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.

Cross-domain and Cross-dimension Learning for Image-to-Graph Transformers

Direct image-to-graph transformation is a challenging task that solves object detection and relationship prediction in a single model. Due to the complexity of this task, large training datasets are rare in many domains, which makes the training of large networks challenging. This data sparsity necessitates the establishment of pre-training strategies akin to the state-of-the-art in computer vision. In this work, we introduce a set of methods enabling cross-domain and cross-dimension transfer learning for image-to-graph transformers. We propose (1) a regularized edge sampling loss for sampling the optimal number of object relationships (edges) across domains, (2) a domain adaptation framework for image-to-graph transformers that aligns features from different domains, and (3) a simple projection function that allows us to pretrain 3D transformers on 2D input data. We demonstrate our method's utility in cross-domain and cross-dimension experiments, where we pretrain our models on 2D satellite images before applying them to vastly different target domains in 2D and 3D. Our method consistently outperforms a series of baselines on challenging benchmarks, such as retinal or whole-brain vessel graph extraction.

A Learnable Prior Improves Inverse Tumor Growth Modeling

Biophysical modeling, particularly involving partial differential equations (PDEs), offers significant potential for tailoring disease treatment protocols to individual patients. However, the inverse problem-solving aspect of these models presents a substantial challenge, either due to the high computational requirements of model-based approaches or the limited robustness of deep learning (DL) methods. We propose a novel framework that leverages the unique strengths of both approaches in a synergistic manner. Our method incorporates a DL ensemble for initial parameter estimation, facilitating efficient downstream evolutionary sampling initialized with this DL-based prior. We showcase the effectiveness of integrating a rapid deep-learning algorithm with a high-precision evolution strategy in estimating brain tumor cell concentrations from magnetic resonance images. The DL-Prior plays a pivotal role, significantly constraining the effective sampling-parameter space. This reduction results in a fivefold convergence acceleration and a Dice-score of 95%

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.

Personalized Predictions of Glioblastoma Infiltration: Mathematical Models, Physics-Informed Neural Networks and Multimodal Scans

Predicting the infiltration of Glioblastoma (GBM) from medical MRI scans is crucial for understanding tumor growth dynamics and designing personalized radiotherapy treatment plans.Mathematical models of GBM growth can complement the data in the prediction of spatial distributions of tumor cells. However, this requires estimating patient-specific parameters of the model from clinical data, which is a challenging inverse problem due to limited temporal data and the limited time between imaging and diagnosis. This work proposes a method that uses Physics-Informed Neural Networks (PINNs) to estimate patient-specific parameters of a reaction-diffusion PDE model of GBM growth from a single 3D structural MRI snapshot. PINNs embed both the data and the PDE into a loss function, thus integrating theory and data. Key innovations include the identification and estimation of characteristic non-dimensional parameters, a pre-training step that utilizes the non-dimensional parameters and a fine-tuning step to determine the patient specific parameters. Additionally, the diffuse domain method is employed to handle the complex brain geometry within the PINN framework. Our method is validated both on synthetic and patient datasets, and shows promise for real-time parametric inference in the clinical setting for personalized GBM treatment.

Shallow learning enables real-time inference of molecular composition changes from broadband-near-infrared spectroscopy of brain tissue

Spectroscopy-based imaging modalities such as near-infrared spectroscopy (NIRS) and hyperspectral imaging (HSI) represent a promising alternative for low-cost, non-invasive, and fast monitoring of functional and structural properties of living tissue. Particularly, the possibility of extracting the molecular composition of the tissue from the optical spectra in real-time deems the spectroscopy techniques as unique diagnostic tools. However, due to the highly limited availability of paired optical and molecular profiling studies, building a mapping between a spectral signature and a corresponding set of molecular concentrations is still an unsolved problem. Moreover, there are no yet established methods to streamline inference of the biochemical composition from the optical spectrum for real-time applications such as surgical monitoring. In this paper, we develop a technique for fast inference of changes in the molecular composition of brain tissue. We base our method on the Beer-Lambert law to analytically connect the spectra with concentrations and use a deep-learning approach to significantly speed up the concentration inference compared to traditional optimization methods. We test our approach on real data obtained from the broadband NIRS study of piglets' brains. The results demonstrate that the proposed method enables real-time molecular composition inference while maintaining the accuracy of traditional optimization.

A skeletonization algorithm for gradient-based optimization

The skeleton of a digital image is a compact representation of its topology, geometry, and scale. It has utility in many computer vision applications, such as image description, segmentation, and registration. However, skeletonization has only seen limited use in contemporary deep learning solutions. Most existing skeletonization algorithms are not differentiable, making it impossible to integrate them with gradient-based optimization. Compatible algorithms based on morphological operations and neural networks have been proposed, but their results often deviate from the geometry and topology of the true medial axis. This work introduces the first three-dimensional skeletonization algorithm that is both compatible with gradient-based optimization and preserves an object's topology. Our method is exclusively based on matrix additions and multiplications, convolutional operations, basic non-linear functions, and sampling from a uniform probability distribution, allowing it to be easily implemented in any major deep learning library. In benchmarking experiments, we prove the advantages of our skeletonization algorithm compared to non-differentiable, morphological, and neural-network-based baselines. Finally, we demonstrate the utility of our algorithm by integrating it with two medical image processing applications that use gradient-based optimization: deep-learning-based blood vessel segmentation, and multimodal registration of the mandible in computed tomography and magnetic resonance images.

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.