Medical images commonly exhibit multiple abnormalities. Predicting them requires multi-class classifiers whose training and desired reliable performance can be affected by a combination of factors, ...such as, dataset size, data source, distribution, and the loss function used to train deep neural networks. Currently, the cross-entropy loss remains the de-facto loss function for training deep learning classifiers. This loss function, however, asserts equal learning from all classes, leading to a bias toward the majority class. Although the choice of the loss function impacts model performance, to the best of our knowledge, we observed that no literature exists that performs a comprehensive analysis and selection of an appropriate loss function toward the classification task under study. In this work, we benchmark various state-of-the-art loss functions, critically analyze model performance, and propose improved loss functions for a multi-class classification task. We select a pediatric chest X-ray (CXR) dataset that includes images with no abnormality (normal), and those exhibiting manifestations consistent with bacterial and viral pneumonia. We construct prediction-level and model-level ensembles to improve classification performance. Our results show that compared to the individual models and the state-of-the-art literature, the weighted averaging of the predictions for top-3 and top-5 model-level ensembles delivered significantly superior classification performance (p < 0.05) in terms of MCC (0.9068, 95% confidence interval (0.8839, 0.9297)) metric. Finally, we performed localization studies to interpret model behavior and confirm that the individual models and ensembles learned task-specific features and highlighted disease-specific regions of interest. The code is available at https://github.com/sivaramakrishnan-rajaraman/multiloss_ensemble_models.
The proposed study evaluates the efficacy of knowledge transfer gained through an ensemble of modality-specific deep learning models toward improving the state-of-the-art in Tuberculosis (TB) ...detection. A custom convolutional neural network (CNN) and selected popular pretrained CNNs are trained to learn modality-specific features from large-scale publicly available chest x-ray (CXR) collections including (i) RSNA dataset (normal = 8851, abnormal = 17833), (ii) Pediatric pneumonia dataset (normal = 1583, abnormal = 4273), and (iii) Indiana dataset (normal = 1726, abnormal = 2378). The knowledge acquired through modality-specific learning is transferred and fine-tuned for TB detection on the publicly available Shenzhen CXR collection (normal = 326, abnormal = 336). The predictions of the best performing models are combined using different ensemble methods to demonstrate improved performance over any individual constituent model in classifying TB-infected and normal CXRs. The models are evaluated through cross-validation (n = 5) at the patient-level with an aim to prevent overfitting, improve robustness and generalization. It is observed that a stacked ensemble of the top-3 retrained models demonstrates promising performance (accuracy: 0.941; 95% confidence interval (CI): 0.899, 0.985, area under the curve (AUC): 0.995; 95% CI: 0.945, 1.00). One-way ANOVA analyses show there are no statistically significant differences in accuracy (P = .759) and AUC (P = .831) among the ensemble methods. Knowledge transferred through modality-specific learning of relevant features helped improve the classification. The ensemble model resulted in reduced prediction variance and sensitivity to training data fluctuations. Results from their combined use are superior to the state-of-the-art.
Malaria is a life-threatening disease caused by
parasites that infect the red blood cells (RBCs). Manual identification and counting of parasitized cells in microscopic thick/thin-film blood ...examination remains the common, but burdensome method for disease diagnosis. Its diagnostic accuracy is adversely impacted by inter/intra-observer variability, particularly in large-scale screening under resource-constrained settings.
State-of-the-art computer-aided diagnostic tools based on data-driven deep learning algorithms like convolutional neural network (CNN) has become the architecture of choice for image recognition tasks. However, CNNs suffer from high variance and may overfit due to their sensitivity to training data fluctuations.
The primary aim of this study is to reduce model variance, improve robustness and generalization through constructing model ensembles toward detecting parasitized cells in thin-blood smear images.
We evaluate the performance of custom and pretrained CNNs and construct an optimal model ensemble toward the challenge of classifying parasitized and normal cells in thin-blood smear images. Cross-validation studies are performed at the patient level to ensure preventing data leakage into the validation and reduce generalization errors. The models are evaluated in terms of the following performance metrics: (a) Accuracy; (b) Area under the receiver operating characteristic (ROC) curve (AUC); (c) Mean squared error (MSE); (d) Precision; (e) F-score; and (f) Matthews Correlation Coefficient (MCC).
It is observed that the ensemble model constructed with VGG-19 and SqueezeNet outperformed the state-of-the-art in several performance metrics toward classifying the parasitized and uninfected cells to aid in improved disease screening.
Ensemble learning reduces the model variance by optimally combining the predictions of multiple models and decreases the sensitivity to the specifics of training data and selection of training algorithms. The performance of the model ensemble simulates real-world conditions with reduced variance, overfitting and leads to improved generalization.
Human papillomavirus vaccination and cervical screening are lacking in most lower resource settings, where approximately 80% of more than 500 000 cancer cases occur annually. Visual inspection of the ...cervix following acetic acid application is practical but not reproducible or accurate. The objective of this study was to develop a "deep learning"-based visual evaluation algorithm that automatically recognizes cervical precancer/cancer.
A population-based longitudinal cohort of 9406 women ages 18-94 years in Guanacaste, Costa Rica was followed for 7 years (1993-2000), incorporating multiple cervical screening methods and histopathologic confirmation of precancers. Tumor registry linkage identified cancers up to 18 years. Archived, digitized cervical images from screening, taken with a fixed-focus camera ("cervicography"), were used for training/validation of the deep learning-based algorithm. The resultant image prediction score (0-1) could be categorized to balance sensitivity and specificity for detection of precancer/cancer. All statistical tests were two-sided.
Automated visual evaluation of enrollment cervigrams identified cumulative precancer/cancer cases with greater accuracy (area under the curve AUC = 0.91, 95% confidence interval CI = 0.89 to 0.93) than original cervigram interpretation (AUC = 0.69, 95% CI = 0.63 to 0.74; P < .001) or conventional cytology (AUC = 0.71, 95% CI = 0.65 to 0.77; P < .001). A single visual screening round restricted to women at the prime screening ages of 25-49 years could identify 127 (55.7%) of 228 precancers (cervical intraepithelial neoplasia 2/cervical intraepithelial neoplasia 3/adenocarcinoma in situ AIS) diagnosed cumulatively in the entire adult population (ages 18-94 years) while referring 11.0% for management.
The results support consideration of automated visual evaluation of cervical images from contemporary digital cameras. If achieved, this might permit dissemination of effective point-of-care cervical screening.
Data-driven deep learning (DL) methods using convolutional neural networks (CNNs) demonstrate promising performance in natural image computer vision tasks. However, their use in medical computer ...vision tasks faces several limitations, viz., (i) adapting to visual characteristics that are unlike natural images; (ii) modeling random noise during training due to stochastic optimization and backpropagation-based learning strategy; (iii) challenges in explaining DL black-box behavior to support clinical decision-making; and (iv) inter-reader variability in the ground truth (GT) annotations affecting learning and evaluation. This study proposes a systematic approach to address these limitations through application to the pandemic-caused need for Coronavirus disease 2019 (COVID-19) detection using chest X-rays (CXRs). Specifically, our contribution highlights significant benefits obtained through (i) pretraining specific to CXRs in transferring and fine-tuning the learned knowledge toward improving COVID-19 detection performance; (ii) using ensembles of the fine-tuned models to further improve performance over individual constituent models; (iii) performing statistical analyses at various learning stages for validating results; (iv) interpreting learned individual and ensemble model behavior through class-selective relevance mapping (CRM)-based region of interest (ROI) localization; and, (v) analyzing inter-reader variability and ensemble localization performance using Simultaneous Truth and Performance Level Estimation (STAPLE) methods. We find that ensemble approaches markedly improved classification and localization performance, and that inter-reader variability and performance level assessment helps guide algorithm design and parameter optimization. To the best of our knowledge, this is the first study to construct ensembles, perform ensemble-based disease ROI localization, and analyze inter-reader variability and algorithm performance for COVID-19 detection in CXRs.
Malaria is a blood disease caused by the
parasites transmitted through the bite of female Anopheles mosquito. Microscopists commonly examine thick and thin blood smears to diagnose disease and ...compute parasitemia. However, their accuracy depends on smear quality and expertise in classifying and counting parasitized and uninfected cells. Such an examination could be arduous for large-scale diagnoses resulting in poor quality. State-of-the-art image-analysis based computer-aided diagnosis (CADx) methods using machine learning (ML) techniques, applied to microscopic images of the smears using hand-engineered features demand expertise in analyzing morphological, textural, and positional variations of the region of interest (ROI). In contrast, Convolutional Neural Networks (CNN), a class of deep learning (DL) models promise highly scalable and superior results with end-to-end feature extraction and classification. Automated malaria screening using DL techniques could, therefore, serve as an effective diagnostic aid. In this study, we evaluate the performance of pre-trained CNN based DL models as feature extractors toward classifying parasitized and uninfected cells to aid in improved disease screening. We experimentally determine the optimal model layers for feature extraction from the underlying data. Statistical validation of the results demonstrates the use of pre-trained CNNs as a promising tool for feature extraction for this purpose.
We demonstrate use of iteratively pruned deep learning model ensembles for detecting pulmonary manifestations of COVID-19 with chest X-rays. This disease is caused by the novel Severe Acute ...Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus, also known as the novel Coronavirus (2019-nCoV). A custom convolutional neural network and a selection of ImageNet pretrained models are trained and evaluated at patient-level on publicly available CXR collections to learn modality-specific feature representations. The learned knowledge is transferred and fine-tuned to improve performance and generalization in the related task of classifying CXRs as normal, showing bacterial pneumonia, or COVID-19-viral abnormalities. The best performing models are iteratively pruned to reduce complexity and improve memory efficiency. The predictions of the best-performing pruned models are combined through different ensemble strategies to improve classification performance. Empirical evaluations demonstrate that the weighted average of the best-performing pruned models significantly improves performance resulting in an accuracy of 99.01% and area under the curve of 0.9972 in detecting COVID-19 findings on CXRs. The combined use of modality-specific knowledge transfer, iterative model pruning, and ensemble learning resulted in improved predictions. We expect that this model can be quickly adopted for COVID-19 screening using chest radiographs.
In medical image classification tasks, it is common to find that the number of normal samples far exceeds the number of abnormal samples. In such class-imbalanced situations, reliable training of ...deep neural networks continues to be a major challenge, therefore biasing the predicted class probabilities toward the majority class. Calibration has been proposed to alleviate some of these effects. However, there is insufficient analysis explaining whether and when calibrating a model would be beneficial. In this study, we perform a systematic analysis of the effect of model calibration on its performance on two medical image modalities, namely, chest X-rays and fundus images, using various deep learning classifier backbones. For this, we study the following variations: (i) the degree of imbalances in the dataset used for training; (ii) calibration methods; and (iii) two classification thresholds, namely, default threshold of 0.5, and optimal threshold from precision-recall (PR) curves. Our results indicate that at the default classification threshold of 0.5, the performance achieved through calibration is significantly superior (p < 0.05) to using uncalibrated probabilities. However, at the PR-guided threshold, these gains are not significantly different (p > 0.05). This observation holds for both image modalities and at varying degrees of imbalance. The code is available at https://github.com/sivaramakrishnan-rajaraman/Model_calibration.
Pneumonia affects 7% of the global population, resulting in 2 million pediatric deaths every year. Chest X-ray (CXR) analysis is routinely performed to diagnose the disease. Computer-aided diagnostic ...(CADx) tools aim to supplement decision-making. These tools process the handcrafted and/or convolutional neural network (CNN) extracted image features for visual recognition. However, CNNs are perceived as black boxes since their performance lack explanations. This is a serious bottleneck in applications involving medical screening/diagnosis since poorly interpreted model behavior could adversely affect the clinical decision. In this study, we evaluate, visualize, and explain the performance of customized CNNs to detect pneumonia and further differentiate between bacterial and viral types in pediatric CXRs. We present a novel visualization strategy to localize the region of interest (ROI) that is considered relevant for model predictions across all the inputs that belong to an expected class. We statistically validate the models' performance toward the underlying tasks. We observe that the customized VGG16 model achieves 96.2% and 93.6% accuracy in detecting the disease and distinguishing between bacterial and viral pneumonia respectively. The model outperforms the state-of-the-art in all performance metrics and demonstrates reduced bias and improved generalization.
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic resulting in over 2.7 million infected individuals and over 190,000 deaths and growing. Assertions in the ...literature suggest that respiratory disorders due to COVID-19 commonly present with pneumonia-like symptoms which are radiologically confirmed as opacities. Radiology serves as an adjunct to the reverse transcription-polymerase chain reaction test for confirmation and evaluating disease progression. While computed tomography (CT) imaging is more specific than chest X-rays (CXR), its use is limited due to cross-contamination concerns. CXR imaging is commonly used in high-demand situations, placing a significant burden on radiology services. The use of artificial intelligence (AI) has been suggested to alleviate this burden. However, there is a dearth of sufficient training data for developing image-based AI tools. We propose increasing training data for recognizing COVID-19 pneumonia opacities using weakly labeled data augmentation. This follows from a hypothesis that the COVID-19 manifestation would be similar to that caused by other viral pathogens affecting the lungs. We expand the training data distribution for supervised learning through the use of weakly labeled CXR images, automatically pooled from publicly available pneumonia datasets, to classify them into those with bacterial or viral pneumonia opacities. Next, we use these selected images in a stage-wise, strategic approach to train convolutional neural network-based algorithms and compare against those trained with non-augmented data. Weakly labeled data augmentation expands the learned feature space in an attempt to encompass variability in unseen test distributions, enhance inter-class discrimination, and reduce the generalization error. Empirical evaluations demonstrate that simple weakly labeled data augmentation (Acc: 0.5555 and Acc: 0.6536) is better than baseline non-augmented training (Acc: 0.2885 and Acc: 0.5028) in identifying COVID-19 manifestations as viral pneumonia. Interestingly, adding COVID-19 CXRs to simple weakly labeled augmented training data significantly improves the performance (Acc: 0.7095 and Acc: 0.8889), suggesting that COVID-19, though viral in origin, creates a uniquely different presentation in CXRs compared with other viral pneumonia manifestations.
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