Can Deep Adult Lung Segmentation Models Generalize to the Pediatric Population?

Lung segmentation in chest X-rays (CXRs) is an important prerequisite for improving the specificity of diagnoses of cardiopulmonary diseases in a clinical decision support system. Current deep learning models for lung segmentation are trained and evaluated on CXR datasets in which the radiographic projections are captured predominantly from the adult population. However, the shape of the lungs is reported to be significantly different across the developmental stages from infancy to adulthood. This might result in age-related data domain shifts that would adversely impact lung segmentation performance when the models trained on the adult population are deployed for pediatric lung segmentation. In this work, our goal is to (i) analyze the generalizability of deep adult lung segmentation models to the pediatric population and (ii) improve performance through a stage-wise, systematic approach consisting of CXR modality-specific weight initializations, stacked ensembles, and an ensemble of stacked ensembles. To evaluate segmentation performance and generalizability, novel evaluation metrics consisting of mean lung contour distance (MLCD) and average hash score (AHS) are proposed in addition to the multi-scale structural similarity index measure (MS-SSIM), the intersection of union (IoU), Dice score, 95% Hausdorff distance (HD95), and average symmetric surface distance (ASSD). Our results showed a significant improvement (p < 0.05) in cross-domain generalization through our approach. This study could serve as a paradigm to analyze the cross-domain generalizability of deep segmentation models for other medical imaging modalities and applications.

Advances in Deep Learning for Tuberculosis Screening using Chest X-rays: The Last 5 Years Review.

There has been an explosive growth in research over the last decade exploring machine learning techniques for analyzing chest X-ray (CXR) images for screening cardiopulmonary abnormalities. In particular, we have observed a strong interest in screening for tuberculosis (TB). This interest has coincided with the spectacular advances in deep learning (DL) that is primarily based on convolutional neural networks (CNNs). These advances have resulted in significant research contributions in DL techniques for TB screening using CXR images. We review the research studies published over the last five years (2016-2021). We identify data collections, methodical contributions, and highlight promising methods and challenges. Further, we discuss and compare studies and identify those that offer extension beyond binary decisions for TB, such as region-of-interest localization. In total, we systematically review 54 peer-reviewed research articles and perform meta-analysis.

Malaria Screener: a smartphone application for automated malaria screening.

BACKGROUND: Light microscopy is often used for malaria diagnosis in the field. However, it is time-consuming and quality of the results depends heavily on the skill of microscopists. Automating malaria light microscopy is a promising solution, but it still remains a challenge and an active area of research. Current tools are often expensive and involve sophisticated hardware components, which makes it hard to deploy them in resource-limited areas. RESULTS: We designed an Android mobile application called Malaria Screener, which makes smartphones an affordable yet effective solution for automated malaria light microscopy. The mobile app utilizes high-resolution cameras and computing power of modern smartphones to screen both thin and thick blood smear images for P. falciparum parasites. Malaria Screener combines image acquisition, smear image analysis, and result visualization in its slide screening process, and is equipped with a database to provide easy access to the acquired data. CONCLUSION: Malaria Screener makes the screening process faster, more consistent, and less dependent on human expertise. The app is modular, allowing other research groups to integrate their methods and models for image processing and machine learning, while acquiring and analyzing their data.

Uncovering the effects of model initialization on deep model generalization: A study with adult and pediatric chest X-ray images.

Model initialization techniques are vital for improving the performance and reliability of deep learning models in medical computer vision applications. While much literature exists on non-medical images, the impacts on medical images, particularly chest X-rays (CXRs) are less understood. Addressing this gap, our study explores three deep model initialization techniques: Cold-start, Warm-start, and Shrink and Perturb start, focusing on adult and pediatric populations. We specifically focus on scenarios with periodically arriving data for training, thereby embracing the real-world scenarios of ongoing data influx and the need for model updates. We evaluate these models for generalizability against external adult and pediatric CXR datasets. We also propose novel ensemble methods: F-score-weighted Sequential Least-Squares Quadratic Programming (F-SLSQP) and Attention-Guided Ensembles with Learnable Fuzzy Softmax to aggregate weight parameters from multiple models to capitalize on their collective knowledge and complementary representations. We perform statistical significance tests with 95% confidence intervals and p-values to analyze model performance. Our evaluations indicate models initialized with ImageNet-pretrained weights demonstrate superior generalizability over randomly initialized counterparts, contradicting some findings for non-medical images. Notably, ImageNet-pretrained models exhibit consistent performance during internal and external testing across different training scenarios. Weight-level ensembles of these models show significantly higher recall (p<0.05) during testing compared to individual models. Thus, our study accentuates the benefits of ImageNet-pretrained weight initialization, especially when used with weight-level ensembles, for creating robust and generalizable deep learning solutions.

Semantically redundant training data removal and deep model classification performance: A study with chest X-rays.

Deep learning (DL) has demonstrated its innate capacity to independently learn hierarchical features from complex and multi-dimensional data. A common understanding is that its performance scales up with the amount of training data. However, the data must also exhibit variety to enable improved learning. In medical imaging data, semantic redundancy, which is the presence of similar or repetitive information, can occur due to the presence of multiple images that have highly similar presentations for the disease of interest. Also, the common use of augmentation methods to generate variety in DL training could limit performance when indiscriminately applied to such data. We hypothesize that semantic redundancy would therefore tend to lower performance and limit generalizability to unseen data and question its impact on classifier performance even with large data. We propose an entropy-based sample scoring approach to identify and remove semantically redundant training data and demonstrate using the publicly available NIH chest X-ray dataset that the model trained on the resulting informative subset of training data significantly outperforms the model trained on the full training set, during both internal (recall: 0.7164 vs 0.6597, p<0.05) and external testing (recall: 0.3185 vs 0.2589, p<0.05). Our findings emphasize the importance of information-oriented training sample selection as opposed to the conventional practice of using all available training data.

Assessing the Impact of Image Resolution on Deep Learning for TB Lesion Segmentation on Frontal Chest X-rays.

Deep learning (DL) models are state-of-the-art in segmenting anatomical and disease regions of interest (ROIs) in medical images. Particularly, a large number of DL-based techniques have been reported using chest X-rays (CXRs). However, these models are reportedly trained on reduced image resolutions for reasons related to the lack of computational resources. Literature is sparse in discussing the optimal image resolution to train these models for segmenting the tuberculosis (TB)-consistent lesions in CXRs. In this study, we investigated the performance variations with an Inception-V3 UNet model using various image resolutions with/without lung ROI cropping and aspect ratio adjustments and identified the optimal image resolution through extensive empirical evaluations to improve TB-consistent lesion segmentation performance. We used the Shenzhen CXR dataset for the study, which includes 326 normal patients and 336 TB patients. We proposed a combinatorial approach consisting of storing model snapshots, optimizing segmentation threshold and test-time augmentation (TTA), and averaging the snapshot predictions, to further improve performance with the optimal resolution. Our experimental results demonstrate that higher image resolutions are not always necessary; however, identifying the optimal image resolution is critical to achieving superior performance.

Does image resolution impact chest X-ray based fine-grained Tuberculosis-consistent lesion segmentation?

Deep learning (DL) models are state-of-the-art in segmenting anatomical and disease regions of interest (ROIs) in medical images. Particularly, a large number of DL-based techniques have been reported using chest X-rays (CXRs). However, these models are reportedly trained on reduced image resolutions for reasons related to the lack of computational resources. Literature is sparse in discussing the optimal image resolution to train these models for segmenting the Tuberculosis (TB)-consistent lesions in CXRs. In this study, we investigated the performance variations using an Inception-V3 UNet model using various image resolutions with/without lung ROI cropping and aspect ratio adjustments, and (ii) identified the optimal image resolution through extensive empirical evaluations to improve TB-consistent lesion segmentation performance. We used the Shenzhen CXR dataset for the study which includes 326 normal patients and 336 TB patients. We proposed a combinatorial approach consisting of storing model snapshots, optimizing segmentation threshold and test-time augmentation (TTA), and averaging the snapshot predictions, to further improve performance with the optimal resolution. Our experimental results demonstrate that higher image resolutions are not always necessary, however, identifying the optimal image resolution is critical to achieving superior performance.

Data Characterization for Reliable AI in Medicine.

Research in Artificial Intelligence (AI)-based medical computer vision algorithms bear promises to improve disease screening, diagnosis, and subsequently patient care. However, these algorithms are highly impacted by the characteristics of the underlying data. In this work, we discuss various data characteristics, namely Volume, Veracity, Validity, Variety, and Velocity, that impact the design, reliability, and evolution of machine learning in medical computer vision. Further, we discuss each characteristic and the recent works conducted in our research lab that informed our understanding of the impact of these characteristics on the design of medical decision-making algorithms and outcome reliability.

Cross Dataset Analysis of Domain Shift in CXR Lung Region Detection.

Domain shift is one of the key challenges affecting reliability in medical imaging-based machine learning predictions. It is of significant importance to investigate this issue to gain insights into its characteristics toward determining controllable parameters to minimize its impact. In this paper, we report our efforts on studying and analyzing domain shift in lung region detection in chest radiographs. We used five chest X-ray datasets, collected from different sources, which have manual markings of lung boundaries in order to conduct extensive experiments toward this goal. We compared the characteristics of these datasets from three aspects: information obtained from metadata or an image header, image appearance, and features extracted from a pretrained model. We carried out experiments to evaluate and compare model performances within each dataset and across datasets in four scenarios using different combinations of datasets. We proposed a new feature visualization method to provide explanations for the applied object detection network on the obtained quantitative results. We also examined chest X-ray modality-specific initialization, catastrophic forgetting, and model repeatability. We believe the observations and discussions presented in this work could help to shed some light on the importance of the analysis of training data for medical imaging machine learning research, and could provide valuable guidance for domain shift analysis.

Semantically Redundant Training Data Removal and Deep Model Classification Performance: A Study with Chest X-rays.

Deep learning (DL) has demonstrated its innate capacity to independently learn hierarchical features from complex and multi-dimensional data. A common understanding is that its performance scales up with the amount of training data. Another data attribute is the inherent variety. It follows, therefore, that semantic redundancy, which is the presence of similar or repetitive information, would tend to lower performance and limit generalizability to unseen data. In medical imaging data, semantic redundancy can occur due to the presence of multiple images that have highly similar presentations for the disease of interest. Further, the common use of augmentation methods to generate variety in DL training may be limiting performance when applied to semantically redundant data. We propose an entropy-based sample scoring approach to identify and remove semantically redundant training data. We demonstrate using the publicly available NIH chest X-ray dataset that the model trained on the resulting informative subset of training data significantly outperforms the model trained on the full training set, during both internal (recall: 0.7164 vs 0.6597, p<0.05) and external testing (recall: 0.3185 vs 0.2589, p<0.05). Our findings emphasize the importance of information-oriented training sample selection as opposed to the conventional practice of using all available training data.

Automatic Quantification of COVID-19 Pulmonary Edema by Self-supervised Contrastive Learning.

We proposed a self-supervised machine learning method to automatically rate the severity of pulmonary edema in the frontal chest X-ray radiographs (CXR) which could be potentially related to COVID-19 viral pneumonia. For this we use the modified radiographic assessment of lung edema (mRALE) scoring system. The new model was first optimized with the simple Siamese network (SimSiam) architecture where a ResNet-50 pretrained by ImageNet database was used as the backbone. The encoder projected a 2048-dimension embedding as representation features to a downstream fully connected deep neural network for mRALE score prediction. A 5-fold cross-validation with 2,599 frontal CXRs was used to examine the new model's performance with comparison to a non-pretrained SimSiam encoder and a ResNet-50 trained from scratch. The mean absolute error (MAE) of the new model is 5.05 (95%CI 5.03-5.08), the mean squared error (MSE) is 66.67 (95%CI 66.29-67.06), and the Spearman's correlation coefficient (Spearman ρ) to the expert-annotated scores is 0.77 (95%CI 0.75-0.79). All the performance metrics of the new model are superior to the two comparators (P<0.01), and the scores of MSE and Spearman ρ of the two comparators have no statistical difference (P>0.05). The model also achieved a prediction probability concordance of 0.811 and a quadratic weighted kappa of 0.739 with the medical expert annotations in external validation. We conclude that the self-supervised contrastive learning method is an effective strategy for mRALE automated scoring. It provides a new approach to improve machine learning performance and minimize the expert knowledge involvement in quantitative medical image pattern learning.

Evaluation of an artificial intelligence-based system for echocardiographic estimation of right atrial pressure.

Current noninvasive estimation of right atrial pressure (RAP) by inferior vena cava (IVC) measurement during echocardiography may have significant inter-rater variability due to different levels of observers' experience. Therefore, there is a need to develop new approaches to decrease the variability of IVC analysis and RAP estimation. This study aims to develop a fully automated artificial intelligence (AI)-based system for automated IVC analysis and RAP estimation. We presented a multi-stage AI system to identify the IVC view, select good quality images, delineate the IVC region and quantify its thickness, enabling temporal tracking of its diameter and collapsibility changes. The automated system was trained and tested on expert manual IVC and RAP reference measurements obtained from 255 patients during routine clinical workflow. The performance was evaluated using Pearson correlation and Bland-Altman analysis for IVC values, as well as macro accuracy and chi-square test for RAP values. Our results show an excellent agreement (r=0.96) between automatically computed versus manually measured IVC values, and Bland-Altman analysis showed a small bias of [Formula: see text]0.33 mm. Further, there is an excellent agreement ([Formula: see text]) between automatically estimated versus manually derived RAP values with a macro accuracy of 0.85. The proposed AI-based system accurately quantified IVC diameter, collapsibility index, both are used for RAP estimation. This automated system could serve as a paradigm to perform IVC analysis in routine echocardiography and support various cardiac diagnostic applications.

Assessing Inter-Annotator Agreement for Medical Image Segmentation.

Artificial Intelligence (AI)-based medical computer vision algorithm training and evaluations depend on annotations and labeling. However, variability between expert annotators introduces noise in training data that can adversely impact the performance of AI algorithms. This study aims to assess, illustrate and interpret the inter-annotator agreement among multiple expert annotators when segmenting the same lesion(s)/abnormalities on medical images. We propose the use of three metrics for the qualitative and quantitative assessment of inter-annotator agreement: 1) use of a common agreement heatmap and a ranking agreement heatmap; 2) use of the extended Cohen's kappa and Fleiss' kappa coefficients for a quantitative evaluation and interpretation of inter-annotator reliability; and 3) use of the Simultaneous Truth and Performance Level Estimation (STAPLE) algorithm, as a parallel step, to generate ground truth for training AI models and compute Intersection over Union (IoU), sensitivity, and specificity to assess the inter-annotator reliability and variability. Experiments are performed on two datasets, namely cervical colposcopy images from 30 patients and chest X-ray images from 336 tuberculosis (TB) patients, to demonstrate the consistency of inter-annotator reliability assessment and the importance of combining different metrics to avoid bias assessment.

Editorial on Special Issue "Artificial Intelligence in Image-Based Screening, Diagnostics, and Clinical Care of Cardiopulmonary Diseases".

Cardiopulmonary diseases are a significant cause of mortality and morbidity worldwide [...].

A Deep Modality-Specific Ensemble for Improving Pneumonia Detection in Chest X-rays.

Pneumonia is an acute respiratory infectious disease caused by bacteria, fungi, or viruses. Fluid-filled lungs due to the disease result in painful breathing difficulties and reduced oxygen intake. Effective diagnosis is critical for appropriate and timely treatment and improving survival. Chest X-rays (CXRs) are routinely used to screen for the infection. Computer-aided detection methods using conventional deep learning (DL) models for identifying pneumonia-consistent manifestations in CXRs have demonstrated superiority over traditional machine learning approaches. However, their performance is still inadequate to aid in clinical decision-making. This study improves upon the state of the art as follows. Specifically, we train a DL classifier on large collections of CXR images to develop a CXR modality-specific model. Next, we use this model as the classifier backbone in the RetinaNet object detection network. We also initialize this backbone using random weights and ImageNet-pretrained weights. Finally, we construct an ensemble of the best-performing models resulting in improved detection of pneumonia-consistent findings. Experimental results demonstrate that an ensemble of the top-3 performing RetinaNet models outperformed individual models in terms of the mean average precision (mAP) metric (0.3272, 95% CI: (0.3006,0.3538)) toward this task, which is markedly higher than the state of the art (mAP: 0.2547). This performance improvement is attributed to the key modifications in initializing the weights of classifier backbones and constructing model ensembles to reduce prediction variance compared to individual constituent models.

Open World Active Learning for Echocardiography View Classification.

Existing works for automated echocardiography view classification are designed under the assumption that the views in the testing set must belong to a limited number of views that have appeared in the training set. Such a design is called closed world classification. This assumption may be too strict for real-world environments that are open and often have unseen examples, drastically weakening the robustness of the classical view classification approaches. In this work, we developed an open world active learning approach for echocardiography view classification, where the network classifies images of known views into their respective classes and identifies images of unknown views. Then, a clustering approach is used to cluster the unknown views into various groups to be labeled by echocardiologists. Finally, the new labeled samples are added to the initial set of known views and used to update the classification network. This process of actively labeling unknown clusters and integrating them into the classification model significantly increases the efficiency of data labeling and the robustness of the classifier. Our results using an echocardiography dataset containing known and unknown views showed the superiority of the proposed approach as compared to the closed world view classification approaches.

Deep learning model calibration for improving performance in class-imbalanced medical image classification tasks.

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.

Detecting Tuberculosis-Consistent Findings in Lateral Chest X-Rays Using an Ensemble of CNNs and Vision Transformers.

Research on detecting Tuberculosis (TB) findings on chest radiographs (or Chest X-rays: CXR) using convolutional neural networks (CNNs) has demonstrated superior performance due to the emergence of publicly available, large-scale datasets with expert annotations and availability of scalable computational resources. However, these studies use only the frontal CXR projections, i.e., the posterior-anterior (PA), and the anterior-posterior (AP) views for analysis and decision-making. Lateral CXRs which are heretofore not studied help detect clinically suspected pulmonary TB, particularly in children. Further, Vision Transformers (ViTs) with built-in self-attention mechanisms have recently emerged as a viable alternative to the traditional CNNs. Although ViTs demonstrated notable performance in several medical image analysis tasks, potential limitations exist in terms of performance and computational efficiency, between the CNN and ViT models, necessitating a comprehensive analysis to select appropriate models for the problem under study. This study aims to detect TB-consistent findings in lateral CXRs by constructing an ensemble of the CNN and ViT models. Several models are trained on lateral CXR data extracted from two large public collections to transfer modality-specific knowledge and fine-tune them for detecting findings consistent with TB. We observed that the weighted averaging ensemble of the predictions of CNN and ViT models using the optimal weights computed with the Sequential Least-Squares Quadratic Programming method delivered significantly superior performance (MCC: 0.8136, 95% confidence intervals (CI): 0.7394, 0.8878, p < 0.05) compared to the individual models and other ensembles. We also interpreted the decisions of CNN and ViT models using class-selective relevance maps and attention maps, respectively, and combined them to highlight the discriminative image regions contributing to the final output. We observed that (i) the model accuracy is not related to disease region of interest (ROI) localization and (ii) the bitwise-AND of the heatmaps of the top-2-performing models delivered significantly superior ROI localization performance in terms of mean average precision [mAP@(0.1 0.6) = 0.1820, 95% CI: 0.0771,0.2869, p < 0.05], compared to other individual models and ensembles. The code is available at https://github.com/sivaramakrishnan-rajaraman/Ensemble-of-CNN-and-ViT-for-TB-detection-in-lateral-CXR.

Real-time echocardiography image analysis and quantification of cardiac indices.

Deep learning has a huge potential to transform echocardiography in clinical practice and point of care ultrasound testing by providing real-time analysis of cardiac structure and function. Automated echocardiography analysis is benefited through use of machine learning for tasks such as image quality assessment, view classification, cardiac region segmentation, and quantification of diagnostic indices. By taking advantage of high-performing deep neural networks, we propose a novel and eicient real-time system for echocardiography analysis and quantification. Our system uses a self-supervised modality-specific representation trained using a publicly available large-scale dataset. The trained representation is used to enhance the learning of target echo tasks with relatively small datasets. We also present a novel Trilateral Attention Network (TaNet) for real-time cardiac region segmentation. The proposed network uses a module for region localization and three lightweight pathways for encoding rich low-level, textural, and high-level features. Feature embeddings from these individual pathways are then aggregated for cardiac region segmentation. This network is fine-tuned using a joint loss function and training strategy. We extensively evaluate the proposed system and its components, which are echo view retrieval, cardiac segmentation, and quantification, using four echocardiography datasets. Our experimental results show a consistent improvement in the performance of echocardiography analysis tasks with enhanced computational eiciency that charts a path toward its adoption in clinical practice. Specifically, our results show superior real-time performance in retrieving good quality echo from individual cardiac view, segmenting cardiac chambers with complex overlaps, and extracting cardiac indices that highly agree with the experts' values. The source code of our implementation can be found in the project's GitHub page.

DeBoNet: A deep bone suppression model ensemble to improve disease detection in chest radiographs.

Automatic detection of some pulmonary abnormalities using chest X-rays may be impacted adversely due to obscuring by bony structures like the ribs and the clavicles. Automated bone suppression methods would increase soft tissue visibility and enhance automated disease detection. We evaluate this hypothesis using a custom ensemble of convolutional neural network models, which we call DeBoNet, that suppresses bones in frontal CXRs. First, we train and evaluate variants of U-Nets, Feature Pyramid Networks, and other proposed custom models using a private collection of CXR images and their bone-suppressed counterparts. The DeBoNet, constructed using the top-3 performing models, outperformed the individual models in terms of peak signal-to-noise ratio (PSNR) (36.7977±1.6207), multi-scale structural similarity index measure (MS-SSIM) (0.9848±0.0073), and other metrics. Next, the best-performing bone-suppression model is applied to CXR images that are pooled from several sources, showing no abnormality and other findings consistent with COVID-19. The impact of bone suppression is demonstrated by evaluating the gain in performance in detecting pulmonary abnormality consistent with COVID-19 disease. We observe that the model trained on bone-suppressed CXRs (MCC: 0.9645, 95% confidence interval (0.9510, 0.9780)) significantly outperformed (p < 0.05) the model trained on non-bone-suppressed images (MCC: 0.7961, 95% confidence interval (0.7667, 0.8255)) in detecting findings consistent with COVID-19 indicating benefits derived from automatic bone suppression on disease classification. The code is available at https://github.com/sivaramakrishnan-rajaraman/Bone-Suppresion-Ensemble.