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In this paper, we propose a methodology for extracting molecular tumor biomarkers from hyperspectral imaging (HSI), an emerging technology for intraoperative tissue assessment. To achieve this, we employ spectral unmixing, allowing to decompose the spectral signals recorded by the HSI camera into their constituent molecular components. Traditional unmixing approaches are based on physical models that establish a relationship between tissue molecules and the recorded spectra. However, these methods commonly assume a linear relationship between the spectra and molecular content, which does not capture the whole complexity of light-matter interaction. To address this limitation, we introduce a novel unmixing procedure that allows to take into account non-linear optical effects while preserving the computational benefits of linear spectral unmixing. We validate our methodology on an in-vivo brain tissue HSI dataset and demonstrate that the extracted molecular information leads to superior classification performance.

Glioblastoma, a highly aggressive brain tumor, poses major challenges due to its poor prognosis and high morbidity rates. Partial differential equation-based models offer promising potential to enhance therapeutic outcomes by simulating patient-specific tumor behavior for improved radiotherapy planning. However, model calibration remains a bottleneck due to the high computational demands of optimization methods like Monte Carlo sampling and evolutionary algorithms. To address this, we recently introduced an approach leveraging a neural forward solver with gradient-based optimization to significantly reduce calibration time. This approach requires a highly accurate and fully differentiable forward model. We investigate multiple architectures, including (i) an enhanced TumorSurrogate, (ii) a modified nnU-Net, and (iii) a 3D Vision Transformer (ViT). The optimized TumorSurrogate achieved the best overall results, excelling in both tumor outline matching and voxel-level prediction of tumor cell concentration. It halved the MSE relative to the baseline model and achieved the highest Dice score across all tumor cell concentration thresholds. Our study demonstrates significant enhancement in forward solver performance and outlines important future research directions.

Biophysical modeling of brain tumors has emerged as a promising strategy for personalizing radiotherapy planning by estimating the otherwise hidden distribution of tumor cells within the brain. However, many existing state-of-the-art methods are computationally intensive, limiting their widespread translation into clinical practice. In this work, we propose an efficient and direct method that utilizes soft physical constraints to estimate the tumor cell concentration from preoperative MRI of brain tumor patients. Our approach optimizes a 3D tumor concentration field by simultaneously minimizing the difference between the observed MRI and a physically informed loss function. Compared to existing state-of-the-art techniques, our method significantly improves predicting tumor recurrence on two public datasets with a total of 192 patients while maintaining a clinically viable runtime of under one minute - a substantial reduction from the 30 minutes required by the current best approach. Furthermore, we showcase the generalizability of our framework by incorporating additional imaging information and physical constraints, highlighting its potential to translate to various medical diffusion phenomena with imperfect data.

This paper presents FedPID, our submission to the Federated Tumor Segmentation Challenge 2024 (FETS24). Inspired by FedCostWAvg and FedPIDAvg, our winning contributions to FETS21 and FETS2022, we propose an improved aggregation strategy for federated and collaborative learning. FedCostWAvg is a method that averages results by considering both the number of training samples in each group and how much the cost function decreased in the last round of training. This is similar to how the derivative part of a PID controller works. In FedPIDAvg, we also included the integral part that was missing. Another challenge we faced were vastly differing dataset sizes at each center. We solved this by assuming the sizes follow a Poisson distribution and adjusting the training iterations for each center accordingly. Essentially, this part of the method controls that outliers that require too much training time are less frequently used. Based on these contributions we now adapted FedPIDAvg by changing how the integral part is computed. Instead of integrating the loss function we measure the global drop in cost since the first round.

High-throughput image analysis in the biomedical domain has gained significant attention in recent years, driving advancements in drug discovery, disease prediction, and personalized medicine. Organoids, specifically, are an active area of research, providing excellent models for human organs and their functions. Automating the quantification of organoids in microscopy images would provide an effective solution to overcome substantial manual quantification bottlenecks, particularly in high-throughput image analysis. However, there is a notable lack of open biomedical datasets, in contrast to other domains, such as autonomous driving, and, notably, only few of them have attempted to quantify annotation uncertainty. In this work, we present MultiOrg a comprehensive organoid dataset tailored for object detection tasks with uncertainty quantification. This dataset comprises over 400 high-resolution 2d microscopy images and curated annotations of more than 60,000 organoids. Most importantly, it includes three label sets for the test data, independently annotated by two experts at distinct time points. We additionally provide a benchmark for organoid detection, and make the best model available through an easily installable, interactive plugin for the popular image visualization tool Napari, to perform organoid quantification.

Physical models in the form of partial differential equations serve as important priors for many under-constrained problems. One such application is tumor treatment planning, which relies on accurately estimating the spatial distribution of tumor cells within a patient's anatomy. While medical imaging can detect the bulk of a tumor, it cannot capture the full extent of its spread, as low-concentration tumor cells often remain undetectable, particularly in glioblastoma, the most common primary brain tumor. Machine learning approaches struggle to estimate the complete tumor cell distribution due to a lack of appropriate training data. Consequently, most existing methods rely on physics-based simulations to generate anatomically and physiologically plausible estimations. However, these approaches face challenges with complex and unknown initial conditions and are constrained by overly rigid physical models. In this work, we introduce a novel method that integrates data-driven and physics-based cost functions, akin to Physics-Informed Neural Networks (PINNs). However, our approach parametrizes the solution directly on a dynamic discrete mesh, allowing for the effective modeling of complex biomechanical behaviors. Specifically, we propose a unique discretization scheme that quantifies how well the learned spatiotemporal distributions of tumor and brain tissues adhere to their respective growth and elasticity equations. This quantification acts as a regularization term, offering greater flexibility and improved integration of patient data compared to existing models. We demonstrate enhanced coverage of tumor recurrence areas using real-world data from a patient cohort, highlighting the potential of our method to improve model-driven treatment planning for glioblastoma in clinical practice., Comment: Accepted to NeurIPS 2024

Accurate calibration of finite element (FE) models is essential across various biomechanical applications, including human intervertebral discs (IVDs), to ensure their reliability and use in diagnosing and planning treatments. However, traditional calibration methods are computationally intensive, requiring iterative, derivative-free optimization algorithms that often take days to converge. This study addresses these challenges by introducing a novel, efficient, and effective calibration method demonstrated on a human L4-L5 IVD FE model as a case study 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 SOTA Genetic Algorithm and inverse model baselines on synthetic and in vitro experimental datasets. Our approach demonstrates superior performance on synthetic data, achieving an 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. While our approach requires initial dataset generation and surrogate training, these steps are performed only once, and the actual calibration takes under three seconds. In contrast, traditional calibration time scales linearly with the number of specimens, taking up to 8 days in the worst-case. Such efficiency paves the way for applying more complex FE models, potentially extending beyond IVDs, and enabling accurate patient-specific simulations., Comment: In review. Project code: https://github.com/matanat/IVD-CalibNN/

Pediatric central nervous system tumors are the leading cause of cancer-related deaths in children. The five-year survival rate for high-grade glioma in children is less than 20%. The development of new treatments is dependent upon multi-institutional collaborative clinical trials requiring reproducible and accurate centralized response assessment. We present the results of the BraTS-PEDs 2023 challenge, the first Brain Tumor Segmentation (BraTS) challenge focused on pediatric brain tumors. This challenge utilized data acquired from multiple international consortia dedicated to pediatric neuro-oncology and clinical trials. BraTS-PEDs 2023 aimed to evaluate volumetric segmentation algorithms for pediatric brain gliomas from magnetic resonance imaging using standardized quantitative performance evaluation metrics employed across the BraTS 2023 challenges. The top-performing AI approaches for pediatric tumor analysis included ensembles of nnU-Net and Swin UNETR, Auto3DSeg, or nnU-Net with a self-supervised framework. The BraTSPEDs 2023 challenge fostered collaboration between clinicians (neuro-oncologists, neuroradiologists) and AI/imaging scientists, promoting faster data sharing and the development of automated volumetric analysis techniques. These advancements could significantly benefit clinical trials and improve the care of children with brain tumors.

In this article we consider spherical hypersurfaces in $\mathbb C^2$ with a fixed Reeb vector field as 3-dimensional Sasakian manifolds. We establish the correspondence between three different sets of parameters, namely, those arising from representing the Reeb vector field as an automorphism of the Heisenberg sphere, the parameters used in Stanton's description of rigid spheres, and the parameters arising from the rigid normal forms. We also geometrically describe the moduli space for rigid spheres, and provide geometric distinction between Stanton's hypersurfaces and those found by Ezhov and Schmalz. Finally, we determine the Sasakian automorphism groups of the rigid spheres and detect the homogeneous Sasakian manifolds among them.

Intraoperative optical imaging is a localization technique for the functional areas of the human brain cortex during neurosurgical procedures. These areas can be assessed by monitoring cerebral hemodynamics and metabolism. A robust quantification of these biomarkers is complicated to perform during neurosurgery due to the critical context of the operating room. In actual devices, the inhomogeneities of the optical properties of exposed brain cortex are poorly taken into consideration, which introduce quantification errors of biomarkers of brain functionality. Moreover, the choice of the best spectral configuration is still based on an empirical approach. We propose a digital instrument simulator to optimize the development of hyperspectral systems. This simulator can provide a realistic modelling of the cerebral cortex and the identification of the optimal wavelengths to monitor cerebral hemodynamics (oxygenated and deoxygenated hemoglobin) and metabolism (oxidized state of cytochromes b, c and cytochrome-c-oxidase). The digital instrument allows the modelling of intensity maps collected by a camera sensor as well as images of pathlength to take into account the inhomogeneities of the optical properties. The optimization procedure helps to identify the best wavelength combination of 18 wavelengths that reduce the quantification errors in HbO2, Hb, oxCCO of 61%, 29% and 82% compared to the gold standard of 121 wavelengths between 780 and 900 nm. The optimization procedure does not help to resolve changes in cytochrome b and c in a significant way but help to better resolve oxCCO changes. We proposed a digital instrument simulator to optimize the development of hyperspectral systems for intraoperative brain mapping studies. This digital instrument simulator and this optimization framework could be used to optimize the design of hyperspectral imaging devices.

Histopathological examination of surgical biopsies, such as in glioma and glioblastoma resection, is hindered in current clinical practice by the long times required for the laboratory analysis and pathological screening, typically taking several days or even weeks to be completed. We propose here a transportable, high-density, spectral-scanning based hyperspectral imaging setup, named HyperProbe1, that can provide in situ, fast biochemical analysis and mapping of fresh surgical tissue samples, right after excision, and without the need of fixing or staining. HyperProbe1 is based on spectral scanning via supercontinuum laser illumination filtered with acousto-optic tuneable filters. Such methodology allows the user to select any number and type of wavelength bands in the visible and near-infrared range between 510 and 900 nm (up to 79), and to reconstruct 3D hypercubes composed of high-resolution, widefield images of the surgical samples, where each pixel is associated with a complete spectrum. The system is applied on 11 fresh surgical biopsies of glioma from routine patients, including different grades of tumour classification. Quantitative analysis of the composition of the tissue is performed via fast spectral unmixing to reconstruct mapping of major biomarkers. We also provided a preliminary attempt to infer tumour classification based on differences of composition in the samples, suggesting the possibility to use lipid content and differential cytochrome-c-oxidase concentrations to distinguish between lower and higher grade gliomas. A proof-of-concept of the performances of HyperProbe1 for quantitative, biochemical mapping of surgical biopsies is demonstrated, paving the way for improving current post-surgical, histopathological practice via non-destructive, in situ streamlined screening of fresh tissue samples in a matter of minutes after excision.

We propose a method for depth estimation under different illumination conditions, i.e., day and night time. As photometry is uninformative in regions under low-illumination, we tackle the problem through a multi-sensor fusion approach, where we take as input an additional synchronized sparse point cloud (i.e., from a LiDAR) projected onto the image plane as a sparse depth map, along with a camera image. The crux of our method lies in the use of the abundantly available synthetic data to first approximate the 3D scene structure by learning a mapping from sparse to (coarse) dense depth maps along with their predictive uncertainty - we term this, SpaDe. In poorly illuminated regions where photometric intensities do not afford the inference of local shape, the coarse approximation of scene depth serves as a prior; the uncertainty map is then used with the image to guide refinement through an uncertainty-driven residual learning (URL) scheme. The resulting depth completion network leverages complementary strengths from both modalities - depth is sparse but insensitive to illumination and in metric scale, and image is dense but sensitive with scale ambiguity. SpaDe can be used in a plug-and-play fashion, which allows for 25% improvement when augmented onto existing methods to preprocess sparse depth. We demonstrate URL on the nuScenes dataset where we improve over all baselines by an average 11.65% in all-day scenarios, 11.23% when tested specifically for daytime, and 13.12% for nighttime scenes., Comment: 8 pages, 4 figures

We describe the design and results from the BraTS 2023 Intracranial Meningioma Segmentation Challenge. The BraTS Meningioma Challenge differed from prior BraTS Glioma challenges in that it focused on meningiomas, which are typically benign extra-axial tumors with diverse radiologic and anatomical presentation and a propensity for multiplicity. Nine participating teams each developed deep-learning automated segmentation models using image data from the largest multi-institutional systematically expert annotated multilabel multi-sequence meningioma MRI dataset to date, which included 1000 training set cases, 141 validation set cases, and 283 hidden test set cases. Each case included T2, FLAIR, T1, and T1Gd brain MRI sequences with associated tumor compartment labels delineating enhancing tumor, non-enhancing tumor, and surrounding non-enhancing FLAIR hyperintensity. Participant automated segmentation models were evaluated and ranked based on a scoring system evaluating lesion-wise metrics including dice similarity coefficient (DSC) and 95% Hausdorff Distance. The top ranked team had a lesion-wise median dice similarity coefficient (DSC) of 0.976, 0.976, and 0.964 for enhancing tumor, tumor core, and whole tumor, respectively and a corresponding average DSC of 0.899, 0.904, and 0.871, respectively. These results serve as state-of-the-art benchmarks for future pre-operative meningioma automated segmentation algorithms. Additionally, we found that 1286 of 1424 cases (90.3%) had at least 1 compartment voxel abutting the edge of the skull-stripped image edge, which requires further investigation into optimal pre-processing face anonymization steps., Comment: Accepted for publication at the Journal of Machine Learning for Biomedical Imaging (MELBA) https://melba-journal.org/2025:003 22 pages, 6 tables, 12 figures, MICCAI, MELBA

Pediatric tumors of the central nervous system are the most common cause of cancer-related death in children. The five-year survival rate for high-grade gliomas in children is less than 20%. Due to their rarity, the diagnosis of these entities is often delayed, their treatment is mainly based on historic treatment concepts, and clinical trials require multi-institutional collaborations. Here we present the CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs challenge, focused on pediatric brain tumors with data acquired across multiple international consortia dedicated to pediatric neuro-oncology and clinical trials. The CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs challenge brings together clinicians and AI/imaging scientists to lead to faster development of automated segmentation techniques that could benefit clinical trials, and ultimately the care of children with brain tumors., Comment: arXiv admin note: substantial text overlap with arXiv:2305.17033

The Spin Physics Detector collaboration proposes to install a universal detector in the second interaction point of the NICA collider under construction (JINR, Dubna) to study the spin structure of the proton and deuteron and other spin-related phenomena using a unique possibility to operate with polarized proton and deuteron beams at a collision energy up to 27 GeV and a luminosity up to $10^{32}$ cm$^{-2}$ s$^{-1}$. As the main goal, the experiment aims to provide access to the gluon TMD PDFs in the proton and deuteron, as well as the gluon transversity distribution and tensor PDFs in the deuteron, via the measurement of specific single and double spin asymmetries using different complementary probes such as charmonia, open charm, and prompt photon production processes. Other polarized and unpolarized physics is possible, especially at the first stage of NICA operation with reduced luminosity and collision energy of the proton and ion beams. This document is dedicated exclusively to technical issues of the SPD setup construction.

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.

Uncertainty in medical image segmentation tasks, especially inter-rater variability, arising from differences in interpretations and annotations by various experts, presents a significant challenge in achieving consistent and reliable image segmentation. This variability not only reflects the inherent complexity and subjective nature of medical image interpretation but also directly impacts the development and evaluation of automated segmentation algorithms. Accurately modeling and quantifying this variability is essential for enhancing the robustness and clinical applicability of these algorithms. We report the set-up and summarize the benchmark results of the Quantification of Uncertainties in Biomedical Image Quantification Challenge (QUBIQ), which was organized in conjunction with International Conferences on Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2020 and 2021. The challenge focuses on the uncertainty quantification of medical image segmentation which considers the omnipresence of inter-rater variability in imaging datasets. The large collection of images with multi-rater annotations features various modalities such as MRI and CT; various organs such as the brain, prostate, kidney, and pancreas; and different image dimensions 2D-vs-3D. A total of 24 teams submitted different solutions to the problem, combining various baseline models, Bayesian neural networks, and ensemble model techniques. The obtained results indicate the importance of the ensemble models, as well as the need for further research to develop efficient 3D methods for uncertainty quantification methods in 3D segmentation tasks., Comment: initial technical report

Direct image-to-graph transformation is a challenging task that involves solving object detection and relationship prediction in a single model. Due to this task's complexity, large training datasets are rare in many domains, making the training of deep-learning methods challenging. This data sparsity necessitates transfer learning strategies akin to the state-of-the-art in general computer vision. In this work, we introduce a set of methods enabling cross-domain and cross-dimension learning for image-to-graph transformers. We propose (1) a regularized edge sampling loss to effectively learn object relations in multiple domains with different numbers of edges, (2) a domain adaptation framework for image-to-graph transformers aligning image- and graph-level features from different domains, and (3) a projection function that allows using 2D data for training 3D transformers. We demonstrate our method's utility in cross-domain and cross-dimension experiments, where we utilize labeled data from 2D road networks for simultaneous learning in vastly different target domains. Our method consistently outperforms standard transfer learning and self-supervised pretraining on challenging benchmarks, such as retinal or whole-brain vessel graph extraction.

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%.

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. The TopCoW dataset was the first public dataset with voxel-level annotations for thirteen possible CoW vessel components, enabled by virtual-reality (VR) technology. It was also the first large dataset with paired MRA and CTA from the same patients. TopCoW challenge formalized the CoW characterization problem as a multiclass anatomical segmentation task with an emphasis on topological metrics. We invited submissions worldwide for the CoW segmentation task, which attracted over 140 registered participants from four continents. 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 topology accurately. TopCoW represented a first attempt at benchmarking the CoW anatomical segmentation task for MRA and CTA, both morphologically and topologically., Comment: 24 pages, 11 figures, 9 tables. Summary Paper for the MICCAI TopCoW 2023 Challenge

Brain tumor growth is unique to each glioma patient and extends beyond what is visible in imaging scans, infiltrating surrounding brain tissue. Understanding these hidden patient-specific progressions is essential for effective therapies. Current treatment plans for brain tumors, such as radiotherapy, typically involve delineating a uniform margin around the visible tumor on pre-treatment scans to target this invisible tumor growth. This "one size fits all" approach is derived from population studies and often fails to account for the nuances of individual patient conditions. We present the GliODIL framework, which infers the full spatial distribution of tumor cell concentration from available multi-modal imaging, leveraging a Fisher-Kolmogorov type physics model to describe tumor growth. This is achieved through the newly introduced method of Optimizing the Discrete Loss (ODIL), where both data and physics-based constraints are softly assimilated into the solution. Our test dataset comprises 152 glioblastoma patients with pre-treatment imaging and post-treatment follow-ups for tumor recurrence monitoring. By blending data-driven techniques with physics-based constraints, GliODIL enhances recurrence prediction in radiotherapy planning, challenging traditional uniform margins and strict adherence to the Fisher-Kolmogorov partial differential equation (PDE) model, which is adapted for complex cases., Comment: 22 pages, 7 figures, 1 table. Associated GitHub: https://github.com/m1balcerak/GliODIL

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., Comment: 15 pages, 6 figures, 3 tables

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.

Diffuse optical modalities such as broadband near-infrared spectroscopy (bNIRS) 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 a unique diagnostic tool. However, no established method exists to streamline the inference of the biochemical composition from the optical spectrum for real-time applications such as surgical monitoring. In this paper, we analyse a machine learning technique for fast and accurate inference of changes in the molecular composition of brain tissue. We reconsider and propose modifications to the existing learnable methodology based on the Beer-Lambert law, which analytically connects the spectra with concentrations. We evaluate the method's applicability to linear and non-linear formulations of the Beer-Lambert law. The approach is tested on real data obtained from the bNIRS- and HSI-based optical monitoring of brain tissue. The results demonstrate that the proposed method enables real-time molecular composition inference while maintaining the accuracy of traditional linear and non-linear optimization solvers. Preliminary findings show that Beer-Lambert law-based spectral unmixing allows to contrast brain anatomy semantics such as the vessel tree and tumor area.

In 2022, a group of basic and clinical virologists, bioinformaticians, and evolutionary and structural biologists met in Oxford, UK, to develop a consensus on methodologies used to classify viruses. They concluded that virus taxonomy, which is hierarchical and based on evolution, is only one of many possible ways to classify viruses. This taxonomy, while satisfying the four principles they set out, faces difficulties in coordinating with other classification systems useful to clinicians, infectious disease specialists, agronomists, etc. One example discussed is the grouping of different viral strains that cause different diseases into the species Enterovirus C. Here we show that the use of a previously proposed variant of a natural virus classification system based on the use of Neural Replicator Analysis can resolve this contradiction by establishing the fine structure of the Enterovirus C species, in which strains that cause different diseases are placed in several different cells of the binomial table of viruses. A key element in enabling this is the sophisticated preprocessing of the original viral genomes using neural replicators., Comment: 11 pages, 4 figures. arXiv admin note: substantial text overlap with arXiv:2212.05476

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., Comment: Accepted at ICCV 2023

Accurate image registration is pivotal in biomedical image analysis, where selecting suitable registration algorithms demands careful consideration. While numerous algorithms are available, the evaluation metrics to assess their performance have remained relatively static. This study addresses this challenge by introducing a novel evaluation metric termed Landmark Hit Rate (HitR), which focuses on the clinical relevance of image registration accuracy. Unlike traditional metrics such as Target Registration Error, which emphasize subresolution differences, HitR considers whether registration algorithms successfully position landmarks within defined confidence zones. This paradigm shift acknowledges the inherent annotation noise in medical images, allowing for more meaningful assessments. To equip HitR with label-noise-awareness, we propose defining these confidence zones based on an Inter-rater Variance analysis. Consequently, hit rate curves are computed for varying landmark zone sizes, enabling performance measurement for a task-specific level of accuracy. Our approach offers a more realistic and meaningful assessment of image registration algorithms, reflecting their suitability for clinical and biomedical applications.

The results of applying neural replicator analysis (NRA) to the genomes of viruses belonging to the genus Flavivirus are presented. It is shown that the viral genomes considered in this study can be placed in five different cells of the viral genome table. Some of these cells appear for the first time and are characterized by 9-periodicity of WS-encoded genomic sequences. It is noteworthy that Japanese encephalitis viral strains and Zika viral strains occupy not one, but two common cells of this table. We also present the results of the NRA of Zika viral strains and suggest that the earliest strain in Asia is an Indian strain that spread from Africa (Uganda) to the East. The fine structure of the sets of Japanese encephalitis viral strains is presented and it is shown that their generally accepted genotypes 1 and 3 can be clearly divided into two subgenotypes. It is also shown that probably not Indonesian, but Indian strains of this virus can be considered the earliest known strains that further evolved and spread in Asian countries., Comment: 17 pages, 7 figures

The translation of AI-generated brain metastases (BM) segmentation into clinical practice relies heavily on diverse, high-quality annotated medical imaging datasets. The BraTS-METS 2023 challenge has gained momentum for testing and benchmarking algorithms using rigorously annotated internationally compiled real-world datasets. This study presents the results of the segmentation challenge and characterizes the challenging cases that impacted the performance of the winning algorithms. Untreated brain metastases on standard anatomic MRI sequences (T1, T2, FLAIR, T1PG) from eight contributed international datasets were annotated in stepwise method: published UNET algorithms, student, neuroradiologist, final approver neuroradiologist. Segmentations were ranked based on lesion-wise Dice and Hausdorff distance (HD95) scores. False positives (FP) and false negatives (FN) were rigorously penalized, receiving a score of 0 for Dice and a fixed penalty of 374 for HD95. Eight datasets comprising 1303 studies were annotated, with 402 studies (3076 lesions) released on Synapse as publicly available datasets to challenge competitors. Additionally, 31 studies (139 lesions) were held out for validation, and 59 studies (218 lesions) were used for testing. Segmentation accuracy was measured as rank across subjects, with the winning team achieving a LesionWise mean score of 7.9. Common errors among the leading teams included false negatives for small lesions and misregistration of masks in space.The BraTS-METS 2023 challenge successfully curated well-annotated, diverse datasets and identified common errors, facilitating the translation of BM segmentation across varied clinical environments and providing personalized volumetric reports to patients undergoing BM treatment.

Pediatric tumors of the central nervous system are the most common cause of cancer-related death in children. The five-year survival rate for high-grade gliomas in children is less than 20\%. Due to their rarity, the diagnosis of these entities is often delayed, their treatment is mainly based on historic treatment concepts, and clinical trials require multi-institutional collaborations. The MICCAI Brain Tumor Segmentation (BraTS) Challenge is a landmark community benchmark event with a successful history of 12 years of resource creation for the segmentation and analysis of adult glioma. Here we present the CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs 2023 challenge, which represents the first BraTS challenge focused on pediatric brain tumors with data acquired across multiple international consortia dedicated to pediatric neuro-oncology and clinical trials. The BraTS-PEDs 2023 challenge focuses on benchmarking the development of volumentric segmentation algorithms for pediatric brain glioma through standardized quantitative performance evaluation metrics utilized across the BraTS 2023 cluster of challenges. Models gaining knowledge from the BraTS-PEDs multi-parametric structural MRI (mpMRI) training data will be evaluated on separate validation and unseen test mpMRI dataof high-grade pediatric glioma. The CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs 2023 challenge brings together clinicians and AI/imaging scientists to lead to faster development of automated segmentation techniques that could benefit clinical trials, and ultimately the care of children with brain tumors.

Automated brain tumor segmentation methods have become well-established and reached performance levels offering clear clinical utility. These methods typically rely on four input magnetic resonance imaging (MRI) modalities: T1-weighted images with and without contrast enhancement, T2-weighted images, and FLAIR images. However, some sequences are often missing in clinical practice due to time constraints or image artifacts, such as patient motion. Consequently, the ability to substitute missing modalities and gain segmentation performance is highly desirable and necessary for the broader adoption of these algorithms in the clinical routine. In this work, we present the establishment of the Brain MR Image Synthesis Benchmark (BraSyn) in conjunction with the Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2023. The primary objective of this challenge is to evaluate image synthesis methods that can realistically generate missing MRI modalities when multiple available images are provided. The ultimate aim is to facilitate automated brain tumor segmentation pipelines. The image dataset used in the benchmark is diverse and multi-modal, created through collaboration with various hospitals and research institutions., Comment: Technical report of BraSyn

A myriad of algorithms for the automatic analysis of brain MR images is available to support clinicians in their decision-making. For brain tumor patients, the image acquisition time series typically starts with an already pathological scan. This poses problems, as many algorithms are designed to analyze healthy brains and provide no guarantee for images featuring lesions. Examples include, but are not limited to, algorithms for brain anatomy parcellation, tissue segmentation, and brain extraction. To solve this dilemma, we introduce the BraTS inpainting challenge. Here, the participants explore inpainting techniques to synthesize healthy brain scans from lesioned ones. The following manuscript contains the task formulation, dataset, and submission procedure. Later, it will be updated to summarize the findings of the challenge. The challenge is organized as part of the ASNR-BraTS MICCAI challenge., Comment: 14 pages, 6 figures

Meningiomas are the most common primary intracranial tumor in adults and can be associated with significant morbidity and mortality. Radiologists, neurosurgeons, neuro-oncologists, and radiation oncologists rely on multiparametric MRI (mpMRI) for diagnosis, treatment planning, and longitudinal treatment monitoring; yet automated, objective, and quantitative tools for non-invasive assessment of meningiomas on mpMRI are lacking. The BraTS meningioma 2023 challenge will provide a community standard and benchmark for state-of-the-art automated intracranial meningioma segmentation models based on the largest expert annotated multilabel meningioma mpMRI dataset to date. Challenge competitors will develop automated segmentation models to predict three distinct meningioma sub-regions on MRI including enhancing tumor, non-enhancing tumor core, and surrounding nonenhancing T2/FLAIR hyperintensity. Models will be evaluated on separate validation and held-out test datasets using standardized metrics utilized across the BraTS 2023 series of challenges including the Dice similarity coefficient and Hausdorff distance. The models developed during the course of this challenge will aid in incorporation of automated meningioma MRI segmentation into clinical practice, which will ultimately improve care of patients with meningioma.

This paper presents FedPIDAvg, the winning submission to the Federated Tumor Segmentation Challenge 2022 (FETS22). Inspired by FedCostWAvg, our winning contribution to FETS21, we contribute an improved aggregation strategy for federated and collaborative learning. FedCostWAvg is a weighted averaging method that not only considers the number of training samples of each cluster but also the size of the drop of the respective cost function in the last federated round. This can be interpreted as the derivative part of a PID controller (proportional-integral-derivative controller). In FedPIDAvg, we further add the missing integral term. Another key challenge was the vastly varying size of data samples per center. We addressed this by modeling the data center sizes as following a Poisson distribution and choosing the training iterations per center accordingly. Our method outperformed all other submissions.

Even though simultaneous optimization of similarity metrics is a standard procedure in the field of semantic segmentation, surprisingly, this is much less established for image registration. To help closing this gap in the literature, we investigate in a complex multi-modal 3D setting whether simultaneous optimization of registration metrics, here implemented by means of primitive summation, can benefit image registration. We evaluate two challenging datasets containing collections of pre- to post-operative and pre- to intra-operative MR images of glioma. Employing the proposed optimization, we demonstrate improved registration accuracy in terms of TRE on expert neuroradiologists' landmark annotations.

International benchmarking competitions have become fundamental for the comparative performance assessment of image analysis methods. However, little attention has been given to investigating what can be learnt from these competitions. Do they really generate scientific progress? What are common and successful participation strategies? What makes a solution superior to a competing method? To address this gap in the literature, we performed a multi-center study with all 80 competitions that were conducted in the scope of IEEE ISBI 2021 and MICCAI 2021. Statistical analyses performed based on comprehensive descriptions of the submitted algorithms linked to their rank as well as the underlying participation strategies revealed common characteristics of winning solutions. These typically include the use of multi-task learning (63%) and/or multi-stage pipelines (61%), and a focus on augmentation (100%), image preprocessing (97%), data curation (79%), and postprocessing (66%). The "typical" lead of a winning team is a computer scientist with a doctoral degree, five years of experience in biomedical image analysis, and four years of experience in deep learning. Two core general development strategies stood out for highly-ranked teams: the reflection of the metrics in the method design and the focus on analyzing and handling failure cases. According to the organizers, 43% of the winning algorithms exceeded the state of the art but only 11% completely solved the respective domain problem. The insights of our study could help researchers (1) improve algorithm development strategies when approaching new problems, and (2) focus on open research questions revealed by this work., Comment: accepted to CVPR 2023

Hyperspectral imaging (HSI) is an optical technique that processes the electromagnetic spectrum at a multitude of monochromatic, adjacent frequency bands. The wide-bandwidth spectral signature of a target object's reflectance allows fingerprinting its physical, biochemical, and physiological properties. HSI has been applied for various applications, such as remote sensing and biological tissue analysis. Recently, HSI was also used to differentiate between healthy and pathological tissue under operative conditions in a surgery room on patients diagnosed with brain tumors. In this article, we perform a statistical analysis of the brain tumor patients' HSI scans from the HELICoiD dataset with the aim of identifying the correlation between reflectance spectra and absorption spectra of tissue chromophores. By using the principal component analysis (PCA), we determine the most relevant spectral features for intra- and inter-tissue class differentiation. Furthermore, we demonstrate that such spectral features are correlated with the spectra of cytochrome, i.e., the chromophore highly involved in (hyper) metabolic processes. Identifying such fingerprints of chromophores in reflectance spectra is a key step for automated molecular profiling and, eventually, expert-free biomarker discovery.

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. Current grading systems based on imaging biomarkers only coarsely group disease stages into broad categories and are unable to predict future disease progression. It is widely believed that this is due to their focus on a single point in time, disregarding the dynamic nature of the disease. In this work, we present the first method to automatically discover biomarkers that capture temporal dynamics of disease progression. Our method represents patient time series as trajectories in a latent feature space built with contrastive learning. Then, individual trajectories are partitioned into atomic sub-sequences that encode transitions between disease states. These are clustered using a newly introduced distance metric. In quantitative experiments we found our method yields temporal biomarkers that are predictive of conversion to late AMD. Furthermore, these clusters were highly interpretable to ophthalmologists who confirmed that many of the clusters represent dynamics that have previously been linked to the progression of AMD, even though they are currently not included in any clinical grading system., Comment: Submitted to MICCAI2023

Machine learning models are typically evaluated by computing similarity with reference annotations and trained by maximizing similarity with such. Especially in the biomedical domain, annotations are subjective and suffer from low inter- and intra-rater reliability. Since annotations only reflect one interpretation of the real world, this can lead to sub-optimal predictions even though the model achieves high similarity scores. Here, the theoretical concept of PGT is introduced. PGT marks the point beyond which an increase in similarity with the \emph{reference annotation} stops translating to better RWMP. Additionally, a quantitative technique to approximate PGT by computing inter- and intra-rater reliability is proposed. Finally, four categories of PGT-aware strategies to evaluate and improve model performance are reviewed., Comment: 7pages, 2 figures (minor corrections to text, affiliations and layout)