Henkjan Huisman

Bram de Wilde, Anindo Saha, Maarten de Rooij et al.

Diffusion models for text-to-image generation, known for their efficiency, accessibility, and quality, have gained popularity. While inference with these systems on consumer-grade GPUs is increasingly feasible, training from scratch requires large captioned datasets and significant computational resources. In medical image generation, the limited availability of large, publicly accessible datasets with text reports poses challenges due to legal and ethical concerns. This work shows that adapting pre-trained Stable Diffusion models to medical imaging modalities is achievable by training text embeddings using Textual Inversion. In this study, we experimented with small medical datasets (100 samples each from three modalities) and trained within hours to generate diagnostically accurate images, as judged by an expert radiologist. Experiments with Textual Inversion training and inference parameters reveal the necessity of larger embeddings and more examples in the medical domain. Classification experiments show an increase in diagnostic accuracy (AUC) for detecting prostate cancer on MRI, from 0.78 to 0.80. Further experiments demonstrate embedding flexibility through disease interpolation, combining pathologies, and inpainting for precise disease appearance control. The trained embeddings are compact (less than 1 MB), enabling easy data sharing with reduced privacy concerns.

Yiwen Li, Yunguan Fu, Iani Gayo et al.

The prowess that makes few-shot learning desirable in medical image analysis is the efficient use of the support image data, which are labelled to classify or segment new classes, a task that otherwise requires substantially more training images and expert annotations. This work describes a fully 3D prototypical few-shot segmentation algorithm, such that the trained networks can be effectively adapted to clinically interesting structures that are absent in training, using only a few labelled images from a different institute. First, to compensate for the widely recognised spatial variability between institutions in episodic adaptation of novel classes, a novel spatial registration mechanism is integrated into prototypical learning, consisting of a segmentation head and an spatial alignment module. Second, to assist the training with observed imperfect alignment, support mask conditioning module is proposed to further utilise the annotation available from the support images. Extensive experiments are presented in an application of segmenting eight anatomical structures important for interventional planning, using a data set of 589 pelvic T2-weighted MR images, acquired at seven institutes. The results demonstrate the efficacy in each of the 3D formulation, the spatial registration, and the support mask conditioning, all of which made positive contributions independently or collectively. Compared with the previously proposed 2D alternatives, the few-shot segmentation performance was improved with statistical significance, regardless whether the support data come from the same or different institutes.

Michelle Stegeman, Lena Philipp, Fennie van der Graaf et al.

Medical foundation models show promise to learn broadly generalizable features from large, diverse datasets. This could be the base for reliable cross-modality generalization and rapid adaptation to new, task-specific goals, with only a few task-specific examples. Yet, evidence for this is limited by the lack of public, standardized, and reproducible evaluation frameworks, as existing public benchmarks are often fragmented across task-, organ-, or modality-specific settings, limiting assessment of cross-task generalization. We introduce UNICORN, a public benchmark designed to systematically evaluate medical foundation models under a unified protocol. To isolate representation quality, we built the benchmark on a novel two-step framework that decouples model inference from task-specific evaluation based on standardized few-shot adaptation. As a central design choice, we constructed indirectly accessible sequestered test sets derived from clinically relevant cohorts, along with standardized evaluation code and a submission interface on an open benchmarking platform. Performance is aggregated into a single UNICORN Score, a new metric that we introduce to support direct comparison of foundation models across diverse medical domains, modalities, and task types. The UNICORN test dataset includes data from more than 2,400 patients, including over 3,700 vision cases and over 2,400 clinical reports collected from 17 institutions across eight countries. The benchmark spans eight anatomical regions and four imaging modalities. Both task-specific and aggregated leaderboards enable accessible, standardized, and reproducible evaluation. By standardizing multi-task, multi-modality assessment, UNICORN establishes a foundation for reproducible benchmarking of medical foundation models. Data, baseline methods, and the evaluation platform are publicly available via unicorn.grand-challenge.org.

Hao Li, Han Liu, Heinrich von Busch et al.

Our hypothesis is that UDA using diffusion-weighted images, generated with a unified model, offers a promising and reliable strategy for enhancing the performance of supervised learning models in multi-site prostate lesion detection, especially when various b-values are present. This retrospective study included data from 5,150 patients (14,191 samples) collected across nine different imaging centers. A novel UDA method using a unified generative model was developed for multi-site PCa detection. This method translates diffusion-weighted imaging (DWI) acquisitions, including apparent diffusion coefficient (ADC) and individual DW images acquired using various b-values, to align with the style of images acquired using b-values recommended by Prostate Imaging Reporting and Data System (PI-RADS) guidelines. The generated ADC and DW images replace the original images for PCa detection. An independent set of 1,692 test cases (2,393 samples) was used for evaluation. The area under the receiver operating characteristic curve (AUC) was used as the primary metric, and statistical analysis was performed via bootstrapping. For all test cases, the AUC values for baseline SL and UDA methods were 0.73 and 0.79 (p<.001), respectively, for PI-RADS>=3, and 0.77 and 0.80 (p<.001) for PI-RADS>=4 PCa lesions. In the 361 test cases under the most unfavorable image acquisition setting, the AUC values for baseline SL and UDA were 0.49 and 0.76 (p<.001) for PI-RADS>=3, and 0.50 and 0.77 (p<.001) for PI-RADS>=4 PCa lesions. The results indicate the proposed UDA with generated images improved the performance of SL methods in multi-site PCa lesion detection across datasets with various b values, especially for images acquired with significant deviations from the PI-RADS recommended DWI protocol (e.g. with an extremely high b-value).

Gabriele Lozupone, Alessandro Bria, Francesco Fontanella et al.

This study presents Latent Diffusion Autoencoder (LDAE), a novel encoder-decoder diffusion-based framework for efficient and meaningful unsupervised learning in medical imaging, focusing on Alzheimer disease (AD) using brain MR from the ADNI database as a case study. Unlike conventional diffusion autoencoders operating in image space, LDAE applies the diffusion process in a compressed latent representation, improving computational efficiency and making 3D medical imaging representation learning tractable. To validate the proposed approach, we explore two key hypotheses: (i) LDAE effectively captures meaningful semantic representations on 3D brain MR associated with AD and ageing, and (ii) LDAE achieves high-quality image generation and reconstruction while being computationally efficient. Experimental results support both hypotheses: (i) linear-probe evaluations demonstrate promising diagnostic performance for AD (ROC-AUC: 90%, ACC: 84%) and age prediction (MAE: 4.1 years, RMSE: 5.2 years); (ii) the learned semantic representations enable attribute manipulation, yielding anatomically plausible modifications; (iii) semantic interpolation experiments show strong reconstruction of missing scans, with SSIM of 0.969 (MSE: 0.0019) for a 6-month gap. Even for longer gaps (24 months), the model maintains robust performance (SSIM > 0.93, MSE < 0.004), indicating an ability to capture temporal progression trends; (iv) compared to conventional diffusion autoencoders, LDAE significantly increases inference throughput (20x faster) while also enhancing reconstruction quality. These findings position LDAE as a promising framework for scalable medical imaging applications, with the potential to serve as a foundation model for medical image analysis. Code available at https://github.com/GabrieleLozupone/LDAE

Matin Hosseinzadeh, Anindo Saha, Joeran Bosma et al.

Quality of deep convolutional neural network predictions strongly depends on the size of the training dataset and the quality of the annotations. Creating annotations, especially for 3D medical image segmentation, is time-consuming and requires expert knowledge. We propose a novel semi-supervised learning (SSL) approach that requires only a relatively small number of annotations while being able to use the remaining unlabeled data to improve model performance. Our method uses a pseudo-labeling technique that employs recent deep learning uncertainty estimation models. By using the estimated uncertainty, we were able to rank pseudo-labels and automatically select the best pseudo-annotations generated by the supervised model. We applied this to prostate zonal segmentation in T2-weighted MRI scans. Our proposed model outperformed the semi-supervised model in experiments with the ProstateX dataset and an external test set, by leveraging only a subset of unlabeled data rather than the full collection of 4953 cases, our proposed model demonstrated improved performance. The segmentation dice similarity coefficient in the transition zone and peripheral zone increased from 0.835 and 0.727 to 0.852 and 0.751, respectively, for fully supervised model and the uncertainty-aware semi-supervised learning model (USSL). Our USSL model demonstrates the potential to allow deep learning models to be trained on large datasets without requiring full annotation. Our code is available at https://github.com/DIAGNijmegen/prostateMR-USSL.

Joeran S. Bosma, Anindo Saha, Matin Hosseinzadeh et al.

Deep learning-based diagnostic performance increases with more annotated data, but large-scale manual annotations are expensive and labour-intensive. Experts evaluate diagnostic images during clinical routine, and write their findings in reports. Leveraging unlabelled exams paired with clinical reports could overcome the manual labelling bottleneck. We hypothesise that detection models can be trained semi-supervised with automatic annotations generated using model predictions, guided by sparse information from clinical reports. To demonstrate efficacy, we train clinically significant prostate cancer (csPCa) segmentation models, where automatic annotations are guided by the number of clinically significant findings in the radiology reports. We included 7,756 prostate MRI examinations, of which 3,050 were manually annotated. We evaluated prostate cancer detection performance on 300 exams from an external centre with histopathology-confirmed ground truth. Semi-supervised training improved patient-based diagnostic area under the receiver operating characteristic curve from $87.2 \pm 0.8\%$ to $89.4 \pm 1.0\%$ ($P<10^{-4}$) and improved lesion-based sensitivity at one false positive per case from $76.4 \pm 3.8\%$ to $83.6 \pm 2.3\%$ ($P<10^{-4}$). Semi-supervised training was 14$\times$ more annotation-efficient for case-based performance and 6$\times$ more annotation-efficient for lesion-based performance. This improved performance demonstrates the feasibility of our training procedure. Source code is publicly available at github.com/DIAGNijmegen/Report-Guided-Annotation. Best csPCa detection algorithm is available at grand-challenge.org/algorithms/bpmri-cspca-detection-report-guided-annotations/.

Alessa Hering, Sarah de Boer, Anindo Saha et al.

The PI-CAI (Prostate Imaging: Cancer AI) challenge led to expert-level diagnostic algorithms for clinically significant prostate cancer detection. The algorithms receive biparametric MRI scans as input, which consist of T2-weighted and diffusion-weighted scans. These scans can be misaligned due to multiple factors in the scanning process. Image registration can alleviate this issue by predicting the deformation between the sequences. We investigate the effect of image registration on the diagnostic performance of AI-based prostate cancer diagnosis. First, the image registration algorithm, developed in MeVisLab, is analyzed using a dataset with paired lesion annotations. Second, the effect on diagnosis is evaluated by comparing case-level cancer diagnosis performance between using the original dataset, rigidly aligned diffusion-weighted scans, or deformably aligned diffusion-weighted scans. Rigid registration showed no improvement. Deformable registration demonstrated a substantial improvement in lesion overlap (+10% median Dice score) and a positive yet non-significant improvement in diagnostic performance (+0.3% AUROC, p=0.18). Our investigation shows that a substantial improvement in lesion alignment does not directly lead to a significant improvement in diagnostic performance. Qualitative analysis indicated that jointly developing image registration methods and diagnostic AI algorithms could enhance diagnostic accuracy and patient outcomes.

Anindo Saha, Joeran S. Bosma, Jasper J. Twilt et al.

In this intercontinental, confirmatory study, we include a retrospective cohort of 22,481 MRI examinations (21,288 patients; 46 cities in 22 countries) to train and externally validate the PI-CAI-2B model, i.e., an efficient, next-generation iteration of the state-of-the-art AI system that was developed for detecting Gleason grade group $\geq$2 prostate cancer on MRI during the PI-CAI study. Of these examinations, 20,471 cases (19,278 patients; 26 cities in 14 countries) from two EU Horizon projects (ProCAncer-I, COMFORT) and 12 independent centers based in Europe, North America, Asia and Africa, are used for training and internal testing. Additionally, 2010 cases (2010 patients; 20 external cities in 12 countries) from population-based screening (STHLM3-MRI, IP1-PROSTAGRAM trials) and primary diagnostic settings (PRIME trial) based in Europe, North and South Americas, Asia and Australia, are used for external testing. Primary endpoint is the proportion of AI-based assessments in agreement with the standard of care diagnoses (i.e., clinical assessments made by expert uropathologists on histopathology, if available, or at least two expert urogenital radiologists in consensus; with access to patient history and peer consultation) in the detection of Gleason grade group $\geq$2 prostate cancer within the external testing cohorts. Our statistical analysis plan is prespecified with a hypothesis of diagnostic interchangeability to the standard of care at the PI-RADS $\geq$3 (primary diagnosis) or $\geq$4 (screening) cut-off, considering an absolute margin of 0.05 and reader estimates derived from the PI-CAI observer study (62 radiologists reading 400 cases). Secondary measures comprise the area under the receiver operating characteristic curve (AUROC) of the AI system stratified by imaging quality, patient age and patient ethnicity to identify underlying biases (if any).

Hongwei Bran Li, Fernando Navarro, Ivan Ezhov et al.

Uncertainty in medical image segmentation tasks, especially inter-rater variability, arising from differences in interpretations and annotations by various experts, presents a significant challenge in achieving consistent and reliable image segmentation. This variability not only reflects the inherent complexity and subjective nature of medical image interpretation but also directly impacts the development and evaluation of automated segmentation algorithms. Accurately modeling and quantifying this variability is essential for enhancing the robustness and clinical applicability of these algorithms. We report the set-up and summarize the benchmark results of the Quantification of Uncertainties in Biomedical Image Quantification Challenge (QUBIQ), which was organized in conjunction with International Conferences on Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2020 and 2021. The challenge focuses on the uncertainty quantification of medical image segmentation which considers the omnipresence of inter-rater variability in imaging datasets. The large collection of images with multi-rater annotations features various modalities such as MRI and CT; various organs such as the brain, prostate, kidney, and pancreas; and different image dimensions 2D-vs-3D. A total of 24 teams submitted different solutions to the problem, combining various baseline models, Bayesian neural networks, and ensemble model techniques. The obtained results indicate the importance of the ensemble models, as well as the need for further research to develop efficient 3D methods for uncertainty quantification methods in 3D segmentation tasks.

Yiwen Li, Yunguan Fu, Qianye Yang et al.

The ability to adapt medical image segmentation networks for a novel class such as an unseen anatomical or pathological structure, when only a few labelled examples of this class are available from local healthcare providers, is sought-after. This potentially addresses two widely recognised limitations in deploying modern deep learning models to clinical practice, expertise-and-labour-intensive labelling and cross-institution generalisation. This work presents the first 3D few-shot interclass segmentation network for medical images, using a labelled multi-institution dataset from prostate cancer patients with eight regions of interest. We propose an image alignment module registering the predicted segmentation of both query and support data, in a standard prototypical learning algorithm, to a reference atlas space. The built-in registration mechanism can effectively utilise the prior knowledge of consistent anatomy between subjects, regardless whether they are from the same institution or not. Experimental results demonstrated that the proposed registration-assisted prototypical learning significantly improved segmentation accuracy (p-values<0.01) on query data from a holdout institution, with varying availability of support data from multiple institutions. We also report the additional benefits of the proposed 3D networks with 75% fewer parameters and an arguably simpler implementation, compared with existing 2D few-shot approaches that segment 2D slices of volumetric medical images.

Natália Alves, Megan Schuurmans, Geke Litjens et al.

Early detection improves prognosis in pancreatic ductal adenocarcinoma (PDAC) but is challenging as lesions are often small and poorly defined on contrast-enhanced computed tomography scans (CE-CT). Deep learning can facilitate PDAC diagnosis, however current models still fail to identify small (<2cm) lesions. In this study, state-of-the-art deep learning models were used to develop an automatic framework for PDAC detection, focusing on small lesions. Additionally, the impact of integrating surrounding anatomy was investigated. CE-CT scans from a cohort of 119 pathology-proven PDAC patients and a cohort of 123 patients without PDAC were used to train a nnUnet for automatic lesion detection and segmentation (nnUnet_T). Two additional nnUnets were trained to investigate the impact of anatomy integration: (1) segmenting the pancreas and tumor (nnUnet_TP), (2) segmenting the pancreas, tumor, and multiple surrounding anatomical structures (nnUnet_MS). An external, publicly available test set was used to compare the performance of the three networks. The nnUnet_MS achieved the best performance, with an area under the receiver operating characteristic curve of 0.91 for the whole test set and 0.88 for tumors <2cm, showing that state-of-the-art deep learning can detect small PDAC and benefits from anatomy information.

Anindo Saha, Joeran Bosma, Jasper Linmans et al.

We hypothesize that probabilistic voxel-level classification of anatomy and malignancy in prostate MRI, although typically posed as near-identical segmentation tasks via U-Nets, require different loss functions for optimal performance due to inherent differences in their clinical objectives. We investigate distribution, region and boundary-based loss functions for both tasks across 200 patient exams from the publicly-available ProstateX dataset. For evaluation, we conduct a thorough comparative analysis of model predictions and calibration, measured with respect to multi-class volume segmentation of the prostate anatomy (whole-gland, transitional zone, peripheral zone), as well as, patient-level diagnosis and lesion-level detection of clinically significant prostate cancer. Notably, we find that distribution-based loss functions (in particular, focal loss) are well-suited for diagnostic or panoptic segmentation tasks such as lesion detection, primarily due to their implicit property of inducing better calibration. Meanwhile, (with the exception of focal loss) both distribution and region/boundary-based loss functions perform equally well for anatomical or semantic segmentation tasks, such as quantification of organ shape, size and boundaries.

Bram de Wilde, Richard P. G. ten Broek, Henkjan Huisman

Adhesions are an important cause of chronic pain following abdominal surgery. Recent developments in abdominal cine-MRI have enabled the non-invasive diagnosis of adhesions. Adhesions are identified on cine-MRI by the absence of sliding motion during movement. Diagnosis and mapping of adhesions improves the management of patients with pain. Detection of abdominal adhesions on cine-MRI is challenging from both a radiological and deep learning perspective. We focus on classifying presence or absence of adhesions in sagittal abdominal cine-MRI series. We experimented with spatio-temporal deep learning architectures centered around a ConvGRU architecture. A hybrid architecture comprising a ResNet followed by a ConvGRU model allows to classify a whole time-series. Compared to a stand-alone ResNet with a two time-point (inspiration/expiration) input, we show an increase in classification performance (AUROC) from 0.74 to 0.83 ($p<0.05$). Our full temporal classification approach adds only a small amount (5%) of parameters to the entire architecture, which may be useful for other medical imaging problems with a temporal dimension.

Michela Antonelli, Annika Reinke, Spyridon Bakas et al.

International challenges have become the de facto standard for comparative assessment of image analysis algorithms given a specific task. Segmentation is so far the most widely investigated medical image processing task, but the various segmentation challenges have typically been organized in isolation, such that algorithm development was driven by the need to tackle a single specific clinical problem. We hypothesized that a method capable of performing well on multiple tasks will generalize well to a previously unseen task and potentially outperform a custom-designed solution. To investigate the hypothesis, we organized the Medical Segmentation Decathlon (MSD) - a biomedical image analysis challenge, in which algorithms compete in a multitude of both tasks and modalities. The underlying data set was designed to explore the axis of difficulties typically encountered when dealing with medical images, such as small data sets, unbalanced labels, multi-site data and small objects. The MSD challenge confirmed that algorithms with a consistent good performance on a set of tasks preserved their good average performance on a different set of previously unseen tasks. Moreover, by monitoring the MSD winner for two years, we found that this algorithm continued generalizing well to a wide range of other clinical problems, further confirming our hypothesis. Three main conclusions can be drawn from this study: (1) state-of-the-art image segmentation algorithms are mature, accurate, and generalize well when retrained on unseen tasks; (2) consistent algorithmic performance across multiple tasks is a strong surrogate of algorithmic generalizability; (3) the training of accurate AI segmentation models is now commoditized to non AI experts.

Anindo Saha, Matin Hosseinzadeh, Henkjan Huisman

We present a multi-stage 3D computer-aided detection and diagnosis (CAD) model for automated localization of clinically significant prostate cancer (csPCa) in bi-parametric MR imaging (bpMRI). Deep attention mechanisms drive its detection network, targeting salient structures and highly discriminative feature dimensions across multiple resolutions. Its goal is to accurately identify csPCa lesions from indolent cancer and the wide range of benign pathology that can afflict the prostate gland. Simultaneously, a decoupled residual classifier is used to achieve consistent false positive reduction, without sacrificing high sensitivity or computational efficiency. In order to guide model generalization with domain-specific clinical knowledge, a probabilistic anatomical prior is used to encode the spatial prevalence and zonal distinction of csPCa. Using a large dataset of 1950 prostate bpMRI paired with radiologically-estimated annotations, we hypothesize that such CNN-based models can be trained to detect biopsy-confirmed malignancies in an independent cohort. For 486 institutional testing scans, the 3D CAD system achieves 83.69$\pm$5.22% and 93.19$\pm$2.96% detection sensitivity at 0.50 and 1.46 false positive(s) per patient, respectively, with 0.882$\pm$0.030 AUROC in patient-based diagnosis $-$significantly outperforming four state-of-the-art baseline architectures (U-SEResNet, UNet++, nnU-Net, Attention U-Net) from recent literature. For 296 external biopsy-confirmed testing scans, the ensembled CAD system shares moderate agreement with a consensus of expert radiologists (76.69%; $kappa$ $=$ 0.51$\pm$0.04) and independent pathologists (81.08%; $kappa$ $=$ 0.56$\pm$0.06); demonstrating strong generalization to histologically-confirmed csPCa diagnosis.

Anindo Saha, Matin Hosseinzadeh, Henkjan Huisman

We hypothesize that anatomical priors can be viable mediums to infuse domain-specific clinical knowledge into state-of-the-art convolutional neural networks (CNN) based on the U-Net architecture. We introduce a probabilistic population prior which captures the spatial prevalence and zonal distinction of clinically significant prostate cancer (csPCa), in order to improve its computer-aided detection (CAD) in bi-parametric MR imaging (bpMRI). To evaluate performance, we train 3D adaptations of the U-Net, U-SEResNet, UNet++ and Attention U-Net using 800 institutional training-validation scans, paired with radiologically-estimated annotations and our computed prior. For 200 independent testing bpMRI scans with histologically-confirmed delineations of csPCa, our proposed method of encoding clinical priori demonstrates a strong ability to improve patient-based diagnosis (upto 8.70% increase in AUROC) and lesion-level detection (average increase of 1.08 pAUC between 0.1-10 false positives per patient) across all four architectures.

Shi Hu, Daniel Worrall, Stefan Knegt et al.

The accurate estimation of predictive uncertainty carries importance in medical scenarios such as lung node segmentation. Unfortunately, most existing works on predictive uncertainty do not return calibrated uncertainty estimates, which could be used in practice. In this work we exploit multi-grader annotation variability as a source of 'groundtruth' aleatoric uncertainty, which can be treated as a target in a supervised learning problem. We combine this groundtruth uncertainty with a Probabilistic U-Net and test on the LIDC-IDRI lung nodule CT dataset and MICCAI2012 prostate MRI dataset. We find that we are able to improve predictive uncertainty estimates. We also find that we can improve sample accuracy and sample diversity. In real-world applications, our method could inform doctors about the confidence of the segmentation results.

Germonda Mooij, Ines Bagulho, Henkjan Huisman

Convolutional networks have become state-of-the-art techniques for automatic medical image analysis, with the U-net architecture being the most popular at this moment. In this article we report the application of a 3D version of U-net to the automatic segmentation of prostate peripheral and transition zones in 3D MRI images. Our results are slightly better than recent studies that used 2D U-net and handcrafted feature approaches. In addition, we test ideas for improving the 3D U-net setup, by 1) letting the network segment surrounding tissues, making use of the fixed anatomy, and 2) adjusting the network architecture to reflect the anisotropy in the dimensions of the MRI image volumes. While the latter adjustment gave a marginal improvement, the former adjustment showed a significant deterioration of the network performance. We were able to explain this deterioration by inspecting feature map activations in all layers of the network. We show that to segment more tissues the network replaces feature maps that were dedicated to detecting prostate peripheral zones, by feature maps detecting the surrounding tissues.

Ard de Gelder, Henkjan Huisman

Organ image segmentation can be improved by implementing prior knowledge about the anatomy. One way of doing this is by training an autoencoder to learn a lowdimensional representation of the segmentation. In this paper, this is applied in multi-label prostate MR segmentation, with some positive results.