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This article has been accepted for publication in a future issue of this journal, but has not been

fully edited. Content may change prior to final publication. Citation information: DOI
10.1109/ACCESS.2019.2893357, IEEE Access

Date of publication xxxx 00, 0000, date of current version xxxx 00, 0000.
Digital Object Identifier 10.1109/ACCESS.2019.Doi Number

A Fuzzy Reasoning Model for Cervical


Intraepithelial Neoplasia Classification using
Temporal Grayscale Change and Textures of
Cervical Images during Acetic Acid Tests
Jun Liu1, Yun Peng2, and Yingchun Zhang2
1
College of Information Engineering, Nanchang Hangkong University, Nanchang, Jiangxi, China
2
Department of Biomedical Engineering, University of Houston, Houston, Texas, United States
Corresponding author: Yun Peng (e-mail: yunpeng05@gmail.com)
This work was supported in part by the National Nature Science Foundation of China under Grant 61772255.

ABSTRACT Objective: A novel fuzzy reasoning model using temporal grayscale change and texture
information of acetic acid test cervical images was developed to classify patients at risk for Cervical
Intraepithelial Neoplasia (CIN). Methods: Pre- and post- acetic acid test images were obtained from 505
patients (383 CIN negative, 122 CIN positive). An automatic image segmentation algorithm was
implemented to extract the acetowhite region, followed by feature extraction of the: (1) temporal grayscale
change from pre- to post- images, (2) texture coarseness and (3) texture complexity of post-test images. An
index of CIN was derived based on fuzzy reasoning incorporating expert knowledge. Logistic regression
was built with cross-validation to compare the classification performance between different combinations
of features. Results: The averaged sensitivity was 80.8%, 80.9%, 82.8% and specificity was 82.0%, 87.4%,
86.2% for three individual features, respectively. The combination of all three features significantly
improved the sensitivity (84.7%) without a significant loss of specificity (86.5%). The fuzzy reasoning
model further improved the sensitivity significantly (sensitivity 85.9%, specificity 86.6%). Conclusion:
Image texture features outperformed temporal grayscale change in specificity. Combining grayscale-based
and texture-based features could improve the overall classification performance, creating a synergistic
effect. The proposed fuzzy reasoning model could further increase the sensitivity without requiring
additional features. Significance: The proposed automatic CIN classification algorithm could provide a
useful screening tool in the prevention of cervical cancers.

INDEX TERMS Cervical cancer screening, acetic acid test, fuzzy reasoning, texture feature.

I. INTRODUCTION almost 100% [10].


Cervical cancer is the second most common malignancy Biopsy provides the ultimate truth of cervical cancer
and cause of cancer-related death in women worldwide [1] stages, allowing the confirmation of Cervical Intraepithelial
[2]. Despite a trend of decreased incidence of cervical Neoplasia (CIN), with CIN positive including Low-grade
cancer in developed countries [3-6], in developing or Squamous Intraepithelial Lesions (LSIL) or High-grade
underdeveloped countries, the incidence of cervical cancer Squamous Intraepithelial Lesions (HSIL) [11, 12].
is increasing [7]. Effective screening tools play a critical However, biopsy cannot serve as a routine population-
role in the early detection of cervical cancer [8, 9]. As it based screening tool mainly because of its high
takes several years for the epithelium to change from invasiveness as well as the complexity in procedure.
precancerous stages to invasive cancer, there is adequate Recently, the Visual Inspection with Acetic acid (VIA) is
time for the screening and detection of the precancerous becoming a popular screening tool for cervical cancers
stages. With an effective screen tool for early stage because of its effectiveness and convenience [13, 14]. In a
detection, the survivor rate of cervical cancer could reach typical VIA test, the acetic acid is applied to the cervix and

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turns the dysplastic epithelium into white regions


(acetowhite) [15]. The CIN status (CIN positive or negative)
could be estimated according to the color change from pre-
to post-acetic acid test images as well as the morphology of
the acetowhite region on post-test images. The VIA test is
suitable for a wide application particularly in developing
countries, in contrast to other major screening tools such as
Papanicolaou (Pap) smear test or Human Papillomavirus
(HPV) test, as VIA using colposcopy is less demanding in
operator skills and costs [16]. It only requires a colposcopy
(a medical diagnostic procedure to examine an illuminated,
magnified view of the cervix). Furthermore, the technical
simplicity does not come with the cost of reduced diagnosis
accuracy. Recent studies have shown that VIA tests
demonstrated comparable accuracy in cervical cancer
detection with Pap smear and HPV tests [17]. Besides,
cervical images on colposcopy are often inevitably obtained
in Pap smear or HPV tests to assist the biopsy as a final
confirmation of cervical cancer. Therefore, VIA test could
potentially serve as a reliable and low cost screening tool
for cervical cancers.
Nevertheless, one limitation of the VIA test is its
dependence on operator’s subjective definition of a lesion FIGURE 1. The flowchart of this study. The pre- and post- acetic acid
region [18, 19], which are based on main attributes of color, images were first registered and then segmented for the cervix region
and surface reflection region. Features based on the greyscale intensity,
vascular patterns and lesion margins [20]. Several factors energy and entropy were extracted and imported to the fuzzy reasoning
could interfere with the visual inspection, e.g., the mucus classifier to derive the index of CIN.
on the cervical surface or reflective spots [21], making CIN
classification challenging for less experienced operators classification performance. Despite its successful
and the application of VIA test in regions lacking application in many image-based classification of breast
experienced doctors difficult. The recent advance of cancer [23, 24], bladder cancer [25] or lung cancer [26], the
machine learning in medical imaging analysis has provided fuzzy reasoning method has yet been applied in classifying
a promising solution. According to a recent state-of-art the risk for cervical cancer using acetic-acid images.
review, a number of algorithms of automatic acetowhite Therefore, in this study, a novel fuzzy reasoning model
regions detection have been proposed [16, 22]. Despite a using temporal grayscale change and texture of cervical
great success has been achieved, there are two major images during a VIA test was proposed to classify women
obstacles remaining. First, existing algorithms almost with low-risk (CIN negative) or at risk (CIN positive,
exclusively relied on the color-based feature (e.g., grayscale including LSIL and HSIL). This novel fuzzy reasoning
intensity) of the acetowhite region to differentiate model, by integrating the expert knowledge and mimicking
cancerous and healthy tissues. Though the temporal color the expert decision making process, could potentially
change during a VIA test (from pre- to post- acetic acid contribute to the clinical practice as a useful
tests) is the most prominent observation of CIN, in practice, complementary tool to assist the diagnosis and therefore
the texture features, such as the lesion margins and vascular alleviate the burden of medical doctors. The main objective
was to evaluate whether this novel fuzzy reasoning model
patterns, provide equally important complementary
could improve the classification performance over
information used by experienced oncologists. VIA-based
traditional temporal grayscale change feature, image texture
imaging studies utilizing both color-based and texture-
features or their combinations.
based features remain scarce in the current literature, which
could potentially further enhance the classification
II. MATERIALS AND METHODS
performance. Second, existing classification algorithms
often did not adopt expert knowledge, e.g., how to properly A. STUDY OVERVIEW
weigh different features to achieve optimal classification This study was conducted at the Nanchang Hangkong
results. As a result, a large volume of training dataset University, in collaboration with the Jiangxi Maternal and
became inevitable to properly train the algorithm, Child Health Hospital. Pre- and post-acetic acid test images
presenting a demanding requirement. To overcome this, the were obtained from a total number of 505 patients (383
fuzzy reasoning method could be used to properly CIN negative, 122 CIN positive). The VIA test was
incorporate expert knowledge, potentially enhancing the performed using colposcopy, with the acetowhite region

2 VOLUME XX, 2019

2169-3536 (c) 2018 IEEE. Translations and content mining are permitted for academic research only. Personal use is also permitted, but republication/redistribution requires IEEE permission. See
http://www.ieee.org/publications_standards/publications/rights/index.html for more information.
This article has been accepted for publication in a future issue of this journal, but has not been fully edited. Content may change prior to final publication. Citation information: DOI
10.1109/ACCESS.2019.2893357, IEEE Access
Jun Liu et al.: A Fuzzy Reasoning Model for Cervical Intraepithelial Neoplasia Classification using Temporal Grayscale Change and
Textures of Cervical Images during Acetic Acid Tests

FIGURE 2. Representative pre- and post-acetic acid test images from (a)
healthy patient (CIN negative), (b) patient with LSIL and (c) patient with
HSIL. The left side is the pre-test images and the right side is the post-
test images.

marked digitally on post-acetic acid test image by an


experienced gynecologic oncologist, who recommended the
CIN status and patient disposition. Ground truth of positive
CIN class was confirmed by the follow-up biopsy test.

B. REGISTRATION OF PRE- AND POST-ACETIC ACID


TEST IMAGES
An overview of the study flowchart is provided in Fig. 1. FIGURE 3. The image segmenting procedure for the region of interest.
First, a precancerous colposcopic diagnosis system (Fook The green line denotes the segmented cervical region. The blue line
indicates the detected specular reflection.
Medical Technology Corp, Fuzhou, Jiangxi, China) was used
during the acetic-acid test. This device is featured with its
location. An affine transformation model was used, as shown
multimodal imaging function and software support system. in (1):
High-resolution images of the cervix 1920 × 1080 were
 x
acquired using a smart colposcopy as part of the diagnosis
 x*   r1 r2 r3   
system. For the convenience of data analysis and better  *  
r6   
y (1)
clinical utility, images were down-sampled to size of 384 ×  y   r4 r5
216. Representative pre- and post-acetic acid test images are  1 
shown in Fig. 2.
The detection of the acetowhite region after the application where (x,y) and (x*,y*) are the corresponding pixels in the
of acetic acid represents a key step in a VIA test. However, mask and floating images, respectively and (r1,r2,…,r6) are
the grayscale intensity of an acetowhite region may vary the parameters to be optimized in the affine model.
markedly among different patients due to differences in The similarity function used in the registration was the
patient conditions, testing environment, operators and grayscale correlation and was optimized by the genetic
devices used, making it challenging to perform CIN algorithm. After successfully registering the pre- and post-
classification based solely on post-acetic acid test images. test images, the temporal change of grayscale intensity at
Therefore, both pre- and post-acetic acid images were each pixel was calculated.
acquired to best quantify the change of grayscale intensities
within the same patients (temporal color change). C. IMAGE SEGMENTATION
Next, a registration of pre- and post-acetic acid images Two regions, the cervix region (interests) and specular
was performed to allow for the quantification of the temporal reflection (artifacts) region, were segmented in this step. The
change in grayscale intensity at the same physical tissue purpose of the cervix region segmentation was to remove the

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irrelevant information, such as the vaginal wall tissues or the


colposcopy device. It was found that the cervical region,
compared to irrelevant regions, was featured with greater
grayscale intensity, greater red color intensity and more
centered locations. As a result, for an image with size of m by
n, an objective function F(x,y) was constructed and
optimized to best capture these characteristics, as shown in
(2).

 F ( x, y )  D  D  D  D
 1 2 3 4

 D1  1 *( Ar ( x, y )  Ag ( x, y )  Ab ( x, y )) / (256*3)

 D2  2 *(2* Ar ( x, y )  Ag ( x, y )  Ab ( x, y )) / 256 (2)

 D3  3 *( Ba ( x, y )  128) / 256 FIGURE 4. Conversion of the scale of input and output values to a
 m n m n
standard continuous domain of [1,10].

 D4  4 * (( x  ) 2  ( y  ) 2 ) / (( ) 2  ( ) 2 )
 2 2 2 2 where Gray(x,y) denotes the grayscale intensity at pixel (x,y),
ranging from 0 to 255. Next, a ratio image was defined using
(4):
where Ar(x,y), Ag(x,y) and Ab(x,y) represent the RGB
post _ image( x, y) / avg _ post _ image
components of the pixel (x,y), Ba(x,y) represents the ratio _ image( x, y)  (4)
component of channel A in the LAB space, and D1,D2,D3 pre _ image( x, y) / avg _ pre _ image
and D4 are user-defined functions to describe the overall
grayscale intensity, the red-channel intensity in RGB color where pre_image(x,y) and post_image(x,y) represent the
space, the A-channel intensity in LAB color space and grayscale intensity at pixel (x,y) on the pre- and post-acetic
central location tendency, with λ1, λ2, λ3 and λ4 being the acid images, respectively, avg_pre_image and
weighting coefficients which are solved by the k-means avg_post_image represent the averaged grayscale intensity of
clustering algorithm. the pre- and post- acetic acid images, respectively, and the
The segmentation of the cervix region was performed in ratio_image(x,y) indicates the temporal grayscale intensity
both pre- and post-acetic acid test images. Only the change normalized according to the global intensity level.
overlapping regions in both pre- and post-acetic acid test Based on the ratio image, the first feature was defined as
images were considered as the region of interest where the the percentage area in the region of interest that showed a
subsequent feature extraction is performed. ratio value greater than 1.2 (greater value in CIN region),
Specular reflection is often encountered in colposcopy using (5):
images and interferes with the true change of grayscale
intensities [21, 27-29]. A threshold method was therefore area _ AW
Feature _1  (5)
used. A pixel was labeled as a specular reflection if its G and area _ ROI
B components in RGB color space were both greater than
200 (for the grayscale within 0-255). All specular reflection where area_AW represents the area of region that shows a
regions were excluded from the region of interest. An ratio greater than 1.2, and area_ROI represents the area of
illustration of this step is provided in Fig. 3. the total region of interest.

D. FEATURE EXTRACTION BASED ON TEMPORAL E. FEATURE EXTRACTION BASED ON POST-ACETIC


GRAYSCALE CHANGE ACID TEST IMAGE TEXTURE
The registered region of interest in both pre- and post-acetic In medical image analysis, object texture provides a useful
test images was first converted from RGB format to feature in classifying objects of interest. To quantify image
grayscale, using (3): textures of the acetowhite region, a gray-level co-occurrence
( R( x, y )  G ( x, y )  B( x, y ))
Gray ( x, y )  matrix was defined, using (6) on post-acetic acid test images.
3 (3)

max( R( x, y )  G ( x, y ) , R( x, y )  B( x, y ) , G ( x, y )  B( x, y ) ) p(w, v)  P{ f ( x, y)  w, f ( x  d cos  , y  d sin  )  v} (6)
3
where f(x,y) and f(x+dcosθ, y+dsinθ) are the grayscale
intensity of two pixels on the post-acetic acid test image and
p(w,v) is considered as the appearance probability that the

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2169-3536 (c) 2018 IEEE. Translations and content mining are permitted for academic research only. Personal use is also permitted, but republication/redistribution requires IEEE permission. See
http://www.ieee.org/publications_standards/publications/rights/index.html for more information.
This article has been accepted for publication in a future issue of this journal, but has not been fully edited. Content may change prior to final publication. Citation information: DOI
10.1109/ACCESS.2019.2893357, IEEE Access
Jun Liu et al.: A Fuzzy Reasoning Model for Cervical Intraepithelial Neoplasia Classification using Temporal Grayscale Change and
Textures of Cervical Images during Acetic Acid Tests

TABLE I L L
FUZZY REASONING RULES
Feature _ 3  entropy   p(w, v) log[ p( w, v)] (8)
Index of
Rule # Feature_1 Feature_2 Feature_3 w1 v 1
CIN
1 Big Big Big Big
2 Big Big Medium Big F. INDEX OF CIN – FEATURE FROM FUZZY
3 Big Big Small Medium REASONING MODEL
4 Big Medium Big Big
5 Big Medium Medium Medium
Fuzzy reasoning model concerns vague aspects related to
6 Big Medium Small Medium information, and it is less restrictive and suitable to handle
7 Big Small Big Medium information provided by human. It extends the classic binary
8 Big Small Medium Medium
logic reasoning to a continue domain using a gradual
9 Big Small Small Medium
10 Medium Big Big Medium transition between pertinence and non-pertinence of an
11 Medium Big Medium Medium element within a set. The above mentioned three features
12 Medium Big Small Medium were used as inputs to the fuzzy reasoning model. The output
13 Medium Medium Big Medium
14 Medium Medium Medium Medium was termed as the “index of CIN”, a final feature to assess
15 Medium Medium Small Medium the severity of intraepithelial neoplasia. To do this, the input
16 Medium Small Big Medium and output values were projected to a continuous universe of
17 Medium Small Medium Small
18 Medium Small Small Small [1, 10] according to the relation shown in Fig. 4. Next, the
19 Small Big Big Medium domain value was categorized into three sets (‘Small’,
20 Small Big Medium Medium ‘Medium’ and ‘Big’) according to the membership functions
21 Small Big Small Small
22 Small Medium Big Small
shown in Fig. 5 for each input feature or the index of CIN.
23 Small Medium Medium Small Lastly, fuzzy reasoning rules were developed based on the
24 Small Medium Small Small expert knowledge of an experienced gynecologic oncologist,
25 Small Small Big Small as shown in Table I.
26 Small Small Medium Small
27 Small Small Small Small During implementation, the continuous domain of [1, 10]
for each feature and the output were discretized in to a set of
grayscale intensities of the two pixels are w and v with spatial [1, 2, 3, 4, 5, 6, 7, 8, 9, 10]. The reasoning process of the
distance of d and intersectional angle of θ respectively. In our fuzzy system was determined using (9) and (10), by the
experiment, w and v were in the range of [0,255], d and θ combination of input subsets and corresponding output
were set as 2 pixel distance and 0 degree respectively. As the subsets based on Table I. For our fuzzy model with three
most prominent feature of acetowhite region was within the features and three subsets per feature, 27 rules existed in the
region with an increased grayscale level database.
27
(ratio_image(x,y)>1), the co-occurrence matrix p(w,v) was
only calculated within the region with ratio_image(x,y)>1, in
R F1 (i)  F2 (i)  F3 (i)  P(i) (9)
i 1
order to minimize the influence of non-acetowhite region on
the extraction of subsequent texture features.
where ‘ ∧ ’ represents intersection operation and ‘U’
The energy and entropy of the gray-level co-occurrence
represents union operation, R is the rule database, F1(i), F2(i)
matrix were calculated from the images according to (7) and
and F3(i) are the subsets of three inputs for i-th rule and P(i)
(8), in which L denotes the highest gray-level of the image.
is the subset of the output for i-th rule.
The energy of the co-occurrence matrix could reflect the
image texture coarseness (greater energy less coarse) or
texture smoothness (greater energy higher smoothness), Pj*  ( F1*j  F2*j  F3*j ) R
while the entropy of the co-occurrence matrix could reflect (10)
 ( p j1 , p j 2 , p j10 ) ( j  1 1000)
the image texture complexity (greater entropy more
complexity) [30, 31]. Consequently, the second feature was
conveniently defined as the inverse of the energy of the co- where ‘o’ represents max-min composition of fuzzy relations
occurrence matrix, representing image texture coarseness [32], F*1j, F*2j, and F*3j are the subsets of each input for j-th
(greater value in CIN positive patients), and the third feature combination (in total 10 by 10 by 10 combinations) and P*j is
was defined directly as the entropy of the co-occurrence the output for j-th combination that consisted by ten
matrix, representing image texture complexity (greater value components (pj1, pj2,…pj10), and it can be defuzzified to the
in CIN positive patients). universe space of [1,10] according to (11) [33] and then
1 1 mapped to the CIN index range of [0,100] according to Fig. 4
Feature _ 2   L L
(7) and (12). The input-output matrix (10 by 10 by 10) was
1000*  p ( w, v)
1000* energy 2 calculated offline and saved locally to facilitate the
w1 v 1 calculation of any new input combinations based on a linear
interpolation.

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2169-3536 (c) 2018 IEEE. Translations and content mining are permitted for academic research only. Personal use is also permitted, but republication/redistribution requires IEEE permission. See
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FIGURE 5. Relation of membership (subsets) and corresponding standardized input and output values. The red line, green line and blue line denote
the fuzzy set of ‘Small’, ‘Medium’ and ‘Big’ respectively.

10 (CIN negative or positive) was reported based on the testing


p ji *i dataset for each model and compared between models using
index( j )  i 1
10
( j  1 1000) (11) paired t test (alpha = 0.05). All codes in this study were

p
i 1
ji
implemented in Matlab R2014a with a laptop with 2.53 GHz
CPU and 4G RAM.
100
CIN _ index( j )  [index( j )  1]* ( j  1 1000) (12) III. RESULTS
9
A. IMAGE REGISTRATION AND SEGMENTATION AND
FEATURE EXTRACTION
G. DATA ANALYSIS For all patients, pre-to-post acid test image registration and
A total number of 505 pairs of pre- and post-acetic acid test
segmentation were successfully implemented, with
images were obtained (383 healthy CIN negative and 122
exemplary pre- and post-test images registration from three
CIN positive). To compare the performance of the index of
subjects shown in Fig. 6 and exemplary automatic
CIN (derived from fuzzy-reasoning) and individual features
segmentation of the acetowhite region from nine subjects
or their combinations, a logistical regression model was built shown in Fig. 7. Based on the image registration and
separately using the following independent variables: (1) segmentation results, the proposed three features were
feature 1 (temporal grayscale change), (2) feature 2 (image extracted and the index of CIN was derived using the
texture coarseness), (3) feature 3 (image texture complexity), proposed fuzzy reasoning model. A comparison of each
(3) feature 2 and 3 (image texture), (4) feature 1, 2 and 3 individual feature and the index of CIN between CIN
(temporal grayscale change and texture feature, without negative and positive patients is shown in Fig. 8.
fuzzy reasoning) and (5) index of CIN (fuzzy reasoning In CIN negative and CIN positive patients respectively,
based on image temporal grayscale change and textures). A feature 1 (temporal grayscale change) was 0.112±0.104 and
five-fold cross-validation was repeated 1000 times, by 0.206±0.178, feature 2 (image texture coarseness) was
randomly selecting 80% of the low-risk and at-risk samples 0.975±0.746 and 1.734±1.685 and feature 3 (image texture
as the training dataset and the remaining 20% of negative and complexity) was 7.220±0.784 and 7.756±0.770, and the
positive samples as testing dataset in each repetition. The index of CIN after fuzzy reasoning was 24.057±20.299 and
parameters of logistic regression from the training dataset 62.360±48.793. All comparisons reached statistical
were used to predict the classifications in the testing dataset. significance upon independent two sample t test (p<0.05).
The averaged sensitivity and specificity in CIN classification

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2169-3536 (c) 2018 IEEE. Translations and content mining are permitted for academic research only. Personal use is also permitted, but republication/redistribution requires IEEE permission. See
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This article has been accepted for publication in a future issue of this journal, but has not been fully edited. Content may change prior to final publication. Citation information: DOI
10.1109/ACCESS.2019.2893357, IEEE Access
Jun Liu et al.: A Fuzzy Reasoning Model for Cervical Intraepithelial Neoplasia Classification using Temporal Grayscale Change and
Textures of Cervical Images during Acetic Acid Tests

Figure 6. Representative image registration results for three patients, Figure 7. Representative images of cervix region and specular
with pre-test images shown in the upper panel, post-test images in the reflection region segmentation from nine patients. The green curves
mid panel and registered image in the lower panel. The ‘+” marker indicate the segmented cervix region by using the presented algorithm
indicates references pixels for comparison. and the red curves are the cervix region drawn by the expert. The blue
curves are the segmented specular reflection region by using the
reported method.

B. CLASSIFICATION PERFORMANCE USING When both texture features were used (F2 + F3, Fig. 9), the
INDIVIDUAL FEATURES
sensitivity and specificity was 82.5% and 85.1%. Compared
A summary of sensitivity and specificity for different feature
to individual F2 or F3, their combination maintained the
inputs is shown in Fig. 9. Comparing the classification
relatively high sensitivity performance offered by F3 alone,
performance with individual features could provide useful
and showed a slightly reduced specificity. Such a lack of
insights into the separated roles of image color and image
synergistic effect may result from the fact that these two
texture features. The sensitivity and specificity reached
features, originating from the same co-occurrence matrix,
80.8% and 82.0% with feature 1 (temporal grayscale change),
were both based on the texture information and as a result,
80.9% and 87.4% with feature 2 (image texture coarseness),
shared a lot of common information. However, when the
and 82.8% and 86.2% with feature 3 (image texture
temporal grayscale change feature (F1) was additionally
complexity). Compared to the temporal grayscale change,
included, a significant increase was observed in both
both image texture features significantly improved the
sensitivity and specificity (p<0.001), suggesting a synergistic
specificity (p<0.001), while the image texture complexity
effect. Therefore, our findings provide evidence of a
additionally improved the sensitivity significantly (p<0.001).
synergistic effect between temporal grayscale change and
These results suggested that using texture features could
image texture features, further supporting the use of texture
effectively enhance the classification performance in
features in addition to traditionally used image color-based
detecting false positives, compared to temporal grayscale
features.
change alone. One possible explanation is that there may still
be residual artifacts (non-cervical tissues, such as the D. CLASSIFICATION PERFORMANCE USING THE
colposcopy device or specular reflections) that also exhibited INDEX OF CIN FROM FUZZY REASONING MODEL
a great increase in grayscale intensity from pre- to post-test Lastly, we evaluated the performance of the index of CIN
conditions, despite an automatic segmentation and specular that was derived from the proposed fuzzy reasoning model.
reflection algorithm have been implemented to mitigate this Compared with the combination of all three features, the
influence. Such artificial increase in image color could result index of CIN reached a sensitivity of 85.9% and specificity
in false positive predictions. In contrast, image texture of 86.6%, with the sensitivity significantly improved and
features were insensitive to the temporal change between being the highest among all models. As the CIN positive
pre- and post-test conditions; rather, they were based on the group in our study included patients with LSIL, who were
coarseness and complexity of the overall image. Such image usually difficult to identify from CIN negative patients, a
texture features could more reliably rule out the interference high sensitivity is critical as these patients were not without
from artifacts, which lacked identifiable textures of cervical risk of cervical cancer and should be carefully examined.
tissues (e.g., vascular patterns, lesion margins). As currently Considering the fact that the fuzzy reasoning model was
the majority of existing VIA-based algorithms are based on essentially based on the same feature inputs, the increase in
color-based features of the acetowhite region, our finding sensitivity without requiring additional features became a
provided evidences to support the use of image texture particularly useful advantage, largely owning to the model’s
features in CIN classification. capability in incorporating expert knowledge. This advantage
may be particularly useful in clinical practice without placing
C. CLASSIFICATION PERFORMANCE USING a demanding requirement on the training dataset size.
COMBINATIONAL FEATURES

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Figure 8. The box-plot distribution of three features and the index of CIN after fuzzy reasoning in each patient group.

Figure 9. A summary of sensitivity and specificity for different feature inputs used in the classification.

to 94% and from 70% to 98% [16, 22, 35-43]. The


IV. DISCUSSION inconsistent results are likely due to heterogeneity between
Cervical cancer is the leading cause of cancer death for different studies, such as patient selection criteria, patient
women in developing countries [34]. With early detection, it grouping method, classification algorithms, features, data
can often be cured by removing the affected tissues [22]. sample size, etc. As a result, a proper comparison between
Automated CIN classification using digital cervix images these studies is difficult. In the current study, based on the
acquired during VIA is of great value in developing countries same patient dataset verified by biopsy, we compared the
where clinical resources are lacking. Recently, there has been performance of traditionally used color-based grayscale
an increasing volume of studies investigating the change feature and novel image texture features, and further
classification of CIN based on acetic acid test images [16]. investigated the performance of a fuzzy reasoning model.
However, reported classification performance varied There are three main strengths of our study. First, our
markedly, with sensitivity and specificity ranging from 60% model utilized both pre- and post-acetic acid images for

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Jun Liu et al.: A Fuzzy Reasoning Model for Cervical Intraepithelial Neoplasia Classification using Temporal Grayscale Change and
Textures of Cervical Images during Acetic Acid Tests

acetowhite region segmentation and temporal grayscale There are several limitations of our research which provide
change characterization. According to a recent state-of-art us the future research directions. First, we only implemented
review [16], the majority of existing studies relied heavily on the classification between CIN negative cases and CIN
the post-acetic acid images for CIN grading (without using positive cases. Though this classification boundary is
temporal acetowhite patterns intrinsic to color changes). As important, it would be equally important to further
multiple factors could affect the image acquisition process, distinguish cancer or HSIL cases from LSIL cases. Second,
e.g., camera positions, overall intensity, use of exposure, the current sample size is relatively small, limiting the total
distance of camera from cervix, etc., variations across number of features we could use (because of the risk of
subjects added additional difficulty in CIN classification that overfitting) and the comparison to other existing studies that
was based solely on post-test images. In contrast, our study used different features. With a continuing effort to recruit
employed an automatic cervical region segmentation more subjects, we aim to compare our results with existing
algorithm to extract and align the cervical region in both pre- studies, including some benchmark databases, using the same
and post-test images and then extracted the temporal features once a much larger sample size has been reached.
grayscale change by referencing the post-test image to the Similarly, more features will be implemented to further
pre-test image, effectively utilizing patient-specific temporal strengthen the proposed algorithm.
information during the acetic acid test and eliminating
variations in baseline images and image acquisition process. V. CONCLUSION
Second, although color-based feature of the acetowhite In this paper, we presented a novel fuzzy reasoning model
region represents the signature for suspicious CIN, texture using temporal grayscale and texture features of the
features of the acetowhite region provide equally important acetowhite region during an acetic-acid test for the CIN
information regarding the health of cervical tissues. For classification. The results showed that image texture features
example, in the REID Index system, a commonly used tool provided useful information in adjunct to color-based
for colposcopic grading of CIN levels by gynecologic features by effectively ruling out false positives. Compared
oncologists [20], the final combined colposcopic index was to non-fuzzy reasoning-based methods, the proposed fuzzy
based on the assessment of not only the color (e.g., oyster- reasoning model showed a significantly increased sensitivity
white dull color), but also features related to the image without losing specificity. The proposed model has the
textures (e.g., tissue margin being rolled) or vascular patterns potential to serve as a useful screening tool in the prevention
(e.g., mosaic or definite punctuation) [44]. However, there is of cervical cancers for women.
a lack of automatic CIN classification algorithms combining
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http://www.ieee.org/publications_standards/publications/rights/index.html for more information.
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10.1109/ACCESS.2019.2893357, IEEE Access

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