MRI and CT are essential clinical cross-sectional imaging techniques for diagnosing complex conditions. However, large 3D datasets with annotations for deep learning are scarce. While methods like DINOv2 are encouraging for 2D image analysis, these methods have not been applied to 3D medical images. Furthermore, deep learning models often lack explainability due to their "black-box" nature. This study aims to extend 2D self-supervised models, specifically DINOv2, to 3D medical imaging while evaluating their potential for explainable outcomes. We introduce the Medical Slice Transformer (MST) framework to adapt 2D self-supervised models for 3D medical image analysis. MST combines a Transformer architecture with a 2D feature extractor, i.e., DINOv2. We evaluate its diagnostic performance against a 3D convolutional neural network (3D ResNet) across three clinical datasets: breast MRI (651 patients), chest CT (722 patients), and knee MRI (1199 patients). Both methods were tested for diagnosing breast cancer, predicting lung nodule dignity, and detecting meniscus tears. Diagnostic performance was assessed by calculating the Area Under the Receiver Operating Characteristic Curve (AUC). Explainability was evaluated through a radiologist's qualitative comparison of saliency maps based on slice and lesion correctness. P-values were calculated using Delong's test. MST achieved higher AUC values compared to ResNet across all three datasets: breast (0.94$\pm$0.01 vs. 0.91$\pm$0.02, P=0.02), chest (0.95$\pm$0.01 vs. 0.92$\pm$0.02, P=0.13), and knee (0.85$\pm$0.04 vs. 0.69$\pm$0.05, P=0.001). Saliency maps were consistently more precise and anatomically correct for MST than for ResNet. Self-supervised 2D models like DINOv2 can be effectively adapted for 3D medical imaging using MST, offering enhanced diagnostic accuracy and explainability compared to convolutional neural networks.
In this study, we propose a novel and robust framework, Self-DenseMobileNet, designed to enhance the classification of nodules and non-nodules in chest radiographs (CXRs). Our approach integrates advanced image standardization and enhancement techniques to optimize the input quality, thereby improving classification accuracy. To enhance predictive accuracy and leverage the strengths of multiple models, the prediction probabilities from Self-DenseMobileNet were transformed into tabular data and used to train eight classical machine learning (ML) models; the top three performers were then combined via a stacking algorithm, creating a robust meta-classifier that integrates their collective insights for superior classification performance. To enhance the interpretability of our results, we employed class activation mapping (CAM) to visualize the decision-making process of the best-performing model. Our proposed framework demonstrated remarkable performance on internal validation data, achieving an accuracy of 99.28\% using a Meta-Random Forest Classifier. When tested on an external dataset, the framework maintained strong generalizability with an accuracy of 89.40\%. These results highlight a significant improvement in the classification of CXRs with lung nodules.
Lung cancer is responsible for 21% of cancer deaths in the UK and five-year survival rates are heavily influenced by the stage the cancer was identified at. Recent studies have demonstrated the capability of AI methods for accurate and early diagnosis of lung cancer from routine scans. However, this evidence has not translated into clinical practice with one barrier being a lack of interpretable models. This study investigates the application Variational Autoencoders (VAEs), a type of generative AI model, to lung cancer lesions. Proposed models were trained on lesions extracted from 3D CT scans in the LIDC-IDRI public dataset. Latent vector representations of 2D slices produced by the VAEs were explored through clustering to justify their quality and used in an MLP classifier model for lung cancer diagnosis, the best model achieved state-of-the-art metrics of AUC 0.98 and 93.1% accuracy. Cluster analysis shows the VAE latent space separates the dataset of malignant and benign lesions based on meaningful feature components including tumour size, shape, patient and malignancy class. We also include a comparative analysis of the standard Gaussian VAE (GVAE) and the more recent Dirichlet VAE (DirVAE), which replaces the prior with a Dirichlet distribution to encourage a more explainable latent space with disentangled feature representation. Finally, we demonstrate the potential for latent space traversals corresponding to clinically meaningful feature changes.
Following the great success of various deep learning methods in image and object classification, the biomedical image processing society is also overwhelmed with their applications to various automatic diagnosis cases. Unfortunately, most of the deep learning-based classification attempts in the literature solely focus on the aim of extreme accuracy scores, without considering interpretability, or patient-wise separation of training and test data. For example, most lung nodule classification papers using deep learning randomly shuffle data and split it into training, validation, and test sets, causing certain images from the CT scan of a person to be in the training set, while other images of the exact same person to be in the validation or testing image sets. This can result in reporting misleading accuracy rates and the learning of irrelevant features, ultimately reducing the real-life usability of these models. When the deep neural networks trained on the traditional, unfair data shuffling method are challenged with new patient images, it is observed that the trained models perform poorly. In contrast, deep neural networks trained with strict patient-level separation maintain their accuracy rates even when new patient images are tested. Heat-map visualizations of the activations of the deep neural networks trained with strict patient-level separation indicate a higher degree of focus on the relevant nodules. We argue that the research question posed in the title has a positive answer only if the deep neural networks are trained with images of patients that are strictly isolated from the validation and testing patient sets.
This paper presents and validates a novel lung nodule classification algorithm that uses multifractal features found in X-ray images. The proposed method includes a pre-processing step where two enhancement techniques are applied: histogram equalization and a combination of wavelet decomposition and morphological operations. As a novelty, multifractal features using wavelet leader based formalism are used with Support Vector Machine classifier; other classical texture features were also included. Best results were obtained when using multifractal features in combination with classical texture features, with a maximum ROC AUC of 75\%. The results show improvements when using data augmentation technique, and parameter optimization. The proposed method proved to be more efficient and accurate than Modulus Maxima Wavelet Formalism in both computational cost and accuracy when compared in a similar experimental set up.
Lung cancer is a severe menace to human health, due to which millions of people die because of late diagnoses of cancer; thus, it is vital to detect the disease as early as possible. The Computerized chest analysis Tomography of scan is assumed to be one of the efficient solutions for detecting and classifying lung nodules. The necessity of high accuracy of analyzing C.T. scan images of the lung is considered as one of the crucial challenges in detecting and classifying lung cancer. A new long-short-term-memory (LSTM) based deep fusion structure, is introduced, where, the texture features computed from lung nodules through new volumetric grey-level-co-occurrence-matrices (GLCM) computations are applied to classify the nodules into: benign, malignant and ambiguous. An improved Otsu segmentation method combined with the water strider optimization algorithm (WSA) is proposed to detect the lung nodules. Otsu-WSA thresholding can overcome the restrictions present in previous thresholding methods. Extended experiments are run to assess this fusion structure by considering 2D-GLCM computations based 2D-slices fusion, and an approximation of this 3D-GLCM with volumetric 2.5D-GLCM computations-based LSTM fusion structure. The proposed methods are trained and assessed through the LIDC-IDRI dataset, where 94.4%, 91.6%, and 95.8% Accuracy, sensitivity, and specificity are obtained, respectively for 2D-GLCM fusion and 97.33%, 96%, and 98%, accuracy, sensitivity, and specificity, respectively, for 2.5D-GLCM fusion. The yield of the same are 98.7%, 98%, and 99%, for the 3D-GLCM fusion. The obtained results and analysis indicate that the WSA-Otsu method requires less execution time and yields a more accurate thresholding process. It is found that 3D-GLCM based LSTM outperforms its counterparts.
Recent evolution in deep learning has proven its value for CT-based lung nodule classification. Most current techniques are intrinsically black-box systems, suffering from two generalizability issues in clinical practice. First, benign-malignant discrimination is often assessed by human observers without pathologic diagnoses at the nodule level. We termed these data as "unsure data". Second, a classifier does not necessarily acquire reliable nodule features for stable learning and robust prediction with patch-level labels during learning. In this study, we construct a sure dataset with pathologically-confirmed labels and propose a collaborative learning framework to facilitate sure nodule classification by integrating unsure data knowledge through nodule segmentation and malignancy score regression. A loss function is designed to learn reliable features by introducing interpretability constraints regulated with nodule segmentation maps. Furthermore, based on model inference results that reflect the understanding from both machine and experts, we explore a new nodule analysis method for similar historical nodule retrieval and interpretable diagnosis. Detailed experimental results demonstrate that our approach is beneficial for achieving improved performance coupled with faithful model reasoning for lung cancer prediction. Extensive cross-evaluation results further illustrate the effect of unsure data for deep-learning-based methods in lung nodule classification.
Using publicly available data to determine the performance of methodological contributions is important as it facilitates reproducibility and allows scrutiny of the published results. In lung nodule classification, for example, many works report results on the publicly available LIDC dataset. In theory, this should allow a direct comparison of the performance of proposed methods and assess the impact of individual contributions. When analyzing seven recent works, however, we find that each employs a different data selection process, leading to largely varying total number of samples and ratios between benign and malignant cases. As each subset will have different characteristics with varying difficulty for classification, a direct comparison between the proposed methods is thus not always possible, nor fair. We study the particular effect of truthing when aggregating labels from multiple experts. We show that specific choices can have severe impact on the data distribution where it may be possible to achieve superior performance on one sample distribution but not on another. While we show that we can further improve on the state-of-the-art on one sample selection, we also find that on a more challenging sample selection, on the same database, the more advanced models underperform with respect to very simple baseline methods, highlighting that the selected data distribution may play an even more important role than the model architecture. This raises concerns about the validity of claimed methodological contributions. We believe the community should be aware of these pitfalls and make recommendations on how these can be avoided in future work.
Convolutional Neural Networks (CNNs) are widely used for image classification in a variety of fields, including medical imaging. While most studies deploy cross-entropy as the loss function in such tasks, a growing number of approaches have turned to a family of contrastive learning-based losses. Even though performance metrics such as accuracy, sensitivity and specificity are regularly used for the evaluation of CNN classifiers, the features that these classifiers actually learn are rarely identified and their effect on the classification performance on out-of-distribution test samples is insufficiently explored. In this paper, motivated by the real-world task of lung nodule classification, we investigate the features that a CNN learns when trained and tested on different distributions of a synthetic dataset with controlled modes of variation. We show that different loss functions lead to different features being learned and consequently affect the generalization ability of the classifier on unseen data. This study provides some important insights into the design of deep learning solutions for medical imaging tasks.
Early diagnosis of lung cancer is a key intervention for the treatment of lung cancer computer aided diagnosis (CAD) can play a crucial role. However, most published CAD methods treat lung cancer diagnosis as a lung nodule classification problem, which does not reflect clinical practice, where clinicians diagnose a patient based on a set of images of nodules, instead of one specific nodule. Besides, the low interpretability of the output provided by these methods presents an important barrier for their adoption. In this article, we treat lung cancer diagnosis as a multiple instance learning (MIL) problem in order to better reflect the diagnosis process in the clinical setting and for the higher interpretability of the output. We chose radiomics as the source of input features and deep attention-based MIL as the classification algorithm.The attention mechanism provides higher interpretability by estimating the importance of each instance in the set for the final diagnosis.In order to improve the model's performance in a small imbalanced dataset, we introduce a new bag simulation method for MIL.The results show that our method can achieve a mean accuracy of 0.807 with a standard error of the mean (SEM) of 0.069, a recall of 0.870 (SEM 0.061), a positive predictive value of 0.928 (SEM 0.078), a negative predictive value of 0.591 (SEM 0.155) and an area under the curve (AUC) of 0.842 (SEM 0.074), outperforming other MIL methods.Additional experiments show that the proposed oversampling strategy significantly improves the model's performance. In addition, our experiments show that our method provides an indication of the importance of each nodule in determining the diagnosis, which combined with the well-defined radiomic features, make the results more interpretable and acceptable for doctors and patients.
The progression of lung cancer implies the intrinsic ordinal relationship of lung nodules at different stages-from benign to unsure then to malignant. This problem can be solved by ordinal regression methods, which is between classification and regression due to its ordinal label. However, existing convolutional neural network (CNN)-based ordinal regression methods only focus on modifying classification head based on a randomly sampled mini-batch of data, ignoring the ordinal relationship resided in the data itself. In this paper, we propose a Meta Ordinal Weighting Network (MOW-Net) to explicitly align each training sample with a meta ordinal set (MOS) containing a few samples from all classes. During the training process, the MOW-Net learns a mapping from samples in MOS to the corresponding class-specific weight. In addition, we further propose a meta cross-entropy (MCE) loss to optimize the network in a meta-learning scheme. The experimental results demonstrate that the MOW-Net achieves better accuracy than the state-of-the-art ordinal regression methods, especially for the unsure class.
Automatic pulmonary nodules classification is significant for early diagnosis of lung cancers. Recently, deep learning techniques have enabled remarkable progress in this field. However, these deep models are typically of high computational complexity and work in a black-box manner. To combat these challenges, in this work, we aim to build an efficient and (partially) explainable classification model. Specially, we use \emph{neural architecture search} (NAS) to automatically search 3D network architectures with excellent accuracy/speed trade-off. Besides, we use the convolutional block attention module (CBAM) in the networks, which helps us understand the reasoning process. During training, we use A-Softmax loss to learn angularly discriminative representations. In the inference stage, we employ an ensemble of diverse neural networks to improve the prediction accuracy and robustness. We conduct extensive experiments on the LIDC-IDRI database. Compared with previous state-of-the-art, our model shows highly comparable performance by using less than 1/40 parameters. Besides, empirical study shows that the reasoning process of learned networks is in conformity with physicians' diagnosis. Related code and results have been released at: https://github.com/fei-hdu/NAS-Lung.
Purpose: In recent years, Non-Local based methods have been successfully applied to lung nodule classification. However, these methods offer 2D attention or limited 3D attention to low-resolution feature maps. Moreover, they still depend on a convenient local filter such as convolution as full 3D attention is expensive to compute and requires a big dataset, which might not be available. Methods: We propose to use 3D Axial-Attention, which requires a fraction of the computing power of a regular Non-Local network (i.e., self-attention). Unlike a regular Non-Local network, the 3D Axial-Attention network applies the attention operation to each axis separately. Additionally, we solve the invariant position problem of the Non-Local network by proposing to add 3D positional encoding to shared embeddings. Results: We validated the proposed method on 442 benign nodules and 406 malignant nodules, extracted from the public LIDC-IDRI dataset by following a rigorous experimental setup using only nodules annotated by at least three radiologists. Our results show that the 3D Axial-Attention model achieves state-of-the-art performance on all evaluation metrics, including AUC and Accuracy. Conclusions: The proposed model provides full 3D attention, whereby every element (i.e., pixel) in the 3D volume space attends to every other element in the nodule effectively. Thus, the 3D Axial-Attention network can be used in all layers without the need for local filters. The experimental results show the importance of full 3D attention for classifying lung nodules.
Deep learning-based methods have achieved promising performance in early detection and classification of lung nodules, most of which discard unsure nodules and simply deal with a binary classification -- malignant vs benign. Recently, an unsure data model (UDM) was proposed to incorporate those unsure nodules by formulating this problem as an ordinal regression, showing better performance over traditional binary classification. To further explore the ordinal relationship for lung nodule classification, this paper proposes a meta ordinal regression forest (MORF), which improves upon the state-of-the-art ordinal regression method, deep ordinal regression forest (DORF), in three major ways. First, MORF can alleviate the biases of the predictions by making full use of deep features while DORF needs to fix the composition of decision trees before training. Second, MORF has a novel grouped feature selection (GFS) module to re-sample the split nodes of decision trees. Last, combined with GFS, MORF is equipped with a meta learning-based weighting scheme to map the features selected by GFS to tree-wise weights while DORF assigns equal weights for all trees. Experimental results on the LIDC-IDRI dataset demonstrate superior performance over existing methods, including the state-of-the-art DORF.
Lung cancer classification in screening computed tomography (CT) scans is one of the most crucial tasks for early detection of this disease. Many lives can be saved if we are able to accurately classify malignant/cancerous lung nodules. Consequently, several deep learning based models have been proposed recently to classify lung nodules as malignant or benign. Nevertheless, the large variation in the size and heterogeneous appearance of the nodules makes this task an extremely challenging one. We propose a new Progressive Growing Channel Attentive Non-Local (ProCAN) network for lung nodule classification. The proposed method addresses this challenge from three different aspects. First, we enrich the Non-Local network by adding channel-wise attention capability to it. Second, we apply Curriculum Learning principles, whereby we first train our model on easy examples before hard ones. Third, as the classification task gets harder during the Curriculum learning, our model is progressively grown to increase its capability of handling the task at hand. We examined our proposed method on two different public datasets and compared its performance with state-of-the-art methods in the literature. The results show that the ProCAN model outperforms state-of-the-art methods and achieves an AUC of 98.05% and an accuracy of 95.28% on the LIDC-IDRI dataset. Moreover, we conducted extensive ablation studies to analyze the contribution and effects of each new component of our proposed method.
We present a hybrid algorithm to estimate lung nodule malignancy that combines imaging biomarkers from Radiologist's annotation with image classification of CT scans. Our algorithm employs a 3D Convolutional Neural Network (CNN) as well as a Random Forest in order to combine CT imagery with biomarker annotation and volumetric radiomic features. We analyze and compare the performance of the algorithm using only imagery, only biomarkers, combined imagery + biomarkers, combined imagery + volumetric radiomic features and finally the combination of imagery + biomarkers + volumetric features in order to classify the suspicion level of nodule malignancy. The National Cancer Institute (NCI) Lung Image Database Consortium (LIDC) IDRI dataset is used to train and evaluate the classification task. We show that the incorporation of semi-supervised learning by means of K-Nearest-Neighbors (KNN) can increase the available training sample size of the LIDC-IDRI thereby further improving the accuracy of malignancy estimation of most of the models tested although there is no significant improvement with the use of KNN semi-supervised learning if image classification with CNNs and volumetric features are combined with descriptive biomarkers. Unexpectedly, we also show that a model using image biomarkers alone is more accurate than one that combines biomarkers with volumetric radiomics, 3D CNNs, and semi-supervised learning. We discuss the possibility that this result may be influenced by cognitive bias in LIDC-IDRI because malignancy estimates were recorded by the same radiologist panel as biomarkers, as well as future work to incorporate pathology information over a subset of study participants.
The popular softmax loss and its recent extensions have achieved great success in the deep learning-based image classification. However, the data for training image classifiers usually has different quality. Ignoring such problem, the correct classification of low quality data is hard to be solved. In this paper, we discover the positive correlation between the feature norm of an image and its quality through careful experiments on various applications and various deep neural networks. Based on this finding, we propose a contraction mapping function to compress the range of feature norms of training images according to their quality and embed this contraction mapping function into softmax loss or its extensions to produce novel learning objectives. The experiments on various classification applications, including handwritten digit recognition, lung nodule classification, face verification and face recognition, demonstrate that the proposed approach is promising to effectively deal with the problem of learning on the data with different quality and leads to the significant and stable improvements in the classification accuracy.
Machine learning methods with quantitative imaging features integration have recently gained a lot of attention for lung nodule classification. However, there is a dearth of studies in the literature on effective features ranking methods for classification purpose. Moreover, optimal number of features required for the classification task also needs to be evaluated. In this study, we investigate the impact of supervised and unsupervised feature selection techniques on machine learning methods for nodule classification in Computed Tomography (CT) images. The research work explores the classification performance of Naive Bayes and Support Vector Machine(SVM) when trained with 2, 4, 8, 12, 16 and 20 highly ranked features from supervised and unsupervised ranking approaches. The best classification results were achieved using SVM trained with 8 radiomic features selected from supervised feature ranking methods and the accuracy was 100%. The study further revealed that very good nodule classification can be achieved by training any of the SVM or Naive Bayes with a fewer radiomic features. A periodic increment in the number of radiomic features from 2 to 20 did not improve the classification results whether the selection was made using supervised or unsupervised ranking approaches.
Purpose: Lung nodules have very diverse shapes and sizes, which makes classifying them as benign/malignant a challenging problem. In this paper, we propose a novel method to predict the malignancy of nodules that have the capability to analyze the shape and size of a nodule using a global feature extractor, as well as the density and structure of the nodule using a local feature extractor. Methods: We propose to use Residual Blocks with a 3x3 kernel size for local feature extraction, and Non-Local Blocks to extract the global features. The Non-Local Block has the ability to extract global features without using a huge number of parameters. The key idea behind the Non-Local Block is to apply matrix multiplications between features on the same feature maps. Results: We trained and validated the proposed method on the LIDC-IDRI dataset which contains 1,018 computed tomography (CT) scans. We followed a rigorous procedure for experimental setup namely, 10-fold cross-validation and ignored the nodules that had been annotated by less than 3 radiologists. The proposed method achieved state-of-the-art results with AUC=95.62%, while significantly outperforming other baseline methods. Conclusions: Our proposed Deep Local-Global network has the capability to accurately extract both local and global features. Our new method outperforms state-of-the-art architecture including Densenet and Resnet with transfer learning.
This paper investigates lung nodule classification by using deep neural networks (DNNs). Hyperparameter optimization in DNNs is a computationally expensive problem, where evaluating a hyperparameter configuration may take several hours or even days. Bayesian optimization has been recently introduced for the automatically searching of optimal hyperparameter configurations of DNNs. It applies probabilistic surrogate models to approximate the validation error function of hyperparameter configurations, such as Gaussian processes, and reduce the computational complexity to a large extent. However, most existing surrogate models adopt stationary covariance functions to measure the difference between hyperparameter points based on spatial distance without considering its spatial locations. This distance-based assumption together with the condition of constant smoothness throughout the whole hyperparameter search space clearly violates the property that the points far away from optimal points usually get similarly poor performance even though each two of them have huge spatial distance between them. In this paper, a non-stationary kernel is proposed which allows the surrogate model to adapt to functions whose smoothness varies with the spatial location of inputs, and a multi-level convolutional neural network (ML-CNN) is built for lung nodule classification whose hyperparameter configuration is optimized by using the proposed non-stationary kernel based Gaussian surrogate model. Our algorithm searches the surrogate for optimal setting via hyperparameter importance based evolutionary strategy, and the experiments demonstrate our algorithm outperforms manual tuning and well-established hyperparameter optimization methods such as Random search, Gaussian processes with stationary kernels, and recently proposed Hyperparameter Optimization via RBF and Dynamic coordinate search.