Magnetic resonance imaging (MRI) is critical for diagnosing neurodegenerative diseases, yet accurately assessing mild cortical atrophy remains a challenge due to its subtlety. Automated cortex reconstruction, paired with healthy reference ranges, aids in pinpointing pathological atrophy, yet their generalization is limited by biases from image acquisition and processing. We introduce the concept of stochastic cortical self-reconstruction (SCSR) that creates a subject-specific healthy reference by taking MRI-derived thicknesses as input and, therefore, implicitly accounting for potential confounders. SCSR randomly corrupts parts of the cortex and self-reconstructs them from the remaining information. Trained exclusively on healthy individuals, repeated self-reconstruction generates a stochastic reference cortex for assessing deviations from the norm. We present three implementations of this concept: XGBoost applied on parcels, and two autoencoders on vertex level -- one based on a multilayer perceptron and the other using a spherical U-Net. These models were trained on healthy subjects from the UK Biobank and subsequently evaluated across four public Alzheimer's datasets. Finally, we deploy the model on clinical in-house data, where deviation maps' high spatial resolution aids in discriminating between four types of dementia.
Reconstructing the cortex from longitudinal MRI is indispensable for analyzing morphological changes in the human brain. Despite the recent disruption of cortical surface reconstruction with deep learning, challenges arising from longitudinal data are still persistent. Especially the lack of strong spatiotemporal point correspondence hinders downstream analyses due to the introduced noise. To address this issue, we present V2C-Long, the first dedicated deep learning-based cortex reconstruction method for longitudinal MRI. In contrast to existing methods, V2C-Long surfaces are directly comparable in a cross-sectional and longitudinal manner. We establish strong inherent spatiotemporal correspondences via a novel composition of two deep mesh deformation networks and fast aggregation of feature-enhanced within-subject templates. The results on internal and external test data demonstrate that V2C-Long yields cortical surfaces with improved accuracy and consistency compared to previous methods. Finally, this improvement manifests in higher sensitivity to regional cortical atrophy in Alzheimer's disease.
The reconstruction of cortical surfaces is a prerequisite for quantitative analyses of the cerebral cortex in magnetic resonance imaging (MRI). Existing segmentation-based methods separate the surface registration from the surface extraction, which is computationally inefficient and prone to distortions. We introduce Vox2Cortex-Flow (V2C-Flow), a deep mesh-deformation technique that learns a deformation field from a brain template to the cortical surfaces of an MRI scan. To this end, we present a geometric neural network that models the deformation-describing ordinary differential equation in a continuous manner. The network architecture comprises convolutional and graph-convolutional layers, which allows it to work with images and meshes at the same time. V2C-Flow is not only very fast, requiring less than two seconds to infer all four cortical surfaces, but also establishes vertex-wise correspondences to the template during reconstruction. In addition, V2C-Flow is the first approach for cortex reconstruction that models white matter and pial surfaces jointly, therefore avoiding intersections between them. Our comprehensive experiments on internal and external test data demonstrate that V2C-Flow results in cortical surfaces that are state-of-the-art in terms of accuracy. Moreover, we show that the established correspondences are more consistent than in FreeSurfer and that they can directly be utilized for cortex parcellation and group analyses of cortical thickness.
Explaining predictions of black-box neural networks is crucial when applied to decision-critical tasks. Thus, attribution maps are commonly used to identify important image regions, despite prior work showing that humans prefer explanations based on similar examples. To this end, ProtoPNet learns a set of class-representative feature vectors (prototypes) for case-based reasoning. During inference, similarities of latent features to prototypes are linearly classified to form predictions and attribution maps are provided to explain the similarity. In this work, we evaluate whether architectures for case-based reasoning fulfill established axioms required for faithful explanations using the example of ProtoPNet. We show that such architectures allow the extraction of faithful explanations. However, we prove that the attribution maps used to explain the similarities violate the axioms. We propose a new procedure to extract explanations for trained ProtoPNets, named ProtoPFaith. Conceptually, these explanations are Shapley values, calculated on the similarity scores of each prototype. They allow to faithfully answer which prototypes are present in an unseen image and quantify each pixel's contribution to that presence, thereby complying with all axioms. The theoretical violations of ProtoPNet manifest in our experiments on three datasets (CUB-200-2011, Stanford Dogs, RSNA) and five architectures (ConvNet, ResNet, ResNet50, WideResNet50, ResNeXt50). Our experiments show a qualitative difference between the explanations given by ProtoPNet and ProtoPFaith. Additionally, we quantify the explanations with the Area Over the Perturbation Curve, on which ProtoPFaith outperforms ProtoPNet on all experiments by a factor $>10^3$.
Recent years have witnessed a surge of interest in integrating high-dimensional data captured by multisource sensors, driven by the impressive success of neural networks in the integration of multimodal data. However, the integration of heterogeneous multimodal data poses a significant challenge, as confounding effects and dependencies among such heterogeneous data sources introduce unwanted variability and bias, leading to suboptimal performance of multimodal models. Therefore, it becomes crucial to normalize the low- or high-level features extracted from data modalities before their fusion takes place. This paper introduces a novel approach for the normalization of multimodal data, called RegBN, that incorporates regularization. RegBN uses the Frobenius norm as a regularizer term to address the side effects of confounders and underlying dependencies among different data sources. The proposed method generalizes well across multiple modalities and eliminates the need for learnable parameters, simplifying training and inference. We validate the effectiveness of RegBN on eight databases from five research areas, encompassing diverse modalities such as language, audio, image, video, depth, tabular, and 3D MRI. The proposed method demonstrates broad applicability across different architectures such as multilayer perceptrons, convolutional neural networks, and vision transformers, enabling effective normalization of both low- and high-level features in multimodal neural networks. RegBN is available at \url{https://github.com/mogvision/regbn}.
We present MedShapeNet, a large collection of anatomical shapes (e.g., bones, organs, vessels) and 3D surgical instrument models. Prior to the deep learning era, the broad application of statistical shape models (SSMs) in medical image analysis is evidence that shapes have been commonly used to describe medical data. Nowadays, however, state-of-the-art (SOTA) deep learning algorithms in medical imaging are predominantly voxel-based. In computer vision, on the contrary, shapes (including, voxel occupancy grids, meshes, point clouds and implicit surface models) are preferred data representations in 3D, as seen from the numerous shape-related publications in premier vision conferences, such as the IEEE/CVF Conference on Computer Vision and Pattern Recognition (CVPR), as well as the increasing popularity of ShapeNet (about 51,300 models) and Princeton ModelNet (127,915 models) in computer vision research. MedShapeNet is created as an alternative to these commonly used shape benchmarks to facilitate the translation of data-driven vision algorithms to medical applications, and it extends the opportunities to adapt SOTA vision algorithms to solve critical medical problems. Besides, the majority of the medical shapes in MedShapeNet are modeled directly on the imaging data of real patients, and therefore it complements well existing shape benchmarks comprising of computer-aided design (CAD) models. MedShapeNet currently includes more than 100,000 medical shapes, and provides annotations in the form of paired data. It is therefore also a freely available repository of 3D models for extended reality (virtual reality - VR, augmented reality - AR, mixed reality - MR) and medical 3D printing. This white paper describes in detail the motivations behind MedShapeNet, the shape acquisition procedures, the use cases, as well as the usage of the online shape search portal: https://medshapenet.ikim.nrw/
Abdominal multi-organ segmentation from CT and MRI is an essential prerequisite for surgical planning and computer-aided navigation systems. Three-dimensional numeric representations of abdominal shapes are further important for quantitative and statistical analyses thereof. Existing methods in the field, however, are unable to extract highly accurate 3D representations that are smooth, topologically correct, and match points on a template. In this work, we present UNetFlow, a novel diffeomorphic shape deformation approach for abdominal organs. UNetFlow combines the advantages of voxel-based and mesh-based approaches for 3D shape extraction. Our results demonstrate high accuracy with respect to manually annotated CT data and better topological correctness compared to previous methods. In addition, we show the generalization of UNetFlow to MRI.
The wide range of research in deep learning-based medical image segmentation pushed the boundaries in a multitude of applications. A clinically relevant problem that received less attention is the handling of scans with irregular anatomy, e.g., after organ resection. State-of-the-art segmentation models often lead to organ hallucinations, i.e., false-positive predictions of organs, which cannot be alleviated by oversampling or post-processing. Motivated by the increasing need to develop robust deep learning models, we propose HALOS for abdominal organ segmentation in MR images that handles cases after organ resection surgery. To this end, we combine missing organ classification and multi-organ segmentation tasks into a multi-task model, yielding a classification-assisted segmentation pipeline. The segmentation network learns to incorporate knowledge about organ existence via feature fusion modules. Extensive experiments on a small labeled test set and large-scale UK Biobank data demonstrate the effectiveness of our approach in terms of higher segmentation Dice scores and near-to-zero false positive prediction rate.
Alzheimer's disease (AD) has a complex and multifactorial etiology, which requires integrating information about neuroanatomy, genetics, and cerebrospinal fluid biomarkers for accurate diagnosis. Hence, recent deep learning approaches combined image and tabular information to improve diagnostic performance. However, the black-box nature of such neural networks is still a barrier for clinical applications, in which understanding the decision of a heterogeneous model is integral. We propose PANIC, a prototypical additive neural network for interpretable AD classification that integrates 3D image and tabular data. It is interpretable by design and, thus, avoids the need for post-hoc explanations that try to approximate the decision of a network. Our results demonstrate that PANIC achieves state-of-the-art performance in AD classification, while directly providing local and global explanations. Finally, we show that PANIC extracts biologically meaningful signatures of AD, and satisfies a set of desirable desiderata for trustworthy machine learning. Our implementation is available at https://github.com/ai-med/PANIC .