Michal Tepper Under the supervision of Prof. Israel Gannot.
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Transcript of Michal Tepper Under the supervision of Prof. Israel Gannot.
![Page 1: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/1.jpg)
Michal TepperUnder the supervision of Prof. Israel Gannot
![Page 2: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/2.jpg)
IntroductionSpectroscopy of biological tissues is a
powerful tool for evaluation of tissue composition and functionality.
Photothermal spectroscopy is a method for performing tissue spectroscopy, based on measuring tissue thermal changes due to light excitation.
![Page 3: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/3.jpg)
Previous Photothermal ResearchPhotothermal spectroscopy was shown to
be valuable for surface measurements (Milner, 1998)
Single particles can be detected (Zharov, 2003)
Measurements through fiber bundles are a new field and offer new possibilities
![Page 4: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/4.jpg)
The MethodThe temperature increase depends on tissue
composition, its optical properties and the exciting laser wavelength.
Using several wavelengths for the excitation will allow us to estimate tissue composition.
The method can be applied to internal cavities using a commercially available endoscope.
![Page 5: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/5.jpg)
The Method
COHERENT WAVEGUIDE BUNDLE
TISSUE
LASER
THERMAL
CAMERA
ENDOSCOPE
OPTICAL FIBER
![Page 6: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/6.jpg)
The GoalOne promising application is the
determination of the oxygenation of a tissue, a widely researched subject due to its clinical importance:Tumor detection (90% of human cancers arise
from epithelial cells)Cancer treatment adjustmentHypoxia detection
![Page 7: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/7.jpg)
Research StagesCreating a theoretical modelDeveloping an algorithm suitable
for different types of tissueTissue-like-phantoms experimentsTissue engineered phantoms
experimentsIn-vivo experiments
WE ARE HERE
![Page 8: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/8.jpg)
The Theoretical Model
Defining material concentration (water, melanin, hemoglobin)
Calculating optical properties of the tissue’s layers
Calculating absorption using MCML
Calculating tissue temperature distribution using COMSOL
Calculating the thermal image seen by the camera
• Simulating temperature rise in the tissue as a result of laser illumination:
![Page 9: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/9.jpg)
Skin Tissue Model
ThicknessngH2O%Blood%
stratum corneum201.50.860.052.1*10-4
epidermis801.340.80.22.1*10-4
papillary dermis1501.40.90.50.02
upper blood net dermis801.390.950.60.3
reticular dermis15001.40.80.70.04
deep blood net dermis801.380.950.70.1
hypodermis60901.440.750.70.05
A seven layer skin tissue model was selected.
![Page 10: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/10.jpg)
Results Monte-Carlo
Melanin absorption in epidermis
Hemoglobin absorption in dermis
Baseline absorption
J/cm3
r [cm]
z [cm]
Illumination
![Page 11: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/11.jpg)
Results COMSOL
r [cm]
z [cm]
T [K]
![Page 12: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/12.jpg)
Thermal Image SimulationT [K]
x [cm]
y [
cm]
![Page 13: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/13.jpg)
Preliminary ResultsSelection of excitation wavelengths:
saturation evaluation is limited by skin color
5% melanin
25% melanin
15% melanin
Wavelength [nm] Wavelength [nm]
T [
K]
T [
K]
![Page 14: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/14.jpg)
Hemoglobin Optical Absorption
![Page 15: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/15.jpg)
LimitationsSolving the equation system is inaccurate
because of measurement errors.The model might be inaccurate and
parameters might change between people and between different locations.
We want to develop a generic algorithm suitable for different tissues and wavelengths.
![Page 16: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/16.jpg)
IntuitionExamining the shape of the temperature
function and not the values.
Wavelength [nm]
Wavelength [nm]
T [
K]
µa
![Page 17: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/17.jpg)
The SolutionThe measured temperature is a function of
several unknowns, including the saturation.The unknowns can be estimated using a
simple curve fitting algorithm.The curve fitting algorithm depends on the
initial guess for each of the unknowns. Therefore, an initial guess algorithm for the saturation was also developed.
![Page 18: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/18.jpg)
Temperature Function
T1=f1()A1
T2=f2(A1 ,)A2
T3=f3(A1 , A2 ,)A3
The absorption of each layer is affected by the absorption of upper layers
A1=Σ µi·ci
Effective absorption of layer 1
![Page 19: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/19.jpg)
Temperature FunctionThe temperature rise is the sum of
effective contributions of all the layers:
Each layer affects deeper layers:
The functions fi can be approximated using Taylor approximation:
( ) ( 1) ( 2) ( 3)T T layer T layer T layer
0 1 1 2 1 2 3 1 2 3( ) ,T T f A f A A f A A A
2' ''2 1 2 2 1 2 1
10 0 0
2f A f f A f A
22 1 1 2 1 3 1f A b b A b A
![Page 20: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/20.jpg)
Temperature FunctionComparing computational results to the
theoretical equations enables us to estimate some of the coefficients:
![Page 21: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/21.jpg)
For skin tissue (containing melanin):
For “internal” tissue (skin tissue without melanin):
0 1 2 3 4
1
Melanin Baseline Melanin Baseline Hemoglobin
Hemoglobin HbO Hb
T T a a a a
S S
20 1 2
2 2 23 4 5
Baseline Baseline
Baseline Hemoglobin Baseline Hemoglobin Hemoglobin
T T a a
a a a
Temperature Function
![Page 22: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/22.jpg)
Results of the initial guess algorithm for skin tissue with 7.5-10% melanin:
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 10
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
True saturation
Est
imat
ed s
atur
atio
nEst
imate
d s
atu
rati
on
True saturation
Results
![Page 23: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/23.jpg)
Results of the saturation estimation algorithm for the tissue:
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 10
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
True saturation
Est
imat
ed s
atur
atio
nEst
imate
d s
atu
rati
on
True saturation
Results
![Page 24: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/24.jpg)
The results of the algorithm demonstrated considerable agreement with the model’s actual oxygenation values.
RMS of the error is reasonable. Hemoglobin:9g/l10.5g/l12g/l13.5g/l15g/lTotal
2.5% melanin8%7.6%6.8%7.7%8.1%7.7%
5% melanin8.7%5.1%6.3%5.4%6.8%6.6%
7.5% melanin5.2%6.4%5.9%6.4%8.1%6.5%
10% melanin9.1%6.4%7.1%8.4%5.7%7.5%
Results
![Page 25: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/25.jpg)
Tumor Oxygenation ValuesTissueMedian satuationReference value
Spleen92.796
Subcutis8596-97
Gastric mucosa82.697
Uterine cervix6997
Liver42.798
Cervix cancer3-3297-98
Adenocarcinomas9-1396-97
Squamous cell carcinomas1996-98
Breast cancers2496-98
![Page 26: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/26.jpg)
Results of the initial guess algorithm for skin tissue without melanin, representing internal tissue:
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 10
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
True saturation
Estim
ate
d s
atu
ration
Est
imate
d s
atu
rati
on
True saturation
Results
![Page 27: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/27.jpg)
Results of the saturation estimation algorithm the tissue:
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 10
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
True saturation
Est
imat
ed s
atur
atio
nEst
imate
d s
atu
rati
on
True saturation
Results
![Page 28: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/28.jpg)
Results for skin tissue without melanin.
RMS of the error is relatively small.
Hemoglobin:9g/l10.5g/l12g/l13.5g/l15g/lTotal
0% melanin5.3%4.8%4.2%5.3%5.2%5%
Results
![Page 29: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/29.jpg)
The phantoms were created using various types of absorbers.
Experimental Setup
![Page 30: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/30.jpg)
The agar used in the phantoms simulates the thermal properties of the skin.
Experimental Setup
![Page 31: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/31.jpg)
Absorption spectraThe selected absorbers were
Methylene Blue, Indocyanine Green (ICG) and ink.
![Page 32: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/32.jpg)
Experimental SetupThe phantoms are excited by 3900s
tunable laser, pumped by Millenia Vs Laser.
![Page 33: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/33.jpg)
The relative intensity of the illumination is measured using an integration sphere.
Experimental Setup
![Page 34: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/34.jpg)
The temperature is measured by thermoVision A40 IR camera.
The experiments can be monitored using MicroMax CCD camera.
Experimental Setup
![Page 35: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/35.jpg)
The setup can be further simplified by using diodes and thermocouples.
Experimental Setup
![Page 36: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/36.jpg)
Temperature measurement
0 500 1000 1500292.6
292.8
293
293.2
293.4
293.6
293.8
294
294.2
294.4
294.6
time [sec]
T [
K]
Calibration drift
Max temperature not reached
Noisy measurements
![Page 37: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/37.jpg)
Temperature measurementThe temperature is estimated using a
curve fitting algorithm.
0 100 200 300 400 500 600 700292
292.2
292.4
292.6
292.8
293
293.2
293.4
150 200 250 300 350292.2
292.4
292.6
292.8
293
293.2
293.4
fit_ys vs. fit_xs
fit 1
T0
Tsat
![Page 38: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/38.jpg)
Intensity CalibrationCalculated using measurements with the
integration sphere
![Page 39: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/39.jpg)
Calibrated Measurement ResultsTemperature increase, normalized according
to intensity
![Page 40: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/40.jpg)
Estimated temperature function
0 1 2
(1 )B G
T T I a a
S S
01 2
T TT a a
I
a1, a2 and S are unknowns and will be estimated using the curve fitting algorithm. a1 and a2 are a function
of the materials thermal and physical properties and concentrations. S is the saturation. (ratio between ICG and Methylene Blue)
![Page 41: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/41.jpg)
Experimental StagesPreliminary measurements: Used to
fine-tune experimental procedures and algorithms and to adjust material concentrations.
Repeating measurements with a larger number of phantoms
Validating the algorithms
![Page 42: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/42.jpg)
ResultsPreliminary measurements: Five agar
models containing two materials.For each sample there are 5 measurements
and 3 unknowns.
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 10
0.2
0.4
0.6
0.8
1
Real ratio
Est
imat
ed r
atio
![Page 43: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/43.jpg)
ResultsThe adjusted procedures were used to
measure 11 phantoms.
![Page 44: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/44.jpg)
ResultsPreliminary measurements of phantoms
with upper absorbing layer (simulating the epidermal layer).
![Page 45: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/45.jpg)
Future ResearchLayered agar phantoms with increasing
complexityAdjusting the algorithmsTissue engineered phantomsFiber bundle experimentsIn-vivo experiments
Collaboration with Rabin Medical Center
![Page 46: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/46.jpg)
Fiber Bundle ExperimentsInfrared imaging bundles can be used to detect tumors
in internal organs.
The bundles can be integrated to a commercially available endoscope.
900 fibers HGW
![Page 47: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/47.jpg)
Fiber Bundle ExperimentsA preliminary experiment with 1mm fiber
bundle was performed on an agar model.
Results are satisfying for a first experiment:
The measured signal is clearly reduced
Reference value: 100%
![Page 48: Michal Tepper Under the supervision of Prof. Israel Gannot.](https://reader034.fdocuments.in/reader034/viewer/2022052414/56649f135503460f94c279d4/html5/thumbnails/48.jpg)
Thank you..