Alexander Denker

Imraj RD Singh, Alexander Denker, Riccardo Barbano et al.

Score-based generative models have demonstrated highly promising results for medical image reconstruction tasks in magnetic resonance imaging or computed tomography. However, their application to Positron Emission Tomography (PET) is still largely unexplored. PET image reconstruction involves a variety of challenges, including Poisson noise with high variance and a wide dynamic range. To address these challenges, we propose several PET-specific adaptations of score-based generative models. The proposed framework is developed for both 2D and 3D PET. In addition, we provide an extension to guided reconstruction using magnetic resonance images. We validate the approach through extensive 2D and 3D $\textit{in-silico}$ experiments with a model trained on patient-realistic data without lesions, and evaluate on data without lesions as well as out-of-distribution data with lesions. This demonstrates the proposed method's robustness and significant potential for improved PET reconstruction.

Fabian Altekrüger, Alexander Denker, Paul Hagemann et al.

Learning neural networks using only few available information is an important ongoing research topic with tremendous potential for applications. In this paper, we introduce a powerful regularizer for the variational modeling of inverse problems in imaging. Our regularizer, called patch normalizing flow regularizer (patchNR), involves a normalizing flow learned on small patches of very few images. In particular, the training is independent of the considered inverse problem such that the same regularizer can be applied for different forward operators acting on the same class of images. By investigating the distribution of patches versus those of the whole image class, we prove that our model is indeed a MAP approach. Numerical examples for low-dose and limited-angle computed tomography (CT) as well as superresolution of material images demonstrate that our method provides very high quality results. The training set consists of just six images for CT and one image for superresolution. Finally, we combine our patchNR with ideas from internal learning for performing superresolution of natural images directly from the low-resolution observation without knowledge of any high-resolution image.

Riccardo Barbano, Alexander Denker, Hyungjin Chung et al.

Denoising diffusion models have emerged as the go-to generative framework for solving inverse problems in imaging. A critical concern regarding these models is their performance on out-of-distribution tasks, which remains an under-explored challenge. Using a diffusion model on an out-of-distribution dataset, realistic reconstructions can be generated, but with hallucinating image features that are uniquely present in the training dataset. To address this discrepancy during train-test time and improve reconstruction accuracy, we introduce a novel sampling framework called Steerable Conditional Diffusion. Specifically, this framework adapts the diffusion model, concurrently with image reconstruction, based solely on the information provided by the available measurement. Utilising our proposed method, we achieve substantial enhancements in out-of-distribution performance across diverse imaging modalities, advancing the robust deployment of denoising diffusion models in real-world applications.

Elizabeth L. Baker, Alexander Denker, Jes Frellsen

Score-based diffusion models have recently been extended to infinite-dimensional function spaces, with uses such as inverse problems arising from partial differential equations. In the Bayesian formulation of inverse problems, the aim is to sample from a posterior distribution over functions obtained by conditioning a prior on noisy observations. While diffusion models provide expressive priors in function space, the theory of conditioning them to sample from the posterior remains open. We address this, assuming that either the prior lies in the Cameron-Martin space, or is absolutely continuous with respect to a Gaussian measure. We prove that the models can be conditioned using an infinite-dimensional extension of Doob's $h$-transform, and that the conditional score decomposes into an unconditional score and a guidance term. As the guidance term is intractable, we propose a simulation-free score matching objective (called Supervised Guidance Training) enabling efficient and stable posterior sampling. We illustrate the theory with numerical examples on Bayesian inverse problems in function spaces. In summary, our work offers the first function-space method for fine-tuning trained diffusion models to accurately sample from a posterior.

Alexander Denker, Moshe Eliasof, Zeljko Kereta et al.

Flow-based generative models have emerged as powerful priors for solving inverse problems. One option is to directly optimize the initial latent code (noise), such that the flow output solves the inverse problem. However, this requires backpropagating through the entire generative trajectory, incurring high memory costs and numerical instability. We propose MS-Flow, which represents the trajectory as a sequence of intermediate latent states rather than a single initial code. By enforcing the flow dynamics locally and coupling segments through trajectory-matching penalties, MS-Flow alternates between updating intermediate latent states and enforcing consistency with observed data. This reduces memory consumption while improving reconstruction quality. We demonstrate the effectiveness of MS-Flow over existing methods on image recovery and inverse problems, including inpainting, super-resolution, and computed tomography.

George Webber, Alexander Denker, Riccardo Barbano et al.

Flow-based generative models provide strong unconditional priors for inverse problems, but guiding their dynamics for conditional generation remains challenging. Recent work casts training-free conditional generation in flow models as an optimal control problem; however, solving the resulting trajectory optimisation is computationally and memory intensive, requiring differentiation through the flow dynamics or adjoint solves. We propose MPC-Flow, a model predictive control framework that formulates inverse problem solving with flow-based generative models as a sequence of control sub-problems, enabling practical optimal control-based guidance at inference time. We provide theoretical guarantees linking MPC-Flow to the underlying optimal control objective and show how different algorithmic choices yield a spectrum of guidance algorithms, including regimes that avoid backpropagation through the generative model trajectory. We evaluate MPC-Flow on benchmark image restoration tasks, spanning linear and non-linear settings such as in-painting, deblurring, and super-resolution, and demonstrate strong performance and scalability to massive state-of-the-art architectures via training-free guidance of FLUX.2 (32B) in a quantised setting on consumer hardware.

Riccardo Barbano, Alexander Denker, Zeljko Kereta et al.

Continuous-time generative models have achieved remarkable success in image restoration and synthesis. However, controlling the composition of multiple pre-trained models remains an open challenge. Current approaches largely treat composition as an algebraic composition of probability densities, such as via products or mixtures of experts. This perspective assumes the target distribution is known explicitly, which is almost never the case. In this work, we propose a different paradigm that formulates compositional generation as a cooperative Stochastic Optimal Control problem. Rather than combining probability densities, we treat pre-trained diffusion models as interacting agents whose diffusion trajectories are jointly steered, via optimal control, toward a shared objective defined on their aggregated output. We validate our framework on conditional MNIST generation and compare it against a naive inference-time DPS-style baseline replacing learned cooperative control with per-step gradient guidance.

Alexander Denker, Johannes Hertrich, Sebastian Neumayer

Generative (diffusion) priors demonstrate remarkable performance in addressing inverse problems in imaging. Yet, for scientific and medical imaging, it is crucial that reconstruction techniques remain stable and reliable under imperfect settings. Typical definitions of stability encompass the notion of ''convergent regularization'', robustness to out-of-distribution data, and to inaccuracies in the forward operator or noise model. We evaluate these properties numerically. Furthermore, we benchmark generative approaches against modern optimization-based methods inspired by the widely used variational techniques. Our results give insights for which settings and applications generative priors can deliver state-of-the-art reconstructions, and on those in which they fall short or may even be problematic.

James Rowbottom, Elizabeth L. Baker, Nick Huang et al.

Score-based diffusion models in infinite-dimensional function spaces provide a mathematically principled framework for modelling function-valued data, offering key advantages such as resolution invariance and the ability to handle irregular discretisations. However, practical implementations have struggled to fully realise these benefits. Existing backbones like Fourier neural operators are often biased towards regular grids and fail to generalise to complex domain topologies. We propose a novel architecture for function-space diffusion models that represents generalised graph convolutional kernels as finite element functions, enabling the model to naturally handle unstructured meshes and complex geometries. We demonstrate the efficacy of our network architecture through a series of unconditional and conditional sampling experiments across diverse geometries, including non-convex and multiply-connected domains. Our results show that the proposed method maintains resolution invariance and achieves high fidelity in capturing functional distributions on non-trivial geometries.

Johannes Hertrich, Hok Shing Wong, Alexander Denker et al.

In recent years, a variety of learned regularization frameworks for solving inverse problems in imaging have emerged. These offer flexible modeling together with mathematical insights. The proposed methods differ in their architectural design and training strategies, making direct comparison challenging due to non-modular implementations. We address this gap by collecting and unifying the available code into a common framework. This unified view allows us to systematically compare the approaches and highlight their strengths and limitations, providing valuable insights into their future potential. We also provide concise descriptions of each method, complemented by practical guidelines.

Alexander Denker, Shreyas Padhy, Francisco Vargas et al.

Diffusion models are an important tool for generative modelling, serving as effective priors in applications such as imaging and protein design. A key challenge in applying diffusion models for downstream tasks is efficiently sampling from resulting posterior distributions, which can be addressed using the $h$-transform. This work introduces a self-supervised algorithm for fine-tuning diffusion models by estimating the $h$-transform, enabling amortised conditional sampling. Our method iteratively refines the $h$-transform using a synthetic dataset resampled with path-based importance weights. We demonstrate the effectiveness of this framework on class-conditional sampling, inverse problems and reward fine-tuning for text-to-image diffusion models.

Alexander Denker, Johannes Hertrich, Zeljko Kereta et al.

Ptychography is a coherent diffraction imaging method that uses phase retrieval techniques to reconstruct complex-valued images. It achieves this by sequentially illuminating overlapping regions of a sample with a coherent beam and recording the diffraction pattern. Although this addresses traditional imaging system challenges, it is computationally intensive and highly sensitive to noise, especially with reduced illumination overlap. Data-driven regularisation techniques have been applied in phase retrieval to improve reconstruction quality. In particular, plug-and-play (PnP) offers flexibility by integrating data-driven denoisers as implicit priors. In this work, we propose a half-quadratic splitting framework for using PnP and other data-driven priors for ptychography. We evaluate our method both on natural images and real test objects to validate its effectiveness for ptychographic image reconstruction.

Serban C. Tudosie, Alexander Denker, Zeljko Kereta et al.

Single-Pixel Imaging enables reconstructing objects using a single detector through sequential illuminations with structured light patterns. We propose a bilevel optimisation method for learning task-specific, binary illumination patterns, optimised for applications like single-pixel fluorescence microscopy. We address the non-differentiable nature of binary pattern optimisation using the Straight-Through Estimator and leveraging a Total Deep Variation regulariser in the bilevel formulation. We demonstrate our method on the CytoImageNet microscopy dataset and show that learned patterns achieve superior reconstruction performance compared to baseline methods, especially in highly undersampled regimes.

William Lauga, James Rowbottom, Alexander Denker et al.

We present a framework for solving a broad class of ill-posed inverse problems governed by partial differential equations (PDEs), where the target coefficients of the forward operator are recovered through an iterative regularization scheme that alternates between FEM-based inversion and learned graph neural regularization. The forward problem is numerically solved using the finite element method (FEM), enabling applicability to a wide range of geometries and PDEs. By leveraging the graph structure inherent to FEM discretizations, we employ physics-inspired graph neural networks as learned regularizers, providing a robust, interpretable, and generalizable alternative to standard approaches. Numerical experiments demonstrate that our framework outperforms classical regularization techniques and achieves accurate reconstructions even in highly ill-posed scenarios.

Alexander Denker, Francisco Vargas, Shreyas Padhy et al.

Generative modelling paradigms based on denoising diffusion processes have emerged as a leading candidate for conditional sampling in inverse problems. In many real-world applications, we often have access to large, expensively trained unconditional diffusion models, which we aim to exploit for improving conditional sampling. Most recent approaches are motivated heuristically and lack a unifying framework, obscuring connections between them. Further, they often suffer from issues such as being very sensitive to hyperparameters, being expensive to train or needing access to weights hidden behind a closed API. In this work, we unify conditional training and sampling using the mathematically well-understood Doob's h-transform. This new perspective allows us to unify many existing methods under a common umbrella. Under this framework, we propose DEFT (Doob's h-transform Efficient FineTuning), a new approach for conditional generation that simply fine-tunes a very small network to quickly learn the conditional $h$-transform, while keeping the larger unconditional network unchanged. DEFT is much faster than existing baselines while achieving state-of-the-art performance across a variety of linear and non-linear benchmarks. On image reconstruction tasks, we achieve speedups of up to 1.6$\times$, while having the best perceptual quality on natural images and reconstruction performance on medical images. Further, we also provide initial experiments on protein motif scaffolding and outperform reconstruction guidance methods.

Alexander Denker, Zeljko Kereta, Imraj Singh et al.

Electrical impedance tomography (EIT) plays a crucial role in non-invasive imaging, with both medical and industrial applications. In this paper, we present three data-driven reconstruction methods for EIT imaging. These three approaches were originally submitted to the Kuopio tomography challenge 2023 (KTC2023). First, we introduce a post-processing approach, which achieved first place at KTC2023. Further, we present a fully learned and a conditional diffusion approach. All three methods are based on a similar neural network as a backbone and were trained using a synthetically generated data set, providing with an opportunity for a fair comparison of these different data-driven reconstruction methods.

Pascal Fernsel, Željko Kereta, Alexander Denker

The incorporation of generative models as regularisers within variational formulations for inverse problems has proven effective across numerous image reconstruction tasks. However, the resulting optimisation problem is often non-convex and challenging to solve. In this work, we show that score-based generative models (SGMs) can be used in a graduated optimisation framework to solve inverse problems. We show that the resulting graduated non-convexity flow converge to stationary points of the original problem and provide a numerical convergence analysis of a 2D toy example. We further provide experiments on computed tomography image reconstruction, where we show that this framework is able to recover high-quality images, independent of the initial value. The experiments highlight the potential of using SGMs in graduated optimisation frameworks. The source code is publicly available on GitHub.

Riccardo Barbano, Johannes Leuschner, Maximilian Schmidt et al.

Deep image prior (DIP) was recently introduced as an effective unsupervised approach for image restoration tasks. DIP represents the image to be recovered as the output of a deep convolutional neural network, and learns the network's parameters such that the output matches the corrupted observation. Despite its impressive reconstructive properties, the approach is slow when compared to supervisedly learned, or traditional reconstruction techniques. To address the computational challenge, we bestow DIP with a two-stage learning paradigm: (i) perform a supervised pretraining of the network on a simulated dataset; (ii) fine-tune the network's parameters to adapt to the target reconstruction task. We provide a thorough empirical analysis to shed insights into the impacts of pretraining in the context of image reconstruction. We showcase that pretraining considerably speeds up and stabilizes the subsequent reconstruction task from real-measured 2D and 3D micro computed tomography data of biological specimens. The code and additional experimental materials are available at https://educateddip.github.io/docs.educated_deep_image_prior/.

Alexander Denker, Anastasia Steshina, Theresa Grooss et al.

We present the GeneScore, a concept of feature reduction for Machine Learning analysis of biomedical data. Using expert knowledge, the GeneScore integrates different molecular data types into a single score. We show that the GeneScore is superior to a binary matrix in the classification of cancer entities from SNV, Indel, CNV, gene fusion and gene expression data. The GeneScore is a straightforward way to facilitate state-of-the-art analysis, while making use of the available scientific knowledge on the nature of molecular data features used.