Florian Mueller

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).

Arthur Imbert, Florian Mueller, Thomas Walter

Subcellular RNA localization is a critical mechanism for the spatial control of gene expression. Its mechanism and precise functional role is not yet very well understood. Single Molecule Fluorescence in Situ Hybridization (smFISH) images allow for the detection of individual RNA molecules with subcellular accuracy. In return, smFISH requires robust methods to quantify and classify RNA spatial distribution. Here, we present PointFISH, a novel computational approach for the recognition of RNA localization patterns. PointFISH is an attention-based network for computing continuous vector representations of RNA point clouds. Trained on simulations only, it can directly process extracted coordinates from experimental smFISH images. The resulting embedding allows scalable and flexible spatial transcriptomics analysis and matches performance of hand-crafted pipelines.

Wei Ouyang, Florian Mueller, Martin Hjelmare et al.

Deep learning methods have shown extraordinary potential for analyzing very diverse biomedical data, but their dissemination beyond developers is hindered by important computational hurdles. We introduce ImJoy (https://imjoy.io/), a flexible and open-source browser-based platform designed to facilitate widespread reuse of deep learning solutions in biomedical research. We highlight ImJoy's main features and illustrate its functionalities with deep learning plugins for mobile and interactive image analysis and genomics.

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.