COVID-19 has caused a global pandemic and become the most urgent threat to the entire world. Tremendous efforts and resources have been invested in developing diagnosis, prognosis and treatment strategies to combat the disease. Although nucleic acid detection has been mainly used as the gold standard to confirm this RNA virus-based disease, it has been shown that such a strategy has a high false negative rate, especially for patients in the early stage, and thus CT imaging has been applied as a major diagnostic modality in confirming positive COVID-19. Despite the various, urgent advances in developing artificial intelligence (AI)-based computer-aided systems for CT-based COVID-19 diagnosis, most of the existing methods can only perform classification, whereas the state-of-the-art segmentation method requires a high level of human intervention. In this paper, we propose a fully-automatic, rapid, accurate, and machine-agnostic method that can segment and quantify the infection regions on CT scans from different sources. Our method is founded upon two innovations: 1) the first CT scan simulator for COVID-19, by fitting the dynamic change of real patients' data measured at different time points, which greatly alleviates the data scarcity issue; and 2) a novel deep learning algorithm to solve the large-scene-small-object problem, which decomposes the 3D segmentation problem into three 2D ones, and thus reduces the model complexity by an order of magnitude and, at the same time, significantly improves the segmentation accuracy. Comprehensive experimental results over multi-country, multi-hospital, and multi-machine datasets demonstrate the superior performance of our method over the existing ones and suggest its important application value in combating the disease.

Pulmonary artery-vein segmentation is critical for disease diagnosis and surgical planning. Traditional methods rely on Computed Tomography Pulmonary Angiography (CTPA), which requires contrast agents with potential health risks. Non-contrast CT, a safer and more widely available approach, however, has long been considered impossible for this task. Here we propose High-abundant Pulmonary Artery-vein Segmentation (HiPaS), enabling accurate segmentation across both non-contrast CT and CTPA at multiple resolutions. HiPaS integrates spatial normalization with an iterative segmentation strategy, leveraging lower-level vessel segmentations as priors for higher-level segmentations. Trained on a multi-center dataset comprising 1073 CT volumes with manual annotations, HiPaS achieves superior performance (dice score: 91.8%, sensitivity: 98.0%) and demonstrates non-inferiority on non-contrast CT compared to CTPA. Furthermore, HiPaS enables large-scale analysis of 11,784 participants, revealing associations between vessel abundance and sex, age, and diseases, under lung-volume control. HiPaS represents a promising, non-invasive approach for clinical diagnostics and anatomical research.

Tremendous efforts have been made to improve diagnosis and treatment of COVID-19, but knowledge on long-term complications is limited. In particular, a large portion of survivors has respiratory complications, but currently, experienced radiologists and state-of-the-art artificial intelligence systems are not able to detect many abnormalities from follow-up computerized tomography (CT) scans of COVID-19 survivors. Here we propose Deep-LungParenchyma-Enhancing (DLPE), a computer-aided detection (CAD) method for detecting and quantifying pulmonary parenchyma lesions on chest CT. Through proposing a number of deep-learning-based segmentation models and assembling them in an interpretable manner, DLPE removes irrelevant tissues from the perspective of pulmonary parenchyma, and calculates the scan-level optimal window, which considerably enhances parenchyma lesions relative to the lung window. Aided by DLPE, radiologists discovered novel and interpretable lesions from COVID-19 inpatients and survivors, which were previously invisible under the lung window. Based on DLPE, we removed the scan-level bias of CT scans, and then extracted precise radiomics from such novel lesions. We further demonstrated that these radiomics have strong predictive power for key COVID-19 clinical metrics on an inpatient cohort of 1,193 CT scans and for sequelae on a survivor cohort of 219 CT scans. Our work sheds light on the development of interpretable medical artificial intelligence and showcases how artificial intelligence can discover medical findings that are beyond sight.