Mueller imaging polarimetry for biomedical research · 2017. 6. 5. · Mueller imaging polarimetry...
Transcript of Mueller imaging polarimetry for biomedical research · 2017. 6. 5. · Mueller imaging polarimetry...
Mueller imaging polarimetry for biomedical research
Tatiana Novikova1, Jean Rehbinder1, Stanislas Deby1, Angelo Pierangelo1, Pierre Validire2, Abdelali Benali2, Brice Gayet3, Benjamin Teig4, André Nazac5, François
Moreau1 and R. Ossikovski1
1 LPICM, CNRS, Ecole polytechnique, Université Paris-Saclay, Palaiseau France
2 Département d'Anatomopathologie de l'Institut Mutualiste Montsouris, Paris, France
3 Département médico-chirurgical de pathologie digestive de l’Institut Mutualiste Montsouris, Paris, France
4 Service d’anatomie pathologique, CHU de Bicêtre, Le Kremlin-Bicêtre, France
5 Service de gynécologie et obstétrique, CHU de Bicêtre, Le Kremlin-Bicêtre, France
June 1, 2017, Photonics Summer School, Oulu, Finland
Outline
• Stokes-Mueller formalism
• Mueller matrix images of colon – Early cancer detection
• Mueller matrix images of uterine cervix – Mueller matrix images of fresh specimens
– Mueller matrix images of fixed specimens
• Conclusions
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Polarization of light
The light propagation in time and space can be fully described by Maxwell’s equations. This varying spatio-temporal field has vectorial nature.
What kind of temporal evolution of the electric field vector E(r,t) occurs in a given point of space?
1. If the temporal evolution does not change in any fixed point of space => light is said to be polarized. NB: it is not necessarily the same in two different points in space.
2. Otherwise the light is said to be partially polarized or non-polarized
S. Huard, Polarization of Light (Wiley, New York, 1997). 3
4
Polarized monochromatic wave
0
)cos(~
)cos(~
0
),( yy
xx
y
x
kztE
kztE
E
E
tz
E
Linear
Circular
Elliptical
)exp(Re),( krErE tjt
Ellipse of
polarization
Monochromatic plane wave
Jones formalism We define the Jones vector E - field
complex amplitudes as:
y
x
yy
xx
E
E
jE
jE
)exp(~
)exp(~
E
Examples of Jones vectors of polarized light
e > 0 e < 0
Jones matrix J describes the transformation
of the Jones vector by the interaction of
the polarized light with an object
iny
inx
yyyx
xyxx
outy
outx
E
E
JJ
JJ
E
E
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H V 45° -45° Left C Right C Elliptical
Correlation matrix of 2 complex components of electric field
Stokes formalism y
x
θ
ε
Partially polarized light
• « disordered » motion of the electric field vector
• only probability distribution of E can be defined
Linear optics (intensity measurements)
• only the second moments of the probability distribution of E are relevant
**
**
yyxy
yxxx
EEEE
EEEEC
Stokes vector
**
**
**
**
3
2
1
0
xyyx
xyyx
yyxx
yyxx
RL
4545
yx
yx
EEEEj
EEEE
EEEE
EEEE
II
II
II
II
V
U
Q
I
S
S
S
S
S
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Degree of polarization
)10(
I
VUQ 222
Coherence vector
Tyyxyyxxx EEEEEEEE ),,,(' ****C
in
in
in
in
out
out
out
out
S
S
S
S
MMMM
MMMM
MMMM
MMMM
S
S
S
S
3
2
1
0
44434241
34333231
24232221
14131211
3
2
1
0
Sin Sout
M
Sout=M·Sin
Linear optical system is characterized by the real
4×4 matrix which is called Mueller matrix
Stokes formalism: Mueller matrix
Mueller matrix M
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General principle of any polarimetric technique
Source
PSG
Sample
PSA Detector
• In order to determine optical properties of the sample one needs to measure
polarization changes occurring in the probing beam light after interaction with the
sample.
• Initial polarization state of the beam is defined by Polarization State Generator
(PSG). The output state is analyzed by Polarization State Analyzer (PSA)
followed by a detector, according to the general schema outlined above.
• Typically, the incident polarizations defined by the PSG and those detected by
the PSA may vary during a given experiment.
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Interpretation of Mueller matrices
So what to do when a model is not readily available?
Experimental Mueller matrix
EM model relating the physical properties of measured structure to M
Classic physical approach
Phenomenological approach
Experimental Mueller matrix
M1 M2
M3
Lu-Chipman product decomposition represent any depolarizing M as a series combination of three basic blocks: diattenuator, retarder and depolarizer
M = MΔ MR MD 9
…..
S. Y. Lu R. Chipman, JOSA A 13(5) 1106 (1996)
Mueller matrix imaging polarimeter
Multi-spectral visible wavelength Mueller matrix imaging system installed and tested at IMM Anatomopathology Department, Paris, France
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Cancer evolution
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Source: http://www.ndhealthfacts.org/wiki/Oncology_%28Cancer%29
Epithelial cancer > 80%
• Epithelial tissues line the cavities and surfaces of organs throughout the body
• Epithelial layers contain no blood vessels, so they receive nourishment via
diffusion of substances from the underlying connective tissue
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Colon specimens: early stage cancer
Colon
Cancer
Healthy
tissue
Mueller matrix images taken at 550 nm
Common features
•Mueller matrices are diagonal :
tissues exhibit depolarization, wihout
signifiant retardation nor diattenuation
•M22=M33>M44, meaning that circularly
polarized light is more depolarized
than linearly polarized light. This
behaviour is typical of « small »
scatterers (Rayleigh regime)
•Depolarization increases with
wavelength in the visible, probably
due to decrease of absorption
•Tumoral tissue is less depolarizing
than healthy tissue, at all wavelenghts
from 500 to 700 nm. T. Novikova et al., OPN, OSA, October 2012
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5 c
m
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p:/
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/in
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Normal CIN I CIN II CIN III
Larger
and
more dense
nuclei!!
Histological
slides
of cervical
tissue
Cervical
Intraepithelial
Neoplasia
Diagnosis of cervical cancer
300 µm
• Cervical cancer is the second most frequent cancer affecting women, and causes 275 000 deaths per year worldwide mostly in developing countries
.
• In the vast majority (95 to 98%) of cases the disease is due to infection by various types of Human Papillomavirus (HPV)
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(Medical diagnostic procedure
to examine an illuminated,
magnified view of the cervix)
(Cytology) (Histology)
Diagnosis of cervical cancer
Colposcopy: Precancerous (CIN2+) lesions are very difficult to visualize. Results are very operator dependent.
Conization : the surgical margins are poorly defined
Screening : Systematic Pap smear cannot be implemented in low income countries.
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Polaimetric images of cervical specimens 2 c
m
Intensity image
A. Pierangelo et al., Opt. Express 21 (12), 14120 (2013)
Mueller matrix images of uterine cervix
Pathology map
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Lu Chipman product decomposition M = MΔ MR MD
Ex vivo images of uterine cervix specimen
A. Pierangelo et al., Opt. Express 21 (12), 14120 (2013)
Depolarization @500nm Pathology map Scalar retardance @500nm
Healthy
CIN3
Healthy
CIN3
Healthy
CIN3
50°
0°
1
0
(a) (b) (c)
2 c
m
• Intensity and polarimetric images of a healthy cervix (the positions of histological cuts, which confirmed that the sample was healthy, are shown with white lines)
Depolarization @550nm
Intensity image
Scalar birefringence @550nm
Ex vivo images of fresh cervical specimen
A. Pierangelo et al., Opt. Express 19 (2), (2011) 17
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Typical experimental trends
• Healthy cervical tissue exhibits a significant birefringence
• Birefringence disappears already at stage CIN1
• Depolarization values: glandular < CIN3 < CIN2 < CIN1 <
healthy squamous epithelium
Ex-vivo studies of fixed cervical specimens
Mueller matrix
Fixed conization
specimen
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17 patients
Tag Type of tissue
HSE Healthy squamos epitelium
SEM Squamous epithelium metaplasia
GE Glandular epithelium
CIN1 Cervical intraepitelial neoplasia (mild)
CIN2/3 Cervical intraepitelial neoplasia (moderate-severe)
Histological diagnosis mapping
CIN1
CIN2/3
HSE
SEM
GE
Scalar retardance (550nm)
Conization specimen
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Sensitivity and specificity
Test of MP technique with gold standard histological diagnosis
Disease No disease
Postive test TP FP
Negative test FN TN
Se = 𝑇𝑃
𝑇𝑃 + 𝐹𝑁 Sp =
𝑇𝑁
𝑇𝑁 + 𝐹𝑃
Ability of test technique to correctly detect disease
Classical colposcopy: Se~60-70%
Ability of test technique to correctly detect healthy conditions
Classical colposcopy: Sp < 50%
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Scalar retardance treshold = 5°
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First statistical evaluation
Scalar retardance treshold = 10°
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First statistical evaluation
Scalar retardance treshold = 15°
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First statistical evaluation
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Scalar retardance treshold = 20°
First statistical evaluation
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Scalar retardance treshold = 25°
First statistical evaluation
J. Rehbinder et al J. Biomed. Opt. 21(7) (2016) 27
First statistical evaluation
AUC = 0.9
Conclusions
• Enhancement of contrast between healthy and cancerous zones on polarimetric images using Lu-Chipman decomposition of Mueller matrices
• Light is mainly backscattered by small scatterers in our experiments
• Dumping of scattering and increase of absorption better preservation of backscattered light polarization from cancerous zone
• Depolarizing and birefringent healthy uterine cervix
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T. Novikova et al., OPN, OSA, October 2012
Thank you for your attention
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Acknowledgement for funding: • PAIR Gyneco project of INCa • French ANR TWIST4NET project • CampusFrance POLHIS project
Dr Tatiana Novikova gratefully achowledges the sponsorship of OSA Traveling Lecturer Program