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Josien P. W. Pluim

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Published work

11 published item(s)

preprint2026arXiv

Attention-Based Multimodal Survival Prediction with Cross-Modal Bilinear Fusion

We propose a novel multimodal deep learning framework for patient-level survival prediction, which integrates whole-slide histology features, RNA-seq expression profiles, and clinical variables. Our architecture combines an ABMIL module~\cite{ilse2018attention} for slide-level representation with feedforward encoders for RNA and clinical data. These embeddings are then integrated through low-rank bilinear cross-modal fusion~\cite{liu2018efficient} to model conditional interactions across modalities while controlling parameter growth. The model outputs continuous risk scores that are subsequently mapped to survival times using a nonparametric calibration procedure based on the Kaplan--Meier estimator~\cite{kaplan1958nonparametric}. By decomposing multimodal reasoning into independent pairwise interactions, the proposed fusion design promotes structural interpretability and parameter efficiency compared with full tensor and hierarchical fusion strategies. Experiments on the CHIMERA challenge dataset demonstrate improved predictive performance over concatenation-based baselines and competitive generalization on hidden evaluation cohorts. These results indicate that the proposed framework is a promising approach for multimodal survival prediction in HR-NMIBC. The implementation is publicly available at https://github.com/hassancpu/ChimeraChallenge2025_Task_3.

preprint2022arXiv

clDice -- A Novel Topology-Preserving Loss Function for Tubular Structure Segmentation

Accurate segmentation of tubular, network-like structures, such as vessels, neurons, or roads, is relevant to many fields of research. For such structures, the topology is their most important characteristic; particularly preserving connectedness: in the case of vascular networks, missing a connected vessel entirely alters the blood-flow dynamics. We introduce a novel similarity measure termed centerlineDice (short clDice), which is calculated on the intersection of the segmentation masks and their (morphological) skeleta. We theoretically prove that clDice guarantees topology preservation up to homotopy equivalence for binary 2D and 3D segmentation. Extending this, we propose a computationally efficient, differentiable loss function (soft-clDice) for training arbitrary neural segmentation networks. We benchmark the soft-clDice loss on five public datasets, including vessels, roads and neurons (2D and 3D). Training on soft-clDice leads to segmentation with more accurate connectivity information, higher graph similarity, and better volumetric scores.

preprint2022arXiv

Generalized Probabilistic U-Net for medical image segementation

We propose the Generalized Probabilistic U-Net, which extends the Probabilistic U-Net by allowing more general forms of the Gaussian distribution as the latent space distribution that can better approximate the uncertainty in the reference segmentations. We study the effect the choice of latent space distribution has on capturing the uncertainty in the reference segmentations using the LIDC-IDRI dataset. We show that the choice of distribution affects the sample diversity of the predictions and their overlap with respect to the reference segmentations. For the LIDC-IDRI dataset, we show that using a mixture of Gaussians results in a statistically significant improvement in the generalized energy distance (GED) metric with respect to the standard Probabilistic U-Net. We have made our implementation available at https://github.com/ishaanb92/GeneralizedProbabilisticUNet

preprint2021arXiv

Using uncertainty estimation to reduce false positives in liver lesion detection

Despite the successes of deep learning techniques at detecting objects in medical images, false positive detections occur which may hinder an accurate diagnosis. We propose a technique to reduce false positive detections made by a neural network using an SVM classifier trained with features derived from the uncertainty map of the neural network prediction. We demonstrate the effectiveness of this method for the detection of liver lesions on a dataset of abdominal MR images. We find that the use of a dropout rate of 0.5 produces the least number of false positives in the neural network predictions and the trained classifier filters out approximately 90% of these false positives detections in the test-set.

preprint2020arXiv

Orientation-Disentangled Unsupervised Representation Learning for Computational Pathology

Unsupervised learning enables modeling complex images without the need for annotations. The representation learned by such models can facilitate any subsequent analysis of large image datasets. However, some generative factors that cause irrelevant variations in images can potentially get entangled in such a learned representation causing the risk of negatively affecting any subsequent use. The orientation of imaged objects, for instance, is often arbitrary/irrelevant, thus it can be desired to learn a representation in which the orientation information is disentangled from all other factors. Here, we propose to extend the Variational Auto-Encoder framework by leveraging the group structure of rotation-equivariant convolutional networks to learn orientation-wise disentangled generative factors of histopathology images. This way, we enforce a novel partitioning of the latent space, such that oriented and isotropic components get separated. We evaluated this structured representation on a dataset that consists of tissue regions for which nuclear pleomorphism and mitotic activity was assessed by expert pathologists. We show that the trained models efficiently disentangle the inherent orientation information of single-cell images. In comparison to classical approaches, the resulting aggregated representation of sub-populations of cells produces higher performances in subsequent tasks.

preprint2020arXiv

Primary Tumor Origin Classification of Lung Nodules in Spectral CT using Transfer Learning

Early detection of lung cancer has been proven to decrease mortality significantly. A recent development in computed tomography (CT), spectral CT, can potentially improve diagnostic accuracy, as it yields more information per scan than regular CT. However, the shear workload involved with analyzing a large number of scans drives the need for automated diagnosis methods. Therefore, we propose a detection and classification system for lung nodules in CT scans. Furthermore, we want to observe whether spectral images can increase classifier performance. For the detection of nodules we trained a VGG-like 3D convolutional neural net (CNN). To obtain a primary tumor classifier for our dataset we pre-trained a 3D CNN with similar architecture on nodule malignancies of a large publicly available dataset, the LIDC-IDRI dataset. Subsequently we used this pre-trained network as feature extractor for the nodules in our dataset. The resulting feature vectors were classified into two (benign/malignant) and three (benign/primary lung cancer/metastases) classes using support vector machine (SVM). This classification was performed both on nodule- and scan-level. We obtained state-of-the art performance for detection and malignancy regression on the LIDC-IDRI database. Classification performance on our own dataset was higher for scan- than for nodule-level predictions. For the three-class scan-level classification we obtained an accuracy of 78\%. Spectral features did increase classifier performance, but not significantly. Our work suggests that a pre-trained feature extractor can be used as primary tumor origin classifier for lung nodules, eliminating the need for elaborate fine-tuning of a new network and large datasets. Code is available at \url{https://github.com/tueimage/lung-nodule-msc-2018}.

preprint2020arXiv

Quantifying Graft Detachment after Descemet's Membrane Endothelial Keratoplasty with Deep Convolutional Neural Networks

Purpose: We developed a method to automatically locate and quantify graft detachment after Descemet's Membrane Endothelial Keratoplasty (DMEK) in Anterior Segment Optical Coherence Tomography (AS-OCT) scans. Methods: 1280 AS-OCT B-scans were annotated by a DMEK expert. Using the annotations, a deep learning pipeline was developed to localize scleral spur, center the AS-OCT B-scans and segment the detached graft sections. Detachment segmentation model performance was evaluated per B-scan by comparing (1) length of detachment and (2) horizontal projection of the detached sections with the expert annotations. Horizontal projections were used to construct graft detachment maps. All final evaluations were done on a test set that was set apart during training of the models. A second DMEK expert annotated the test set to determine inter-rater performance. Results: Mean scleral spur localization error was 0.155 mm, whereas the inter-rater difference was 0.090 mm. The estimated graft detachment lengths were in 69% of the cases within a 10-pixel (~150μm) difference from the ground truth (77% for the second DMEK expert). Dice scores for the horizontal projections of all B-scans with detachments were 0.896 and 0.880 for our model and the second DMEK expert respectively. Conclusion: Our deep learning model can be used to automatically and instantly localize graft detachment in AS-OCT B-scans. Horizontal detachment projections can be determined with the same accuracy as a human DMEK expert, allowing for the construction of accurate graft detachment maps. Translational Relevance: Automated localization and quantification of graft detachment can support DMEK research and standardize clinical decision making.

preprint2020arXiv

Roto-Translation Equivariant Convolutional Networks: Application to Histopathology Image Analysis

Rotation-invariance is a desired property of machine-learning models for medical image analysis and in particular for computational pathology applications. We propose a framework to encode the geometric structure of the special Euclidean motion group SE(2) in convolutional networks to yield translation and rotation equivariance via the introduction of SE(2)-group convolution layers. This structure enables models to learn feature representations with a discretized orientation dimension that guarantees that their outputs are invariant under a discrete set of rotations. Conventional approaches for rotation invariance rely mostly on data augmentation, but this does not guarantee the robustness of the output when the input is rotated. At that, trained conventional CNNs may require test-time rotation augmentation to reach their full capability. This study is focused on histopathology image analysis applications for which it is desirable that the arbitrary global orientation information of the imaged tissues is not captured by the machine learning models. The proposed framework is evaluated on three different histopathology image analysis tasks (mitosis detection, nuclei segmentation and tumor classification). We present a comparative analysis for each problem and show that consistent increase of performances can be achieved when using the proposed framework.

preprint2016arXiv

Cutting out the middleman: measuring nuclear area in histopathology slides without segmentation

The size of nuclei in histological preparations from excised breast tumors is predictive of patient outcome (large nuclei indicate poor outcome). Pathologists take into account nuclear size when performing breast cancer grading. In addition, the mean nuclear area (MNA) has been shown to have independent prognostic value. The straightforward approach to measuring nuclear size is by performing nuclei segmentation. We hypothesize that given an image of a tumor region with known nuclei locations, the area of the individual nuclei and region statistics such as the MNA can be reliably computed directly from the image data by employing a machine learning model, without the intermediate step of nuclei segmentation. Towards this goal, we train a deep convolutional neural network model that is applied locally at each nucleus location, and can reliably measure the area of the individual nuclei and the MNA. Furthermore, we show how such an approach can be extended to perform combined nuclei detection and measurement, which is reminiscent of granulometry.

preprint2016arXiv

Gland Segmentation in Colon Histology Images: The GlaS Challenge Contest

Colorectal adenocarcinoma originating in intestinal glandular structures is the most common form of colon cancer. In clinical practice, the morphology of intestinal glands, including architectural appearance and glandular formation, is used by pathologists to inform prognosis and plan the treatment of individual patients. However, achieving good inter-observer as well as intra-observer reproducibility of cancer grading is still a major challenge in modern pathology. An automated approach which quantifies the morphology of glands is a solution to the problem. This paper provides an overview to the Gland Segmentation in Colon Histology Images Challenge Contest (GlaS) held at MICCAI'2015. Details of the challenge, including organization, dataset and evaluation criteria, are presented, along with the method descriptions and evaluation results from the top performing methods.

preprint2014arXiv

Assessment of algorithms for mitosis detection in breast cancer histopathology images

The proliferative activity of breast tumors, which is routinely estimated by counting of mitotic figures in hematoxylin and eosin stained histology sections, is considered to be one of the most important prognostic markers. However, mitosis counting is laborious, subjective and may suffer from low inter-observer agreement. With the wider acceptance of whole slide images in pathology labs, automatic image analysis has been proposed as a potential solution for these issues. In this paper, the results from the Assessment of Mitosis Detection Algorithms 2013 (AMIDA13) challenge are described. The challenge was based on a data set consisting of 12 training and 11 testing subjects, with more than one thousand annotated mitotic figures by multiple observers. Short descriptions and results from the evaluation of eleven methods are presented. The top performing method has an error rate that is comparable to the inter-observer agreement among pathologists.