To develop and evaluate the clinical application of a multimodal colposcopy combining multispectral reflectance, autofluorescence, and red, green, blue (RGB) imaging for noninvasive characterization of cervical intraepithelial neoplasia (CIN). We developed a multimodal colposcopy system that combined multispectral reflectance, autofluorescence, and RGB imaging for noninvasive characterization of CIN. We studied the optical properties of cervical tissue first; then the imaging system was designed and tested in a clinical trial where comprehensive datasets were acquired and analyzed to differentiate between squamous normal and high grade types of cervical tissue. The custom-designed multimodal colposcopy is capable of acquiring multispectral reflectance images, autofluorescence images, and RGB images of cervical tissue consecutively. The classification algorithm was employed on both normal and abnormal cases for image segmentation. The performance characteristics of this system were comparable to the gold standard histopathologic measurements with statistical significance. Our pilot study demonstrated the clinical potential of this multimodal colposcopic system for noninvasive characterization of CIN. The proposed system was simple, noninvasive, cost-effective, and portable, making it a suitable device for deployment in developing countries or rural regions of limited resources.

References

1.
Thekkek
,
N.
, and
Richards-Kortum
,
R.
,
2008
, “
Optical Imaging for Cervical Cancer Detection: Solutions for a Continuing Global Problem
,”
Nat. Rev. Cancer
,
8
(
9
), pp.
725
731
.
2.
Parkin
,
D. M.
,
Bray
,
F.
,
Ferlay
,
J.
, and
Pisani
,
P.
,
2005
Global Cancer Statistics, 2002
,”
CA-Cancer J. Clin.
,
55
(
2
), pp.
74
108
.
3.
Drezek
,
R. A.
,
Richards-Kortum
,
R.
,
Brewer
,
M. A.
,
Feld
,
M. S.
,
Pitris
,
C.
,
Ferenczy
,
A.
,
Faupel
,
M. L.
, and
Follen
,
M.
,
2003
, “
Optical Imaging of the Cervix
,”
Cancer
,
98
(S9), pp.
2015
2027
.
4.
Orfanoudaki
,
I. M.
,
Kappou
,
D.
, and
Sifakis
,
S.
,
2011
, “
Recent Advances in Optical Imaging for Cervical Cancer Detection
,”
Arch. Gynecol. Obstet.
,
284
(
5
), pp.
1197
1208
.
5.
Tan
,
J. H. J.
, and
Wrede
,
C. D. H.
,
2011
, “
New Technologies and Advances in Colposcopic Assessment
,”
Best Pract. Res. Clin.: Obstet. Gynecol.
,
25
(
5
), pp.
667
677
.
6.
Freeberg
,
J. A.
,
Serachitopol
,
D. M.
,
McKinnon
,
N.
,
Price
,
R.
,
Atkinson
,
E. N.
,
Cox
,
D. D.
,
MacAulay
,
C.
,
Richards-Kortum
,
R.
,
Follen
,
M.
, and
Pikkula
,
B.
,
2007
, “
Fluorescence and Reflectance Device Variability Throughout the Progression of a Phase II Clinical Trial to Detect and Screen for Cervical Neoplasia Using a Fiber Optic Probe
,”
J. Biomed. Opt.
,
12
(
3
), p.
034015
.
7.
Balas
,
C.
,
2001
, “
A Novel Optical Imaging Method for the Early Detection, Quantitative Grading, and Mapping of Cancerous and Precancerous Lesions of Cervix
,”
IEEE Trans. Biomed. Eng.
,
48
(
1
), pp.
96
104
.
8.
Mirabal
,
Y. N.
,
Chang
,
S. K.
,
Atkinson
,
E. N.
,
Malpica
,
A.
,
Follen
,
M.
, and
Richards-Kortum
,
R.
,
2002
, “
Reflectance Spectroscopy for In Vivo Detection of Cervical Precancer
,”
J. Biomed. Opt.
,
7
(
4
), pp.
587
594
.
9.
Arifler
,
D.
,
MacAulay
,
C.
,
Follen
,
M.
, and
Richards-Kortum
,
R.
,
2006
, “
Spatially Resolved Reflectance Spectroscopy for Diagnosis of Cervical Precancer: Monte Carlo Modeling and Comparison to Clinical Measurements
,”
J. Biomed. Opt.
,
11
(
6
), p.
064027
.
10.
Zheng
,
W.
,
Wang
,
C.
,
Chang
,
S.
,
Zhang
,
S.
, and
Xu
,
R. X.
,
2015
, “
Hyperspectral Wide Gap Second Derivative Analysis for In Vivo Detection of Cervical Intraepithelial Neoplasia
,”
J. Biomed. Opt.
,
20
(
12
), p.
121303
.
11.
Drezek
,
R.
,
Sokolov
,
K.
,
Utzinger
,
U.
,
Boiko
,
I.
,
Malpica
,
A.
,
Follen
,
M.
, and
Richards-Kortum
,
R.
,
2001
, “
Understanding the Contributions of NADH and Collagen to Cervical Tissue Fluorescence Spectra: Modeling, Measurements, and Implications
,”
J. Biomed. Opt.
,
6
(
4
), pp.
385
396
.
12.
Drezek
,
R.
,
Brookner
,
C.
,
Pavlova
,
I.
,
Boiko
,
I.
,
Malpica
,
A.
,
Lotan
,
R.
,
Follen
,
M.
, and
Richards-Kortum
,
R.
,
2001
, “
Autofluorescence Microscopy of Fresh Cervical-Tissue Sections Reveals Alterations in Tissue Biochemistry With Dysplasia
,”
Photochem. Photobiol.
,
73
(
6
), pp.
636
641
.
13.
Pavlova
,
I.
,
Sokolov
,
K.
,
Drezek
,
R.
,
Malpica
,
A.
,
Follen
,
M.
, and
Richards-Kortum
,
R.
,
2003
, “
Microanatomical and Biochemical Origins of Normal and Precancerous Cervical Autofluorescence Using Laser-Scanning Fluorescence Confocal Microscopy
,”
Photochem. Photobiol.
,
77
(
5
), pp.
550
555
.
14.
Zheng
,
W.
,
Lau
,
W.
,
Cheng
,
C.
,
Soo
,
K. C.
, and
Olivo
,
M.
,
2003
, “
Optimal Excitation-Emission Wavelengths for Autofluorescence Diagnosis of Bladder Tumors
,”
Int. J. Cancer
,
104
(
4
), pp.
477
481
.
15.
Schomacker
,
K. T.
,
Meese
,
T. M.
,
Jiang
,
C.
,
Abele
,
C. C.
,
Dickson
,
K.
,
Sum
,
S. T.
, and
Flewelling
,
R. F.
,
2006
, “
Novel Optical Detection System for In Vivo Identification and Localization of Cervical Intraepithelial Neoplasia
,”
J. Biomed. Opt.
,
11
(
3
), p.
34009
.
16.
Ren
,
W.
,
Gan
,
Q.
,
Wu
,
Q.
,
Zhang
,
S.
, and
Xu
,
R.
,
2015
, “
Quasi-Simultaneous Multimodal Imaging of Cutaneous Tissue Oxygenation and Perfusion
,”
J. Biomed. Opt.
,
20
(
12
), p.
121307
.
17.
Zhang
,
S.
,
Gnyawali
,
S.
,
Huang
,
J.
,
Ren
,
W.
,
Gordillo
,
G.
,
Sen
,
C. K.
, and
Xu
,
R.
,
2015
, “
Multimodal Imaging of Cutaneous Wound Tissue
,”
J. Biomed. Opt.
,
20
(
1
), p.
016016
.
18.
Milbourne
,
A.
,
Park
,
S. Y.
,
Benedet
,
J. L.
,
Miller
,
D.
,
Ehlen
,
T.
,
Rhodes
,
H.
,
Malpica
,
A.
,
Matisic
,
J.
,
Van Niekirk
,
D.
,
Atkinson
,
E. N.
,
Hadad
,
N.
,
Mackinnon
,
N.
,
Macaulay
,
C.
,
Richards-Kortum
,
R.
, and
Follen
,
M.
,
2005
, “
Results of a Pilot Study of Multispectral Digital Colposcopy for the In Vivo Detection of Cervical Intraepithelial Neoplasia
,”
Gynecol. Oncol.
,
99
(
3
), pp.
S67
S75
.
19.
Gustafsson
,
U. P.
,
McLaughlin
,
E.
,
Jacobsen
,
E.
,
Hakansson
,
J.
,
Troy
,
P.
,
DeWeert
,
M. J.
,
Svanberg
,
K.
,
Palsson
,
S.
,
Thompson
,
M. S.
, and
Svanberg
,
S.
,
2003
, “
In-Vivo Fluorescence and Reflectance Imaging of Human Cervical Tissue
,”
Proc. SPIE
,
5031
, pp.
521
530
.
20.
Redden Weber
,
C.
,
Schwarz
,
R. A.
,
Atkinson
,
E. N.
,
Cox
,
D. D.
,
Macaulay
,
C.
,
Follen
,
M.
, and
Richards-Kortum
,
R.
,
2008
, “
Model-Based Analysis of Reflectance and Fluorescence Spectra for In Vivo Detection of Cervical Dysplasia and Cancer
,”
J. Biomed. Opt.
,
13
(
6
), p.
064016
.
21.
Wang
,
L.
,
Jacques
,
S. L.
, and
Zheng
,
L.
,
1995
, “
MCML—Monte Carlo Modeling of Light Transport in Multi-Layered Tissues
,”
Comput. Methods Programs Biomed.
,
47
(
2
), pp.
131
146
.
22.
Prahl
,
S. A.
,
2002
, “
Simple and Accurate Approximations for Reflectance From a Semi-Infinite Turbid Medium
,”
OSA Biomedical Topical Meeting
, Miami Beach, FL, Apr. 7, Paper No. TuF4, pp.
613
614
.https://www.osapublishing.org/abstract.cfm?uri=bio-2002-TuF4&origin=search
23.
Myers
,
D. E.
,
Anderson
,
L. D.
,
Seifert
,
R. P.
,
Ortner
,
J. P.
,
Cooper
,
C. E.
,
Beilman
,
G. J.
, and
Mowlem
,
J. D.
,
2005
, “
Noninvasive Method for Measuring Local Hemoglobin Oxygen Saturation in Tissue Using Wide Gap Second Derivative Near-Infrared Spectroscopy
,”
J. Biomed. Opt.
,
10
(
3
), p.
034017
.
24.
Chang
,
S. K.
,
Arifler
,
D.
,
Drezek
,
R.
,
Follen
,
M.
, and
Richards-Kortum
,
R.
,
2004
, “
Analytical Model to Describe Fluorescence Spectra of Normal and Preneoplastic Epithelial Tissue: Comparison With Monte Carlo Simulations and Clinical Measurements
,”
J. Biomed. Opt.
,
9
(
3
), pp.
511
522
.
25.
Parker
,
M. F.
,
Mooradian
,
G. C.
,
Okimoto
,
G. S.
,
O'Connor
,
D. M.
,
Miyazawa
,
K.
, and
Saggese
,
S. J.
,
2002
, “
Initial Neural Net Construction for the Detection of Cervical Intraepithelial Neoplasia by Fluorescence Imaging
,”
Am. J. Obstet. Gyencol.
,
187
(
2
), pp.
398
402
.
26.
Park
,
S. Y.
,
Follen
,
M.
,
Milbourne
,
A.
,
Rhodes
,
H.
,
Malpica
,
A.
,
MacKinnon
,
N.
,
MacAulay
,
C.
,
Markey
,
M. K.
, and
Richards-Kortum
,
R.
,
2008
, “
Automated Image Analysis of Digital Colposcopy for the Detection of Cervical Neoplasia
,”
J. Biomed. Opt.
,
13
(
1
), p.
014029
.
27.
Pogue
,
B. W.
,
Mycek
,
M.-A.
, and
Harper
,
D.
,
2000
, “
Image Analysis for Discrimination of Cervical Neoplasia
,”
J. Biomed. Opt.
,
5
(
1
), pp.
72
82
.
28.
Orfanoudaki
,
I. M.
,
Themelis
,
G. C.
,
Sifakis
,
S. K.
,
Fragouli
,
D. H.
,
Panayiotides
,
J. G.
,
Vazgiouraki
,
E. M.
, and
Koumantakis
,
E. E.
,
2005
, “
A Clinical Study of Optical Biopsy of the Uterine Cervix Using a Multispectral Imaging System
,”
Gynecol. Oncol.
,
96
(
1
), pp.
119
131
.
29.
Pogue
,
B. W.
,
Kaufman
,
H. B.
,
Zelenchuk
,
A.
,
Harper
,
W.
,
Burke
,
G. C.
,
Burke
,
E. E.
, and
Harper
,
D. M.
,
2001
, “
Analysis of Acetic Acid-Induced Whitening of High-Grade Squamous Intraepithelial Lesions
,”
J. Biomed. Opt.
,
6
(
4
), pp.
397
403
.
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