Jonas Teuwen

Tianyu Zhang, Luyi Han, Anna D'Angelo et al.

Magnetic resonance imaging (MRI) is the most sensitive technique for breast cancer detection among current clinical imaging modalities. Contrast-enhanced MRI (CE-MRI) provides superior differentiation between tumors and invaded healthy tissue, and has become an indispensable technique in the detection and evaluation of cancer. However, the use of gadolinium-based contrast agents (GBCA) to obtain CE-MRI may be associated with nephrogenic systemic fibrosis and may lead to bioaccumulation in the brain, posing a potential risk to human health. Moreover, and likely more important, the use of gadolinium-based contrast agents requires the cannulation of a vein, and the injection of the contrast media which is cumbersome and places a burden on the patient. To reduce the use of contrast agents, diffusion-weighted imaging (DWI) is emerging as a key imaging technique, although currently usually complementing breast CE-MRI. In this study, we develop a multi-sequence fusion network to synthesize CE-MRI based on T1-weighted MRI and DWIs. DWIs with different b-values are fused to efficiently utilize the difference features of DWIs. Rather than proposing a pure data-driven approach, we invent a multi-sequence attention module to obtain refined feature maps, and leverage hierarchical representation information fused at different scales while utilizing the contributions from different sequences from a model-driven approach by introducing the weighted difference module. The results show that the multi-b-value DWI-based fusion model can potentially be used to synthesize CE-MRI, thus theoretically reducing or avoiding the use of GBCA, thereby minimizing the burden to patients. Our code is available at \url{https://github.com/Netherlands-Cancer-Institute/CE-MRI}.

Luyi Han, Tao Tan, Tianyu Zhang et al.

Multi-sequence MRIs can be necessary for reliable diagnosis in clinical practice due to the complimentary information within sequences. However, redundant information exists across sequences, which interferes with mining efficient representations by modern machine learning or deep learning models. To handle various clinical scenarios, we propose a sequence-to-sequence generation framework (Seq2Seq) for imaging-differentiation representation learning. In this study, not only do we propose arbitrary 3D/4D sequence generation within one model to generate any specified target sequence, but also we are able to rank the importance of each sequence based on a new metric estimating the difficulty of a sequence being generated. Furthermore, we also exploit the generation inability of the model to extract regions that contain unique information for each sequence. We conduct extensive experiments using three datasets including a toy dataset of 20,000 simulated subjects, a brain MRI dataset of 1,251 subjects, and a breast MRI dataset of 2,101 subjects, to demonstrate that (1) our proposed Seq2Seq is efficient and lightweight for complex clinical datasets and can achieve excellent image quality; (2) top-ranking sequences can be used to replace complete sequences with non-inferior performance; (3) combining MRI with our imaging-differentiation map leads to better performance in clinical tasks such as glioblastoma MGMT promoter methylation status prediction and breast cancer pathological complete response status prediction. Our code is available at https://github.com/fiy2W/mri_seq2seq.

Sarthak Pati, Ujjwal Baid, Brandon Edwards et al.

Although machine learning (ML) has shown promise in numerous domains, there are concerns about generalizability to out-of-sample data. This is currently addressed by centrally sharing ample, and importantly diverse, data from multiple sites. However, such centralization is challenging to scale (or even not feasible) due to various limitations. Federated ML (FL) provides an alternative to train accurate and generalizable ML models, by only sharing numerical model updates. Here we present findings from the largest FL study to-date, involving data from 71 healthcare institutions across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, utilizing the largest dataset of such patients ever used in the literature (25,256 MRI scans from 6,314 patients). We demonstrate a 33% improvement over a publicly trained model to delineate the surgically targetable tumor, and 23% improvement over the tumor's entire extent. We anticipate our study to: 1) enable more studies in healthcare informed by large and diverse data, ensuring meaningful results for rare diseases and underrepresented populations, 2) facilitate further quantitative analyses for glioblastoma via performance optimization of our consensus model for eventual public release, and 3) demonstrate the effectiveness of FL at such scale and task complexity as a paradigm shift for multi-site collaborations, alleviating the need for data sharing.

Tianyu Zhang, Tao Tan, Luyi Han et al.

Magnetic resonance imaging (MRI) is highly sensitive for lesion detection in the breasts. Sequences obtained with different settings can capture the specific characteristics of lesions. Such multi-parameter MRI information has been shown to improve radiologist performance in lesion classification, as well as improving the performance of artificial intelligence models in various tasks. However, obtaining multi-parameter MRI makes the examination costly in both financial and time perspectives, and there may be safety concerns for special populations, thus making acquisition of the full spectrum of MRI sequences less durable. In this study, different than naive input fusion or feature concatenation from existing MRI parameters, a novel $\textbf{I}$ntegrated MRI $\textbf{M}$ulti-$\textbf{P}$arameter reinf$\textbf{O}$rcement fusion generato$\textbf{R}$ wi$\textbf{T}$h $\textbf{A}$tte$\textbf{NT}$ion Network (IMPORTANT-Net) is developed to generate missing parameters. First, the parameter reconstruction module is used to encode and restore the existing MRI parameters to obtain the corresponding latent representation information at any scale level. Then the multi-parameter fusion with attention module enables the interaction of the encoded information from different parameters through a set of algorithmic strategies, and applies different weights to the information through the attention mechanism after information fusion to obtain refined representation information. Finally, a reinforcement fusion scheme embedded in a $V^{-}$-shape generation module is used to combine the hierarchical representations to generate the missing MRI parameter. Results showed that our IMPORTANT-Net is capable of generating missing MRI parameters and outperforms comparable state-of-the-art networks. Our code is available at https://github.com/Netherlands-Cancer-Institute/MRI_IMPORTANT_NET.

Tim Veenboer, George Yiasemis, Eric Marcus et al.

Existing foundation models (FMs) in the medical domain often require extensive fine-tuning or rely on training resource-intensive decoders, while many existing encoders are pretrained with objectives biased toward specific tasks. This illustrates a need for a strong, task-agnostic foundation model that requires minimal fine-tuning beyond feature extraction. In this work, we introduce a suite of task-agnostic pretraining of CT foundation models (TAP-CT): a simple yet effective adaptation of Vision Transformers (ViTs) and DINOv2 for volumetric data, enabling scalable self-supervised pretraining directly on 3D CT volumes. Our approach incorporates targeted modifications to patch embeddings, positional encodings, and volumetric augmentations, making the architecture depth-aware while preserving the simplicity of the underlying architectures. We show that large-scale 3D pretraining on an extensive in-house CT dataset (105K volumes) yields stable, robust frozen representations that generalize strongly across downstream tasks. To promote transparency and reproducibility, and to establish a powerful, low-resource baseline for future research in medical imaging, we will release all pretrained models, experimental configurations, and downstream benchmark code at https://huggingface.co/fomofo/tap-ct-b-3d.

Teaghan O'Briain, Carlos Uribe, Kwang Moo Yi et al.

To correct for respiratory motion in PET imaging, an interpretable and unsupervised deep learning technique, FlowNet-PET, was constructed. The network was trained to predict the optical flow between two PET frames from different breathing amplitude ranges. The trained model aligns different retrospectively-gated PET images, providing a final image with similar counting statistics as a non-gated image, but without the blurring effects. FlowNet-PET was applied to anthropomorphic digital phantom data, which provided the possibility to design robust metrics to quantify the corrections. When comparing the predicted optical flows to the ground truths, the median absolute error was found to be smaller than the pixel and slice widths. The improvements were illustrated by comparing against images without motion and computing the intersection over union (IoU) of the tumors as well as the enclosed activity and coefficient of variation (CoV) within the no-motion tumor volume before and after the corrections were applied. The average relative improvements provided by the network were 64%, 89%, and 75% for the IoU, total activity, and CoV, respectively. FlowNet-PET achieved similar results as the conventional retrospective phase binning approach, but only required one sixth of the scan duration. The code and data have been made publicly available (https://github.com/teaghan/FlowNet_PET).

George Yiasemis, Clara I. Sánchez, Jan-Jakob Sonke et al.

Acquiring fully-sampled MRI $k$-space data is time-consuming, and collecting accelerated data can reduce the acquisition time. Employing 2D Cartesian-rectilinear subsampling schemes is a conventional approach for accelerated acquisitions; however, this often results in imprecise reconstructions, even with the use of Deep Learning (DL), especially at high acceleration factors. Non-rectilinear or non-Cartesian trajectories can be implemented in MRI scanners as alternative subsampling options. This work investigates the impact of the $k$-space subsampling scheme on the quality of reconstructed accelerated MRI measurements produced by trained DL models. The Recurrent Variational Network (RecurrentVarNet) was used as the DL-based MRI-reconstruction architecture. Cartesian, fully-sampled multi-coil $k$-space measurements from three datasets were retrospectively subsampled with different accelerations using eight distinct subsampling schemes: four Cartesian-rectilinear, two Cartesian non-rectilinear, and two non-Cartesian. Experiments were conducted in two frameworks: scheme-specific, where a distinct model was trained and evaluated for each dataset-subsampling scheme pair, and multi-scheme, where for each dataset a single model was trained on data randomly subsampled by any of the eight schemes and evaluated on data subsampled by all schemes. In both frameworks, RecurrentVarNets trained and evaluated on non-rectilinearly subsampled data demonstrated superior performance, particularly for high accelerations. In the multi-scheme setting, reconstruction performance on rectilinearly subsampled data improved when compared to the scheme-specific experiments. Our findings demonstrate the potential for using DL-based methods, trained on non-rectilinearly subsampled measurements, to optimize scan time and image quality.

George Yiasemis, Nikita Moriakov, Jan-Jakob Sonke et al.

Medical Imaging (MI) tasks, such as accelerated parallel Magnetic Resonance Imaging (MRI), often involve reconstructing an image from noisy or incomplete measurements. This amounts to solving ill-posed inverse problems, where a satisfactory closed-form analytical solution is not available. Traditional methods such as Compressed Sensing (CS) in MRI reconstruction can be time-consuming or prone to obtaining low-fidelity images. Recently, a plethora of Deep Learning (DL) approaches have demonstrated superior performance in inverse-problem solving, surpassing conventional methods. In this study, we propose vSHARP (variable Splitting Half-quadratic ADMM algorithm for Reconstruction of inverse Problems), a novel DL-based method for solving ill-posed inverse problems arising in MI. vSHARP utilizes the Half-Quadratic Variable Splitting method and employs the Alternating Direction Method of Multipliers (ADMM) to unroll the optimization process. For data consistency, vSHARP unrolls a differentiable gradient descent process in the image domain, while a DL-based denoiser, such as a U-Net architecture, is applied to enhance image quality. vSHARP also employs a dilated-convolution DL-based model to predict the Lagrange multipliers for the ADMM initialization. We evaluate vSHARP on tasks of accelerated parallel MRI Reconstruction using two distinct datasets and on accelerated parallel dynamic MRI Reconstruction using another dataset. Our comparative analysis with state-of-the-art methods demonstrates the superior performance of vSHARP in these applications.

Joren Brunekreef, Eric Marcus, Ray Sheombarsing et al.

Image segmentation algorithms can be understood as a collection of pixel classifiers, for which the outcomes of nearby pixels are correlated. Classifier models can be calibrated using Inductive Conformal Prediction, but this requires holding back a sufficiently large calibration dataset for computing the distribution of non-conformity scores of the model's predictions. If one only requires only marginal calibration on the image level, this calibration set consists of all individual pixels in the images available for calibration. However, if the goal is to attain proper calibration for each individual pixel classifier, the calibration set consists of individual images. In a scenario where data are scarce (such as the medical domain), it may not always be possible to set aside sufficiently many images for this pixel-level calibration. The method we propose, dubbed ``Kandinsky calibration'', makes use of the spatial structure present in the distribution of natural images to simultaneously calibrate the classifiers of ``similar'' pixels. This can be seen as an intermediate approach between marginal (imagewise) and conditional (pixelwise) calibration, where non-conformity scores are aggregated over similar image regions, thereby making more efficient use of the images available for calibration. We run experiments on segmentation algorithms trained and calibrated on subsets of the public MS-COCO and Medical Decathlon datasets, demonstrating that Kandinsky calibration method can significantly improve the coverage. When compared to both pixelwise and imagewise calibration on little data, the Kandinsky method achieves much lower coverage errors, indicating the data efficiency of the Kandinsky calibration.

George Yiasemis, Nikita Moriakov, Jan-Jakob Sonke et al.

Cardiac magnetic resonance imaging is a valuable non-invasive tool for identifying cardiovascular diseases. For instance, Cine MRI is the benchmark modality for assessing the cardiac function and anatomy. On the other hand, multi-contrast (T1 and T2) mapping has the potential to assess pathologies and abnormalities in the myocardium and interstitium. However, voluntary breath-holding and often arrhythmia, in combination with MRI's slow imaging speed, can lead to motion artifacts, hindering real-time acquisition image quality. Although performing accelerated acquisitions can facilitate dynamic imaging, it induces aliasing, causing low reconstructed image quality in Cine MRI and inaccurate T1 and T2 mapping estimation. In this work, inspired by related work in accelerated MRI reconstruction, we present a deep learning (DL)-based method for accelerated cine and multi-contrast reconstruction in the context of dynamic cardiac imaging. We formulate the reconstruction problem as a least squares regularized optimization task, and employ vSHARP, a state-of-the-art DL-based inverse problem solver, which incorporates half-quadratic variable splitting and the alternating direction method of multipliers with neural networks. We treat the problem in two setups; a 2D reconstruction and a 2D dynamic reconstruction task, and employ 2D and 3D deep learning networks, respectively. Our method optimizes in both the image and k-space domains, allowing for high reconstruction fidelity. Although the target data is undersampled with a Cartesian equispaced scheme, we train our model using both Cartesian and simulated non-Cartesian undersampling schemes to enhance generalization of the model to unseen data. Furthermore, our model adopts a deep neural network to learn and refine the sensitivity maps of multi-coil k-space data. Lastly, our method is jointly trained on both, undersampled cine and multi-contrast data.

Nikita Moriakov, Jim Peters, Ritse Mann et al.

Lesion volume is an important predictor for prognosis in breast cancer. We make a step towards a more accurate lesion volume measurement on digital mammograms by developing a model that allows to estimate lesion volumes on processed mammograms, which are the images routinely used by radiologists in clinical practice as well as in breast cancer screening and are available in medical centers. Processed mammograms are obtained from raw mammograms, which are the X-ray data coming directly from the scanner, by applying certain vendor-specific non-linear transformations. At the core of our volume estimation method is a physics-based algorithm for measuring lesion volumes on raw mammograms. We subsequently extend this algorithm to processed mammograms via a deep learning image-to-image translation model that produces synthetic raw mammograms from processed mammograms in a multi-vendor setting. We assess the reliability and validity of our method using a dataset of 1778 mammograms with an annotated mass. Firstly, we investigate the correlations between lesion volumes computed from mediolateral oblique and craniocaudal views, with a resulting Pearson correlation of 0.93 [95% confidence interval (CI) 0.92 - 0.93]. Secondly, we compare the resulting lesion volumes from true and synthetic raw data, with a resulting Pearson correlation of 0.998 [95% CI 0.998 - 0.998] . Finally, for a subset of 100 mammograms with a malign mass and concurrent MRI examination available, we analyze the agreement between lesion volume on mammography and MRI, resulting in an intraclass correlation coefficient of 0.81 [95% CI 0.73 - 0.87] for consistency and 0.78 [95% CI 0.66 - 0.86] for absolute agreement. In conclusion, we developed an algorithm to measure mammographic lesion volume that reached excellent reliability and good validity, when using MRI as ground truth.

George Yiasemis, Nikita Moriakov, Clara I. Sánchez et al.

Magnetic Resonance Imaging (MRI) represents an important diagnostic modality; however, its inherently slow acquisition process poses challenges in obtaining fully-sampled $k$-space data under motion. In the absence of fully-sampled acquisitions, serving as ground truths, training deep learning algorithms in a supervised manner to predict the underlying ground truth image becomes challenging. To address this limitation, self-supervised methods have emerged as a viable alternative, leveraging available subsampled $k$-space data to train deep neural networks for MRI reconstruction. Nevertheless, these approaches often fall short when compared to supervised methods. We propose Joint Supervised and Self-supervised Learning (JSSL), a novel training approach for deep learning-based MRI reconstruction algorithms aimed at enhancing reconstruction quality in cases where target datasets containing fully-sampled $k$-space measurements are unavailable. JSSL operates by simultaneously training a model in a self-supervised learning setting, using subsampled data from the target dataset(s), and in a supervised learning manner, utilizing datasets with fully-sampled $k$-space data, referred to as proxy datasets. We demonstrate JSSL's efficacy using subsampled prostate or cardiac MRI data as the target datasets, with fully-sampled brain and knee, or brain, knee and prostate $k$-space acquisitions, respectively, as proxy datasets. Our results showcase substantial improvements over conventional self-supervised methods, validated using common image quality metrics. Furthermore, we provide theoretical motivations for JSSL and establish "rule-of-thumb" guidelines for training MRI reconstruction models. JSSL effectively enhances MRI reconstruction quality in scenarios where fully-sampled $k$-space data is not available, leveraging the strengths of supervised learning by incorporating proxy datasets.

Eric Marcus, Ray Sheombarsing, Jan-Jakob Sonke et al.

Deep Neural Networks (DNNs) are widely used for their ability to effectively approximate large classes of functions. This flexibility, however, makes the strict enforcement of constraints on DNNs an open problem. Here we present a framework that, under mild assumptions, allows the exact enforcement of constraints on parameterized sets of functions such as DNNs. Instead of imposing "soft'' constraints via additional terms in the loss, we restrict (a subset of) the DNN parameters to a submanifold on which the constraints are satisfied exactly throughout the entire training procedure. We focus on constraints that are outside the scope of equivariant networks used in Geometric Deep Learning. As a major example of the framework, we restrict filters of a Convolutional Neural Network (CNN) to be wavelets, and apply these wavelet networks to the task of contour prediction in the medical domain.

Tianyu Zhang, Xinglong Liang, Jarek van Dijk et al.

Synthesizing high fidelity contrast enhanced MRI is clinically valuable for safer and more efficient breast cancer screening, yet remains challenging due to complex lesion textures and heterogeneous enhancement patterns.

Xin Wang, Tao Tan, Yuan Gao et al.

Precision breast cancer (BC) risk assessment is crucial for developing individualized screening and prevention. Despite the promising potential of recent mammogram (MG) based deep learning models in predicting BC risk, they mostly overlook the 'time-to-future-event' ordering among patients and exhibit limited explorations into how they track history changes in breast tissue, thereby limiting their clinical application. In this work, we propose a novel method, named OA-BreaCR, to precisely model the ordinal relationship of the time to and between BC events while incorporating longitudinal breast tissue changes in a more explainable manner. We validate our method on public EMBED and inhouse datasets, comparing with existing BC risk prediction and time prediction methods. Our ordinal learning method OA-BreaCR outperforms existing methods in both BC risk and time-to-future-event prediction tasks. Additionally, ordinal heatmap visualizations show the model's attention over time. Our findings underscore the importance of interpretable and precise risk assessment for enhancing BC screening and prevention efforts. The code will be accessible to the public.

Nikita Moriakov, Efstratios Gavves, Jonathan H. Mason et al.

Cone Beam CT (CBCT) is an important imaging modality nowadays, however lower image quality of CBCT compared to more conventional Computed Tomography (CT) remains a limiting factor in CBCT applications. Deep learning reconstruction methods are a promising alternative to classical analytical and iterative reconstruction methods, but applying such methods to CBCT is often difficult due to the lack of ground truth data, memory limitations and the need for fast inference at clinically-relevant resolutions. In this work we propose LIRE++, an end-to-end rotationally-equivariant multiscale learned invertible primal-dual scheme for fast and memory-efficient CBCT reconstruction. Memory optimizations and multiscale reconstruction allow for fast training and inference, while rotational equivariance improves parameter efficiency. LIRE++ was trained on simulated projection data from a fast quasi-Monte Carlo CBCT projection simulator that we developed as well. Evaluated on synthetic data, LIRE++ gave an average improvement of 1 dB in Peak Signal-to-Noise Ratio over alternative deep learning baselines. On real clinical data, LIRE++ improved the average Mean Absolute Error between the reconstruction and the corresponding planning CT by 10 Hounsfield Units with respect to current proprietary state-of-the-art hybrid deep-learning/iterative method.

Luyi Han, Tao Tan, Tianyu Zhang et al.

Clinicians compare breast DCE-MRI after neoadjuvant chemotherapy (NAC) with pre-treatment scans to evaluate the response to NAC. Clinical evidence supports that accurate longitudinal deformable registration without deforming treated tumor regions is key to quantifying tumor changes. We propose a conditional pyramid registration network based on unsupervised keypoint detection and selective volume-preserving to quantify changes over time. In this approach, we extract the structural and the abnormal keypoints from DCE-MRI, apply the structural keypoints for the registration algorithm to restrict large deformation, and employ volume-preserving loss based on abnormal keypoints to keep the volume of the tumor unchanged after registration. We use a clinical dataset with 1630 MRI scans from 314 patients treated with NAC. The results demonstrate that our method registers with better performance and better volume preservation of the tumors. Furthermore, a local-global-combining biomarker based on the proposed method achieves high accuracy in pathological complete response (pCR) prediction, indicating that predictive information exists outside tumor regions. The biomarkers could potentially be used to avoid unnecessary surgeries for certain patients. It may be valuable for clinicians and/or computer systems to conduct follow-up tumor segmentation and response prediction on images registered by our method. Our code is available on \url{https://github.com/fiy2W/Treatment-aware-Longitudinal-Registration}.

Xin Wang, Yuan Gao, George Yiasemis et al.

Efficient and explainable breast cancer (BC) risk prediction is critical for large-scale population-based screening. Breast MRI provides functional information for personalized risk assessment. Yet effective modeling remains challenging as fully 3D CNNs capture volumetric context at high computational cost, whereas lightweight 2D CNNs fail to model inter-slice continuity. Importantly, breast MRI modeling for shor- and long-term BC risk stratification remains underexplored. In this study, we propose LoGo-MR, a 2.5D local-global structural modeling framework for five-year BC risk prediction. Aligned with clinical interpretation, our framework first employs neighbor-slice encoding to capture subtle local cues linked to short-term risk. It then integrates transformer-enhanced multiple-instance learning (MIL) to model distributed global patterns related to long-term risk and provide interpretable slice importance. We further apply this framework across axial, sagittal, and coronal planes as LoGo3-MR to capture complementary volumetric information. This multi-plane formulation enables voxel-level risk saliency mapping, which may assist radiologists in localizing risk-relevant regions during breast MRI interpretation. Evaluated on a large breast MRI screening cohort (~7.5K), our method outperforms 2D/3D baselines and existing SOTA MIL methods, achieving AUCs of 0.77-0.69 for 1- to 5-year prediction and improving C-index by ~6% over 3D CNNs. LoGo3-MR further improves overall performance with interpretable localization across three planes, and validation across seven backbones shows consistent gains. These results highlight the clinical potential of efficient MRI-based BC risk stratification for large-scale screening. Code will be released publicly.

Yoni Schirris, Eric Marcus, Jonas Teuwen et al.

Explaining deep learning models is essential for clinical integration of medical image analysis systems. A good explanation highlights if a model depends on spurious features that undermines generalization and harms a subset of patients or, conversely, may present novel biological insights. Although techniques like GradCAM can identify influential features, they are measurement tools that do not themselves form an explanation. We propose a human-machine-VLM interaction system tailored to explaining classifiers in computational pathology, including multi-instance learning for whole-slide images. Our proof of concept comprises (1) an AI-integrated slide viewer to run sliding-window experiments to test claims of an explanation, and (2) quantification of an explanation's predictiveness using general-purpose vision-language models. The results demonstrate that this allows us to qualitatively test claims of explanations and can quantifiably distinguish competing explanations. This offers a practical path from explainable AI to explained AI in digital pathology and beyond. Code and prompts are available at https://github.com/nki-ai/x2x.

Yoni Schirris, Rosie Voorthuis, Mark Opdam et al.

The level of tumour-infiltrating lymphocytes (TILs) is a prognostic factor for patients with (triple-negative) breast cancer (BC). Computational TIL assessment (CTA) has the potential to assist pathologists in this labour-intensive task, but current CTA models rely heavily on many detailed annotations. We propose and validate a fundamentally simpler deep learning based CTA that can be trained in only ten minutes on hundredfold fewer pathologist annotations. We collected whole slide images (WSIs) with TILs scores and clinical data of 2,340 patients with BC from six cohorts including three randomised clinical trials. Morphological features were extracted from whole slide images (WSIs) using a pathology foundation model. Our label-efficient Computational stromal TIL assessment model (ECTIL) directly regresses the TILs score from these features. ECTIL trained on only a few hundred samples (ECTIL-TCGA) showed concordance with the pathologist over five heterogeneous external cohorts (r=0.54-0.74, AUROC=0.80-0.94). Training on all slides of five cohorts (ECTIL-combined) improved results on a held-out test set (r=0.69, AUROC=0.85). Multivariable Cox regression analyses indicated that every 10% increase of ECTIL scores was associated with improved overall survival independent of clinicopathological variables (HR 0.86, p<0.01), similar to the pathologist score (HR 0.87, p<0.001). We demonstrate that ECTIL is highly concordant with an expert pathologist and obtains a similar hazard ratio. ECTIL has a fundamentally simpler design than existing methods and can be trained on orders of magnitude fewer annotations. Such a CTA may be used to pre-screen patients for, e.g., immunotherapy clinical trial inclusion, or as a tool to assist clinicians in the diagnostic work-up of patients with BC. Our model is available under an open source licence (https://github.com/nki-ai/ectil).

Edwin D. de Jong, Eric Marcus, Jonas Teuwen

Pathology Foundation Models (FMs) hold great promise for healthcare. Before they can be used in clinical practice, it is essential to ensure they are robust to variations between medical centers. We measure whether pathology FMs focus on biological features like tissue and cancer type, or on the well known confounding medical center signatures introduced by staining procedure and other differences. We introduce the Robustness Index. This novel robustness metric reflects to what degree biological features dominate confounding features. Ten current publicly available pathology FMs are evaluated. We find that all current pathology foundation models evaluated represent the medical center to a strong degree. Significant differences in the robustness index are observed. Only one model so far has a robustness index greater than one, meaning biological features dominate confounding features, but only slightly. A quantitative approach to measure the influence of medical center differences on FM-based prediction performance is described. We analyze the impact of unrobustness on classification performance of downstream models, and find that cancer-type classification errors are not random, but specifically attributable to same-center confounders: images of other classes from the same medical center. We visualize FM embedding spaces, and find these are more strongly organized by medical centers than by biological factors. As a consequence, the medical center of origin is predicted more accurately than the tissue source and cancer type. The robustness index introduced here is provided with the aim of advancing progress towards clinical adoption of robust and reliable pathology FMs.

Ecem Sogancioglu, Bram van Ginneken, Finn Behrendt et al.

Pulmonary nodules may be an early manifestation of lung cancer, the leading cause of cancer-related deaths among both men and women. Numerous studies have established that deep learning methods can yield high-performance levels in the detection of lung nodules in chest X-rays. However, the lack of gold-standard public datasets slows down the progression of the research and prevents benchmarking of methods for this task. To address this, we organized a public research challenge, NODE21, aimed at the detection and generation of lung nodules in chest X-rays. While the detection track assesses state-of-the-art nodule detection systems, the generation track determines the utility of nodule generation algorithms to augment training data and hence improve the performance of the detection systems. This paper summarizes the results of the NODE21 challenge and performs extensive additional experiments to examine the impact of the synthetically generated nodule training images on the detection algorithm performance.

Jonah Kömen, Edwin D. de Jong, Julius Hense et al.

Biomedical Foundation Models (FMs) are rapidly transforming AI-enabled healthcare research and entering clinical validation. However, their susceptibility to learning non-biological technical features -- including variations in surgical/endoscopic techniques, laboratory procedures, and scanner hardware -- poses risks for clinical deployment. We present the first systematic investigation of pathology FM robustness to non-biological features. Our work (i) introduces measures to quantify FM robustness, (ii) demonstrates the consequences of limited robustness, and (iii) proposes a framework for FM robustification to mitigate these issues. Specifically, we developed PathoROB, a robustness benchmark with three novel metrics, including the robustness index, and four datasets covering 28 biological classes from 34 medical centers. Our experiments reveal robustness deficits across all 20 evaluated FMs, and substantial robustness differences between them. We found that non-robust FM representations can cause major diagnostic downstream errors and clinical blunders that prevent safe clinical adoption. Using more robust FMs and post-hoc robustification considerably reduced (but did not yet eliminate) the risk of such errors. This work establishes that robustness evaluation is essential for validating pathology FMs before clinical adoption and demonstrates that future FM development must integrate robustness as a core design principle. PathoROB provides a blueprint for assessing robustness across biomedical domains, guiding FM improvement efforts towards more robust, representative, and clinically deployable AI systems that prioritize biological information over technical artifacts.

George Yiasemis, Jan-Jakob Sonke, Jonas Teuwen

$\textbf{Background:}$ Accelerating dynamic MRI is vital for advancing clinical applications and improving patient comfort. Commonly, deep learning (DL) methods for accelerated dynamic MRI reconstruction typically rely on uniformly applying non-adaptive predetermined or random subsampling patterns across all temporal frames of the dynamic acquisition. This approach fails to exploit temporal correlations or optimize subsampling on a case-by-case basis. $\textbf{Purpose:}$ To develop an end-to-end approach for adaptive dynamic MRI subsampling and reconstruction, capable of generating customized sampling patterns maximizing at the same time reconstruction quality. $\textbf{Methods:}$ We introduce the End-to-end Adaptive Dynamic Sampling and Reconstruction (E2E-ADS-Recon) for MRI framework, which integrates an adaptive dynamic sampler (ADS) that adapts the acquisition trajectory to each case for a given acceleration factor with a state-of-the-art dynamic reconstruction network, vSHARP, for reconstructing the adaptively sampled data into a dynamic image. The ADS can produce either frame-specific patterns or unified patterns applied to all temporal frames. E2E-ADS-Recon is evaluated under both frame-specific and unified 1D or 2D sampling settings, using dynamic cine cardiac MRI data and compared with vSHARP models employing standard subsampling trajectories, as well as pipelines where ADS was replaced by parameterized samplers optimized for dataset-specific schemes. $\textbf{Results:}$ E2E-ADS-Recon exhibited superior reconstruction quality, especially at high accelerations, in terms of standard quantitative metrics (SSIM, pSNR, NMSE). $\textbf{Conclusion:}$ The proposed framework improves reconstruction quality, highlighting the importance of case-specific subsampling optimization in dynamic MRI applications.

George Yiasemis, Nikita Moriakov, Jan-Jakob Sonke et al.

Cardiac MRI (CMRI) is a cornerstone imaging modality that provides in-depth insights into cardiac structure and function. Multi-contrast CMRI (MCCMRI), which acquires sequences with varying contrast weightings, significantly enhances diagnostic capabilities by capturing a wide range of cardiac tissue characteristics. However, MCCMRI is often constrained by lengthy acquisition times and susceptibility to motion artifacts. To mitigate these challenges, accelerated imaging techniques that use k-space undersampling via different sampling schemes at acceleration factors have been developed to shorten scan durations. In this context, we propose a deep learning-based reconstruction method for 2D dynamic multi-contrast, multi-scheme, and multi-acceleration MRI. Our approach integrates the state-of-the-art vSHARP model, which utilizes half-quadratic variable splitting and ADMM optimization, with a Variational Network serving as an Auxiliary Refinement Network (ARN) to better adapt to the diverse nature of MCCMRI data. Specifically, the subsampled k-space data is fed into the ARN, which produces an initial prediction for the denoising step used by vSHARP. This, along with the subsampled k-space, is then used by vSHARP to generate high-quality 2D sequence predictions. Our method outperforms traditional reconstruction techniques and other vSHARP-based models.

Vivien van Veldhuizen, Vanessa Botha, Chunyao Lu et al.

Foundation models (FMs) are changing the way medical images are analyzed by learning from large collections of unlabeled data. Instead of relying on manually annotated examples, FMs are pre-trained to learn general-purpose visual features that can later be adapted to specific clinical tasks with little additional supervision. In this review, we examine how FMs are being developed and applied in pathology, radiology, and ophthalmology, drawing on evidence from over 150 studies. We explain the core components of FM pipelines, including model architectures, self-supervised learning methods, and strategies for downstream adaptation. We also review how FMs are being used in each imaging domain and compare design choices across applications. Finally, we discuss key challenges and open questions to guide future research.

George Yiasemis, Jan-Jakob Sonke, Jonas Teuwen

Dynamic MRI enables a range of clinical applications, including cardiac function assessment, organ motion tracking, and radiotherapy guidance. However, fully sampling the dynamic k-space data is often infeasible due to time constraints and physiological motion such as respiratory and cardiac motion. This necessitates undersampling, which degrades the quality of reconstructed images. Poor image quality not only hinders visualization but also impairs the estimation of deformation fields, crucial for registering dynamic (moving) images to a static reference image. This registration enables tasks such as motion correction, treatment planning, and quantitative analysis in applications like cardiac imaging and MR-guided radiotherapy. To overcome the challenges posed by undersampling and motion, we introduce an end-to-end deep learning (DL) framework that integrates adaptive dynamic k-space sampling, reconstruction, and registration. Our approach begins with a DL-based adaptive sampling strategy, optimizing dynamic k-space acquisition to capture the most relevant data for each specific case. This is followed by a DL-based reconstruction module that produces images optimized for accurate deformation field estimation from the undersampled moving data. Finally, a registration module estimates the deformation fields aligning the reconstructed dynamic images with a static reference. The proposed framework is independent of specific reconstruction and registration modules allowing for plug-and-play integration of these components. The entire framework is jointly trained using a combination of supervised and unsupervised loss functions, enabling end-to-end optimization for improved performance across all components. Through controlled experiments and ablation studies, we validate each component, demonstrating that each choice contributes to robust motion estimation from undersampled dynamic data.

Nikita Moriakov, Jan-Jakob Sonke, Jonas Teuwen

Cone Beam CT (CBCT) is an essential imaging modality nowadays, but the image quality of CBCT still lags behind the high quality standards established by the conventional Computed Tomography. We propose LIRE+, a learned iterative scheme for fast and memory-efficient CBCT reconstruction, which is a substantially faster and more parameter-efficient alternative to the recently proposed LIRE method. LIRE+ is a rotationally-equivariant multiscale learned invertible primal-dual iterative scheme for CBCT reconstruction. Memory usage is optimized by relying on simple reversible residual networks in primal/dual cells and patch-wise computations inside the cells during forward and backward passes, while increased inference speed is achieved by making the primal-dual scheme multiscale so that the reconstruction process starts at low resolution and with low resolution primal/dual latent vectors. A LIRE+ model was trained and validated on a set of 260 + 22 thorax CT scans and tested using a set of 142 thorax CT scans with additional evaluation with and without finetuning on an out-of-distribution set of 79 Head and Neck (HN) CT scans. Our method surpasses classical and deep learning baselines, including LIRE, on the thorax test set. For a similar inference time and with only 37 % of the parameter budget, LIRE+ achieves a +0.2 dB PSNR improvement over LIRE, while being able to match the performance of LIRE in 45 % less inference time and with 28 % of the parameter budget. Rotational equivariance ensures robustness of LIRE+ to patient orientation, while LIRE and other deep learning baselines suffer from substantial performance degradation when patient orientation is unusual. On the HN dataset in the absence of finetuning, LIRE+ is generally comparable to LIRE in performance apart from a few outlier cases, whereas after identical finetuning LIRE+ demonstates a +1.02 dB PSNR improvement over LIRE.

George Yiasemis, Jan-Jakob Sonke, Clarisa Sánchez et al.

Magnetic Resonance Imaging can produce detailed images of the anatomy and physiology of the human body that can assist doctors in diagnosing and treating pathologies such as tumours. However, MRI suffers from very long acquisition times that make it susceptible to patient motion artifacts and limit its potential to deliver dynamic treatments. Conventional approaches such as Parallel Imaging and Compressed Sensing allow for an increase in MRI acquisition speed by reconstructing MR images from sub-sampled MRI data acquired using multiple receiver coils. Recent advancements in Deep Learning combined with Parallel Imaging and Compressed Sensing techniques have the potential to produce high-fidelity reconstructions from highly accelerated MRI data. In this work we present a novel Deep Learning-based Inverse Problem solver applied to the task of Accelerated MRI Reconstruction, called the Recurrent Variational Network (RecurrentVarNet), by exploiting the properties of Convolutional Recurrent Neural Networks and unrolled algorithms for solving Inverse Problems. The RecurrentVarNet consists of multiple recurrent blocks, each responsible for one iteration of the unrolled variational optimization scheme for solving the inverse problem of multi-coil Accelerated MRI Reconstruction. Contrary to traditional approaches, the optimization steps are performed in the observation domain ($k$-space) instead of the image domain. Each block of the RecurrentVarNet refines the observed $k$-space and comprises a data consistency term and a recurrent unit which takes as input a learned hidden state and the prediction of the previous block. Our proposed method achieves new state of the art qualitative and quantitative reconstruction results on 5-fold and 10-fold accelerated data from a public multi-coil brain dataset, outperforming previous conventional and deep learning-based approaches.

Ray Sheombarsing, Nikita Moriakov, Jan-Jakob Sonke et al.

We propose a novel deep learning framework for fast prediction of boundaries of two-dimensional simply connected domains using wavelets and Multi Resolution Analysis (MRA). The boundaries are modelled as (piecewise) smooth closed curves using wavelets and the so-called Pyramid Algorithm. Our network architecture is a hybrid analog of the U-Net, where the down-sampling path is a two-dimensional encoder with learnable filters, and the upsampling path is a one-dimensional decoder, which builds curves up from low to high resolution levels. Any wavelet basis induced by a MRA can be used. This flexibility allows for incorporation of priors on the smoothness of curves. The effectiveness of the proposed method is demonstrated by delineating boundaries of simply connected domains (organs) in medical images using Debauches wavelets and comparing performance with a U-Net baseline. Our model demonstrates up to 5x faster inference speed compared to the U-Net, while maintaining similar performance in terms of Dice score and Hausdorff distance.

Yoni Schirris, Mendel Engelaer, Andreas Panteli et al.

We present WeakSTIL, an interpretable two-stage weak label deep learning pipeline for scoring the percentage of stromal tumor infiltrating lymphocytes (sTIL%) in H&E-stained whole-slide images (WSIs) of breast cancer tissue. The sTIL% score is a prognostic and predictive biomarker for many solid tumor types. However, due to the high labeling efforts and high intra- and interobserver variability within and between expert annotators, this biomarker is currently not used in routine clinical decision making. WeakSTIL compresses tiles of a WSI using a feature extractor pre-trained with self-supervised learning on unlabeled histopathology data and learns to predict precise sTIL% scores for each tile in the tumor bed by using a multiple instance learning regressor that only requires a weak WSI-level label. By requiring only a weak label, we overcome the large annotation efforts required to train currently existing TIL detection methods. We show that WeakSTIL is at least as good as other TIL detection methods when predicting the WSI-level sTIL% score, reaching a coefficient of determination of $0.45\pm0.15$ when compared to scores generated by an expert pathologist, and an AUC of $0.89\pm0.05$ when treating it as the clinically interesting sTIL-high vs sTIL-low classification task. Additionally, we show that the intermediate tile-level predictions of WeakSTIL are highly interpretable, which suggests that WeakSTIL pays attention to latent features related to the number of TILs and the tissue type. In the future, WeakSTIL may be used to provide consistent and interpretable sTIL% predictions to stratify breast cancer patients into targeted therapy arms.

George Yiasemis, Chaoping Zhang, Clara I. Sánchez et al.

In spite of its extensive adaptation in almost every medical diagnostic and examinatorial application, Magnetic Resonance Imaging (MRI) is still a slow imaging modality which limits its use for dynamic imaging. In recent years, Parallel Imaging (PI) and Compressed Sensing (CS) have been utilised to accelerate the MRI acquisition. In clinical settings, subsampling the k-space measurements during scanning time using Cartesian trajectories, such as rectilinear sampling, is currently the most conventional CS approach applied which, however, is prone to producing aliased reconstructions. With the advent of the involvement of Deep Learning (DL) in accelerating the MRI, reconstructing faithful images from subsampled data became increasingly promising. Retrospectively applying a subsampling mask onto the k-space data is a way of simulating the accelerated acquisition of k-space data in real clinical setting. In this paper we compare and provide a review for the effect of applying either rectilinear or radial retrospective subsampling on the quality of the reconstructions outputted by trained deep neural networks. With the same choice of hyper-parameters, we train and evaluate two distinct Recurrent Inference Machines (RIMs), one for each type of subsampling. The qualitative and quantitative results of our experiments indicate that the model trained on data with radial subsampling attains higher performance and learns to estimate reconstructions with higher fidelity paving the way for other DL approaches to involve radial subsampling.

Yoni Schirris, Efstratios Gavves, Iris Nederlof et al.

We propose a Deep learning-based weak label learning method for analyzing whole slide images (WSIs) of Hematoxylin and Eosin (H&E) stained tumor tissue not requiring pixel-level or tile-level annotations using Self-supervised pre-training and heterogeneity-aware deep Multiple Instance LEarning (DeepSMILE). We apply DeepSMILE to the task of Homologous recombination deficiency (HRD) and microsatellite instability (MSI) prediction. We utilize contrastive self-supervised learning to pre-train a feature extractor on histopathology tiles of cancer tissue. Additionally, we use variability-aware deep multiple instance learning to learn the tile feature aggregation function while modeling tumor heterogeneity. For MSI prediction in a tumor-annotated and color normalized subset of TCGA-CRC (n=360 patients), contrastive self-supervised learning improves the tile supervision baseline from 0.77 to 0.87 AUROC, on par with our proposed DeepSMILE method. On TCGA-BC (n=1041 patients) without any manual annotations, DeepSMILE improves HRD classification performance from 0.77 to 0.81 AUROC compared to tile supervision with either a self-supervised or ImageNet pre-trained feature extractor. Our proposed methods reach the baseline performance using only 40% of the labeled data on both datasets. These improvements suggest we can use standard self-supervised learning techniques combined with multiple instance learning in the histopathology domain to improve genomic label classification performance with fewer labeled data.

Andreas Panteli, Jonas Teuwen, Hugo Horlings et al.

Object localisation, in the context of regular images, often depicts objects like people or cars. In these images, there is typically a relatively small number of objects per class, which usually is manageable to annotate. However, outside the setting of regular images, we are often confronted with a different situation. In computational pathology, digitised tissue sections are extremely large images, whose dimensions quickly exceed 250'000x250'000 pixels, where relevant objects, such as tumour cells or lymphocytes can quickly number in the millions. Annotating them all is practically impossible and annotating sparsely a few, out of many more, is the only possibility. Unfortunately, learning from sparse annotations, or sparse-shot learning, clashes with standard supervised learning because what is not annotated is treated as a negative. However, assigning negative labels to what are true positives leads to confusion in the gradients and biased learning. To this end, we present exclusive cross-entropy, which slows down the biased learning by examining the second-order loss derivatives in order to drop the loss terms corresponding to likely biased terms. Experiments on nine datasets and two different localisation tasks, detection with YOLLO and segmentation with Unet, show that we obtain considerable improvements compared to cross-entropy or focal loss, while often reaching the best possible performance for the model with only 10-40% of annotations.

Fazael Ayatollahi, Shahriar B. Shokouhi, Ritse M. Mann et al.

Purpose: We propose a deep learning-based computer-aided detection (CADe) method to detect breast lesions in ultrafast DCE-MRI sequences. This method uses both the three-dimensional spatial information and temporal information obtained from the early-phase of the dynamic acquisition. Methods: The proposed CADe method, based on a modified 3D RetinaNet model, operates on ultrafast T1 weighted sequences, which are preprocessed for motion compensation, temporal normalization, and are cropped before passing into the model. The model is optimized to enable the detection of relatively small breast lesions in a screening setting, focusing on detection of lesions that are harder to differentiate from confounding structures inside the breast. Results: The method was developed based on a dataset consisting of 489 ultrafast MRI studies obtained from 462 patients containing a total of 572 lesions (365 malignant, 207 benign) and achieved a detection rate, sensitivity, and detection rate of benign lesions of 0.90 (0.876-0.934), 0.95 (0.934-0.980), and 0.81 (0.751-0.871) at 4 false positives per normal breast with 10-fold cross-testing, respectively. Conclusions: The deep learning architecture used for the proposed CADe application can efficiently detect benign and malignant lesions on ultrafast DCE-MRI. Furthermore, utilizing the less visible hard-to detect-lesions in training improves the learning process and, subsequently, detection of malignant breast lesions.

Matthew J. Muckley, Bruno Riemenschneider, Alireza Radmanesh et al.

Accelerating MRI scans is one of the principal outstanding problems in the MRI research community. Towards this goal, we hosted the second fastMRI competition targeted towards reconstructing MR images with subsampled k-space data. We provided participants with data from 7,299 clinical brain scans (de-identified via a HIPAA-compliant procedure by NYU Langone Health), holding back the fully-sampled data from 894 of these scans for challenge evaluation purposes. In contrast to the 2019 challenge, we focused our radiologist evaluations on pathological assessment in brain images. We also debuted a new Transfer track that required participants to submit models evaluated on MRI scanners from outside the training set. We received 19 submissions from eight different groups. Results showed one team scoring best in both SSIM scores and qualitative radiologist evaluations. We also performed analysis on alternative metrics to mitigate the effects of background noise and collected feedback from the participants to inform future challenges. Lastly, we identify common failure modes across the submissions, highlighting areas of need for future research in the MRI reconstruction community.

Youssef Beauferris, Jonas Teuwen, Dimitrios Karkalousos et al.

Deep-learning-based brain magnetic resonance imaging (MRI) reconstruction methods have the potential to accelerate the MRI acquisition process. Nevertheless, the scientific community lacks appropriate benchmarks to assess MRI reconstruction quality of high-resolution brain images, and evaluate how these proposed algorithms will behave in the presence of small, but expected data distribution shifts. The Multi-Coil Magnetic Resonance Image (MC-MRI) Reconstruction Challenge provides a benchmark that aims at addressing these issues, using a large dataset of high-resolution, three-dimensional, T1-weighted MRI scans. The challenge has two primary goals: 1) to compare different MRI reconstruction models on this dataset and 2) to assess the generalizability of these models to data acquired with a different number of receiver coils. In this paper, we describe the challenge experimental design, and summarize the results of a set of baseline and state of the art brain MRI reconstruction models. We provide relevant comparative information on the current MRI reconstruction state-of-the-art and highlight the challenges of obtaining generalizable models that are required prior to broader clinical adoption. The MC-MRI benchmark data, evaluation code and current challenge leaderboard are publicly available. They provide an objective performance assessment for future developments in the field of brain MRI reconstruction.

Jonas Teuwen, Nikita Moriakov, Christian Fedon et al.

The two-dimensional nature of mammography makes estimation of the overall breast density challenging, and estimation of the true patient-specific radiation dose impossible. Digital breast tomosynthesis (DBT), a pseudo-3D technique, is now commonly used in breast cancer screening and diagnostics. Still, the severely limited 3rd dimension information in DBT has not been used, until now, to estimate the true breast density or the patient-specific dose. This study proposes a reconstruction algorithm for DBT based on deep learning specifically optimized for these tasks. The algorithm, which we name DBToR, is based on unrolling a proximal-dual optimization method. The proximal operators are replaced with convolutional neural networks and prior knowledge is included in the model. This extends previous work on a deep learning-based reconstruction model by providing both the primal and the dual blocks with breast thickness information, which is available in DBT. Training and testing of the model were performed using virtual patient phantoms from two different sources. Reconstruction performance, and accuracy in estimation of breast density and radiation dose, were estimated, showing high accuracy (density <+/-3%; dose <+/-20%) without bias, significantly improving on the current state-of-the-art. This work also lays the groundwork for developing a deep learning-based reconstruction algorithm for the task of image interpretation by radiologists.

Nikita Moriakov, Jonas Adler, Jonas Teuwen

Unpaired image-to-image translation has attracted significant interest due to the invention of CycleGAN, a method which utilizes a combination of adversarial and cycle consistency losses to avoid the need for paired data. It is known that the CycleGAN problem might admit multiple solutions, and our goal in this paper is to analyze the space of exact solutions and to give perturbation bounds for approximate solutions. We show theoretically that the exact solution space is invariant with respect to automorphisms of the underlying probability spaces, and, furthermore, that the group of automorphisms acts freely and transitively on the space of exact solutions. We examine the case of zero `pure' CycleGAN loss first in its generality, and, subsequently, expand our analysis to approximate solutions for `extended' CycleGAN loss where identity loss term is included. In order to demonstrate that these results are applicable, we show that under mild conditions nontrivial smooth automorphisms exist. Furthermore, we provide empirical evidence that neural networks can learn these automorphisms with unexpected and unwanted results. We conclude that finding optimal solutions to the CycleGAN loss does not necessarily lead to the envisioned result in image-to-image translation tasks and that underlying hidden symmetries can render the result utterly useless.

Patrick Putzky, Dimitrios Karkalousos, Jonas Teuwen et al.

We, team AImsterdam, summarize our submission to the fastMRI challenge (Zbontar et al., 2018). Our approach builds on recent advances in invertible learning to infer models as presented in Putzky and Welling (2019). Both, our single-coil and our multi-coil model share the same basic architecture.

Yeman Brhane Hagos, Albert Gubern Merida, Jonas Teuwen

Convolutional Neural Networks (CNN) have had a huge success in many areas of computer vision and medical image analysis. However, there is still an immense potential for performance improvement in mammogram breast cancer detection Computer-Aided Detection (CAD) systems by integrating all the information that the radiologist utilizes, such as symmetry and temporal data. In this work, we proposed a patch based multi-input CNN that learns symmetrical difference to detect breast masses. The network was trained on a large-scale dataset of 28294 mammogram images. The performance was compared to a baseline architecture without symmetry context using Area Under the ROC Curve (AUC) and Competition Performance Metric (CPM). At candidate level, AUC value of 0.933 with 95% confidence interval of [0.920, 0.954] was obtained when symmetry information is incorporated in comparison with baseline architecture which yielded AUC value of 0.929 with [0.919, 0.947] confidence interval. By incorporating symmetrical information, although there was no a significant candidate level performance again (p = 0.111), we have found a compelling result at exam level with CPM value of 0.733 (p = 0.001). We believe that including temporal data, and adding benign class to the dataset could improve the detection performance.

Joris van Vugt, Elena Marchiori, Ritse Mann et al.

Computer-aided detection aims to improve breast cancer screening programs by helping radiologists to evaluate digital mammography (DM) exams. DM exams are generated by devices from different vendors, with diverse characteristics between and even within vendors. Physical properties of these devices and postprocessing of the images can greatly influence the resulting mammogram. This results in the fact that a deep learning model trained on data from one vendor cannot readily be applied to data from another vendor. This paper investigates the use of tailored transfer learning methods based on adversarial learning to tackle this problem. We consider a database of DM exams (mostly bilateral and two views) generated by Hologic and Siemens vendors. We analyze two transfer learning settings: 1) unsupervised transfer, where Hologic data with soft lesion annotation at pixel level and Siemens unlabelled data are used to annotate images in the latter data; 2) weak supervised transfer, where exam level labels for images from the Siemens mammograph are available. We propose tailored variants of recent state-of-the-art methods for transfer learning which take into account the class imbalance and incorporate knowledge provided by the annotations at exam level. Results of experiments indicate the beneficial effect of transfer learning in both transfer settings. Notably, at 0.02 false positives per image, we achieve a sensitivity of 0.37, compared to 0.30 of a baseline with no transfer. Results indicate that using exam level annotations gives an additional increase in sensitivity.

Nikita Moriakov, Koen Michielsen, Jonas Adler et al.

Digital breast tomosynthesis is rapidly replacing digital mammography as the basic x-ray technique for evaluation of the breasts. However, the sparse sampling and limited angular range gives rise to different artifacts, which manufacturers try to solve in several ways. In this study we propose an extension of the Learned Primal-Dual algorithm for digital breast tomosynthesis. The Learned Primal-Dual algorithm is a deep neural network consisting of several `reconstruction blocks', which take in raw sinogram data as the initial input, perform a forward and a backward pass by taking projections and back-projections, and use a convolutional neural network to produce an intermediate reconstruction result which is then improved further by the successive reconstruction block. We extend the architecture by providing breast thickness measurements as a mask to the neural network and allow it to learn how to use this thickness mask. We have trained the algorithm on digital phantoms and the corresponding noise-free/noisy projections, and then tested the algorithm on digital phantoms for varying level of noise. Reconstruction performance of the algorithms was compared visually, using MSE loss and Structural Similarity Index. Results indicate that the proposed algorithm outperforms the baseline iterative reconstruction algorithm in terms of reconstruction quality for both breast edges and internal structures and is robust to noise.

Timothy de Moor, Alejandro Rodriguez-Ruiz, Albert Gubern Mérida et al.

Computer-aided detection or decision support systems aim to improve breast cancer screening programs by helping radiologists to evaluate digital mammography (DM) exams. Commonly such methods proceed in two steps: selection of candidate regions for malignancy, and later classification as either malignant or not. In this study, we present a candidate detection method based on deep learning to automatically detect and additionally segment soft tissue lesions in DM. A database of DM exams (mostly bilateral and two views) was collected from our institutional archive. In total, 7196 DM exams (28294 DM images) acquired with systems from three different vendors (General Electric, Siemens, Hologic) were collected, of which 2883 contained malignant lesions verified with histopathology. Data was randomly split on an exam level into training (50\%), validation (10\%) and testing (40\%) of deep neural network with u-net architecture. The u-net classifies the image but also provides lesion segmentation. Free receiver operating characteristic (FROC) analysis was used to evaluate the model, on an image and on an exam level. On an image level, a maximum sensitivity of 0.94 at 7.93 false positives (FP) per image was achieved. Similarly, per exam a maximum sensitivity of 0.98 at 7.81 FP per image was achieved. In conclusion, the method could be used as a candidate selection model with high accuracy and with the additional information of lesion segmentation.

Mohsen Ghafoorian, Jonas Teuwen, Rashindra Manniesing et al.

Ventricular volume and its progression are known to be linked to several brain diseases such as dementia and schizophrenia. Therefore accurate measurement of ventricle volume is vital for longitudinal studies on these disorders, making automated ventricle segmentation algorithms desirable. In the past few years, deep neural networks have shown to outperform the classical models in many imaging domains. However, the success of deep networks is dependent on manually labeled data sets, which are expensive to acquire especially for higher dimensional data in the medical domain. In this work, we show that deep neural networks can be trained on much-cheaper-to-acquire pseudo-labels (e.g., generated by other automated less accurate methods) and still produce more accurate segmentations compared to the quality of the labels. To show this, we use noisy segmentation labels generated by a conventional region growing algorithm to train a deep network for lateral ventricle segmentation. Then on a large manually annotated test set, we show that the network significantly outperforms the conventional region growing algorithm which was used to produce the training labels for the network. Our experiments report a Dice Similarity Coefficient (DSC) of $0.874$ for the trained network compared to $0.754$ for the conventional region growing algorithm ($p < 0.001$).