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Deep learning techniques for anatomical landmark localization (ALL) have shown great success, but their reliance on large annotated datasets remains a problem due to the tedious and costly nature of medical data acquisition and annotation. While traditional data augmentation, variational autoencoders (VAEs), and generative adversarial networks (GANs) have already been used to synthetically expand medical datasets, diffusion-based generative models have recently started to gain attention for their ability to generate high-quality synthetic images. In this study, we explore the use of denoising diffusion probabilistic models (DDPMs) for generating medical images and their corresponding heatmaps of landmarks to enhance the training of a supervised deep learning model for ALL. Our novel approach involves a DDPM with a 2-channel input, incorporating both the original medical image and its heatmap of annotated landmarks. We also propose a novel way to assess the quality of the generated images using a Markov Random Field (MRF) model for landmark matching and a Statistical Shape Model (SSM) to check landmark plausibility, before we evaluate the DDPM-augmented dataset in the context of an ALL task involving hand X-Rays., Comment: Accepted for the SASHIMI workshop of MICCAI 2024

Myocardial infarction (MI) is one of the most prevalent cardiovascular diseases and consequently, a major cause for mortality and morbidity worldwide. Accurate assessment of myocardial tissue viability for post-MI patients is critical for diagnosis and treatment planning, e.g. allowing surgical revascularization, or to determine the risk of adverse cardiovascular events in the future. Fine-grained analysis of the myocardium and its surrounding anatomical structures can be performed by combining the information obtained from complementary medical imaging techniques. In this work, we use late gadolinium enhanced (LGE) magnetic resonance (MR), T2-weighted (T2) MR and balanced steady-state free precession (bSSFP) cine MR in order to semantically segment the left and right ventricle, healthy and scarred myocardial tissue, as well as edema. To this end, we propose the Multi-Sequence Cascading Refinement CNN (MS-CaRe-CNN), a 2-stage CNN cascade that receives multi-sequence data and generates predictions of the anatomical structures of interest without considering tissue viability at Stage 1. The prediction of Stage 1 is then further refined in Stage 2, where the model additionally distinguishes myocardial tissue based on viability, i.e. healthy, scarred and edema regions. Our proposed method is set up as a 5-fold ensemble and semantically segments scar tissue achieving 62.31% DSC and 82.65% precision, as well as 63.78% DSC and 87.69% precision for the combined scar and edema region. These promising results for such small and challenging structures confirm that MS-CaRe-CNN is well-suited to generate semantic segmentations to assess the viability of myocardial tissue, enabling downstream tasks like personalized therapy planning.

Interpretable machine learning has emerged as central in leveraging artificial intelligence within high-stakes domains such as healthcare, where understanding the rationale behind model predictions is as critical as achieving high predictive accuracy. In this context, feature selection assumes a pivotal role in enhancing model interpretability by identifying the most important input features in black-box models. While random forests are frequently used in biomedicine for their remarkable performance on tabular datasets, the accuracy gained from aggregating decision trees comes at the expense of interpretability. Consequently, feature selection for enhancing interpretability in random forests has been extensively explored in supervised settings. However, its investigation in the unsupervised regime remains notably limited. To address this gap, the study introduces novel methods to construct feature graphs from unsupervised random forests and feature selection strategies to derive effective feature combinations from these graphs. Feature graphs are constructed for the entire dataset as well as individual clusters leveraging the parent-child node splits within the trees, such that feature centrality captures their relevance to the clustering task, while edge weights reflect the discriminating power of feature pairs. Graph-based feature selection methods are extensively evaluated on synthetic and benchmark datasets both in terms of their ability to reduce dimensionality while improving clustering performance, as well as to enhance model interpretability. An application on omics data for disease subtyping identifies the top features for each cluster, showcasing the potential of the proposed approach to enhance interpretability in clustering analyses and its utility in a real-world biomedical application.

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. This work establishes a powerful framework for advancing precision medicine through unsupervised random-forest-based clustering and federated computing. 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. Moreover, 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 data sets as well as on cancer data from The Cancer Genome Atlas (TCGA). 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.

The localization of teeth and segmentation of periapical lesions in cone-beam computed tomography (CBCT) images are crucial tasks for clinical diagnosis and treatment planning, which are often time-consuming and require a high level of expertise. However, automating these tasks is challenging due to variations in shape, size, and orientation of lesions, as well as similar topologies among teeth. Moreover, the small volumes occupied by lesions in CBCT images pose a class imbalance problem that needs to be addressed. In this study, we propose a deep learning-based method utilizing two convolutional neural networks: the SpatialConfiguration-Net (SCN) and a modified version of the U-Net. The SCN accurately predicts the coordinates of all teeth present in an image, enabling precise cropping of teeth volumes that are then fed into the U-Net which detects lesions via segmentation. To address class imbalance, we compare the performance of three reweighting loss functions. After evaluation on 144 CBCT images, our method achieves a 97.3% accuracy for teeth localization, along with a promising sensitivity and specificity of 0.97 and 0.88, respectively, for subsequent lesion detection., Comment: Accepted for VISIGRAPP 2024 (Track: VISAPP), 8 pages

Late gadolinium enhanced (LGE) magnetic resonance (MR) imaging is widely established to assess the viability of myocardial tissue of patients after acute myocardial infarction (MI). We propose the Cascading Refinement CNN (CaRe-CNN), which is a fully 3D, end-to-end trained, 3-stage CNN cascade that exploits the hierarchical structure of such labeled cardiac data. Throughout the three stages of the cascade, the label definition changes and CaRe-CNN learns to gradually refine its intermediate predictions accordingly. Furthermore, to obtain more consistent qualitative predictions, we propose a series of post-processing steps that take anatomical constraints into account. Our CaRe-CNN was submitted to the FIMH 2023 MYOSAIQ challenge, where it ranked second out of 18 participating teams. CaRe-CNN showed great improvements most notably when segmenting the difficult but clinically most relevant myocardial infarct tissue (MIT) as well as microvascular obstructions (MVO). When computing the average scores over all labels, our method obtained the best score in eight out of ten metrics. Thus, accurate cardiac segmentation after acute MI via our CaRe-CNN allows generating patient-specific models of the heart serving as an important step towards personalized medicine., Comment: Accepted at VISIGRAPP 2024, 12 pages

With the advancement in robotics, it is becoming increasingly common for large factories and warehouses to incorporate visual SLAM (vSLAM) enabled automated robots that operate closely next to humans. This makes any adversarial attacks on vSLAM components potentially detrimental to humans working alongside them. Loop Closure Detection (LCD) is a crucial component in vSLAM that minimizes the accumulation of drift in mapping, since even a small drift can accumulate into a significant drift over time. A prior work by Kim et al., SymbioLCD2, unified visual features and semantic objects into a single graph structure for finding loop closure candidates. While this provided a performance improvement over visual feature-based LCD, it also created a single point of vulnerability for potential graph-based adversarial attacks. Unlike previously reported visual-patch based attacks, small graph perturbations are far more challenging to detect, making them a more significant threat. In this paper, we present Adversarial-LCD, a novel black-box evasion attack framework that employs an eigencentrality-based perturbation method and an SVM-RBF surrogate model with a Weisfeiler-Lehman feature extractor for attacking graph-based LCD. Our evaluation shows that the attack performance of Adversarial-LCD with the SVM-RBF surrogate model was superior to that of other machine learning surrogate algorithms, including SVM-linear, SVM-polynomial, and Bayesian classifier, demonstrating the effectiveness of our attack framework. Furthermore, we show that our eigencentrality-based perturbation method outperforms other algorithms, such as Random-walk and Shortest-path, highlighting the efficiency of Adversarial-LCD's perturbation selection method., Comment: Accepted at VISIGRAPP 2024, 8 pages

Prior to the deep learning era, shape was commonly used to describe the objects. Nowadays, state-of-the-art (SOTA) algorithms in medical imaging are predominantly diverging from computer vision, where voxel grids, meshes, point clouds, and implicit surface models are used. This is seen from numerous shape-related publications in premier vision conferences as well as the growing popularity of ShapeNet (about 51,300 models) and Princeton ModelNet (127,915 models). For the medical domain, we present a large collection of anatomical shapes (e.g., bones, organs, vessels) and 3D models of surgical instrument, called MedShapeNet, created to facilitate the translation of data-driven vision algorithms to medical applications and to adapt SOTA vision algorithms to medical problems. As a unique feature, we directly model the majority of shapes on the imaging data of real patients. As of today, MedShapeNet includes 23 dataset with more than 100,000 shapes that are paired with annotations (ground truth). Our data is freely accessible via a web interface and a Python application programming interface (API) and can be used for discriminative, reconstructive, and variational benchmarks as well as various applications in virtual, augmented, or mixed reality, and 3D printing. Exemplary, we present use cases in the fields of classification of brain tumors, facial and skull reconstructions, multi-class anatomy completion, education, and 3D printing. In future, we will extend the data and improve the interfaces. The project pages are: https://medshapenet.ikim.nrw/ and https://github.com/Jianningli/medshapenet-feedback, Comment: 16 pages

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., Comment: 8 pages. Accepted at 2022 IEEE/RSJ International Conference on Intelligent Robots and Systems (IROS)

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 create 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., Comment: 7 pages. Accepted at 2021 IEEE/RSJ International Conference on Intelligent Robots and Systems (IROS)

In landmark localization, due to ambiguities in defining their exact position, landmark annotations may suffer from large observer variabilities, which result in uncertain annotations. To model the annotation ambiguities of the training dataset, we propose to learn anisotropic Gaussian parameters modeling the shape of the target heatmap during optimization. Furthermore, our method models the prediction uncertainty of individual samples by fitting anisotropic Gaussian functions to the predicted heatmaps during inference. Besides state-of-the-art results, our experiments on datasets of hand radiographs and lateral cephalograms also show that Gaussian functions are correlated with both localization accuracy and observer variability. As a final experiment, we show the importance of integrating the uncertainty into decision making by measuring the influence of the predicted location uncertainty on the classification of anatomical abnormalities in lateral cephalograms., Comment: Accepted for publication at the Journal of Machine Learning for Biomedical Imaging (MELBA) https://melba-journal.org

The treatment of degenerative spinal disorders requires an understanding of the individual spinal anatomy and curvature in 3D. An upright spinal pose (i.e. standing) under natural weight bearing is crucial for such bio-mechanical analysis. 3D volumetric imaging modalities (e.g. CT and MRI) are performed in patients lying down. On the other hand, radiographs are captured in an upright pose, but result in 2D projections. This work aims to integrate the two realms, i.e. it combines the upright spinal curvature from radiographs with the 3D vertebral shape from CT imaging for synthesizing an upright 3D model of spine, loaded naturally. Specifically, we propose a novel neural network architecture working vertebra-wise, termed \emph{TransVert}, which takes orthogonal 2D radiographs and infers the spine's 3D posture. We validate our architecture on digitally reconstructed radiographs, achieving a 3D reconstruction Dice of $95.52\%$, indicating an almost perfect 2D-to-3D domain translation. Deploying our model on clinical radiographs, we successfully synthesise full-3D, upright, patient-specific spine models for the first time.

Additionally to the extensive use in clinical medicine, biological age (BA) in legal medicine is used to assess unknown chronological age (CA) in applications where identification documents are not available. Automatic methods for age estimation proposed in the literature are predicting point estimates, which can be misleading without the quantification of predictive uncertainty. In our multi-factorial age estimation method from MRI data, we used the Variational Inference approach to estimate the uncertainty of a Bayesian CNN model. Distinguishing model uncertainty from data uncertainty, we interpreted data uncertainty as biological variation, i.e. the range of possible CA of subjects having the same BA., Comment: accepted at Medical Imaging Meets NeurIPS 2019

Vertebral labelling and segmentation are two fundamental tasks in an automated spine processing pipeline. Reliable and accurate processing of spine images is expected to benefit clinical decision-support systems for diagnosis, surgery planning, and population-based analysis on spine and bone health. However, designing automated algorithms for spine processing is challenging predominantly due to considerable variations in anatomy and acquisition protocols and due to a severe shortage of publicly available data. Addressing these limitations, the Large Scale Vertebrae Segmentation Challenge (VerSe) was organised in conjunction with the International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI) in 2019 and 2020, with a call for algorithms towards labelling and segmentation of vertebrae. Two datasets containing a total of 374 multi-detector CT scans from 355 patients were prepared and 4505 vertebrae have individually been annotated at voxel-level by a human-machine hybrid algorithm (https://osf.io/nqjyw/, https://osf.io/t98fz/). A total of 25 algorithms were benchmarked on these datasets. In this work, we present the the results of this evaluation and further investigate the performance-variation at vertebra-level, scan-level, and at different fields-of-view. We also evaluate the generalisability of the approaches to an implicit domain shift in data by evaluating the top performing algorithms of one challenge iteration on data from the other iteration. The principal takeaway from VerSe: the performance of an algorithm in labelling and segmenting a spine scan hinges on its ability to correctly identify vertebrae in cases of rare anatomical variations. The content and code concerning VerSe can be accessed at: https://github.com/anjany/verse., Comment: Challenge report for the VerSe 2019 and 2020. Published in Medical Image Analysis (DOI: https://doi.org/10.1016/j.media.2021.102166)

In many medical image analysis applications, often only a limited amount of training data is available, which makes training of convolutional neural networks (CNNs) challenging. 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 need for large training datasets. Our fully convolutional SpatialConfiguration-Net (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 experimental evaluation, we show that the proposed SCN outperforms related methods in terms of landmark localization error on size-limited datasets., Comment: MIDL 2019 [arXiv:1907.08612]

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 arduous due to the large variation of the heart shape, and different image qualities of the clinical data. To achieve this goal, a set of training data is generally needed for constructing priors or for training. In addition, 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 provides 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 show that many of the deep learning (DL) based methods achieved high accuracy, even though the number of training datasets was limited. A number of them also reported poor results in the blinded evaluation, probably due to overfitting in their training. The conventional algorithms, mainly based on multi-atlas segmentation, demonstrated robust and stable performance, even though the accuracy is not as good as the best DL method in CT segmentation. The challenge, including the 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 (\url{www.sdspeople.fudan.edu.cn/zhuangxiahai/0/mmwhs/})., Comment: 14 pages, 7 figures, sumitted to Medical Image Analysis

Different to semantic segmentation, instance segmentation assigns unique labels to each individual instance of the same class. In this work, we propose a novel recurrent fully convolutional network architecture for tracking such instance segmentations over time. The network architecture incorporates convolutional gated recurrent units (ConvGRU) into a stacked hourglass network to utilize temporal video information. Furthermore, we train the network with a novel embedding loss based on cosine similarities, such that the network predicts unique embeddings for every instance throughout videos. Afterwards, these embeddings are clustered among subsequent video frames to create the final tracked instance segmentations. We evaluate the recurrent hourglass network by segmenting left ventricles in MR videos of the heart, where it outperforms a network that does not incorporate video information. Furthermore, we show applicability of the cosine embedding loss for segmenting leaf instances on still images of plants. Finally, we evaluate the framework for instance segmentation and tracking on six datasets of the ISBI celltracking challenge, where it shows state-of-the-art performance., Comment: Accepted for ORAL presentation at MICCAI 2018

Colorectal adenocarcinoma originating in intestinal glandular structures is the most common form of colon cancer. In clinical practice, the morphology of intestinal glands, including architectural appearance and glandular formation, is used by pathologists to inform prognosis and plan the treatment of individual patients. However, achieving good inter-observer as well as intra-observer reproducibility of cancer grading is still a major challenge in modern pathology. An automated approach which quantifies the morphology of glands is a solution to the problem. This paper provides an overview to the Gland Segmentation in Colon Histology Images Challenge Contest (GlaS) held at MICCAI'2015. Details of the challenge, including organization, dataset and evaluation criteria, are presented, along with the method descriptions and evaluation results from the top performing methods.

Segmentation of histopathology sections is an ubiquitous requirement in digital pathology and due to the large variability of biological tissue, machine learning techniques have shown superior performance over standard image processing methods. As part of the GlaS@MICCAI2015 colon gland segmentation challenge, we present a learning-based algorithm to segment glands in tissue of benign and malignant colorectal cancer. Images are preprocessed according to the Hematoxylin-Eosin staining protocol and two deep convolutional neural networks (CNN) are trained as pixel classifiers. The CNN predictions are then regularized using a figure-ground segmentation based on weighted total variation to produce the final segmentation result. On two test sets, our approach achieves a tissue classification accuracy of 98% and 94%, making use of the inherent capability of our system to distinguish between benign and malignant tissue., Comment: An extended version of this work has been published in PeerJ (https://doi.org/10.7717/peerj.3874), so please cite our journal version instead of this preprint