Fabian Wagner

Mingxuan Gu, Sulaiman Vesal, Mareike Thies et al. · stanford

Unsupervised domain adaptation (UDA) aims to transfer knowledge learned from a labeled source domain to an unlabeled target domain. Contrastive learning (CL) in the context of UDA can help to better separate classes in feature space. However, in image segmentation, the large memory footprint due to the computation of the pixel-wise contrastive loss makes it prohibitive to use. Furthermore, labeled target data is not easily available in medical imaging, and obtaining new samples is not economical. As a result, in this work, we tackle a more challenging UDA task when there are only a few (fewshot) or a single (oneshot) image available from the target domain. We apply a style transfer module to mitigate the scarcity of target samples. Then, to align the source and target features and tackle the memory issue of the traditional contrastive loss, we propose the centroid-based contrastive learning (CCL) and a centroid norm regularizer (CNR) to optimize the contrastive pairs in both direction and magnitude. In addition, we propose multi-partition centroid contrastive learning (MPCCL) to further reduce the variance in the target features. Fewshot evaluation on MS-CMRSeg dataset demonstrates that ConFUDA improves the segmentation performance by 0.34 of the Dice score on the target domain compared with the baseline, and 0.31 Dice score improvement in a more rigorous oneshot setting.

Mareike Thies, Fabian Wagner, Noah Maul et al.

Incorporating computed tomography (CT) reconstruction operators into differentiable pipelines has proven beneficial in many applications. Such approaches usually focus on the projection data and keep the acquisition geometry fixed. However, precise knowledge of the acquisition geometry is essential for high quality reconstruction results. In this paper, the differentiable formulation of fan-beam CT reconstruction is extended to the acquisition geometry. This allows to propagate gradient information from a loss function on the reconstructed image into the geometry parameters. As a proof-of-concept experiment, this idea is applied to rigid motion compensation. The cost function is parameterized by a trained neural network which regresses an image quality metric from the motion affected reconstruction alone. Using the proposed method, we are the first to optimize such an autofocus-inspired algorithm based on analytical gradients. The algorithm achieves a reduction in MSE by 35.5 % and an improvement in SSIM by 12.6 % over the motion affected reconstruction. Next to motion compensation, we see further use cases of our differentiable method for scanner calibration or hybrid techniques employing deep models.

Noah Maul, Katharina Zinn, Fabian Wagner et al.

Patient-specific hemodynamics assessment could support diagnosis and treatment of neurovascular diseases. Currently, conventional medical imaging modalities are not able to accurately acquire high-resolution hemodynamic information that would be required to assess complex neurovascular pathologies. Therefore, computational fluid dynamics (CFD) simulations can be applied to tomographic reconstructions to obtain clinically relevant information. However, three-dimensional (3D) CFD simulations require enormous computational resources and simulation-related expert knowledge that are usually not available in clinical environments. Recently, deep-learning-based methods have been proposed as CFD surrogates to improve computational efficiency. Nevertheless, the prediction of high-resolution transient CFD simulations for complex vascular geometries poses a challenge to conventional deep learning models. In this work, we present an architecture that is tailored to predict high-resolution (spatial and temporal) velocity fields for complex synthetic vascular geometries. For this, an octree-based spatial discretization is combined with an implicit neural function representation to efficiently handle the prediction of the 3D velocity field for each time step. The presented method is evaluated for the task of cerebral hemodynamics prediction before and during the injection of contrast agent in the internal carotid artery (ICA). Compared to CFD simulations, the velocity field can be estimated with a mean absolute error of 0.024 m/s, whereas the run time reduces from several hours on a high-performance cluster to a few seconds on a consumer graphical processing unit.

Mareike Thies, Fabian Wagner, Noah Maul et al.

In computed tomography (CT), the projection geometry used for data acquisition needs to be known precisely to obtain a clear reconstructed image. Rigid patient motion is a cause for misalignment between measured data and employed geometry. Commonly, such motion is compensated by solving an optimization problem that, e.g., maximizes the quality of the reconstructed image with respect to the projection geometry. So far, gradient-free optimization algorithms have been utilized to find the solution for this problem. Here, we show that gradient-based optimization algorithms are a possible alternative and compare the performance to their gradient-free counterparts on a benchmark motion compensation problem. Gradient-based algorithms converge substantially faster while being comparable to gradient-free algorithms in terms of capture range and robustness to the number of free parameters. Hence, gradient-based optimization is a viable alternative for the given type of problems.

Fabian Wagner, Mareike Thies, Laura Pfaff et al.

Computed tomography (CT) is routinely used for three-dimensional non-invasive imaging. Numerous data-driven image denoising algorithms were proposed to restore image quality in low-dose acquisitions. However, considerably less research investigates methods already intervening in the raw detector data due to limited access to suitable projection data or correct reconstruction algorithms. In this work, we present an end-to-end trainable CT reconstruction pipeline that contains denoising operators in both the projection and the image domain and that are optimized simultaneously without requiring ground-truth high-dose CT data. Our experiments demonstrate that including an additional projection denoising operator improved the overall denoising performance by 82.4-94.1%/12.5-41.7% (PSNR/SSIM) on abdomen CT and 1.5-2.9%/0.4-0.5% (PSNR/SSIM) on XRM data relative to the low-dose baseline. We make our entire helical CT reconstruction framework publicly available that contains a raw projection rebinning step to render helical projection data suitable for differentiable fan-beam reconstruction operators and end-to-end learning.

Fabian Wagner, Mareike Thies, Felix Denzinger et al.

Low-dose computed tomography (CT) denoising algorithms aim to enable reduced patient dose in routine CT acquisitions while maintaining high image quality. Recently, deep learning~(DL)-based methods were introduced, outperforming conventional denoising algorithms on this task due to their high model capacity. However, for the transition of DL-based denoising to clinical practice, these data-driven approaches must generalize robustly beyond the seen training data. We, therefore, propose a hybrid denoising approach consisting of a set of trainable joint bilateral filters (JBFs) combined with a convolutional DL-based denoising network to predict the guidance image. Our proposed denoising pipeline combines the high model capacity enabled by DL-based feature extraction with the reliability of the conventional JBF. The pipeline's ability to generalize is demonstrated by training on abdomen CT scans without metal implants and testing on abdomen scans with metal implants as well as on head CT data. When embedding two well-established DL-based denoisers (RED-CNN/QAE) in our pipeline, the denoising performance is improved by $10\,\%$/$82\,\%$ (RMSE) and $3\,\%$/$81\,\%$ (PSNR) in regions containing metal and by $6\,\%$/$78\,\%$ (RMSE) and $2\,\%$/$4\,\%$ (PSNR) on head CT data, compared to the respective vanilla model. Concluding, the proposed trainable JBFs limit the error bound of deep neural networks to facilitate the applicability of DL-based denoisers in low-dose CT pipelines.

Fabian Wagner, Mareike Thies, Laura Pfaff et al.

Self-supervised image denoising techniques emerged as convenient methods that allow training denoising models without requiring ground-truth noise-free data. Existing methods usually optimize loss metrics that are calculated from multiple noisy realizations of similar images, e.g., from neighboring tomographic slices. However, those approaches fail to utilize the multiple contrasts that are routinely acquired in medical imaging modalities like MRI or dual-energy CT. In this work, we propose the new self-supervised training scheme Noise2Contrast that combines information from multiple measured image contrasts to train a denoising model. We stack denoising with domain-transfer operators to utilize the independent noise realizations of different image contrasts to derive a self-supervised loss. The trained denoising operator achieves convincing quantitative and qualitative results, outperforming state-of-the-art self-supervised methods by 4.7-11.0%/4.8-7.3% (PSNR/SSIM) on brain MRI data and by 43.6-50.5%/57.1-77.1% (PSNR/SSIM) on dual-energy CT X-ray microscopy data with respect to the noisy baseline. Our experiments on different real measured data sets indicate that Noise2Contrast training generalizes to other multi-contrast imaging modalities.

Jonas Utz, Tobias Weise, Maja Schlereth et al.

Annotating nuclei in microscopy images for the training of neural networks is a laborious task that requires expert knowledge and suffers from inter- and intra-rater variability, especially in fluorescence microscopy. Generative networks such as CycleGAN can inverse the process and generate synthetic microscopy images for a given mask, thereby building a synthetic dataset. However, past works report content inconsistencies between the mask and generated image, partially due to CycleGAN minimizing its loss by hiding shortcut information for the image reconstruction in high frequencies rather than encoding the desired image content and learning the target task. In this work, we propose to remove the hidden shortcut information, called steganography, from generated images by employing a low pass filtering based on the DCT. We show that this increases coherence between generated images and cycled masks and evaluate synthetic datasets on a downstream nuclei segmentation task. Here we achieve an improvement of 5.4 percentage points in the F1-score compared to a vanilla CycleGAN. Integrating advanced regularization techniques into the CycleGAN architecture may help mitigate steganography-related issues and produce more accurate synthetic datasets for nuclei segmentation.

Fabian Wagner, Mareike Thies, Noah Maul et al.

The diagnostic quality of computed tomography (CT) scans is usually restricted by the induced patient dose, scan speed, and image quality. Sparse-angle tomographic scans reduce radiation exposure and accelerate data acquisition, but suffer from image artifacts and noise. Existing image processing algorithms can restore CT reconstruction quality but often require large training data sets or can not be used for truncated objects. This work presents a self-supervised projection inpainting method that allows optimizing missing projective views via gradient-based optimization. By reconstructing independent stacks of projection data, a self-supervised loss is calculated in the CT image domain and used to directly optimize projection image intensities to match the missing tomographic views constrained by the projection geometry. Our experiments on real X-ray microscope (XRM) tomographic mouse tibia bone scans show that our method improves reconstructions by 3.1-7.4%/7.7-17.6% in terms of PSNR/SSIM with respect to the interpolation baseline. Our approach is applicable as a flexible self-supervised projection inpainting tool for tomographic applications.

Mareike Thies, Fabian Wagner, Mingxuan Gu et al.

Intravital X-ray microscopy (XRM) in preclinical mouse models is of vital importance for the identification of microscopic structural pathological changes in the bone which are characteristic of osteoporosis. The complexity of this method stems from the requirement for high-quality 3D reconstructions of the murine bones. However, respiratory motion and muscle relaxation lead to inconsistencies in the projection data which result in artifacts in uncompensated reconstructions. Motion compensation using epipolar consistency conditions (ECC) has previously shown good performance in clinical CT settings. Here, we explore whether such algorithms are suitable for correcting motion-corrupted XRM data. Different rigid motion patterns are simulated and the quality of the motion-compensated reconstructions is assessed. The method is able to restore microscopic features for out-of-plane motion, but artifacts remain for more realistic motion patterns including all six degrees of freedom of rigid motion. Therefore, ECC is valuable for the initial alignment of the projection data followed by further fine-tuning of motion parameters using a reconstruction-based method.

Yipeng Sun, Linda-Sophie Schneider, Mingxuan Gu et al.

Effective denoising is crucial in low-dose CT to enhance subtle structures and low-contrast lesions while preventing diagnostic errors. Supervised methods struggle with limited paired datasets, and self-supervised approaches often require multiple noisy images and rely on deep networks like U-Net, offering little insight into the denoising mechanism. To address these challenges, we propose an interpretable self-supervised single-image denoising framework -- Filter2Noise (F2N). Our approach introduces an Attention-Guided Bilateral Filter that adapted to each noisy input through a lightweight module that predicts spatially varying filter parameters, which can be visualized and adjusted post-training for user-controlled denoising in specific regions of interest. To enable single-image training, we introduce a novel downsampling shuffle strategy with a new self-supervised loss function that extends the concept of Noise2Noise to a single image and addresses spatially correlated noise. On the Mayo Clinic 2016 low-dose CT dataset, F2N outperforms the leading self-supervised single-image method (ZS-N2N) by 4.59 dB PSNR while improving transparency, user control, and parametric efficiency. These features provide key advantages for medical applications that require precise and interpretable noise reduction. Our code is demonstrated at https://github.com/sypsyp97/Filter2Noise.git .

Jonas Utz, Stefan Vocht, Anne Tjorven Buessen et al.

In recent years, numerous neural network architectures specifically designed for the instance segmentation of nuclei in microscopic images have been released. These models embed nuclei-specific priors to outperform generic architectures like U-Nets; however, they require large annotated datasets, which are often not available. Generative models (GANs, diffusion models) have been used to compensate for this by synthesizing training data. These two-stage approaches are computationally expensive, as first a generative model and then a segmentation model has to be trained. We propose CyclePose, a hybrid framework integrating synthetic data generation and segmentation training. CyclePose builds on a CycleGAN architecture, which allows unpaired translation between microscopy images and segmentation masks. We embed a segmentation model into CycleGAN and leverage a cycle consistency loss for self-supervision. Without annotated data, CyclePose outperforms other weakly or unsupervised methods on two public datasets. Code is available at https://github.com/jonasutz/CyclePose

Fabian Wagner, Mareike Thies, Mingxuan Gu et al.

Computed tomography is widely used as an imaging tool to visualize three-dimensional structures with expressive bone-soft tissue contrast. However, CT resolution and radiation dose are tightly entangled, highlighting the importance of low-dose CT combined with sophisticated denoising algorithms. Most data-driven denoising techniques are based on deep neural networks and, therefore, contain hundreds of thousands of trainable parameters, making them incomprehensible and prone to prediction failures. Developing understandable and robust denoising algorithms achieving state-of-the-art performance helps to minimize radiation dose while maintaining data integrity. This work presents an open-source CT denoising framework based on the idea of bilateral filtering. We propose a bilateral filter that can be incorporated into a deep learning pipeline and optimized in a purely data-driven way by calculating the gradient flow toward its hyperparameters and its input. Denoising in pure image-to-image pipelines and across different domains such as raw detector data and reconstructed volume, using a differentiable backprojection layer, is demonstrated. Although only using three spatial parameters and one range parameter per filter layer, the proposed denoising pipelines can compete with deep state-of-the-art denoising architectures with several hundred thousand parameters. Competitive denoising performance is achieved on x-ray microscope bone data (0.7053 and 33.10) and the 2016 Low Dose CT Grand Challenge dataset (0.9674 and 43.07) in terms of SSIM and PSNR. Due to the extremely low number of trainable parameters with well-defined effect, prediction reliance and data integrity is guaranteed at any time in the proposed pipelines, in contrast to most other deep learning-based denoising architectures.

Mareike Thies, Fabian Wagner, Noah Maul et al.

Cone-beam computed tomography (CBCT) systems, with their flexibility, present a promising avenue for direct point-of-care medical imaging, particularly in critical scenarios such as acute stroke assessment. However, the integration of CBCT into clinical workflows faces challenges, primarily linked to long scan duration resulting in patient motion during scanning and leading to image quality degradation in the reconstructed volumes. This paper introduces a novel approach to CBCT motion estimation using a gradient-based optimization algorithm, which leverages generalized derivatives of the backprojection operator for cone-beam CT geometries. Building on that, a fully differentiable target function is formulated which grades the quality of the current motion estimate in reconstruction space. We drastically accelerate motion estimation yielding a 19-fold speed-up compared to existing methods. Additionally, we investigate the architecture of networks used for quality metric regression and propose predicting voxel-wise quality maps, favoring autoencoder-like architectures over contracting ones. This modification improves gradient flow, leading to more accurate motion estimation. The presented method is evaluated through realistic experiments on head anatomy. It achieves a reduction in reprojection error from an initial average of 3mm to 0.61mm after motion compensation and consistently demonstrates superior performance compared to existing approaches. The analytic Jacobian for the backprojection operation, which is at the core of the proposed method, is made publicly available. In summary, this paper contributes to the advancement of CBCT integration into clinical workflows by proposing a robust motion estimation approach that enhances efficiency and accuracy, addressing critical challenges in time-sensitive scenarios.

Noah Maul, Annette Birkhold, Fabian Wagner et al.

Three-dimensional Digital Subtraction Angiography (3D-DSA) is a well-established X-ray-based technique for visualizing vascular anatomy. Recently, four-dimensional DSA (4D-DSA) reconstruction algorithms have been developed to enable the visualization of volumetric contrast flow dynamics through time-series of volumes. . This reconstruction problem is ill-posed mainly due to vessel overlap in the projection direction and geometric vessel foreshortening, which leads to information loss in the recorded projection images. However, knowledge about the underlying fluid dynamics can be leveraged to constrain the solution space. In our work, we implicitly include this information in a neural network-based model that is trained on a dataset of image-based blood flow simulations. The model predicts the spatially averaged contrast agent concentration for each centerline point of the vasculature over time, lowering the overall computational demand. The trained network enables the reconstruction of relative contrast agent concentrations with a mean absolute error of 0.02 $\pm$ 0.02 and a mean absolute percentage error of 5.31 % $\pm$ 9.25 %. Moreover, the network is robust to varying degrees of vessel overlap and vessel foreshortening. Our approach demonstrates the potential of the integration of machine learning and blood flow simulations in time-resolved angiographic flow reconstruction.

Dennis Possart, Leonid Mill, Florian Vollnhals et al.

Nanomaterials exhibit distinctive properties governed by parameters such as size, shape, and surface characteristics, which critically influence their applications and interactions across technological, biological, and environmental contexts. Accurate quantification and understanding of these materials are essential for advancing research and innovation. In this regard, deep learning segmentation networks have emerged as powerful tools that enable automated insights and replace subjective methods with precise quantitative analysis. However, their efficacy depends on representative annotated datasets, which are challenging to obtain due to the costly imaging of nanoparticles and the labor-intensive nature of manual annotations. To overcome these limitations, we introduce DiffRenderGAN, a novel generative model designed to produce annotated synthetic data. By integrating a differentiable renderer into a Generative Adversarial Network (GAN) framework, DiffRenderGAN optimizes textural rendering parameters to generate realistic, annotated nanoparticle images from non-annotated real microscopy images. This approach reduces the need for manual intervention and enhances segmentation performance compared to existing synthetic data methods by generating diverse and realistic data. Tested on multiple ion and electron microscopy cases, including titanium dioxide (TiO$_2$), silicon dioxide (SiO$_2$)), and silver nanowires (AgNW), DiffRenderGAN bridges the gap between synthetic and real data, advancing the quantification and understanding of complex nanomaterial systems.

Siyuan Mei, Fuxin Fan, Mareike Thies et al.

Recently, X-ray microscopy (XRM) and light-sheet fluorescence microscopy (LSFM) have emerged as pivotal tools in preclinical research, particularly for studying bone remodeling diseases such as osteoporosis. These modalities offer micrometer-level resolution, and their integration allows for a complementary examination of bone microstructures which is essential for analyzing functional changes. However, registering high-resolution volumes from these independently scanned modalities poses substantial challenges, especially in real-world and reference-free scenarios. This paper presents BigReg, a fast, two-stage pipeline designed for large-volume registration of XRM and LSFM data. The first stage involves extracting surface features and applying two successive point cloud-based methods for coarse alignment. The subsequent stage refines this alignment using a modified cross-correlation technique, achieving precise volumetric registration. Evaluations using expert-annotated landmarks and augmented test data demonstrate that BigReg approaches the accuracy of landmark-based registration with a landmark distance (LMD) of 8.36\,\textmu m\,$\pm$\,0.12\,\textmu m and a landmark fitness (LM fitness) of 85.71\%\,$\pm$\,1.02\%. Moreover, BigReg can provide an optimal initialization for mutual information-based methods which otherwise fail independently, further reducing LMD to 7.24\,\textmu m\,$\pm$\,0.11\,\textmu m and increasing LM fitness to 93.90\%\,$\pm$\,0.77\%. Ultimately, key microstructures, notably lacunae in XRM and bone cells in LSFM, are accurately aligned, enabling unprecedented insights into the pathology of osteoporosis.

Mareike Thies, Noah Maul, Siyuan Mei et al.

Motion artifacts can compromise the diagnostic value of computed tomography (CT) images. Motion correction approaches require a per-scan estimation of patient-specific motion patterns. In this work, we train a score-based model to act as a probability density estimator for clean head CT images. Given the trained model, we quantify the deviation of a given motion-affected CT image from the ideal distribution through likelihood computation. We demonstrate that the likelihood can be utilized as a surrogate metric for motion artifact severity in the CT image facilitating the application of an iterative, gradient-based motion compensation algorithm. By optimizing the underlying motion parameters to maximize likelihood, our method effectively reduces motion artifacts, bringing the image closer to the distribution of motion-free scans. Our approach achieves comparable performance to state-of-the-art methods while eliminating the need for a representative data set of motion-affected samples. This is particularly advantageous in real-world applications, where patient motion patterns may exhibit unforeseen variability, ensuring robustness without implicit assumptions about recoverable motion types.

Siyuan Mei, Fuxin Fan, Fabian Wagner et al.

Deep learning-based medical image processing algorithms require representative data during development. In particular, surgical data might be difficult to obtain, and high-quality public datasets are limited. To overcome this limitation and augment datasets, a widely adopted solution is the generation of synthetic images. In this work, we employ conditional diffusion models to generate knee radiographs from contour and bone segmentations. Remarkably, two distinct strategies are presented by incorporating the segmentation as a condition into the sampling and training process, namely, conditional sampling and conditional training. The results demonstrate that both methods can generate realistic images while adhering to the conditioning segmentation. The conditional training method outperforms the conditional sampling method and the conventional U-Net.

Felix Denzinger, Michael Wels, Oliver Taubmann et al.

Coronary artery disease (CAD) is often treated minimally invasively with a catheter being inserted into the diseased coronary vessel. If a patient exhibits a Shepherd's Crook (SC) Right Coronary Artery (RCA) - an anatomical norm variant of the coronary vasculature - the complexity of this procedure is increased. Automated reporting of this variant from coronary CT angiography screening would ease prior risk assessment. We propose a 1D convolutional neural network which leverages a sequence of residual dilated convolutions to automatically determine this norm variant from a prior extracted vessel centerline. As the SC RCA is not clearly defined with respect to concrete measurements, labeling also includes qualitative aspects. Therefore, 4.23% samples in our dataset of 519 RCA centerlines were labeled as unsure SC RCAs, with 5.97% being labeled as sure SC RCAs. We explore measures to handle this label uncertainty, namely global/model-wise random assignment, exclusion, and soft label assignment. Furthermore, we evaluate how this uncertainty can be leveraged for the determination of a rejection class. With our best configuration, we reach an area under the receiver operating characteristic curve (AUC) of 0.938 on confident labels. Moreover, we observe an increase of up to 0.020 AUC when rejecting 10% of the data and leveraging the labeling uncertainty information in the exclusion process.

Mareike Thies, Fabian Wagner, Mingxuan Gu et al.

Learned iterative reconstruction algorithms for inverse problems offer the flexibility to combine analytical knowledge about the problem with modules learned from data. This way, they achieve high reconstruction performance while ensuring consistency with the measured data. In computed tomography, extending such approaches from 2D fan-beam to 3D cone-beam data is challenging due to the prohibitively high GPU memory that would be needed to train such models. This paper proposes to use neural ordinary differential equations to solve the reconstruction problem in a residual formulation via numerical integration. For training, there is no need to backpropagate through several unrolled network blocks nor through the internals of the solver. Instead, the gradients are obtained very memory-efficiently in the neural ODE setting allowing for training on a single consumer graphics card. The method is able to reduce the root mean squared error by over 30% compared to the best performing classical iterative reconstruction algorithm and produces high quality cone-beam reconstructions even in a sparse view scenario.