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Christian Ledig

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5 papers

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TMLR Journal 2026 Journal Article

HypCBC: Domain-Invariant Hyperbolic Cross-Branch Consistency for Generalizable Medical Image Analysis

Francesco Di Salvo
Sebastian Doerrich
Jonas Alle
Christian Ledig

Robust generalization beyond training distributions remains a critical challenge for deep neural networks. This is especially pronounced in medical image analysis, where data is often scarce and covariate shifts arise from different hardware devices, imaging protocols, and heterogeneous patient populations. These factors collectively hinder reliable performance and slow down clinical adoption. Despite recent progress, existing learning paradigms primarily rely on the Euclidean manifold, whose flat geometry fails to capture the complex, hierarchical structures present in clinical data. In this work, we exploit the advantages of hyperbolic manifolds to model complex data characteristics. We present the first comprehensive validation of hyperbolic representation learning for medical image analysis and demonstrate statistically significant gains across eleven in-distribution datasets and three ViT models. We further propose an unsupervised, domain-invariant hyperbolic cross-branch consistency constraint. Extensive experiments confirm that our proposed method promotes domain-invariant features and outperforms state-of-the-art Euclidean methods by an average of $+2.1\%$ AUC on three domain generalization benchmarks: Fitzpatrick17k, Camelyon17-WILDS, and a cross-dataset setup for retinal imaging. These datasets span different imaging modalities, data sizes, and label granularities, confirming generalization capabilities across substantially different conditions.

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TMLR Journal 2025 Journal Article

An Embedding is Worth a Thousand Noisy Labels

Francesco Di Salvo
Sebastian Doerrich
Ines Rieger
Christian Ledig

The performance of deep neural networks scales with dataset size and label quality, rendering the efficient mitigation of low-quality data annotations crucial for building robust and cost-effective systems. Existing strategies to address label noise exhibit severe limitations due to computational complexity and application dependency. In this work, we propose WANN, a Weighted Adaptive Nearest Neighbor approach that builds on self-supervised feature representations obtained from foundation models. To guide the weighted voting scheme, we introduce a reliability score $\eta$, which measures the likelihood of a data label being correct. WANN outperforms reference methods, including a linear layer trained with robust loss functions, on diverse datasets of varying size and under various noise types and severities. WANN also exhibits superior generalization on imbalanced data compared to both Adaptive-NNs (ANN) and fixed k-NNs. Furthermore, the proposed weighting scheme enhances supervised dimensionality reduction under noisy labels. This yields a significant boost in classification performance with 10x and 100x smaller image embeddings, minimizing latency and storage requirements. Our approach, emphasizing efficiency and explainability, emerges as a simple, robust solution to overcome inherent limitations of deep neural network training.

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YNICL Journal 2017 Journal Article

Five-class differential diagnostics of neurodegenerative diseases using random undersampling boosting

Tong Tong
Christian Ledig
Ricardo Guerrero
Andreas Schuh
Juha Koikkalainen
Antti Tolonen
Hanneke Rhodius
Frederik Barkhof

Differentiating between different types of neurodegenerative diseases is not only crucial in clinical practice when treatment decisions have to be made, but also has a significant potential for the enrichment of clinical trials. The purpose of this study is to develop a classification framework for distinguishing the four most common neurodegenerative diseases, including Alzheimer's disease, frontotemporal lobe degeneration, Dementia with Lewy bodies and vascular dementia, as well as patients with subjective memory complaints. Different biomarkers including features from images (volume features, region-wise grading features) and non-imaging features (CSF measures) were extracted for each subject. In clinical practice, the prevalence of different dementia types is imbalanced, posing challenges for learning an effective classification model. Therefore, we propose the use of the RUSBoost algorithm in order to train classifiers and to handle the class imbalance training problem. Furthermore, a multi-class feature selection method based on sparsity is integrated into the proposed framework to improve the classification performance. It also provides a way for investigating the importance of different features and regions. Using a dataset of 500 subjects, the proposed framework achieved a high accuracy of 75.2% with a balanced accuracy of 69.3% for the five-class classification using ten-fold cross validation, which is significantly better than the results using support vector machine or random forest, demonstrating the feasibility of the proposed framework to support clinical decision making.

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YNICL Journal 2016 Journal Article

Differential diagnosis of neurodegenerative diseases using structural MRI data

Juha Koikkalainen
Hanneke Rhodius-Meester
Antti Tolonen
Frederik Barkhof
Betty Tijms
Afina W. Lemstra
Tong Tong
Ricardo Guerrero

Different neurodegenerative diseases can cause memory disorders and other cognitive impairments. The early detection and the stratification of patients according to the underlying disease are essential for an efficient approach to this healthcare challenge. This emphasizes the importance of differential diagnostics. Most studies compare patients and controls, or Alzheimer's disease with one other type of dementia. Such a bilateral comparison does not resemble clinical practice, where a clinician is faced with a number of different possible types of dementia. Here we studied which features in structural magnetic resonance imaging (MRI) scans could best distinguish four types of dementia, Alzheimer's disease, frontotemporal dementia, vascular dementia, and dementia with Lewy bodies, and control subjects. We extracted an extensive set of features quantifying volumetric and morphometric characteristics from T1 images, and vascular characteristics from FLAIR images. Classification was performed using a multi-class classifier based on Disease State Index methodology. The classifier provided continuous probability indices for each disease to support clinical decision making. A dataset of 504 individuals was used for evaluation. The cross-validated classification accuracy was 70.6% and balanced accuracy was 69.1% for the five disease groups using only automatically determined MRI features. Vascular dementia patients could be detected with high sensitivity (96%) using features from FLAIR images. Controls (sensitivity 82%) and Alzheimer's disease patients (sensitivity 74%) could be accurately classified using T1-based features, whereas the most difficult group was the dementia with Lewy bodies (sensitivity 32%). These results were notable better than the classification accuracies obtained with visual MRI ratings (accuracy 44.6%, balanced accuracy 51.6%). Different quantification methods provided complementary information, and consequently, the best results were obtained by utilizing several quantification methods. The results prove that automatic quantification methods and computerized decision support methods are feasible for clinical practice and provide comprehensive information that may help clinicians in the diagnosis making.

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YNIMG Journal 2015 Journal Article

Standardized evaluation of algorithms for computer-aided diagnosis of dementia based on structural MRI: The CADDementia challenge

Esther E. Bron
Marion Smits
Wiesje M. van der Flier
Hugo Vrenken
Frederik Barkhof
Philip Scheltens
Janne M. Papma
Rebecca M.E. Steketee

Algorithms for computer-aided diagnosis of dementia based on structural MRI have demonstrated high performance in the literature, but are difficult to compare as different data sets and methodology were used for evaluation. In addition, it is unclear how the algorithms would perform on previously unseen data, and thus, how they would perform in clinical practice when there is no real opportunity to adapt the algorithm to the data at hand. To address these comparability, generalizability and clinical applicability issues, we organized a grand challenge that aimed to objectively compare algorithms based on a clinically representative multi-center data set. Using clinical practice as the starting point, the goal was to reproduce the clinical diagnosis. Therefore, we evaluated algorithms for multi-class classification of three diagnostic groups: patients with probable Alzheimer's disease, patients with mild cognitive impairment and healthy controls. The diagnosis based on clinical criteria was used as reference standard, as it was the best available reference despite its known limitations. For evaluation, a previously unseen test set was used consisting of 354 T1-weighted MRI scans with the diagnoses blinded. Fifteen research teams participated with a total of 29 algorithms. The algorithms were trained on a small training set (n=30) and optionally on data from other sources (e. g. , the Alzheimer's Disease Neuroimaging Initiative, the Australian Imaging Biomarkers and Lifestyle flagship study of aging). The best performing algorithm yielded an accuracy of 63. 0% and an area under the receiver-operating-characteristic curve (AUC) of 78. 8%. In general, the best performances were achieved using feature extraction based on voxel-based morphometry or a combination of features that included volume, cortical thickness, shape and intensity. The challenge is open for new submissions via the web-based framework: http: //caddementia. grand-challenge. org.

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