ISLES'24: Improving final infarct prediction in ischemic stroke using multimodal imaging and clinical data

Accurate estimation of core (irreversibly damaged tissue) and penumbra (salvageable tissue) volumes is essential for ischemic stroke treatment decisions. Perfusion CT, the clinical standard, estimates these volumes but is affected by variations in deconvolution algorithms, implementations, and thresholds. Core tissue expands over time, with growth rates influenced by thrombus location, collateral circulation, and inherent patient-specific factors. Understanding this tissue growth is crucial for determining the need to transfer patients to comprehensive stroke centers, predicting the benefits of additional reperfusion attempts during mechanical thrombectomy, and forecasting final clinical outcomes. This work presents the ISLES'24 challenge, which addresses final post-treatment stroke infarct prediction from pre-interventional acute stroke imaging and clinical data. ISLES'24 establishes a unique 360-degree setting where all feasibly accessible clinical data are available for participants, including full CT acute stroke imaging, sub-acute follow-up MRI, and clinical tabular data. The contributions of this work are two-fold: first, we introduce a standardized benchmarking of final stroke infarct segmentation algorithms through the ISLES'24 challenge; second, we provide insights into infarct segmentation using multimodal imaging and clinical data strategies by identifying outperforming methods on a finely curated dataset. The outputs of this challenge are anticipated to enhance clinical decision-making and improve patient outcome predictions. All ISLES'24 materials, including data, performance evaluation scripts, and leading algorithmic strategies, are available to the research community following \url{https://isles-24.grand-challenge.org/}.

ISLES 2024: The first longitudinal multimodal multi-center real-world dataset in (sub-)acute stroke

Stroke remains a leading cause of global morbidity and mortality, placing a heavy socioeconomic burden. Over the past decade, advances in endovascular reperfusion therapy and the use of CT and MRI imaging for treatment guidance have significantly improved patient outcomes and are now standard in clinical practice. To develop machine learning algorithms that can extract meaningful and reproducible models of brain function for both clinical and research purposes from stroke images - particularly for lesion identification, brain health quantification, and prognosis - large, diverse, and well-annotated public datasets are essential. While only a few datasets with (sub-)acute stroke data were previously available, several large, high-quality datasets have recently been made publicly accessible. However, these existing datasets include only MRI data. In contrast, our dataset is the first to offer comprehensive longitudinal stroke data, including acute CT imaging with angiography and perfusion, follow-up MRI at 2-9 days, as well as acute and longitudinal clinical data up to a three-month outcome. The dataset includes a training dataset of n = 150 and a test dataset of n = 100 scans. Training data is publicly available, while test data will be used exclusively for model validation. We are making this dataset available as part of the 2024 edition of the Ischemic Stroke Lesion Segmentation (ISLES) challenge (https://www.isles-challenge.org/), which continuously aims to establish benchmark methods for acute and sub-acute ischemic stroke lesion segmentation, aiding in creating open stroke imaging datasets and evaluating cutting-edge image processing algorithms.

Don't You (Project Around Discs)? Neural Network Surrogate and Projected Gradient Descent for Calibrating an Intervertebral Disc Finite Element Model

Accurate calibration of finite element (FE) models of human intervertebral discs (IVDs) is essential for their reliability and application in diagnosing and planning treatments for spinal conditions. Traditional calibration methods are computationally intensive, requiring iterative, derivative-free optimization algorithms that often take hours or days to converge. This study addresses these challenges by introducing a novel, efficient, and effective calibration method for an L4-L5 IVD FE model using a neural network (NN) surrogate. The NN surrogate predicts simulation outcomes with high accuracy, outperforming other machine learning models, and significantly reduces the computational cost associated with traditional FE simulations. Next, a Projected Gradient Descent (PGD) approach guided by gradients of the NN surrogate is proposed to efficiently calibrate FE models. Our method explicitly enforces feasibility with a projection step, thus maintaining material bounds throughout the optimization process. The proposed method is evaluated against state-of-the-art Genetic Algorithm (GA) and inverse model baselines on synthetic and in vitro experimental datasets. Our approach demonstrates superior performance on synthetic data, achieving a Mean Absolute Error (MAE) of 0.06 compared to the baselines' MAE of 0.18 and 0.54, respectively. On experimental specimens, our method outperforms the baseline in 5 out of 6 cases. Most importantly, our approach reduces calibration time to under three seconds, compared to up to 8 days per sample required by traditional calibration. Such efficiency paves the way for applying more complex FE models, enabling accurate patient-specific simulations and advancing spinal treatment planning.

Counterfactual Explanations for Medical Image Classification and Regression using Diffusion Autoencoder

Counterfactual explanations (CEs) aim to enhance the interpretability of machine learning models by illustrating how alterations in input features would affect the resulting predictions. Common CE approaches require an additional model and are typically constrained to binary counterfactuals. In contrast, we propose a novel method that operates directly on the latent space of a generative model, specifically a Diffusion Autoencoder (DAE). This approach offers inherent interpretability by enabling the generation of CEs and the continuous visualization of the model's internal representation across decision boundaries. Our method leverages the DAE's ability to encode images into a semantically rich latent space in an unsupervised manner, eliminating the need for labeled data or separate feature extraction models. We show that these latent representations are helpful for medical condition classification and the ordinal regression of severity pathologies, such as vertebral compression fractures (VCF) and diabetic retinopathy (DR). Beyond binary CEs, our method supports the visualization of ordinal CEs using a linear model, providing deeper insights into the model's decision-making process and enhancing interpretability. Experiments across various medical imaging datasets demonstrate the method's advantages in interpretability and versatility. The linear manifold of the DAE's latent space allows for meaningful interpolation and manipulation, making it a powerful tool for exploring medical image properties. Our code is available at https://github.com/matanat/dae_counterfactual.

A Robust Ensemble Algorithm for Ischemic Stroke Lesion Segmentation: Generalizability and Clinical Utility Beyond the ISLES Challenge

Diffusion-weighted MRI (DWI) is essential for stroke diagnosis, treatment decisions, and prognosis. However, image and disease variability hinder the development of generalizable AI algorithms with clinical value. We address this gap by presenting a novel ensemble algorithm derived from the 2022 Ischemic Stroke Lesion Segmentation (ISLES) challenge. ISLES'22 provided 400 patient scans with ischemic stroke from various medical centers, facilitating the development of a wide range of cutting-edge segmentation algorithms by the research community. Through collaboration with leading teams, we combined top-performing algorithms into an ensemble model that overcomes the limitations of individual solutions. Our ensemble model achieved superior ischemic lesion detection and segmentation accuracy on our internal test set compared to individual algorithms. This accuracy generalized well across diverse image and disease variables. Furthermore, the model excelled in extracting clinical biomarkers. Notably, in a Turing-like test, neuroradiologists consistently preferred the algorithm's segmentations over manual expert efforts, highlighting increased comprehensiveness and precision. Validation using a real-world external dataset (N=1686) confirmed the model's generalizability. The algorithm's outputs also demonstrated strong correlations with clinical scores (admission NIHSS and 90-day mRS) on par with or exceeding expert-derived results, underlining its clinical relevance. This study offers two key findings. First, we present an ensemble algorithm (https://github.com/Tabrisrei/ISLES22_Ensemble) that detects and segments ischemic stroke lesions on DWI across diverse scenarios on par with expert (neuro)radiologists. Second, we show the potential for biomedical challenge outputs to extend beyond the challenge's initial objectives, demonstrating their real-world clinical applicability.

SPINEPS -- Automatic Whole Spine Segmentation of T2-weighted MR images using a Two-Phase Approach to Multi-class Semantic and Instance Segmentation

Purpose. To present SPINEPS, an open-source deep learning approach for semantic and instance segmentation of 14 spinal structures (ten vertebra substructures, intervertebral discs, spinal cord, spinal canal, and sacrum) in whole body T2w MRI. Methods. During this HIPPA-compliant, retrospective study, we utilized the public SPIDER dataset (218 subjects, 63% female) and a subset of the German National Cohort (1423 subjects, mean age 53, 49% female) for training and evaluation. We combined CT and T2w segmentations to train models that segment 14 spinal structures in T2w sagittal scans both semantically and instance-wise. Performance evaluation metrics included Dice similarity coefficient, average symmetrical surface distance, panoptic quality, segmentation quality, and recognition quality. Statistical significance was assessed using the Wilcoxon signed-rank test. An in-house dataset was used to qualitatively evaluate out-of-distribution samples. Results. On the public dataset, our approach outperformed the baseline (instance-wise vertebra dice score 0.929 vs. 0.907, p-value<0.001). Training on auto-generated annotations and evaluating on manually corrected test data from the GNC yielded global dice scores of 0.900 for vertebrae, 0.960 for intervertebral discs, and 0.947 for the spinal canal. Incorporating the SPIDER dataset during training increased these scores to 0.920, 0.967, 0.958, respectively. Conclusions. The proposed segmentation approach offers robust segmentation of 14 spinal structures in T2w sagittal images, including the spinal cord, spinal canal, intervertebral discs, endplate, sacrum, and vertebrae. The approach yields both a semantic and instance mask as output, thus being easy to utilize. This marks the first publicly available algorithm for whole spine segmentation in sagittal T2w MR imaging.

Benchmarking the CoW with the TopCoW Challenge: Topology-Aware Anatomical Segmentation of the Circle of Willis for CTA and MRA

The Circle of Willis (CoW) is an important network of arteries connecting major circulations of the brain. Its vascular architecture is believed to affect the risk, severity, and clinical outcome of serious neuro-vascular diseases. However, characterizing the highly variable CoW anatomy is still a manual and time-consuming expert task. The CoW is usually imaged by two angiographic imaging modalities, magnetic resonance angiography (MRA) and computed tomography angiography (CTA), but there exist limited public datasets with annotations on CoW anatomy, especially for CTA. Therefore we organized the TopCoW Challenge in 2023 with the release of an annotated CoW dataset and invited submissions worldwide for the CoW segmentation task, which attracted over 140 registered participants from four continents. TopCoW dataset was the first public dataset with voxel-level annotations for CoW's 13 vessel components, made possible by virtual-reality (VR) technology. It was also the first dataset with paired MRA and CTA from the same patients. TopCoW challenge aimed to tackle the CoW characterization problem as a multiclass anatomical segmentation task with an emphasis on topological metrics. The top performing teams managed to segment many CoW components to Dice scores around 90%, but with lower scores for communicating arteries and rare variants. There were also topological mistakes for predictions with high Dice scores. Additional topological analysis revealed further areas for improvement in detecting certain CoW components and matching CoW variant's topology accurately. TopCoW represented a first attempt at benchmarking the CoW anatomical segmentation task for MRA and CTA, both morphologically and topologically.

Panoptica -- instance-wise evaluation of 3D semantic and instance segmentation maps

This paper introduces panoptica, a versatile and performance-optimized package designed for computing instance-wise segmentation quality metrics from 2D and 3D segmentation maps. panoptica addresses the limitations of existing metrics and provides a modular framework that complements the original intersection over union-based panoptic quality with other metrics, such as the distance metric Average Symmetric Surface Distance. The package is open-source, implemented in Python, and accompanied by comprehensive documentation and tutorials. panoptica employs a three-step metrics computation process to cover diverse use cases. The efficacy of panoptica is demonstrated on various real-world biomedical datasets, where an instance-wise evaluation is instrumental for an accurate representation of the underlying clinical task. Overall, we envision panoptica as a valuable tool facilitating in-depth evaluation of segmentation methods.

3D Arterial Segmentation via Single 2D Projections and Depth Supervision in Contrast-Enhanced CT Images

Automated segmentation of the blood vessels in 3D volumes is an essential step for the quantitative diagnosis and treatment of many vascular diseases. 3D vessel segmentation is being actively investigated in existing works, mostly in deep learning approaches. However, training 3D deep networks requires large amounts of manual 3D annotations from experts, which are laborious to obtain. This is especially the case for 3D vessel segmentation, as vessels are sparse yet spread out over many slices and disconnected when visualized in 2D slices. In this work, we propose a novel method to segment the 3D peripancreatic arteries solely from one annotated 2D projection per training image with depth supervision. We perform extensive experiments on the segmentation of peripancreatic arteries on 3D contrast-enhanced CT images and demonstrate how well we capture the rich depth information from 2D projections. We demonstrate that by annotating a single, randomly chosen projection for each training sample, we obtain comparable performance to annotating multiple 2D projections, thereby reducing the annotation effort. Furthermore, by mapping the 2D labels to the 3D space using depth information and incorporating this into training, we almost close the performance gap between 3D supervision and 2D supervision. Our code is available at: https://github.com/alinafdima/3Dseg-mip-depth.

Framing image registration as a landmark detection problem for better representation of clinical relevance

Nowadays, registration methods are typically evaluated based on sub-resolution tracking error differences. In an effort to reinfuse this evaluation process with clinical relevance, we propose to reframe image registration as a landmark detection problem. Ideally, landmark-specific detection thresholds are derived from an inter-rater analysis. To approximate this costly process, we propose to compute hit rate curves based on the distribution of errors of a sub-sample inter-rater analysis. Therefore, we suggest deriving thresholds from the error distribution using the formula: median + delta * median absolute deviation. The method promises differentiation of previously indistinguishable registration algorithms and further enables assessing the clinical significance in algorithm development.