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. 2022 Jan 13;17(1):e0261659. doi: 10.1371/journal.pone.0261659

Automated selection of mid-height intervertebral disc slice in traverse lumbar spine MRI using a combination of deep learning feature and machine learning classifier

Friska Natalia 1, Julio Christian Young 1, Nunik Afriliana 1, Hira Meidia 1, Reyhan Eddy Yunus 2, Sud Sudirman 3,*
Editor: Nguyen Quoc Khanh Le4
PMCID: PMC8758114  PMID: 35025904

Abstract

Abnormalities and defects that can cause lumbar spinal stenosis often occur in the Intervertebral Disc (IVD) of the patient’s lumbar spine. Their automatic detection and classification require an application of an image analysis algorithm on suitable images, such as mid-sagittal images or traverse mid-height intervertebral disc slices, as inputs. Hence the process of selecting and separating these images from other medical images in the patient’s set of scans is necessary. However, the technological progress in making this process automated is still lagging behind other areas in medical image classification research. In this paper, we report the result of our investigation on the suitability and performance of different approaches of machine learning to automatically select the best traverse plane that cuts closest to the half-height of an IVD from a database of lumbar spine MRI images. This study considers images features extracted using eleven different pre-trained Deep Convolution Neural Network (DCNN) models. We investigate the effectiveness of three dimensionality-reduction techniques and three feature-selection techniques on the classification performance. We also investigate the performance of five different Machine Learning (ML) algorithms and three Fully Connected (FC) neural network learning optimizers which are used to train an image classifier with hyperparameter optimization using a wide range of hyperparameter options and values. The different combinations of methods are tested on a publicly available lumbar spine MRI dataset consisting of MRI studies of 515 patients with symptomatic back pain. Our experiment shows that applying the Support Vector Machine algorithm with a short Gaussian kernel on full-length image features extracted using a pre-trained DenseNet201 model is the best approach to use. This approach gives the minimum per-class classification performance of around 0.88 when measured using the precision and recall metrics. The median performance measured using the precision metric ranges from 0.95 to 0.99 whereas that using the recall metric ranges from 0.93 to 1.0. When only considering the L3/L4, L4/L5, and L5/S1 classes, the minimum F1-Scores range between 0.93 to 0.95, whereas the median F1-Scores range between 0.97 to 0.99.

1. Introduction

The success of many modern therapeutics for an illness relies on speedy and accurate diagnoses of the illness. And obtaining speedy and accurate diagnoses of illnesses is a fundamental challenge for global healthcare systems. This is the reason why computer-aided diagnosis (CAD) is seen as a potential solution to overcome this challenge. A CAD system can help doctors understand the cause of an illness better by automating some steps in the diagnosis process. In a CAD system that uses medical images, the system applies image analysis algorithms to different types or modalities of medical imaging, such as Magnetic Resonance Imaging (MRI), of the patient [13]. In the case of MRI, for example, a CAD system might use the two modalities of MRI, namely the T1-weighted and T2-weighted MRI, which can differently highlight various types of tissues based on their fat and water composition. An example of a T1-weighted and a T2-weighted traverse MRI images of the L3/L4 Intervertebral Disc (IVD) of the same patient are shown in Fig 1. The algorithms may also require images with specific properties and criteria as inputs. Some algorithms require mid-sagittal MRI images as inputs [46] whereas some others require traverse images taken at certain locations as inputs [710]. When these algorithms were proposed in the literature, it is often assumed that a selection process has been carried out beforehand that identifies appropriate and suitable images as their input. In practice, however, these selection processes are not straightforward since a patient’s data repository contains more than just these specific images, hence the process to select the suitable images is often done manually. Therefore, to make the CAD system more automated, this selection process also needs to be automated.

Fig 1. A T1-weighted (left) and a T2-weighted (right) traverse MRI images of the L3/L4 Intervertebral Disc of a patient are shown.

Fig 1

One marked difference in the two images is the cerebrospinal fluid (CSF) in the spinal canal that appears black on the T1-weighted image but as a brighter region on the T2-weighted image because of its low fat contents.

Our review of the literature discovers that the classification of brain MRI images, and more particularly the selection of mid-sagittal plane in brain MRI, has been a popular research topic in the last three decades [11] due to its uses in brain image processing such as spatial normalization, anatomical standardization, and image registration. However, the topic of plane selection in spinal images has not taken up much researchers’ attention despite the need for such technology. To the best of our knowledge, no method in the literature has been proposed to select the best traverse plane that cuts closest to the half-height of an IVD in a lumbar spine MRI. These images are very useful for detecting abnormalities in lumbar IVDs including those resulted from Lumbar Spine Stenosis (LSS), a condition that causes low back pain because of the pressures exerted on the spinal nerve [12]. Most LSS occurs in the last three lumbar IVDs namely the L3/L4, L4/L5, and L5/S1 IVDs due to the heavier weight they have to support in comparison to other IVDs and MRI is the most commonly used imaging technology for diagnosing LSS due to its high soft-tissue resolution [12]. When attempting to diagnose LSS using MRI, a neuroradiologist almost always starts his or her inspection of those three IVDs in the mid-sagittal view (as illustrated in Fig 2) since it can provide a general overview of the lumbar spine’s condition. This is also reflected in the popularity of image analysis methods in the literature that use sagittal MRI images to detect LSS [6, 1316]. However, a more accurate assessment of the actual location and the extent of the LSS can only be obtained through inspection of the suspected IVD in traverse view (as illustrated in Fig 3) [17, 18]. Traverse images taken from planes that cut closest to the half-height of the L3/L4, L4/L5, and L5/S1 IVDs are generally considered as the best images to use when the neuroradiologist inspects the disc because they contain the best information that reflects the condition of the IVDs. Fig 2 shows the intersection lines between the mid-sagittal plane and each of the nine traverse planes. The lines marked in red are the intersection lines, which according to our expert’s view, of traverse planes that cut closest to the half-height of an IVD.

Fig 2. A mid-sagittal view of a lumbar spine MRI showing the intersection lines between the sagittal plane and the traverse planes that are shown in Fig 3.

Fig 2

The lines marked in red are the intersection lines of traverse planes that cut closest to the half-height of an IVD.

Fig 3. An example of nine traverse images of a lumbar spine.

Fig 3

Image 2, 5, and 8 are from the planes that cut closest to the half-height of L3/L4, L4/L5, and L5/S1 IVD, respectively.

The task of selecting these traverse images falls into the category of image classification and can be solved using machine learning (ML). A typical approach in image classification using machine learning involves two stages, with the first being the extraction of relevant information from the images via the calculation of low-level handcrafted features [1921]. This is then followed by a classification of the calculated features using trainable ML classifiers. Despite the success of this approach, it has a significant drawback when used in a wider image classification problem since the features are often task dependent. In other words, the handcrafted image features that are optimized for a particular task often perform poorly when used in a different task, and the accuracy of the classification is very dependent on the design of these features. Deep Convolutional Neural Network (DCNN) was proposed to overcome the problems associated with the traditional approach of image classification by allowing automatic learning of such features through forward and backward propagation of information in a series of convolutional and non-linear neural network layers [22, 23].

DCNN is one of several types of deep neural networks that gain popularity in recent years to solve many artificial intelligence problems. Different types of deep neural networks have significantly different architectures and are designed to solve different types of problems. DCNNs are typically used for image classification. Recurrent Neural Networks, such as Long Short-Term Memory [24], are used to recognize patterns in sequences of data such as time-series data, speech, and texts. There are also Fully Convolutional Neural Networks, such as U-net [25] and SegNet [26] that are used mainly for semantic image segmentation. Some DCNNs have also been modified to become Region-based CNNs [27, 28] to detect and recognize multiple objects within an image.

Training DCNN models take a long time hence there exist several pre-trained DCNN models that are readily usable for image classification [29, 30]. Many of the most popular pre-trained DCNN models were developed using real (i.e., non-synthesized) photographic (i.e., non-medical) images from the ImageNet database [31] and the original task is to detect the types of objects that are typically present in photographs such as cars, fruits, animals, and so on. However, despite being extracted using a model trained using photographic images, these learnable features are sufficiently general that they can be used in many other types of image classification tasks, including medical image classification, through a method called Transfer Learning [32, 33], which process is elucidated in Fig 4. This method is performed by replacing the Fully Connected (FC) Neural Network classification layers of the DCNN with new ones before retraining them using the images from the new target dataset.

Fig 4. A flowchart describing the traditional Transfer Learning approach of using Deep Convolutional Neural Network for medical image classification, where a) depicts the training process and b) depicts the inference step.

Fig 4

The classification of medical images has unique challenges compared to the classification of other more general images. Firstly, they have relatively high intra-class variation and inter-class similarity compared to other types of images [34] and secondly, the size of the medical image dataset is considerably smaller than datasets of other types of images. The latter is particularly problematic in the application of any machine learning methodology, including DCNN, because it violates the assumption that the number of samples is greater than the number of features. One of the possible solutions to solve this is through the application of Dimensionality Reduction (DR) or Feature Selection (FS) techniques to transform the data from a high-dimensional space into a lower-dimensional space while retaining much of the useful properties of the original data.

Based on the above argument, we believe that both a) the lack of directly relevant methods proposed in the literature that selects the best traverse plane that cuts closest to the half-height of an IVD in a lumbar spine MRI and b) the wide range of potentially suitable DR or FS methods and image classification methods, provide the rationale and urgency for this study. The aim of this study is to find the best method to select the best traverse plane that cuts closest to the half-height of an IVD in a lumbar spine MRI by studying and comparing the different combinations of machine learning methods and approaches. We report the result of our investigation on the suitability and performance of different approaches of machine learning in solving the aforementioned medical image classification challenge. The contributions of this work are summarized as follows:

  • a) Investigated the classification performance using image features calculated using eleven different pre-trained DCNN models.

  • b) Investigated the effect of three dimensionality-reduction techniques and three feature-selection techniques on the classification performance.

  • c) Investigated the performance of five different ML algorithms and three FC learning optimizers which are trained with hyperparameter optimization using a wide range of hyperparameter options and values.

The organization of this paper is as follows. Section 2 describes the dataset used in the research and the proposed method. The experimental results, analysis, and discussion are discussed in detail in Section 3. We then provide the conclusion of our findings in the last section of the paper.

2. Material and method

We can confirm that all procedures performed in this study are in accordance with the ethical standards of both the United Kingdom and the Kingdom of Jordan and comply with the 1964 Helsinki declaration and its later amendments. The approval was granted by the Medical Ethical Committee of Irbid Speciality Hospital in Jordan where the original MRI dataset was procured. The data were analyzed anonymously.

The material used in this research is taken from our Lumbar Spine MRI Dataset which is available publicly [9, 35]. This dataset contains anonymized clinical MRI studies of 515 patients with symptomatic back pains. The dataset consists of 48,345 T1-weighted and T2-weighted traverse and sagittal images of the patients’ lumbar spine in the Digital Imaging and Communications in Medicine (DICOM) format. The images were taken using a 1.5-Tesla Siemens Magnetom Essenza MRI scanner. Most of the images were taken when the patients were in the Head-First-Supine position, though a few were taken when they were in the Feet-First-Supine position. The duration of each patient study ranges between 15 to 45 minutes with time gaps between taking the T1- and T2-weighted scans ranging between 1 to 9 minutes. The patient might have made some movements between the T1 and T2 recordings, which suggests that corresponding T1- and T2- slices may not necessarily align and may require an application of an image registration algorithm to align them. The scanning sequence used in all scans is Spin Echo (SE), which is produced by pairs of radiofrequency pulses, with segmented k-space (SK), spoiled (SP), and oversampling phase (OSP) sequence variant. Fat-Sat pulses were applied just before the start of each imaging sequence to saturate the signal from fat matters to make it appear distinct to water. The range of acquisition parameter values used during traverse MRI scans is provided in Table 1.

Table 1. The range of acquisition parameter values used during traverse MRI scans.

Sequence Types T1-weighted T2-weighted
Number of Echoes (ETL) 3 9 to 16
Repetition Time (milliseconds) 385 to 953 1900 to 5000
Echo Time (milliseconds) 11.0 84.0 to 96.0
Slice Thickness (mm) 4.0 3.0 to 5.0
Spacing Between Slices (mm) 4.4 3.3 to 6.5
Field of View (mm) 220 220
Matrix (Freq. x Phase) 100% 100%
Imaging Frequency (MHz) 63.7 63.7
Number of Phase Encoding Steps 295 to 336 272 to 360
Scanning Sequence SE SE
Sequence Variant SK\SP\OSP SK\SP\OSP
Scan Options Fat-Sat Fat-Sat
Number of Averages 2 or 3 1 or 2
Echo Train Length 3 9, 13, 15, or 16
Percent Sampling 65 to 75 70 to 78
Percent Phase Field of View 96.9 to 100 90.6 to 100
Pixel Bandwidth 150 or 205 165, 190 or 225
Flip Angle 150 150

From the 48,345 images in the dataset, some 17,872 traverse images were taken. These traverse images cut across the lowest three vertebrae, the first sacrum, and the lowest three IVDs including the one between the last vertebrae and the sacrum. An example of the slicing position of these traverse images is shown in Fig 2. These 17,872 traverse images are made up of 8,936 pairs of T1-weighted and T2- weighted images. They are composed of 515 pairs that cut halfway across the height of L3/L4 IVD, 515 pairs that cut halfway across the height of L4/L5 IVD, 515 pairs that cut halfway across the height of L5/S1 IVD, and the other 7,391 pairs that do not cut halfway across the height of any IVDs. The categorization of the images is made by an expert radiologist by viewing the images using DICOM viewer software and manually identifying the three mid-height slices. We consider the radiologist’s decision as the ground truth, which the results of automatic classification will be compared against.

From each pair of T1-weighted and T2-weighted images, a 3-channel composite image is created resulting in 8,936 composite images. The first channel of the composite image is constructed from the T1-weighted image, the second channel is constructed from the image-registered T2-weighted image, and the last channel is constructed from the Manhattan distance of the two. The image used to construct the second channel is obtained by performing image registration on the T2-weighted image to its T1-weighted counterpart to ensure that every pixel at the same location in both images corresponds to the same voxel in an organ or tissue. This is performed by finding the minimum difference between the fixed T1-weighted image and a set of transformed T2-weighted images calculated over a search space of affine transforms. Mathematically, the process can be described as follows: Let IR(v) be the reference 2D image and IT(v) be the to-be-transformed 2D image, where v = [x, y, z]T is a real-valued voxel location. The voxel location v is defined on the continuous domains VR and VT, that corresponds to each pixel in IR and IT, respectively. Note that in our case, IR and IT are the T1-weighted image and the T2-weighted image, respectively. The image registration that we employ in this method is a process that seeks a set of transformation parameters μ^ from all sets of transformation parameters μ that minimizes the image discrepancy function S

μ^=argminμS(IR,ITgvμ) (1)

We calculate S using Matte’s mutual information metric described in [36] over a search space in μ domain. The search process uses an iterative process called the Evolutionary Algorithm that perturbs, or mutates, the parameters from the last iteration. If the new perturbed parameters yield a better result than the last iteration, then more perturbation is applied to the parameters in the next iteration, otherwise a less aggressive perturbation is applied. The search process is optimized using the (1+1)-Evolutionary Strategy [37] which locally adjusts the search direction and step size and provides a mechanism to step out of non-optimal local minima. The search is carried out up to 300 iterations with a parameter growth factor of 1.05. A sequence of parametric bias field estimation and correction method, called PABIC [37], is applied to counter the effect of low-frequency inhomogeneity field and high-frequency noise on both T1 and T2 modalities.

Out of the 8,936 attempts to register the T1 and T2 images, 25 failed because the algorithm is unable to converge. This could be because the patient’s position and orientation when the two scans were recorded differ significantly. In this case, the images were removed from the dataset resulting in 8,910 composite images. We show in Fig 5, two example cases where the image registration process succeeded (left column) and failed (right column).

Fig 5. Two example cases where the image registration process succeeded (left column) and failed (right column).

Fig 5

The top row shows the T1-weighted images, the middle row shows T2-weighted images, and the bottom row shows the resulting composite images after image registration.

Each composite image is labeled according to which group of images they are taken. They are labeled as best_d3 for those that cut halfway across the height of L3/L4 IVD, or as best_d4 for those that cut halfway across the height of L4/L5 IVD, or as best_d5 for those that cut halfway across the height of L5/S1 IVD, or as other_slices otherwise. Since we have a class imbalance problem, we augment the dataset by randomly sampling the other_slices class and oversampling the other classes. The class population sizes before and after augmentation are shown in Table 2. The dataset is then split into two mutually exclusive subsets namely the training set and the test set with an 80:20 ratio, respectively. The training set is used to develop machine learning models for the image classification whereas the test set is used to measure the classification performance of the developed machine learning models.

Table 2. Dataset sizes (number of images).

Class Original Size (T1 and T2 pairs) After Registration (Composite Images) After Augmentation (Composite Images)
best_d3 515 513 1,026
best_d3 515 513 1,026
best_d3 515 513 1,026
other_slices 7,391 7,371 1,539
Total 8,936 8,910 4,617

The methodology that we adopt to solve the research challenge is finding the best combination of image features, feature dimension reduction or feature selection method (if applicable), and machine learning classifier or neural network from a comprehensive set of method combinations. An overview of the method used in this study is shown as a flowchart in Fig 6. It starts with an image-features extraction process using a pre-trained DCNN model. The image features are extracted by taking the outputs of the last feature extraction layer just before the classification layers. In practice, this is obtained by removing the classification layers before recording the output signals of the DCNN for each input image. Since the feature dimension is high we can reduce it by applying a DR or an FS technique. Both techniques reduce the feature’s length while retaining much of the useful properties of the full-length feature. The difference being, while an FS technique only selects a subset of the dimension directly from the entire dimension set, a DR technique applies a transform function to the feature vector prior to selecting the subset. In this study, we investigated the applicability of three popular DR methods namely the Principal Component Analysis (PCA), Independent Component Analysis (ICA) [38], and Factor Analysis (FA) [39]. PCA uses linear transformation functions to separate the data into their major components by projecting them onto a set of feature subspaces that maximizes the components’ variance. Rather differently from PCA, the ICA and FA methods use statistical methods to transform the data. ICA transforms the data into independent non-Gaussian components by maximizing the statistical independence of the estimated components whereas FA reduces the number of variables in the data by leveraging interdependencies between the observed variables. Feature selection techniques, on the other hand, work by ranking the untransformed features according to their importance. There are several feature ranking techniques in the literature, and in this study, we investigate three of the most popular ones including the Neighborhood Component Analysis (NCA) [40], the Minimum Redundancy Maximum Relevance (MRMR) [41], and the Chi-Square tests (CHI2) [42].

Fig 6. A flowchart describing the methodology used where a) depicts the feature extraction step, b) depicts the DR and FS modeling step, c) depicts the ML and FC training step and d) depicts the inference/classification step.

Fig 6

We use eleven DCNN architectures with each model pre-trained using the ImageNet database [31]. The list of the DCNNs and the summary of their architecture are shown in Table 3.

Table 3. The list of the DCNNs used and the summary of their architecture.

Architecture Depth (layers) Parameters (millions) Image Size (pixels)
AlexNet (2012) [43] 8 61.0 227×227
DenseNet201 (2017) [44] 201 11.7 224×224
Inception-ResNet-V2 (2016) [45] 164 55.9 299×299
InceptionV3 (2016) [46] 48 23.9 299×299
MobileNetV2 (2018) [47] 53 3.5 224×224
ResNet18, ResNet50 and ResNet101 (2016) [48] 18, 50 and 101 11.7, 25.6 and 44.6 224×224
VGG16 and VGG19 (2015) [49] 16 and 19 138 and 144 224×224
Xception (2017) [50] 71 22.9 299×299

The image features produced by each DCNN are then reduced in length before being used to train several ML models and FC neural network models. In this study, we use the popular algorithm called FastICA [38] to realize the dimensionality reduction of the features using independent component analysis. Our approach also examines using the full-length (FL) image features, i.e., without applying any DR or FS technique, for the same purpose. In total, we have six sets of method combinations for each DCNN to compare with, namely DR-ML, DR-FC, FS-ML, FS-FC, FL-ML, and FL-FC. The DR-XX set consists of PCA-XX, FA-XX, and FastICA-XX whereas the FS-XX set consists of NCA-XX, MRMR-XX, and CHI2-XX, where XX denotes the classifier type which is either ML or FC. A tree diagram depicting the method combination is shown in Fig 7.

Fig 7. A tree diagram depicting the method combination used in this study.

Fig 7

For the classification step, we use five different ML algorithms trained with hyperparameter optimization using a wide range of hyperparameter options and values. The ML algorithms that we used are K-Nearest Neighbor (KNN), Binary Decision Tree [51], Support Vector Machine (SVM) [52], Discriminant Analysis [53], and Ensemble of Tree Classifiers [52]. Each of the algorithms may have more than one training setup. We group the different setups of hyperparameter optimization of all ML algorithms into 20 ML learners. The description of the hyperparameter optimization options and values for each ML learner is described in Table 4.

Table 4. The description of the hyperparameter optimization options and range of values for each ML learner.

Learner ID Name Fixed Parameters Optimized Hyperparameters
Fine KNN (FKNN) Type: K-Nearest Neighbor
  • Distance Metric: Euclidean

  • Distance Weight: Equal

  • Max node size: 50

  • Prior probability: Empirical

  • Number of Neighbors (1–10)

  • Multiclass Decomposition Strategy (One-vs-One or One-vs-All)

  • Input standardization (Yes or No)

Medium KNN (MKNN) Type: K-Nearest Neighbor
  • Distance Metric: Euclidean

  • Distance Weight: Equal

  • Max node size: 50

  • Prior probability: Empirical

  • Number of Neighbors (10–100)

  • Multiclass Decomposition Strategy (One-vs-One or One-vs-All)

  • Input standardization (Yes or No)

Coarse KNN (CKNN) Type: K-Nearest Neighbor
  • Distance Metric: Euclidean

  • Distance Weight: Equal

  • Max node size: 50

  • Prior probability: Empirical

  • Number of Neighbors (100–1000)

  • Multiclass Decomposition Strategy [54] (One-vs-One or One-vs-All)

  • Input standardization (Yes or No)

Cosine KNN (COSKNN) Type: K-Nearest Neighbor
  • Distance Metric: Cosine

  • Distance Weight: Equal

  • Max node size: 50

  • Prior probability: Empirical

  • Number of Neighbors (10–100)

  • Multiclass Decomposition Strategy (One-vs-One or One-vs-All)

  • Input standardization (Yes or No)

Cubic KNN (CUBKNN) Type: K-Nearest Neighbor
  • Distance Metric: Minkowski

  • Distance Weight: Equal

  • Max node size: 50

  • Prior probability: Empirical

  • Exponent: 3

  • Score transform (Yes or No)

  • Number of Neighbors (10–100)

  • Multiclass Decomposition Strategy (One-vs-One or One-vs-All)

  • Input standardization (Yes or No)

Weighted KNN (WKNN) Type: K-Nearest Neighbor
  • Distance Metric: Euclidean

  • Distance Weight: Squared Inverse (1/d2)

  • Max node size: 50

  • Prior probability: Empirical

  • Score transform (Yes or No)

  • Number of Neighbors (10–100)

  • Multiclass Decomposition Strategy (One-vs-One or One-vs-All)

  • Input standardization (Yes or No)

Coarse Tree (CTREE) Type: Binary Decision Tree [51]
  • Min Leaf Size (1)

  • Min Parent Size (10)

  • Prior probability (Empirical)

  • Score transform (None)

  • Split Criterion (Gini-Simpson diversity index [55])

  • Max Number of Decision Splits (4–20)

  • Multiclass Decomposition Strategy (One-vs-One or One-vs-All)

Medium Tree (MTREE) Type: Binary Decision Tree
  • Min Leaf Size (1)

  • Min Parent Size (10)

  • Prior probability (Empirical)

  • Score transform (None)

    Split Criterion (Gini-Simpson diversity index)

  • Max Number of Decision Splits (20–100)

  • Multiclass Decomposition Strategy (One-vs-One or One-vs-All)

Fine Tree (FTREE) Type: Binary Decision Tree
  • Min Leaf Size (1)

  • Min Parent Size (10)

  • Prior probability (Empirical)

  • Score transform (None)

  • Split Criterion (Gini-Simpson diversity index)

  • Max Number of Decision Splits (100–1000)

  • Multiclass Decomposition Strategy (One-vs-One or One-vs-All)

Linear SVM (LSVM) Type: Support Vector Machine (SVM)
  • Kernel Function: Linear

  • Misclassification Penalty Cost (0.001–1000)

  • Multiclass Decomposition Strategy (One-vs-One or One-vs-All)

  • Input standardization (Yes or No)

Quadratic SVM (QSVM) Type: Support Vector Machine (SVM)
  • Kernel Function: Polynomial

  • Polynomial Order: 2

  • Misclassification Penalty Cost (0.001–1000)

  • Multiclass Decomposition Strategy (One-vs-One or One-vs-All)

  • Input standardization (Yes or No)

Cubic SVM (CSVM) Type: Support Vector Machine (SVM)
  • Kernel Function: Polynomial

  • Polynomial Order: 3

  • Misclassification Penalty Cost (0.001–1000)

  • Multiclass Decomposition Strategy (One-vs-One or One-vs-All)

  • Input standardization (Yes or No)

Fine Gaussian SVM (FGSVM) Type: Support Vector Machine (SVM)
  • Kernel Function: Gaussian

  • Kernel Scale: (10–40)

  • Misclassification Penalty Cost (0.001–1000)

  • Multiclass Decomposition Strategy (One-vs-One or One-vs-All)

  • Input standardization (Yes or No)

Medium Gaussian SVM (MGSVM) Type: Support Vector Machine (SVM)
  • Kernel Function: Gaussian

  • Kernel Scale: (40–80)

  • Misclassification Penalty Cost (0.001–1000)

  • Multiclass Decomposition Strategy (One-vs-One or One-vs-All)

  • Input standardization (Yes or No)

Coarse Gaussian SVM (CGSVM) Type: Support Vector Machine (SVM)
  • Kernel Function: Gaussian

  • Kernel Scale: (80–160)

  • Misclassification Penalty Cost (0.001–1000)

  • Multiclass Decomposition Strategy (One-vs-One or One-vs-All)

  • Input standardization (Yes or No)

Linear Discriminant (LD) Type: Discriminant Analysis
  • Discriminant Type: Pseudolinear

  • Linear coefficient threshold (0.000001–1000)

  • Regularization amount: (0–1)

  • Multiclass Decomposition Strategy (One-vs-One or One-vs-All)

Quadratic Discriminant (QD) Type: Discriminant Analysis
  • Discriminant Type: Pseudo quadratic

  • Regularization amount: (0–1)

  • Multiclass Decomposition Strategy (One-vs-One or One-vs-All)

Bagged Trees Classifier (BAG) Type: Ensemble of Tree Classifiers
  • Method: Bootstrap Aggregation [56]

  • Min Leaf Size (1)

  • Min Parent Size (10)

  • Prior probability (empirical)

  • Score transform (none)

  • Split Criterion (Gini-Simpson diversity index)

  • Number of Learning Cycles: (10–50)

  • Max Number of Splits: (3500–4500)

Boosted Trees Classifier (BOOST) Type: Ensemble of Tree Classifiers
  • Method: AdaBoostM2 [57]

  • Min Leaf Size (1)

  • Min Parent Size (10)

  • Prior probability (empirical)

  • Score transform (none)

  • Split Criterion (Gini-Simpson diversity index)

  • Learning rate (0.001–0.1)

  • Number of Learning Cycles: (10–50)

  • Max Number of Splits: (3500–4500)

Random Under Sampling (RUS) Boosting Type: Ensemble of Tree Classifiers
  • Random Under Sampling Boosting [58]

  • Min Leaf Size (1)

  • Min Parent Size (10)

  • Prior probability (empirical)

  • Score transform (none)

  • Split Criterion (Gini-Simpson diversity index)

  • Learning rate (0.001–0.1)

  • Number of Learning Cycles: (10–50)

  • Max Number of Splits: (3500–4500)

There are three training setups for the FC neural network, each corresponds to a different learning optimization algorithm, which is the Stochastic Gradient Descent with Momentum (SGDM) [59], the Root Mean Square Propagation (RMSP) [60], and the Adam (ADAM) [61] optimizers. The description of the hyperparameter optimization options and values for each ML learner is described in Table 5.

Table 5. The description of the hyperparameter optimization options and values for each FC learning optimization algorithm.

Classifier ID Name Fixed Parameters Optimized Hyperparameters
Stochastic Gradient Descent with Momentum (SGDM) Optimizer Type: Stochastic Gradient Descent with Momentum
  • Shuffle Every Epoch (True)

  • Max Epochs (30)

  • Constant learning rate per each training (as set by the Hyperparameters Optimization process)

  • Validation frequency (3 iterations)

  • All mini-batch lengths to match the longest mini-batch by zero-padding.

  • Mini Batch Size (10–20)

  • Initial Learning Rate (0.001–0.1)

  • L2 Regularization Coefficient (10−10–10−2)

  • Momentum (0.8–0.98)

Root Mean Square Propagation (RMSP) Optimizer: Root Mean Square Propagation
  • Shuffle Every Epoch (True)

  • Max Epochs (30)

  • Constant learning rate per each training (as set by the Hyperparameters Optimization process)

  • Validation frequency (3 iterations)

  • All mini-batch lengths to match the longest mini-batch by zero-padding

  • Mini Batch Size (10–20)

  • Initial Learning Rate (0.001–0.1)

  • L2 Regularization Coefficient (10−10–10−2)

  • Squared Gradient Decay Factor (0.8–0.98)

Adam Optimizer (ADAM) Optimizer: Adam Optimizer
  • Shuffle Every Epoch (True)

  • Max Epochs (30)

  • Constant learning rate per each training (as set by the Hyperparameters Optimization process)

  • Validation frequency (3 iterations)

  • All mini-batch lengths to match the longest mini-batch by zero-padding.

  • Mini Batch Size (10–20)

  • Initial Learning Rate (0.001–0.1)

  • L2 Regularization Coefficient (10−10–10−2)

  • Gradient Decay Factor (0.8–0.98)

We used Bayesian optimization to search the hyperparameter space to find the best set of hyperparameter values for the classification model that produces the lowest output to the objective function which, in our case, is the misclassification rate. The Bayesian optimization method works by building a probability model of the objective function and using it to select the most promising hyperparameters to evaluate in the true objective function. The popular Expected Improvement (EI) method [62] was used as the acquisition function to guide how the hyperparameter space should be explored. The technique combines the predicted mean and the predicted variance generated by a Gaussian process model used during the optimization into a criterion that will direct the search. In general, any acquisition function needs to find a good trade-off between exploitation which focuses on searching the vicinity of the current best hyperparameter values, and exploration which pushes the search towards unexplored areas in the hyperparameter space. The EI method that we used was found to provide a good balance between exploitation and exploration [63]. Furthermore, an improvement technique as suggested in [64] was applied that modifies the behavior of the EI method when it is found to be overexploiting an area and allow it to escape a local objective function minimum.

With respect to the total number of methods in each combination shown in Fig 7, the DR-ML and FS-ML categories consist of 660 different methods. They are a combination of 11 DCNNs, 3 DR and 3 FS techniques, and 20 ML learners. On the other hand, the DR-FC and FS-FC categories consist of 99 different methods. They are a combination of 11 DCNNs, 3 DR and 3 FS techniques, and 3 FC optimization algorithms. It is important to note that the traditional transfer learning approach as depicted in Fig 4 is the FL-FC method.

3. Experimental results, analysis, and discussion

3.1. Feature dimension reduction and feature selection

Before we could proceed with implementing the image classification processes, we need to determine the best feature length for each combination of DCNN model and DR/FS method. For PCA we use the popular 0.95 explained-variance threshold [65]. For the others, we tested different length percentages (ranging from 5 to 25% in 5% increments) for each classifier and identify one that gives the best overall accuracy. We select one representative length for each DCNN-DR/FS combination by calculating the average value over all classifiers. The resulting feature length values for each DCNN-DR/FS combination are shown in Table 6.

Table 6. The feature length of each DCNN model and DR/FS method combination.

PCA FA FastICA NCA MRMR CHI2 Full Length
AlexNet 381 410 614 819 2048 1638 4096
DenseNet201 318 288 192 768 960 768 1920
Inception-ResNetv2 174 307 384 614 614 768 1536
Inceptionv3 377 205 205 819 819 819 2048
MobileNetv2 344 192 320 512 640 640 1280
ResNet18 158 102 128 256 256 256 512
ResNet50 305 307 205 1024 614 410 2048
ResNet101 274 410 205 1024 410 614 2048
VGG16 310 410 819 1638 2048 1638 4096
VGG19 311 410 410 1638 2048 1638 4096
Xception 338 410 410 614 819 1024 2048

The last column shows the full length of the DCNN features.

3.2. Performance metrics

The classification performance of each method is measured using four performance metrics namely the overall Accuracy, Precision, Recall, and F1-Score. The overall Accuracy, denoted as A, is the ratio of the number of correctly classified images and the total number of test images. Using the standard notations of true positive (tp), true negative (tn), false positive (fp), and false negative (fn), the metrics are calculated as:

A=tp+tntp+tn+fp+fn

Since the Accuracy metric could provide a misleading assessment of a method’s performance on an imbalanced dataset, we also employ the other three metrics to provide us with a more complete picture of the method’s performance. The Precision, Recall, and their harmonic mean F1-Score metrics are calculated as:

P=1CiCPi
R=1CiCRi
F=2CiCPiRiPi+Ri

Where Pi, Ri, and Fi denote the respective class-based metrics of the ith class, which are the class precision, the class recall, and the class F1-Score, respectively. The notation i, where i ∈ {1, 2, 3, 4}, is the respective index of each of the four classes. These class-based metrics provide a measure of each method’s performance on each individual class and are calculated as:

Pi=tpitpi+fpi
Ri=tpitpi+fni
Fi=2×PiRiPi+Ri

3.3. Experimental results, analysis, and discussion

We implemented each method combination 20 times, each with a different combination of training and test sets, to provide us with statistically representative results. The average of each performance metric over the 20 repeats of each method combination is calculated. The ML learner or FC optimizer that produces the highest performance of each method combination is then identified. The results are shown in Tables 714.

Table 7. The best ML learner for each combination method and its average classification performance (using Accuracy metric).

PCA-ML FA-ML FastICA-ML NCA-ML MRMR-ML CHI2-ML FL-ML
AlexNet 0.96 0.95 0.96 0.96 0.96 0.96 0.95
FGSVM CSVM FGSVM FGSVM FGSVM FGSVM FGSVM
DenseNet201 0.96 0.97 0.96 0.97 0.97 0.97 0.97
CSVM FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM
Inception-ResNetv2 0.95 0.96 0.96 0.95 0.95 0.95 0.95
FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM
Inceptionv3 0.96 0.95 0.96 0.97 0.96 0.96 0.96
FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM
MobileNetv2 0.96 0.95 0.96 0.96 0.96 0.96 0.96
FGSVM CSVM FGSVM FGSVM FGSVM FGSVM FGSVM
ResNet18 0.94 0.93 0.94 0.94 0.94 0.94 0.95
FGSVM BAG FGSVM FGSVM FGSVM FGSVM FGSVM
ResNet50 0.96 0.95 0.96 0.97 0.95 0.96 0.96
FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM
ResNet101 0.96 0.96 0.96 0.95 0.95 0.96 0.96
FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM
VGG16 0.95 0.95 0.96 0.94 0.94 0.94 0.95
FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM
VGG19 0.96 0.96 0.96 0.95 0.95 0.95 0.94
FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM
Xception 0.96 0.96 0.96 0.95 0.96 0.96 0.96
FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM

Table 14. The best FC learning optimizer for each combination method and its average classification performance (using F1-Score metric).

PCA-FC FA-FC FastICA-FC NCA-FC MRMR-FC CHI2-FC FL-FC
AlexNet 0.84 0.81 0.88 0.88 0.96 0.91 0.96
RMSP RMSP ADAM ADAM ADAM ADAM ADAM
DenseNet201 0.88 0.87 0.75 0.86 0.83 0.81 0.93
RMSP RMSP ADAM RMSP SGDM RMSP SGDM
Inception-ResNetv2 0.72 0.81 0.77 0.76 0.76 0.70 0.88
ADAM SGDM ADAM RMSP RMSP ADAM RMSP
Inceptionv3 0.84 0.74 0.66 0.86 0.85 0.83 0.89
RMSP SGDM RMSP RMSP RMSP RMSP RMSP
MobileNetv2 0.88 0.81 0.80 0.87 0.84 0.87 0.95
RMSP SGDM ADAM RMSP RMSP RMSP RMSP
ResNet18 0.77 0.72 0.63 0.73 0.76 0.73 0.76
SGDM ADAM ADAM ADAM RMSP RMSP SGDM
ResNet50 0.86 0.82 0.73 0.89 0.82 0.81 0.96
ADAM RMSP ADAM RMSP RMSP RMSP ADAM
ResNet101 0.82 0.90 0.69 0.86 0.77 0.85 0.93
ADAM SGDM ADAM ADAM ADAM RMSP RMSP
VGG16 0.82 0.86 0.84 0.96 0.96 0.94 0.94
ADAM RMSP ADAM ADAM ADAM ADAM ADAM
VGG19 0.85 0.89 0.80 0.97 0.95 0.91 0.97
RMSP RMSP ADAM ADAM ADAM ADAM ADAM
Xception 0.84 0.88 0.76 0.76 0.83 0.84 0.86
ADAM SGDM ADAM ADAM RMSP RMSP RMSP

Table 8. The best ML learner for each combination method and its average classification performance (using Precision metric).

PCA-ML FA-ML FastICA-ML NCA-ML MRMR-ML CHI2-ML FL-ML
AlexNet 0.96 0.95 0.96 0.96 0.95 0.95 0.95
FGSVM CSVM FGSVM FGSVM FGSVM FGSVM FGSVM
DenseNet201 0.95 0.97 0.96 0.97 0.97 0.97 0.97
FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM
Inception-ResNetv2 0.95 0.95 0.96 0.95 0.95 0.95 0.95
FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM
Inceptionv3 0.96 0.95 0.96 0.96 0.96 0.96 0.96
FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM
MobileNetv2 0.96 0.95 0.96 0.96 0.95 0.96 0.96
FGSVM CSVM FGSVM FGSVM FGSVM FGSVM FGSVM
ResNet18 0.94 0.93 0.94 0.94 0.94 0.94 0.95
FGSVM BAG FGSVM FGSVM FGSVM FGSVM FGSVM
ResNet50 0.95 0.95 0.96 0.97 0.95 0.96 0.96
FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM
ResNet101 0.96 0.96 0.95 0.95 0.95 0.95 0.95
FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM
VGG16 0.94 0.95 0.96 0.94 0.94 0.94 0.95
FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM
VGG19 0.96 0.96 0.96 0.94 0.95 0.95 0.94
FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM
Xception 0.96 0.96 0.96 0.95 0.96 0.96 0.96
FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM

Table 9. The best ML learner for each combination method and its average classification performance (using Recall metric).

PCA-ML FA-ML FastICA-ML NCA-ML MRMR-ML CHI2-ML FL-ML
AlexNet 0.96 0.96 0.96 0.96 0.96 0.96 0.96
FGSVM CSVM FGSVM FGSVM FGSVM FGSVM FGSVM
DenseNet201 0.96 0.97 0.97 0.97 0.97 0.97 0.98
CSVM FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM
Inception-ResNetv2 0.96 0.96 0.96 0.96 0.96 0.96 0.96
FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM
Inceptionv3 0.96 0.96 0.96 0.97 0.96 0.97 0.97
FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM
MobileNetv2 0.96 0.96 0.96 0.96 0.96 0.97 0.97
FGSVM CSVM FGSVM FGSVM FGSVM FGSVM FGSVM
ResNet18 0.95 0.94 0.95 0.95 0.95 0.95 0.96
CSVM BAG FGSVM FGSVM FGSVM FGSVM FGSVM
ResNet50 0.96 0.96 0.96 0.97 0.96 0.97 0.97
FGSVM CSVM FGSVM FGSVM CSVM FGSVM FGSVM
ResNet101 0.96 0.96 0.96 0.96 0.96 0.96 0.96
FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM
VGG16 0.95 0.95 0.96 0.95 0.95 0.95 0.96
FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM
VGG19 0.97 0.96 0.96 0.95 0.96 0.95 0.95
FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM
Xception 0.96 0.96 0.96 0.96 0.96 0.96 0.96
FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM

Table 12. The best FC learning optimizer for each combination method and its average classification performance (using Precision metric).

PCA-FC FA-FC FastICA-FC NCA-FC MRMR-FC CHI2-FC FL-FC
AlexNet 0.84 0.81 0.89 0.89 0.96 0.93 0.96
RMSP ADAM ADAM RMSP ADAM ADAM ADAM
DenseNet201 0.88 0.87 0.80 0.88 0.86 0.82 0.93
RMSP RMSP ADAM RMSP ADAM RMSP SGDM
Inception-ResNetv2 0.72 0.81 0.81 0.81 0.77 0.81 0.87
ADAM SGDM ADAM ADAM RMSP RMSP RMSP
Inceptionv3 0.83 0.74 0.75 0.88 0.86 0.85 0.92
RMSP SGDM RMSP RMSP RMSP RMSP RMSP
MobileNetv2 0.89 0.81 0.84 0.89 0.87 0.87 0.95
RMSP SGDM ADAM RMSP ADAM SGDM RMSP
ResNet18 0.77 0.72 0.71 0.76 0.77 0.75 0.82
SGDM ADAM RMSP ADAM RMSP RMSP ADAM
ResNet50 0.86 0.83 0.78 0.91 0.87 0.82 0.96
ADAM RMSP ADAM RMSP ADAM RMSP ADAM
ResNet101 0.82 0.90 0.74 0.86 0.80 0.85 0.95
ADAM SGDM ADAM ADAM RMSP RMSP RMSP
VGG16 0.82 0.86 0.87 0.95 0.96 0.95 0.96
ADAM RMSP ADAM ADAM ADAM ADAM ADAM
VGG19 0.85 0.89 0.83 0.97 0.94 0.93 0.98
RMSP RMSP ADAM ADAM ADAM ADAM ADAM
Xception 0.84 0.88 0.80 0.77 0.83 0.85 0.87
ADAM SGDM ADAM ADAM RMSP ADAM RMSP

Table 13. The best FC learning optimizer for each combination method and its average classification performance (using Recall metric).

PCA-FC FA-FC FastICA-FC NCA-FC MRMR-FC CHI2-FC FL-FC
AlexNet 0.85 0.83 0.87 0.89 0.97 0.90 0.96
RMSP SGDM ADAM ADAM ADAM ADAM ADAM
DenseNet201 0.89 0.88 0.74 0.86 0.84 0.80 0.93
RMSP RMSP ADAM RMSP SGDM RMSP SGDM
Inception-ResNetv2 0.73 0.82 0.75 0.76 0.76 0.72 0.89
ADAM SGDM ADAM RMSP RMSP ADAM RMSP
Inceptionv3 0.84 0.75 0.64 0.85 0.84 0.84 0.89
RMSP SGDM ADAM RMSP RMSP ADAM ADAM
MobileNetv2 0.88 0.81 0.79 0.87 0.87 0.90 0.95
RMSP SGDM ADAM RMSP RMSP RMSP RMSP
ResNet18 0.77 0.72 0.62 0.73 0.76 0.73 0.76
SGDM ADAM ADAM ADAM RMSP RMSP SGDM
ResNet50 0.87 0.83 0.71 0.89 0.82 0.82 0.97
ADAM RMSP ADAM RMSP RMSP RMSP ADAM
ResNet101 0.83 0.92 0.68 0.88 0.79 0.85 0.94
ADAM SGDM ADAM ADAM ADAM RMSP ADAM
VGG16 0.83 0.87 0.82 0.96 0.96 0.93 0.92
ADAM RMSP ADAM ADAM ADAM ADAM ADAM
VGG19 0.86 0.89 0.78 0.97 0.96 0.90 0.96
RMSP RMSP ADAM ADAM ADAM ADAM ADAM
Xception 0.85 0.89 0.74 0.76 0.84 0.85 0.86
ADAM ADAM ADAM ADAM RMSP RMSP ADAM

Through observation of the experimental results shown in those tables, we can deduce several findings. Firstly, the performance of DR-ML methods is very good and stable with a range of values from 0.93 to 0.97. The performance of FS-ML methods is also very good and stable with a range of values from 0.94 to 0.97. Likewise, the performance of FL-ML methods is also very good and stable with a range of values from 0.94 to 0.98. On the other hand, the performance of DR-FC, FS-FC, and FL-FC method combinations is generally poorer and more unpredictable. This can be seen from the bigger range in performance the method combinations produce. Therefore, we can say that ML approaches are better and more predictable than FC approaches. Secondly, we find that Fine Gaussian SVM (FGSVM) is the best learner to use in the ML category as it consistently produces the highest performance in all four metrics. This learner uses the Support Vector Machine algorithm with a short Gaussian kernel. On the other hand, there is no clear best optimizer in the FC category as both ADAM and RMSP optimizers are relatively equal. However, when full-length features from ResNet50, ResNet101, VGG16, and VGG19 DCNNs were used ADAM optimizer produces generally higher performance than the other two.

We also found that applying DR or FS to the features has little impact on the performance when ML classifiers were used. However, this is not the case when FC Neural Networks were used. This can be seen from the summary of the classification performance of ML classifiers and FC Neural Networks that are tabulated in Tables 15 and 16 which contain the minimum, the maximum, and the mean values of the performance over the eleven DCNNs provided in Tables 710 and 1114, respectively. Here we can see that the average performance drops significantly from around 0.91 ~ 0.92 (in the case of FL-FC) to 0.80 (in the case of DR-FC) or 0.85 (in the case of FS-FC) whereas there is hardly any difference in average performance between FL-ML, DR-ML, and FS-ML.

Table 15. Summary of the classification performance of ML learners using features from 11 DCNNs.

DR-ML FS-ML FL-ML
A P R F A P R F A P R F
Min 0.93 0.93 0.94 0.94 0.94 0.94 0.95 0.94 0.94 0.94 0.95 0.94
Max 0.97 0.97 0.97 0.97 0.97 0.97 0.97 0.97 0.97 0.97 0.98 0.97
Mean 0.96 0.95 0.96 0.96 0.95 0.95 0.96 0.96 0.96 0.96 0.96 0.96

The table header A, P. R, and F are the shorthand of Accuracy, Precision, Recall, and F1-Score, respectively.

Table 16. Summary of the classification performance of FC neural networks using features from 11 DCNNs.

DR-FC FS-FC FL-FC
A P R F A P R F A P R F
Min 0.67 0.71 0.62 0.63 0.72 0.75 0.72 0.70 0.78 0.82 0.76 0.76
Max 0.91 0.90 0.92 0.90 0.97 0.97 0.97 0.97 0.97 0.98 0.97 0.97
Mean 0.81 0.82 0.80 0.80 0.85 0.86 0.85 0.85 0.91 0.92 0.91 0.91

The table header A, P. R, and F are the shorthand of Accuracy, Precision, Recall, and F1-Score, respectively.

Table 10. The best ML learner for each combination method and its average classification performance (using F1-Score metric).

PCA-ML FA-ML FastICA-ML NCA-ML MRMR-ML CHI2-ML FL-ML
AlexNet 0.96 0.95 0.96 0.96 0.96 0.96 0.96
FGSVM CSVM FGSVM FGSVM FGSVM FGSVM FGSVM
DenseNet201 0.96 0.97 0.96 0.97 0.97 0.97 0.97
CSVM FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM
Inception-ResNetv2 0.95 0.96 0.96 0.95 0.95 0.95 0.95
FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM
Inceptionv3 0.96 0.96 0.96 0.97 0.96 0.96 0.96
FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM
MobileNetv2 0.96 0.95 0.96 0.96 0.96 0.96 0.96
FGSVM CSVM FGSVM FGSVM FGSVM FGSVM FGSVM
ResNet18 0.94 0.94 0.94 0.94 0.94 0.95 0.96
FGSVM BAG FGSVM FGSVM FGSVM FGSVM FGSVM
ResNet50 0.96 0.95 0.96 0.97 0.95 0.96 0.96
FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM
ResNet101 0.96 0.96 0.96 0.95 0.95 0.96 0.96
FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM
VGG16 0.95 0.95 0.96 0.95 0.94 0.94 0.95
FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM
VGG19 0.96 0.96 0.96 0.95 0.95 0.95 0.94
FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM
Xception 0.96 0.96 0.96 0.95 0.96 0.96 0.96
FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM FGSVM

Table 11. The best FC learning optimizer for each combination method and its average classification performance (using Accuracy metric).

PCA-FC FA-FC FastICA-FC NCA-FC MRMR-FC CHI2-FC FL-FC
AlexNet 0.85 0.82 0.89 0.88 0.96 0.92 0.96
RMSP SGDM ADAM RMSP ADAM ADAM ADAM
DenseNet201 0.88 0.88 0.77 0.87 0.84 0.82 0.93
RMSP RMSP ADAM RMSP RMSP RMSP SGDM
Inception-ResNetv2 0.73 0.82 0.78 0.78 0.78 0.72 0.88
ADAM SGDM ADAM RMSP RMSP RMSP RMSP
Inceptionv3 0.84 0.75 0.68 0.86 0.85 0.84 0.90
RMSP SGDM RMSP RMSP RMSP RMSP RMSP
MobileNetv2 0.89 0.82 0.81 0.88 0.85 0.88 0.95
RMSP SGDM ADAM RMSP RMSP SGDM RMSP
ResNet18 0.78 0.74 0.67 0.76 0.78 0.75 0.78
SGDM ADAM ADAM ADAM RMSP RMSP ADAM
ResNet50 0.87 0.83 0.75 0.90 0.82 0.83 0.96
ADAM SGDM ADAM RMSP RMSP RMSP ADAM
ResNet101 0.83 0.91 0.72 0.86 0.78 0.85 0.93
ADAM SGDM ADAM ADAM RMSP RMSP ADAM
VGG16 0.82 0.87 0.85 0.96 0.96 0.94 0.94
ADAM RMSP ADAM ADAM ADAM ADAM ADAM
VGG19 0.86 0.90 0.80 0.97 0.95 0.91 0.97
RMSP RMSP ADAM ADAM ADAM ADAM ADAM
Xception 0.84 0.88 0.77 0.77 0.84 0.85 0.87
ADAM SGDM ADAM ADAM RMSP RMSP RMSP

By comparing the results in both tables, we conclude that using an ML algorithm is a better option to take than using an FC neural network. Therefore, from the perspective of choosing the best DCNN, we can base our decision only on the ML algorithm classification results. To find out which DCNN that provides the best feature, we tabulate the minimum, maximum, and mean values of the classification performance for each DCNN in Table 17. From the table, we can see that DenseNet201 provides the best performance compared to the other DCNNs as it produces consistently high classification results which range from 0.95 to 0.98 in all performance metrics.

Table 17. Summary of classification performance of ML methods for each DCNN.

Accuracy Precision Recall F1-Score
Min Max Mean Min Max Mean Min Max Mean Min Max Mean
AlexNet 0.95 0.96 0.96 0.95 0.96 0.95 0.96 0.96 0.96 0.95 0.96 0.96
DenseNet201 0.96 0.97 0.97 0.95 0.97 0.96 0.96 0.98 0.97 0.96 0.97 0.97
Inception-ResNetv2 0.95 0.96 0.95 0.95 0.96 0.95 0.96 0.96 0.96 0.95 0.96 0.95
Inceptionv3 0.95 0.96 0.96 0.95 0.96 0.96 0.96 0.97 0.96 0.95 0.97 0.96
MobileNetv2 0.95 0.96 0.96 0.95 0.96 0.96 0.96 0.97 0.96 0.95 0.96 0.96
ResNet18 0.93 0.95 0.94 0.93 0.95 0.94 0.94 0.96 0.95 0.94 0.95 0.94
ResNet50 0.95 0.97 0.96 0.95 0.97 0.96 0.96 0.97 0.96 0.95 0.97 0.96
ResNet101 0.95 0.96 0.95 0.95 0.96 0.95 0.96 0.96 0.96 0.95 0.96 0.96
VGG16 0.94 0.96 0.95 0.94 0.96 0.95 0.95 0.96 0.95 0.94 0.96 0.95
VGG19 0.94 0.96 0.95 0.94 0.96 0.95 0.95 0.96 0.96 0.94 0.96 0.95
Xception 0.95 0.96 0.96 0.95 0.96 0.96 0.96 0.96 0.96 0.95 0.96 0.96

The maximum value in each column is marked in bold text.

We can then determine, using the DenseNet201 results, which DR/FS method to choose and how its performance compares to using the full-length feature. For this, we show in Figs 811, the boxplots of each method’s performance calculated over the 20 experiment repeats when the DenseNet201 feature is used. The ML learners that produce the best performance shown in those figures can be found in the second row of Tables 710, respectively.

Fig 8. The Accuracy of DR/FS/FL-ML methods using DenseNet201 features.

Fig 8

The ML learners used can be found in the second row of Table 7.

Fig 11. The F1-Score of DR/FS/FL-ML methods using DenseNet201 features.

Fig 11

The ML learners used can be found in the second row of Table 10.

Fig 9. The Precision of DR/FS/FL-ML methods using DenseNet201 features.

Fig 9

The ML learners used can be found in the second row of Table 8.

Fig 10. The Recall of DR/FS/FL-ML methods using DenseNet201 features.

Fig 10

The ML learners used can be found in the second row of Table 9.

From observing the figures, we conclude that applying a DR or FS method before classification slightly reduces the performance when compared to using the full-length feature, although in most cases the differences do not seem to be statistically significant. Given the fact that applying a DR or FS method adds computational cost and time to the process, we concluded that using the full-length feature is the best approach to take. Therefore, we decide that the best combination method is using the full length of the DenseNet201 feature with a Fine Gaussian SVM learner (FL-FGSVM). Using this setup, we can then show the best classification results from the entire set of experiments for each class. These are shown as the per-class classification performance using the Precision, Recall, and F1-score metrics in Figs 1214.

Fig 12. Per-class classification performance using Fine Gaussian SVM classifier on full-length DenseNet201 features (Precision).

Fig 12

Fig 14. Per-class classification performance using Fine Gaussian SVM classifier on full-length DenseNet201 features (F1-Score).

Fig 14

From Figs 12 and 13, we find that the minimum class precision and recall is around 0.88. The median performance measured using the precision metric ranges from 0.95 to 0.99 whereas that using the recall metric ranges from 0.93 to 1.0. It is worth noting that, in most cases, a computer algorithm is only needed to automatically find the correct L3/L4, L4/L5, and L5/S1 images. In that respect, we can claim that the classification of those three classes when measured using F1-Score, which is the harmonic mean of the precision and recall metrics, is very good. From Fig 14, we can see that the minimum F1-Scores of those three classes range between 0.93 to 0.95, whereas the median F1-Scores range between 0.97 to 0.99.

Fig 13. Per-class classification performance using Fine Gaussian SVM classifier on full-length DenseNet201 features (Recall).

Fig 13

3.4. Consideration on the practical implementation

The whole process we described in this paper has been implemented using MATLAB version 2021a on three different computer setups. One setup has an Intel(R) i7-10700K CPU @ 3.80GHz, 16 GB RAM, and NVIDIA GeForce RTX 3080 with 10 GB VRAM. Another setup has an Intel(R) i7-7700 CPU @ 3.60GHz, 64 GB RAM, and 2x NVIDIA TITAN X with 24 GB VRAM. The last setup has an Intel(R) i9-7900X CPU @ 3.30GHz, 128 GB RAM, and 4x NVIDIA TITAN XP with 48 GB VRAM. One of the bottlenecks in the experiment is the time taken to train the ML learners and FC neural networks using hyperparameter optimization, which can take hours on the above machines. The source code, dataset, and result files have been made available for review from Mendeley Data [66]. The procedure starts by providing the program with two folders containing identical numbers of T1-weighted and T2-weighted traverse lumbar spine MRI images. The program would assume that the image files in both folders are in the same correct order when sorted alphabetically before applying the image registration step. The image registration results are then stored in another folder. The ground truth information, as a comma-separated value (CSV) file, containing indices of the images that belong to each category is supplied. The program then split the dataset into four folders depending on the CSV file. The program then loads a DCNN and applies it to each image and records the resulting image features. The program also allows a DS or FS algorithm to be applied before using the features for training an ML learner or an FC neural network. The program then uses the trained ML learner or an FC neural network to classify a new image based on the image features. The time taken to extract the feature from an image ranges from 1 to 14 milliseconds and the time to classify one image takes less than 10 milliseconds. The total time would be much faster than manual selection which takes between 30 to 60 seconds, especially if the process is done in big batches.

The same approach can be adopted in a clinic provided that the necessary hardware and software requirements are met, which can be obtained from the MATLAB official website. Some modifications to the source code might be needed to adapt it to each user’s setup and requirement. A similar approach can also be implemented using Python programming language together with the necessary deep learning library (such as Keras [67]) and machine learning library (such as Scikit-Learn [68]). Much of the MATLAB code can be translated to Python but some low-level function implementations could be different.

4. Conclusion

We have detailed in this paper, our approach for selecting traverse images that cut closest to the half-height of an Intervertebral Disc from a dataset of traverse lumbar spine MRI. The method is based on using the image features extracted from a Deep Convolutional Neural Network to train a Machine Learning classifier or a Fully Connected Neural Network. We investigated the suitability and usefulness of applying a Dimensionality Reduction technique or a Feature Selection technique prior to the training as well as using the full-length features. In total, we tested eleven Deep Convolutional Neural Network models, three Dimensionality Reduction techniques, three Feature Selection techniques, twenty Machine Learning learners, and three Fully Connected Neural Network learning optimizers. The learners and optimizers were trained using hyperparameter optimization to ensure that they produce the best result they can. We implemented the different method combinations twenty times to get representative results from each method. Our experiment shows that applying the Support Vector Machine algorithm with a short Gaussian kernel on full-length DenseNet201 is the best approach to use. This approach gives the minimum per-class classification performance of around 0.88 when measured using the precision and recall metrics. The median performance measured using the precision metric ranges from 0.95 to 0.99 whereas that using the recall metric ranges from 0.93 to 1.0. When only considering the L3/L4, L4/L5, and L5/S1 classes, the minimum F1-Scores range between 0.93 to 0.95, whereas the median F1-Scores range between 0.97 to 0.99.

4.1. Appendix

The MATLAB source files and traverse image subset of the Lumbar Spine MRI Dataset [35] used in this experiment can be downloaded from Mendeley Data [66].

Supporting information

S1 Data. A Word document containing URL of the dataset.

Models and PYTHON/MATLAB source code to reproduce the results.

(DOCX)

Data Availability

We have made our dataset and source code published and open to the public. They are on Mendeley Data. URL: https://data.mendeley.com/datasets/ggjtzh452d/1 DOI: 10.17632/ggjtzh452d.1 Further instructions and information can be found in the paper’s Supporting information files.

Funding Statement

Grant Holder: FN Grant Number: 9/E1/KPT/2020 Funder: The Indonesian Ministry of Research, Technology and Higher Education. Funder URL: https://www.ristekbrin.go.id/ The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Decision Letter 0

Nguyen Quoc Khanh Le

11 Apr 2021

PONE-D-21-04349

Automated Selection of Mid-Height Intervertebral Disc Slice in Traverse Lumbar Spine MRI using Transfer Learning and Dimensionality Reduction of Pre-trained DCNN Features

PLOS ONE

Dear Dr. Sudirman,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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Reviewer #2: Yes

Reviewer #3: Partly

Reviewer #4: Partly

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #1: The technical detail of this work is missing. Authors should add the technical detail related to proposed method. Without technical detail, the manuscript is not acceptable. Also, based on just results, it is not possible to accept this version.

Reviewer #2: This paper still needs improvement before acceptance for publication. My detailed comments and suggestions are given as follows:

1. The Introduction needs to be revised and should emphasize the challenges and corresponding techniques.

2. More comparative experiments should be added to illustrate the superiority of the propose method, and the experimental results should be further analyzed.

3. Training details should be presented, such as the setting of learning rate and the decay of loss function.

4. Discussions about the generalization performance of deep learning model are encouraged.

5. Many figures are so blurred that they cannot be read, such as Fig. 11, Fig .12, and Fig. 13.

Reviewer #3: In this paper, the authors tackled an interesting problem of selecting specific slices from lumbar spine MRI. The motivation behind this work is clear, and the ideas presented in this manuscript are valid, but it suffers from the following shortcomings that need to be addressed before it could be considered for publication:

1. The authors sort of failed to contextualize their work within the state of the art, as reducing the dimensionality of deep features extracted using deep models is not novel. As the examples, see the following works: https://www.sciencedirect.com/science/article/abs/pii/S1047320319301932, https://link.springer.com/chapter/10.1007/978-3-319-77538-8_34. The authors should not only discuss such techniques in the related literature part of the manuscript, but should also confront their dimensionality reduction technique with other feature extraction and selection algorithms.

2. I suggest removing acronyms from the title.

3. Overall, the quality of the figures is very low and should be substantially improved.

4. The authors should discuss the models presented in Table 1 in much more detail. Specifically, I encourage the authors to prepare a taxonomy of investigated deep architectures (with special emphasis put on their architectural choices that are specific). To this end, the authors should make sure that the manuscript is self-contained. Also, please add the year for each model in Table 1.

5. Please discuss the co-registration process in more detail (lines starting from 296).

6. The authors should perform rigorous crossvalidation to fully understand the generalization abilities of the algorithms (a single 80/20 split may be not enough to infer correct conclusions).

7. Although the authors did try to show different experimental aspects of various architectures, the experiments are rather not thorough. It would be best to present the ablation study (e.g., selection of optimizers) for a wider range of investigated models. Overall, the authors should rework their experimental part of the paper to make it more thorough.

Reviewer #4: Review Manuscript PONE-D-21-04349

The authors present an alternative methodology to assess the selection of mid-high IVD image slide from MRI acquisitions.

This is an interesting work for the spine community since it states a possible automatic way the selection of suitable images of the IVD in lumbar spine. The use deep learning algorithm to a large number of images to test their technique. This work presents a really nice use of deep learning to tackle a difficulty of obtaining better information of the lumbar IVDs. However, the manuscript summited is not ready to be published since there are some aspects to be considered. These aspects are listed as follow:

- Most of the research articles follow the structure: Introduction, Materials and methods, Results, Discussion, Conclusions (sometimes included at the end of the discussion section). This structure is not totally followed by the authors making difficult the follow up of the paper.

- I really enjoyed the introduction part, it was really instructive and easy to follow. Nevertheless, a clear aim of the study is missing. At lines 91-92 the mentioned “In this paper, we detailed our approach to automatically …” but if this is an objective is vague, they need to specify the objective(s) of their study.

- The second section can be reduced and included in the introduction that also need to be reduced. In general, the introduction should not be larger than 2 pages, but some exception are in order when the paper is a review which is not the case.

- Material and methods section: it is poor. In this section the authors should present the steps they did in the study, a description of the methods, i.e. what they did, what they use, what they modified. The database use, the test they did and what were the variable measured/evaluated, they will compare their results with what database to validate.

- Part 4, is a mix of several part. Here the authors present, part of the methods, then present the results, and discuss a little bit about the results. I highly suggest to the authors to follow the article structure previous mentioned.

- Results: in general, they are interesting. They should have a separate section where they can be presented in a proper way

- Discussion: The results are poorly discussed. The authors make some interesting comments regarding the results. However, a comparison with other studies, what are the similarities and differences, and the explanation of the differences, what are the limitations of the method propose, are missed in the manuscript presented.

- Conclusions: is weak. It is not clear the contribution of the new technique to the spine community, does the outcomes obtained are better than the one obtained manually? Is it faster? Can be implemented easily in clinic?

- Figures with bars: It might be better to present a feature with the modes used instead of having them separated. I mean, for example figure 6, the metric accuracy can have the bars for SGDM and Adam, as such, it can be seen better the differences between the two models used.

- Tables 2 and 3: please rearrange the information to better understand the content, also when present statistical results avoid to use scientific notation for the numbers, it is better and more easy to evaluate the number with decimals.

- Anachronisms, check that all of them are previously introduced.

-Experiments: the word “experiment” is most common for cells, object, assay experiments. It is better to use test when you use numerical “experiment”, e.g. testing a new numerical algorithm against another one to evaluate its performance.

- Lines 527 -528: the authors present that their method improves upon the benchmark TL/FT methods by presenting increments in the mean values. How this is true? I mean, how the fact that the mean is higher, is a sign of improvement?

The manuscript is well written and the study is really interesting for spine community. The reviewer encourages the authors to consider all the comments mentioned previously. With the changes suggested in this review, the authors can resubmit the manuscript for publication.

**********

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PLoS One. 2022 Jan 13;17(1):e0261659. doi: 10.1371/journal.pone.0261659.r002

Author response to Decision Letter 0


2 Jul 2021

Dear reviewers,

Thank you for all your effort and help in improving our paper. We appreciate your comments, suggestions, and critique. Based on your feedback, we have reworked much of our methodology and experimentation. Our approach was previously proposed using one specific combination of Deep Convolutional Neural Networks and one Dimensionality Reduction to perform the image classification. Our approach now is to test and compare many different combinations of Deep Convolutional Neural Networks for feature extraction, Dimensionality Reduction as well as Feature Selection techniques, several Machine Learning algorithms, several learning optimizers for Fully Connected Neural Networks, and use hyperparameter optimization to get the best classifier for each combination.

As a result, we pretty much changed over 95% of the texts in the paper.

Furthermore, the time taken to conduct the experiment had significantly increased hence the long delay in resubmitting this revision.

I hope you will find the new version of our paper much better than the last version.

Kind regards

Sud

Reviewer #1: The technical detail of this work is missing. Authors should add the technical detail related to proposed method. Without technical detail, the manuscript is not acceptable. Also, based on just results, it is not possible to accept this version.

Thank you for your feedback. The requested technical detail has been added to the paper by expanding the Material section and adding a table. The added information reads:

The material used in this research is taken from our Lumbar Spine MRI Dataset which is available publicly [6,23]. This dataset contains anonymized clinical MRI studies of 515 patients with symptomatic back pains. The dataset consists of 48,345 T1-weighted and T2-weighted traverse and sagittal images of the patients’ lumbar spine in the Digital Imaging and Communications in Medicine (DICOM) format. The images were taken using a 1.5-Tesla Siemens Magnetom Essenza MRI scanner. Most of the images were taken when the patients were in the Head-First-Supine position, though a few were taken when they were in the Feet-First-Supine position. The duration of each patient study ranges between 15 to 45 minutes with time gaps between taking the T1- and T2-weighted scans ranging between 1 to 9 minutes. The patient might have made some movements between the T1 and T2 recordings, which suggests that corresponding T1- and T2- slices may not necessarily align and may require an application of an image registration algorithm to align them. The scanning sequence used in all scans is Spin Echo (SE), which is produced by pairs of radiofrequency pulses, with segmented k-space (SK), spoiled (SP), and oversampling phase (OSP) sequence variant. Fat-Sat pulses were applied just before the start of each imaging sequence to saturate the signal from fat matters to make it appear distinct to water. The summary of the technical information of the scanning parameters carried out when recording these images is provided in Table 1.

Reviewer #2: This paper still needs improvement before acceptance for publication. My detailed comments and suggestions are given as follows:

1. The Introduction needs to be revised and should emphasize the challenges and corresponding techniques.

Thank you for your comments. The Introduction section has been revised and the challenges of the problem and the corresponding techniques have been added. The specific part of the section that addresses this now reads:

Based on the above argument, we believe that both a) the lack of directly relevant methods proposed in the literature that selects the best traverse plane that cuts closest to the half-height of an IVD in a lumbar spine MRI and b) the wide range of potentially suitable DR or FS methods and image classification methods, provide the rationale and urgency for this study. The aim of this study is to find the best method to select the best traverse plane that cuts closest to the half-height of an IVD in a lumbar spine MRI by studying and comparing the different combination of machine learning methods and approaches. We report the result of our investigation on the suitability and performance of different approaches of machine learning in solving the aforementioned medical image classification challenge. The contributions of this work are summarized as follows:

Investigated the classification performance using image features calculated using eleven different pre-trained DCNN models.

Investigated the effect of three dimensionality-reduction techniques and three feature-selection techniques on the classification performance.

Investigated the performance of five different ML algorithms and three FC learning optimizers which are trained with hyperparameter optimization using a wide range of hyperparameter options and values.

2. More comparative experiments should be added to illustrate the superiority of the propose method, and the experimental results should be further analyzed.

We have reworked the methodology by using and comparing a) the image features of eleven Deep Convolution Neural Network architectures, b) Three Dimensionality Reduction techniques (PCA, FA and Fast ICA) and three Feature Selection techniques (NCA, MRMR and CHI2), and c) Five different Machine Learning algorithms and three Fully Connected neural Network learning optimizers. The results have been comparatively analyzed in the Experimental Results and Analysis section. The best method, which was found to be using full length DenseNet201 features with Support Vector Machine algorithm and a short Gaussian kernel, was found by comparing the results of all combinations.

3. Training details should be presented, such as the setting of learning rate and the decay of loss function.

The training details have been presented in Table 4 and Table 5. These include all the fixed and variables and range of values used during the hyperparameter optimization. Due to the large number of models trained it is very impractical to add present how the loss values decay during training.

4. Discussions about the generalization performance of deep learning model are encouraged.

We conducted the experiment 20 times, each using different training and test sets, although the ratio remains the same (which is 80:20). The generalization of the performance is discussed by presenting and analyzing the statistics of the results including the minimum, maximum and median values of the performance metrics used (line 463-559).

5. Many figures are so blurred that they cannot be read, such as Fig. 11, Fig .12, and Fig. 13.

All the figures have been redone as part of the rework of the experimentation. 

Reviewer #3: In this paper, the authors tackled an interesting problem of selecting specific slices from lumbar spine MRI. The motivation behind this work is clear, and the ideas presented in this manuscript are valid, but it suffers from the following shortcomings that need to be addressed before it could be considered for publication:

1. The authors sort of failed to contextualize their work within the state of the art, as reducing the dimensionality of deep features extracted using deep models is not novel. As the examples, see the following works: https://hes32-ctp.trendmicro.com:443/wis/clicktime/v1/query?url=https%3a%2f%2fwww.sciencedirect.com%2fscience%2farticle%2fabs%2fpii%2fS1047320319301932&umid=2356ab6a-0087-4c78-a443-85e54e732539&auth=768f192bba830b801fed4f40fb360f4d1374fa7c-1e228c95a24c231c547f34926f2ce63065296b67, https://hes32-ctp.trendmicro.com:443/wis/clicktime/v1/query?url=https%3a%2f%2flink.springer.com%2fchapter%2f10.1007%2f978%2d3%2d319%2d77538%2d8%5f34&umid=2356ab6a-0087-4c78-a443-85e54e732539&auth=768f192bba830b801fed4f40fb360f4d1374fa7c-6295542040e70308207ac0bfc066063669ba3bd9. The authors should not only discuss such techniques in the related literature part of the manuscript, but should also confront their dimensionality reduction technique with other feature extraction and selection algorithms.

Thank you for your advice.

We have reworked the methodology by using and comparing a) the image features of eleven Deep Convolution Neural Network architectures, b) Three Dimensionality Reduction techniques (PCA, FA and Fast ICA) and three Feature Selection techniques (NCA, MRMR and CHI2), and c) Five different Machine Learning algorithms and three Fully Connected neural Network learning optimizers. The results have been comparatively analyzed in the Experimental Results and Analysis section. In the new version of the paper, we emphasize on the comprehensiveness of the combination of methods that we implemented and the approach that we took to get the best overall method combination from them. The best method, which was found to be using full length DenseNet201 features with Support Vector Machine algorithm and a short Gaussian kernel, was found by comparing the results of all combinations.

2. I suggest removing acronyms from the title.

All acronyms have been removed from the title and the title has been replaced to reflect the new methodology better.

3. Overall, the quality of the figures is very low and should be substantially improved.

All the figures have been redone as part of the rework of the experimentation.

4. The authors should discuss the models presented in Table 1 in much more detail. Specifically, I encourage the authors to prepare a taxonomy of investigated deep architectures (with special emphasis put on their architectural choices that are specific). To this end, the authors should make sure that the manuscript is self-contained. Also, please add the year for each model in Table 1.

We could not find any resources in the literature that provides a good taxonomy of DCNN architecture. Hence, it is difficult for us to provide one. However, we added a short taxonomy of deep neural network architectures in general that reads:

DCNN is one of several types of deep neural networks that gain popularity in recent years to solve many artificial intelligence problems. Different types of deep neural networks have significantly different architectures and are designed to solve different types of problems. DCNNs are typically used for image classification. Recurrent Neural Networks, such as Long Short-Term Memory [21], are used to recognize patterns in sequences of data such as time-series data, speech, and texts. There are also Fully Convolutional Neural Networks, such as U-net [22] and SegNet [23] that are used mainly for semantic image segmentation. Some DCNNs have also been modified to become Region-based CNNs [24,25] to detect and recognize multiple objects within an image.

In the previous version, we only investigated two deep convolutional neural network (DCNN) architectures. Now we have used eleven architectures. We have added the year information to the summary of the architectures used as shown in Table 3.

5. Please discuss the co-registration process in more detail (lines starting from 296).

More information on the image registration process and examples of the results have been added. The texts now become:

From each pair of T1-weighted and T2-weighted images, a 3-channel composite image is created resulting in 8,936 composite images. The first channel of the composite image is constructed from the T1-weighted image, the second channel is constructed from the image-registered T2-weighted image, and the last channel is constructed from the Manhattan distance of the two. The image used to construct the second channel is obtained by performing image registration on the T2-weighted image to its T1-weighted counterpart to ensure that every pixel at the same location in both images corresponds to the same voxel in an organ or tissue. This is performed by finding the minimum difference between the fixed T1-weighted image and a set of transformed T2-weighted images calculated over a search space of affine transforms. Mathematically, the process can be described as follows: Let I_R (v) be the reference 2D image and I_T (v) be the to-be-transformed 2D image, where v=〖[x,y,z]〗^Tis a real-valued voxel location. The voxel location v is defined on the continuous domains V_R and V_T, that corresponds to each pixel in I_R and I_T, respectively. Note that in our case, I_R and I_T are the T1-weighted image and the T2-weighted image, respectively. The image registration that we employ in this method is a process that seeks a set of transformation parameters μ ^ from all sets of transformation parameters μ that minimizes the image discrepancy function S

μ ^=(arg min)┬μ⁡〖S(I_R,I_T∘g(v│μ))〗 (1)

We calculate S using Matte’s mutual information metric described in [29] over a search space in μ domain. The search process uses an iterative process called the Evolutionary Algorithm that perturbs, or mutates, the parameters from the last iteration. If the new perturbed parameters yield a better result than the last iteration, then more perturbation is applied to the parameters in the next iteration, otherwise a less aggressive perturbation is applied. The search process is optimized using the (1+1)-Evolutionary Strategy [30] which locally adjusts the search direction and step size and provides a mechanism to step out of non-optimal local minima. The search is carried out up to 300 iterations with a parameter growth factor of 1.05. A sequence of parametric bias field estimation and correction method, called PABIC [30], is applied to counter the effect of low-frequency inhomogeneity field and high-frequency noise on both T1 and T2 modalities.

There are several cases where the image registration process fails because the algorithm is unable to converge. This could be because the patient’s position and orientation when the two scans were recorded differ significantly. In this case, the images were removed from the dataset. We show in Figure 4, two example cases where the image registration process succeeded (left column) and failed (right column).

Figure 4. Two example cases where the image registration process succeeded (left column) and failed (right column). The top row shows the T1-weighted images, the middle row shows T2-weighted images, and the bottom row shows the resulting composite images after image registration.

6. The authors should perform rigorous crossvalidation to fully understand the generalization abilities of the algorithms (a single 80/20 split may be not enough to infer correct conclusions).

We have reworked the methodology by using and comparing a) the image features of eleven Deep Convolution Neural Network architectures, b) Three Dimensionality Reduction techniques (PCA, FA and Fast ICA) and three Feature Selection techniques (NCA, MRMR and CHI2), and c) Five different Machine Learning algorithms and three Fully Connected neural Network learning optimizers. The results have been comparatively analyzed in the Experimental Results and Analysis section.

We conducted the experiment 20 times, each using different training and test sets, although the ratio remains the same (which is 80:20). During training, a smaller subset of the training set is allocated as the validation set to measure the classifier’s performance during training. The generalization of the performance is discussed by presenting and analyzing the statistics of the results including the minimum, maximum and median values of the performance metrics used (line 450-546).

7. Although the authors did try to show different experimental aspects of various architectures, the experiments are rather not thorough. It would be best to present the ablation study (e.g., selection of optimizers) for a wider range of investigated models. Overall, the authors should rework their experimental part of the paper to make it more thorough.

In this new version of the paper, the Machine Learning algorithms have been trained with hyperparameter optimization using a wide range of hyperparameter options and values. Similarly, the Fully Connected Neural Networks have been trained using three different learning optimizers with a wide range of hyperparameter options and values. The list of hyperparameter optimization values, range of values and options is given in Table 4 and 5. 

Reviewer #4: Review Manuscript PONE-D-21-04349

The authors present an alternative methodology to assess the selection of mid-high IVD image slide from MRI acquisitions.

This is an interesting work for the spine community since it states a possible automatic way the selection of suitable images of the IVD in lumbar spine. The use deep learning algorithm to a large number of images to test their technique. This work presents a really nice use of deep learning to tackle a difficulty of obtaining better information of the lumbar IVDs. However, the manuscript summited is not ready to be published since there are some aspects to be considered. These aspects are listed as follow:

- Most of the research articles follow the structure: Introduction, Materials and methods, Results, Discussion, Conclusions (sometimes included at the end of the discussion section). This structure is not totally followed by the authors making difficult the follow up of the paper.

Thank you for your feedback.

We have restructured the organization of the paper to follow your suggestion. There are now Introduction section, Material and Method section, Experimental Results, Analysis and Discussion section, and lastly the Conclusion section. We opted to combine the presentation of experimental results, with their analysis and the discussion into one section to make it easier to discuss the many different results and points.

- I really enjoyed the introduction part, it was really instructive and easy to follow. Nevertheless, a clear aim of the study is missing. At lines 91-92 the mentioned “In this paper, we detailed our approach to automatically …” but if this is an objective is vague, they need to specify the objective(s) of their study.

We have reworded much of the Introduction section to provide the rationale of the study. In addition, a summary of the study rationale, aim and contribution is given at the end of the section which reads:

Based on the above argument, we believe that both a) the lack of directly relevant methods proposed in the literature that selects the best traverse plane that cuts closest to the half-height of an IVD in a lumbar spine MRI and b) the wide range of potentially suitable DR or FS methods and image classification methods, provide the rationale and urgency for this study. The aim of this study is to find the best method to select the best traverse plane that cuts closest to the half-height of an IVD in a lumbar spine MRI by studying and comparing the different combination of machine learning methods and approaches. We report the result of our investigation on the suitability and performance of different approaches of machine learning in solving the aforementioned medical image classification challenge. The contributions of this work are summarized as follows:

a) Investigated the classification performance using image features calculated using eleven different pre-trained DCNN models.

b) Investigated the effect of three dimensionality-reduction techniques and three feature-selection techniques on the classification performance.

c) Investigated the performance of five different ML algorithms and three FC learning optimizers which are trained with hyperparameter optimization using a wide range of hyperparameter options and values.

- The second section can be reduced and included in the introduction that also need to be reduced. In general, the introduction should not be larger than 2 pages, but some exception are in order when the paper is a review which is not the case.

The two sections have been combined and reduced in length. However, it is still not of two pages that you recommended this is due to we use the section to provide a) background information, b) relevant technologies and techniques (since we no longer have the related work section), c) rationale for the study, and d) adding additional information requested by other reviewers.

- Material and methods section: it is poor. In this section the authors should present the steps they did in the study, a description of the methods, i.e. what they did, what they use, what they modified. The database use, the test they did and what were the variable measured/evaluated, they will compare their results with what database to validate.

We have reworked the Material and Method section which now contains more detailed information, including technical information about the dataset and the methodology used. We used a standard approach in machine learning by training and testing the classifiers using a mutually exclusive sets called training and test sets, respectively. The sets are determined randomly from the entire dataset. The experiment is repeated 20 times, each using different training and test sets, although the ratio remains the same (which is 80:20).

Since the classifiers are tested using a different set of images for its training, we can infer on the generality of the classifier by analyzing its performance.

- Part 4, is a mix of several part. Here the authors present, part of the methods, then present the results, and discuss a little bit about the results. I highly suggest to the authors to follow the article structure previous mentioned.

We have now separated the methodology from the experiment result analysis and discussion. The two sections now will read very distinctly.

- Results: in general, they are interesting. They should have a separate section where they can be presented in a proper way

- Discussion: The results are poorly discussed. The authors make some interesting comments regarding the results. However, a comparison with other studies, what are the similarities and differences, and the explanation of the differences, what are the limitations of the method propose, are missed in the manuscript presented.

We have one section that present the results, their analysis and the discussion. We have tried before to separate the three but due to the large number of results to present, as well as the interconnection between one sets of results to the next, we feel that doing so will make the paper even hard to read. So, we decided to put them into one section so we can present, analyze and discuss each set of results in order.

- Conclusions: is weak. It is not clear the contribution of the new technique to the spine community, does the outcomes obtained are better than the one obtained manually? Is it faster? Can be implemented easily in clinic?

We have added a subsection in section 3 called “Consideration on the practical implementation” where we discussed the above points. the subsection reads:

3.4 Consideration on the practical implementation

The whole process we described in this paper has been implemented using MATLAB version 2021a on three different computer setups. One setup has an Intel(R) i7-10700K CPU @ 3.80GHz, 16 GB RAM, and NVIDIA GeForce RTX 3080 with 10 GB VRAM. Another setup has an Intel(R) i7-7700 CPU @ 3.60GHz, 64 GB RAM, and 2x NVIDIA TITAN X with 24 GB VRAM. The last setup has an Intel(R) i9-7900X CPU @ 3.30GHz, 128 GB RAM, and 4x NVIDIA TITAN XP with 48 GB VRAM. One of the bottlenecks in the experiment is the time taken to train the ML learners and FC neural networks using hyperparameter optimization, which can take hours on the above machines. The source code, dataset, and result files have been made available for review from Mendeley Data [59]. The procedure starts by providing the program with two folders containing identical numbers of T1-weighted and T2-weighted traverse lumbar spine MRI images. The program would assume that the image files in both folders are in the same correct order when sorted alphabetically before applying the image registration step. The image registration results are then stored in another folder. The ground truth information, as a comma-separated value (CSV) file, containing indices of the images that belong to each category is supplied. The program then split the dataset into four folders depending on the CSV file. The program then loads a DCNN and applies it to each image and records the resulting image features. The program also allows a DS or FS algorithm to be applied before using the features for training an ML learner or an FC neural network. The program then uses the trained ML learner or an FC neural network to classify a new image based on the image features. The time taken to extract the feature from an image ranges from 1 to 14 milliseconds and the time to classify one image takes less than 10 milliseconds. The total time would be much faster than manual selection which takes between 30 to 60 seconds, especially if the process is done in big batches.

The same approach can be adopted in a clinic provided that the necessary hardware and software requirements are met, which can be obtained from the MATLAB official website. Some modifications to the source code might be needed to adapt it to each user’s setup and requirement. A similar approach can also be implemented using Python programming language together with the necessary deep learning library (such as Keras [60]) and machine learning library (such as Scikit-Learn [61]). Much of the MATLAB code can be translated to Python but some low-level function implementations could be different.

- Figures with bars: It might be better to present a feature with the modes used instead of having them separated. I mean, for example figure 6, the metric accuracy can have the bars for SGDM and Adam, as such, it can be seen better the differences between the two models used.

These figures are no longer in the paper. The experiment results are now presented with boxplot which is a more standard way to present and compare distribution of values statistically.

- Tables 2 and 3: please rearrange the information to better understand the content, also when present statistical results avoid to use scientific notation for the numbers, it is better and more easy to evaluate the number with decimals.

The paper now uses decimal numbers and no longer contains scientific notation for the numbers.

- Anachronisms, check that all of them are previously introduced.

We have checked and made sure that all of acronyms have been previously introduced before using them.

-Experiments: the word “experiment” is most common for cells, object, assay experiments. It is better to use test when you use numerical “experiment”, e.g. testing a new numerical algorithm against another one to evaluate its performance.

We have made the necessary changes on the paper.

- Lines 527 -528: the authors present that their method improves upon the benchmark TL/FT methods by presenting increments in the mean values. How this is true? I mean, how the fact that the mean is higher, is a sign of improvement?

The values that are presented are accuracy, precision, recall and F1-score performance metrics which range from 0 (the worst) to one (the best). The zero value means none of the images are classified correctly whereas one means all of the images are classified correctly. We conducted the experiment 20 times, to ensure that the results that we have is not based on chance and we presented the mean as well as the spread of the result values (as box plots) so that the reader can get a fuller picture of the results.

The manuscript is well written and the study is really interesting for spine community. The reviewer encourages the authors to consider all the comments mentioned previously. With the changes suggested in this review, the authors can resubmit the manuscript for publication.

Thank you for your feedback. I hope the changes that we made have addressed all your concerns.

Attachment

Submitted filename: Response to Reviewers.docx

Decision Letter 1

Nguyen Quoc Khanh Le

2 Aug 2021

PONE-D-21-04349R1

Automated Selection of Mid-Height Intervertebral Disc Slice in Traverse Lumbar Spine MRI using a Combination of Deep Learning Feature and Machine Learning Classifier.

PLOS ONE

Dear Dr. Sudirman,

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Reviewer #2: All comments have been addressed

Reviewer #3: All comments have been addressed

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Reviewer #2: No

Reviewer #3: Yes

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes

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Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: (No Response)

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Reviewer #2: Yes

Reviewer #3: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: 1) "A CAD system can help doctors understand the cause of an illness better by automating some steps in the diagnosis process. In a CAD system that uses medical images, the system applies image analysis algorithms to different types or modalities of medical imaging, such as Magnetic Resonance Imaging (MRI), of the patient."- add reference for this statement. I suggest the following:

- Skin lesion segmentation and multiclass classification using deep learning features and improved moth flame optimization

- Computer Decision Support System for Skin Cancer Localization and Classification

- Multimodal brain tumor classification using deep learning and robust feature selection: A machine learning application for radiologists

2) "In the case of MRI, for example, a CAD system might use the two modalities of MRI, namely the T1-weighted and T2-weighted MRI, which can differently highlight various types of tissues based on their fat and water composition."- add figures of T1, T2, T1W, and Flair. You can take this figure from the following:

- A Decision Support System for Multimodal Brain Tumor Classification using Deep Learning

- Microscopic brain tumor detection and classification using 3D CNN and feature selection architecture

3) "Training DCNN models take a long time hence there exist several pre-trained DCNN models that are readily usable for image classification."- add reference for this statement.

4) "used in many other types of image classification tasks, including medical image classification, through a method called Transfer Learning"- add reference for this statement: I suggest the folowing:

- Attributes based skin lesion detection and recognition: A mask RCNN and transfer learning-based deep learning framework

- A deep neural network and classical features based scheme for objects recognition: an application for machine inspection

5) Add manuscript organization before materials and methods section.

6) What represent Table 1?

Reviewer #2: The revision of opinions is not satisfactory. The overall expression and organization of the paper should be further improved.

Reviewer #3: (No Response)

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

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While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2022 Jan 13;17(1):e0261659. doi: 10.1371/journal.pone.0261659.r004

Author response to Decision Letter 1


4 Aug 2021

Dear reviewers,

Thank you once again for all your effort and help in improving our paper. We appreciate your comments, suggestions, and critique. Based on your latest feedback, we have made the required changes to the paper. I hope that this latest version of the paper is of your satisfaction.

Kind regards

Sud

Reviewer #1:

1) "A CAD system can help doctors understand the cause of an illness better by automating some steps in the diagnosis process. In a CAD system that uses medical images, the system applies image analysis algorithms to different types or modalities of medical imaging, such as Magnetic Resonance Imaging (MRI), of the patient."- add reference for this statement. I suggest the following:

- Skin lesion segmentation and multiclass classification using deep learning features and improved moth flame optimization

- Computer Decision Support System for Skin Cancer Localization and Classification

- Multimodal brain tumor classification using deep learning and robust feature selection: A machine learning application for radiologists

We have added the relevant references to the paper. That sentence now reads, “A CAD system can help doctors understand the cause of an illness better by automating some steps in the diagnosis process. In a CAD system that uses medical images, the system applies image analysis algorithms to different types or modalities of medical imaging, such as Magnetic Resonance Imaging (MRI), of the patient [1–3].”

The added references are:

1. Khan MA, Sharif M, Akram T, Damaševičius R, Maskeliūnas R. Skin lesion segmentation and multiclass classification using deep learning features and improved moth flame optimization. Diagnostics. 2021;11(5):811.

2. Khan MA, Akram T, Sharif M, Kadry S, Nam Y. Computer Decision Support System for Skin Cancer Localization and Classification. C Mater Contin. 2021;68(1):1041–64.

3. Khan MA, Ashraf I, Alhaisoni M, Damaševičius R, Scherer R, Rehman A, Bukhari SAC. Multimodal brain tumor classification using deep learning and robust feature selection: A machine learning application for radiologists. Diagnostics. 2020;10(8):565.

2) "In the case of MRI, for example, a CAD system might use the two modalities of MRI, namely the T1-weighted and T2-weighted MRI, which can differently highlight various types of tissues based on their fat and water composition."- add figures of T1, T2, T1W, and Flair. You can take this figure from the following:

- A Decision Support System for Multimodal Brain Tumor Classification using Deep Learning

- Microscopic brain tumor detection and classification using 3D CNN and feature selection architecture

Unfortunately, the figures in those papers are copyrighted materials and we are not allowed to reproduce them in our paper without the publisher’s permission. In their place, we added two examples taken from our dataset. Since we only used T1- and T2-weighted images hence it is only appropriate that we include these two examples only. In the paper, after that sentence we insert the following sentence: “An example of a T1-weighted and a T2-weighted traverse MRI images of the L3/L4 Intervertebral Disc (IVD) of the same patient are shown in Figure 1.”

Figure 1. A T1-weighted (left) and a T2-weighted (right) traverse MRI images of the L3/L4 Intervertebral Disc of a patient are shown. One marked difference in the two images is the cerebrospinal fluid (CSF) in the spinal canal that appears black on the T1-weighted image but as a brighter region on the T2-weighted image because of its low fat contents.

I hope this additional information is a sufficient substitute to your original suggestion.

3) "Training DCNN models take a long time hence there exist several pre-trained DCNN models that are readily usable for image classification."- add reference for this statement.

We have added the relevant references to the paper. That sentence now reads, “Training DCNN models take a long time hence there exist several pre-trained DCNN models that are readily usable for image classification [29,30]”

The added references are:

29. Kornblith S, Shlens J, Le Q V. Do better imagenet models transfer better? In: Proceedings of the IEEE/CVF Conference on Computer Vision and Pattern Recognition. 2019. p. 2661–71.

30. Morid MA, Borjali A, Del Fiol G. A scoping review of transfer learning research on medical image analysis using ImageNet. Comput Biol Med. 2020;128:104115.

4) "used in many other types of image classification tasks, including medical image classification, through a method called Transfer Learning"- add reference for this statement: I suggest the folowing:

- Attributes based skin lesion detection and recognition: A mask RCNN and transfer learning-based deep learning framework

- A deep neural network and classical features based scheme for objects recognition: an application for machine inspection

We have added the relevant references to the paper. The complete sentence now reads, “However, despite being extracted using a model trained using photographic images, these learnable features are sufficiently general that they can be used in many other types of image classification tasks, including medical image classification, through a method called Transfer Learning [32,33], which process is elucidated in Figure 4.”

The added references are:

32. Khan MA, Akram T, Zhang Y-D, Sharif M. Attributes based skin lesion detection and recognition: A mask RCNN and transfer learning-based deep learning framework. Pattern Recognit Lett. 2021;143:58–66.

33. Hussain N, Khan MA, Sharif M, Khan SA, Albesher AA, Saba T, Armaghan A. A deep neural network and classical features based scheme for objects recognition: an application for machine inspection. Multimed Tools Appl. 2020;1–23.

5) Add manuscript organization before materials and methods section.

We have added paper organization before materials and methods section that reads: “The organization of this paper is as follows. Section 2 describes the dataset used in the research and the proposed method. The experimental results, analysis, and discussion are discussed in detail in Section 3. We then provide the conclusion of our findings in the last section of the paper.”

6) What represent Table 1?

Table 1 shows the range of acquisition parameter values used during traverse MRI scan. The acquisition parameters are a set of values that the radiologist or technician used when the MRI images are being recorded. The values can be fixed (e.g., in case of Field of View, Matrix, Imaging Frequency, and Flip Angle) or differ from one patient to another depending on the decision made by the technician at that time. This information is extracted from the DICOM images from the dataset and description of each parameter can be found on https://dicom.innolitics.com/ciods/ct-performed-procedure-protocol/performed-ct-reconstruction/00189934/00180050

We have altered the caption of the table slightly to improve the description of the table. It now reads,

Table 1. The range of acquisition parameter values used during traverse MRI scans

Also, for your information, Table 1 is included in the paper because in the previous round of review one of the reviewers required us to include the technical detail of the dataset.

Thank you for your feedback. I hope al the changes that we made above have addressed all your concerns. 

Reviewer #2: The revision of opinions is not satisfactory. The overall expression and organization of the paper should be further improved.

Thank you for your feedback. I hope the changes that we made as part of the review from the other reviewer have addressed all your concerns. 

Reviewer #3: (No Response)

Attachment

Submitted filename: Response to Reviewers.docx

Decision Letter 2

Nguyen Quoc Khanh Le

4 Oct 2021

PONE-D-21-04349R2Automated Selection of Mid-Height Intervertebral Disc Slice in Traverse Lumbar Spine MRI using a Combination of Deep Learning Feature and Machine Learning Classifier.PLOS ONE

Dear Dr. Sudirman,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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We look forward to receiving your revised manuscript.

Kind regards,

Khanh N.Q. Le

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Partly

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: No

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: No

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: 1. A large number of deep learning models have been applied to experiments, but their training details have been ignored.

2. Many figures are still of low quality and cannot be seen clearly.

3. Intermediate experimental results should also be presented.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2022 Jan 13;17(1):e0261659. doi: 10.1371/journal.pone.0261659.r006

Author response to Decision Letter 2


18 Nov 2021

Please see the attached document entitled "Response to Reviewer.docx" which includes the text below and relevant images.

Reviewer #2:

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

2. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #2: Partly

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: No

We believe we have included comprehensively the experimental results in the manuscript. We implemented each of the 759 method combinations 20 times, each with a different combination of training and test sets, to provide us with statistically representative results. And we shown the average result of the 20 repeats of each method combination using four performance metrics.

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: No

We had made our raw MRI data, PNG images, MATLAB and PYTHON source code, and experimental results available in all previous submissions through Mendeley Data (link provided in the Data Statement). This section, if we recall correctly, has not been commented as NO before. We believe that there may be a confusion on how to download the file since in order to access the file one has to have an Elsevier account. Creating this account is free. So, we added more information on the Data Statement document regarding this.

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2:

1. A large number of deep learning models have been applied to experiments, but their training details have been ignored.

The training details of each model were given in Table 4 and Table 5. The tables contain both the fixed settings (the ones that do not get searched by the hyperparameter optimization process) and the variable settings/parameters (the ones that are searched automatically by the hyperparameter optimization process).

But we have rechecked the information in the table for completeness to make sure we have included all the training parameters and settings. As a result, we have added three additional parameters to Table 5 (for Fully Connected Neural Network training).

2. Many figures are still of low quality and cannot be seen clearly.

We have made queries to PLOS ONE regarding this since we have followed all the required steps to produce the figures. The original figures that we uploaded are of highest quality and very clear but for some reason when they are embedded to the pdf their quality is reduced significantly. However, the original image file can be accessed by clicking the link at the top-right of the page where the figure is displayed (see the illustration below).

3. Intermediate experimental results should also be presented.

Unfortunately, we cannot make this change since we are not sure what intermediate experimental results are needed. We have tried searching the literature for what intermediate experimental results might be, but we cannot find anything. We have also reached out to the PLOS ONE editorial team requesting for more description from the reviewers. Unfortunately, the team did not receive any response from the reviewers by the resubmission deadline. However, it is our we firm belief that our paper has included all the necessary results to base our findings. Furthermore, since we made the data and source code available, the readers should be able to reproduce the experimental results including any intermediate results if so desired.

Attachment

Submitted filename: Response to Reviewers.docx

Decision Letter 3

Nguyen Quoc Khanh Le

9 Dec 2021

Automated Selection of Mid-Height Intervertebral Disc Slice in Traverse Lumbar Spine MRI using a Combination of Deep Learning Feature and Machine Learning Classifier.

PONE-D-21-04349R3

Dear Dr. Sudirman,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

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Kind regards,

Nguyen Quoc Khanh Le

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Acceptance letter

Nguyen Quoc Khanh Le

5 Jan 2022

PONE-D-21-04349R3

Automated Selection of Mid-Height Intervertebral Disc Slice in Traverse Lumbar Spine MRI using a Combination of Deep Learning Feature and Machine Learning Classifier.

Dear Dr. Sudirman:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Nguyen Quoc Khanh Le

Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Data. A Word document containing URL of the dataset.

    Models and PYTHON/MATLAB source code to reproduce the results.

    (DOCX)

    Attachment

    Submitted filename: Response to Reviewers.docx

    Attachment

    Submitted filename: Response to Reviewers.docx

    Attachment

    Submitted filename: Response to Reviewers.docx

    Data Availability Statement

    We have made our dataset and source code published and open to the public. They are on Mendeley Data. URL: https://data.mendeley.com/datasets/ggjtzh452d/1 DOI: 10.17632/ggjtzh452d.1 Further instructions and information can be found in the paper’s Supporting information files.


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