed and treated.
[0005] Another area in need of an objective device and method for
characterization of soft tissue is in detection of pelvic organ
prolapse, a major cause of female incontinence. Pelvic organ
prolapse (POP) is a highly prevalent condition affecting at least
50% of women in the US at some point during their lifetimes. One
recent study including 27,342 women revealed that 40% percent of
women aged 50 to 79 years have some form of pelvic organ prolapse.
Some loss of utero-vaginal support occurs in most adult women.
However, the true etiology of prolapse and differences seen among
individuals are not entirely understood. Changes in the elasticity
of the vaginal walls, connective support tissues, and muscles are
thought to be significant factors in the development of pelvic
organ prolapse. The high incidence of POP dictates the need for
effective means of its early detection and characterization as well
as evaluating the risk of further prolapse development.
[0006] Aspiration methods for assessment of elasticity of skin and
other soft tissues are generally known. Typically, a device forms a
cavity over a tissue sample. Air is then aspirated causing the
tissue to be drawn into the cavity. Extent of tissue prolapse into
the cavity is measured by various mechanical, optical or other
means. Tissue elasticity is then determined based on the degree of
such prolapse and the level of vacuum achieved by the device.
Examples of prior art attempts at various devices based on this
aspiration method are found in U.S. Pat. Nos. 4,365,638; 4,976,272;
5,278,776; 7,556,605; US Patent Application Publication No.
2008/0234607 and the PCT Publication No. WO 03/105689. These
devices however lack the ability for a comprehensive assessment of
tissue which goes beyond simple elasticity measurements.
[0007] Other areas of interest for detection of tissue elasticity
include intraoperative detection of lesion boundaries during open
surgery procedures.
[0008] The need therefore exists for improved methods and devices
to measure various viscoelastic properties of soft tissues such as
elasticity modulus, tissue viscosity and tissue creep.
SUMMARY OF INVENTION
[0009] Accordingly, it is an object of the present invention to
overcome these and other drawbacks of the prior art by providing
novel methods and devices for objective evaluation of viscoelastic
properties of soft tissues.
[0010] It is another object of the invention to provide an
aspiration method for objective evaluation of viscoelastic
properties of soft tissues allowing for comprehensive tissue
evaluation beyond determination of tissue elasticity by Young's
modulus. Other properties of interest that can be determined using
the method of the invention include tissue viscosity and tissue
creep.
[0011] A novel aspiration method for measuring soft tissue
mechanical properties uses a probe having a cavity with an outer
edge adapted to sealingly come in contact with the tissue test
area. A small diameter tube enters the cavity in its center and
extends inside thereof to end at a specific distance from the plane
defined by the outer edge of the cavity. A vacuum pump and pressure
sensor are connected to other end of the tube. The vacuum pump is
activated to aspirate air from the cavity placed over the tissue
test area. This draws tissue inside the probe cavity. The
aspiration rate is constant creating a linear relationship between
the negative pressure inside the probe cavity and time. The domed
tissue keeps moving into the cavity until it finally reaches the
inner tube and closes its opening. At this point, the remaining
cavity volume is isolated from the pump, the drop in pressure
inside the cavity is stopped and the tissue remains in the same
position despite continuous draw of the vacuum pump. The small
volume inside the tube is the only volume exposed to continuing
aspiration. An abrupt change in volume under continuing vacuum is
detected by the pressure sensor as an abrupt change in slope of
continuous pressure drop. The device monitors negative pressure in
the probe to identify the inflection point in its slope indicating
the touching of the end of the tube by the tissue. The Young's
modulus is then calculated based for example on a predetermined
calibration data and displayed on a screen. Performing successive
measurements with different rates of air aspiration and with
variable intervals between successive measurements allows
determination of other rheological characteristics of tissue such
as viscosity and shear creep.
[0012] The aspiration method of the invention comprising the steps
of: [0013] a. providing a test cavity in a sealed contact with the
tissue, the test cavity includes an opening connected to an
aspiration system, [0014] b. activating the aspiration system to
evacuate air from the cavity at a first rate of aspiration, [0015]
c. conducting pressure measurements in the test cavity as a
function of time, [0016] d. detecting a first slope of the pressure
measurements in the test cavity, [0017] e. detecting a first
inflection point in the pressure measurements defining a first
pressure level and a first time point at which the pressure
measurements deviate from the first slope indicating closure of the
opening by the tissue being drawn into the test cavity, the first
inflection point is detected using one of methods selected as
follows: [0018] i. detecting deviation of the first slope above a
predetermined slope deviation threshold, [0019] ii. detecting a
first derivative of said first slope exceeding a predetermined
first derivative threshold, and [0020] iii. detecting a second
derivative of said first slope exceeding a predetermined second
derivative threshold, [0021] f. determining elasticity of the
tissue using the first pressure level.
[0022] Additional steps allow detecting other tissue parameters
like viscosity and creep from repeated test measurements conducted
at different rates of aspiration and with different waiting periods
between the tests.
BRIEF DESCRIPTION OF THE DRAWINGS
[0023] A more complete appreciation of the subject matter of the
present invention and the various advantages thereof can be
realized by reference to the following detailed description in
which reference is made to the accompanying drawings in which:
[0024] FIG. 1 is a block-diagram of the system of present
invention,
[0025] FIG. 2A is an enlarged cross-sectional side view of a probe
cavity at the start of measurement procedure,
[0026] FIG. 2B is an enlarged cross-sectional side view of a probe
cavity at the end of measurement procedure,
[0027] FIG. 3 is a typical pressure-time plot,
[0028] FIG. 4 is a pressure-time plot for different ratios of
cavity volume to tube volume,
[0029] FIG. 5 is a pressure-time plot for probe cavities with
different volume,
[0030] FIG. 6 is an elevation view of a general purpose probe
tip,
[0031] FIG. 7 is an elevation view of a probe tip with small
diameter,
[0032] FIG. 8 is an elevation view of a right-angled probe tip,
[0033] FIG. 9 is an elevation view of a miniature probe tip,
[0034] FIG. 10 is a pressure-time plot for tissue samples with
different elasticity Young's modulus,
[0035] FIG. 11 is a pressure-time plot with its first derivative
and its second derivative,
[0036] FIG. 12 illustrates the characteristic pressure inflection
point calculation procedure,
[0037] FIG. 13 is a block-diagram of an advanced system of present
invention having multiple aspiration tubes,
[0038] FIGS. 14A and 14B are pressure-time plots for different
aspiration speeds allowing assessment of tissue viscosity,
[0039] FIGS. 15A and 15B are pressure-time plots developed for
assessment of tissue shear creep,
[0040] FIG. 16 is an example of a recorded pressure plot, its first
derivative and second derivative, and
[0041] FIG. 17 is an example of device calibration curve with a
range of elasticity moduli.
DETAILED DESCRIPTION OF THE INVENTION
[0042] A detailed description of the present invention follows with
reference to accompanying drawings in which like elements are
indicated by like reference letters and numerals. FIG. 1
illustrates a block diagram of the device of the invention. Arrows
indicate electrical connections, while double lines indicate
pneumatic connections. The device consists primarily of four basic
components: a specially designed probe tip 1, a vacuum pump 2, a
pressure sensor 3, and an electronic unit 4 for data acquisition,
calculation and displaying the measurement results. An optional
vent valve 5 is used to quickly release vacuum from the measuring
cavity of the probe: it is closed when the measurement starts, and
is opened to vent the cavity to atmosphere when the measurement is
complete. A capillary restrictor 6 can be used for adjusting the
rate of aspiration. The combined internal volume of all internal
connection tubes, primarily internal volume 14 of tube 10 is
assigned a value V.sub.1. The open end cavity of the probe tip is
placed on the tissue test area 8 to seal the volume V.sub.2 inside
the probe test cavity.
[0043] Pumping speed S defines aspiration rate of the cavity,
governed by vacuum pump 2 and restrictor 6 properties, which in
turn defines dependence of pressure P versus time t. For a pumped
volume V in an air-tight system, the pressure change is described
by the following general equation:
dP = - S V Pdt ##EQU00001##
[0044] For small pressure changes, the value S may be considered a
constant, so that
P ( t ) = P 0 - S V ( t - t 0 ) or P ( t ) = P 0 ( 1 - S V ( t - t
0 ) ) when V S ( t - t 0 ) . ##EQU00002##
[0045] These equations indicate that a large aspiration volume V
will result in a lower slope of pressure change, while a higher
pumping speed S will result in a higher slope of pressure change
inside the probe cavity.
[0046] The basic principle behind the aspiration method of the
invention is illustrated in FIG. 2. Cross-section of the probe
cavity is shown here at the time when the measurement commences
(FIG. 2A) and at the time when the tissue reaches the end of the
tube causing an inflection point in the time-pressure plot (FIG.
2B). The small diameter tube 10 passes through the probe tip 11. To
begin the test procedure, the probe cavity is placed in contact
with the tissue test area 12, thereby creating a closed space 15
with volume V.sub.2 between probe tip cavity and tissue 8. When the
measurement is initiated, the vacuum pump 2 creates negative
pressure in this closed space. This in turn draws the tissue
towards the center of cavity. At this time, the speed S at which
the negative pressure is created is constant and the total volume
being aspirated is defined by the sum of volume V.sub.1 of internal
space 14 of tube 10 and volume V.sub.2 of the closed space 15
(V=V.sub.1+V.sub.2). The time dependence of negative pressure
P.sub.v=P.sub.0-P(t) at this point is shown in FIG. 3 as line 41
that can be described by the following equation:
P v = P 0 S V 1 + V 2 t ( 1 ) ##EQU00003##
[0047] The arrows in FIG. 2A show evacuated air going through the
tube 10 leaving cavity space 15. The domed tissue 13 keeps
extending inside the cavity until it finally touches the small
diameter inner tube. At this point (shown in FIG. 2B), the volume
V.sub.2 of space 15 is isolated from the pump 2 and tube 10, and as
a result the rate at which negative pressure is created changes
depending on the internal volume 14 of tube 10. The arrow in FIG.
2B shows that air is aspirated just from volume V.sub.1 of tube 10.
Time dependence of negative pressure at this time is shown in FIG.
3 as line 42 described by the following equation:
P v = P A + P 0 S V 1 ( t - t A ) ( 2 ) ##EQU00004##
[0048] Importantly, the pressure-time plot changes slope at
inflection point A in FIG. 3. The higher the difference between
V.sub.1+V.sub.2 and V.sub.1, the sharper the bending of curve will
be at inflection point A.
[0049] FIG. 4 illustrates how the ratio of volumes V.sub.1 and
V.sub.2 characterize the bend in pressure curve. With the same
total volume V.sub.1+V.sub.2, curve 43 shows the bend when
9V.sub.1=V.sub.2, curve 44 shows the bend when V.sub.1=V.sub.2, and
curve 45 shows the bend when V.sub.1=9V.sub.2. This figure
illustrates that the finding of inflection point is easier (with a
smaller error) when volume V.sub.1 of tube 14 is considerably
smaller then internal cavity volume V.sub.2. For practical
purposes, the ratio of cavity volume to the volume of tube 10 is
selected to be between 2 and 10. Higher than 10 ratios do not
considerably improve measurement accuracy but cause an undesirable
increase in test duration. FIG. 5 illustrates how the negative
pressure changes in time for different probe tips. Activation of
the vacuum pump 2 creates a negative pressure inside the probe
cavity and the pressure-time plot shows a closely linear
characteristic in accordance with equation (1). For a given volume
V.sub.1 of tube 10, the larger the volume V.sub.2 of the probe
cavity, the smaller is the slope of this line. Curve 31 (thicker
line) illustrates a pressure-time plot for a probe tip with a
smaller volume V.sub.2 as compared with the curve 32.
[0050] Different kinds of probe tips are shown in FIGS. 6 through
9. One advantage of the device of the invention is that the tip
containing the test cavity may have provisions allowing it to
detach from the probe. This in turn allows the replaceable tip to
be optionally disposable so as to avoid the need for sterilization
of the entire probe between patient examinations. The simplest (see
FIG. 6) is a general purpose tip. It consists of a small diameter
tube 10 inside the probe tip 11, which is a hollow cylinder with an
open end. The diameter D of this cylinder characterizes the area
the probe that covers the tested tissue. Tube 10 is placed in the
center of the cylinder and ends at a specific distance L from the
open end plane (refer to cross-section shown in FIG. 2). For
applications where the tissue sample has only a small test area
available for evaluation, a probe tip with smaller tip diameter is
required. Such a probe is shown in FIG. 7. It is similar to the
general purpose tip with the exception of structural tube holder 21
that provides access to tissue at a distance. To produce a sharp
inflection point, the internal space of the structural tube holder
21 can be connected to the internal space of probe head 23 through
holes 22. For difficult to reach applications, a right angled probe
tip 24 can be used as shown in FIG. 8. Subminiature probe tips are
shown in FIG. 9. A distinctive feature of this tip is a miniature
tip diameter D, as compared to other tips. Internal space of
structural tube holder 21 is used to provide additional aspiration
volume. A conical head 25 provides transition to the small diameter
opening of the probe.
[0051] The probe tip diameter D and distance L between the open end
plane of this tip and tube with small diameter (see FIG. 6) define
the pressure required to reach an inflection point for a sample
tissue with elasticity module E. Thus values D, L and range of
measured pressures should be optimized to reach acceptable accuracy
for specific measuring range of values E. The test time depends on
the volume of the probe and aspiration rate of the vacuum pump 2
(with capillary restrictor 6, if used). It should be optimized to
reach acceptable accuracy of measurement in a reasonable time.
Using probe tips with different values D and L provides an
opportunity to examine the elasticity modulus of different
biological tissues (skin, muscles, vessels), as well as
non-biological soft materials (silicones, gels etc.).
[0052] FIG. 10 illustrates how the pressure in the cavity changes
with respect to aspiration time for samples with different
mechanical properties. The softer the tissue, the sooner the
inflection point is reached on the pressure plot. The tissue with
inflection point A (thick curve 33, FIG. 10) is softer then tissue
with inflection point B (thin curve 34, FIG. 10), because
P.sub.A<P.sub.B. Based on this dependence, device can be
programmed to determine elasticity modulus as a function of the
pressure level at the inflection.
[0053] FIG. 11 illustrates different methods of finding the
inflection point and a corresponding pressure level. One method is
to identify the inflection point on the pressure-time plot as a
sharp bend (point A). This can be done when the pressure
measurements deviate from the detected slope by more than a
predetermined threshold. The threshold is selected to avoid false
positives caused by measurement noise. A second method is to detect
the inflection point when a first derivative of the pressure plot
exceeds a predetermined first derivative threshold level, which is
selected above the measurements noise level. And lastly, the
inflection pressure point can be detected as a point at which the
second derivative of the pressure plot peaks above a predetermined
second derivative threshold level, which is selected to be above
the noise level of measurements.
[0054] Practical pressure sensor readings may represent a number of
distinct individual measurements at a certain sampling frequency
rather than a continuous curve as shown in FIG. 12. Detecting an
inflection point may be difficult as it can fall in between
individual pressure measurements. In this case, a preliminary
inflection point A, circled in the figure, can be found using one
of the above mentioned methods. The final inflection point B is
then corrected and defined as the intersection of a best-fit
straight line 35 (solid line) through pressure measurements prior
to point A and a best-fit straight line 36 (dashed line) through
the pressure measurements after point A on the pressure-time plot.
In this example, the corrected inflection point falls between the
pressure measurement points. The arrow in FIG. 10 indicates the
corrected more accurate inflection point.
[0055] One advantageous way to change the aspiration rate from the
measuring cavity is to change the speed of vacuum pump 2,
preferably in known increments defining various known aspiration
rates.
[0056] FIG. 13 illustrates another alternate way to adjust the rate
of aspiration in a block-diagram of a more advanced device than the
one shown in FIG. 1. This device allows measurement of tissue
viscosity and shear creep in addition to tissue elasticity. This is
achieved by providing an ability to create negative pressure in the
test cavity at different rates of aspiration. Main elements of this
device are the same as described above but instead of one capillary
restrictor 6, there is provided a set of several (three in this
case) parallel restrictors 6', 6'', and 6''' connected through
corresponding shut-off valves 7', 7'', and 7''' to the vacuum pump
2. Each capillary restrictor optionally has a different diameter
and as a result different resistance to air flow therethrough. A
set of three restrictor valves provides a total of seven different
possible speeds of aspiration depending on the opening of one, two
or three valves 7. The electronic unit drives the pump 2 and valves
7 and monitors the pressure sensor readings based on the pressure
inside the probe cavity. Vent valve 5 is used to quickly release
vacuum from the probe when the test is over.
[0057] The method of evaluation of tissue viscosity according to
the invention is based on dependence between the rate of aspiration
and inflection point. For a non-viscous media or low viscosity
tissue, the inflection point does not change with various
aspiration speeds. The pressure-time plot in FIG. 14A shows the
influence of different aspiration rates on inflection point. Thick
curve 37 with inflection point A illustrates faster aspiration rate
than thin curve 38 with inflection point B (t.sub.A<t.sub.B,
thin curve has larger slope), while the inflection pressure is the
same (P0=P.sub.A=P.sub.B). According to the method of the
invention, the test is first conducted with a first rate of
aspiration and then with a second rate of aspiration. A first
waiting period is included between the first and a second
measurement to allow the tissue to relax completely to its initial
state.
[0058] The pressure-time plot in FIG. 14B shows the influence of
aspiration rates on inflection pressure for a tissue sample having
higher tissue viscosity. Thick curve 39 with inflection point A
illustrates faster aspiration rate then thin curve 40 with
inflection point B (t.sub.A<t.sub.B, thin curve has larger
slope). Because vacuum should be applied longer to overcome tissue
sample's resistance for motion (viscosity), the inflection pressure
for fast aspiration rate is higher (P.sub.A>P.sub.B). The device
can be calibrated with samples of known viscosity to evaluate
functional dependence of tissue viscosity on pressure difference
dP0=P.sub.A-P.sub.B for a specific change in aspiration rate. The
accuracy of viscosity evaluation can be improved by testing
different aspiration rates and choosing the optimal difference.
Once calibration is obtained, tissue testing can be accomplished by
repeating aspiration procedures at different aspiration rates.
[0059] The method of evaluation of tissue creep is based on
identifying the change in inflection point pressure when the test
is repeated for a second time after a predetermined relax time
period. For a low creep tissue sample, the inflection pressure
P.sub.0 stays the same when the test is repeated again, as shown in
FIG. 15A. FIG. 15B illustrates a pressure-time plot of repeated
tests for a sample having higher tissue creep. Each successive test
results in a lower inflection pressure due to residual deformation
of tissue remaining from a previous test (P.sub.A>P.sub.B). The
device can be calibrated with known samples to evaluate functional
dependence of tissue creep on pressure difference. The accuracy of
creep evaluation can be improved by optimization of a relax time
period. Properly selected relax time period for measuring tissue
creep does not necessarily allow it to get back to its original
condition so as to detect the difference between the first and the
second measurement.
[0060] In case both the tissue elasticity and tissue creep are
measured, the test can be repeated at least three times with
variable rates of aspiration and waiting times between the
tests.
[0061] The above mentioned principles were implemented in a device
that monitors negative pressure inside the tip cavity, identifies
the point of abrupt change in pressure defining an inflection point
that depends on mechanical properties of the sample, calculates the
Young's modulus based on programmed calibration and displays this
value on LCD. Examples of a pressure sensor reading together with
its first and second derivatives obtained by this device are shown
in FIG. 16. An example of a calibration curve for certain range of
tissue elasticity is shown in FIG. 17. The curve demonstrates
close-to-linear dependence between pressure and elasticity
modulus.
[0062] In all of the above methods of evaluation of tissue
viscoelastic properties, the presence of the inflection point is
continuously monitored and once detected, the test is stopped and
the cavity is immediately vented to release the test tissue and
avoid its bruising from continuous exposure to vacuum.
[0063] Although the invention herein has been described with
respect to particular embodiments, it is understood that these
embodiments are merely illustrative of the principles and
applications of the present invention. It is therefore to be
understood that numerous modifications may be made to the
illustrative embodiments and that other arrangements may be devised
without departing from the spirit and scope of the present
invention as defined by the appended claims.
* * * * *