Flow matching has emerged as a promising generative approach that addresses the lengthy sampling times associated with state-of-the-art diffusion models and enables a more flexible trajectory design, while maintaining high-quality image generation. This capability makes it suitable as a generative prior for image restoration tasks. Although current methods leveraging flow models have shown promising results in restoration, some still suffer from long processing times or produce over-smoothed results. To address these challenges, we introduce Restora-Flow, a training-free method that guides flow matching sampling by a degradation mask and incorporates a trajectory correction mechanism to enforce consistency with degraded inputs. We evaluate our approach on both natural and medical datasets across several image restoration tasks involving a mask-based degradation, i.e., inpainting, super-resolution and denoising. We show superior perceptual quality and processing time compared to diffusion and flow matching-based reference methods. Code is available at https://github.com/imigraz/Restora-Flow.

Computational models of atrial electrophysiology (EP) are increasingly utilized for applications such as the development of advanced mapping systems, personalized clinical therapy planning, and the generation of virtual cohorts and digital twins. These models have the potential to establish robust causal links between simulated in silico behaviors and observed human atrial EP, enabling safer, cost-effective, and comprehensive exploration of atrial dynamics. However, current state-of-the-art approaches lack the fidelity and scalability required for regulatory-grade applications, particularly in creating high-quality virtual cohorts or patient-specific digital twins. Challenges include anatomically accurate model generation, calibration to sparse and uncertain clinical data, and computational efficiency within a streamlined workflow. This study addresses these limitations by introducing novel methodologies integrated into an automated end-to-end workflow for generating high-fidelity digital twin snapshots and virtual cohorts of atrial EP. These innovations include: (i) automated multi-scale generation of volumetric biatrial models with detailed anatomical structures and fiber architecture; (ii) a robust method for defining space-varying atrial parameter fields; (iii) a parametric approach for modeling inter-atrial conduction pathways; and (iv) an efficient forward EP model for high-fidelity electrocardiogram computation. We evaluated this workflow on a cohort of 50 atrial fibrillation patients, producing high-quality meshes suitable for reaction-eikonal and reaction-diffusion models and demonstrating the ability to simulate atrial ECGs under parametrically controlled conditions. These advancements represent a critical step toward scalable, precise, and clinically applicable digital twin models and virtual cohorts, enabling enhanced patient-specific predictions and therapeutic planning.

MOTIVATION: In the realm of precision medicine, effective patient stratification and disease subtyping demand innovative methodologies tailored for multi-omics data. Clustering techniques applied to multi-omics data have become instrumental in identifying distinct subgroups of patients, enabling a finer-grained understanding of disease variability. Meanwhile, clinical datasets are often small and must be aggregated from multiple hospitals. Online data sharing, however, is seen as a significant challenge due to privacy concerns, potentially impeding big data's role in medical advancements using machine learning. This work establishes a powerful framework for advancing precision medicine through unsupervised random forest-based clustering in combination with federated computing. RESULTS: We introduce a novel multi-omics clustering approach utilizing unsupervised random forests. The unsupervised nature of the random forest enables the determination of cluster-specific feature importance, unraveling key molecular contributors to distinct patient groups. Our methodology is designed for federated execution, a crucial aspect in the medical domain where privacy concerns are paramount. We have validated our approach on machine learning benchmark datasets as well as on cancer data from The Cancer Genome Atlas. Our method is competitive with the state-of-the-art in terms of disease subtyping, but at the same time substantially improves the cluster interpretability. Experiments indicate that local clustering performance can be improved through federated computing. AVAILABILITY AND IMPLEMENTATION: The proposed methods are available as an R-package (https://github.com/pievos101/uRF).

In Simultaneous Localization and Mapping (SLAM), Loop Closure Detection (LCD) is essential to minimize drift when recognizing previously visited places. Visual Bag- of-Words (vBoW) has been an LCD algorithm of choice for many state-of-the-art SLAM systems. It uses a set of visual features to provide robust place recognition but fails to perceive the semantics or spatial relationship between feature points. Previous work has mainly focused on addressing these issues by combining vBoW with semantic and spatial information from objects in the scene. However, they are unable to exploit spatial information of local visual features and lack a structure that unifies semantic objects and visual features, therefore limiting the symbiosis between the two components. This paper proposes SymbioLCD2, which creates a unified graph structure to integrate semantic objects and visual features symbiotically. Our novel graph-based LCD system utilizes the unified graph structure by applying a Weisfeiler-Lehman graph kernel with temporal constraints to robustly predict loop closure candidates. Evaluation of the proposed system shows that having a unified graph structure incorporating semantic objects and visual features improves LCD prediction accuracy, illustrating that the proposed graph structure provides a strong symbiosis between these two complementary components. It also outperforms other Machine Learning algorithms - such as SVM, Decision Tree, Random Forest, Neural Network and GNN based Graph Matching Networks. Furthermore, it has shown good performance in detecting loop closure candidates earlier than state-of-the-art SLAM systems, demonstrating that extended semantic and spatial awareness from the unified graph structure significantly impacts LCD performance.

Loop closure detection is an essential tool of Simultaneous Localization and Mapping (SLAM) to minimize drift in its localization. Many state-of-the-art loop closure detection (LCD) algorithms use visual Bag-of-Words (vBoW), which is robust against partial occlusions in a scene but cannot perceive the semantics or spatial relationships between feature points. CNN object extraction can address those issues, by providing semantic labels and spatial relationships between objects in a scene. Previous work has mainly focused on replacing vBoW with CNN derived features. In this paper we propose SymbioLCD, a novel ensemble-based LCD that utilizes both CNN-extracted objects and vBoW features for LCD candidate prediction. When used in tandem, the added elements of object semantics and spatial-awareness creates a more robust and symbiotic loop closure detection system. The proposed SymbioLCD uses scale-invariant spatial and semantic matching, Hausdorff distance with temporal constraints, and a Random Forest that utilizes combined information from both CNN-extracted objects and vBoW features for predicting accurate loop closure candidates. Evaluation of the proposed method shows it outperforms other Machine Learning (ML) algorithms - such as SVM, Decision Tree and Neural Network, and demonstrates that there is a strong symbiosis between CNN-extracted object information and vBoW features which assists accurate LCD candidate prediction. Furthermore, it is able to perceive loop closure candidates earlier than state-of-the-art SLAM algorithms, utilizing added spatial and semantic information from CNN-extracted objects.

Cardiac digital twins (Cardiac Digital Twin (CDT)s) of human electrophysiology (Electrophysiology (EP)) are digital replicas of patient hearts derived from clinical data that match like-for-like all available clinical observations. Due to their inherent predictive potential, CDTs show high promise as a complementary modality aiding in clinical decision making and also in the cost-effective, safe and ethical testing of novel EP device therapies. However, current workflows for both the anatomical and functional twinning phases within CDT generation, referring to the inference of model anatomy and parameters from clinical data, are not sufficiently efficient, robust and accurate for advanced clinical and industrial applications. Our study addresses three primary limitations impeding the routine generation of high-fidelity CDTs by introducing; a comprehensive parameter vector encapsulating all factors relating to the ventricular EP; an abstract reference frame within the model allowing the unattended manipulation of model parameter fields; a novel fast-forward electrocardiogram (Electrocardiogram (ECG)) model for efficient and bio-physically-detailed simulation required for parameter inference. A novel workflow for the generation of CDTs is then introduced as an initial proof of concept. Anatomical twinning was performed within a reasonable time compatible with clinical workflows (<4h) for 12 subjects from clinically-attained magnetic resonance images. After assessment of the underlying fast forward ECG model against a gold standard bidomain ECG model, functional twinning of optimal parameters according to a clinically-attained 12 lead ECG was then performed using a forward Saltelli sampling approach for a single subject. The achieved results in terms of efficiency and fidelity demonstrate that our workflow is well-suited and viable for generating biophysically-detailed CDTs at scale.

In many medical image analysis applications, only a limited amount of training data is available due to the costs of image acquisition and the large manual annotation effort required from experts. Training recent state-of-the-art machine learning methods like convolutional neural networks (CNNs) from small datasets is a challenging task. In this work on anatomical landmark localization, we propose a CNN architecture that learns to split the localization task into two simpler sub-problems, reducing the overall need for large training datasets. Our fully convolutional SpatialConfiguration-Net (SCN) learns this simplification due to multiplying the heatmap predictions of its two components and by training the network in an end-to-end manner. Thus, the SCN dedicates one component to locally accurate but ambiguous candidate predictions, while the other component improves robustness to ambiguities by incorporating the spatial configuration of landmarks. In our extensive experimental evaluation, we show that the proposed SCN outperforms related methods in terms of landmark localization error on a variety of size-limited 2D and 3D landmark localization datasets, i.e., hand radiographs, lateral cephalograms, hand MRIs, and spine CTs.

Differently to semantic segmentation, instance segmentation assigns unique labels to each individual instance of the same object class. In this work, we propose a novel recurrent fully convolutional network architecture for tracking such instance segmentations over time, which is highly relevant, e.g., in biomedical applications involving cell growth and migration. Our network architecture incorporates convolutional gated recurrent units (ConvGRU) into a stacked hourglass network to utilize temporal information, e.g., from microscopy videos. Moreover, we train our network with a novel embedding loss based on cosine similarities, such that the network predicts unique embeddings for every instance throughout videos, even in the presence of dynamic structural changes due to mitosis of cells. To create the final tracked instance segmentations, the pixel-wise embeddings are clustered among subsequent video frames by using the mean shift algorithm. After showing the performance of the instance segmentation on a static in-house dataset of muscle fibers from H&E-stained microscopy images, we also evaluate our proposed recurrent stacked hourglass network regarding instance segmentation and tracking performance on six datasets from the ISBI celltracking challenge, where it delivers state-of-the-art results.

Highly relevant for both clinical and legal medicine applications, the established radiological methods for estimating unknown age in children and adolescents are based on visual examination of bone ossification in X-ray images of the hand. Our group has initiated the development of fully automatic age estimation methods from 3D MRI scans of the hand, in order to simultaneously overcome the problems of the radiological methods including (1) exposure to ionizing radiation, (2) necessity to define new, MRI specific staging systems, and (3) subjective influence of the examiner. The present work provides a theoretical background for understanding the nonlinear regression problem of biological age estimation and chronological age approximation. Based on this theoretical background, we comprehensively evaluate machine learning methods (random forests, deep convolutional neural networks) with different simplifications of the image information used as an input for learning. Trained on a large dataset of 328 MR images, we compare the performance of the different input strategies and demonstrate unprecedented results. For estimating biological age, we obtain a mean absolute error of 0.37 ± 0.51 years for the age range of the subjects ≤ 18 years, i.e. where bone ossification has not yet saturated. Finally, we validate our findings by adapting our best performing method to 2D images and applying it to a publicly available dataset of X-ray images, showing that we are in line with the state-of-the-art automatic methods for this task.

Knowledge of whole heart anatomy is a prerequisite for many clinical applications. Whole heart segmentation (WHS), which delineates substructures of the heart, can be very valuable for modeling and analysis of the anatomy and functions of the heart. However, automating this segmentation can be challenging due to the large variation of the heart shape, and different image qualities of the clinical data. To achieve this goal, an initial set of training data is generally needed for constructing priors or for training. Furthermore, it is difficult to perform comparisons between different methods, largely due to differences in the datasets and evaluation metrics used. This manuscript presents the methodologies and evaluation results for the WHS algorithms selected from the submissions to the Multi-Modality Whole Heart Segmentation (MM-WHS) challenge, in conjunction with MICCAI 2017. The challenge provided 120 three-dimensional cardiac images covering the whole heart, including 60 CT and 60 MRI volumes, all acquired in clinical environments with manual delineation. Ten algorithms for CT data and eleven algorithms for MRI data, submitted from twelve groups, have been evaluated. The results showed that the performance of CT WHS was generally better than that of MRI WHS. The segmentation of the substructures for different categories of patients could present different levels of challenge due to the difference in imaging and variations of heart shapes. The deep learning (DL)-based methods demonstrated great potential, though several of them reported poor results in the blinded evaluation. Their performance could vary greatly across different network structures and training strategies. The conventional algorithms, mainly based on multi-atlas segmentation, demonstrated good performance, though the accuracy and computational efficiency could be limited. The challenge, including provision of the annotated training data and the blinded evaluation for submitted algorithms on the test data, continues as an ongoing benchmarking resource via its homepage (www.sdspeople.fudan.edu.cn/zhuangxiahai/0/mmwhs/).

Age estimation from radiologic data is an important topic both in clinical medicine as well as in forensic applications, where it is used to assess unknown chronological age or to discriminate minors from adults. In this paper, we propose an automatic multi-factorial age estimation method based on MRI data of hand, clavicle, and teeth to extend the maximal age range from up to 19 years, as commonly used for age assessment based on hand bones, to up to 25 years, when combined with clavicle bones and wisdom teeth. Fusing age-relevant information from all three anatomical sites, our method utilizes a deep convolutional neural network that is trained on a dataset of 322 subjects in the age range between 13 and 25 years, to achieve a mean absolute prediction error in regressing chronological age of 1.01±0.74 years. Furthermore, when used for majority age classification, we show that a classifier derived from thresholding our regression-based predictor is better suited than a classifier directly trained with a classification loss, especially when taking into account that those cases of minors being wrongly classified as adults need to be minimized. In conclusion, we overcome the limitations of the multi-factorial methods currently used in forensic practice, i.e., dependence on ionizing radiation, subjectivity in quantifying age-relevant information, and lack of an established approach to fuse this information from individual anatomical sites.

In approaches for automatic localization of multiple anatomical landmarks, disambiguation of locally similar structures as obtained by locally accurate candidate generation is often performed by solely including high level knowledge about geometric landmark configuration. In our novel localization approach, we propose to combine both image appearance information and geometric landmark configuration into a unified random forest framework integrated into an optimization procedure that iteratively refines joint landmark predictions by using the coordinate descent algorithm. Depending on how strong multiple landmarks are correlated in a specific localization task, this integration has the benefit that it remains flexible in deciding whether appearance information or the geometric configuration of multiple landmarks is the stronger cue for solving a localization problem both accurately and robustly. Furthermore, no preliminary choice on how to encode a graphical model describing landmark configuration has to be made. In an extensive evaluation on five challenging datasets involving different 2D and 3D imaging modalities, we show that our proposed method is widely applicable and delivers state-of-the-art results when compared to various other related methods.

EMPIRE10 (Evaluation of Methods for Pulmonary Image REgistration 2010) is a public platform for fair and meaningful comparison of registration algorithms which are applied to a database of intrapatient thoracic CT image pairs. Evaluation of nonrigid registration techniques is a nontrivial task. This is compounded by the fact that researchers typically test only on their own data, which varies widely. For this reason, reliable assessment and comparison of different registration algorithms has been virtually impossible in the past. In this work we present the results of the launch phase of EMPIRE10, which comprised the comprehensive evaluation and comparison of 20 individual algorithms from leading academic and industrial research groups. All algorithms are applied to the same set of 30 thoracic CT pairs. Algorithm settings and parameters are chosen by researchers expert in the configuration of their own method and the evaluation is independent, using the same criteria for all participants. All results are published on the EMPIRE10 website (http://empire10.isi.uu.nl). The challenge remains ongoing and open to new participants. Full results from 24 algorithms have been published at the time of writing. This paper details the organization of the challenge, the data and evaluation methods and the outcome of the initial launch with 20 algorithms. The gain in knowledge and future work are discussed.

We present an approach for unsupervised alignment of an ensemble of images called congealing. Our algorithm is based on image registration using the mutual information measure as a cost function. The cost function is optimized by a standard gradient descent method in a multiresolution scheme. As opposed to other congealing methods, which use the SSD measure, the mutual information measure is better suited as a similarity measure for registering images since no prior assumptions on the relation of intensities between images are required. We present alignment results on the MNIST handwritten digit database and on facial images obtained from the CVL database.

This paper introduces an unsupervised color segmentation method. The underlying idea is to segment the input image several times, each time focussing on a different salient part of the image and to subsequently merge all obtained results into one composite segmentation. We identify salient parts of the image by applying affinity propagation clustering to efficiently calculated local color and texture models. Each salient region then serves as an independent initialization for a figure/ground segmentation. Segmentation is done by minimizing a convex energy functional based on weighted total variation leading to a global optimal solution. Each salient region provides an accurate figure/ ground segmentation highlighting different parts of the image. These highly redundant results are combined into one composite segmentation by analyzing local segmentation certainty. Our formulation is quite general, and other salient region detection algorithms in combination with any semi-supervised figure/ground segmentation approach can be used. We demonstrate the high quality of our method on the well-known Berkeley segmentation database. Furthermore we show that our method can be used to provide good spatial support for recognition frameworks.

Biometrics is a huge and very fast growing domain of methods for uniquely recognizing humans based on one or more intrinsic physical or behavioral traits with applications in many different areas, e.g., surveillance, person verification and identification. The International Civil Aviation Organization (ICAO) provides a number of specifications to prepare automated recognition from travel document photos. The goal of these specifications is to increase security in civil aviation on the basis of standardized biometric data. Due to this international standard, there is a high demand for automatically checking face images to assist civil service employees in decision-making. In this work, we present a face normalization and analysis system implementing several parts of the ICAO specification. Our key contribution of this analysis is the fusion of different established classifiers to boost performance of the overall system. Our results show the superior checking quality on facial images due to utilizing classifier fusion compared to a single classifier decision.