Volkmar Schulz

Raphael Schäfer, Till Nicke, Henning Höfener et al.

Foundational models, pretrained on a large scale, have demonstrated substantial success across non-medical domains. However, training these models typically requires large, comprehensive datasets, which contrasts with the smaller and more heterogeneous datasets common in biomedical imaging. Here, we propose a multi-task learning strategy that decouples the number of training tasks from memory requirements. We trained a Universal bioMedical PreTrained model (UMedPT) on a multi-task database including tomographic, microscopic, and X-ray images, with various labelling strategies such as classification, segmentation, and object detection. The UMedPT foundational model outperformed ImageNet pretraining and the previous state-of-the-art models. For tasks related to the pretraining database, it maintained its performance with only 1% of the original training data and without fine-tuning. For out-of-domain tasks it required not more than 50% of the original training data. In an external independent validation imaging features extracted using UMedPT proved to be a new standard for cross-center transferability.

Stephan Naunheim, Yannick Kuhl, David Schug et al.

Artificial intelligence (AI) is entering medical imaging, mainly enhancing image reconstruction. Nevertheless, improvements throughout the entire processing, from signal detection to computation, potentially offer significant benefits. This work presents a novel and versatile approach to detector optimization using machine learning (ML) and residual physics. We apply the concept to positron emission tomography (PET), intending to improve the coincidence time resolution (CTR). PET visualizes metabolic processes in the body by detecting photons with scintillation detectors. Improved CTR performance offers the advantage of reducing radioactive dose exposure for patients. Modern PET detectors with sophisticated concepts and read-out topologies represent complex physical and electronic systems requiring dedicated calibration techniques. Traditional methods primarily depend on analytical formulations successfully describing the main detector characteristics. However, when accounting for higher-order effects, additional complexities arise matching theoretical models to experimental reality. Our work addresses this challenge by combining traditional calibration with AI and residual physics, presenting a highly promising approach. We present a residual physics-based strategy using gradient tree boosting and physics-guided data generation. The explainable AI framework SHapley Additive exPlanations (SHAP) was used to identify known physical effects with learned patterns. In addition, the models were tested against basic physical laws. We were able to improve the CTR significantly (more than 20%) for clinically relevant detectors of 19 mm height, reaching CTRs of 185 ps (450-550 keV).

Rüveyda Yilmaz, Yuli Wu, Johannes Stegmaier et al.

Positron Emission Tomography (PET) image reconstruction is inherently challenged by Poisson noise and physical degradation factors, which are further exacerbated in limited-angle acquisitions. While deep learning methods demonstrate promising performance, their generalization to unseen clinical data distributions remains limited without extensive retraining. We propose PET-Adapter, a test-time domain adaptation framework for generative PET reconstruction models pretrained solely on phantom data. Our method enables adaptation to clinical datasets with varying anatomies, tracers, and scanner configurations without requiring paired ground truth. PET-Adapter introduces layer-wise low-rank anatomical conditioning during adaptation and Ordered Subset Expectation Maximization-based warm-starting that initializes the generation from physics-informed reconstructions, reducing diffusion steps from 50 to 2 without compromising quality. Experiments across multiple clinical datasets demonstrate superior 3D reconstruction performance in both full-angle and limited-angle settings, highlighting the clinical feasibility and computational efficiency of the proposed approach.

Rüveyda Yilmaz, Julian Thull, Johannes Stegmaier et al.

Accurate PET imaging increasingly requires methods that support unconstrained detector layouts from walk-through designs to long-axial rings where gaps and open sides lead to severely undersampled sinograms. Instead of constraining the hardware to form complete cylinders, we propose treating the missing lines-of-responses as a learnable prior. Data-driven approaches, particularly generative models, offer a promising pathway to recover this missing information. In this work, we explore the use of conditional diffusion models to interpolate sparsely sampled sinograms, paving the way for novel, cost-efficient, and patient-friendly PET geometries in real clinical settings.

Ankit Amrutkar, Björn Kampa, Volkmar Schulz et al.

Computer-generated holography (CGH) enables applications in holographic augmented reality (AR), 3D displays, systems neuroscience, and optical trapping. The fundamental challenge in CGH is solving the inverse problem of phase retrieval from intensity measurements. Physics-inspired neural networks (PINNs), especially Gerchberg-Saxton-based PINNs (GS-PINNs), have advanced phase retrieval capabilities. However, their performance strongly depends on forward models (FMs) and their hyperparameters (FMHs), limiting generalization, complicating benchmarking, and hindering hardware optimization. We present a systematic sensitivity analysis framework based on Saltelli's extension of Sobol's method to quantify FMH impacts on GS-PINN performance. Our analysis demonstrates that SLM pixel-resolution is the primary factor affecting neural network sensitivity, followed by pixel-pitch, propagation distance, and wavelength. Free space propagation forward models demonstrate superior neural network performance compared to Fourier holography, providing enhanced parameterization and generalization. We introduce a composite evaluation metric combining performance consistency, generalization capability, and hyperparameter perturbation resilience, establishing a unified benchmarking standard across CGH configurations. Our research connects physics-inspired deep learning theory with practical CGH implementations through concrete guidelines for forward model selection, neural network architecture, and performance evaluation. Our contributions advance the development of robust, interpretable, and generalizable neural networks for diverse holographic applications, supporting evidence-based decisions in CGH research and implementation.

Stephan Naunheim, Luis Lopes de Paiva, Vanessa Nadig et al.

PET is a functional imaging method that visualizes metabolic processes. TOF information can be derived from coincident detector signals and incorporated into image reconstruction to enhance the SNR. PET detectors are typically assessed by their CTR, but timing performance is degraded by various factors. Research on timing calibration seeks to mitigate these degradations and restore accurate timing information. While many calibration methods use analytical approaches, machine learning techniques have recently gained attention due to their flexibility. We developed a residual physics-based calibration approach that combines prior domain knowledge with the power of machine learning models. This approach begins with an initial analytical calibration addressing first-order skews. The remaining deviations, regarded as residual effects, are used to train machine learning models to eliminate higher-order skews. The key advantage is that the experimenter guides the learning process through the definition of timing residuals. In earlier studies, we developed models that directly predicted the expected time difference, which offered corrections only implicitly (implicit correction models). In this study, we introduce a new definition for timing residuals, enabling us to train models that directly predict correction values (explicit correction models). The explicit correction approach significantly simplifies data acquisition, improves linearity, and enhances timing performance from $371 \pm 6$ ps to $281 \pm 5$ ps for coincidences from 430 keV to 590 keV. Additionally, the new definition reduces model size, making it suitable for high-throughput applications like PET scanners. Experiments were conducted using two detector stacks composed of $4 \times 4$ LYSO:Ce,Ca crystals ($3.8\times 3.8\times 20$ mm$^{3}$) coupled to $4 \times 4$ Broadcom NUV-MT SiPMs and digitized with the TOFPET2 ASIC.

Tianyu Han, Jakob Nikolas Kather, Federico Pedersoli et al.

Disease-modifying management aims to prevent deterioration and progression of the disease, not just relieve symptoms. Unfortunately, the development of necessary therapies is often hampered by the failure to recognize the presymptomatic disease and limited understanding of disease development. We present a generic solution for this problem by a methodology that allows the prediction of progression risk and morphology in individuals using a latent extrapolation optimization approach. To this end, we combined a regularized generative adversarial network (GAN) and a latent nearest neighbor algorithm for joint optimization to generate plausible images of future time points. We evaluated our method on osteoarthritis (OA) data from a multi-center longitudinal study (the Osteoarthritis Initiative, OAI). With presymptomatic baseline data, our model is generative and significantly outperforms the end-to-end learning model in discriminating the progressive cohort. Two experiments were performed with seven experienced radiologists. When no synthetic follow-up radiographs were provided, our model performed better than all seven radiologists. In cases where the synthetic follow-ups generated by our model were available, the specificity and sensitivity of all readers in discriminating progressors increased from $72.3\%$ to $88.6\%$ and from $42.1\%$ to $51.6\%$, respectively. Our results open up a new possibility of using model-based morphology and risk prediction to make predictions about future disease occurrence, as demonstrated in the example of OA.

Tianyu Han, Sven Nebelung, Federico Pedersoli et al.

Unmasking the decision-making process of machine learning models is essential for implementing diagnostic support systems in clinical practice. Here, we demonstrate that adversarially trained models can significantly enhance the usability of pathology detection as compared to their standard counterparts. We let six experienced radiologists rate the interpretability of saliency maps in datasets of X-rays, computed tomography, and magnetic resonance imaging scans. Significant improvements were found for our adversarial models, which could be further improved by the application of dual batch normalization. Contrary to previous research on adversarially trained models, we found that the accuracy of such models was equal to standard models when sufficiently large datasets and dual batch norm training were used. To ensure transferability, we additionally validated our results on an external test set of 22,433 X-rays. These findings elucidate that different paths for adversarial and real images are needed during training to achieve state of the art results with superior clinical interpretability.