Conference PaperPDF Available

Near infrared light interaction with lung cancer cells

Authors:
  • Echonous Inc

Abstract

The objective of this study is to explore the phenomenology of near infrared (NIR) light interaction with healthy and early-lung cancer by combining efficient polarimetric backscattering detection techniques with Polarimetric Exploratory Data Analysis (pEDA). Preliminary results indicate that enhanced discrimination signatures can be obtained for certain types of lung cancers.
Near Infrared Light Interaction with Lung Cancer
Cells
G.C. Giakos [1]-[2], S. Marotta [2], C. Narayan [2], J.
Petermann [1], S. Sestra, D. Pingili [1], S. A.
Tsokaktsidis [1], D.B. Sheffer [1], and W. Xu [1]
[1] Department of Electrical and Computer
Engineering
[2] Department of Biomedical Engineering
The University of Akron
Akron, Ohio 44325
USA
e-mail:giakos@uakron.edu
M. Zervakis [3], G. Livanos [3], M. Kounelakis [3]
Department of Electronic and Computer Engineering
Technical University of Crete
Chania 73100, Greece
e-mail: michalis@display.tuc.gr
Abstract— The objective of this study is to explore the
phenomenology of near infrared (NIR) light interaction with
healthy and early-lung cancer by combining efficient
polarimetric backscattering detection techniques with
Polarimetric Exploratory Data Analysis (pEDA). Preliminary
results indicate that enhanced discrimination signatures can be
obtained for certain types of lung cancers.
Keywords-lung cancer; early detection and enhanced
discrimination; physical phenomenology of polarized light with
cancer tissue pathologies; Polarimetric Exploratory Data Analysis
(pEDA)
I. INTRODUCTION
The purpose of this study is to develop efficient and reliable
techniques that would lead to an early identification and
discrimination of precancerous and cancerous lung pathologies
so that to lead to accurate diagnosis and efficient treatment of
lung cancer.
Early detection of lung cancer is of paramount
significance. Latest multi-year trials revealed that low-dose
spiral computed tomography (CT) can be promising modality
for lung cancer screening. However, spiral CT is limited for
detecting small peripheral lesions. On the other hand, heavy
smokers develop tumors located in the central airways; as
result, other techniques besides CT are needed for early
detection. For instance, squamous cell carcinoma of the central
airway is thought as a multistep process starting from a
squamous metaplasia which progresses to dysplasia, followed
by carcinoma in situ (CIS), finally, progressing to invasive
cancer [1]-[4].
Central tumors are generally squamous cell carcinomas, while
most peripheral tumors are adenocarcinomas or large cell
carcinomas are peripherally located. Because of their
peripheral location, adenocarcinomas may not call attention to
themselves until they have developed extrathoracic
metastases. For example, patients may present with clinical
signs of bone spread or intracranial metastatic disease.
1) Non-small cell lung cancer (NSCLC)
NSCLC accounts for about 80% of lung cancers. There are
different types of NSCLC, including:
1) Adenocarcinoma. This is the most common type of
NSCLC (about 40%). This cancer is comprised of
cells that excrete mucus and occurs mostly at the
periphery of the lung. It can be divided into four
categories:
xAcinar
xBronchoalveolar
xMucus-secreting
xPapillary
Because of their peripheral location, adenocarcinomas may
stay unobserved until they have developed extrathoracic
metastases.
1. Squamous cell carcinoma. This is the second most
common type of NSCLC. It forms in the trachea and
bronchi and exhibits a remarkable dose-dependence
with cigarette smoking.
2. Large-cell carcinoma (about 10% of all lung
cancers). This cancer grows rapidly near the surface,
or outer edges, of the lungs.
2) Small cell lung cancer (SCLC)
SCLC accounts for about 10-15% of all lung cancers. They
usually grow on the bronchial tree, but they mostly stay on the
lung side of the bronchus rather than growing in the airway.
Although the cells are small, they multiply quickly and form
large tumors that can spread throughout the body. Smoking is
almost always the cause of SCLC. Due to the rapid spread of
978-1-4244-7935-1/11/$26.00 ©2011 IEEE
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g
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rmation relat
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mical inform
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[5]-[15].
a
ncer, localiz
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is rarely a sin
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n of non-sm
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r
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oscopic tech
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scopy with p
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pecific meth
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epithelial cel
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ned and the
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epithelial cel
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h
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e
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attering char
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l
arized illumi
n
t
ered light wa
s
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flectance spe
c
a
ntitative mor
p
y
be used f
o
e
s [2].
m
bining both
e
ndent metho
d
T
he outcome o
n
scattering i
scatterers bei
n
e
althy cells c
o
highlights th
e
cal tissue dia
g
f
wavelength
-
cattering mea
s
c
ation of cult
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ectroscopy,
p
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ar discrimin
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ent patholog
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xcitation lase
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other hand
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unique adva
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assification p
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m
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ge conditions
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e structure
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ologies that
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vasive stage.
epithelial cel
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o
larized light
h
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dology, sing
l
l
s and multipl
index of ref
r
l
s were assess
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thod for sele
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cteristics of
e
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ation and pol
a
s
presented. T
h
c
troscopy wit
h
p
hological in
f
o
r non-invasi
v
wavelength-
d
d
s changes i
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f that study re
v
s attributed
t
n
g a few tens
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mpared with
e
significance
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nostic metho
d
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dependent an
d
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urements to c
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red human l
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p
rincipal co
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at
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g
cells, along
w
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w
r
at 532 nm [
4
,
polarimetri
c
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oblems, due
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high-specifici
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,
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racterization
o
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ancer (NSC
L
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tilize white li
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p
p
tical cohere
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hance the abi
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y scattered li
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action and s
i
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tive detection
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pithelial cells
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rization sensit
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ormation wh
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ependent an
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light scatte
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ealed that th
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t
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e
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of developin
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e
d
polarizatio
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e
ll morpholog
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ng cancer c
e
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ponent anal
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(LDA). Ra
m
w
ith four can
c
w
ere successf
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4
].
c
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e
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d
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iological me
d
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same insta
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n
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o
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C)
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i
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r
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er
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ce
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heno
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Polari
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ossib
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rogre
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adenoc
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resen
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Fig. 1
D
outcome
A. Mu
Th
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total o
f
in the
s
using t
h
Specif
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ࡹൌ
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ing efficient
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etric Explora
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tissue, carcin
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e
o
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d
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e. In Fig. 1,
s
sion of diseas
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Most periph
arcinomas.
B
arcinoma ma
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ed extrathora
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a
tic disease
D
iagram highlight
i
of this study
II. T
H
eller Matrix
D
e
full Mueller
m
f
16 polarizati
o
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ample. The ac
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r
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r matrices of t
h
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t
i
ve of this
n
ear infrared (
N
l
ung cancer
polarimetric
t
ory Data An
a
comparing
d
o
ma in situ (p
r
o
f the applie
d
e
d discrimina
t
d
etect and iden
t
stages so th
a
a diagram hi
g
e
and the outc
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eral tumors ar
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B
ecause of
t
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g
c
ic metastases
.
l signs of b
o
i
ng the lung-canc
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H
EORETICA
L
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ecomposition
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atrices were
c
o
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quired polari
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trix decompos
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ured Mueller
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N
IR) light int
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h
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lysis (pEDA),
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etected signa
t
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ify early eno
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me of this stu
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.
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e
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FORMALIS
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etric data wer
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ition techniqu
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n
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e
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raction with
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proposed by
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o
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patients may
r
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M
m
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n
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Th
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at
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is i
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h
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e
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D
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t
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s of enha
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criptors, in t
h
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cer detection
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h
ology, drug
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referring to F
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troduced as
ܴ
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2 Histogram of
p
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0
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0.01
0.015
0.02
0.025
0.03
0.035
0.04
0.045
0.05
Hist o
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Normal
r
the linear bir
e
h
e effects of li
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h
ese matrices
o
n characterist
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o
n is quantifie
d
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ng to:
ͳെ
σ
೔ೕ
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ି
ξ
Mueller matri
x
l
oratory Data
A
olarimetric m
e
a
rimetric Expl
o
c
ed [11]. Th
i
a
cteristics of
t
ed or backsc
a
n
ced contrast
h
e areas of
m
,
characteriza
t
d
elivery, and r
e
i
g. 2, a new de
ʹ
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ʹ
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h
at half maxi
m
ݒ
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p
olarimetric data
fi
380 390
Amplit ude (mV)
Carcinoma In-Sit u Lung Ti
s
g
ram of Data fit with Normal
e
nfringence a
n
n
ear and circu
l
the diattenu
a
i
cs of the me
d
d
in terms of t
h
ି
బబ
(
2
x
elements.
A
nalysis (pE
D
e
trics definiti
o
o
ratory Data
A
i
s metrics is a
i
transmitted
o
a
ttered throug
h
and potent
i
m
olecular bi
o
ion and diffe
r
e
mote sensing.
finition of dy
n
(
4
(
5
m
um is given a
s
݊ʹߪ ؄ ʹǤ͵ͷ
Ͷ
fi
tting on a Gaussi
a
400 410 42
0
s
sue
Distribut ion
n
d optical activ
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ar dichroism.
a
tion, retardan
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ium are rea
d
h
e depolarizat
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2
)
D
A)
o
n is introduc
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A
nalysis (pE
D
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med to quant
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r backscatte
r
h
/from media
i
al discrimin
a
o
photonics, e
a
r
entiation, tis
s
n
amic range (
D
(3)
4
)
5
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s
:
Ͷ
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a
n
i.
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ity
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ily
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on
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ify
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ed
in
a
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rly
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R)
Theref
o
within
ߪൌ
ி
ଶǤ
A. A. Cal
i
consist
B. Opt
i
optimi
z
p
olari
m
C. Cal
i
calibra
t
[12].
B
p
resen
c
corres
p
oscillo
s
obtain
e
angle
incide
n
transm
i
rotated
observ
e
p
olariz
values
P1 an
d
said to
oriente
minim
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p
erpen
d
Fig. 3 T
h
D. C
a
m
a
T
h
p
olariz
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r
o
re, the centr
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a standard de
v
ுெ
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III. EXP
E
i
bration Proce
d
A three-st
e
ing of the foll
o
i
cal
s
ystem ali
g
The align
m
z
ed so that to
m
etric quantiti
e
i
bration of the
p
The polari
z
t
ed applying t
h
B
y rotating th
c
e of the a
n
p
onding inten
s
s
cope. The an
g
e
d was marke
d
such that it
n
t light. Keepi
n
i
ssion angle, t
h
from 0
o
to
e
d on the o
s
er P2 at whic
were obtaine
d
d
P2 are orien
t
be co-
p
olariz
e
d for maxim
u
u
m transmissi
o
d
icular to eac
h
h
e experimental ar
r
a
libration usi
n
a
trix (Accurac
y
h
e Mueller m
a
ers and retar
d
r
ing their
m
o
id of Gaussi
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iation:
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E
RIMENTAL
M
d
ures
e
p calibratio
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o
wing steps:
g
nmen
t
m
ent of the
minimize err
o
e
s.
p
olarizers
z
ers and retar
h
e methodolo
g
e transmitter
n
alyzer polari
z
s
ity variation
s
g
le at which t
h
d
and the pol
a
allows maxi
m
n
g the polariz
e
h
e analyzer po
360
o
and the
s
cilloscope.
T
h the maxim
u
d
were marke
d
t
ed for maxi
m
e
d or parallel t
o
u
m transmissi
o
o
n, they are s
a
h
other.
r
angement for cal
i
n
g known ta
r
y
Test).
a
trix of the
k
d
ers were exp
m
odulated int
e
an peak can
b
(7)
M
ETHODOL
O
n
procedure
polarimeter
o
rs in the esti
m
ders of our
s
g
ies described
polarizer, P1,
z
er from 0
o
s
were obse
r
h
e maximum
i
a
rizer P1 was
m
um transmi
s
e
r P1 fixed at t
h
larizer P2 was
intensity va
r
T
he orientatio
n
u
m and mini
m
d
. When both
t
m
um transmiss
o
each other a
n
o
n and P2 is
a
id to be cros
s
i
bration of the pol
a
r
gets with kn
o
k
nown targets
erimentally d
e
e
nsities, usin
g
b
e estimated
O
GY
took place
system was
m
ation of the
s
ystem were
in [5], [10],
without the
to 360
o
the
r
ved on the
i
ntensity was
fixed at that
s
sion of the
h
e maximum
inserted was
r
iations were
n
angles of
m
um intensity
t
he polarizers
ion, they are
n
d when P1 is
oriented for
s
-polarized or
a
rizers
o
wn Mueller
such as air,
e
termined by
g
both two
est
a
Re
t
Re
d
res
p
ex
p
tar
g
p
lo
est
i
Ro
t
int
e
M
u
M
M
wh
M
M
Fig.
the
g
B.
I
n
t
W
a
un
d
ex
p
no
r
sta
g
n
m
50
0
sys
b
r
a
78
5
ge
n
lin
e
at
0
ini
t
NormalizedI ntensities (V)
a
blished me
t
t
arder metho
d
d
uction Tech
p
ective ideal
m
p
erimentally o
b
g
et, in this c
a
t
t
ed in Fig. 4.
i
mated using
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ating Retard
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u
eller matrix o
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)( IDEALLHP
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ile the experi
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4 Comparison of
g
enerator retarder
t
errogation of
a
ves- Circularl
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The opt
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er backscatt
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eriment, thre
r
mal lung tissu
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e I carcinom
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, soli
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-state la
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MHz using
em containe
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nch and a po
l
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nm laser
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erating branc
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ar polarizer P
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), so that th
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ial polarizatio
n
020 40
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c
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hodologies,
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[10] and
nique” [5],
m
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tained modul
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se a linear h
o
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using a) Li
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r method [
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zontal polarizer
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the present st
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, shown in
u
ng tissues
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carcinoma in
s
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ted Intensities
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s
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a
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trix of LHP
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[5] and Du
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ar results.
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trix is,
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during calibratio
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nearly Polari
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Fig. 5. In t
h
w
ere studied:
s
itu (CIS); an
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er. The imag
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consist
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geome
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i
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n
sm
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r pulses were
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en backscatte
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ing of a qua
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in front a Ne
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nder collin
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and Matlab
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ircularly pol
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e
EXPERIME
N
n
g the exp
e
a
ttered signa
c
erous tissue
(
were obtaine
d
t
ry.
i
stological d
e
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d in these exp
e
n
g Carcinoma
a
ll cell lung
c
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amous featur
e
c
ified, fib
r
r
ring. Resecti
o
u
carcinoma.
The experimenta
l
transmitted th
r
ancer tissue
g
r
ed in the dir
e
r
te
r
-wave ret
a
polarizer P2
(
w
Focus 2151
a
s 1 mm diame
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ivalent powe
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o
n gain of
A
/W. Optical
m
e
ar (co-
p
olar
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c
onfiguration.
histograms
w
Wave Anal
y
s
ubroutines. I
n
a
rized waves
a
e
rence to Figs.
N
TAL
RESUL
T
e
rimental arr
a
l contributio
n
(
carcinoma n
s
d
under copo
e
scription of
e
riments is the
In Situ (CIS):
c
arcinoma(NS
C
e
s, apparently
r
otic nodu
l
o
n margin de
m
l
arrangement
r
ough the gen
e
g
lass slide arr
a
e
ction of the
a
a
rder R
2
, aga
i
(
parallel to P
1
femtowatt p
ter aperture a
n
r
(NEP) 15
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, an
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easurements
w
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r
The acquire
d
w
ere then reco
y
zer, then pro
c
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deed, preli
m
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re described
a
10-11.
T
S
AND
DISC
U
a
ngement of
n
s from he
a
s
itu) and stag
e
larized and c
r
t
he lung ca
n
following:
Poorly diffe
r
C
LC), with
g
arising in ass
o
l
es and
m
onstrates pa
t
e
rator system
a
y. The light
a
nalyzer arm
i
n set at 0
0
,
1
) which was
hotodetector.
n
d exhibits an
fW/Hz
1/2
, a
d
a typical
w
ere obtained
r
osspolarized
d
waveforms
rded using a
c
essed using
m
inary results
a
t the end of
U
SSION
Figure 5,
a
lthy tissue,
e
I cancerous
r
osspolarized
n
cer samples
r
entiated non
g
landular and
o
ciation with
sub-plueral
t
chy, focal in
B. Stage I Lung Carcinoma: Non-small cell lung carcinoma
(NSCLC)-adenocarcinoma with papillary
bronchioloalveolar pattern, T1, N0, G2.
Both types of cancers are not invasive.
At first place, repeatability experiments took place
aimed at assessing the stability of the polarimetric system.
In Fig. 6 and 7, repeated measurements of detected
amplitudes of backscattered signal contributions under
copolarized and crosspolarized geometries are reported. A
comparison between mean backscattered signal amplitudes
for both geometries is shown in Fig. 8. In Fig. 9, the degree
of linear polarization (DOLP) between normal lung tissue,
stage I lung carcinoma, and glass (reference material) is
shown. The DOLP has been estimated based on Eq. 8
where the tissue contributions are normalized with respect
to the glass.
Fig. 6 Normal versus stage I Lung Tissue
Amplitude (under copolarized geometry)
Fig. 7 Normal versus Stage I Carcinoma Lung Tissue
Amplitude (under crosspolarized Geometry)
Fig. 8 Mean amplitude comparison among different tissue pathologies
(collinearly polarized light)
Fig. 9 Degree of Linear Polarization (DOLP) comparison between stage I and
normal lung cancer tissue
(8)
By applying the Mueller matrix decomposition
technique described in Section II.A, the intensities of a total of
sixteen 1-d Mueller matrix elements imaging signals for
different samples are shown.
Fig. 10 Depolarization Mueller matrix elements for different lung tissue
pathologies
0
50
100
150
200
250
300
350
400
12345
DetectedAmplitude(mV)
MeasurementNumber
Normal Mean
Amp.
StageI Mean
Amp.
Glass Mean
Amp
0
10
20
30
40
50
60
70
123
DetectedAmplitude(mV)
MeasurementNumber
Normal Mean
Amp.
StageI Mean
Amp.
Glass Mean
Amp.
0
100
200
300
400
Copolarized Crosspolarized
MeanAmplitude
(mV)
Normal
StageI
Glass
0.0000
0.2000
0.4000
0.6000
Normal StageI
DOLP
0.4
0.2
0
0.2
0.4
0.6
0.8
1
1.2
m11
m12
m13
m14
m21
m22
m23
m24
m31
m32
m33
m34
m41
m42
m43
m44
NormalLung CarcinomaInSitu
StageICarcinoma
glass
sample
glassII
sampleII
glass
sample
glassII
sampleII
I
I
I
I
I
I
I
I
DOLP
_
_
_
_
_
_
_
_
A
A
A
A
Following the treatment of Section 2.B the dynamic range of
histograms fitted on a normal distribution are plotted for
different samples is shown in Fig. 11.
Fig. 11 Dynamic range of histograms fitted to Gaussians for different lung
tissue pathologies (glass serves as reference)
The experimental findings of this study supports the
observation trends of other studies on different types of
cancer, like oral and colon cancers, that early cancerous
lesions depolarize light less than healthy tissues [14]-[15].
This statement should be applied with cautiousness as
applicable only for certain types of cancers, because of the
diverse histological, morphological and molecular information
exhibited by different cancer types. The depolarization
Mueller matrix elements for different lung cancer tissue
pathologies indicate that enhanced discrimination among
different lung cancer is obtained through circularly type
polarized waves rather than linearly polarized waves; these
experimental data are supported by sound statistics as shown
in a companion paper. The dynamic range metrics is
proportional to the degree of polarization of light.
V. CONCLUSION
The phenomenology of light interaction with lung cancer
cells was presented. The outcome of this preliminary study
highlights the importance of polarized light interrogation of
lung cancer tissues as an indispensible diagnostic tool aimed at
enhancing the early detection and discrimination potential
among different lung cancer types. Further research is in
process in order to assess, identify, and classify different types
of early lung cancers with high accuracy, specificity, and low-
false alarm rate.
VI. REFERENCES
[1] V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R.R. Dasari, L.T.
Perelman, M.S. Feld, “Polarized light scattering spectroscopy for quantitative
measurement of epithelial cellular structures in situ”, IEEE Journal on
Selected Topics in Quantum Electronics, vol. 5 Issue, 4, 1019 – 1026, 2002.
[2] K. Sokolov, R. Drezek, K. Gossage, and R. Richards-Kortum,
"Reflectance spectroscopy with polarized light: is it sensitive to cellular and
nuclear morphology," Opt. Express 5, 302-317 (1999).
[3] J. R. Mourant, A. H. Hielscher Ph.D., A. A. Eick B.S., T. M. Johnson, J. P.
Freyer , “Evidence of intrinsic differences in the light scattering properties of
tumorigenic and nontumorigenic cells”, Cancer Cytopathology, Vol. 84, Issue
6, pages 366–374, 1998.
[4] A. Gakuin, “Discrimination analysis of human lung cancer cells associated
with histological type and malignancy using Raman spectroscopy”, J. Biomed.
Opt., Vol. 15, 2010.
[5] R.A. Chipman, Polarimetry Handbook of Optics. 2
nd
Ed. McGraw-Hill,
New York. Vol. 2, Ch. 22, 1995.
[6] G. C. Giakos, Multifusion Multispectral Lightwave Polarimetric Detection
Principles and Systems, IEEE Transactions on Instrumentation and
Measurement, vol. 55, no. 6, pp. 1904-1912, 2006.
[7] R.M.A. Azzam, “Photopolarimetric measurement of the Mueller matrix by
Fourier analysis of a single detected signal”, Optics Letters, Vol.2, No.6,
pp.148-150, June1978.
[8] D. H. Goldstein, “Mueller matrix dual-rotating retarder polarimeter,”
Applied Optics, 31, 31, pp 6676-6683, 1992.
[9] M.H. Smith, “Optimization of a dual-rotating–retarder Mueller matrix
Polarimeter”, Applied Optics, Vol. 41, No. 13, May 2002.
[10] D. B. Chenault, J. L. Pezzaniti, and R. A. Chipman, “Mueller matrix
algorithms,” SPIE Polarization Analysis and Measurement, 1746, pp 231-246,
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[11] G. C. Giakos, “Novel Biological Metamaterials, Nanoscale Optical
Devices and Polarimetric Exploratory Data Analysis (pEDA),” Int. J. Signal
and Imaging Systems Engineering, Vol 3, No 1, pp 3-12, 2010.
[12] G.C. Giakos, K. Valluru, K. Ambadipudi, S. Paturi, P. Bathini, M.
Becker, P. Farajipour, S. Marotta, J. Paxitzis, B. Mandadi , Stokes Parameters
Imaging of Multi-index of Refraction Biological Phantoms utilizing Optically
Active Molecular Contrast Agents, Measurement Science and Technology,
Institute of Physics (IOP), vol. 20, 2209, pp. 1-12, September 2009.
[13] S. Lu and R. A. Chipman, “Interpretation of Mueller matrices
based on polar decomposition,” J. Opt. Soc. Am. A 13, 1106–1113, 1996.
[14] Antonelli M.-R., Pierangelo, A., Novikova, T., Validire, P., Benali, A.,
Gayet, B., et al., “Mueller matrix imaging of human colon tissue for
cancer diagnostics: how Monte Carlo modeling can help in the interpretation
of experimental data”, Optics express, vol. 18(10), pp. 10200-8, 2010
[15] J. Chung, W. Jung, M.J. Hammer-Wilson, P. Wilder-Smith, and Z. Chen,
“Use of polar decomposition for the diagnosis of oral precancer”, Applied
Optics, vol. 46(15), pp. 3038-45, 2007.
0.1000
0.1200
0.1400
0.1600
0.1800
0.2000
Glass Normal InSitu StageI
D.R.(dB)
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