Interpretable Embeddings for Segmentation-Free Single-Cell Analysis in Multiplex Imaging

Multiplex Imaging (MI) enables the simultaneous visualization of multiple biological markers in separate imaging channels at subcellular resolution, providing valuable insights into cell-type heterogeneity and spatial organization. However, current computational pipelines rely on cell segmentation algorithms, which require laborious fine-tuning and can introduce downstream errors due to inaccurate single-cell representations. We propose a segmentation-free deep learning approach that leverages grouped convolutions to learn interpretable embedded features from each imaging channel, enabling robust cell-type identification without manual feature selection. Validated on an Imaging Mass Cytometry dataset of 1.8 million cells from neuroblastoma patients, our method enables the accurate identification of known cell types, showcasing its scalability and suitability for high-dimensional MI data.

FISHing in Uncertainty: Synthetic Contrastive Learning for Genetic Aberration Detection

Detecting genetic aberrations is crucial in cancer diagnosis, typically through fluorescence in situ hybridization (FISH). However, existing FISH image classification methods face challenges due to signal variability, the need for costly manual annotations and fail to adequately address the intrinsic uncertainty. We introduce a novel approach that leverages synthetic images to eliminate the requirement for manual annotations and utilizes a joint contrastive and classification objective for training to account for inter-class variation effectively. We demonstrate the superior generalization capabilities and uncertainty calibration of our method, which is trained on synthetic data, by testing it on a manually annotated dataset of real-world FISH images. Our model offers superior calibration in terms of classification accuracy and uncertainty quantification with a classification accuracy of 96.7% among the 50% most certain cases. The presented end-to-end method reduces the demands on personnel and time and improves the diagnostic workflow due to its accuracy and adaptability. All code and data is publicly accessible at: https://github.com/SimonBon/FISHing

Multi-Center Fetal Brain Tissue Annotation (FeTA) Challenge 2022 Results

Segmentation is a critical step in analyzing the developing human fetal brain. There have been vast improvements in automatic segmentation methods in the past several years, and the Fetal Brain Tissue Annotation (FeTA) Challenge 2021 helped to establish an excellent standard of fetal brain segmentation. However, FeTA 2021 was a single center study, and the generalizability of algorithms across different imaging centers remains unsolved, limiting real-world clinical applicability. The multi-center FeTA Challenge 2022 focuses on advancing the generalizability of fetal brain segmentation algorithms for magnetic resonance imaging (MRI). In FeTA 2022, the training dataset contained images and corresponding manually annotated multi-class labels from two imaging centers, and the testing data contained images from these two imaging centers as well as two additional unseen centers. The data from different centers varied in many aspects, including scanners used, imaging parameters, and fetal brain super-resolution algorithms applied. 16 teams participated in the challenge, and 17 algorithms were evaluated. Here, a detailed overview and analysis of the challenge results are provided, focusing on the generalizability of the submissions. Both in- and out of domain, the white matter and ventricles were segmented with the highest accuracy, while the most challenging structure remains the cerebral cortex due to anatomical complexity. The FeTA Challenge 2022 was able to successfully evaluate and advance generalizability of multi-class fetal brain tissue segmentation algorithms for MRI and it continues to benchmark new algorithms. The resulting new methods contribute to improving the analysis of brain development in utero.

Fetal Brain Tissue Annotation and Segmentation Challenge Results

In-utero fetal MRI is emerging as an important tool in the diagnosis and analysis of the developing human brain. Automatic segmentation of the developing fetal brain is a vital step in the quantitative analysis of prenatal neurodevelopment both in the research and clinical context. However, manual segmentation of cerebral structures is time-consuming and prone to error and inter-observer variability. Therefore, we organized the Fetal Tissue Annotation (FeTA) Challenge in 2021 in order to encourage the development of automatic segmentation algorithms on an international level. The challenge utilized FeTA Dataset, an open dataset of fetal brain MRI reconstructions segmented into seven different tissues (external cerebrospinal fluid, grey matter, white matter, ventricles, cerebellum, brainstem, deep grey matter). 20 international teams participated in this challenge, submitting a total of 21 algorithms for evaluation. In this paper, we provide a detailed analysis of the results from both a technical and clinical perspective. All participants relied on deep learning methods, mainly U-Nets, with some variability present in the network architecture, optimization, and image pre- and post-processing. The majority of teams used existing medical imaging deep learning frameworks. The main differences between the submissions were the fine tuning done during training, and the specific pre- and post-processing steps performed. The challenge results showed that almost all submissions performed similarly. Four of the top five teams used ensemble learning methods. However, one team's algorithm performed significantly superior to the other submissions, and consisted of an asymmetrical U-Net network architecture. This paper provides a first of its kind benchmark for future automatic multi-tissue segmentation algorithms for the developing human brain in utero.

Motion Correction and Volumetric Reconstruction for Fetal Functional Magnetic Resonance Imaging Data

Motion correction is an essential preprocessing step in functional Magnetic Resonance Imaging (fMRI) of the fetal brain with the aim to remove artifacts caused by fetal movement and maternal breathing and consequently to suppress erroneous signal correlations. Current motion correction approaches for fetal fMRI choose a single 3D volume from a specific acquisition timepoint with least motion artefacts as reference volume, and perform interpolation for the reconstruction of the motion corrected time series. The results can suffer, if no low-motion frame is available, and if reconstruction does not exploit any assumptions about the continuity of the fMRI signal. Here, we propose a novel framework, which estimates a high-resolution reference volume by using outlier-robust motion correction, and by utilizing Huber L2 regularization for intra-stack volumetric reconstruction of the motion-corrected fetal brain fMRI. We performed an extensive parameter study to investigate the effectiveness of motion estimation and present in this work benchmark metrics to quantify the effect of motion correction and regularised volumetric reconstruction approaches on functional connectivity computations. We demonstrate the proposed framework's ability to improve functional connectivity estimates, reproducibility and signal interpretability, which is clinically highly desirable for the establishment of prognostic noninvasive imaging biomarkers. The motion correction and volumetric reconstruction framework is made available as an open-source package of NiftyMIC.

4D iterative reconstruction of brain fMRI in the moving fetus

Resting-state functional Magnetic Resonance Imaging (fMRI) is a powerful imaging technique for studying functional development of the brain in utero. However, unpredictable and excessive movement of fetuses has limited clinical application since it causes substantial signal fluctuations which can systematically alter observed patterns of functional connectivity. Previous studies have focused on the accurate estimation of the motion parameters in case of large fetal head movement and used a 3D single step interpolation approach at each timepoint to recover motion-free fMRI images. This does not guarantee that the reconstructed image corresponds to the minimum error representation of fMRI time series given the acquired data. Here, we propose a novel technique based on four dimensional iterative reconstruction of the scattered slices acquired during fetal fMRI. The accuracy of the proposed method was quantitatively evaluated on a group of real clinical fMRI fetuses. The results indicate improvements of reconstruction quality compared to the conventional 3D interpolation approach.