Odyssée Merveille

Morgane des Ligneris, Nathan Painchaud, Allan Serva et al.

Pulmonary embolism, the obstruction of a pulmonary artery by a blood clot, is one of the leading causes of acute cardiovascular syndrome. In clinical practice, therapeutic decisions after diagnosis via computed tomography pulmonary angiography rely on risk stratification, which categorizes 30-day mortality risk into three categories. This stratification depends on the right-to-left ventricular diameter ratio and blood levels of two cardiac enzymes. However, blood biomarkers are not always available in emergency settings, and manual calculation of established severity scores - such as Qanadli and Mastora - is time-consuming and rarely performed in clinical routine practice. This study introduces an automated pipeline that models a directed graph representation of the pulmonary arterial tree, labeling its hierarchical structure and characterizing pulmonary embolism. The pipeline derives image-based biomarkers, including local artery-level features (morphological information, hierarchical position, clot volume, and resulting obstruction) and global patient-level biomarkers such as automatically calculated severity scores (Qanadli and Mastora) and the total embolic volume distribution by lobes and hierarchical levels. Using artificial-intelligence-generated binary masks of arteries, emboli, lungs, and lobes, it creates a patient digital twin of the arterial structure. Validation of the pipeline through comparison to an existing pipeline, anatomical expectations, and manual severity score calculations demonstrates the pipeline's ability to automatically generate anatomically accurate digital twins and severity scores with strong agreement. This supports the potential of these image-derived biomarkers to automatically provide rapid, precise information on thrombotic burden and spatial clot distribution.

Pierre Rougé, Nicolas Passat, Odyssée Merveille

Vessel segmentation and centerline extraction are two crucial preliminary tasks for many computer-aided diagnosis tools dealing with vascular diseases. Recently, deep-learning based methods have been widely applied to these tasks. However, classic deep-learning approaches struggle to capture the complex geometry and specific topology of vascular networks, which is of the utmost importance in most applications. To overcome these limitations, the clDice loss, a topological loss that focuses on the vessel centerlines, has been recently proposed. This loss requires computing, with a proposed soft-skeleton algorithm, the skeletons of both the ground truth and the predicted segmentation. However, the soft-skeleton algorithm provides suboptimal results on 3D images, which makes the clDice hardly suitable on 3D images. In this paper, we propose to replace the soft-skeleton algorithm by a U-Net which computes the vascular skeleton directly from the segmentation. We show that our method provides more accurate skeletons than the soft-skeleton algorithm. We then build upon this network a cascaded U-Net trained with the clDice loss to embed topological constraints during the segmentation. The resulting model is able to predict both the vessel segmentation and centerlines with a more accurate topology.

Nathan Painchaud, Tristan Habémont, Morgane des Ligneris et al.

Risk stratification for pulmonary embolism (PE) is critical for clinical decision-making. Stratification guidelines are based on patient medical records, parameters measured from computed tomography pulmonary angiography (CTPA), and blood tests. However, blood tests are often missing in routine practice. This work studies whether state-of-the-art models can accurately classify risk stratification from only medical records and biomarkers extracted from CTPA images. We benchmark different approaches to combine medical records and cardiac biomarkers with rich pulmonary vascular information; we add vascular biomarkers to tabular models and apply graph neural networks (GNNs) on the vascular tree's intrinsic graph representation. We use a private dataset (n=353) with uniquely complete data for PE risk stratification. Our results show that, among global features, medical records and cardiac biomarkers are the most significant predictors, while vascular biomarkers do not further improve stratification. Even more surprising, even GNNs on vascular graphs fail to outperform strong tabular baseline on global features. We consider hypotheses, on both models and data, that could explain this suboptimal performance. Our investigation suggests that, counter-intuitively, vascular graphs might hold no discriminative information for PE risk stratification. Code is available from https://github.com/creatis-myriad/GENESIS.

Pierre Rougé, Pierre-Henri Conze, Nicolas Passat et al.

Segmentation in medical imaging is an essential and often preliminary task in the image processing chain, driving numerous efforts towards the design of robust segmentation algorithms. Supervised learning methods achieve excellent performances when fed with a sufficient amount of labeled data. However, such labels are typically highly time-consuming, error-prone and expensive to produce. Alternatively, semi-supervised learning approaches leverage both labeled and unlabeled data, and are very useful when only a small fraction of the dataset is labeled. They are particularly useful for cerebrovascular segmentation, given that labeling a single volume requires several hours for an expert. In addition to the challenge posed by insufficient annotations, there are concerns regarding annotation consistency. The task of annotating the cerebrovascular tree is inherently ambiguous. Due to the discrete nature of images, the borders and extremities of vessels are often unclear. Consequently, annotations heavily rely on the expert subjectivity and on the underlying clinical objective. These discrepancies significantly increase the complexity of the segmentation task for the model and consequently impair the results. Consequently, it becomes imperative to provide clinicians with precise guidelines to improve the annotation process and construct more uniform datasets. In this article, we investigate the data dependency of deep learning methods within the context of imperfect data and semi-supervised learning, for cerebrovascular segmentation. Specifically, this study compares various state-of-the-art semi-supervised methods based on unsupervised regularization and evaluates their performance in diverse quantity and quality data scenarios. Based on these experiments, we provide guidelines for the annotation and training of cerebrovascular segmentation models.

Odyssee Merveille, Thomas Lampert, Jessica Schmitz et al.

Objective: This article presents an automatic image processing framework to extract quantitative high-level information describing the micro-environment of glomeruli in consecutive whole slide images (WSIs) processed with different staining modalities of patients with chronic kidney rejection after kidney transplantation. Methods: This four-step framework consists of: 1) approximate rigid registration, 2) cell and anatomical structure segmentation 3) fusion of information from different stainings using a newly developed registration algorithm 4) feature extraction. Results: Each step of the framework is validated independently both quantitatively and qualitatively by pathologists. An illustration of the different types of features that can be extracted is presented. Conclusion: The proposed generic framework allows for the analysis of the micro-environment surrounding large structures that can be segmented (either manually or automatically). It is independent of the segmentation approach and is therefore applicable to a variety of biomedical research questions. Significance: Chronic tissue remodelling processes after kidney transplantation can result in interstitial fibrosis and tubular atrophy (IFTA) and glomerulosclerosis. This pipeline provides tools to quantitatively analyse, in the same spatial context, information from different consecutive WSIs and help researchers understand the complex underlying mechanisms leading to IFTA and glomerulosclerosis.

Thomas Lampert, Odyssée Merveille, Jessica Schmitz et al.

An important part of Digital Pathology is the analysis of multiple digitised whole slide images from differently stained tissue sections. It is common practice to mount consecutive sections containing corresponding microscopic structures on glass slides, and to stain them differently to highlight specific tissue components. These multiple staining modalities result in very different images but include a significant amount of consistent image information. Deep learning approaches have recently been proposed to analyse these images in order to automatically identify objects of interest for pathologists. These supervised approaches require a vast amount of annotations, which are difficult and expensive to acquire---a problem that is multiplied with multiple stainings. This article presents several training strategies that make progress towards stain invariant networks. By training the network on one commonly used staining modality and applying it to images that include corresponding but differently stained tissue structures, the presented unsupervised strategies demonstrate significant improvements over standard training strategies.