Sivaramakrishnan Rajaraman

Sivaramakrishnan Rajaraman, Ghada Zamzmi, Feng Yang et al.

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.

Sivaramakrishnan Rajaraman, Ghada Zamzmi, Feng Yang et al.

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-pre-trained 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.

Sivaramakrishnan Rajaraman, Feng Yang, Ghada Zamzmi et al.

Automated segmentation of tuberculosis (TB)-consistent lesions in chest X-rays (CXRs) using deep learning (DL) methods can help reduce radiologist effort, supplement clinical decision-making, and potentially result in improved patient treatment. The majority of works in the literature discuss training automatic segmentation models using coarse bounding box annotations. However, the granularity of the bounding box annotation could result in the inclusion of a considerable fraction of false positives and negatives at the pixel level that may adversely impact overall semantic segmentation performance. This study (i) evaluates the benefits of using fine-grained annotations of TB-consistent lesions and (ii) trains and constructs ensembles of the variants of U-Net models for semantically segmenting TB-consistent lesions in both original and bone-suppressed frontal CXRs. We evaluated segmentation performance using several ensemble methods such as bitwise AND, bitwise-OR, bitwise-MAX, and stacking. We observed that the stacking ensemble demonstrated superior segmentation performance (Dice score: 0.5743, 95% confidence interval: (0.4055,0.7431)) compared to the individual constituent models and other ensemble methods. To the best of our knowledge, this is the first study to apply ensemble learning to improve fine-grained TB-consistent lesion segmentation performance.

Sivaramakrishnan Rajaraman, Feng Yang, Ghada Zamzmi et al.

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.

Sivaramakrishnan Rajaraman, Feng Yang, Ghada Zamzmi et al.

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.

Zhaohui Liang, Sivaramakrishnan Rajaraman, Niccolo Marini et al.

CLIP and BiomedCLIP are examples of vision-language foundation models and offer strong cross-modal embeddings; however, they are not optimized for fine-grained medical retrieval tasks, such as retrieving clinically relevant radiology reports using chest X-ray (CXR) image queries. To address this shortcoming, we propose a multi-task learning framework to fine-tune BiomedCLIP and evaluate improvements to CXR image-text retrieval. Using BiomedCLIP as the backbone, we incorporate a lightweight MLP projector head trained with a multi-task composite loss function that includes: (1) a binary cross-entropy loss to distinguish normal from abnormal CXR studies, (2) a supervised contrastive loss to reinforce intra-class consistency, and (3) a CLIP loss to maintain cross-modal alignment. Experimental results demonstrate that the fine-tuned model achieves more balanced and clinically meaningful performance across both image-to-text and text-to-image retrieval tasks compared to the pretrained BiomedCLIP and general-purpose CLIP models. Furthermore, t-SNE visualizations reveal clearer semantic clustering of normal and abnormal cases, demonstrating the model's enhanced diagnostic sensitivity. These findings highlight the value of domain-adaptive, multi-task learning for advancing cross-modal retrieval in biomedical applications.

Niccolo Marini, Zhaohui Liang, Sivaramakrishnan Rajaraman et al.

Multimodal (MM) learning is emerging as a promising paradigm in biomedical artificial intelligence (AI) applications, integrating complementary modality, which highlight different aspects of patient health. The scarcity of large heterogeneous biomedical MM data has restrained the development of robust models for medical AI applications. In the dermatology domain, for instance, skin lesion datasets typically include only images linked to minimal metadata describing the condition, thereby limiting the benefits of MM data integration for reliable and generalizable predictions. Recent advances in Large Language Models (LLMs) enable the synthesis of textual description of image findings, potentially allowing the combination of image and text representations. However, LLMs are not specifically trained for use in the medical domain, and their naive inclusion has raised concerns about the risk of hallucinations in clinically relevant contexts. This work investigates strategies for generating synthetic textual clinical notes, in terms of prompt design and medical metadata inclusion, and evaluates their impact on MM architectures toward enhancing performance in classification and cross-modal retrieval tasks. Experiments across several heterogeneous dermatology datasets demonstrate that synthetic clinical notes not only enhance classification performance, particularly under domain shift, but also unlock cross-modal retrieval capabilities, a downstream task that is not explicitly optimized during training.

Sivaramakrishnan Rajaraman, Gregg Cohen, Lillian Spear et al.

Chest X-ray (CXR) is a widely performed radiology examination that helps to detect abnormalities in the tissues and organs in the thoracic cavity. Detecting pulmonary abnormalities like COVID-19 may become difficult due to that they are obscured by the presence of bony structures like the ribs and the clavicles, thereby resulting in screening/diagnostic misinterpretations. Automated bone suppression methods would help suppress these bony structures and increase soft tissue visibility. In this study, we propose to build an ensemble of convolutional neural network models to suppress bones in frontal CXRs, improve classification performance, and reduce interpretation errors related to COVID-19 detection. The ensemble is constructed by (i) measuring the multi-scale structural similarity index (MS-SSIM) score between the sub-blocks of the bone-suppressed image predicted by each of the top-3 performing bone-suppression models and the corresponding sub-blocks of its respective ground truth soft-tissue image, and (ii) performing a majority voting of the MS-SSIM score computed in each sub-block to identify the sub-block with the maximum MS-SSIM score and use it in constructing the final bone-suppressed image. We empirically determine the sub-block size that delivers superior bone suppression performance. It is observed that the bone suppression model ensemble outperformed the individual models in terms of MS-SSIM and other metrics. A CXR modality-specific classification model is retrained and evaluated on the non-bone-suppressed and bone-suppressed images to classify them as showing normal lungs or other COVID-19-like manifestations. We observed that the bone-suppressed model training significantly outperformed the model trained on non-bone-suppressed images toward detecting COVID-19 manifestations.

Sivaramakrishnan Rajaraman, Ghada Zamzmi, Sameer Antani

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 the 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. In this work, we benchmark various state-of-the-art loss functions that are suitable for multi-class classification, critically analyze model performance, and propose improved loss functions. 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, respectively, 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 behaviors to visualize and confirm that the individual models and ensembles learned meaningful features and highlighted disease manifestations.

Sivaramakrishnan Rajaraman, Prasanth Ganesan, Sameer Antani

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. Under these circumstances, the predicted class probabilities may be biased toward the majority class. Calibration has been suggested to alleviate some of these effects. However, there is insufficient analysis explaining when and whether calibrating a model would be beneficial in improving performance. 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 decision threshold of 0.5, and optimal threshold from precision-recall curves. Our results indicate that at the default operating 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 finding holds for both image modalities and at varying degrees of imbalance.

Sivaramakrishnan Rajaraman, Ghada Zamzmi, Les Folio et al.

Chest X-rays are the most commonly performed diagnostic examination to detect cardiopulmonary abnormalities. However, the presence of bony structures such as ribs and clavicles can obscure subtle abnormalities, resulting in diagnostic errors. This study aims to build a deep learning-based bone suppression model that identifies and removes these occluding bony structures in frontal CXRs to assist in reducing errors in radiological interpretation, including DL workflows, related to detecting manifestations consistent with tuberculosis (TB). Several bone suppression models with various deep architectures are trained and optimized using the proposed combined loss function and their performances are evaluated in a cross-institutional test setting. The best-performing model is used to suppress bones in the publicly available Shenzhen and Montgomery TB CXR collections. A VGG-16 model is pretrained on a large collection of publicly available CXRs. The CXR-pretrained model is then fine-tuned individually on the non-bone-suppressed and bone-suppressed CXRs of Shenzhen and Montgomery TB CXR collections to classify them as showing normal lungs or TB manifestations. The performances of these models are compared using several performance metrics, analyzed for statistical significance, and their predictions are qualitatively interpreted through class-selective relevance maps. It is observed that the models trained on bone-suppressed CXRs significantly outperformed (p<0.05) the models trained on the non-bone-suppressed CXRs. Models trained on bone-suppressed CXRs improved detection of TB-consistent findings and resulted in compact clustering of the data points in the feature space signifying that bone suppression improved the model sensitivity toward TB classification.

Sivaramakrishnan Rajaraman, Les Folio, Jane Dimperio et al.

Deep learning (DL) has drawn tremendous attention in object localization and recognition for both natural and medical images. U-Net segmentation models have demonstrated superior performance compared to conventional handcrafted feature-based methods. Medical image modality-specific DL models are better at transferring domain knowledge to a relevant target task than those that are pretrained on stock photography images. This helps improve model adaptation, generalization, and class-specific region of interest (ROI) localization. In this study, we train chest X-ray (CXR) modality-specific U-Nets and other state-of-the-art U-Net models for semantic segmentation of tuberculosis (TB)-consistent findings. Automated segmentation of such manifestations could help radiologists reduce errors and supplement decision-making while improving patient care and productivity. Our approach uses the publicly available TBX11K CXR dataset with weak TB annotations, typically provided as bounding boxes, to train a set of U-Net models. Next, we improve the results by augmenting the training data with weak localizations, post-processed into an ROI mask, from a DL classifier that is trained to classify CXRs as showing normal lungs or suspected TB manifestations. Test data are individually derived from the TBX11K CXR training distribution and other cross-institutional collections including the Shenzhen TB and Montgomery TB CXR datasets. We observe that our augmented training strategy helped the CXR modality-specific U-Net models achieve superior performance with test data derived from the TBX11K CXR training distribution as well as from cross-institutional collections (p < 0.05).

Ghada Zamzmi, Sivaramakrishnan Rajaraman, Sameer Antani

Medical image analysis typically includes several tasks such as enhancement, segmentation, and classification. Traditionally, these tasks are implemented using separate deep learning models for separate tasks, which is not efficient because it involves unnecessary training repetitions, demands greater computational resources, and requires a relatively large amount of labeled data. In this paper, we propose a multi-task training approach for medical image analysis, where individual tasks are fine-tuned simultaneously through relevant knowledge transfer using a unified modality-specific feature representation (UMS-Rep). We explore different fine-tuning strategies to demonstrate the impact of the strategy on the performance of target medical image tasks. We experiment with different visual tasks (e.g., image denoising, segmentation, and classification) to highlight the advantages offered with our approach for two imaging modalities, chest X-ray and Doppler echocardiography. Our results demonstrate that the proposed approach reduces the overall demand for computational resources and improves target task generalization and performance. Further, our results prove that the performance of target tasks in medical images is highly influenced by the utilized fine-tuning strategy.

Sivaramakrishnan Rajaraman, Jen Siegelman, Philip O. Alderson et al.

We demonstrate use of iteratively pruned deep learning model ensembles for detecting pulmonary manifestation 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.