Automated Pulmonary Tuberculosis Severity Assessment on Chest X-rays.

According to the 2022 World Health Organization's Global Tuberculosis (TB) report, an estimated 10.6 million people fell ill with TB, and 1.6 million died from the disease in 2021. In addition, 2021 saw a reversal of a decades-long trend of declining TB infections and deaths, with an estimated increase of 4.5% in the number of people who fell ill with TB compared to 2020, and an estimated yearly increase of 450,000 cases of drug resistant TB. Estimating the severity of pulmonary TB using frontal chest X-rays (CXR) can enable better resource allocation in resource constrained settings and monitoring of treatment response, enabling prompt treatment modifications if disease severity does not decrease over time. The Timika score is a clinically used TB severity score based on a CXR reading. This work proposes and evaluates three deep learning-based approaches for predicting the Timika score with varying levels of explainability. The first approach uses two deep learning-based models, one to explicitly detect lesion regions using YOLOV5n and another to predict the presence of cavitation using DenseNet121, which are then utilized in score calculation. The second approach uses a DenseNet121-based regression model to directly predict the affected lung percentage and another to predict cavitation presence using a DenseNet121-based classification model. Finally, the third approach directly predicts the Timika score using a DenseNet121-based regression model. The best performance is achieved by the second approach with a mean absolute error of 13-14% and a Pearson correlation of 0.7-0.84 using three held-out datasets for evaluating generalization.

Combining Radiological and Genomic TB Portals Data for Drug Resistance Analysis.

Tuberculosis (TB) drug resistance is a worldwide public health problem. It decreases the likelihood of a positive outcome for the individual patient and increases the likelihood of disease spread. Therefore, early detection of TB drug resistance is crucial for improving outcomes and controlling disease transmission. While drug-sensitive tuberculosis cases are declining worldwide because of effective treatment, the threat of drug-resistant tuberculosis is growing, and the success rate of drug-resistant tuberculosis treatment is only around 60%. The TB Portals program provides a publicly accessible repository of TB case data with an emphasis on collecting drug-resistant cases. The dataset includes multi-modal information such as socioeconomic/geographic data, clinical characteristics, pathogen genomics, and radiological features. The program is an international collaboration whose participants are typically under a substantial burden of drug-resistant tuberculosis, with data collected from standard clinical care provided to the patients. Consequentially, the TB Portals dataset is heterogenous in nature, with data representing multiple treatment centers in different countries and containing cross-domain information. This study presents the challenges and methods used to address them when working with this real-world dataset. Our goal was to evaluate whether combining radiological features derived from a chest X-ray of the host and genomic features from the pathogen can potentially improve the identification of the drug susceptibility type, drug-sensitive (DS-TB) or drug-resistant (DR-TB), and the length of the first successful drug regimen. To perform these studies, significantly imbalanced data needed to be processed, which included a much larger number of DR-TB cases than DS-TB, many more cases with radiological findings than genomic ones, and the sparse high dimensional nature of the genomic information. Three evaluation studies were carried out. First, the DR-TB/DS-TB classification model achieved an average accuracy of 92.4% when using genomic features alone or when combining radiological and genomic features. Second, the regression model for the length of the first successful treatment had a relative error of 53.5% using radiological features, 25.6% using genomic features, and 22.0% using both radiological and genomic features. Finally, the relative error of the third regression model predicting the length of the first treatment using the most common drug combination varied depending on the feature type used. When using radiological features alone, the relative error was 17.8%. For genomic features alone, the relative error increased to 19.9%. The model had a relative error of 19.0% when both radiological and genomic features were combined. Although combining radiological and genomic features did not improve upon the use of genomic features when classifying DR-TB/DS-TB, the combination of the two feature types improved the relative error of the predictive model for the length of the first successful treatment. Furthermore, the regression model trained on radiological features achieved the best performance when predicting the treatment length of the most common drug combination.

Generalization Challenges in Drug-Resistant Tuberculosis Detection from Chest X-rays.

Classification of drug-resistant tuberculosis (DR-TB) and drug-sensitive tuberculosis (DS-TB) from chest radiographs remains an open problem. Our previous cross validation performance on publicly available chest X-ray (CXR) data combined with image augmentation, the addition of synthetically generated and publicly available images achieved a performance of 85% AUC with a deep convolutional neural network (CNN). However, when we evaluated the CNN model trained to classify DR-TB and DS-TB on unseen data, significant performance degradation was observed (65% AUC). Hence, in this paper, we investigate the generalizability of our models on images from a held out country's dataset. We explore the extent of the problem and the possible reasons behind the lack of good generalization. A comparison of radiologist-annotated lesion locations in the lung and the trained model's localization of areas of interest, using GradCAM, did not show much overlap. Using the same network architecture, a multi-country classifier was able to identify the country of origin of the X-ray with high accuracy (86%), suggesting that image acquisition differences and the distribution of non-pathological and non-anatomical aspects of the images are affecting the generalization and localization of the drug resistance classification model as well. When CXR images were severely corrupted, the performance on the validation set was still better than 60% AUC. The model overfitted to the data from countries in the cross validation set but did not generalize to the held out country. Finally, we applied a multi-task based approach that uses prior TB lesions location information to guide the classifier network to focus its attention on improving the generalization performance on the held out set from another country to 68% AUC.

Differentiating between drug-sensitive and drug-resistant tuberculosis with machine learning for clinical and radiological features.

BACKGROUND: Tuberculosis (TB) drug resistance is a worldwide public health problem that threatens progress made in TB care and control. Early detection of drug resistance is important for disease control, with discrimination between drug-resistant TB (DR-TB) and drug-sensitive TB (DS-TB) still being an open problem. The objective of this work is to investigate the relevance of readily available clinical data and data derived from chest X-rays (CXRs) in DR-TB prediction and to investigate the possibility of applying machine learning techniques to selected clinical and radiological features for discrimination between DR-TB and DS-TB. We hypothesize that the number of sextants affected by abnormalities such as nodule, cavity, collapse and infiltrate may serve as a radiological feature for DR-TB identification, and that both clinical and radiological features are important factors for machine classification of DR-TB and DS-TB. METHODS: We use data from the NIAID TB Portals program (https://tbportals.niaid.nih.gov), 1,455 DR-TB cases and 782 DS-TB cases from 11 countries. We first select three clinical features and 26 radiological features from the dataset. Then, we perform Pearson's chi-squared test to analyze the significance of the selected clinical and radiological features. Finally, we train machine classifiers based on different features and evaluate their ability to differentiate between DR-TB and DS-TB. RESULTS: Pearson's chi-squared test shows that two clinical features and 23 radiological features are statistically significant regarding DR-TB vs. DS-TB. A ten-fold cross-validation using a support vector machine shows that automatic discrimination between DR-TB and DS-TB achieves an average accuracy of 72.34% and an average AUC value of 78.42%, when combing all 25 statistically significant features. CONCLUSIONS: Our study suggests that the number of affected lung sextants can be used for predicting DR-TB, and that automatic discrimination between DR-TB and DS-TB is possible, with a combination of clinical features and radiological features providing the best performance.

Identifying Drug-Resistant Tuberculosis in Chest Radiographs: Evaluation of CNN Architectures and Training Strategies.

Tuberculosis (TB) is a serious infectious disease that mainly affects the lungs. Drug resistance to the disease makes it more challenging to control. Early diagnosis of drug resistance can help with decision making resulting in appropriate and successful treatment. Chest X-rays (CXRs) have been pivotal to identifying tuberculosis and are widely available. In this work, we utilize CXRs to distinguish between drug-resistant and drug-sensitive tuberculosis. We incorporate Convolutional Neural Network (CNN) based models to discriminate the two types of TB, and employ standard and deep learning based data augmentation methods to improve the classification. Using labeled data from NIAID TB Portals and additional non-labeled sources, we were able to achieve an Area Under the ROC Curve (AUC) of up to 85% using a pretrained InceptionV3 network.