Professional Documents
Culture Documents
fully edited. Content may change prior to final publication. Citation information: DOI
10.1109/ACCESS.2020.3012292, IEEE Access
Date of publication xxxx 00, 0000, date of current version xxxx 00, 0000.
Digital Object Identifier 10.1109/ACCESS.2017.DOI
ABSTRACT Leukocytes, produced in the bone marrow, make up around one percent of all blood
cells. Uncontrolled growth of these white blood cells leads to the birth of blood cancer. Out of the
three different types of cancers, the proposed study provides a robust mechanism for the classification of
Acute Lymphoblastic Leukemia (ALL) and Multiple Myeloma (MM) using the SN-AM dataset. Acute
lymphoblastic leukemia (ALL) is a type of cancer where the bone marrow forms too many lymphocytes.
On the other hand, Multiple myeloma (MM), a different kind of cancer, causes cancer cells to accumulate
in the bone marrow rather than releasing them into the bloodstream. Therefore, they crowd out and prevent
the production of healthy blood cells. Conventionally, the process was carried out manually by a skilled
professional in a considerable amount of time. The proposed model eradicates the probability of errors
in the manual process by employing deep learning techniques, namely convolutional neural networks. The
model, trained on cells’ images, first pre-processes the images and extracts the best features. This is followed
by training the model with the optimized Dense Convolutional neural network framework (termed DCNN
here) and finally predicting the type of cancer present in the cells. The model was able to reproduce all the
measurements correctly while it recollected the samples exactly 94 times out of 100. The overall accuracy
was recorded to be 97.2%, which is better than the conventional machine learning methods like Support
Vector Machine (SVMs), Decision Trees, Random Forests, Naive Bayes, etc. This study indicates that the
DCNN model’s performance is close to that of the established CNN architectures with far fewer parameters
and computation time tested on the retrieved dataset. Thus, the model can be used effectively as a tool for
determining the type of cancer in the bone marrow.
INDEX TERMS Acute Lymphoblastic Leukemia, Classification algorithms, Deep Learning, Convolutional
neural networks, Image processing, Multiple Myeloma
I. INTRODUCTION is the main cause of blood cancer. There are three main types
ELLS Cells that comprise the blood are three types: of blood cancers: leukemia, myeloma, and lymphoma. Bone
C platelets, red blood cells, and white blood cells. Each of
them is made continuously in the bone marrow and released
marrow is the infected area for a white blood cancer type
cancer called Acute Lymphocytic Leukemia (ALL). "Acute"
timely in the bloodstream. The normal blood cell growth, indicates the fast progress of the disease, and if it does not get
hampered by the exponential growth of abnormal blood cells, treated in the early stages, it might prove to be fatal within a
VOLUME x, 20xx 1
This work is licensed under a Creative Commons Attribution 4.0 License. For more information, see https://creativecommons.org/licenses/by/4.0/.
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.2020.3012292, IEEE Access
Kumar et al.: Automatic Detection of White Blood Cancer from bone marrow microscopic images using Convolutional Neural Networks
short span [1], [2]. ALL is classified into L1, L2, and L3 [3]. • With less computation time need and trainable parame-
Multiple Myeloma (MM) is an immature teratoma of cells ters, the proposed model outperforms existing machine
called plasma, which helps to scrape off the infection [4]. learning and pre-trained deep learning models in identi-
It is thrice as common as ALL. The blood count remains fying the type of cancer.
normal in this case, unlike leukemia, but the infected one This paper was structured as follows: Section II describes
is found to have anemia (low red blood count) because the the related work. Section III outlines the proposed technique
space for RBCs is occupied by the unhealthy cells. Multiple for classifying blood cancer, learning measures, an overview
myeloma is responsible for low platelet count in the blood, of the dataset, and assessment strategy. Extensive experi-
which is called thrombocytopenia. [5] It also causes erosion ments on the proposed model were conducted in Section
of bones called bone lesions diagnosed in CT scans. [6] IV, and the final results were compared with traditional
Approximately 1500 people who died due to this disease algorithms for machine learning.
contribute to 0.2% of the total deaths caused by cancer alone
in 2019 [7]. There are nearly 20,000 people diagnosed with II. RELATED WORK
myeloma every year in the US. Treatment for blood cancer The infected blood cell image analysis is typically divided
depends on the age of the patient, type, how fast the cancer is into three stages: preprocessing of images, extraction, selec-
progressing, infected areas, etc. [8]. The blood count is one tion of features, and classification. There has been extensive
of the prime factors for the distinction for categorizing the research on different types of cancer, namely leukemia, lym-
type of blood cancer. The counting can be done manually and phoma, and myeloma. Zhang et al. proposed a convolutional
automatically. The manual method gives a 100% recognition neural network model for direct classification of cervical
rate if done by a skilled person but is also a time-consuming cells into infected and uninfected cells without segmenting
process [9]. them [13]. Zhao et al. proposed machine learning algorithms
On the other hand, automatic counting is a faster process like CNN, SVM, Random Forests, etc. for classifying various
but has got higher risks of the count being wrong. Thus, both types of white blood cells(WBCs) present in the body [12].
methods have their pros and cons. This paper gives an outline Stain Deconvolution Layer (SD Layer) was proposed for
of the automatic approach to determine the type of white determining cancer as well as healthy cells in which instead
blood cancer. The automated method of classification is cost- of training the images in RGB space, the classifier learned
effective and can be deployed quickly in both rural and urban from the images in the Optical Density (OD) space [14].
areas. The problems that are invaded through the proposed FORAN et al. developed an administered clinical decision
system include the inconsistencies caused due to labor work support prototype for differentiating among various hemato-
of manual classification, the requirement of a skilled profes- logic malignancies based on image processing. The system
sional, the errors due to cells being indistinguishable when allowed the analysis of images based on the "gold standard"
observed under a microscope, etc. dataset and suggested treatment based on the collected cases’
Deep learning-based methods can help in resolving all plurality rationale [15]. The paper exhibits a structure for
the enlisted challenges because they derive desirable features classification of Human Epithelial Type 2 cell IIF images
from the raw data themselves [10]. Deep Learning is known by first enhancing, then augmenting, and finally processing
to demonstrate better functioning than accustomed Machine the training data and then feeding it into a convolutional
Learning for processing a large number of images [11]. Con- neural network (CNN) framework for image classification
volution Neural Networks (CNNs) combine various multi- [16]. For classifying acute myeloid leukemia, the ALL-IDB
layer perceptron and display efficient results with a little pre- dataset is initially augmented by applying several alterations
processing. [12] CNN’s themselves act as a feature extractor like histogram equalization, reflection, translation, rotation,
as each convolution layer of the network learns a new feature blurring, etc. Finally, a 7-layer convolutional neural network
that is present in the images and hence produces a high activa- is used [17]. Shrutika Mahajan et al. proposed an SVM-based
tion. In the proposed study, a robust and vigorous automated system with changes in texture, geometry, and histogram
classification method for the type of white blood cancer, i.e., as the classifier’s inputs to distinguish Acute Lymphocytic
ALL and MM using Convolution Neural Networks is pre- Leukemia (ALL) by microscopic blood sample images [18].
sented. The article consequently evaluates the performance of One of the papers contemplated a green plane extraction im-
the proposed deep learning model using accuracy, precision, age preprocessing followed by a reinforcement algorithm for
recall, sensitivity, and specificity as comparison parameters. feature extraction. Finally, it used SVM and Nearest Neigh-
bor Network as tools for classifying leukemia efficiently
The key contributions of this article are:
[19]. Markiewicz, Tomasz et al. put forward a system for
• The proposed model follows a generic approach to the classification of 17 types of blood cells of myelogenous
predict the type of cancer on a small dataset. For gen- leukemia using the images of bone marrow. This system first
eralization, data augmentation has been used. categorized and extracted only the best out of all the available
• A comparative analysis has shown that the proposed features and then used the Gaussian Kernel Support Vector
DCNN out-performs specific state-of-art CNN models Machine (SVM) for final grouping [20]. N.H.A. Halim et al.
on the dataset hence retrieved and prepared. proposed an automatic method for counting of infected cells
2 VOLUME x, 20xx
This work is licensed under a Creative Commons Attribution 4.0 License. For more information, see https://creativecommons.org/licenses/by/4.0/.
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.2020.3012292, IEEE Access
Kumar et al.: Automatic Detection of White Blood Cancer from bone marrow microscopic images using Convolutional Neural Networks
This work is licensed under a Creative Commons Attribution 4.0 License. For more information, see https://creativecommons.org/licenses/by/4.0/.
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.2020.3012292, IEEE Access
Kumar et al.: Automatic Detection of White Blood Cancer from bone marrow microscopic images using Convolutional Neural Networks
FIGURE 2: Sample images of ALL Dataset. (a) ALL sample (a) (b)
image, (b) ALL background mask, (c) ALL nucleus mask.
ALL indicates acute lymphoblastic leukemia.
This work is licensed under a Creative Commons Attribution 4.0 License. For more information, see https://creativecommons.org/licenses/by/4.0/.
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.2020.3012292, IEEE Access
Kumar et al.: Automatic Detection of White Blood Cancer from bone marrow microscopic images using Convolutional Neural Networks
calculates the scores for each feature and then removes all the for i = 1, ..., K and z = (z1 , ..., zK ) ∈ <K , where K
features except the K best features with the highest scores. is the total number of elements of the input vector z and zi
Equation (1) shows the formula used by the chi-squared represents each element of the input vector z.
statistical test.
PA P[x, y] = (I ∗ f ) [x, y]
2 (3)
(O − E) = i j I [i, j] f [x − i, y − i]
χ2 = (1)
E where I is the input image, f is the kernel function, x and
where O is the number of observations of the class, E is y are the numbers of rows and columns of the output matrix
the number of expected observations of class if there was no respectively, i and j are the number of rows and columns of
relation between the feature and the output. the input image matrix, respectively.
This work is licensed under a Creative Commons Attribution 4.0 License. For more information, see https://creativecommons.org/licenses/by/4.0/.
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.2020.3012292, IEEE Access
Kumar et al.: Automatic Detection of White Blood Cancer from bone marrow microscopic images using Convolutional Neural Networks
The algorithm used to classify the images using the deep end of 1000 iterations. Figure 7 shows the confusion matrix
learning approach is shown in pseudo-code Algorithm 1. for the binary classification of malignant white blood cancer
using the CNN model. Using CNN’s specificity of 95.19%
IV. RESULTS AND ANALYSIS and an accuracy of 97.25% is achieved, as shown in Table 2.
The classification model is built using TensorFlow, an end-
to-end open-source platform. A binary classification model
p
w(n) = w(n − 1) − α ∗ m(t)/ v(t) + (5)
was trained on 424 images in 1000 iterations. Each iteration
optimizes the loss function using Adam Optimizer yielding where w is the weight matrix, α is the learning rate,
minimum loss at the last iteration. The trained model was m(t), and v(t) are the first and second moments’ bias-
then used for predicting the type of cancer in the images. K80 corrected estimators. Figure 8 depicts a plot of loss during
GPU is used for training the model. the training period. Figure 9 shows the ROC (Receiver Op-
The subsequent section initially describes the proposed erating Characteristic) curve for the proposed model. The
model results. Comparison and analysis of the proposed ROC curve is formed by plotting the true positive rate (TPR)
model with state-of-art machine learning and deep learning at different threshold settings against the false positive rate
models are also explained. (FPR). Precision - recall curves are usually zig-zag curves
that tend to cross each other very frequently. Due to this, a
A. DEEP LEARNING APPROACH comparison between curves becomes very difficult. Thus we
In the CNN section, our network is trained using Adam Opti- define a perfect test case that says that the curves passing or
mizer with a learning rate of 0.01 by updating the weights inclined more towards the upper right corner is the perfect
using equation (5). The loss function used is the sigmoid case of precision and recall curves. For the proposed model,
cross-entropy loss function, which is optimized by the Adam precision and recall are 1 and 0.93, respectively. Figure 10
optimizer. Figure 8 illustrates the subsidence of loss as the shows the relationship between precision and recall for every
number of iterations increases. As shown in the figure, the possible cutoff. From Figure 10, we can observe that our
training loss acquires a constant value after 800 iterations. classification results tend towards the perfect case of the
Thus, the minimum value, i.e., 0.5034, is obtained at the precision-recall curve.
6 VOLUME x, 20xx
This work is licensed under a Creative Commons Attribution 4.0 License. For more information, see https://creativecommons.org/licenses/by/4.0/.
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.2020.3012292, IEEE Access
Kumar et al.: Automatic Detection of White Blood Cancer from bone marrow microscopic images using Convolutional Neural Networks
AC = (T P + T N )/(T P + T N + F P + F N ) (6)
P = T P/(T P + F P ) (7)
R = T P/(T P + F N ) (8)
FIGURE 8: Plot of Loss versus Iterations during training
period S = T N/(T N + F P ) (9)
VOLUME x, 20xx 7
This work is licensed under a Creative Commons Attribution 4.0 License. For more information, see https://creativecommons.org/licenses/by/4.0/.
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.2020.3012292, IEEE Access
Kumar et al.: Automatic Detection of White Blood Cancer from bone marrow microscopic images using Convolutional Neural Networks
8 VOLUME x, 20xx
This work is licensed under a Creative Commons Attribution 4.0 License. For more information, see https://creativecommons.org/licenses/by/4.0/.
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.2020.3012292, IEEE Access
Kumar et al.: Automatic Detection of White Blood Cancer from bone marrow microscopic images using Convolutional Neural Networks
(a) (b)
(c) (d)
(e)
FIGURE 11: Confusion Matrices for Machine Learning algorithms. (a) Support Vector Machines(SVM), (b) Random Forests,
(c) Decision Trees, (d) Naive Bayes, and (d) VGG-16
VOLUME x, 20xx 9
This work is licensed under a Creative Commons Attribution 4.0 License. For more information, see https://creativecommons.org/licenses/by/4.0/.
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.2020.3012292, IEEE Access
Kumar et al.: Automatic Detection of White Blood Cancer from bone marrow microscopic images using Convolutional Neural Networks
[15] David J Foran, Dorin Comaniciu, Peter Meer, and Lauri A Good- convolutional neural network. In 2018 IEEE Winter Conference on
ell. Computer-assisted discrimination among malignant lymphomas Applications of Computer Vision (WACV), pages 314–322. IEEE, 2018.
and leukemia using immunophenotyping, intelligent image repositories, [37] Nuh Hatipoglu and Gokhan Bilgin. Classification of histopathological
and telemicroscopy. IEEE Transactions on Information Technology in images using convolutional neural network. In 2014 4th International
Biomedicine, 4(4):265–273, 2000. Conference on Image Processing Theory, Tools and Applications (IPTA),
[16] Neslihan Bayramoglu, Juho Kannala, and Janne Heikkilä. Human epithe- pages 1–6. IEEE, 2014.
lial type 2 cell classification with convolutional neural networks. In 2015 [38] Philipp Prahs, Viola Radeck, Christian Mayer, Yordan Cvetkov, Nadezhda
IEEE 15th International Conference on Bioinformatics and Bioengineer- Cvetkova, Horst Helbig, and David Märker. Oct-based deep learning
ing (BIBE), pages 1–6. IEEE, 2015. algorithm for the evaluation of treatment indication with anti-vascular
[17] TTP Thanh, Caleb Vununu, Sukhrob Atoev, Suk-Hwan Lee, and Ki-Ryong endothelial growth factor medications. Graefe’s Archive for Clinical and
Kwon. Leukemia blood cell image classification using convolutional neu- Experimental Ophthalmology, 256(1):91–98, 2018.
ral network. International Journal of Computer Theory and Engineering,
10(2):54–58, 2018.
[18] Shrutika Mahaja, Snehal S Golait, Ashwini Meshram, and Nilima Jich-
lkan. Detection of types of acute leukemia. 2014.
[19] Jyoti Rawat, Annapurna Singh, HS Bhadauria, and Jitendra Virmani. Com-
puter aided diagnostic system for detection of leukemia using microscopic DEEPIKA KUMAR is currently working as
images. Procedia Computer Science, 70:748–756, 2015. an Assistant Professor in the Department of
[20] Tomasz Markiewicz, Stanislaw Osowski, Bonenza Marianska, and Leszek Computer Science & Engineering at Bharati
Moszczynski. Automatic recognition of the blood cells of myelogenous Vidyapeeth’s College of Engineering, New Delhi.
leukemia using svm. In Proceedings. 2005 IEEE International Joint She received her MTech degree in Information
Conference on Neural Networks, 2005., volume 4, pages 2496–2501. System from NSIT, Delhi. Currently, she is pur-
IEEE, 2005. suing a Ph.D. in the area of Machine Learning
[21] Nurul Hazwani Abd Halim, Mohd Yusoff Mashor, and Rosline Hassan. and Bioinformatics. She has published and pre-
Automatic blasts counting for acute leukemia based on blood samples. sented many research papers in various interna-
International Journal of Research and Reviews in Computer Science,
tional Journals and International Conferences.
2(4):971, 2011.
[22] Jianhua Wu, Pingping Zeng, Yuan Zhou, and Christian Olivier. A novel
color image segmentation method and its application to white blood
cell image analysis. In 2006 8th international Conference on Signal
Processing, volume 2. IEEE, 2006.
[23] Aimi Salihah, Abdul Nasir, N Mustafa, Nashrul Fazli, and Mohd Nasir. NIKITA JAIN has received her M.Tech degree in
Application of thresholding technique in determining ratio of blood cells 2014 from IIIT Delhi (A state university under
for leukemia detection. 2009. Govt. of NCT Delhi) with a specialization in In-
[24] Yoshimasa Horie, Toshiyuki Yoshio, Kazuharu Aoyama, Shoichi formation Security. Currently, she is an Assistant
Yoshimizu, Yusuke Horiuchi, Akiyoshi Ishiyama, Toshiaki Hirasawa, To-
Professor in the Department of Computer Science
mohiro Tsuchida, Tsuyoshi Ozawa, Soichiro Ishihara, et al. Diagnostic
& Engineering at Bharati Vidyapeeth’s College
outcomes of esophageal cancer by artificial intelligence using convolu-
tional neural networks. Gastrointestinal endoscopy, 89(1):25–32, 2019. of Engineering. She is a Ph.D. Research scholar
[25] Tanzila Saba, Muhammad Attique Khan, Amjad Rehman, and at Guru Gobind Singh Indraprastha University in
Souad Larabi Marie-Sainte. Region extraction and classification of Computer science specializing in Remote sensing
skin cancer: A heterogeneous framework of deep cnn features fusion and and information retrieval since 2016. She has more
reduction. Journal of medical systems, 43(9):289, 2019. than 20 publications in various national and international conferences and
[26] Kaushik Sekaran, P Chandana, N Murali Krishna, and Seifedine Kadry. journals of high repute.
Deep learning convolutional neural network (cnn) with gaussian mixture
model for predicting pancreatic cancer. Multimedia Tools and Applica-
tions, pages 1–15, 2019.
[27] Juan Zuluaga-Gomez, Zeina Al Masry, Khaled Benaggoune, Safa Mer-
aghni, and Noureddine Zerhouni. A cnn-based methodology for breast
cancer diagnosis using thermal images. arXiv preprint arXiv:1910.13757, AAYUSH KHURANA is currently pursuing
2019. B.Tech (2017-2021) from Bharati Vidyapeeth’s
[28] Sumaiya Dabeer, Maha Mohammed Khan, and Saiful Islam. Cancer College of Engineering, Delhi (Under GGSIP Uni-
diagnosis in histopathological image: Cnn based approach. Informatics versity), in the field of Computer Science. He com-
in Medicine Unlocked, 16:100231, 2019. pleted his high school from Delhi Public School,
[29] Anudba Gupta and Gupta Ritu. Sn-am dataset: White blood cancer dataset Dwarka. He is a Machine Learning Enthusiast and
of b-all and mm for stain normalization [data set]. https://doi.org/10.7937/ a keen researcher. He likes to develop new models
tcia.2019.of2w8lxr. with research interests in Artificial Intelligence,
[30] Taco Cohen and Max Welling. Group equivariant convolutional networks. Image Processing, Data Science, and Computer
In International conference on machine learning, pages 2990–2999, 2016. Vision using Deep Learning.
[31] Johan AK Suykens and Joos Vandewalle. Least squares support vector
machine classifiers. Neural processing letters, 9(3):293–300, 1999.
[32] Irina Rish et al. An empirical study of the naive bayes classifier. In IJCAI
2001 workshop on empirical methods in artificial intelligence, volume 3,
pages 41–46, 2001.
[33] Yael Ben-Haim and Elad Tom-Tov. A streaming parallel decision tree SWETA MITTAL is currently pursuing B.Tech
algorithm. Journal of Machine Learning Research, 11(2), 2010. (2017-2021) from Bharti Vidyapeeth’s College Of
[34] Andy Liaw, Matthew Wiener, et al. Classification and regression by Engineering, Delhi (Under GGSIP University), in
randomforest. R news, 2(3):18–22, 2002. the field of Computer Science. She completed her
[35] Wei Yu, Kuiyuan Yang, Yalong Bai, Tianjun Xiao, Hongxun Yao, and high school from Birla Balika Vidyapeeth, Pilani.
Yong Rui. Visualizing and comparing alexnet and vgg using deconvo- Her current research interests are Machine Learn-
lutional layers. In Proceedings of the 33 rd International Conference on ing, Computer Vision using Deep Learning.
Machine Learning, 2016.
[36] Ivan F Rodriguez, Rémi Mégret, Edgar Acuna, Jose L Agosto-Rivera,
and Tugrul Giray. Recognition of pollen-bearing bees from video using
10 VOLUME x, 20xx
This work is licensed under a Creative Commons Attribution 4.0 License. For more information, see https://creativecommons.org/licenses/by/4.0/.
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.2020.3012292, IEEE Access
Kumar et al.: Automatic Detection of White Blood Cancer from bone marrow microscopic images using Convolutional Neural Networks
VOLUME x, 20xx 11
This work is licensed under a Creative Commons Attribution 4.0 License. For more information, see https://creativecommons.org/licenses/by/4.0/.