Knowledge and Information Systems (2023) 65:3881–3921

https://doi.org/10.1007/s10115-023-01894-7

REVIEW

Computer-aided diagnosis systems: a comparative study of

classical machine learning versus deep learning-based
approaches

Ramzi Guetari1 · Helmi Ayari1 · Houneida Sakly2

Received: 23 September 2022 / Revised: 23 April 2023 / Accepted: 25 April 2023 /

Published online: 24 May 2023
© The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature 2023

Abstract
The diagnostic phase of the treatment process is essential for patient guidance and follow-up.
The accuracy and effectiveness of this phase can determine the life or death of a patient.
For the same symptoms, different doctors may come up with different diagnoses whose
treatments may, instead of curing a patient, be fatal. Machine learning (ML) brings new
solutions to healthcare professionals to save time and optimize the appropriate diagnosis.
ML is a data analysis method that automates the creation of analytical models and promotes
predictive data. There are several ML models and algorithms that rely on features extracted
from, for example, a patient’s medical images to indicate whether a tumor is benign or
malignant. The models differ in the way they operate and the method used to extract the
discriminative features of the tumor. In this article, we review different ML models for
tumor classification and COVID-19 infection to evaluate the different works. The computer-
aided diagnosis (CAD) systems, which we referred to as classical, are based on accurate
feature identification, usually performed manually or with other ML techniques that are not
involved in classification. The deep learning-based CAD systems automatically perform the
identification and extraction of discriminative features. The results show that the two types
of DAC have quite close performances but the use of one or the other type depends on the
datasets. Indeed, manual feature extraction is necessary when the size of the dataset is small;
otherwise, deep learning is used.

Keywords Machine learning · Deep learning · Computer-aided diagnosis system (CAD) ·

Feature extraction · Convolutional neural network · Tumor classification

B Ramzi Guetari
[email protected]
Helmi Ayari
[email protected]
Houneida Sakly
[email protected]
1 SERCOM Laboratory, Polytechnic School of Tunisia, University of Carthage, PO Box 743, La
Marsa 2078, Tunisia
2 RIADI Laboratory, National School of Computer Sciences, University of Manouba, Manouba 2010,
Tunisia

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1 Introduction

Medical imaging is becoming one of the most important techniques for the detection and
treatment of pathology, because of the numerous advantages it presents as well as its pro-
gressions and ranks that are steadily increasing. The various medical imaging modalities
allow the acquisition of information on tissues and/or certain functions while minimizing
the invasive manipulations for the patient and also guide the practitioner in the treatment
procedure.
There are two essential steps in interpreting the diagnostic information from medical
imaging: the first one is the identification of patterns, called “forms” in the lexicon of image
processing, while the second one is the association of these models with a suspected diagnosis.
The success of these two steps is strongly related to the clinician’s skills and is always subject
to his judgment. It is well known that two practitioners, having the same level of expertise,
often give more or less different interpretations of the same imaging data. In addition, the
tasks of identifying structures are tedious for a human operator, especially when it comes to
3D acquisitions.
In addition to the subjectivity of each practitioner’s diagnosis, the human perception,
especially the vision system, has its own limitations and may be unable to recognize certain
relevant information. For example, in traditional medicine, the processing of information
provided by medical magnetic resonance imaging (MRI) datasets usually relies on the prin-
ciples of “expert’s opinion” and the specialist’s experience in diagnosis and interpretation.
For the evaluation of most neuroradiology problems, this method, e.g., research, description,
and evaluation of focal lesions, is completely sufficient in daily clinical usage. This becomes
more difficult in case of diseases only detectable by subtle volumetric changes or by signal
disturbances. In this case, human perception is often unable to detect information relevant to
the correct diagnosis.
In order to make the diagnostic task as objective as possible, different systems for analyzing
and processing various types of medical images have been developed in recent years. These
systems allow especially to characterize human tissues, suspicious regions, pathologies, etc.,
and to produce an automatic or semi-automatic diagnosis [1]. These are computer-aided
diagnosis (CAD) systems. CAD systems use the most advanced image processing techniques
combined with AI and ML to establish the most reliable diagnosis possible. They have the
advantage of going beyond the limits of human memory and being able to detect pathological
changes that cannot be detected by physicians. They are intended to improve the quality of
patient care [2].
There are two main types of CAD systems developed by the scientific community: (i)
systems that operate based on features extracted by human experts and (ii) systems that learn
by themselves the features they rely on to discriminate pathologies. There are also hybrid
systems that rely on both manually extracted features from human experts and automatically
learned features, but these are not the focus of this work.
This paper reviews recent works in the field of CAD considering the two main identified
categories (Classical CAD and DL). The classification of thyroid and pulmonary nodules as
well as the COVID-19 diseases was interested to study and evaluate these CAD systems.
The paper highlighted the advantages and disadvantages of each of the two types of CAD,
to identify when it is appropriate to use the first or the second type, and to conclude with
perspectives for the improvement of computer-aided diagnosis systems.
The paper is organized as follows: Section 1 is the introduction; Sect. 2 presents the strat-
egy followed to collect the research materials that made this work possible. Section 3 covers

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Table 1 Selected digital libraries Digital libraries URL

SpringerLink http://link.springer.com
IEEE Xplore http://ieeexplore.ieee.org
Google Scholar http://scholar.google.com
ACM Digital Library http://dl.acm.org

the fundamentals of supervised machine learning models. Section 4 provides an overview of

the medical decision support system. Image feature extraction is covered in Sect. 5. Section 6
presents CADs based on handcrafted features and the corresponding ML models. Section 7
discusses deep learning-based CADs with as well as the most popular models used in design-
ing CADs. Section 8 is a discussion about the models as well as different works, and finally,
Sect. 9 concludes the whole work.

2 Search strategy

The bibliographic references used in this work were collected from four digital libraries:
SpringerLink, IEEE Xplore, Google Scholar and ACM Digital Library. The summary is
presented in Table 1. The choice of these digital libraries was guided by the ease of access and
the availability of a significant number of documents related to our research topic, which made
the task of selecting articles quite complex. Our choices were guided by certain questions
that we asked ourselves as well as by the date of publication. We have privileged the most
recent ones.
A total of 122 references were finally selected to conduct this research. The large majority
of the publications we have selected are papers published in journals (75%) and conferences
(22%). We have considered only a few articles (3%) from workshops, books or other sources.
Our investigations were mainly guided by the following research questions:

• RQ1: What are the research works carried out on CAD systems in the medical field?
• RQ2: What are the machine learning models used in CAD systems?
• RQ3: What are the metrics used for the evaluation of CAD systems?
• RQ4: On which features are CAD systems based to establish a diagnosis?
• RQ5: How are these characteristics identified?
• RQ6: What technical problems do CAD systems face?

3 Supervised machine learning

Today, when one talks about AI, most people think of ML. In reality, ML is one of the areas
of AI that focuses on the ability to learn how to perform a task based on observation of
an environment. It is the development, analysis, and implementation of methods that allow
a machine to evolve through a learning process and thus perform tasks that are difficult
or impossible to accomplish by more traditional algorithmic means. ML algorithms allow
computers to train on data inputs and use statistical analysis to produce values that fall within
a specific range. For this reason, ML facilitates the use of computers in building models from
sample data to automate decision-making processes based on the input data [3]. Applied

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to classification problems, it is about learning to distinguish the different elements of this

environment through the observation of examples.
Supervised learning consists of having a learning set, whose objects are labeled. For exam-
ple, a label could be a clearly identified class to which an object belongs. A test set composed
of objects whose membership classes are unknown is also needed in supervised learning.
The goal of learning from labeled examples is to construct a function that best approximates
an unknown function that generates random, independent, and identically distributed data,
of which one has only a few examples. A learning system based on examples is composed
of three main modules:
• A generator that generates random data called input vectors. These vectors are inde-
pendent and identically distributed according to an unknown probability distribution
P(x).
• A supervisor that associates for each input vector x an output y (the class) following an
equally unknown probability distribution P(x, y).
• A learning machine that implements a family of functions that must produce for each
input vector x an output ŷ as close as possible to the output y of the supervisor.

3.1 Supervised machine learning models

As applications of ML, classifiers can be built to distinguish an edible mushroom from a

poisonous one, to predict whether it will rain tomorrow based on current weather conditions,
or to produce a medical diagnosis (determining whether a patient has a disease based on
a set of symptoms). The considerable challenge in ML is to develop an algorithm that can
efficiently solve classification problems of different types. The quality of a learning algorithm
thus depends on its ability to build a classifier that generalizes the observed phenomenon.
ML approaches are continuously developed but some stand out for their efficiency and the
applications in which they are implemented. Among these algorithms, the K-nearest neighbor
method (KNN) [4, 5], artificial neural networks (ANN) [6], decision trees and random forests
[7], and genetic algorithms [8, 9] can be mentioned.
Generally speaking, a ML-based system searches for regularities in an available dataset
to extract the appropriate knowledge, without a predefined model. This method is now being
developed thanks to the increase in computer power and the accumulation of huge quantities
of data [10]. The regularities that a ML model looks for are translated into a features map.
These features, depending on the learning model, can be defined by experts or automatically
identified by the model itself.
Recently, the emergence of techniques based on ANNs has revitalized AI in general and
the design of CAD tools in particular. ANNs are highly connected networks of elementary
processors (Neurons) organized in layers and operating in parallel. Each neural network has
an input layer, an output layer and a number of intermediate layers called hidden layers.
Each artificial neuron receives a variable number of inputs from the upstream neurons and
produces a unique output. Each of these inputs is associated with a weight w representative
of the strength of the connection. The output of an artificial neuron then branches to feed a
variable number of downstream neurons.
An artificial neuron computes thevalue a which is the weighted sum of the inputs according
to the following expression: a = wi · xi + bi , where wi is the weight and bi is a bias.
The connections between the neurons that make up the network describe the topology of
the model; it can be any, but most often it is possible to distinguish a certain regularity. The
collective behavior of a set of neurons allows the emergence of higher-order functions with

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Fig. 1 Linear separation

respect to the elementary function of a single neuron. The setting of the values of the weights
which link the layers in the network is what constitutes the training of the system. Supervised
learning involves associating the inputs xi of a neural network with well-defined outputs yi
during the learning phase. The idea is therefore to provide much-known input–output pairs
(xi , yi ) of data and to vary the weights according to these samples in order to reduce the
error between the output of the network and the desired output. In other words, the goal is to
progressively improve the neural network to predict the correct y given x.

3.2 The learning process

 
Supervised learning requires a set of data Sn = { x (i) , y (i) , i = 1, . . . , n} called the training
set. The value n indicates the cardinal of the set S, x (i) is the ith object to be classified and
y (i) is the label associated with x (i) . Sn is the information provided to the learning algorithm
to train it. A classifier h is an application defined by: h :  −→ I where h is the classifier,
 is the vector space where the feature vectors representing the objects to be classified are
defined and I is the set of labels. I can for example be the set {−1, +1}, where −1 could
mean “malignant tumor” and +1 “benign tumor”.
The task of the learning algorithm given an object x (i) is to find the corresponding label
y (i) . Considering the tumor classification task, the classifier divides the space into two halves:
one labeled benign tumor, and the other malignant tumor. The classifier determines the
hyperplane (known as the decision boundary, Fig. 1) defined by the parameters θ and θ0 such
that θ · x + θ0 = 0, θ ∈  and θ0 ∈ R.
Then the evaluation of the quality of the classifier is needed with respect to the training
set Sn by computing the training error E n as defined in (1):

1    (i) 
n
E n (h) = h x  = y (i) (1)
n
i=1
  1, if error
h x (i)  = y (i) = (2)
0, otherwise.

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Fig. 2 Classifier optimization

Let’s rewrite the formula of the learning error with respect to θ and θ0 :

1   (i)  
n
E n (θ, θ0 ) = y · θ · x (i) + θ0 ≤ 0 (3)
n
i=1

In the learning phase, it is essential to minimize the learning error or even reduce it to
zero. It is quite possible that there are several classifiers that reduce the learning error to
zero. Which one to choose in this case? The classifier that also minimizes the test error
should be chosen. This error is defined in the same way as the learning error but applies
to a dataset outside the training data and whose labels are unknown. When the classifier
choice problem is transformed into an optimization problem, two aspects should be taken
into account: the “Loss” and the “Generalization”. If the learning and test errors are both large
then the model has not learned to classify objects very well and this phenomenon is called
“underfitting”. If the learning error is minimal but the test error is large then the classifier has
learned the training set with its noise, it is therefore not possible to generalize it; this is called
“overfitting”. Optimizing the “Loss” consists mainly in minimizing the learning error and the
“Regularization” consists in making the model general so that the test error is also minimal
as shown in Fig. 2. The following section will discuss the feed-forward neural network and
how to be trained.

3.3 Training feed-forward neural networks

Feed-forward neural networks with multiple hidden layers are complex models that attempt
to capture the representation of examples to the output unit in a way that facilitates the
actual prediction task. It is this part of learning the representation that makes the learning
problem difficult. It turns out that a simple (stochastic) gradient descent algorithm is capable
of finding a good solution to the resolution parameters, provided that the model is given some
overcapacity. It is therefore necessary to find an algorithm able to evaluate this gradient, i.e.,
the derivative of the loss with respect to the parameters. The solution to this problem is an
algorithm known as the backpropagation algorithm [11–13].
Parameterized models are functions that depend on input data and parameters (weights
and biases) that, when combined with the inputs, produce a result. Since the input data cannot
be modified, the quality of the result produced by the model depends on the parameters that
can be trained. At the initialization of a neural network, the weights and biases of the model

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receive random values, which makes it globally useless and inappropriate for the resolution
of a classification problem for example. It is therefore necessary to train the model so that it
can adjust these parameters in an efficient way allowing it to provide an adequate solution to
the problem at hand. The output of a neural network is a value ŷ = f (x, w), x is the input,
w is the set of trainable parameters, and ŷ is the result.
In supervised learning, this output is subject to a cost function C(y, ŷ), which compares
the real output y with the output of the model ŷ. ML mainly consists in optimizing the cost
function, usually by minimizing them by gradient-based methods. A gradient-based method
is a method/algorithm that finds the minima of a function, assuming that one can easily
compute the gradient of this function which is assumed to be continuous and differentiable
almost everywhere. The update of the parameters is done according to the expression (4) for
the weights and (5) for the biases (where wil j is the weight applied between neuron i of layer
l and neuron j of layer l + 1, bil is the bias and η is the learning rate.).
 
∂C y, ŷ
wi j = wi j − η ·
l l
(4)
∂wil j
 
∂C y, ŷ
bil = bil − η · (5)
∂bil
If the neural network is not trained, there is a very high probability that y and ŷ are very
different and the error is given by the cost function C(y, ŷ). Since the expected value y for
the neurons of the last layer is known, it is quite easy to know to what extent the weights
associated with each neuron of the penultimate layer contributed to this error. And if the
error of the penultimate layer is known, the error of the previous layer could be computed,
and so on, until the first one. The weights and biases are thus adjusted from the last layer
of the network to the first by calculating the appropriate partial derivative and applying the
adjustments formulated in (4) and (5). This process of adjusting the weights and biases of the
last to the first layer is called backpropagation. The feed-forward / backpropagation process
is repeated a number of times to minimize the cost function and allow the network to learn.
The following sections will discuss the most used evaluation metrics for machine learning
models.

3.4 Performance evaluation of classification algorithms models

Many choices of ML models are available to us. The nature of the problem to be solved helps
to guide the appropriate choice. For example, a classification algorithm cannot be applied to a
regression problem. Defining a ML model is important, but it must be relevant. In supervised
learning, the objective is to create models that generalize the learned situation, i.e., when faced
with new data, the machine is able to develop predictive models. It is, therefore, necessary to
know how to evaluate any learning algorithm on its dataset, avoiding as much as possible the
bias of over-fitting. A rigorous evaluation of the performance of an algorithm is an essential
step for its deployment.
In a classification problem, and this is the case in CAD systems, the accuracy is mostly
used to evaluate the performance of the model, but this is not enough to really judge the
model. That said, a model may appear to perform well for one performance indicator and
quite the opposite for another. It is usually necessary to combine two or more indicators
to judge the performance of a model. In the following, some of the most commonly used
performance indicators to evaluate a ML model are presented.

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Fig. 3 The Confusion Matrix

3.4.1 Confusion matrix

A confusion matrix (Fig. 3) is a tool to measure the performance of a ML model by checking

how often its predictions are correct compared to reality in classification problems. Correct
and incorrect predictions are highlighted and divided by class. The results are then compared
with the real values. True positives (TP) are cases where the model has predicted a positive
case and the actual class of the object is also positive. Similarly, true negatives (TN) are cases
where the model has predicted a negative case and the real class of the object is also negative.
False positive (FP) case is referred to when the real class of the object is negative and the
predicted class is positive. The false negative (FN) case is a case where the real class of the
object is positive and the predicted class is negative.

3.4.2 Accuracy

The accuracy is the ratio of the number of correct predictions to the total number of data in
the dataset as expressed by the formula (6).

TP + TN
Accuracy = (6)
TP + TN + FP + FN

Accuracy seems to be a very good indicator of performance and it is if the data is balanced
in the dataset. Otherwise, it becomes almost useless to measure the performance of a ML
model and a very bad model can give good accuracy.

3.4.3 Precision

The precision is the proportion of true positive results in the set of cases having been predicted
positive for a certain class; it is expressed by the formula (7).

TP
Precision = (7)
TP + FP

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3.4.4 Recall (or sensitivity) and specificity

Recall is the fraction of correctly predicted TP cases for a class relative to all cases actually
belonging to that class. This is expressed by the formula (8)

TP
Recall = (8)
TP + FN
The specificity is estimated by the proportion of tn predicted by the model compared to
all the cases listed as negative in the dataset; it corresponds to the expression (9).

TN
Specificity = (9)
TN + FP

3.4.5 F1-score

Precision and recall are complementary measures to the accuracy allowing to better qualify
the performance of a ML model and particularly in cases where the classes are not distributed
in a balanced way. The idea here is to combine the two measures into one to evaluate a ML
model which gives us a metric called F1-score or Sørensen–Dice coefficient or Dice Similarity
Coefficient (DSC). It is the harmonic mean between precision and recall expressed by the
formula (10).

Precision × Recall
F1-score = 2 × (10)
Precision + Recall

3.4.6 Receiver operating characteristic (ROC)

The ROC curve is a graphical representation of the relationship between the sensitivity and
the specificity. The ordinate represents the sensitivity and the abscissa corresponds to the
quantity (1 − Speci f icit y). It illustrates the performance of a binary classification system
when its discrimination threshold varies. Although it is possible to construct the ROC curve
manually, the use of specialized calculation software is recommended because it requires a
precise procedure which will not be detailed in this paper.

3.4.7 Area under the ROC curve (AUC)

The area under the curve (abbreviated as AUC) is the measure of the area under the plot of a
mathematical function. Formally, this value corresponds to the integral of the function studied.
It provides an aggregate measure of performance for all possible classification thresholds.
The value of the AUC varies from 0 to 1. A model whose predictions are 100% false has
an AUC of 0.0; a model whose predictions are 100% correct has an AUC of 1.0. The area
under the ROC curve can be interpreted as the probability that, among two randomly selected
subjects, e.g., one with a disease and one without, the value of the marker is higher for the
diseased than for the non-diseased. Therefore, an AUC of 0.5 (50%) indicates that the marker
is non-informative. An increase in AUC indicates improved discriminatory abilities, with a
maximum of 1.0 (100%).

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4 Medical decision support systems

As medical knowledge has continued to grow, physicians can no longer master all the medical
knowledge needed to recognize diseases or to determine the best therapeutic treatment. They
often use external sources of information, traditionally colleagues, books, and scientific
literature, to find the information they need in order to establish their diagnoses and to define
a therapy procedure. Nevertheless, in spite of the large amount of easily accessible resource
materials available online, the help from colleagues, etc., finding a solution to a given patient’s
problem is a difficult task.
Very early on, the qualities of the computer (memory, speed, computing power) emerged
as potential solutions to this problem, and computer-aided medical decision support systems
(CAMDS) were developed. CAMDS are software systems that “provide clinicians, staff,
patients, and other individuals with knowledge and person-specific information, intelligently
filtered and presented at appropriate times, to enhance health and health care” [14]. These
systems are designed to assist the practitioner in his reasoning with a view to identifying a
diagnosis and choosing the appropriate therapy. They are not intended to replace the decision-
maker by offering “ready-made” solutions.
CAD systems are a category of CAMDS that help radiologists to make an accurate diag-
nosis with the benefit of information generated by computerized image analysis. The concept
of CAD systems has emerged over the last twenty years to provide some answers to problems
related to the limits of human perception capabilities and thus help radiologists to effectively
evaluate medical images to detect lesions and pathological changes at an early stage [15].
The purpose of a CADs is to classify images according to a set of defined classes. CADs are
automated systems that provide radiologists with a second opinion that is devoid of human
subjectivity and assist them in the diagnosis by providing them with a mapping of suspi-
cious parts in the medical images. CAD systems are an interdisciplinary technology, they
use a variety of disciplines and concepts such as AI, computer vision, image processing, etc.
Their principle is the extraction of the characteristics of a medical image and the design of a
prediction and detection model from a learning base. This generally empirical model allows
quantifying the probability that an area of a test image is pathological.
The analysis and processing of medical images is a sensitive area where the cost of the
error can be fatal. The goal of a CAD is to increase the sensitivity of detection and reduce
the rate of false positives and false negatives. A CAD system requires a thorough analysis
of the digitized medical images in order to extract the most significant characteristics that
lead to the automatic or semi-automatic diagnosis. The objective of a CAD is to classify the
analyzed images according to well-defined criteria. For example, it is a question of classifying
suspicious tumor zones of human tissue into benign or malignant tumors. Feature extraction
is a stage of image processing that often goes hand in hand with classification. Indeed, to
establish a rule of classification (supervised or not), one generally bases oneself on a set
of numerical criteria describing the object or the phenomenon observed. In practice and
depending on the context, two types of characteristics can be extracted:

• Generic descriptors that do not necessarily have a physical or biological interpretation

(SIFT [16], SURF [17], oriented gradient histograms [18], shape background [19], bags
of words [20], etc.),
• Descriptors having a physical meaning. Typically, in the biomedical field, these may be
morphological characteristics describing the observed objects (cell size, vessel thickness,
etc.).

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The extraction and selection of features from a medical image is therefore an essential task
that requires sophisticated image processing methods. The performance of a CAD system
depends on this selection since these features are used for image classification and thus for
diagnosis [21].

5 Image feature extraction

In computer science, an image is a 2D digital signal and can be interpreted as a 2D matrix

of brightness or color values. Such an interpretation makes it possible to represent an image
in different ways. Indeed, the images can be seen as a set of pixels, characterized by their
variable light intensity, representing a concrete or abstract scene. They can be modeled as
a function f whose values f (x, y) vary according to the spatial coordinates. An image is
also a 2D signal, or a set of textures or patterns arranged in a specific manner to describe the
scene.
The methods of analysis of images have a common basis: the global or local character-
ization of the images that would be dealt with. This characterization involves the analysis
and processing of the image that focuses on low-level attributes or features (also called
descriptors). These descriptors may be at the pixels level [22, 23] (histograms, co-occurrence
matrices), shapes (geometric attributes), or regions (patterns, textures). A low-level feature
is a set of values that are extracted directly from the image. The extraction of the low-level
characteristics represents the first abstraction with respect to the raw image, the goal is that
this characteristic must be a distinctive criterion with respect to the visual entities that one
seeks to characterize. These low-level descriptors can be used for the entire image as they
can be used for part of the image.
Extracting visual descriptors on the entire image (global descriptors) reduces the amount
of required processing and the cost of searching for the most similar images. Algorithms
allowing the extraction of global descriptors are simple, fast, and not memory-consuming.
These descriptors also are more robust to noise that can affect the signal. However, the
global approach does not allow an efficient search of objects (in a broad sense) in the image.
Moreover, the attributes of small objects are embedded in a single global descriptor of the
image. Conversely, the descriptors extracted from a part of the image (local descriptors) are
efficient but require a lot of processing. Local features, also known as structural features, as
opposed to global features, have locality property and focus specifically on the various areas of
the image. Local descriptors can be (i) regions of the image obtained either by segmentation
of the entire image or by search for regions of interest, or (ii) points of interest. This consists
in treating the shape or the morphology of the image’s characteristics. This analysis is based
on nonlinear image processing techniques. The use of appropriate morphological operations
makes it possible to simplify the images while preserving the essential shape of the geometric
structures (loop cavitations, connected objects, etc.) and eliminating the noise.
The principle of the morphological analysis is to detect in the image elements such as
contour, edge density, edge direction, number of horizontal or vertical lines, co-termination
and parallel lines [24], spatial/layout relations [25], number of endpoints, number of cross
points, horizontal curves at top or bottom, etc. The purpose of contour analysis is to look
for areas of an image with remarkable local properties, such as abrupt and local changes
in intensity, texture changes, specific points, and so on. These techniques are often used in
preprocessing to solve more difficult problems (object detection, interpretation, registration,
tracking of objects in a video, etc.). These techniques have, however, some problems such as

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the noise in the image that can affect the accuracy of the detection and contour coding that
closely depends on the starting point of the tracking algorithm.
Local descriptors allow for keeping localized information in the image, thus avoiding
certain details being lost in the rest of the image. Although this type of representation brings
undeniable advantages such as the coding of certain knowledge on the structure or the supply
of certain knowledge on the type of components constituting this object, it also has very
notable disadvantages. Indeed, they are sensitive to different variations and the quantity of
observations produced is very large, which implies the processing of a large volume of data.
Other descriptors may be extracted from an image using other types of analysis. The
statistical analysis of an image consists of representing objects by statistical measures. The
statistical analysis techniques range from the simplest, such as the distribution of pixels in
the various regions of the image and the histograms, to the more complex ones like principal
component analysis. Metric characteristics are physical measurements of the image such
as the height, width, and ratio of these two measurements. Adaptive features are extracted
directly from the image and require a learning step. Indeed, the system uses a representation
close to the original image and builds the characteristics extractor, and optimizes it. These
descriptors are not very relevant in the field of CAD.
The purpose of the feature extraction process is not only to reduce the amount of input
information but also to obtain the most discriminating information for the recognition step.
This is an essential phase of a recognition system. However, some feature extraction tech-
niques are accompanied by an irreversible loss of information. As a result, a compromise
between the quality and the quantity of information is essential. In the ideal case, the descrip-
tors must be robust to the different variations, especially geometric transformations (rotation,
translation, etc.), the variation of the viewing angles, the variation of scale, etc.
The choice of extracted features is often guided by the desire for invariance or robustness
with respect to transformations of the image. A descriptor is qualified as good if it can
describe the content of the image with great variance of scale and interoperability, and if
it can distinguish any type of objects. A survey of existing methods of extracting feature
descriptors is presented in [26]. These descriptors are subdivided into four classes: shape
descriptors, color descriptors, texture descriptors, and motion descriptors.
When analyzing medical images, which is the subject of this paper, the decision about
the nature of a tumor depends on a number of visual features that can be supplemented
by additional examinations. A CAD system requires the association of symptoms (physical
characteristics of thyroid nodules for example) with features extracted from the images. This
association is performed either manually by specialists or automatically by the CAD system
itself. In both cases, the learning step is the pillar on which the diagnostic assistance will be
based. The success of this step depends on the images that will be used for training (dataset),
the selected discrimination characteristics, the accuracy of the image annotation and, in the
case of manual annotation, the objectivity of this process.

6 CADs based on handcrafted features

The purpose of a CAD based on handcrafted features is to classify images according to a set
of defined classes. Object classification consists of establishing a procedure that associates
a class (among other classes) with a given data. The supervised classification consists of
having a learning set, whose objects and classes to which they belong are clearly identified,
and a test set, composed of objects whose membership classes are unknown.

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Image classification is an important task in the field of computer vision, object recognition,
and ML. The use of low-level image descriptors and the bag-of-words model are at the
heart of today’s image classification systems. Most image classification environments have
three steps: (i) the extraction of the low-level descriptors in images, (ii) the creation of a
vocabulary of visual-words, and (iii) the learning of the model of images’ classes, during
which the procedure (classifier) to associate an object to a class is defined. Then follows the
phase of classification (or prediction) during which the classification rules established (or
learned) during the previous step are used to deduce the class of an object that is, a priori,
unknown.
In the first step of extracting the low-level descriptors [27]. The most common choices in
recent methods are SIFT [16], SURF [17], or DSIFT [28]. The second step is the creation of
the visual vocabulary, the usual choice for this step is the use of a K-means algorithm and the
creation of a bag-of-words. The third step is the training of the classifier, many systems often
choose support vector machines with linear or nonlinear kernels. Most of these systems are
then evaluated on small datasets that fit well in central memory, such as Caltech-101 [29],
Caltech-256 [30], or PASCAL VOC [31].
As an example, the thyroid ultrasound image has different features that can be extracted
visually. These characteristics are interpreted by radiologists and the results of the diag-
nosis depend on the experience of the latter. Several studies have attempted to deal with
the characteristics of thyroid nodules and have identified some features as suggestive ones.
Based on the latter, a Thyroid Imaging Reporting and Data System (TIRADS) [32] has been
developed to classify thyroid nodules based on their probabilities of malignancy. The cre-
ators of TIRADS develop a grouping of ultrasound signs into ten original aspects related to
categories TIRADS 1 to 5 of increasing probability of malignancy. The TIRADS system is
based on 4 signs strongly suggestive of malignancy, namely (i) nodule thicker than wide,
(ii) nodule with irregular borders, (iii) microcalcifications and (iv) very hypoechoic nodule.
The TIRADS classification makes it possible to select the nodules for which an ultrasound-
guided cytopunction is indicated (mandatory examination before any surgical indication).
This system is, however, not always reliable, since accuracy is often based on the personal
experience of radiologists.

6.1 Significant visual attributes

Classification, whether supervised or not, is based on rules established in relation to a set of

numerical criteria of an image describing the object or phenomenon. These criteria represent
visual characteristics and their extraction consists of mathematical transformations calculated
on the pixels of a digital image. The classification rules are similarity rules applied to the
criteria representing an image or a part of an image. The following presents some of the most
important features used in medical image classification.

6.1.1 Texture characteristics

The texture is a local spatial variation in pixel intensities and orientation [33]. It is a very
important characteristic used for object detection in the region of interest (ROI) in the image,
and its goal is to get distinctive features that describe the inner intensity distribution of dif-
ferent classes in images by texture analysis. A number of structural, spectral, and statistical
model-based techniques are used to compute texture feature descriptors such as gray level

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histogram, run-length matrix, gray level cooccurrence matrix (GLCM), and contourlet trans-
form coefficient. GLCM is a widely used statistical texture analysis method that analyzes
regional textures using second-order texture features. It can reflect the position distribution
characteristics between pixels with the same gray level, which is the basis for calculating the
texture feature, as well as the comprehensive information of the gray level of the image in
the adjacent direction [34], the adjacent interval, the amplitude of the change, and so on. It
also describes the frequency with which different gray-scale value combinations appear in
an image and measures the connection between neighbor pixels at four angles (0◦ , 45◦ , 90◦ ,
135◦ ) [35]. Given an image I of size N × N in grayscale, the GLCM matrix is computed by
Eq. (11) where the shift operator (x, y) indicates a position (ignoring edge effects) that
can be applied to any pixel in the image.


N −1 N
 −1
1, if I (x, y) = i and I (x + x, y + y) = j
P (i, j) = (11)
x=0 y=0
0, otherwise.

A whole series of new descriptors have been derived from the GLCM to highlight the
most important parameters of these cooccurrence matrices.

Correlation (12): a measure of the similarity of the image’s different gray levels in the row
and column directions, where μ and σ are the mean and standard deviation, respectively.


N −1
(i − μ)( j − μ)
Correlation = P(i, j) (12)
σ2
i, j=0

Energy (13): the energy is a measure of the image’s localized change and represents the rate
of change in the color/brightness/magnitude of pixels over time and space.


N −1
Energy = P(i, j)2 (13)
i, j=0

Entropy (14): it is defined in images as the corresponding states of intensity level to which
individual pixels can adapt.


N −1
Entropy = − log P(i, j)P(i, j) (14)
i, j=0

Contrast (15): it is the amount of color or grayscale differentiation that exists between
various image features in both analog and digital images.


N −1
Contrast = P(i, j)(i − j)2 (15)
i, j=0

Homogeneity (16): used to determine the distribution of gray and/or color values within an
image.


N −1
P(i, j)
Homogeneity = P(i, j) (16)
1 + (i − j)2
i, j=0

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Auto-correlation (17): the degree of similarity between a given time series and a lagged
version of itself over successive time intervals.

1
Auto-correlation = P(i, j) (17)
i, j=1

Cluster-shade (18): helps assess perceptual concepts of uniformity by measuring the

asymmetry of the GLCM matrix

N −1 N
 −1
 3
Sha = i + j − μx − μ y × P(i, j) (18)
i=0 j=0

Dissimilarity (19): represents the distance between pairs of pixels in the ROI.

N −1 N
 −1
Dissimilarity = |i − j| × P(i, j) (19)
i=0 j=0

6.1.2 Shape characteristics

The shape is a significant visual aspect in image processing. It is defined by a set of char-
acteristics that allow one to identify a specific form of a representative class. Some entity
extraction approaches, such as the Zernike moment [36, 37], domain of shape change, and
one-dimensional function, are employed to define a shape S (Area A defined by Eq. 20,
Perimeter P specified by Eq. 21, Circularity C expressed by Eq. 22, etc.) [38]. The link
between the area of a shape and the area of a circle with the same perimeter is represented
by Circularity [39]. These features describe the irregularities used by radiologists to make a
diagnosis.

A(S) = I (x, y)A (20)

where A symbolizes the size of each pixel and I (x, y) = 1 if the pixel belongs to the
region, (x, y) ∈ S, and 0 else.

P(S) = (xi − xi−1 )2 + (yi − yi−1 )2 (21)

where xi and yi symbolizes the coordinates of pixel i.

4π × A(S)
C(S) = (22)
P(S)2

6.1.3 Intensity characteristics

This feature allows us to characterize the intensity of different regions of an image. One of the
approaches widely used is the histogram approach [38] that allows the analysis by intensity
values on the whole or parts of an image. Intensity is described by parameters such as the
average of the pixel values (23), the variance (24) (and the standard deviation (25)), and the
skewness (26).

n
μ= P(i, j) (23)
i, j=1

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3896 R. Guetari et al.


n
σ2 = P(i, j)(i − μ)2 (24)
i, j=1

 n
σ = P(i, j)(i − μ)2 (25)
i, j=1


n
Skewness = (i − μ)3 P(i, j) (26)
i, j=1

6.2 Feature detection methods

The richness, diversity, and complexity of the data involved in image segmentation make this
feature extraction step necessary. Their theoretical scope covers a wide spectrum, from data
analysis methods to the effective minimization of Bayes’ error. There are many methods for
the detection of various types of features and some of the most popular ones are represented
in the following.

6.2.1 The local binary pattern (LBP)

LBP (27) is an alternative and unifying approach to the traditionally divergent statistical and
structural models of texture analysis [40]. Due to its computational simplicity, efficiency, and
discriminating power, it has been widely used in various applications. It proceeds by labeling
the pixels by thresholding the neighborhood of each pixel to obtain a result considered as a
binary value [34, 41]. It is robust to monotonic changes in the grayscale that can be caused
by illumination variations.

p−1
LBP P,R = s(g p − gc )2 p (27)
n=0

where gc is the gray level intensity value of the center pixel and g p is the value of the center
pixel’s equivalent surrounding pixel. The radius of the circular neighborhood is R, and P is
the number of neighbors. The indicator function, s(x), is defined as in (28).

1, if x ≥ 0
s (x) = (28)
0, if x < 0

6.2.2 Scale invariant feature transform (SIFT)

SIFT is a method, developed in 1999 and very popular in the field of computer vision, to
extract features (or points of interest or key points) [42] from an image and compute their
descriptors. A descriptor is a vector that describes the neighborhood of the feature to which
it is associated [43]. It is used to find the pairs of features that are most similar in two
images. To facilitate this matching step, the descriptor must have many invariance properties
(rotation, scale, illumination). Thus, the descriptors of two features that are identical except
for a geometric or photometric change must be as close as possible. The matching step is
then to compare the descriptors. SIFT has 4 majors steps:
• Key point Detection

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• Key point Localization

• Orientation Assignment
• Key point Descriptor / Feature matching

The algorithm starts the calculation of the difference of Gaussians (DoG) to detect the
local extrema (AKA key points) in the spatial scale. Then, using a threshold value, more
precise key point locations are identified. The third step assigns the orientation to describe
the key points with image rotation invariance. Finally, in the last step, a set of key point
descriptors is generated, each of which generates orientation histograms [43].

6.2.3 Speeded-up robust feature (SURF)

SURF [44] is a local feature detection and descriptor algorithm based on properties similar
to those of SIFT, while reducing complexity. The SURF algorithm is performed in two steps
[45, 46]: a first step in which the points of interest are identified and a second step allowing
the extraction of the descriptors. The detection of the points of interest is performed by
approximating the convolution of the Gaussian second-order partial derivatives using box-
type filters. This first step also allows the construction and localization of the scale space.
In the second step of descriptor extraction, a descriptor vector corresponding to a point
of interest is generated. The pixels included in a circular neighborhood around the point
of interest are considered and the Haar wavelet responses (HWRs) [47] in the horizontal
and vertical directions are calculated. This allows us to obtain the main orientation in an
orientation window of size π/3, which is moved along the given sliding step. A square
region R centered on the point of interest is then oriented along the main orientation to allow
the descriptor vector to be invariant to image rotation. HWRs are again computed for each
pixel in the 4 × 4 sub-regions that make up the square region R. A four-dimensional vector
is then computed for each sub-region from the HWRs of the pixels it contains.

6.2.4 Oriented fast and rotated BRIEF (ORB)

ORB [48] uses features from accelerated segment test (FAST) key point detector and binary
BRIEF descriptor. The concept of ORB is to extract less and the best features from an image
[49]. Compared with SIFT and SURF, the computational cost of ORB is less and its magnitude
is faster than SURF. It detects a large number of key points by using the FAST key point
detector and then to find relevant features that have less sensibility to noise and generate
better results from the extracted key points it uses a Harris corner detector [50]. Moreover,
for the quick key focuses on the direction, ORB uses OFAST and for the BRIEF descriptor
with orientation (rotation) angle it uses RBRIEF, and lastly applies orientation to transform
the used sample in BRIEF descriptor [49, 51].

6.3 Features’ selection

Feature selection is the process of minimizing the data by reducing the redundant, correlated,
and irrelevant features of the dataset. It helps in dimensionality reduction by selecting the
optimal feature subset that contains the necessary information, which could enhance the
learning algorithm speed and improve the performance and the accuracy of the classification
[52]. The importance of feature selection is that it conserves the original meanings of original
features, which provides superior readability and interpretation for the classification model

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[53]. Hereafter, two of the most representative methods for feature selection, namely PCA
and LDA, are represented, knowing that other methods have been used for this purpose such
as the RF used in [38].

6.3.1 Principal component analysis (PCA)

PCA [54] is a linear dimension reduction technique that employs an orthogonal transforma-
tion to transform a set of correlated variables to a set of uncorrelated variables if the dataset
is regularly distributed jointly [55], and is widely applied in many different fields. The main
concept of PCA is to convert a-dimension data into a new b-dimension data called principal
component where (b≤a). Principal components are new orthogonal b-dimensional features
that are built from the original a-dimensional features. In further depth, all of the freshly con-
structed PCs are linear functions with rapid reduction of variance that are uncorrelated with
one another. The first few PCs maintain the majority of the variation from the original data,
whereas the last few PCs with little fluctuation can be useful in outlier detection [56]. PCA
looks for a linear combination of variables from which to extract the most variation. After
removing this variance, PCA looks for a second linear combination that iteratively explains
the greatest proportion of the remaining variation. This method is known as the principal axis
method, and it produces orthogonal (uncorrelated) factors [57]. PCA has 4 steps [55, 58]:
• Step 1: Data Normalization.
• Step 2: Calculation of the covariance matrix of the features.
• Step 3: Calculation of the eigenvector and eigenvalue of the covariance matrix.
• Step 4: Projection of the raw data into k-dimensional subspace.

6.3.2 Linear discriminant analysis (LDA)

LDA [59] is a dimensionality reduction technique and statistical-based pattern ML classifier

widely used in different fields and used to solve many classifications and data visualiza-
tion problems. The concept of LDA is to by maximize the average between-class scatter
and decrease the average within-class scatter. This method uses label information to learn
appropriate transformation directions by using the label information to earn a discriminant
projection [60]. LDA is used to find a linear transformation that categorizes several classes. It
is a simple and robust algorithm [61], and when the datasets are linearly separable, LDA per-
forms exceptionally well in classification tasks. In reality, LDA typically works effectively,
especially for low-dimensional issues [62].

6.4 Classification models

This section describes some of the most common machine learning techniques. There are
numerous classification tasks that can be performed. Because each algorithm is used to solve
a specific problem, each task frequently necessitates a different algorithm. Classification
models include support vector machine, random forest, Naive Bayes, and K nearest neighbor.

6.4.1 Support vector machine (SVM)

SVM [63] is a ML model that is commonly used for regression and classification problems. It
works by mapping a subset of data into a high-dimensional space, where the data is then split

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into two classes by a linear separator (Fig. 1) known as a hyperplane [64]. Note that there
can be an infinite number of hyperplanes to choose from. By lowering the distance between
the hyperplane focuses and maximizing the margin between the classes, SVM can select
the hyperplane that does the best job of classifying the data [65]. The margin is the distance
between each class’s boundary and its nearest point [66]. These points closest to the boundary
are referred to as support vectors [67, 68]. In the linear case [69], The two classes are linearly
separable, which means that it is possible to find at least one hyperplane defined by a vector
with a bias that is capable of separating the classes with zero error. There are many cases
where even the use of the optimal hyperplane will not be effective in linearly separating the
data sets. For that reason, SVM can create a nonlinear hypersurface of decisions to classify
nonlinearly separable data and transform the input vector to a vector with higher dimension
feature space.

6.4.2 Random forest (RF)

RF [70] is a decision tree-based method that performs effectively in a classification task. It

is a mixture of tree predictors, with each tree relying on vector values chosen at random and
independently. By fitting each tree on a bootstrap sample rather than the original sample, it
reduces over-fitting and improves accuracy by averaging prediction across multiple different
trees [71]. RF trains the image dataset by infusing randomness into the training of the trees,
followed by combining the outputs of each trained tree into a single classifier. The test image
is then sent down through each tree until it reaches the leaf node in the second phase. The
average of the posteriors across all trees is then used to classify the input image [43]. The
fundamental difference between the two is that a random forest can produce more reliable
ensemble forecasts than a decision tree [72].

6.4.3 Naive Bayes (NB)

NB [73] is a probabilistic classifier based on the Bayes theorem that describes the probability
of an event based on prior knowledge of the conditions that could be associated with the event.
This model is a relatively simple and sophisticated classification strategy that is suitable for
building and analyzing very large datasets [74]. NB is an extremely capable and scalable
method, and its model is simple to construct and can handle massive amounts of data [68]. It
uses three steps to predict the class label with the highest posterior probability: The dataset is
turned into a frequency table in the first stage. After determining the probabilities, the second
step is to create a likelihood table. In the final stage, the posterior probability for each class
is calculated using the NB equation shown in expression (29)
P (y|a) · P (a)
P (a|y) = (29)
P (y)
where P (a|y) indicates the posterior probability of a class, P(a) represents the class prior
probability, P (y|a) shows the likelihood which is the probability of predictor given class,
and P(y) indicates the predictor’s prior probability.

6.4.4 K nearest neighbors (KNN)

The KNN [75] model is a non-parametric supervised ML algorithm widely used for pattern
classification and regression problems. KNN is a simple and easy classifier to implement, it

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does not require a huge memory for storage and has an impressive performance in multi-model
classes [43]. It acts as a classifier using two factors, namely the similarity measure or distance
function and the chosen k value, with the performance depending on the aforementioned
factors. For any new data point, KNN first calculates the distance between all data points
and gathers those that are close to it. The algorithm then organizes those closest data points
based on their distance from the target data point by employing various distance functions.
Furthermore, the next step is to collect a specific number of data points with the shortest
distance among all of them and categorize them based on their distance.

6.5 Related works

This literature review is particularly interested in work concerning the diagnosis of thyroid
nodules. Several methods were presented to classify thyroid nodules as benign or malignant;
these methods extract diverse attributes to generate the feature vector and employ various
ML techniques (classifiers). Table 2 includes a summary of the related work mentioned in
this paper.
Shankar et al. [69] proposed a model for classifying thyroid data that makes use of optimal
feature selection and a kernel-based classifier process. They used Multi-Kernel SVM (MK-
SVM) to create classification models. The novelty and goal of this proposed model as feature
selection is to improve the performance of the classifying process using improved grey wolf
optimizer [76]. The datasets were obtained from the UCI repository. The proposed thyroid
classification achieves 97.49% accuracy, 99.05% sensitivity,94.5% specificity, and F1-score
of 98.26%.
In [77], the authors used internal characteristics such as content and echogenicity and
external characteristics such as margin, shape, and orientation to determine the malignancy
of the thyroid nodule along with the CAD system. They first applied an adaptive median
filter with by bilateral filter to reduce the noise of the images. Then, active contour and
morphology operations were applied for the segmentation of the nodules. After the extraction
of geometric and texture features, they used the multi-layer perception to classify the internal
characteristics and SVM to classify external characteristics. CaThyDB is the used dataset,
and the classification of this technique achieved 100% sensitivity, 95.45% specificity, 97.78%
accuracy, and 98.87% F1-score which means that the proposed CAD system can be used by
radiologists in classifying thyroid nodules and the perspective of this article is to develop a
fully automatic system.
Prochazka et al. [78] designed a CAD that uses only direction-independent features by
two-threshold binary decomposition. Thus, during image acquisition, the CAD is not influ-
enced by the orientation and inclination angle of the ultrasound transducer. To calculate
direction-independent features, authors applied several algorithms such as histogram analy-
sis and segmentation-based fractal texture analysis algorithm. Axial US images of 40 patients
were obtained from their clinic’s database system. They also extracted various features such
as histogram parameters, fractal dimension, and mean brightness value in different grayscale
bands from 40 thyroid nodules (20 malignant and 20 benign). SVM and RF classifiers were
used to classify data. Along with the use of leave-one-out cross-validation method, SVM
achieved higher accuracy with 94.64%, while random forests achieved 92.42%. Conclud-
ing that the proposed system with SVM classifier has better accuracy and is reliable for
radiologists to use to diagnose the thyroid nodules.
In [79], two distinct ML techniques, SVM and RF were evaluated for thyroid disorder
diagnosis. The experiment was carried out using the Thyroid dataset from the UCI Machine

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 Table 2 Related literature review
Method Classifiers Accuracy (%) Sensitivity (%) Specificity (%) F1-score (%)

Shankar et al. [69] MK-SVM 97.49 99.05 94.50 98.26

Colakoglu et al. [80] RF 86.80 85.20 87.90 85.99
Nugroho et al. [77] SVM 97.78 100.00 95.45 98.87
Ataide et al. [82] RF 99.33 99.39 99.25 99.35
Aboudi et al. [38] SVM 93.29 98.45 90.94 95.80
RF 96.13 93.27 97.04 94.67
Prochazka et al. [78] SVM 94.64 NA NA NA
RF 92.42 NA NA NA
Olatunji et al. [68] RF 90.91 93.00 100.00 96.00
SVM 84.09 86.00 92.00 89.00
NB 81.82 93.00 93.00 93.00
Alyas et al. [81] RF 94.80 94.80 91.00 94.80
Computer-aided diagnosis systems: a comparative study…

NB NA 93.00 78.00 NA
KNN NA 59.00 91.00 NA
Shivastuti et al. [79] SVM 93.00 93.00 NA 91.00
RF 92.00 92.00 NA 88.00
Rehman et al. [65] NB 100.00 100.00 100.00 100.00
LR 100.00 100.00 100.00 100.00
KNN 97.84 96.00 98.00 97.00
SVM 86.02 76.00 80.00 84.00
DT 75.34 67.00 80.00 62.00
Chandel et al. [86] KNN 93.44 NA NA NA
NB 22.56 NA NA NA
Prochazka et al. [83] RF 95.00 95.00 95.00 95.00
SVM 91.60 95.00 90.00 93.26

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Learning Repository. The accuracy, precision, recall, and F-score of these two ML techniques
were compared using four performance metrics. Based on the experimental results shown in
Table 2, SVM is found to be superior to random forest for thyroid disorder diagnosis.
Aboudi et al. [38] presented a new CAD system developed to classify thyroid nodules
trained with 447 US images of thyroid nodules. Statistical feature extraction methods were
used on these images to extract features. The most relevant and non-redundant features
were chosen using a feature selection method based on RF and the multi-objective particle
swarm optimization algorithm. The nodules were then classified using SVM and RF. The
classification performance metrics were evaluated using 10-fold cross-validation. Using the
contour-based ROI, their proposed CAD achieved a maximum accuracy of 94.28% for SVM
and 96.13% for RF.
In [80], Colakoglu et al. evaluate the diagnostic utility of ML-based quantitative texture
analysis for distinguishing benign and malignant thyroid nodules. The RF classifier was used
to evaluate 306 quantitative textural aspects of 235 thyroid nodules from a total of 198 individ-
uals. Reproducibility tests and a wrapper approach were used to select features and reduce
dimensions. The proposed method was compared with histopathologic or cytopathologic
findings as a reference method for diagnostic accuracy, sensitivity, specificity, and AUC. For
the results, 284 of 306 initial texture features demonstrated high reproducibility (intraclass
correlation ≥ 0.80). The RF classifier correctly detected 87 of 102 malignant thyroid nodules
and 117 of 133 benign thyroid nodules, for a diagnostic sensitivity of 85.2%, specificity of
87.9%, F1-score of 85.99%, and accuracy of 86.8%. The AUC of the model was 0.92. ML
classification can accurately distinguish between benign and malignant thyroid nodules using
quantitative textural analysis of thyroid nodules.
In [81], various ML algorithms such as decision tree, RF, KNN, and ANN are applied to a
dataset to create a comparative analysis in order to better predict disease based on parameters
established from the dataset. The dataset was obtained from the UCI data repository on thyroid
disease. It contains 7200 multivariate records. In addition, the dataset has been modified to
ensure accurate classification prediction. For a more accurate comparison of the dataset,
the classification was performed on both the sampled and unsampled datasets. The authors
obtained the highest accuracy for the RF algorithm after manipulating the dataset, as shown
in Table 2.
Ataide et al. [82] used the geometric and morphological (G–M) feature extraction tech-
niques and RF model to classify the thyroid nodules from ultrasound images and to reduce
the subjectivity in the current diagnostic process. The classification of the thyroid nodules is
based on TIRAD guidelines. 27 G–M features were extracted from images and only 11 were
considered significant and were selected according to TIRADS guidelines to be evaluated by
ML techniques. The open-source Digital Database of Thyroid Ultrasound Images (DDTI)
dataset, from the Instituto de Diagnostico Medico, was used for this work. The result of G–M
features combined with RF classifier was compared with state-of-the-art methods showing
the efficiency of the proposed method by achieving 99.33% accuracy, 99.39% sensitivity,
99.25% specificity, and 99.35% F1-score which are the highest values.
In [68], authors developed ML-based system that can serve as early warning systems by
detecting TC at an early stage (pre-symptomatic stage). Furthermore, they aimed to achieve
the highest possible accuracy while using the fewest features possible. While there have
been previous attempts to use ML to predict thyroid cancer, this is the first attempt to use a
Saudi Arabian dataset as well as to target diagnosis in the pre-symptomatic stage (preemptive
diagnosis). RF, ANN, SVM, and NB techniques were used in this work, and each was chosen
for its unique capabilities. The highest accuracy rate obtained was 90.91%, with 93.00%

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sensitivity, 100.00% specificity, and 96.00% F1-score as shown in Table 2 with the RF
technique.
In [83], 60 US images of thyroid nodules (20 malignant, 40 benign) were split into small
patches of 17 × 17 pixels and used to extract various direction-independent features using
two-threshold binary decomposition, a method that decomposes an image into a group of
binary images. The features were then used in RF and SVM classifiers to differentiate between
benign and malignant nodules. The 10-fold cross-validation approach was used to evaluate
the classification. The performance of individual patches was then averaged to classify the
complete nodules. The performance of this approach was evaluated by various performance
indicators (see Table 2) including the area under the ROC curve (0.971 for RF and 0.965 for
SVM) and the F1-score (95% for RF and 93.25% for SVM).
Ur Rehman et al. [65] used a dataset obtained from DHQ Teaching Hospital, Dera Ghazi
Khan, Pakistan with which they trained and validated various classifiers including KNN, NB,
SVM, decision tree, and logistic regression. In addition to the features selected to qualify
the malignant or benign nature of thyroid nodules, they considered three additional fea-
tures namely pulse rate, body mass index, and blood pressure. The experiment consisted
of three iterations; the first iteration did not use feature selection, whereas the second and
third iterations used an L1-, L2-based feature selection technique [84, 85]. The experiment
was evaluated and analyzed, and many factors such as accuracy, precision, and AUC were
considered. The results presented in Table 2 indicate that the classifiers that used L1-based
feature selection achieved higher overall accuracy, sensitivity, specificity, and F1 score with
the same value compared with those that did not use feature selection and the L2-based
feature selection technique.
In [86], the authors experimented with various classical ML models to classify thyroid
diseases based on parameters such as TSH, T4U, and goiter. In particular, they applied the
KNN and NB algorithms and the Rapid miner tool was used for the experimental study. The
accuracy of the KNN algorithm was 93.44%, while that of Naive Bayes was 22.56% which
tells us that KNN is an efficient algorithm for this classification, while Naive Bayes seems
to be inadequate.

7 CADs based on deep learning

In an article published in the journal “Annals of Oncology” [87] researchers showed that a
CAD system based on Google’s Inception v4 Convolutional Neural Network (CNN) archi-
tecture outperformed experienced dermatologists in detecting skin cancer from a series of
digitized images. The system was trained on more than 100,000 dermoscopic images of skin
lesions and moles labeled as benign or malignant. The system’s performance was then com-
pared to that of 58 dermatologists, including 30 experts. The physicians, on average, correctly
identified 87% of melanomas and 71% of non-cancerous lesions. When they obtained larger
images, and more detailed information (age and gender, position of the skin lesion), these
rates grew to 89% and 76%. The machine detected 95% of melanomas from the first set of
images.
Similarly, in a paper published in the journal “Archives of pathology and laboratory
medicine” [88], a team of researchers from the Naval Medical Center and DeepMind (Google
AI) showed the significant superiority of LYNA (Lymph Node Assistant) CAD performance
over that of physicians in diagnosing breast cancer, while doctors on average barely achieve

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Fig. 4 VGG-16 CNN architecture [90]

an AUC of 81%, LYNA achieved a slide-level AUC of 99% and a tumor-level sensitivity of
91%.
These are only two examples among many others of the capabilities of deep learning
in diagnosis assistance. These CAD systems are based on a deep learning model called
convolutional neural networks (ConvNet or CNN) are going to be discussed in the following
section.

7.1 Convolutional neural networks

Before talking about convolutional neural networks (CNN) it is important to define what
deep learning (DL) is. Deep ANNs are distinguished by the existence of many intermediate
layers, hence the notion of depth. This feature allows them to solve much more complex
ML problems than shallow neural networks. Deep learning refers to ML algorithms that are
based on deep ANNs.
CNNs are a particular type of deep ANN. Although capable of solving a multitude of
problems, CNNs are best suited for image classification. They came to prominence in 2012 at
the annual ImageNet Large Scale Visual Recognition Challenge (ILSVRC) when the AlexNet
model broke all records.
CNNs work in a similar way to traditional supervised learning methods except that they
do not need a “manual” feature extraction algorithm, such as SIFT for example. They take
care of all the feature extraction and description work during the learning phase. The primary
goal of this learning phase is to minimize the classification error in order to optimize both the
classifier parameters and the features. Moreover, the specific architecture of CNNs allows to
extract features of different complexity, from the simplest to the most sophisticated [89]. The
automatic extraction and prioritization of features, which are adapted to the given problem,
is one of the strengths of CNNs. The CNN architecture is formed by a stack of distinct layers
(Fig. 4 ; [90]) that transform the input from a given layer into an output to the next one.
CNNs have two components: the Hidden layers allowing extracting the relevant features

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and the classification part. In hidden layers, the network performs a series of convolutions
and pooling operations during which the features are detected. In the classification part, the
fully connected layers serve as a classifier on top of these extracted features [3]. In object
classification, they assign a probability for an object on the image is what the algorithm
predicts it is. The hidden layers of a CNN are a succession of alternations of convolutional
layers and grouping layers.

7.1.1 Convolution layer

The CNNs take their name from this layer because it is its fundamental component. It scans
the image to locate the presence of a set of features by performing a convolution filtering.
The principle of this filtering is to “slide” on the image a window representing the wanted
feature (also called filter) and calculate the convolution product between the feature and each
portion of the scanned image. This convolution filtering operation is applied to each filter
for each image [91]. The result for each pair (image, f ilter ) is a so-called feature map that
indicates the presence of features in the image. The filters are not pre-defined but learned by
the network during the training phase. This is the strength of the CNNs which are able to
determine by themselves the discriminating features of an image, by adapting to the problem
at hand.

7.1.2 Pooling layer

A pooling (sub-sampling) layer is usually placed after a convolution layer. It receives as

input each of the feature maps produced by the layer that precedes it and applies the pooling
operation that consists of reducing the size of the images while preserving their important
characteristics. CNNs apply max pooling which consists in splitting the image into regular
cells, often square and of small size (2 × 2), and to keep only the maximum value of each of
them. The pooling layer allows reducing the number of parameters which also reduces the
computation time in the network. The pooling layer makes the network less sensitive to the
position and orientation of the features.

7.1.3 Rectification layer

A Rectified Linear Unit (ReLU for short) is a nonlinear activation function defined by:
f (x) = max (0, x). Since this function is linear for positive inputs only, it is called a
piecewise linear function or hinge function. Its role is to remove any negative value from
the previous filtering operations by replacing it with zero. It establishes a linear relationship
between each positive input and the dependent variable.

7.1.4 Fully connected layer

The last layer of a CNN is always fully connected and is used for classification. It receives
a vector from the different feature maps computed by the convolution and pooling layers
as input and constructs a vector as output whose size is the number of classes in the image
classification problem [92]. Each element of the vector indicates the probability for the input
image to belong to a class. These probabilities are computed by an activation function, softmax
most often, which returns a value between 0.0 and 1.0, knowing that the sum of all returned
values is equal to 1.0.

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Fig. 5 Dropout

The fully connected layer allows us to reconstruct the image from the various previous
filterings. It determines the link between the position of the features in the image and a class.
Indeed, the input table being the result of the previous layer corresponds to an activation map
for a given feature: the high values indicate the location (more or less precise according to
the pooling) of this feature in the image. If the location of a feature at a certain place in the
image is characteristic of a certain class, then the corresponding value is given a high weight
in the table.

7.1.5 Regularization and optimization techniques

Other layers are very often inserted in the CNNs whose goal is to reduce the learning time
but especially to avoid over-fitting. During training, a regularization function is used to avoid
over-fitting.
Dropout
Over-fitting can be avoided by using a variety of techniques throughout the training phases.
Among these techniques, “dropout” is the best known. The dropout [93] consists in randomly
deleting units and their connections during the learning process (Fig. 5 ), which allows to
generate slightly different models with different neurons configurations at each iteration.
The idea is to force the model to operate each neuron individually, as its neighbors can be
randomly deactivated at any time. The “early stop approach” is used in some circumstances
to protect the system, while it is being trained and verified and to halt the training before the
completion of all epochs to prevent the system from becoming over-fitted.
Batch normalization
The normalization is a pre-processing of numerical data to bring them to a common scale
without distorting their shape. Batch normalization has several beneficial effects that can
be mentioned (i) the acceleration of the learning process, (ii) the resolution of the internal
covariate shift problem: the input of each layer is distributed around the same mean and
standard deviation, and finally (iii) the smoothing of the loss function which, in turn, by
optimizing the model parameters, improves the learning speed of the model.

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Table 3 Results for the 3 Model Accuracy (%) Sensitivity (%) Specificity (%)
architectures
CNN 84.15 83.96 84.32
DNN 82.37 80.66 83.90
SAE 82.59 83.96 81.35

RMSprop
RMSprop [94] is a method of adaptive learning. It was created as a solution to the problem of
the dramatically declining learning rate. In order to dispose of history fast after discovering
a convex bowl, it uses an exponentially declining average. In reality, it resembles Adadelta
and is described in (30) where E|g 2 |t is the averaging factor: gt = ∇θ J (θ ).
⎧
⎨ E|g 2 |t = γ E|g 2 |t−1 + (1 − γ ) g 2
t
η (30)
⎩θt+1 = θt − √ 2 gt
E|g |t +

C-Adam
The Adam optimization algorithm [95] is an extension of stochastic gradient descent that has
recently been more widely adopted for deep learning applications in computer vision and
natural language processing. It is an optimization algorithm for updating iterative network
weights based on training data. The method computes individual adaptive learning rates
for different parameters from estimates of the first and second moments of the gradients.
Empirical results show that Adam works well in practice and compares favorably to other
stochastic optimization methods.

7.2 Related works

CAD systems based on deep learning have been introduced in the fields of medical imag-
ing, overcoming the limitations of the feature extraction step. Indeed, rather than manually
extracting features, deep neural networks allow direct use of the input image and avoid the
programmer having to assume the task of discovering the best representation of the data.
They automatically learn which characteristics are most relevant to a given problem. Table 6
summarizes the related work mentioned in this paper.

7.2.1 Thyroid nodule classification

In [96], Li et al. propose an approach based on the faster R-CNN neural network [97, 98]
to which they have made modifications to make it adapted to the detection of ultrasound
images. These modifications, according to [96], improved the ability of Faster R-CNN to
detect cancerous regions (papillary carcinoma) in thyroid ultrasounds. The basic Faster R-
CNN architecture receives as input a 3 channel image of size 224×224. The first convolution
layer using 96 filters 7 × 7 with a stride of 2 in x and y activated by a ReLU layer. This is
followed by a max pooling layer using the 2 stripe with 3×3 regions, processed by normalized
contrast which gives 96 feature maps 55 × 55. The following layers 2, 3, 4, 5 perform the
same operation as already described. The 6 and 7 layers are fully connected serving to extract
the features from the 5 layer which is input as a vector. The output layer is a softmax layer
for the classification. The modifications consist of concatenating the 3rd and 5th convolution

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layers and adding a spatially constrained layer before the output layer. The concatenation
of shallow and deep layers of the CNN allows to detect fuzzy or small areas of tumor and
the spatial constraint layer allows extracting the characteristics of the surrounding region
in which the cancerous regions reside. The approach was tested on a dataset of ultrasound
images taken on 53 men and 247 women aged 10 to 85 years, of which 250 cases were
diagnosed with papillary thyroid cancer and 50 cases were diagnosed with a normal thyroid.
The dataset contains a total of 4670 images each with one to three cancerous regions. 200
images from this dataset were used for the training of the neural network and 100 for its
validation. The results obtained are as follows: accuracy: 91.6%, precision: 93.3%, recall:
93.5%, specificity: 81.3%, F1-score: 93.4%, and AUC: 0.938.
Ma et al. [99] proposed a hybrid method for diagnosing thyroid nodules in ultrasound
images, consisting of the use of a cascade of two CNNs architectures pre-trained with the
ImageNet dataset and a splitting method, to detect thyroid nodules from these images. The
first CNN architecture consists of 15 convolutional layers and two max pooling layers with
a window size of 3 × 3 that follow the first and the third convolution layers, respectively. A
padding size of two pixels is used in these two pooling layers. In addition, the parametric
rectified linear unit function (PReLu) [100] is used as the activation function. A distribution
over the two class labels is generated after the output of the last convolutional layer with
a softmax layer. The second CNN architecture consists of four convolution layers, four
pooling layers, and two fully connected layers with 64 and 1 outputs respectively. The first
two convolutional layers are both followed by the max pooling layers with a window size of
3, a padding of 1, and a stride of 2. The third convolutional layer is followed by a max pooling
layer with a stride of 2 and a window size of 2. Finally, a max pooling layer with a stride of
8 and a window size of 8 follows the fourth convolutional layer. The activation function is a
rectified linear unit (ReLu). After the output of the second fully connected layer, a softmax
layer is used to generate a distribution over the two class labels by minimizing the cross-
entropy loss between the predicted labels and the ground truth labels. The two networks are
fine tuning and trained separately to obtain feature maps. These maps are merged, and used
as input to a Softmax classifier. A 10-fold cross-validation with the same dataset was used
to refine the architecture. The performance of the system was evaluated by the area under
the ROC curve, the FROC (free-response receiver operating characteristic) analysis [101,
102] and the JAFROC (jackknife alternative free-response receiver operating characteristic)
analysis [103, 104]. Experimental results validated on 15,000 images show that this cascade
architecture is very efficient for the detection of thyroid nodules and results in an AUC
value of 98.51%. The FROC and JAFROC analyses show that the performance of such an
architecture is significantly improved compared to “traditional” methods.
Liu et al. [105] presented a hybrid approach combining traditional hand crafted features and
deep learning attributes to discriminate the nature of thyroid nodules (benign or malignant).
The VGG-F architecture [106], consisting of 5 convolutional pooling groups and 2 fully
connected layers, and pre-trained on the ImageNet dataset was used as the basis for this
architecture. The results from the lower layers represent the low-level features, including
edge, direction, and intensity features, which are combined with those extracted manually
(HOG, LBP, Gray Level Co-Occurrence Matrix), Scale Invariant Feature Transform (SIFT),
and VLAD (Vector of Locally Aggregated Descriptors). The advantage of this combination of
features is that, apart from high-level feature descriptors generalized by CNNs, the manually
extracted ones, which are manufactured low-level feature descriptors, retain their relevance
advantages. 1037 clinically verified ultrasound images of thyroid nodules provided by the
Cancer Hospital of Chinese Academy of Medical Sciences were used for evaluation. This
dataset consisted of 651 images representing benign tumors and 386 images corresponding to

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malignant tumors. The type and location of all nodules were annotated by the physicians. The
results showed the effectiveness of this architecture with an accuracy of 93.1%, a sensitivity
of 90.8%, a specificity of 94.5%, and an AUC of 0.977.
Chen et al. [107] presented a non-invasive and automatic approach for the characterization
of thyroid nodules in ultrasound images based on the adaptation of the parameters of a deep
neural network (DNN) model. Several experiments have been conducted in order to fix the
optimal parameters of the DNN. The confusion matrix was used to compare the difference
between the model’s predictions and actual values. The prediction accuracy of the model
has reached 93%. The Receiver Operating Characteristic (ROC) curve is very close to the
boundary of the rectangle. The AUC (Area Under The Curve) is of 0.935, which shows that
the proposed model is performing well. Experimental results show the superiority of the
proposed DNN algorithm, since it has the highest accuracy rate of 93% and 95% respectively
on the actual medical dataset and the UCI standard dataset, compared to some algorithms
traditional learning such as random forest and other learning algorithms.

7.2.2 Lung nodule classification

In [108] the authors use a model based on residual blocks to classify lung nodules. The latter
are of various shapes and sizes which require focusing on global as well as local features.
Authors use non-local neural networks [109, 110], also known as self-attention layers which
reduce the number of parameters needed. For local feature identification, they use residual
blocks [111] with a kernel size of 3 × 3. The model was trained on the LIDC-IDRI dataset
[112] (containing 1,018 computed tomography (CT) scans annotated by radiologists) and
validated by the “10-fold cross validation” technique. With an AUC=95.62%, the proposed
method significantly outperformed the other reference methods.
Tran et al. [113] propose a CNN architecture named LdcNet, using the focal loss function
proposed by Lin et al. [114]. This architecture has been trained on the LIDC/IDRI dataset
[112] while applying data augmentation to consolidate the initial dataset with new images.
Non-uniform transformations, such as stretching or tilting, were not applied due to the impor-
tance of nodule shape for classification. The LdcNet architecture consists of 3 blocks of 3
successive convolutional layers each, each block is followed by a max pooling layer. Two
fully connected layers complete the architecture and allow the classification of nodules from
the features extracted from the previous convolutional blocks. This architecture achieved a
sensitivity of 96.0%, an accuracy of 97.2% and a specificity of 97.3%.
Song et al. [115] used 3 different techniques for lung nodule classification: a CNN, a DNN,
and a Stacked Autoencoder (SAE). The LIDC-IDRI dataset [112] was used for training and
validation of each of the 3 models.

• The CNN consists of two convolution layers composed of 32 filters of size 5 × 5. Each
convolution layer is followed by a max pooling layer of a kernel of size 2 × 2. Two fully
connected layers followed by a Softmax classifier complete the CNN architecture.
• The DNN consists of an input layer that receives the grayscale images whose size is
28 × 28. The input layer is followed by four fully connected layers of respective sizes
784 × 1, 512 × 1, 256 × 1 and 64 × 1. A dropout layer with a parameter of 0.6 has been
inserted between the third and fourth fully connected layers. The activation function of
the fourth layer is ReLU. A Softmax classifier is applied at the end of the DNN.
• The SAE is a multi-layer sparse auto-encoder. An auto-encoder is an ANN that is often
used in learning discriminative features from a dataset. It consists of an encoder and a
decoder. The encoder consists of a set of layers of neurons, which process the data in order

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Table 4 Results obtained by Vaid Finding Precision (%) Recall (%) F1-score (%)
et al. [116]
Normal 98.6 96.0 97.3
COVID-19 91.7 97.1 94.3

to obtain a new representation of it while the layers of neurons of the decoder analyze
the encoded data and try to rebuild the original data. In [115], several auto-encoders and
Softmax classifiers are combined to build an SAE network with several hidden layers and
a final Softmax classifier. Since the SAE is used for classification in this work, the hidden
layer generated by the auto-encoder is directly used for classification, thus negating the
decoding part of the auto-encoder.
The results obtained by this work are summarized in Table 3 . The CNN architecture
performed the best of the 3 models. These results do not improve on previous work for
fairly obvious reasons. The CNN is not deep enough and the authors could have used for
example 3×3 filters to capture more detail. The poorer performance of the DNN and the SAE
compared to the CNN can be explained by the very nature of these two architectures which are
formed by fully connected layers, although obtained in different ways. The performance of
convolution layers in the extraction of shape and texture features far exceeds the possibilities
of fully connected layers.

7.2.3 Identification of COVID-19 disease infection

The COVID-19 virus does not affect everyone in the same way. It has been verified, in
many cases, that some individuals can contract the virus and therefore be contagious with-
out developing symptoms. The tests for COVID-19 are not 100% reliable. On the other
hand, the symptoms of COVID-19 correspond to the symptoms of other much less danger-
ous respiratory infections. Additional or more reliable methods than the RT-PCR (Reverse
Transcription-Polymerase Chain Reaction) test whose reliability is 95% or the antigenic test
(much less reliable than PCR) are needed. Many research works have focused on the impact
of deep learning in the detection of COVID-19 from medical images, in particular, Chest
X-rays and Computed Tomography (CT) scans.
Vaid et al. [116] adopted a transfer learning approach based on the VGG-19 architecture
for COVID-19 case classification from patient anterior–posterior chest radiographs. They
used a publicly available dataset for learning and evaluating their model.1 This dataset is
composed of frontal chest radiographs from 181 patients from different geographical loca-
tions (Italy, China, Australia, etc.) and labeled by expert radiologists. The small number of
images explains the use of transfer learning. The VGG-19 model was pre-trained on lma-
geNet and modified by adding a multilayer perceptron trained on the chest radiograph dataset
for the classification of COVID-19 positive and negative cases. The results of this model are
presented in Table 4.
In [117], the authors presented a CAD allowing the detection of infections caused by
COVID-19. The process starts with an image pre-processing phase to remove regions unnec-
essary for diagnosis and in particular the diaphragm which is composed of pixels with high
intensity that negatively affect the distinction and quantification of lung disease patterns. The
original image is then processed on one the one hand by a histogram equalization algorithm

1 https://github.com/ieee8023/covid-chestxray-dataset.

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Table 5 Classification report of Precision (%) Recall (%) F1-score (%)

the method proposed in [117]
Normal 96 91 93
COVID-19 73 98 84
Other pneumonia 96 96 96

and on the other hand by the application of a bilateral low pass filter, each of the two pro-
cessing results in a new image. These images are combined with the original image to form
a pseudo-color image. It is this image that is used for classification by a VGG16 model pre-
trained on ImageNet (transfer learning) to classify the chest radiographs into three classes: (i)
infected with COVID-19, (ii) Pneumonia other than COVID-19, and (iii) normal cases (no
pneumonia). The dataset used is an assembly of chest radiography images from several dif-
ferent public medical repositories comprising 8474 posteroanterior 2D radiological images
of the chest. 415 images in the dataset represent confirmed cases of COVID-19 disease, 5179
represent non-COVID-19 pneumonia, and 2880 represent normal cases (no pneumonia). In
this study, the class weight technique, which consists in adjust weights inversely proportional
to class frequencies in the input data, combined with data augmentation, is applied during
training to reduce the potential consequences of imbalanced data. The results of this work
are summarized in Table 5.
In [118] the authors analyzed the effectiveness of a VGG16-based deep learning model for
the identification of pneumonia and COVID-19 from chest radiographs. They used a public
dataset of radiological images of healthy patients, patients with pneumonia, and patients with
COVID-19.2 They applied the hold-out technique to split the dataset into a learning subset
composed of 80% of the dataset content selected at random and a test/validation subset
composed of the remaining 20% of images. The model obtained an Accuracy, a Precision, a
Sensitivity and an F1-Score of 86% each, a Specificity of 93%.
Misra et al. [119] used residual learning based on three multi-channel pre-trained ResNet
architectures for COVID-19 diagnosis from chest radiographs. The three models were
retrained to classify radiographs on a one-against-all basis of (a) normal or diseased, (b)
pneumonia or non-pneumonia, and (c) COVID-19 or non-COVID-19. Slightly more than
6000 chest radiographs from three different public datasets were used for this work. These
data were from the RSNA Pneumonia Detection Challenge,3 the COVID-19 image dataset,4
and the COVID-19 radiographs [120]. The final dataset consisted of 1579 radiographs of
healthy individuals, 4245 individuals with pneumonia and 184 individuals with COVID-19.
The three ResNet architectures were assembled and refined based on the final dataset to
recognize the 3 classes of healthy, pneumonia other than COVID-19, and COVID-19. The
results demonstrated the effectiveness of the approach with 94% accuracy and 100% recall
on the dataset.
In [121], in order to automatically diagnose COVID-19, Ouyang et al. developed a dual-
sampling attention network for thoracic computed tomography (CT) classification. Based on
two 3D ResNet34 networks, the authors used different sampling strategies by integrating a
gradient-based attention mechanism. Gradient-based attention methods are methods usually
conducted offline, allowing to reveal important regions influencing the network prediction. In
2 https://public.roboflow.ai/classification/covid-19-and-pneumoniascans.
3 https://www.rsna.org/education/ai-resources-and-training/ai-image-challenge/RSNA-Pneumonia-
Detection-Challenge-2018.
4 https://www.kaggle.com/datasets/andrewmvd/convid19-x-rays.

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Table 6 Related literature review of deep learning
Method Classifiers Accuracy (%) Sensitivity (%) Specificity (%) Precision (%) AUC (%) F1-score (%)

Thyroid nodule classification

Li et al. [96] R-CNN 91.60 93.50 81.30 93.30 93.80 93.40
Ma et al. [99] CNN NA NA NA NA 98.51 NA
Liu et al. [105] VGG-F 93.10 90.80 94.50 NA 97.70 NA
Chen et al. [107] DNN 95.00 NA NA NA 93.50 NA
Lung nodule classification
Al-Shab et al. [108] ANN NA NA NA NA 95.62 NA
Tran et al. [113] LdcNet 97.20 96.00 97.30 NA NA NA
Song et al. [115] CNN 84.15 83.96 84.32 NA NA NA
DNN 82.37 80.66 83.90 NA NA NA
SAE 82.59 83.96 81.35 NA NA NA
Identification of COVID-19 disease infection
Vaid et al. [116] VGG19 NA 96.00 NA 98.60 NA 97.30
VGG19 NA 97.10 NA 91.70 NA 94.30
Heidari et al. [117] VGG16 NA 91.00 NA 96.00 NA 93.00
VGG16 NA 98.00 NA 73.00 NA 84.00
VGG16 NA 96.00 NA 96.00 NA 96.00
Civit-Masot et al. [118] VGG16 86.00 86.00 93.00 86.00 NA 86.00
Misra et al. [119] ResNet architectures 94.00 100 NA NA NA NA
Ouyang et al. [121] 3D ResNet34 networks 87.50 86.90 90.10 NA 94.40 82.00
R. Guetari et al.
Computer-aided diagnosis systems: a comparative study… 3913

their work, the authors extended gradient-based attention by developing an online trainable
component that uses segmented pneumonia infection regions to ensure that the network
can make decisions based on these infection regions. The dual sampling strategy adopted
in this work is used to mitigate the imbalance in the size of the infected regions between
COVID-19 and Community Acquired Pneumonia. This imbalance is in part a result of the
rapid progression of COVID-19 after symptom appearance. The model was trained, tested,
and validated on one of the largest multi-center CT dataset for COVID-19 from 8 hospitals.
2186 CT scans of 1588 patients were used for the training and validation phase (5-fold cross-
validation). The tests were performed on another dataset composed of 2796 CT scans of 2057
patients. This model obtained an accuracy of 87.5%, a sensitivity of 86.9%, a specificity of
90.1%, an F1 score of 82.0%, and an AUC of 0.944 (Table 6).

8 Discussion

The first finding from this study is the effectiveness of both classical and deep learning
approaches in tumor classification. The question that then arises is “Why continue to explore
both approaches?” Some ask why not focus on deep learning since it relieves us of the tedious
work of feature identification and selection. To answer this kind of question, a step back should
be taken and analyze the effectiveness of each of the two approaches and especially when is
this effectiveness put to the test.
The effectiveness of either approach depends on the efficient and accurate selection of
features to determine whether a tumor is benign or malignant and to differentiate acute
pulmonary edema from COVID-19 pneumonia. Deep learning has demonstrated very good
performances in terms of identification and selection of features, but on the other hand, it
needs a huge volume of data on which it will be trained. The availability of data in sufficient
quantities, to train a CNN for example, is not always guaranteed. And even if these data
are available, if they are not well chosen, they can lead to inefficient systems because of the
phenomena of under-fitting and over-fitting.
Although the performance of both approaches can be affected by an imbalance in the
training data, deep learning is more sensitive to it because the features are extracted automat-
ically. If the dataset representing one of the classes is not sufficient, there is a high chance
that the values of the features learned and representing this class are wrong. In this case, a
performance indicator, such as accuracy, on its own is not very meaningful. Indeed, if for
example in a thyroid nodule dataset, there are 90% benign nodules and 10% malignant nod-
ules, if the classifier is wrong on all the malignant nodules, it will still have an accuracy of
90%, which is not negligible.
If for small datasets deep learning is rather inefficient, this is where classical learning can be
distinguished. As long as the data sets are small, the learning phase is not time-consuming.
The features are chosen by experts on scientific and experimental grounds. Again, it all
depends on the feature selection process which, if done manually, is quite subjective and
prone to interpretation.
To address the issues that arise in each of the two models, solutions have been proposed.
For the handcrafted selection of features, in addition to relying on the expertise of the various
actors involved in the CAD design process, in particular physicians and image processing
experts, rigorous methods based on mathematical and statistical foundations have been devel-
oped to help better identify the relevant features for classification (refer to paragraphs 6.1,
6.2 and 6.3).

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Proven solutions also exist to solve the problem of unbalanced classes. On the one hand,
there is data augmentation which allows, by applying certain modifications on the elements of
the initial dataset, to virtually increase its cardinal. It is thus possible to multiply the number
of objects of a dataset by 5 or even by 6. This solution, which has shown its efficiency in
a good number of applications, does not really solve the problem but allows us to have a
sufficient number of data to learn well the characteristics allowing the classifications. That
said, some transformations may not be adequate for certain types of objects. The paragraph
7.2.2 pointed out that the shape of a lung nodule is crucial for a good diagnosis and, therefore,
non-uniform transformations, such as stretching or tilting should not be applied. Approaches
really dedicated to unbalanced data have been implemented to solve the problem of class
imbalance. Several approaches have been used acting at the data level or at the algorithm
level as well as some hybrid methods. Deep generative models [122] seem to be among
the most promising. These are unsupervised learning methods whose goal is to learn to
describe the underlying distribution of unlabeled training data and, from there, also learn to
generate brand new data from this distribution, thus establishing a balance between classes
by enriching those that lack data.

9 Conclusion

To conclude this comparative study, it is necessary to remind that in the healthcare sector, AI
covers all areas, from biological and imaging diagnostics to technotherapies (technological
therapies: prostheses, connected implants), and even biotherapies (genetic and cell therapy).
AI enables the exploration of medical data accumulated in recent years and has brought
medicine into a new and major phase of innovation comparable to the one that led to the
development of antibiotics after the Second World War. The two major contributions that are
driving AI in the healthcare field are (i) the scientific contribution in terms of R&D, which
promotes discoveries on diagnosis, prognosis, and prediction of the evolution of pathologies,
and (ii) the economic and socio-industrial contributions. This leads to the automation of
numerous tasks, the transformation of care paths, and the organization of care by measuring
the impact of treatments.
In the context of medical diagnosis of a pathology, whether preventive or curative, and
which requires a significant effort from medical staff, AI is emerging as a real alternative that is
transforming the professions and practices of the healthcare sector. Thanks to a great capacity
to analyze data compared to humans, it has facilitated the establishment of a diagnosis for
diseases that are complex to detect: eye diseases, cancers, melanomas, etc. Among the latest
developments in this field, the analysis of medical imagery for the macroscopic recognition
of skin tumors or breast cancer, etc. has been added to these capabilities to further refine the
proposed diagnosis.
The question that arises and that this research attempted to solve through this literature
review is: “In diagnosing, can AI do as well as doctors?” Experience shows that ML now
exceeds the ability of doctors to detect tumors in medical images. This paper has examined
the possibilities of the so-called classical ML algorithms (SVM, RF, KNN, etc.) compared
to deep learning and the performances are quite comparable when the whole process is
established with rigor. It has been presented in the discussion part when one or the other
of the two approaches was necessary and, roughly speaking, deep learning is more efficient
when the learning data is abundant while it presents weaknesses if the datasets are small. In
this case, classical methods are the best choice, provided that the characteristics involved in

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the diagnosis are well-identified. Nevertheless, the choice of one or the other approach is not
only a question of the size of the datasets. Indeed, the size of a dataset can more or less be
rectified by proven techniques such as, for example, data augmentation or data generation
using auto-encoders. Other problems that can affect the quality of an ML model and its
performance are the dataset structure. It has been shown that some poorly compiled datasets
can lead to the over-fitting. The quality of a dataset is not always guaranteed. and software
solutions have been developed to minimize the risk of over-fitting. The first step is to detect
the over-fitting itself by the cross validation technique but this can only be done after the
learning phase. Then, other techniques, such as dropout or ensemble learning can be used to
limit the risk.
What remains to be done? Current work in this area consists of improving the scores
of different algorithms by searching for new models or combining existing models as well
as assessing mathematical means of evaluating loss and generalization functions. Attempts
using reinforcement learning combined with usual classifiers (neural networks, SVM, etc.)
are being investigated. We are almost at the beginning of this revolution in the medical field,
other models and other innovations will surely come in the near future.

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Computer-aided diagnosis systems: a comparative study… 3921

Ramzi Guetari is an Associate Professor in Computer Science at the

Polytechnic School of Tunisia. He obtained his PhD in Computer Sci-
ence from the University of Savoie in France and worked as a Research
Engineer at the French National Institute for Research in Computer Sci-
ence and Control (INRIA) where he was seconded to the World Wide
Web Consortium (W3C). He participated in the development and pro-
motion of Web technologies and notably participated in the development
of Amaya, the W3C test bed. He was at the origin of the internation-
alization of Amaya. For more than 10 years, Ramzi has been working
in the industrial field and has led large-scale missions for international
organizations as well as for important other major international com-
panies. Ramzi’s research work has focused on distributed information
systems and fundamental computing. Over the past ten years, he has
worked on artificial intelligence and machine learning and has super-
vised a substantial number of Master and Doctoral theses.

Helmi Ayari obtained a Master Degree in Intelligent Imaging and Arti-

ficial Vision Systems from the Tunisian Higher Institute of Informatics
(ISI) in 2021. His Master thesis was supervised by Dr. Ramzi Guetari.
He worked on Computer-Aided Diagnosis Systems and in particular on
feature extraction and dimentionality reduction. He is currently pursu-
ing a PhD at the Polytechnic School of Tunisia. His main research area
is financial and credit risk assessment methods using machine learning.

Houneida Sakly is a PhD and Engineer in Medical Informatics. She is

a member of the research program "Deep Learning Analysis of Radio-
logic Imaging" in Stanford university. Certified in Healthcare Innovation
with MIT-Harvard Medical school. Her main field of research is the
Data Science applied to the Healthcare. She is a member of the Inte-
grated Science Association (ISA) at the Universal Scientific Education
and Research Network (USERN) in Tunisia. Currently, she is serving
as a lead editor for various book and special issue in the field of Digital
Transformation and Data Science in Healthcare. Recently, she has won
the Best Researcher Award in the International Conference on Cardiol-
ogy and Cardiovascular Medicine- San Francisco, United States.

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