U.S. patent application number 15/303012 was filed with the patent office on 2017-02-02 for a device and method for cancer detection, diagnosis and treatment guidance using active thermal imaging.
This patent application is currently assigned to H.T BIOIMAGING LTD.. The applicant listed for this patent is H.T BIOIMAGING LTD.. Invention is credited to Sharon GAT, Yoav ROSENBACH, Shani TOLEDANO, Moshe TSHUVA.
Application Number | 20170027450 15/303012 |
Document ID | / |
Family ID | 54323560 |
Filed Date | 2017-02-02 |
United States Patent
Application |
20170027450 |
Kind Code |
A1 |
TOLEDANO; Shani ; et
al. |
February 2, 2017 |
A DEVICE AND METHOD FOR CANCER DETECTION, DIAGNOSIS AND TREATMENT
GUIDANCE USING ACTIVE THERMAL IMAGING
Abstract
The present invention discloses means and methods for detecting
irregularities in the cells throughout a healthy tissue. The method
generally relates to cancer detection, diagnosis and treatment, and
more specifically pertains to detection, diagnosis and treatment
guidance of cancerous or precancerous conditions through the use of
thermal imaging technology and analysis.
Inventors: |
TOLEDANO; Shani; (RISHON
LE-ZION, IL) ; ROSENBACH; Yoav; (RAMAT GAN, IL)
; TSHUVA; Moshe; (TEL AVIV, IL) ; GAT; Sharon;
(BAT HEFER, IL) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
H.T BIOIMAGING LTD. |
RISHON LE-ZION |
|
IL |
|
|
Assignee: |
H.T BIOIMAGING LTD.
RISHON LE-ZION
IL
|
Family ID: |
54323560 |
Appl. No.: |
15/303012 |
Filed: |
April 13, 2015 |
PCT Filed: |
April 13, 2015 |
PCT NO: |
PCT/IL2015/050392 |
371 Date: |
October 10, 2016 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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61978901 |
Apr 13, 2014 |
|
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62110615 |
Feb 2, 2015 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61F 7/00 20130101; A61B
5/015 20130101; A61B 5/08 20130101; A61B 5/742 20130101; A61B
2560/0252 20130101; A61B 5/01 20130101 |
International
Class: |
A61B 5/01 20060101
A61B005/01; A61B 5/00 20060101 A61B005/00; A61B 5/08 20060101
A61B005/08 |
Claims
1-76. (canceled)
77. A method for detecting and diagnosing of at least one
irregularity in an examined tissue, characterized by steps of:
actively thermomodulating at least a portion of said examined
tissue, said active thermomodulation selected from a group
consisting of heating, cooling and any combination thereof, said
active thermomodulation applied according to a pre-determined
protocol selected from a group consisting of: in a continuous
manner, in a pulsed manner and any combination thereof; collecting
time-resolved thermal data at predetermined time intervals over
time t, for a plurality of coordinated locations of at least a
portion of said examined tissue; calculating according to said
time-resolved thermal data, a thermal transfer index, I, for each
of said plurality of coordinated locations; wherein at least one of
the following steps is being held true: determining tissue at at
least one of said plurality of coordinated locations as irregular
if, for said at least one of said plurality of coordinated
locations, said I is greater than a predetermined value I.sub.irr;
determining tissue at at least one of said plurality of coordinated
locations as irregular if, for said at least one of said plurality
of coordinated locations, a ratio between said I and a
predetermined I-scale is greater than a predetermined value
I.sub.irr; determining tissue at a first coordinated location as
irregular if, for at least two of said plurality of coordinated
locations, a ratio between a first I.sub.first for a first
coordinated location and a second I.sub.second for a second
coordinated location is greater than a predetermined value
I.sub.irr, further wherein said processor is configured to generate
a visual presentation of said coordinated locations according to
said I or an inferential thereof.
78. The method according to claim 77, further comprising a step of
defining said I in a manner selected from: according to the
following formula: T=a+b*exp(-I*t) where T is temperature at said
time t and a and b are constants; according to the following
formula: .rho. C = .differential. T .differential. t = .gradient. (
k .gradient. T ) + q + A 0 - b ( T - T b ) ##EQU00034## where: q [
W m 3 ] ##EQU00035## is an external heat source; A 0 [ W m 3 ]
##EQU00036## is a metabolic heat source; b [ W m 3 .degree. C . ]
##EQU00037## is a heat loss due to blood perfusion;
T.sub.b[.degree. C.] is blood temperature; T[.degree. C.] is
temperature; .rho. [ kg m 3 ] ##EQU00038## is density; C p [ J kg
.degree. C . ] ##EQU00039## is heat capacity; and k [ W m .degree.
C . ] ##EQU00040## is thermal conductivity factor; from a thermal
conductivity coefficient, from a thermal diffusion coefficient,
from a heat capacity, from a density, from a heat loss due to blood
perfusion, from a blood temperature, from a heat convection index,
from a metabolic heat source and any combination thereof.
79. The method according to claim 77, further comprising at least
one of the following steps: selecting said at least one
irregularity from a group consisting of a malignant tumor, a
precancerous tumor, a benign tumor, neoplasm, an infection,
pneumonia, a necrotic cell, a blood clot and any combination
thereof; selecting said examined tissue from a group consisting of
lung tissue, skin, cervical tissue, ear tissue, nose tissue, throat
tissue, oral tissue, esophageal tissue, stomach tissue, intestinal
tissue, colon tissue, rectal tissue, kidney tissue, uterine tissue,
urinary tract tissue, bladder tissue, prostate tissue, eye tissue,
and any combination thereof; and selecting said time t to be in a
range from about 10 ns to about 10 min.
80. The method according to claim 77, further comprising steps of
collecting said thermal data using at least one sensor and of
selecting said at least one sensor from a group consisting of: an
IR sensor, Ultrasound a mercury-in-glass thermometer, pill
thermometer, liquid crystal thermometer, thermocouple, thermistor,
resistance temperature detector, silicon bandgap temperature sensor
and any combination thereof.
81. The method according to claim 77, further comprising at least
one of the following steps: producing at least one heat diffusion
image of at least a portion of said examined tissue prior to said
active thermomodulation; image processing said at least one heat
diffusion image by at least one object recognition module, thereby
identifying coordinated locations suspected of containing at least
one said irregularity; and providing at least one spatial
positioner selected from a group consisting of a visible light
imaging means, a CCD camera, an ultrasound scanner, a thermal
camera, a laser rangefinder and any combination thereof, and
correlating said at least one heat diffusion image and at least one
image from said at least one spatial positioner.
82. The method according to claim 77, further comprising a
providing a normalization step, at least one of the following being
held true: said normalizing step comprises normalizing said I to a
predetermined scale, a higher value on said scale indicating a
higher severity of the medical condition of said at least one
irregularity; said normalizing step is selected from a group
consisting of correcting to ambient temperature, correcting to
ambient humidity, correcting to ambient electromagnetic radiation
and any combination thereof; said normalizing step is selected from
a group consisting of correcting for ambient temperature,
correcting for ambient humidity, correcting for ambient
electromagnetic radiation and any combination thereof; and said
heat transfer index is normalized with patient parameters selected
from a group consisting of sex, age, smoking habits, drinking
habits, number of births, height, weight, blood pressure, diabetes
state, medical history, relatives medical history, patient's
previous heat transfer index and any combination thereof.
83. The method according to claim 77, further comprising steps of
selecting said active thermomodulation from a group consisting of
advecting heat, convecting heat, conducting heat, irradiating and
any combination thereof; and of selecting said active
thermomodulation device from a group consisting of hot fluid
inhalation, cold fluid inhalation, hot fluid application, cold
fluid application, halogen lamp exposure, LED light exposure, xenon
lamp exposure, flash lamp exposure, incandescent lamp exposure, IR
emission, electromagnetic vibration heating, mechanical vibration
heating, positioning a heatable solid, positioning a coolable
solid, positioning a heatable patch, positioning a coolable patch,
pharmaceutical temperature modification, chemically induced
heating, chemically induced cooling and any combination
thereof.
84. A system for detecting, diagnosing and guiding treatment of at
least one irregularity in an examined tissue, comprising: an active
thermomodulator configured to apply to at least a portion of said
examined tissue a member of a group consisting of: heating cooling
and any combination thereof, said active thermomodulation
applicable according to a pre-determined protocol selected from a
group consisting of: in a continuous manner, in a pulsed manner and
any combination thereof; at least one thermal sensor configured to
provide at least one signal related to temperature in at least a
part of said at least a portion of said examined tissue; and a
processor configured to execute instructions comprising: collect
time-resolved thermal data, at predetermined intervals over time t,
of a plurality of coordinated locations of at least a portion of
said examined tissue by conversion of said signal from said at
least one thermal sensor to time-resolved and spatially-resolved
thermal data; and calculate, according to said time-resolved
thermal data, a thermal transfer index, I, for each of said
plurality of coordinated locations; wherein at least one of the
following is being held true: if, for at least one of said
plurality of coordinated locations, said I is greater than a
predetermined value I.sub.irr, determining tissue at said least one
coordinated location as irregular; if, for at least one of said
plurality of coordinated locations, a ratio between said I and a
predetermined I-scale is greater than a predetermined value
I.sub.irr, determining tissue at said least one coordinated
location as irregular; if, for at least two of said plurality of
coordinated locations, a ratio between a first Ifirst of a first
coordinated location and a second Isecond of a second coordinated
location is greater than a predetermined value I.sub.irr,
determining tissue at said first coordinated location as irregular;
further wherein said processor is configured to generate a
three-dimensional thermal map of said at least a portion of said
examined tissue.
85. The system according to claim 84, wherein said I is definable
in a manner selected from: according to the following formula:
T=a+b*exp(-I*t) where T is temperature at said time t and a and b
are constants; according to the following formula: .rho. C
.differential. T .differential. t = .gradient. ( k .gradient. T ) +
q + A 0 - b ( T - T b ) ##EQU00041## where: q [ W m 3 ]
##EQU00042## is an external heat source; A 0 [ W m 3 ] ##EQU00043##
is a metabolic heat source; b [ W m 3 .degree. C . ] ##EQU00044##
is a heat loss due to blood perfusion; T.sub.b[.degree. C.] is
blood temperature; T[.degree. C.] is temperature; .rho. [ kg m 3 ]
##EQU00045## is density; C p [ J kg.degree. C . ] ##EQU00046## is
heat capacity; and k [ W m .degree. C . ] ##EQU00047## is thermal
conductivity factor; from a thermal conductivity coefficient, from
a thermal diffusion coefficient, from a heat capacity, from a
density, from a heat loss due to blood perfusion, from a blood
temperature, from a heat convection index, from a metabolic heat
source and any combination thereof.
86. The system according to claim 84, wherein at least one of the
following is held true: said at least one irregularity is selected
from a group consisting of a malignant tumor, a precancerous tumor,
a benign tumor, neoplasm, an infection, pneumonia, a necrotic cell,
a blood clot and any combination thereof; said examined tissue is
selected from a group consisting of lung tissue, skin, cervical
tissue, ear tissue, nose tissue, throat tissue, oral tissue,
esophageal tissue, stomach tissue, intestinal tissue, colon tissue,
rectal tissue, kidney tissue, uterine tissue, urinary tract tissue,
bladder tissue, prostate tissue, eye tissue, and any combination
thereof; and said time t is selected to be in a range from about 10
ns to about 10 min.
87. The system according to claim 84, wherein said at least one
sensor is selected from a group consisting of: an IR sensor,
ultrasound a mercury-in-glass thermometer, pill thermometer, liquid
crystal thermometer, thermocouple, thermistor, resistance
temperature detector, silicon bandgap temperature sensor and any
combination thereof.
88. The system according to claim 84, wherein at least one of the
following is held true: at least one heat diffusion image of at
least a portion of said examined tissue is producible prior to said
active thermomodulation; at least one coordinated location
suspected of containing at least one irregularity is identifiable
by means of image processing of said at least one heat diffusion
image by at least one object recognition module; and said system
additionally comprises at least one spatial positioner selected
from a group consisting of: a visible light imaging means, a CCD
camera, a skin dermoscope, a microscope, an ultrasound scanner, a
thermal camera, a laser rangefinder and any combination thereof,
and said processor additionally comprises instructions configured
to correlate said at least one heat diffusion image and at least
one image from said at least one spatial positioner.
89. The system according to claim 84, wherein said computer program
additionally comprises instructions to provide a normalization
step, at least one of the following being held true: said
normalizing step comprises normalizing said I to a predetermined
scale, a higher value on said scale indicating a higher severity of
the medical condition of said at least one irregularity; said
normalizing step is selected from a group consisting of correcting
to ambient temperature, correcting to ambient humidity, correcting
to ambient electromagnetic radiation and any combination thereof;
said normalizing step is selected from a group consisting of
correcting for ambient temperature, correcting for ambient
humidity, correcting for ambient electromagnetic radiation and any
combination thereof; and said heat transfer index is normalized
with patient parameters selected from a group consisting of sex,
age, smoking habits, drinking habits, number of births, height,
weight, blood pressure, diabetes state, medical history, relatives
medical history, patient's previous heat transfer index and any
combination thereof.
90. The system according to claim 84, wherein said active
thermomodulation is selected from a group consisting of advecting
heat, convecting heat, conducting heat, irradiating and any
combination thereof; and said active thermomodulation device is
selected from a group consisting of hot fluid inhalation, cold
fluid inhalation, hot fluid application, cold fluid application,
halogen lamp exposure, LED light exposure, xenon lamp exposure,
flash lamp exposure, incandescent lamp exposure, IR emission,
electromagnetic vibration heating, mechanical vibration heating,
positioning a heatable solid, positioning a coolable solid,
positioning a heatable patch, positioning a coolable patch,
pharmaceutical temperature modification, chemically induced
heating, chemically induced cooling and any combination
thereof.
91. A computer readable medium (CRM) having instructions which,
when implemented by one or more computers, causes said one or more
computers to: collect time-resolved thermal data, at predetermined
intervals over time t, of a plurality of coordinated locations of
at least a portion of said examined tissue by conversion of said
signal from said at least one thermal sensor to time-resolved and
spatially-resolved thermal data; and calculate, according to said
time-resolved thermal data, a thermal transfer index, I, for each
of said plurality of coordinated locations; wherein at least one of
the following is being held true: if, for at least one of said
plurality of coordinated locations, said I is greater than a
predetermined value I.sub.irr, determining tissue at said least one
coordinated location as irregular; if, for at least one of said
plurality of coordinated locations, a ratio between said I and a
predetermined I-scale is greater than a predetermined value
I.sub.irr, determining tissue at said least one coordinated
location as irregular; if, for at least two of said plurality of
coordinated locations, a ratio between a first I.sub.first of a
first coordinated location and a second I.sub.second of a second
coordinated location is greater than a predetermined value
I.sub.irr, determining tissue at said first coordinated location as
irregular.
92. The CRM according to claim 91, additionally comprising
instructions configured to calculate said I in a manner selected
from: according to the following formula: T=a+b*exp(-I*t) where T
is temperature at said time t and a and b are constants; according
to the following formula: .rho. C .differential. T .differential. t
= .gradient. ( k .gradient. T ) + q + A 0 - b ( T - T b )
##EQU00048## where: q [ W m 3 ] ##EQU00049## is an external heat
source; A 0 [ W m 3 ] ##EQU00050## is a metabolic heat source; b [
W m 3 .degree. C . ] ##EQU00051## is a heat loss due to blood
perfusion; T.sub.b[.degree. C.] is blood temperature; T[.degree.
C.] is temperature; .rho. [ kg m 3 ] ##EQU00052## is density; C p [
J kg.degree. C . ] ##EQU00053## is heat capacity; and k [ W m
.degree. C . ] ##EQU00054## is thermal conductivity factor; from a
thermal conductivity coefficient, from a thermal diffusion
coefficient, from a heat capacity, from a density, from a heat loss
due to blood perfusion, from a blood temperature, from a heat
convection index, from a metabolic heat source and any combination
thereof.
93. The CRM according to claim 91, wherein at least one of the
following is held true: said at least one irregularity is selected
from a group consisting of a malignant tumor, a precancerous tumor,
a benign tumor, neoplasm, an infection, pneumonia, a necrotic cell,
a blood clot and any combination thereof; said examined tissue is
selected from a group consisting of lung tissue, skin, cervical
tissue, ear tissue, nose tissue, throat tissue, oral tissue,
esophageal tissue, stomach tissue, intestinal tissue, colon tissue,
rectal tissue, kidney tissue, uterine tissue, urinary tract tissue,
bladder tissue, prostate tissue, eye tissue, and any combination
thereof; and said time t is selected to be in a range from about 10
ns to about 10 min.
94. The CRM according to claim 91, additionally comprising
instructions configured to execute at least one of the following:
produce at least one heat diffusion image of at least a portion of
said examined tissue prior to said active thermomodulation;
identify at least one coordinated location suspected of containing
at least one irregularity by means of image processing of said at
least one heat diffusion image by at least one object recognition
module; and correlate said at least one heat diffusion image and at
least one image from at least one spatial positioner, said at least
one spatial positioner selected from a group consisting of: a
visible light imaging means, a CCD camera, an ultrasound scanner, a
thermal camera, a laser rangefinder and any combination
thereof.
95. The CRM according to claim 91, additionally comprising
instructions configured to provide a normalization step, at least
one of the following being held true: said normalizing step
comprises normalizing said I to a predetermined scale, a higher
value on said scale indicating a higher severity of the medical
condition associated with said at least one irregularity; said
normalizing step is selected from a group consisting of correcting
to ambient temperature, correcting to ambient humidity, correcting
to ambient electromagnetic radiation and any combination thereof;
said normalizing step is selected from a group consisting of
correcting for ambient temperature, correcting for ambient
humidity, correcting for ambient electromagnetic radiation and any
combination thereof; and said heat transfer index is normalized
with patient parameters selected from a group consisting of sex,
age, smoking habits, drinking habits, number of births, height,
weight, blood pressure, diabetes state, medical history, relatives
medical history, patient's previous heat transfer index and any
combination thereof.
96. The CRM according to claim 91, wherein said active
thermomodulation is selected from a group consisting of advecting
heat, convecting heat, conducting heat, irradiating and any
combination thereof; and said active thermomodulation device is
selected from a group consisting of hot fluid inhalation, cold
fluid inhalation, hot fluid application, cold fluid application,
halogen lamp exposure, LED light exposure, xenon lamp exposure,
flash lamp exposure, incandescent lamp exposure, IR emission,
electromagnetic vibration heating, mechanical vibration heating,
positioning a heatable solid, positioning a coolable solid,
positioning a heatable patch, positioning a coolable patch,
pharmaceutical temperature modification, chemically induced
heating, chemically induced cooling and any combination thereof.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a U.S. National Phase filing under 35
U.S.C. 371 of International (PCT) Patent Application No.
PCT/IL2015/050392, filed 13 Apr. 2015, which claims priority from
U.S. Provisional Patent Application No. 62/110,615, filed 2 Feb.
2015, and from U.S. Provisional Patent Application No. 61/978,901,
filed 13 Apr. 2014, all of which are incorporated by reference in
their entirety.
FIELD OF THE INVENTION
[0002] The present invention relates to cancer detection and
diagnosis, and more specifically the present invention relates to
cancer detection and diagnosis through the use of thermal imaging
technology.
BACKGROUND OF THE INVENTION
[0003] Tumor cells are distinct from their surrounding normal
tissue by several properties, one of which is a thermo-physical
property referred to as thermal diffusivity, which is expected to
be different in cancerous cells compared to healthy cells. Thermal
diffusivity is the combined property of density, heat capacity,
thermal conductivity, blood perfusion and metabolic rate which are
expected to be noticeably different in cancer cells. Importantly,
even precancerous tissues or very young tumors appear to have
distinct thermal diffusivity properties due to an enlarged nucleus,
elevated crowdedness and more.
[0004] Lung cancer is considered the most deadly cancers in men and
women worldwide. Lung cancer is the leading cause of cancer death
among both men and women in the United States.
[0005] Statistical data regarding the extent of lung cancer states
that lung cancer results in about 1.6 million deaths a year
worldwide, being the leading cause of cancer death, at a total of
27% of all cancer related deaths. In the U.S alone 228,190 new
cases are diagnosed, and 160,000 deaths occur annually. In Israel
1,900 new cases are diagnosed and 1,600 deaths occur annually. Only
5% of lung cancers cases are diagnosed in stages that allow
healing.
[0006] This extremely low survival rate of lung cancer is not due
to lung tumors being more aggressive than other malignant tumors
types, but in fact is due to the lack of early detection.
[0007] Since the lung contains no `pain sensing` mechanism and its
gas volume is much greater than its tissue volume, a tumor would
hardly be noticed at early stages. Usually when the patient starts
feeling any discomfort and turns to a physician, the tumor will
already have exceeded the treatable size. Therefore breathing
difficulties and coughing which usually leads to the diagnosis of
the cancer means the tumor is large enough to be noticed and is
probably untreatable. At this stage the cancer is progressive and
usually metastatic and a targeted healing therapy cannot be
considered, resulting in a five year survival rate which is very
low.
[0008] In order to increase survival rate, many screening programs
in the US use low dose CT. Screening reduced lung cancer deaths by
20%. But, while 25% of the tests are positive, 96% of all positive
results are false and do not result in lung cancer diagnosis. About
30% of people with positive CT will go for a biopsy and only 20% of
them will find out they have lung cancer.
[0009] These false positives lead to unnecessary biopsies and
unnecessary treatment for healthy person. Therefore, a `decision
support` system, to inform a clinician whether the positive CT is a
cancer and requires further investigation, would be of considerable
utility. Such a system preferably provides immediate results, does
not involve radiation risks and is independent of the need for an
expert's eye. Preferably, such a test is computerized and automatic
with no need for a long, expensive analysis stage.
[0010] In addition, oncologists treating the cancer have great
difficulty in monitoring the treatment progress, and even
cataloging the different stages of the disease. Many times, after a
relatively long treating period, the physician would find the
treatment had little to no effect. Treatment methods would then be
changed, losing valuable time. In other cases cancer cells would
successfully be destroyed, and turn into necrotic cells, however,
traditional scans would not differentiate them from cancer cells.
Usually in this case, an invasive lung biopsy is needed.
[0011] According to the World Health Organization (WHO), cervical
cancer is the second most commonly prevalent cancer and the third
greatest cause of death in women, with 530,000 new cases discovered
each year.
[0012] Increasing incidences of weakened immune system, rapid
spread of human papillomavirus (HPV) infection among the female
population and long-term use of oral contraceptive pills are the
primary factors responsible for the growth of cervical cancer.
[0013] Currently, cervical cancer screening includes a
cytology-based screening, known as the Pap test or Pap smear. The
main purpose of screening with the Pap test is to detect
precancerous abnormal cells that may develop into cancer if left
untreated, specifically Cervical Intraepithelial Neoplasia (CIN).
In regularly screened populations, the Pap test identifies most
abnormal cells before they become cancer. However, the Pap test
should be taken with caution, as it is approximated that test
incidence of false negatives can be as high as 20%-45%. Moreover,
Pap test is expensive and requires 14-30 days of waiting for the
cytology testing.
[0014] U.S. Pat. No. 8,774,902 discloses a device and method to
diagnose an internal abnormality in a living subject by sensing a
passively occurring electromagnetic radiation signal associated
with the abnormality and inside an orifice of the subject, and U.S.
Pat. No. 7,513,876 discloses a system for passively detecting
thermal discrepancies in vessel walls. However, the use of
passively occurring radiation only renders '902 to be incompetent
in detecting minor differences in cell structure, which are already
found in the precancerous stage.
[0015] U.S. Pat. No. 8,864,669 discloses a method for detecting
abnormal tissue using ultrasound backscattered from the background.
The detection is manifested through different tissues absorbing
ultrasound differently.
[0016] U.S. Pat. No. 8,923,954 discloses an IR detection system for
identifying malignant tumors by identifying areas of increased
metabolic activity, and by assuming that malignant tumors have
increased metabolic activity due to increased blood supply.
However, patent '954 only identifies tumors which have grown in
mass to such extent as to provide evidence of increased metabolic
activity and blood supply.
[0017] US patent publication number US2013/0116573 and US Patent
Publication number US2011/0230942 disclose a thermal imaging system
to scan at least a section of a surface of a subject under
observation, using both a geometrical scanning system and a thermal
(IR) scanning system. A data processing system receives data from
the geometrical scanning system, constructs a surface map of the
section of the surface under observation and identifies geometrical
markers on the surface map based on the data from the geometrical
scanning system. The data processing system also receives data over
a recovery time from the IR imaging system and constructs a thermal
map of the section of the surface, identifying thermal markers on
the thermal map based on the data from the infrared imaging system.
The two maps are then registered based on a correspondence between
at least some of the geometrical and thermal markers and the
locations of lesions at the surface can be determined from the
surface temperature profile as shown in the registered image.
However, in the above documents, to Herman, the skin surface is
cooled by application of cold fluid to a region of the surface, so
that Herman can only identify lesions at or very near the
surface.
[0018] Therefore, a long felt need still exists for a screening
system and method which will provide early pre-cancerous
diagnosis.
SUMMARY OF THE INVENTION
[0019] Therefore, detection of cancer cells using a thermal
diffusivity imaging method is disclosed.
[0020] It is thus an object of the present invention to disclose a
method for detecting and diagnosing of at least one irregularity in
an examined tissue, characterized by steps of: [0021] actively
thermomodulating at least a portion of said examined tissue, said
active thermomodulation selected from a group consisting of
heating, cooling and any combination thereof, said active
thermomodulation applied according to a pre-determined protocol
selected from a group consisting of: in a continuous manner, in a
pulsed manner and any combination thereof; [0022] collecting
time-resolved thermal data at predetermined time intervals over
time t, of a plurality of coordinated locations of at least a
portion of said examined tissue; [0023] calculating according to
said time-resolved thermal data, a thermal transfer index, I, for
each of said plurality of coordinated locations; [0024] wherein at
least one of the following is being held true: [0025] if, for at
least one of said plurality of coordinated locations, said I is
greater than a predetermined value I.sub.irr, determining tissue at
said least one coordinated location as irregular; [0026] if, for at
least one of said plurality of coordinated locations, a ratio
between said I and a predetermined I-scale is greater than a
predetermined value I.sub.irr, determining tissue at said least one
coordinated location as irregular; [0027] if, for at least two of
said plurality of coordinated locations, a ratio between a first
I.sub.first of a first coordinated location and a second
I.sub.second of a second coordinated location is greater than a
predetermined value I.sub.irr, determining tissue at said first
coordinated location as irregular [0028] further wherein said
processor is configured to generate a three-dimensional visual
presentation of said coordinated locations according to said I or
an inferential thereof.
[0029] It is thus another object of the present invention to
disclose the method as described above, further comprising a step
of defining said I in a manner selected from: [0030] according to
the following formula:
[0030] T=a+b*exp(-I*t) [0031] where T is temperature at said time t
and a and b are constants; [0032] according to the following
formula:
[0032] .rho.C .differential. T .differential. t = .gradient. ( k
.gradient. T ) + q + A 0 - b ( T - T b ) ##EQU00001## [0033]
where:
[0033] q [ W m 3 ] ##EQU00002##
is an external heat source;
A 0 [ W m 3 ] ##EQU00003##
is a metabolic heat source;
b [ W m 3 .degree. C . ] ##EQU00004##
is a heat loss due to blood perfusion; T.sub.b[.degree. C.] is
blood temperature; [0034] T[.degree. C.] is temperature;
[0034] .rho. [ kg m 3 ] ##EQU00005##
is density;
C p [ J kg .degree. C . ] ##EQU00006##
is heat capacity; and
k [ W m.degree. C . ] ##EQU00007##
is thermal conductivity factor; [0035] from a thermal conductivity
coefficient, from a thermal diffusion coefficient, from a heat
capacity, from a density, from a heat loss due to blood perfusion,
from a blood temperature, from a heat convection index, from a
metabolic heat source and any combination thereof.
[0036] It is thus another object of the present invention to
disclose the method as described above, further comprising at least
one of the following steps: [0037] selecting said at least one
irregularity from a group consisting of a malignant tumor, a
precancerous tumor, a benign tumor, an infection, pneumonia, a
necrotic cell, a blood clot and any combination thereof; [0038]
selecting said examined tissue from a group consisting of lung
tissue, skin, cervical tissue, ear tissue, nose tissue, throat
tissue, oral tissue, esophageal tissue, stomach tissue, intestinal
tissue, colon tissue, rectal tissue, kidney tissue, uterine tissue,
urinary tract tissue, bladder tissue, prostate tissue, eye tissue,
and any combination thereof; and [0039] selecting said time
interval t to be in a range from about 10 ns to about 10 min.
[0040] It is thus another object of the present invention to
disclose the method as described above, further comprising steps of
collecting said thermal data using at least one sensor and of
selecting said at least one sensor from a group consisting of: an
IR sensor, a mercury-in-glass thermometer, pill thermometer, liquid
crystal thermometer, thermocouple, thermistor, resistance
temperature detector, silicon bandgap temperature sensor and any
combination thereof.
[0041] It is thus another object of the present invention to
disclose the method as described above, further comprising at least
one of the following steps: [0042] producing at least one heat
diffusion image of at least a portion of said examined tissue prior
to said active thermomodulation; [0043] image processing said at
least one heat diffusion image by at least one object recognition
module, thereby identifying coordinated locations suspected of
containing at least one said irregularity; and [0044] providing at
least one spatial positioner selected from a group consisting of a
visible light imaging means, a CCD camera, an ultrasound scanner, a
thermal camera, a laser rangefinder and any combination thereof,
and correlating said at least one heat diffusion image and at least
one image from said at least one spatial positioner.
[0045] It is thus another object of the present invention to
disclose the method as described above, further comprising a
providing a normalization step, at least one of the following being
held true: [0046] said normalizing step comprises normalizing said
I to a predetermined scale, a higher value on said scale indicating
a higher severity of the medical condition of said at least one
irregularity; [0047] said normalizing step is selected from a group
consisting of correcting to ambient temperature, correcting to
ambient humidity, correcting to ambient electromagnetic radiation
and any combination thereof; [0048] said normalizing step is
selected from a group consisting of correcting for ambient
temperature, correcting for ambient humidity, correcting for
ambient electromagnetic radiation and any combination thereof; and
[0049] said heat transfer index is normalized with patient
parameters selected from a group consisting of sex, age, smoking
habits, drinking habits, number of births, height, weight, blood
pressure, diabetes state, medical history, relatives medical
history, patient's previous heat transfer index and any combination
thereof.
[0050] It is thus another object of the present invention to
disclose the method as described above, further comprising steps of
selecting said active thermomodulation from a group consisting of
advecting heat, convecting heat, conducting heat, irradiating and
any combination thereof; and of selecting said active
thermomodulation device from a group consisting of hot fluid
inhalation, cold fluid inhalation, hot fluid application, cold
fluid application, halogen lamp exposure, cold fluid xenon lamp
exposure, flash lamp exposure, incandescent lamp exposure, IR
emission, electromagnetic vibration heating, mechanical vibration
heating, positioning a heatable solid, positioning a coolable
solid, positioning a heatable patch, positioning a coolable patch,
pharmaceutical temperature modification, chemically induced
heating, chemically induced cooling and any combination
thereof.
[0051] It is thus another object of the present invention to
disclose a system for detecting and diagnosing at least one
irregularity in an examined tissue, comprising: [0052] an active
thermomodulator configured to apply to at least a portion of said
examined tissue a member of a group consisting of: heating cooling
and any combination thereof, said active thermomodulation
applicable according to a pre-determined protocol selected from a
group consisting of: in a continuous manner, in a pulsed manner and
any combination thereof; [0053] at least one thermal sensor
configured to provide at least one signal related to temperature in
at least a part of said at least a portion of said examined tissue;
[0054] and [0055] a processor configured to execute instructions
comprising: [0056] collect time-resolved thermal data, at
predetermined intervals over time t, of a plurality of coordinated
locations of at least a portion of said examined tissue by
conversion of said signal from said at least one thermal sensor to
time-resolved and spatially-resolved thermal data; and [0057]
calculate, according to said time-resolved thermal data, a thermal
transfer index, I, for each of said plurality of coordinated
locations; [0058] wherein at least one of the following is being
held true: [0059] if, for at least one of said plurality of
coordinated locations, said I is greater than a predetermined value
I.sub.irr, tissue at said least one coordinated location is
determinable as irregular; [0060] if, for at least one of said
plurality of coordinated locations, a ratio between said I and a
predetermined I-scale is greater than a predetermined value
I.sub.irr, tissue at said least one coordinated location is
determinable as irregular; [0061] if, for at least two of said
plurality of coordinated locations, a ratio between a first
I.sub.first of a first coordinated location and a second
I.sub.second of a second coordinated location is greater than a
predetermined value Iirr, tissue at said first coordinated location
is determinable as irregular; [0062] further wherein said processor
is configured to generate at least one of a group consisting of a
two-dimensional thermal map or a three-dimensional thermal
diffusion image of said at least a portion of said examined
tissue.
[0063] It is thus another object of the present invention to
disclose the system as described above, wherein said I is definable
in a manner selected from: [0064] according to the following
formula:
[0064] T=a+b*exp(-I*t) [0065] where T is temperature at said time t
and a and b are constants; [0066] according to the following
formula:
[0066] .rho.C .differential. T .differential. t = .gradient. ( k
.gradient. T ) + q + A 0 - b ( T - T b ) ##EQU00008## [0067]
where:
[0067] q [ W m 3 ] ##EQU00009##
is an external heat source;
A 0 [ W m 3 ] ##EQU00010##
is a metabolic heat source;
b [ W m 3 .degree. C . ] ##EQU00011##
is a heat loss due to blood perfusion; T.sub.b [.degree. C.] is
blood temperature; [0068] T[.degree. C.] is temperature;
[0068] .rho. [ kg m 3 ] ##EQU00012##
is density;
C p [ J kg.degree. C . ] ##EQU00013##
is heat capacity; and
k [ W m .degree. C . ] ##EQU00014##
is thermal conductivity factor; [0069] from a thermal conductivity
coefficient, from a thermal diffusion coefficient, from a heat
capacity, from a density, from a heat loss due to blood perfusion,
from a blood temperature, from a heat convection index, from a
metabolic heat source and any combination thereof.
[0070] It is thus another object of the present invention to
disclose the system as described above, wherein at least one of the
following is held true: [0071] said at least one irregularity is
selected from a group consisting of a malignant tumor, a
precancerous tumor, a benign tumor, an infection, pneumonia, a
necrotic cell, a blood clot and any combination thereof; [0072]
said examined tissue is selected from a group consisting of lung
tissue, skin, cervical tissue, ear tissue, nose tissue, throat
tissue, oral tissue, esophageal tissue, stomach tissue, intestinal
tissue, colon tissue, rectal tissue, kidney tissue, uterine tissue,
urinary tract tissue, bladder tissue, prostate tissue, eye tissue,
and any combination thereof; and [0073] said time t is selected to
be in a range from about 10 ns to about 10 min.
[0074] It is thus another object of the present invention to
disclose the system as described above, wherein said at least one
sensor is selected from a group consisting of: an IR sensor, a
mercury-in-glass thermometer, pill thermometer, liquid crystal
thermometer, thermocouple, thermistor, resistance temperature
detector, silicon bandgap temperature sensor and any combination
thereof.
[0075] It is thus another object of the present invention to
disclose the system as described above, wherein at least one of the
following is held true: [0076] at least one heat diffusion image of
at least a portion of said examined tissue is producible prior to
said active thermomodulation; [0077] at least one coordinated
location suspected of containing at least one irregularity is
identifiable by means of image processing of said at least one heat
diffusion image by at least one object recognition module; and
[0078] said system additionally comprises at least one spatial
positioner selected from a group consisting of: a visible light
imaging means, a CCD camera, an ultrasound scanner, a thermal
camera, a laser rangefinder and any combination thereof, and said
processor additionally comprises instructions configured to
correlate said at least one heat diffusion image and at least one
image from said at least one spatial positioner.
[0079] It is thus another object of the present invention to
disclose the system as described above, wherein said computer
program additionally comprises instructions to provide a
normalization step, at least one of the following being held true:
[0080] said normalizing step comprises normalizing said I to a
predetermined scale, a higher value on said scale indicating a
higher severity of the medical condition of said at least one
irregularity; [0081] said normalizing step is selected from a group
consisting of correcting to ambient temperature, correcting to
ambient humidity, correcting to ambient electromagnetic radiation
and any combination thereof; [0082] said normalizing step is
selected from a group consisting of correcting for ambient
temperature, correcting for ambient humidity, correcting for
ambient electromagnetic radiation and any combination thereof; and
[0083] said heat transfer index is normalized with patient
parameters selected from a group consisting of sex, age, smoking
habits, drinking habits, number of births, height, weight, blood
pressure, diabetes state, medical history, relatives medical
history, patient's previous heat transfer index and any combination
thereof.
[0084] It is thus another object of the present invention to
disclose the system as described above, wherein said active
thermomodulation is selected from a group consisting of advecting
heat, convecting heat, conducting heat, irradiating and any
combination thereof; and said active thermomodulation device is
selected from a group consisting of hot fluid inhalation, cold
fluid inhalation, hot fluid application, halogen lamp exposure, LED
light exposure, xenon lamp exposure, flash lamp exposure,
incandescent lamp exposure, IR emission, electromagnetic vibration
heating, mechanical vibration heating, positioning a heatable
solid, positioning a coolable solid, positioning a heatable patch,
positioning a coolable patch, pharmaceutical temperature
modification, chemically induced heating, chemically induced
cooling and any combination thereof.
[0085] It is thus another object of the present invention to
disclose a computer readable medium (CRM) having instructions
which, when implemented by one or more computers, causes said one
or more computers to: [0086] collect time-resolved thermal data, at
predetermined intervals over time t, of a plurality of coordinated
locations of at least a portion of said examined tissue by
conversion of said signal from said at least one thermal sensor to
time-resolved and spatially-resolved thermal data; and [0087]
calculate, according to said time-resolved thermal data, a thermal
transfer index, I, for each of said plurality of coordinated
locations; [0088] wherein at least one of the following is being
held true: [0089] if, for at least one of said plurality of
coordinated locations, said I is greater than a predetermined value
Iirr, determine tissue at said least one coordinated location as
irregular; [0090] if, for at least one of said plurality of
coordinated locations, a ratio between said I and a predetermined
I-scale is greater than a predetermined value Iirr, determine
tissue at said least one coordinated location as irregular; [0091]
if, for at least two of said plurality of coordinated locations, a
ratio between a first I.sub.first of a first coordinated location
and a second I.sub.second of a second coordinated location is
greater than a predetermined value I.sub.irr, determine tissue at
said first coordinated location as irregular; [0092] further
wherein said CRM comprises instructions configured to generate a
three or two-dimensional thermal diffusion image of said at least a
portion of said examined tissue.
[0093] It is thus another object of the present invention to
disclose the CRM as described above, additionally comprising
instructions configured to calculate said I in a manner selected
from: [0094] according to the following formula:
[0094] T=a+b*exp(-I*t) [0095] where T is temperature at said time t
and a and b are constants; [0096] according to the following
formula:
[0096] .rho. C .differential. T .differential. t = .gradient. ( k
.gradient. T ) + q + A 0 - b ( T - T b ) ##EQU00015## [0097]
where:
[0097] q [ W m 3 ] ##EQU00016##
is an external heat source;
A 0 [ W m 3 ] ##EQU00017##
is a metabolic heat source;
b [ W m 3 .degree. C . ] ##EQU00018##
is a heat loss due to blood perfusion; T.sub.b[.degree. C.] is
blood temperature; T[.degree. C.] is temperature;
.rho. [ kg m 3 ] ##EQU00019##
is density;
C p [ J kg.degree. C . ] ##EQU00020##
is heat capacity; and
k [ W m .degree. C . ] ##EQU00021##
is thermal conductivity factor; [0098] from a thermal conductivity
coefficient, from a thermal diffusion coefficient, from a heat
capacity, from a density, from a heat loss due to blood perfusion,
from a blood temperature, from a heat convection index, from a
metabolic heat source and any combination thereof.
[0099] It is thus another object of the present invention to
disclose the CRM as described above, wherein at least one of the
following is held true: [0100] said at least one irregularity is
selected from a group consisting of a malignant tumor, a
precancerous tumor, a benign tumor, an infection, pneumonia, a
necrotic cell, a blood clot and any combination thereof; [0101]
said examined tissue is selected from a group consisting of lung
tissue, skin, cervical tissue, ear tissue, nose tissue, throat
tissue, oral tissue, esophageal tissue, stomach tissue, intestinal
tissue, colon tissue, rectal tissue, kidney tissue, uterine tissue,
urinary tract tissue, bladder tissue, prostate tissue, eye tissue,
and any combination thereof; and [0102] said time t is selected to
be in a range from about 10 ns to about 10 min.
[0103] It is thus another object of the present invention to
disclose the CRM as described above, additionally comprising
instructions configured to execute at least one of the following:
[0104] produce at least one heat diffusion image of at least a
portion of said examined tissue prior to said active
thermomodulation; [0105] identify at least one coordinated location
suspected of containing at least one irregularity by means of image
processing of said at least one heat diffusion image by at least
one object recognition module; and [0106] correlate said at least
one heat diffusion image and at least one image from at least one
spatial positioner, said at least one spatial positioner selected
from a group consisting of: a visible light imaging means, a CCD
camera, an ultrasound scanner, a thermal camera, a laser
rangefinder and any combination thereof.
[0107] It is thus another object of the present invention to
disclose the CRM as described above, additionally comprising
instructions configured to provide a normalization step, at least
one of the following being held true: [0108] said normalizing step
comprises normalizing said I to a predetermined scale, a higher
value on said scale indicating a higher severity of the medical
condition associated with said at least one irregularity; [0109]
said normalizing step is selected from a group consisting of
correcting to ambient temperature, correcting to ambient humidity,
correcting to ambient electromagnetic radiation and any combination
thereof; [0110] said normalizing step is selected from a group
consisting of correcting for ambient temperature, correcting for
ambient humidity, correcting for ambient electromagnetic radiation
and any combination thereof; and [0111] said heat transfer index is
normalized with patient parameters selected from a group consisting
of sex, age, smoking habits, drinking habits, number of births,
height, weight, blood pressure, diabetes state, medical history,
relatives medical history, patient's previous heat transfer index
and any combination thereof.
[0112] It is thus another object of the present invention to
disclose the CRM as described above, wherein said active
thermomodulation is selected from a group consisting of advecting
heat, convecting heat, conducting heat, irradiating and any
combination thereof; and said active thermomodulation device is
selected from a group consisting of hot fluid inhalation, cold
fluid inhalation, hot fluid application, cold fluid application,
halogen lamp exposure, LED light exposure, xenon lamp exposure,
flash lamp exposure, incandescent lamp exposure, IR emission,
electromagnetic vibration heating, mechanical vibration heating,
positioning a heatable solid, positioning a coolable solid,
positioning a heatable patch, positioning a coolable patch,
pharmaceutical temperature modification, chemically induced
heating, chemically induced cooling and any combination
thereof.
[0113] It is thus another object of the present invention to
disclose a method for detecting and diagnosing at least one
irregularity in the tissue's cells in an examined tissue,
characterized by steps of: actively thermomodulating said examined
tissue, or a portion thereof; collecting time-resolved thermal
data, over time t, of a plurality of coordinated locations of said
examined tissue; calculating according to said time-resolved
thermal data, a thermal transfer index, I, for each of said
plurality of coordinated locations; wherein at least one of the
following is being held true: if said I is greater than a
predetermined value I.sub.irr, determining said tissue as
irregular; if a ratio between said I and a predetermined I-scale is
greater than a predetermined value I.sub.irr, determining said
tissue as irregular; if a ratio between a first I.sub.first of a
first coordinated location and a second I.sub.second of a second
coordinated location is greater than a predetermined value
I.sub.irr, determining said tissue as irregular.
[0114] It is another object of the present invention to disclose a
method for detecting and diagnosing at least one irregularity in
the tissue's cells in an examined tissue, characterized by steps
of: actively thermomodulating said examined tissue, or a portion
thereof; collecting time-resolved thermal data, over time t, of at
least one coordinated location of said examined tissue; calculating
according to said time-resolved thermal data, a thermal transfer
index, I, for each of said coordinated locations; wherein said I is
defined according to the following formula: T=a+b*exp(-I*t) where a
and b are constants and T is temperature.
[0115] It is also an object of the present invention to provide the
abovementioned method, wherein if said I is greater than a
predetermined value I.sub.irr, determining said tissue as
irregular.
[0116] It is also an object of the present invention to provide the
abovementioned method, wherein if a ratio between said I and a
predetermined I-scale is greater than a predetermined value
I.sub.irr, determining said tissue as irregular.
[0117] It is also an object of the present invention to provide the
abovementioned method, wherein if a ratio between a first
I.sub.first of a first coordinated locations and a second
I.sub.second of a second coordinated locations is greater than a
predetermined value I.sub.irr, determining said tissue as
irregular.
[0118] It is also an object of the present invention to provide any
of the abovementioned methods, further comprising steps of
constructing a visual presentation of said coordinated locations
according to said I or an inferential thereof.
[0119] It is also an object of the present invention to provide any
of the abovementioned methods, wherein said I is selected from the
group consisting of an exponential decay constant calculated
according to said time-resolved thermal data, thermal conductivity
coefficient, thermal diffusion coefficient, heat capacity, density,
heat loss due to blood perfusion, blood temperature, heat
convection index, metabolic heat source and any combination
thereof.
[0120] It is also an object of the present invention to provide any
of the abovementioned methods, further comprising steps of image
processing said visual presentation by an object recognition
module, thereby identifying coordinated locations suspected of
containing at least one irregularity in the tissue's cells.
[0121] It is also an object of the present invention to provide any
of the abovementioned methods, further comprising the step of
normalizing said I to a predetermined scale.
[0122] It is also an object of the present invention to provide any
of the abovementioned methods, wherein said time-resolved thermal
data is a temperature measurement taken at predetermined intervals
over time.
[0123] It is also an object of the present invention to provide any
of the abovementioned methods, further comprising normalization
steps selected from the group consisting of normalizing said I to
ambient temperature, correcting to ambient humidity, correcting to
ambient electromagnetic radiation and any combination thereof.
[0124] It is also an object of the present invention to disclose
any of the aforementioned systems, further comprising a spatial
positioning means selected from the group consisting of a visible
light imaging means, a CCD camera, an ultrasound scanner, a thermal
camera, a laser rangefinder and any combination thereof.
[0125] It is also an object of the present invention to provide a
non-transitory computer readable medium (CRM) having instructions
which, when implemented by one or more computers cause said one or
more computers to: store time-resolved thermal data of a plurality
of coordinated locations of an examined tissue, or portion thereof,
collected over time t; calculate according to said time-resolved
thermal data, a thermal transfer index, I, for each of said
plurality of coordinated locations; wherein at least one of the
following is being held true: if said I is greater than a
predetermined value I.sub.irr, determining said tissue as
irregular; if a ratio between said I and a predetermined I-scale is
greater than a predetermined value I.sub.irr, determining said
tissue as irregular; if a ratio between a first I.sub.first of a
first coordinated location and a second I.sub.second of a second
coordinated location is greater than a predetermined value
I.sub.irr, determining said tissue as irregular.
[0126] It is yet another object of the present invention to provide
a non-transitory computer readable medium (CRM) having instructions
which, when implemented by one or more computers cause said one or
more computers to: store time-resolved thermal data of a plurality
of coordinated locations of an examined tissue, or portion thereof,
collected over time t; calculate according to said time-resolved
thermal data, a thermal transfer index, I, for each of said
plurality of coordinated locations; wherein said I is defined
according to the following formula: T=a+b*exp(-I*t) where a and b
are constants and T is temperature.
[0127] It is thus one object of the present invention to disclose a
method for detecting and diagnosing at least one irregularity in
the tissue's cells in an examined tissue, characterized by steps
of: actively thermomodulating said examined tissue, or a portion
thereof; collecting time-resolved thermal data, over time t, of a
plurality of coordinated locations of said examined tissue;
calculating according to said time-resolved thermal data, a thermal
transfer index, I, for each of said plurality of coordinated
locations; wherein at least one of the following is being held
true: if said I is greater than a predetermined value I.sub.irr,
determining said tissue as irregular; if a ratio between said I and
a predetermined I-scale is greater than a predetermined value
I.sub.irr, determining said tissue as irregular; if a ratio between
a first I.sub.first of a first coordinated location and a second
I.sub.second of a second coordinated location is greater than a
predetermined value I.sub.irr, determining said tissue as
irregular.
[0128] It is another object of the present invention to disclose
method for detecting and diagnosing at least one irregularity in
the tissue's cells in an examined tissue, characterized by steps
of: actively thermomodulating said examined tissue, or a portion
thereof; collecting time-resolved thermal data, over time t, of at
least one coordinated location of said examined tissue; calculating
according to said time-resolved thermal data, a thermal transfer
index, I, for each of said coordinated locations; wherein said I is
defined according to the following formula: T=a+b*exp(-I*t) where T
is the temperature and a and b are constants.
[0129] It is also an object of the present invention to provide the
abovementioned method, wherein if said I is greater than a
predetermined value I.sub.irr, determining said tissue as
irregular.
[0130] It is also an object of the present invention to provide the
abovementioned method, wherein if a ratio between said I and a
predetermined I-scale is greater than a predetermined value
I.sub.irr, determining said tissue as irregular.
[0131] It is also an object of the present invention to provide the
abovementioned method, wherein if a ratio between a first
I.sub.first of a first coordinated locations and a second
I.sub.second of a second coordinated locations is greater than a
predetermined value I.sub.irr, determining said tissue as
irregular.
[0132] It is also an object of the present invention to provide any
of the abovementioned methods, further comprising steps of
constructing a visual presentation of said coordinated locations
according to said I or an inferential thereof.
[0133] It is also an object of the present invention to provide any
of the abovementioned methods, wherein said I is selected from the
group consisting of an exponential decay constant calculated
according to said time-resolved thermal data, thermal conductivity
coefficient, thermal diffusion coefficient, heat capacity, density,
heat loss due to blood perfusion, blood temperature, heat
convection index, metabolic heat source and any combination
thereof.
[0134] It is also an object of the present invention to provide any
of the abovementioned methods, further comprising steps of image
processing said visual presentation by an object recognition
module, thereby identifying coordinated locations suspected of
containing at least one irregularity in the tissue's cells.
[0135] It is also an object of the present invention to provide any
of the abovementioned methods, further comprising the step of
normalizing said I to a predetermined scale.
[0136] It is also an object of the present invention to provide any
of the abovementioned methods, wherein said time-resolved thermal
data is a temperature measurement taken at predetermined intervals
over time.
[0137] It is also an object of the present invention to provide any
of the abovementioned methods, further comprising normalization
steps selected from the group consisting of normalizing said I to
ambient temperature, correcting to ambient humidity, correcting to
ambient electromagnetic radiation and any combination thereof.
[0138] It is also an object of the present invention to disclose
any of the aforementioned systems, further comprising a spatial
positioning means selected from the group consisting of a visible
light imaging means, a CCD camera, an ultrasound scanner, a thermal
camera, a laser rangefinder and any combination thereof.
[0139] It is also an object of the present invention to provide a
non-transitory computer readable medium (CRM) having instructions
which, when implemented by one or more computers cause said one or
more computers to: store time-resolved thermal data of a plurality
of coordinated locations of an examined tissue, or portion thereof,
collected over time t; calculate according to said time-resolved
thermal data, a thermal transfer index, I, for each of said
plurality of coordinated locations; wherein at least one of the
following is being held true: if said I is greater than a
predetermined value I.sub.irr, determining said tissue as
irregular; if a ratio between said I and a predetermined I-scale is
greater than a predetermined value I.sub.irr, determining said
tissue as irregular; if a ratio between a first I.sub.first of a
first coordinated location and a second I.sub.second of a second
coordinated location is greater than a predetermined value
I.sub.irr, determining said tissue as irregular.
[0140] It is yet another object of the present invention to provide
a non-transitory computer readable medium (CRM) having instructions
which, when implemented by one or more computers cause said one or
more computers to: store time-resolved thermal data of a plurality
of coordinated locations of an examined tissue, or portion thereof,
collected over time t; calculate according to said time-resolved
thermal data, a thermal transfer index, I, for each of said
plurality of coordinated locations; wherein said I is defined
according to the following formula: T=a+b*exp(-I*t) where T is the
temperature and a and b are constants.
[0141] It is another object of the present invention to provide a
method for detecting and diagnosing at least one irregularity in
the tissue's cells in an examined tissue, characterized by the
steps of: applying thermomodulating means to at least a portion of
the examined tissue; collecting at least one thermal data of at
least a portion of the tissue over time; and calculating at least
one heat transfer index of the thermal data over time; thereby
detecting and diagnosing at least one irregularity in the tissue's
cells according to the at least one heat transfer index; wherein
the heat transfer index is calculated according to a derivative of
the thermal data over time.
[0142] It is another object of the present invention to provide the
above mentioned method, further comprising the step of selecting
the derivative to be from the group consisting of first derivative,
second derivative, third derivative and any combination
thereof.
[0143] It is another object of the present invention to provide the
above mentioned method, further comprising the step of normalizing
the heat transfer index to a predetermined scale.
[0144] It is another object of the present invention to provide the
above mentioned method, wherein the scale is a numerical scale
between 1 and 10, further wherein a higher value indicates a higher
severity of the medical condition of the at least one irregularity
in the tissue's cells.
[0145] It is another object of the present invention to provide the
above mentioned method, further comprising the step of correlating
the heat transfer index with associated at least one irregularity
in the tissue's cells selected from the group consisting of
malignant tumors, precancerous tumors, benign tumors, infections,
pneumonia, necrotic cells and any combination thereof.
[0146] It is another object of the present invention to provide the
above mentioned method, further comprising the step of collecting
the thermal data using a sensor selected from the group consisting
of an IR sensor, a mercury-in-glass thermometer, pill thermometer,
liquid crystal thermometer, thermocouple, thermistor, resistance
temperature detector, silicon bandgap temperature sensor and any
combination thereof.
[0147] It is another object of the present invention to provide the
above mentioned method, wherein the at least one thermal data is a
temperature measurement of the at least a portion of the tissue
over time.
[0148] It is another object of the present invention to provide the
above mentioned method, further comprising the steps of: collecting
thermal image data of at least a portion of the tissue over time;
calculating heat transfer index of the thermal image data over
time; constructing a heat transfer map comprising, optionally
spatial (i.e. three-dimensional), locations of the heat transfer
index over time; and identifying a designated location in the heat
diffusion image having distinctive heat transfer index from
surrounding spatial locations.
[0149] It is another object of the present invention to provide the
above mentioned method, further comprising the step of producing a
heat diffusion image of the at least a portion of the tissue prior
to the applying thermomodulating means to the tissue.
[0150] It is another object of the present invention to provide the
above mentioned method, further comprising the step of deeming a
designated spatial location of the heat transfer map suspect of at
least one irregularity in the tissue's cells if the designated
spatial location has the heat transfer index falling within a
predetermined heat transfer index range.
[0151] It is another object of the present invention to provide the
above mentioned method, wherein the spatial location is selected
from the group consisting of one pixel, a plurality of pixels, a
sub-pixel and any combination thereof.
[0152] It is another object of the present invention to provide the
above mentioned method, further comprising the step of comparing
the heat transfer map to a spatial image of the examined tissue's
area.
[0153] It is another object of the present invention to provide the
above mentioned method, further comprising a step of selecting said
time t to be in a range from about 10 ns to about 10 min.
[0154] It is another object of the present invention to provide the
above mentioned method, wherein during the step of applying
thermomodulating means to the tissue, the method further comprises
the steps of: collecting thermal data of at least a portion of the
tissue over time, for tracking the thermoregulation; and
calculating heat transfer index of the thermal data in
real-time.
[0155] It is another object of the present invention to provide the
above mentioned method, further comprising the step of constructing
a heat transfer map comprising spatial locations of the real-time
heat transfer index.
[0156] It is another object of the present invention to provide the
above mentioned method, further comprising normalization steps
selected from the group consisting of correcting to ambient
temperature, correcting to ambient humidity, correcting to ambient
electromagnetic radiation and any combination thereof.
[0157] It is another object of the present invention to provide the
above mentioned method, further comprising the steps of providing
access to a cervix area by a mechanical speculum; applying the
heating and/or cooling to the cervix area; and correlating the heat
transfer index with Cervical Intraepithelial Neoplasia (CIN).
[0158] It is another object of the present invention to provide the
above mentioned method, further comprising the step of deriving the
examined tissue from a mammal selected from the group consisting of
human, monkey, rodent, sheep, goat, cow, horse and swine.
[0159] It is another object of the present invention to provide the
above mentioned method, wherein the examined tissue is selected
from the group consisting of lungs, skin, cervix, ear, nose,
throat, oral cavities, esophagus, stomach, intestine, colon,
rectum, kidney, uterus, urinary tract, bladder, prostate, eyes, and
any part of the human body.
[0160] It is another object of the present invention to provide the
above mentioned method, further comprising the step of selecting
the thermomodulating means to operate in a manner selected from the
group consisting of advection, convection, conduction, radiation
and any combination thereof.
[0161] It is another object of the present invention to provide the
above mentioned method, wherein the thermomodulating means is
selected from the group consisting of heating means, cooling means
and any combination thereof.
[0162] It is another object of the present invention to provide the
above mentioned method, further comprising the step of applying the
heating and/or cooling means by a method selected from the group
consisting of hot and/or cold fluid inhalation, hot and/or cold
fluid application, halogen lamp exposure, LED light exposure, xenon
lamp exposure, flash lamp exposure, incandescent lamp exposure, IR
emission, radiation, electromagnetic and/or mechanical vibration
heating, hot and/or cold solid positioning, hot and/or cold patch
positioning, pharmaceutical heat modification, chemically induced
heating and/or cooling and any combination thereof.
[0163] It is another object of the present invention to provide the
above mentioned method, wherein the step of collecting thermal data
of at least a portion of the tissue over time is conducted by a
thermal sensor positioned in a position selected from the group
consisting of mounted outside the body, inserted to the body in an
invasive procedure, inserted to the body in a semi-invasive
procedure and any combination thereof.
[0164] It is another object of the present invention to provide the
above mentioned method, further comprising the step of calculating
the heat transfer index according to the thermal sensor resolution
and sampling rate.
[0165] It is another object of the present invention to provide the
above mentioned method, wherein the examined tissue is a biopsy
sampling of a suspected tissue area.
[0166] It is another object of the present invention to provide the
above mentioned method, further comprising the steps of applying
the method to a second examined tissue being a biopsy sampling of a
healthy tissue area, and obtained heat transfer index is compared
between the suspected tissue area and the healthy tissue area.
[0167] It is another object of the present invention to provide the
above mentioned method, further comprising the steps of using the
heat transfer index for at least one of the following: detecting
and mapping tumor boundaries for tumor removal operations; and
determining medical severity and/or malignancy status of the at
least one irregularity in the tissue's cells.
[0168] It is another object of the present invention to provide the
above mentioned method, further comprising the step of normalizing
the heat transfer index with patient parameters selected from the
group consisting of sex, age, smoking habits, drinking habits,
number of births, height, weight, blood pressure, diabetes state,
medical history, relatives medical history, patient's previous heat
transfer index and any combination thereof.
[0169] It is another object of the present invention to provide the
above mentioned method, further comprising the steps of: applying
thermomodulating means to a second tissue; collecting second
thermal data of at least a portion of the second tissue over time;
calculating a baseline heat transfer index of the second heat
diffusion image data over time; comparing the baseline heat
transfer index to the heat transfer index of the examined tissue;
and detecting and diagnosing at least one irregularity in the
tissue's cells according to a difference between the baseline heat
transfer index of the second tissue to the heat transfer index of
the examined tissue.
[0170] It is another object of the present invention to provide the
above mentioned method, wherein at least one of the following is
being held true: the second tissue is healthy; the second tissue
comprises at least one irregularity in the tissue's cells;
[0171] It is another object of the present invention to provide the
above mentioned method, further comprising the step of obtaining
the baseline heat transfer index from a database comprising heat
transfer index obtained from at least one second tissue deriving
from an examined individual and/or from at least one second
examined individuals.
[0172] It is another object of the present invention to provide the
above mentioned method, further comprising the step of deriving a
ratio between the heat transfer index of the examined tissue and a
second heat transfer index of a second examined tissue, and
comparing the ratio to at least one second ratio between a third
heat transfer index of a third examined tissue, and a fourth heat
transfer index of a fourth examined tissue.
[0173] It is another object of the present invention to provide the
above mentioned method, wherein the second examined tissue is
tissue surrounding the first tissue.
[0174] It is another object of the present invention to provide the
above mentioned method, further comprising the step of obtaining
the third distinctive heat transfer index and fourth heat transfer
index from a database comprising heat transfer index obtained from
a plurality of tissues deriving from an examined individual and/or
a plurality of examined individuals.
[0175] It is another object of the present invention to provide the
above mentioned method, further comprising the step of storing the
baseline heat transfer index in a storing means selected from the
group consisting of a computer readable medium, a server, a
cloud-like server and any combination thereof.
[0176] It is another object of the present invention to provide the
above mentioned method, further comprising the steps of applying
the thermomodulating means according to a manner selected from the
group consisting of according to a pre-determined protocol, in a
continuous manner, in a pulse manner and any combination
thereof.
[0177] It is also an object of the present invention to disclose a
system for detecting and diagnosing at least one irregularity in
the tissue's cells in an examined tissue, comprising: a
thermomodulating means for applying heating and/or cooling to at
least a portion of the examined tissue; a thermal sensor for
collecting at least one thermal data of at least a portion of the
examined tissue over time; and a processor adapted to read a
computer readable medium with instructions for calculating at least
one heat transfer index of the thermal data over time; thereby
detecting and diagnosing at least one irregularity in the tissue's
cells according to the at least one heat transfer index; wherein
the heat transfer index is calculated according to a derivative of
the thermal data over time.
[0178] It is still an object of the present invention to disclose
the aforementioned system, wherein the derivative is selected from
the group consisting of first derivative, second derivative, third
derivative and any combination thereof.
[0179] It is still an object of the present invention to disclose
the aforementioned system, wherein the processor is further adapted
to normalize the heat transfer index to a predetermined scale.
[0180] It is still an object of the present invention to disclose
the aforementioned system, wherein the scale is a numerical scale
between 1 and 10, further wherein a higher value indicates a higher
severity of the medical condition of the at least one irregularity
in the tissue's cells.
[0181] It is still an object of the present invention to disclose
the aforementioned system, wherein the processor is further adapted
to read a computer readable medium with instructions for
correlating the heat transfer index with associated at least one
irregularity in the tissue's cells selected from the group
consisting of malignant tumors, precancerous tumors, benign tumors,
infections, pneumonia, necrotic cells and any combination
thereof.
[0182] It is still an object of the present invention to disclose
the aforementioned system, wherein the thermal sensor is selected
from the group consisting of an IR sensor, a mercury-in-glass
thermometer, pill thermometer, liquid crystal thermometer,
thermocouple, thermistor, resistance temperature detector, silicon
bandgap temperature sensor and any combination thereof.
[0183] It is still an object of the present invention to disclose
the aforementioned system, wherein the at least one thermal data is
a temperature measurement of the at least a portion of the tissue
over time.
[0184] It is still an object of the present invention to disclose
the aforementioned system, further comprising a step of selecting
said time t to be in a range from about 10 ns to about 10 min.
[0185] It is still an object of the present invention to disclose
the aforementioned system, wherein the processor is further adapted
to read a computer readable medium with instructions for:
calculating heat transfer index of thermal image data obtained over
time; constructing a heat transfer map comprising, optionally
spatial, locations of the heat transfer index over time, thereby
generating a thermal diffusivity image; and identifying a
designated spatial location in the thermal diffusivity image having
a distinctive heat transfer index from surrounding spatial
locations.
[0186] It is still an object of the present invention to disclose
the aforementioned system, wherein, if a designated spatial
location of the heat transfer map has the heat transfer index
falling within a predetermined slope, the designated spatial
location is deemed suspect of at least one irregularity in the
tissue's cells.
[0187] It is still an object of the present invention to disclose
the aforementioned system, wherein the spatial location is selected
from the group consisting of one pixel, a plurality of pixels, a
sub-pixel and any combination thereof.
[0188] It is still an object of the present invention to disclose
the aforementioned system, wherein the thermal sensor is adapted to
collect thermal data of at least a portion of the tissue over time,
while the thermomodulating means is applied, thereby enabling the
processor to calculate the heat transfer index in real-time.
[0189] It is still an object of the present invention to disclose
the aforementioned system, further comprising at least one sensor
selected from the group consisting of a thermometer, a hygrometer,
a photodetector and any combination thereof.
[0190] It is still an object of the present invention to disclose
the aforementioned system, further comprising a spatial positioning
means selected from the group consisting of a visible light imaging
means, a CCD camera, an ultrasound scanner, a thermal camera, a
laser rangefinder and any combination thereof.
[0191] It is still an object of the present invention to disclose
the aforementioned system, further comprising a mechanical
speculum.
[0192] It is still an object of the present invention to disclose
the aforementioned system, wherein the distinctive heat transfer
index is correlated with Cervical Intraepithelial Neoplasia
(CIN).
[0193] It is still an object of the present invention to disclose
the aforementioned system, wherein the examined tissue is derived
from a mammal selected from the group consisting of human, monkey,
rodent, sheep, goat, cow, horse and swine.
[0194] It is still an object of the present invention to disclose
the aforementioned system, wherein the examined tissue is selected
from the group consisting of lungs, skin, cervix, ear, nose,
throat, oral cavities, esophagus, stomach, intestine, colon,
rectum, kidney, uterus, urinary tract, bladder, prostate, eyes, and
any part of the human body.
[0195] It is still an object of the present invention to disclose
the aforementioned system, further comprising a display means for
presenting a graphical representation of a feature selected from
the group consisting of a user interface, the heat transfer map,
the heat transfer index analysis, the marking of at least one
irregularity in the tissue's cells, border lines of the marking of
at least one irregularity in the tissue's cells, a visual image of
the examined tissue's area, the thermal data, the thermal image
data, the heat diffusion image and any combination thereof.
[0196] It is still an object of the present invention to disclose
the aforementioned system, wherein the display is adapted to
further display data relating to patient parameters selected from
the group consisting of sex, age, smoking habits, drinking habits,
number of births, height, weight, blood pressure, diabetes state,
medical history, relatives' medical history, patient's previous
heat transfer index analysis and any combination thereof.
[0197] It is still an object of the present invention to disclose
the aforementioned system, wherein the thermomodulating means are
adapted to provide and/or draw heat in a manner selected from the
group consisting of advection, convection, conduction, radiation
and any combination thereof.
[0198] It is still an object of the present invention to disclose
the aforementioned system, wherein the thermomodulating means are
adapted to heat the at least a portion of the examined tissue, or
cool the at least a portion of the examined tissue, or both.
[0199] It is still an object of the present invention to disclose
the aforementioned system, wherein the thermomodulating means are
selected from the group consisting of hot and/or cold fluid
inhalation, hot and/or cold fluid application, halogen lamp
exposure, LED light exposure, xenon lamp exposure, flash lamp
exposure, incandescent lamp exposure, IR emission, radiation,
electromagnetic and/or mechanical vibration heating, hot and/or
cold solid positioning, hot and/or cold patch positioning,
pharmaceutical heat modification, chemically induced heating and/or
cooling and any combination thereof.
[0200] It is still an object of the present invention to disclose
the aforementioned system, wherein the thermal sensor position is
selected from the group consisting of mounted outside the body,
inserted to the body in an invasive procedure, inserted to the body
in a semi-invasive procedure and any combination thereof.
[0201] It is still an object of the present invention to disclose
the aforementioned system, wherein the heat transfer index is
calculated according to the thermal sensor's resolution, sampling
rate and camera sensitivity.
[0202] It is still an object of the present invention to disclose
the aforementioned system, wherein the examined tissue is a biopsy
sampling of a tissue area suspected of having at least one
irregularity in the tissue's cells.
[0203] It is still an object of the present invention to disclose
the aforementioned system, wherein a second examined tissue is a
biopsy sampling of a healthy tissue area, and obtained heat
transfer index is compared between the suspected tissue area and
the healthy tissue area.
[0204] It is still an object of the present invention to disclose
the aforementioned system, wherein the heat transfer index is used
for at least one of the following: detecting and mapping tumor
boundaries for tumor removal operations; and determining medical
severity and/or malignancy status of the at least one irregularity
in the tissue's cells.
[0205] It is still an object of the present invention to disclose
the aforementioned system, further comprising a database containing
at least one heat transfer index of at least one second tissue, and
further wherein the processor is adapted to: compare between the at
least one baseline heat transfer index of at least one second
examined tissue and the at least one heat transfer index of at
least one examined tissue, and detect and diagnose at least one
irregularity in the tissue's cells according to a difference
between the baseline heat transfer index of the second tissue to
the heat transfer index of the examined tissue.
[0206] It is still an object of the present invention to disclose
the aforementioned system, wherein the second examined tissue is
selected from the group consisting of a healthy tissue, a tissue
containing at least one irregularity in the tissue's cells and any
combination thereof.
[0207] It is still an object of the present invention to disclose
the aforementioned system, further comprising a storing means for
storing the database, selected from the group consisting of a
computer readable medium, a server, a cloud-like server and any
combination thereof.
[0208] It is still an object of the present invention to disclose
the aforementioned system, wherein the processor is in operative
communication with the storing means, optionally wirelessly.
[0209] It is also an object of the present invention to provide a
computer readable medium (CRM), or electronics component, having
instructions which, when implemented by one or more computers cause
the one or more computers to: process thermal data derived from a
thermal sensor collected over time; calculate at least one heat
transfer index of the thermal data over time; wherein the heat
transfer index is calculated according to a derivative of the
thermal data over time.
[0210] It is still an object of the present invention to disclose
the aforementioned CRM or electronics component, wherein the
derivative is selected from the group consisting of first
derivative, second derivative, third derivative and any combination
thereof.
[0211] It is still an object of the present invention to disclose
the aforementioned CRM or electronics component, further wherein
the instructions which, when implemented by one or more computers
cause the one or more computers to normalize the heat transfer
index to a predetermined scale.
[0212] It is still an object of the present invention to disclose
the aforementioned CRM or electronics component, wherein the scale
is a numerical scale between 1 and 10, further wherein a higher
value indicates a higher severity of the medical condition of the
at least one irregularity in the tissue's cells.
[0213] It is still an object of the present invention to disclose
the aforementioned CRM or electronics component, further wherein
the instructions which, when implemented by one or more computers
cause the one or more computers to correlate the distinctive heat
transfer index with associated at least one irregularity in the
tissue's cells; thereby detecting and diagnosing at least one
irregularity in the tissue's cells.
[0214] It is still an object of the present invention to disclose
the aforementioned CRM or electronics component, further wherein
the instructions which, when implemented by one or more computers
cause the one or more computers to correlate distinctive the heat
transfer index with associated at least one irregularity in the
tissue's cells selected from the group consisting of malignant
tumors, precancerous tumors, benign tumors, infections, pneumonia,
necrotic cells and any combination thereof.
[0215] It is still an object of the present invention to disclose
the aforementioned CRM or electronics component, further wherein
the instructions which, when implemented by one or more computers
cause the one or more computers to: construct a heat transfer map
comprising, optionally spatial, locations of the heat transfer
index over time; and present on a display unit a designated spatial
location in the heat transfer map having distinctive heat transfer
index from surrounding spatial locations.
[0216] It is still an object of the present invention to disclose
the aforementioned CRM or electronics component, wherein the
instructions which, when implemented by one or more computers cause
the one or more computers to present on a display unit a designated
spatial location in the heat transfer map having distinctive heat
transfer index from surrounding spatial locations, further wherein
the spatial location is selected from the group consisting of one
pixel, a plurality of pixels, a sub-pixel and any combination
thereof.
BRIEF DESCRIPTION OF THE FIGURES
[0217] The novel features believed to be characteristics of the
invention are set forth in the appended claims. The invention
itself, however, as well as the preferred mode of use, further
objects and advantages thereof, will best be understood by
reference to the following detailed description of illustrative
embodiment when read in conjunction with the accompanying drawings,
wherein:
[0218] FIG. 1 presents a top level scheme of the method disclosed
by the present invention;
[0219] FIG. 2 schematically presents high level overview of a
preferred embodiment of the system disclosed by the present
invention;
[0220] FIG. 3 schematically presents a high level overview of a
preferred embodiment of the method disclosed by the present
invention;
[0221] FIG. 4 presents the cell types examined under the present
invention and their index numbers;
[0222] FIG. 5A-B illustrates a first experimental setup using six
cell types for examination. FIG. 5A illustrates the cell types and
their experimental configuration, while FIG. 5B illustrates a
visual demonstration of the heat transfer map of the six cell types
illustrated in FIG. 5A;
[0223] FIG. 6 graphically illustrates temperature decay profiles of
the examined cell populations presented in FIGS. 5A and B;
[0224] FIG. 7 graphically illustrates the first derivative of the
data presented in FIG. 6;
[0225] FIGS. 8A-B show an example of a graphical representation of
data as obtained from a cured swine meat, wherein FIG. 8A
exemplifies a spatial positioning means, i.e. a camera, and FIG. 8B
represents the graphical presentation of the thermal data collected
by a thermal sensor;
[0226] FIG. 9 graphically illustrates temperature decay profiles of
two sets of tissue cultures as presented in FIG. 5;
[0227] FIG. 10 illustrates a CT image of a horizontal slice through
a normal human chest at the level of the heart, with overlay lines
to show the edges of a simplified geometry for a simulation;
[0228] FIG. 11 illustrates the simplified geometry used for
simulation, including a simplified heart, simplified skin, muscle
and bone, and an exemplary growth;
[0229] FIG. 12 illustrates a simulation of a steady-state
temperature map of the slice of the chest;
[0230] FIG. 13 illustrates a simulation of a temperature map of the
slice of the chest after inhalation of a hot gas;
[0231] FIG. 14 illustrates a simulation of the change in the
temperature profile as the chest cools back to its steady state
temperature profile after heating; and
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0232] The following description is provided, alongside all
chapters of the present invention, so that to enable any person
skilled in the art to make use of the invention and sets forth the
best modes contemplated by the inventor of carrying out this
invention. Various modifications, however, will remain apparent to
those skilled in the art, since the generic principles of the
present invention have been defined specifically to provide a
method for detection and diagnosis of at least one irregularity in
the tissue's cells in a healthy tissue.
[0233] The term "at least one irregularity in the tissue's cells"
refers hereinafter to malignant tumors, precancerous tumors, benign
tumors, neoplasms, infections, pneumonia infected cells, necrotic
cells, infected cells, blood clots and any other cell type
exhibiting distinctive thermal transfer properties from healthy
standard tissue.
[0234] The term "camera sensitivity" refers hereinafter to the
capacity to have the signal stand out from the surrounding noise,
i.e. the signal-to-noise ratio acquired by the camera, and in the
case of a thermal sensor, this translates to the capacity to detect
minute temperature differences.
[0235] The term "radiation" refers hereinafter to the use of any
visible or non-visible radiation which has the capacity to elevate
the temperature of the target tissue, such as emitted by, in a
non-limiting manner, halogen lamp, incandescent lamp, IR emission,
and pertaining to any such electromagnetic wave and non-ionizing
radiation.
[0236] The term "hot" or "heating" refers hereinafter to a
temperature higher than the examined tissue, or an object having a
temperature higher than the examined tissue.
[0237] The term "cold" or "cooling" refers hereinafter to a
temperature lower than 37.degree. C., or an object having a
temperature lower than 37.degree. C.
[0238] The term "fluid" refers hereinafter to a liquid or a gas,
which may be hot or cold, and may refer to in a non-limiting
example to atmospheric air, oxygen, nitrogen, helium, hydrogen,
carbon dioxide, steam, water or oil.
[0239] The term "spatial positioner" refers hereinafter to any
imaging device providing information with regards to the physical
position of the examined tissue, and may include visible-light
imaging means, such as a CCD camera, a laser rangefinder, an
ultrasound scanner and so forth, resulting in a spatial image of
the examined tissue's area. Spatial positioning means may give out
results in a one dimensional output, two dimensional or three
dimensional output.
[0240] The term "thermal data" refers hereinafter to any numerical
or image-like data depicting the temperature of at least a portion
of an examined tissue.
[0241] The term "thermal image data" refers hereinafter to a visual
representation of thermal data in the form of a digital image.
[0242] The term "heat transfer map" refers hereinafter to thermal
image data depicting the change in temperature of at least a
portion of an examined tissue over time.
[0243] The term "heat diffusion image" refers hereinafter to an
image depicting the thermal diffusivity of at least a portion of an
examined tissue over time.
[0244] The term "heat transfer index" refers hereinafter to the
rate of heat transfer exhibited by at least a portion of an
examined tissue after being exposed to active thermoregulation.
[0245] The term "tissue" refers hereinafter to any of a tissue
culture, a cell line, a biopsy sampling, an in situ tissue (i.e. in
the examined animal) and the like.
[0246] The term "thermomodulating means" refers hereinafter to any
means or method for heating or cooling a tissue.
[0247] The present invention exploits active thermography to
identify minute variations between healthy tissues as compared to
tissues undergoing cancerous/precancerous stages, or any other
irregularity in at least one cell of the examined tissue. Active
thermography is the induction of a heat flow by energetically
exciting a test object. The heat flow is influenced by interior
material layers and defects. These inhomogeneities can be captured
on the surface by high-precision thermal sensors. The inventors of
the present invention have discovered that even a minor
differentiation of tissue cells, such as in precancerous
conditions, results in biomechanical-thermal differences which lead
to differences in heat flow, and therefore to a distinctive thermal
diffusivity and heat transfer.
[0248] Reference is now made to FIG. 1 illustrating a top level
overview of the core technological features of the present
invention's system 100. Thermal excitation source 101, or
thermomodulating means, is first used on an examined tissue. The
thermal excitation may be through transferring heat to the tissue
by any energy inducing device or through drawing heat from the
tissue through exposure to cold objects, or by any pharmaceutical
administration altering body temperature, or by any chemical
reaction configured to induce temperature alterations in any part
of the body. After such thermal excitation, heat transfer is
induced throughout the tissue. The heat transfer is dependent on
the thermal diffusivity properties of the tissue, such that healthy
tissue has certain thermal diffusivity properties and tissues
having at least one irregularity in the tissue's cells exhibit
distinctive thermal diffusivity properties. Heat transfer may be
the result of advection, convection, conduction, radiation and may
be carried out by any device or means such as, in a non-limiting
example, hot and/or cold fluid inhalation, hot and/or cold fluid
application, halogen lamp exposure, LED light exposure, xenon lamp
exposure, flash lamp exposure, incandescent lamp exposure, IR
emission, radiation, electromagnetic and/or mechanical vibration
heating, hot and/or cold solid positioning, hot and/or cold patch
positioning, pharmaceutical heat modification, chemically induced
heating and/or cooling and any combination thereof.
[0249] In various embodiments of the present invention, the
examined tissue may be at least a section of a tissue in an
examined individual. Such individual may be any mammal, such as in
a non-limiting example, human, monkey, rodent, sheep, goat, cow,
horse and swine, and may be derived from any body part, including
in a non-limiting example, lungs, skin, cervix, ear, nose, throat,
oral cavities, esophagus, stomach, intestine, colon, rectum,
kidney, uterus, urinary tract, bladder, prostate and eyes.
Preferably, the examined body part is of a kind that is accessible
to thermal excitation and thermal sensing.
[0250] In other embodiments of the present invention, the examined
tissue may be an in vitro examined biopsy sample taken from at
least a section of a tissue of an examined individual. The biopsy
sample may be healthy tissue or tissue suspected of having at least
one irregularity in the tissue's cells. And yet in other
embodiments, the examined tissue may be an extracted cell line or
cell culture grown on a dish.
[0251] In preferred embodiments the examined tissue is human cervix
tissue examined in situ i.e. in the patient himself, and the
resultant identified at least one irregularity in the tissue's
cells are Cervical Intraepithelial Neoplasia (CIN). However, at
least one irregularity in the tissue's cells may also refer to any
cancerous or precancerous tissues found in any other part of the
examined body.
[0252] The heat transfer is monitored with thermal sensor 102,
which is preferred to be an IR camera or IR sensor, but may be any
sensor which could provide thermal data, which is preferably
temperature values. Other sensors which may be used are an
ultrasound temperature sensor, a mercury-in-glass thermometer, a
pill thermometer, a liquid crystal thermometer, a thermocouple, a
thermistor, a resistance temperature detector, a silicon bandgap
temperature sensor and any combination thereof. In some
embodiments, the thermal sensor produces thermal data which
consists of a series of time-resolved temperature measurements. In
other embodiments, thermal sensor 102 can produce a plurality of
time-resolved thermal image data, or thermal digital images,
preferably over a time interval in a range from about 10 ns to
about 10 min. Thermal sensor 102 may be mounted outside the body or
inserted into the body in an invasive procedure, or in a
semi-invasive procedure.
[0253] Thermal data, or thermal image data is then transferred to a
processor comprising thermal analysis software 103. This processor
is found in operative communication with thermal sensor 102,
optionally through wireless communication.
[0254] In some embodiments, the thermal analysis software 103 can
contain instructions for calculating the heat transfer index, i.e.
the rate in which the heat transferred through the examined tissue,
according to the thermal data, or thermal image data taken over
time. These calculations include deriving the derivative of the
change in the thermal data detected over time. The derivative may
be a first derivative, a second derivative or a third derivative of
the thermal data, or thermal image data (through spatial location
intensity derivation), and any combination thereof. A plurality of
such heat transfer indexes may be then used to construct a heat
transfer map exhibiting these temporal heat transfer indexes
through spatial locations, which may be at a single pixel
resolution, a plurality of pixel resolution or sub-pixel
resolution, which is less than one pixel, i.e. super-resolution.
Optionally, binning is used to illustrate the heat transfer index,
i.e. through spatial locations which comprise a plurality of
pixels. At least one irregularity in the tissue's cells are
identified by identifying a designated spatial location having a
distinctive heat transfer index from its surrounding spatial
locations. At least one irregularity in the tissue's cells may also
be detected or diagnosed through suspected heat transfer index, or
heat transfer index which is found within a known heat transfer
range to be suspected of at least one irregularity in the tissue's
cells.
[0255] In some embodiments, thermal analysis software 103
calculates the heat transfer index through an algorithm comprising
first measuring the intensity of each of the spatial locations,
followed by determining a first derivative of the measured
intensity over time, and finally determining the heat transfer
index according to the first derivative. In an embodiment of the
present invention, a second or third derivative of the intensity
over time may be used to calculate the heat transfer index. In
various embodiments the heat transfer index is calculated in
accordance with the thermal sensor's resolution, sampling rate and
sensitivity.
[0256] In some embodiments, the thermal analysis software 103
contains instructions for calculating the thermal rate index, which
may be in some embodiments the thermal transfer rate constant, i.e.
the typical time it takes for the active thermo-modulation to decay
or recover in a specific tissue region, for each of the coordinated
locations. Each tissue type, depending on its unique composition
and metabolic activity, exhibits a different rate constant. This
means that coordinated locations comprising portions of the tissue
having at least one irregularity in the tissue's cells, will
exhibit a thermal rate constant which is different from the
surrounding, other healthy portions of the tissue. It is thus
disclosed by the present invention that determining the rate in
which active thermal modulation equilibrates over time in various
tissues reveals nuances and differences between such tissues, which
may not be detected using a different stimulation, detection or
analysis. A plurality of such thermal rate indexes may then be used
to construct a visual presentation, in the form of a map,
exhibiting these temporal thermal rate differences according to the
coordinated locations, which may be at a single pixel resolution, a
plurality of pixel resolution or sub-pixel resolution, which is
less than one pixel, i.e. super-resolution, or may comprise a
single cell resolution, or a plurality of cells. Optionally,
binning is used to illustrate the thermal rate constants, i.e.
through averaging spatial locations which comprise a plurality of
pixels. At least one irregularity in the tissue's cells are
diagnosed by identifying a designated spatial, i.e. coordinated,
location having a distinctive thermal rate index from its
surrounding spatial locations. At least one irregularity in the
tissue's cells may also be detected or diagnosed through thermal
rate constants which are found within a known range suspected of
relating to at least one irregularity in the tissue's cells.
[0257] The thermal transfer index, I, is used to obtain a threshold
value which will be correlated with a predetermined value
I.sub.irr, establishing a diagnosis. The index I may be directly
correlated to the value I.sub.irr, or it may be normalized by a
scale value I.sub.scale. In various embodiments, I is calculated
for at least two distinct coordinated locations, and then a first
calculated I.sub.first is normalized to a second calculated
I.sub.second, and the result is then compared to I.sub.irr.
[0258] In various other embodiments, the thermal transfer index is
defined according to the formula of T=a+b*exp(-I*t), where a and b
are constants, T is the temperature and t is the time over which
the thermal data was collected.
[0259] In various embodiments of the present invention, the thermal
rate index is not used directly in constructing the heat map, or
visual presentation, but an inferential thereof is used. Such
inferential value is derived from the thermal rate index in some
kind of a mathematical manipulation and may lead to important
metabolic parameters such as thermal conductivity coefficient,
thermal diffusion coefficient, heat capacity, density, heat loss
due to blood perfusion, blood temperature, heat convection index,
metabolic heat source and any combination thereof.
[0260] In order to construct the visual presentation, or heat map,
the thermal rate constant, or an inferential thereof, is normalized
to a predetermined numerical scale, which is pre-associated with
color, or pixel intensity, or both. In some embodiments, the scale
is a numerical scale of between 1 and 10, wherein 1 could represent
healthy cells or 1 could represent the most severe case of at least
one irregularity in the tissue's cells. Such a scale should provide
the practitioner using the system and method of the present
invention with a tool for outlining the boundary of the malignant
tissue, by means of the map, and also for estimating the severity
of the condition. Use of the tool can assist a practitioner to
determine a more optimal treatment of the irregularity.
[0261] In preferred embodiments, thermal analysis software 103
calculates the thermal rate constant through an algorithm
comprising first measuring the intensity of each of the spatial
locations, and following the intensity modification over time, and
finally extracting the thermal rate constant, usually by finding
the exponential decay constant of the measured heat decay profile.
In various embodiments of the present invention, the thermal rate
constant may be a heat decay rate detected after heating, or it may
be a heat recovery rate detected after cooling. In various
embodiments the thermal rate constant is calculated in accordance
with the thermal sensor's resolution, sampling rate and
sensitivity.
[0262] In some embodiments, thermal sensor 102 is operated during
the heating and/or cooling applied by thermal excitation source
101, and consequently, thermal analysis software 103 is configured
to calculate the thermal diffusion through the examined tissue, as
a consequence of the application of thermal sensor 101, in
real-time.
[0263] In various embodiments, the heat transfer index is
normalized against personal patient parameters such as, in a
non-limiting example, sex, age, smoking habits, drinking habits,
number of births, height, weight, blood pressure, diabetes state,
medical history, relative's medical history, the patient's own
previous heat transfer index analysis and any combination
thereof.
[0264] In an embodiment of the present invention, the heat transfer
map's emerging markings of distinctive heat transfer indexes is
used for detecting and mapping the at least one irregularity in the
tissue's cells' borders and for surgical removal of the markings
findings.
[0265] Results of thermal analysis software 103 are then displayed
on display means 104 comprising a user interface. The display means
may be a monitor which is part of the system, or of a personal
computer or the screen of any other electronic device such as a
personal tablet, smartphone, smart TV and the like. The electronic
device may comprise the thermal analysis software 103 in itself or
may be in operative communication with the processor comprising
thermal analysis software 103, wirelessly or through wire
communication.
[0266] At least one irregularity in the tissue's cells may be
recognized by correlating the emerging heat transfer index with
associated at least one irregularity in the tissue's cells, which
may be selected from a group consisting of a malignant tumor, a
precancerous tumor, a benign tumor, infections, pneumonia, a
necrotic cell, a blood clot and any combination thereof. At least
one irregularity in the tissue's cells may also be recognized by
comparing the emerging heat transfer indexes to a predetermined
range of slopes which are suspected to be the result of irregular
biomechanical-thermal properties in a tissue. In other embodiments,
the heat transfer indexes may be compared to a baseline of healthy
tissues or other tissues comprising at least one irregularity in
the tissue's cells, whether extracted from the same patient or from
a plurality of other examined individuals.
[0267] In several embodiments, thermal analysis software 103 is
configured to calculate a ratio between the distinctive heat
transfer index of the suspected area to the heat transfer index of
the surrounding tissue area. This ratio can then be compared to
other ratios taken from other examined individuals.
[0268] Display means 104 may illustrate a numerical or graphical
presentation of the gradient temperatures, the heat transfer maps,
the thermal data images, at least one irregularity in the tissue's
cells markings, at least one irregularity in the tissue's cells
border, the patient's personal parameters and the like.
[0269] The procedure includes heating and/or cooling application to
the examined area, forcing the tissue to transfer heat, followed by
monitoring the tissue's heat transfer and cooling by a thermal
sensor screening sampling of multiple thermal images, until full
coverage of examined tissue surface is reached, and finally
constructing temperature profile in relation to time and location,
as measured during the test (marking any irregularities).
[0270] In some embodiments, the device is directed to examining the
lungs. In such an embodiment, heat convection by inhalation of hot
gas, such as atmospheric air, oxygen, helium, hydrogen, nitrogen,
carbon dioxide or any other inhalable gas would supply a heat
application to at least a portion of the lung area, from the
symphonies to the alveolus. The thermal potential created between
the surface lung tissues and the internal ones would transfer heat
to the inner tissues. There, it would be absorbed and spread by the
internal layers. This is done due to several heat transfer
mechanisms found in biological tissues and conduction. This process
would eventually balance at steady state. Since cancerous tissues
vary in thermal properties from healthy ones and specifically the
thermal diffusion, it would stand out of the healthy environment.
Using the thermal camera images taken throughout the procedure,
heat transfer index analysis is made. Area temperature mapping
(According to the camera's resolution), at different times
(according to the camera's sampling rate--FPS) is depicted. This
maps the diffusion properties, revealing the abnormal areas.
Finally a three dimensional map of the examined tissue or organ is
constructed, marking the suspected areas.
[0271] Reference is now made to FIG. 2, illustrating a high level
overview of a preferred embodiment of the system disclosed by the
present invention. The system disclosed by the present invention
may comprise mechanical speculum 110, in order to gain access to
examined tissue 10 which me be an inner tissue area, such as the
cervix. After gaining access to examined tissue 10, scanner module
120 is operated. The module comprises a heat/cool source 121, scan
unit 122, thermal sensor 123, and may further comprise spatial
positioning means 125, which could be in a non-limiting example a
CCD camera, a thermal camera, a laser rangefinder, or an ultrasound
scanner, and may also comprise at least one environmental sensor
adapted to measure various parameters of the ambient environment
where the examination takes place, and this sensor may be, in a
non-limiting example a thermometer, a hygrometer, a photodetector
and any combination thereof.
[0272] In an embodiment of the present invention, the heat/cool
source 121 could be any device which is configured to apply heat to
the surface area of an examined tissue in a manner of advection,
convection, conduction, radiation or any combination thereof. In a
similar manner, cooling may be conducted by using a device which is
configured to remove heat from the surface area of the tissue, in
the manner of advection, convection, conduction, radiation or any
combination thereof. Radiation may be applied in any wave
length.
[0273] Thermal sensor 123 refers to any device providing detection
of thermal energy in a resolution of time and space, and producing
thermal image data. Preferably, thermal sensor 123 is an IR sensor,
but not limited to it, and thermal sensor 123 may also be a
mercury-in-glass thermometer, pill thermometer, liquid crystal
thermometer, thermocouple, thermistor, resistance temperature
detector, silicon bandgap temperature sensor and any combination
thereof.
[0274] In some embodiments, thermal image data can be image
processed by an object recognition module, it can be correlated
with data from other imaging modalities and any combination
thereof. The other imaging modality can be, but not limited to, a
camera image, a CT scan image, an MRI image, an ultrasound image,
and any combination thereof. By this means, coordinated locations
suspected of containing at least one irregularity in the tissue's
cells can be more accurately identified. In some embodiments, the
system can correlate at least one thermal image and at least one
image from at least one spatial positioner to better identify the
locations of any irregularities.
[0275] Thermal image data and any other data is then communicated
to the software module 130, which comprises data collector
submodule 131, data analyzer submodule 132 and results submodule
133. Software module 130 comprises the thermal analysis software
103 and results in temperature measurements which are subjected to
mathematical manipulations including deriving a first, second or
third derivative of the change in temperature over time, resulting
in the heat transfer index. This index may further be used to
construct the heat transfer map or the thermal diffusivity image
exhibiting the suspected areas of at least one irregularity in the
tissue's cells. Data collector 131 is found in operative
communication with scanner module 120, and comprises all the data
available from module 120. Data analyzer 132 is found in
communication with data collector 131 and extracts the relevant
data required for the heat transfer index analysis. Results 133 is
found in communication with data analyzer 132 and contains analyzed
data from cervical scanner 120.
[0276] In some embodiments, image processing by an object
recognition module, correlation with images from other modalities
and any combination thereof can be done with the thermal
diffusivity image.
[0277] The results 133 data, the analysis data of data analyzer 132
and the raw data of data collector 131 are then preferably
transferred to database 140. This database may be found in the same
electronic device as software module 130, or may be in a different
device, and even possibly, the data is wirelessly transmitted to
database 140 which is found at a different location. Database 140
may comprise various submodules, and in the illustrated embodiment
it comprises personal data submodule 141, global data submodule
142, update submodule 143 and extract submodule 144.
[0278] Personal data 141 comprises personal patient parameters
which may contain sex, age, smoking habits, drinking habits, number
of births, height, weight, blood pressure, diabetes state, medical
history, relatives' medical history, patient's previous heat
transfer index and any combination thereof.
[0279] Global data 142 may comprise data relating to examined
tissues or organs in other tissues and/or in other individuals.
Preferably global data 142 contains a database of examinations of a
plurality of tissues (a plurality of tissues from a single
individual, or a plurality of tissues from a plurality of
individuals whose data has been recorded), according to the method
as recited in the present invention. This database collectively
provides a heat transfer index baseline according to which an
immediate examination is referred to. Global data 142 may comprise
raw data taken from the scanner module, at least partially analyzed
data and/or results data. It may also contain personal information
related to the examined individuals participating in the baseline
database. Preferably, global data provides the ratio between
healthy tissues and tissues exhibiting at least one irregularity in
the tissue's cells. The ratio may then be compared between the
patient and a database containing such ratios from other examinees.
The comparison between the patient's ratio and the global data's
ratios will enable a better identification of the irregularity in
the tissue's cells, as well as the severity of the medical
condition and the malignancy status.
[0280] Update 143 provides an updated analysis of the heat transfer
index results 133 derived from scanner module 120, in view of the
baseline data of global data 142. Extract 144 provides the
finalized analysis of the heat transfer index results, after being
compared to the baseline data. The baseline gradient temperature
may refer to healthy tissues, or may refer to any tissue having at
least one irregularity in the tissue's cells. Global data 142 may
comprise a plurality of databases relating to various tissue
conditions, and comparison to the appropriate database may be
determined, inter alia, according to personal data 141.
[0281] The final results of the analyzed tissue heat transfer
provided by database module 140 are then transferred to the user
interface module 150, which preferably comprises processor 151 and
display 152. User interface 150 enables both data representation
and data input by a user, where user of the system provided by the
present invention enters any data which is relevant to the analysis
of the heat transfer index. In addition, the user may decide which
output will be presented to him on the display and in which
manner.
[0282] Reference is now made to FIG. 3, illustrating a high level
overview of a preferred embodiment of the method disclosed by the
present invention. Preferably the method is conducted on the
examined individual, if needed by creating access 210 to the
suspected tissue, using device such as, in a non-limiting example,
a mechanical speculum. After gaining access to the suspected area,
at least a portion of its surface undergoes heating and/or cooling
220. The elevation/reduction in tissue temperature is monitored and
if the temperature has not reached the desired value 230, then a
better access 210 and/or re-heating/cooling 220 is repeated. If the
temperature has reached the desired value, then thermal scanning
240 is conducted next.
[0283] Thermal scanning 240 includes the use of a thermal sensor,
such as preferably an IR sensor, but could also include a
mercury-in-glass thermometer, pill thermometer, liquid crystal
thermometer, thermocouple, thermistor, resistance temperature
detector, silicon bandgap temperature sensor and any combination
thereof, and the heat transfer index analysis, resulting in a heat
transfer map. If no distinctive heat transfer indexes emerge 250,
i.e. the heat transfer map is homogenous and normal tissue status
is displayed 30, showing a numerical or graphical representation of
healthy results. If on the other hand, inhomogeneous regions are
suspected to be in the heat transfer map, the data is preferably
compared to a database 260. The database comprises a baseline
derived from various examinations of other tissues and/or other
examined individuals, as depicted in FIG. 2. According to the
comparison 260, it can be determined if the tissue is
cancerous/precancerous 270, in addition to providing an estimate of
the severity of the medical condition, the extent of at least one
irregularity in the tissue's cells or the malignancy status of the
tumor. Such a comparison may be to the heat transfer index itself,
or to the ratio between the heat transfer index exhibited by the
healthy tissue to the heat transfer index exhibited by the
suspicious tissue. If it is, then marking is displayed for the
cancerous region 20. If the comparison does not result in cancer
suspicious tissue, other pathologies may be diagnosed 280, might be
with the use of other baselines. If other pathologies are
identifies, then markings of the found pathological region is
displayed 21. If no cancer, and no other pathology are found, then
normal tissue status is displayed 31.
[0284] In some embodiments of the system, at least one map of the
examined area is generated. The map can be a two-dimensional map of
a narrow region, a slice of the subject, or a three-dimensional map
of a portion of a subject. The map can be of at least one tissue
parameter or of a time-resolved tissue parameter, where the tissue
parameter can be selected from a group consisting of: thermal
conductivity coefficient, thermal diffusion coefficient, heat
capacity, density, heat loss due to blood perfusion, blood
temperature, heat convection index, metabolic heat source and any
combination thereof. At least one map can be of the analyzed
time-resolved thermal data, for example by color-mapping the
resultant time resolved thermal index, I.
[0285] According to an embodiment of the present invention, the
method can also be applied to diagnosis based on comparison of the
analyzed results to a baseline. This baseline could be any tissue
which was processed using the method proposed in the present
invention, i.e. any healthy or malignant tissue, which has been
applied with heating or cooling, and been scanned for temperature
gradient profiling. The temperature gradient profile, and the
resulting heat transfer index, of the examined tissue can be
compared with the temperature gradient profile, and the resulting
heat transfer index, of the baseline tissue. Identification of
similar patterns will enhance the likelihood of correct diagnosis
and, therefore, selection of suitable treatment routines.
[0286] In various embodiments of the present invention, the heat
transfer index is normalized to provide a scale, preferably a
numerical scale, which has a range between 1 and 10, wherein a
higher value indicates a higher severity of the medical condition
of an irregularity in the tissue's cells, or a later cancer stage.
A value of 0 may indicate healthy tissue.
[0287] Reference is now made to FIGS. 4-7, demonstrating results of
a first experimental set up which includes six experiments
conducted on six cell types cultures. Various cell types are
compared with regards to their thermal properties. As shown in FIG.
4, the compared cell types are: lung tissue, including normal
tissue (fibroblasts) and two types of cancerous tissue (H1299 and
549) and kidney tissue, both normal tissue (AK-epithelial cells)
and cancerous tissue (Wilms tumor from exografts).
[0288] FIG. 5A shows the locations on the plates of FIG. 5B of the
cells of the types listed above and in FIG. 4, while FIG. 5B shows
an example of the temperatures of the cells on the plates during
cooling.
[0289] FIG. 6 shows the differential cooling of the normal kidney
tissue (upper curve) vs. the Warn's tumor tissue (lower curve). The
normal tissue both heats more and cools faster than the Warn's
tumor tissue. FIG. 7 shows the first differential of the curves in
FIG. 6, where the upper curve is for the normal tissue and the
lower curve for the Wilms tumor tissue.
[0290] FIG. 8 exemplifies the data obtained and analyzed, as
collected over a tissue taken from cured swine meat. FIG. 8A shows
an image obtained by spatial positioner, i.e. a camera, while FIG.
8B illustrates thermal data collected by a thermal sensor, in this
example an IR sensor. The image shows the analyzed time-resolved
thermal data by color-mapping the resultant time resolved thermal
index, I. Background has been removed by setting a threshold index
I to present. The index I was calculated according to the
following:
T=a+b*exp(-1*t)
where a and b are constants and T is temperature.
[0291] The graphical presentation shows a proof of concept,
illustrating the high power of the algorithm disclosed by the
present application in distinguishing between tissues by exploiting
their recovery from active thermomodulation.
[0292] FIG. 9 presents thermal decay profiles of two coordinated
locations, one having a cancerous cell sample and the other having
a healthy cell sample, illustrating that the difference in the
apparent decay trend and in the calculated decay rate constant is
significant. In this example, the decaying temperature measurements
were fitted to the following formulas:
T.sub.1/(t)=29.24+(14.74*exp(-0.0148*t))
T.sub.2(t)=29.06+(12.91*exp(-0.0135*t))
where T.sub.1 gives the temperature decay curve for the normal
tissue and T.sub.2 gives the temperature decay curve for the
cancerous tissue, with the cancerous tissue, which is cooler than
the normal tissue, returning to ambient more slowly than the
cancerous tissue. Thus, a significant difference between the index,
I.sub.1, of T.sub.1 and the index, I.sub.2, of T.sub.2 is shown
as:
I.sub.1/I.sub.2=(-0.0148/-0.0135)=1.09
i.e. approximately a 10% difference. This example illustrates that
a calculated ratio between two thermal transfer indexes 1, which is
greater than I.sub.irr=10% corresponds with an irregularity in the
tissue's cells.
[0293] The tested tissue is thermally excited by heating or cooling
the tissue surface, and is then carefully monitored for heat spread
and absorption. Using infrared sensors, thermal surface images are
obtained in various time intervals. Analyzing the temperature
variation from the images, in relation to time and position can
reveal points of irregularity, which suggest pathologic al
tissue.
[0294] Without wishing to be bound by theory, the concept of using
thermal analysis based on thermal diffusivity changes for finding
any irregularities is already successfully implemented in the field
of material analysis. Industrial and research facilities apply
non-destructive tests (NDT) for a variety of materials (such as
metals, polymers, concrete, composite materials and others) using
infrared active analysis. The tested material is thermally excited
by heating the surface, and carefully monitored for heat
conduction. Using infrared sensors, thermal surface images are
obtained for different sampling times. Analyzing the temperature
profile from the images, in relation to time and position can
reveal irregularities. These might be cracks or any other flaws in
the material, which are discovered due to differences in their
thermal properties compared to homogeneous material.
[0295] Hereby is the "Penne's equation", a widely accepted
temperature profiling equation for biological tissues:
.rho. C .differential. T .differential. t = .gradient. ( k
.gradient. T ) + q + A 0 - b ( T - T b ) ##EQU00022##
where:
q [ W m 3 ] ##EQU00023##
External heat source;
A 0 [ W m 3 ] ##EQU00024##
Metabolic heat source
b [ W m 3 .degree. C . ] ##EQU00025##
Heat loss due to blood perfusion; T.sub.b[.degree. C.]--Blood
temperature T[.degree. C.]--Tissue temperature;
.rho. [ kg m 3 ] ##EQU00026##
Density
[0296] C [ J kg .degree. C . ] ##EQU00027##
Heat capacity;
k [ W m .degree. C . ] ##EQU00028##
Thermal Conductivity Factor
[0297] Biological tissues behave much like a homogenous solid whose
thermal properties are defined mostly by its water content. In
addition, there is a dependency of the properties on tissue
temperature.
[0298] Different studies have shown that there is a temperature
rise of approximately 1 degree Celsius in cancer tumor compared a
healthy neighboring tissue. This is due to enhanced metabolic
activity, accelerated growth mechanisms and massive blood vessel
usage of the tumor. It is therefore expected to find a temperature
of 38.degree. Celsius in a lung tumor opposed to normal 37.degree.
Celsius in normal lung tissue. This change of temperature supports
the premises that cancer cells have different thermal properties.
This of course enables the diagnostic of such cells using active
thermal imaging.
[0299] Studies include "Modeling Temperature in a Breast Cancer
Tumor for Ultrasound-Based Hyperthermia Treatment" by Brian Ho et
al.; Strom et al., Cancer research, 1979; "Introduction to NDT by
Active Infrared Thermography" by X. Maldague; "Thermal Properties"
by Holmes; and "T issue Thermal Properties and Perfusion" by
Jonathan W. Valvano, which are incorporated herein as a
reference.
[0300] The thermal conductivity factor "k" for human tissues has
been tested before, however, it was not categorized to different
lung tissues groups. Moreover the data that do exist does not
mention the lung tissue type tested. As in many human tissues, the
lung tissue contains a large amount of water. This makes its
thermal properties very close to those of water and in particular
the conductivity factor.
[0301] According to McIntosh and Anderson's literature survey taken
in 2010, in which several conductivity factor where tested
(McIntosh and Anderson, Biophysical Reviews and Letters, 2010,
incorporated herein as a reference), average values can be
calculated for the factor. It is hereby presented:
Maximum value : 0.28 [ W m .degree. C . ] ##EQU00029## Minimum
value : 0.48 [ W m .degree. C . ] ##EQU00029.2## Average value :
0.38 [ W m .degree. C . ] ##EQU00029.3##
[0302] The lung's "K" factor varies significantly according to the
subject's age. Values could change from 0.3 in a child's to 0.55 in
a grown man with a lung disease.
[0303] The thermal diffusion is a property subjected to changes
according to the three previously mentioned properties in this
manner
.alpha. = K .rho. C ##EQU00030##
Whereas:
[0304] .rho. [ kg m 3 ] ##EQU00031##
Density;
[0305] C [ J kg .degree. C . ] ##EQU00032##
Heat capacity;
k [ W m .degree. C . ] ##EQU00033##
Thermal Conductivity Factor
[0306] The experiment is to prove the differences in thermal
diffusion between a healthy tissue and a cancer one, and that it is
large enough to be successfully identified as an irregularity.
Example 1
[0307] The experimental set up used to evaluate the invention is
comprised of two stages. The second stage is designed to achieve
greater accuracy and elaboration of the results obtained in the
first stage, in addition to handling experimental issues and
difficulties arising in the first experimental stage. The second
stage was conducted in view of the results obtained in the first.
Experimental design goes as follows:
[0308] Image capturing of all cell cultures; Laboratory conditions
take into account: (a) Neutralizing disturbances; (b) Constant
temperature, registration of any alterations. (c) Registration of
humidity values.
[0309] Camera set up: Control set up--heating; Control set
up--cooling; Conduct experiments using heating; Conduct experiments
using cooling.
Example 2
[0310] The system of the present invention can be configured as a
`decision support` system, informing a user such as a clinician as
to whether a positive CT result is a cancer (true positive) and
requires further investigation, or whether the positive CT result
is a false positive.
[0311] With the system of the present invention, the results are
immediate, do not involve radiation risks and are independent of an
expert's eye. The test is computerized and automatic, with no need
for a long, expensive analyzing stage.
[0312] As disclosed above, the technology is based upon analysis of
the temperature decay profile and measurement of heat diffusion in
the lung. It is well known that the density of cancerous cells is
higher than that of normal cells, their shape is different and
their nuclei are enlarged. These differences cause a fundamental
change in the thermal properties of the cells. The planned
operating principle--short heating followed by tracking diffusion
of heat into the tissue and absorption of heat in the tissue.
[0313] An IR camera can be directed through the tumor from outside
the body (or from the inside of the lung) and can be scanned during
the examination. Thermal excitation can be provided by inhalation
of a hot gas, such as hot hot gas, such as atmospheric air, oxygen,
helium, hydrogen, nitrogen, carbon dioxide or any other inhalable
gas, from a dedicated balloon, by irradiating the tissue by light
(such as, but not limited to, infrared light, visible light or
ultraviolet light), or both. After application of the heat, the
heat source can be deactivated and, from that moment, video images
can be taken at a high acquisition rate for several minutes. During
this time, the tissues will cool to a temperature close to their
default, unheated, temperatures.
[0314] An analysis of the temperature decay profile at every point
on the surface can be executed in real time or after a delay. For
non-limiting example, the analysis can take place after data
acquisition is complete. Preferably, any delay in analysis will be
short, typically no more than a few minutes. A comparison can be
carried out between adjacent points in the image (according to the
number of pixels) and a further comparison for the database can be
collected. The measurements can be processed to create a map that
will mark suspected cancerous areas, if any, on a display.
[0315] The method comprises testing the tissues response to thermal
excitation over a short period of time, and therefore can
distinguish between cancer and other pathologies such as benign
growths or necrosis as a result of cancer treatment and surgical
removal.
[0316] The evaluation can be performed with high precision because
the test searches for discontinuities on a continuous surface
pursuant to heat transfer in the tissues.
[0317] Unlike alternatives currently available, the test does not
expose a patient to harmful radiation, can reduce the quantity of
false positive/false negative results obtained and will save the
health system time and money as there is no need for a medical
specialist to perform the test or for an expert to decode the
results.
[0318] The system's principal components: [0319] A dedicated
inhaled excitation device. [0320] An IR camera, either outside the
body or inside the lungs. [0321] A decoding system, which includes
both software and a user interface. [0322] Optionally, a central
server including a cumulative database related to the patient's
medical records, to which new data can be added and re-analysis of
the data can be carried out to provide improved and updated
diagnosis on a timely basis.
Example 3
[0323] A simulation of a method of generating a thermal diffusion
image is demonstrated on a horizontal slice of a human thorax
(chest), which includes the lungs and the heart. FIG. 10 shows a CT
image of a normal human thorax (1000), showing the heart (1010),
spine (1020), lungs (1030), and the bones (1040), muscles (1050)
and fat (1060). These have been overlaid with lines indicating the
simplified shapes for the organs which will be used in the
simulation. The spine (1020) is simulated by a triangle, the heart
(1010) by an oval, with the inner and outer limits of the bone
(1040), muscle (1050) and fat (1060) being indicated by concentric
ovals. The lungs (1030) occupy the space between the oval of the
heart (1010) and the triangle of the spine (1020) as inner limits
to the lungs and the inner perimeter of the bone (1040) as the
outer limits to the bone.
[0324] FIG. 11 shows the simplified shapes of the organs (1100),
without the CT scan. In FIG. 11, the heart (1010) is indicated by
the oval filled with right diagonal lines, the spine (1020) by the
triangle with horizontal lines, the lungs (1030) by left diagonal
lines, the bones (1040) by the dotted region outside the lungs, the
muscles (1050) by the grey region, and the fat (1060) by the
outermost, diamond-filled region. The width of the slice,
side-to-side, is approximately 30 cm.
[0325] Table 1 shows the physical parameters used in the
simulation.
TABLE-US-00001 TABLE 1 Physical parameters used in the simulation
Specific Heat Thermal Heat Generation Tissue Density Conductivity
c.sub.p Perfusion Rate Q Type (kg/m.sup.3) k (W/(m K)) (J/(kg K))
(ml/(min gm)) (W/m.sup.3) Air 1.205 0.0257 1005 -- 0 Lung 427 0.38
3886 0.04 600 Cortical 1460 0.295 1244 0.027 0 Bone Cancellous 1460
0.295 2292 0.027 0 Bone Muscle 1103 0.49 3322 0.0009 684 Fat 909
0.21 2065 0.0002 58 Blood 1060 0.51 3651 -- 0 Heart 1086 0.55 3669
1.17 700 Tumor 1050 0.561 3852 0.009 5000
[0326] FIG. 12 illustrates a simulated steady-state heat
distribution in a chest with a growth (1210) in the lungs. The
center of the growth is at an x-coordinate of about -0.055 m. The
initial conditions for the simulation were a uniform temperature of
37.degree. C. (310 K), with a heat transfer coefficient at the skin
boundary of about 10 and radiative heat transfer from the skin. Of
the normal tissue, the heart is the hottest part of the simulation,
at approximately 310 K, while the lungs, at approximately 304-306
K, are the coolest, while the bone and muscle are about 308-309 K.
The skin is at about 303 K, with the temperature in the fat rising
form about 303 K to about 306 K. The growth (1210), at about 310 K,
is clearly seen on the left side of the figure.
[0327] FIG. 13 illustrates the effect of inhaling a hot gas on the
temperature distribution inside the chest. In this simulation, the
gas was at a temperature of 50.degree. C. (323 K) and was "inhaled"
(provided to the lungs as a heat generation source) for 30 s.
[0328] FIG. 14 illustrates the change in the temperature profile as
measured outside the chest, for example by an imaging device such
as an IR camera, as the chest cools back to its steady state
temperature profile after heating. The uppermost curve (1610)
illustrates the temperature profile immediately after completion of
inhalation of the hot gas, while the lowermost curve (1620)
illustrates the steady-state temperature profile. The anomaly (the
growth 1210) is clearly present, although its center appears to be
at about -0.03, rather than the known central position of about
-0.55.
[0329] These simulations show that the presence and approximate
location of an anomaly can be determined from outside the chest,
that heating from inside the lungs materially affects the
temperature profile inside the body, and that this change in
internal temperature profile is determinable from outside the
body.
[0330] While the invention is susceptible to various modifications
and alternative forms, specific embodiments thereof have been shown
by way of example in the drawings and the above detailed
description. It should be understood, however, that it is not
intended to limit the invention to the particular forms disclosed,
but on the contrary, the intention is to cover all modifications,
equivalents, and alternatives falling within the spirit and scope
of the invention as defined by the appended claims.
* * * * *