Ertunc Erdil

Kerem Cekmeceli, Meva Himmetoglu, Guney I. Tombak et al. · eth-zurich

Neural networks achieve state-of-the-art performance in many supervised learning tasks when the training data distribution matches the test data distribution. However, their performance drops significantly under domain (covariate) shift, a prevalent issue in medical image segmentation due to varying acquisition settings across different scanner models and protocols. Recently, foundational models (FMs) trained on large datasets have gained attention for their ability to be adapted for downstream tasks and achieve state-of-the-art performance with excellent generalization capabilities on natural images. However, their effectiveness in medical image segmentation remains underexplored. In this paper, we investigate the domain generalization performance of various FMs, including DinoV2, SAM, MedSAM, and MAE, when fine-tuned using various parameter-efficient fine-tuning (PEFT) techniques such as Ladder and Rein (+LoRA) and decoder heads. We introduce a novel decode head architecture, HQHSAM, which simply integrates elements from two state-of-the-art decoder heads, HSAM and HQSAM, to enhance segmentation performance. Our extensive experiments on multiple datasets, encompassing various anatomies and modalities, reveal that FMs, particularly with the HQHSAM decode head, improve domain generalization for medical image segmentation. Moreover, we found that the effectiveness of PEFT techniques varies across different FMs. These findings underscore the potential of FMs to enhance the domain generalization performance of neural networks in medical image segmentation across diverse clinical settings, providing a solid foundation for future research. Code and models are available for research purposes at \url{https://github.com/kerem-cekmeceli/Foundation-Models-for-Medical-Imagery}.

Gustav Bredell, Kyriakos Flouris, Krishna Chaitanya et al.

Variational autoencoders (VAEs) are powerful generative modelling methods, however they suffer from blurry generated samples and reconstructions compared to the images they have been trained on. Significant research effort has been spent to increase the generative capabilities by creating more flexible models but often flexibility comes at the cost of higher complexity and computational cost. Several works have focused on altering the reconstruction term of the evidence lower bound (ELBO), however, often at the expense of losing the mathematical link to maximizing the likelihood of the samples under the modeled distribution. Here we propose a new formulation of the reconstruction term for the VAE that specifically penalizes the generation of blurry images while at the same time still maximizing the ELBO under the modeled distribution. We show the potential of the proposed loss on three different data sets, where it outperforms several recently proposed reconstruction losses for VAEs.

Sara Sangalli, Ertunc Erdil, Ender Konukoglu

In human-AI collaboration systems for critical applications, in order to ensure minimal error, users should set an operating point based on model confidence to determine when the decision should be delegated to human experts. Samples for which model confidence is lower than the operating point would be manually analysed by experts to avoid mistakes. Such systems can become truly useful only if they consider two aspects: models should be confident only for samples for which they are accurate, and the number of samples delegated to experts should be minimized. The latter aspect is especially crucial for applications where available expert time is limited and expensive, such as healthcare. The trade-off between the model accuracy and the number of samples delegated to experts can be represented by a curve that is similar to an ROC curve, which we refer to as confidence operating characteristic (COC) curve. In this paper, we argue that deep neural networks should be trained by taking into account both accuracy and expert load and, to that end, propose a new complementary loss function for classification that maximizes the area under this COC curve. This promotes simultaneously the increase in network accuracy and the reduction in number of samples delegated to humans. We perform experiments on multiple computer vision and medical image datasets for classification. Our results demonstrate that the proposed loss improves classification accuracy and delegates less number of decisions to experts, achieves better out-of-distribution samples detection and on par calibration performance compared to existing loss functions.

Ertunc Erdil, Nico Schulthess, Guney Tombak et al. · eth-zurich

DINO models provide rich patch-level representations that have recently enabled strong performance in unsupervised anomaly detection (UAD). Most existing methods extract patch embeddings from ``normal'' images and model them independently, ignoring spatial and neighborhood relationships between patches. This implicitly assumes that self-attention and positional encodings sufficiently encode contextual information within each patch embedding. In addition, the normative distribution is often modeled as memory banks or prototype-based representations, which require storing large numbers of features and performing costly comparisons at inference time, leading to substantial memory and computational overhead. In this work, we address both limitations by proposing a simple and efficient framework that explicitly models spatial and contextual dependencies between patch embeddings using a 2D autoregressive (AR) model. Instead of storing embeddings or clustering prototypes, our approach learns a compact parametric model of the normative distribution via an AR convolutional neural network (CNN). At test time, anomaly detection reduces to a single forward pass through the network and enables fast and memory-efficient inference. We evaluate our method on the BMAD benchmark, which comprises three medical imaging datasets, and compare it against existing work including recent DINO-based methods. Experimental results demonstrate that explicitly modeling spatial dependencies achieves competitive anomaly detection performance while substantially reducing inference time and memory requirements. Code is available at the project page: https://eerdil.github.io/spatial-ar-dinov3-uad/.

Guney Tombak, Ertunc Erdil, Ender Konukoglu

Cross-modal 3D medical image analysis requires voxelwise representations that remain anatomically consistent across imaging contrasts, scanners, and acquisition protocols. Recent work has shown that frozen 2D Vision Transformer (ViT) foundation models can support such representations, but typical pipelines extract features along a single anatomical axis and adapt those features inside a registration solver for one image pair at a time, leaving complementary viewing directions unused and producing representations that do not transfer to new volumes. We introduce VoxCor, a training-free fit--transform method for reusable volumetric feature representations from frozen 2D ViT foundation models. During an offline fitting phase, VoxCor combines triplanar ViT inference with a compact closed-form weighted partial least squares (WPLS) projection that uses fitting-time voxel correspondences to select modality-stable anatomical directions in the triplanar feature space. At transform time, new volumes are mapped by triplanar ViT inference and linear projection alone, without fine-tuning or registration. Voxel correspondences can then be queried directly by nearest-neighbor search. We evaluate VoxCor on intra-subject Abdomen MR--CT and inter-subject HCP T2w--T1w tasks using deformable registration, voxelwise k-nearest-neighbor segmentation, and segmentation-center landmark localization. VoxCor improves the hardest cross-subject, cross-modality transfer settings, reduces encoder sensitivity for dense correspondence transfer, and yields registration performance competitive with handcrafted descriptors and learned 3D features. This positions VoxCor as a reusable feature layer for downstream multimodal analysis beyond pairwise registration. Code, configuration files, and implementation details are publicly available on GitHub at \href{https://github.com/guneytombak/VoxCor}{guneytombak/VoxCor}.

Krishna Chaitanya, Neerav Karani, Christian F. Baumgartner et al.

Supervised learning-based segmentation methods typically require a large number of annotated training data to generalize well at test time. In medical applications, curating such datasets is not a favourable option because acquiring a large number of annotated samples from experts is time-consuming and expensive. Consequently, numerous methods have been proposed in the literature for learning with limited annotated examples. Unfortunately, the proposed approaches in the literature have not yet yielded significant gains over random data augmentation for image segmentation, where random augmentations themselves do not yield high accuracy. In this work, we propose a novel task-driven data augmentation method for learning with limited labeled data where the synthetic data generator, is optimized for the segmentation task. The generator of the proposed method models intensity and shape variations using two sets of transformations, as additive intensity transformations and deformation fields. Both transformations are optimized using labeled as well as unlabeled examples in a semi-supervised framework. Our experiments on three medical datasets, namely cardic, prostate and pancreas, show that the proposed approach significantly outperforms standard augmentation and semi-supervised approaches for image segmentation in the limited annotation setting. The code is made publicly available at https://github.com/krishnabits001/task$\_$driven$\_$data$\_$augmentation.

Ertunc Erdil, Krishna Chaitanya, Neerav Karani et al.

In the recent years, researchers proposed a number of successful methods to perform out-of-distribution (OOD) detection in deep neural networks (DNNs). So far the scope of the highly accurate methods has been limited to image level classification tasks. However, attempts for generally applicable methods beyond classification did not attain similar performance. In this paper, we address this limitation by proposing a simple yet effective task-agnostic OOD detection method. We estimate the probability density functions (pdfs) of intermediate features of a pre-trained DNN by performing kernel density estimation (KDE) on the training dataset. As direct application of KDE to feature maps is hindered by their high dimensionality, we use a set of lower-dimensional marginalized KDE models instead of a single high-dimensional one. At test time, we evaluate the pdfs on a test sample and produce a confidence score that indicates the sample is OOD. The use of KDE eliminates the need for making simplifying assumptions about the underlying feature pdfs and makes the proposed method task-agnostic. We perform extensive experiments on classification tasks using benchmark datasets for OOD detection. Additionally, we perform experiments on medical image segmentation tasks using brain MRI datasets. The results demonstrate that the proposed method consistently achieves high OOD detection performance in both classification and segmentation tasks and improves state-of-the-art in almost all cases. Code is available at \url{https://github.com/eerdil/task_agnostic_ood}

Krishna Chaitanya, Ertunc Erdil, Neerav Karani et al.

A key requirement for the success of supervised deep learning is a large labeled dataset - a condition that is difficult to meet in medical image analysis. Self-supervised learning (SSL) can help in this regard by providing a strategy to pre-train a neural network with unlabeled data, followed by fine-tuning for a downstream task with limited annotations. Contrastive learning, a particular variant of SSL, is a powerful technique for learning image-level representations. In this work, we propose strategies for extending the contrastive learning framework for segmentation of volumetric medical images in the semi-supervised setting with limited annotations, by leveraging domain-specific and problem-specific cues. Specifically, we propose (1) novel contrasting strategies that leverage structural similarity across volumetric medical images (domain-specific cue) and (2) a local version of the contrastive loss to learn distinctive representations of local regions that are useful for per-pixel segmentation (problem-specific cue). We carry out an extensive evaluation on three Magnetic Resonance Imaging (MRI) datasets. In the limited annotation setting, the proposed method yields substantial improvements compared to other self-supervision and semi-supervised learning techniques. When combined with a simple data augmentation technique, the proposed method reaches within 8% of benchmark performance using only two labeled MRI volumes for training, corresponding to only 4% (for ACDC) of the training data used to train the benchmark. The code is made public at https://github.com/krishnabits001/domain_specific_cl.

Neerav Karani, Ertunc Erdil, Krishna Chaitanya et al.

Convolutional Neural Networks (CNNs) work very well for supervised learning problems when the training dataset is representative of the variations expected to be encountered at test time. In medical image segmentation, this premise is violated when there is a mismatch between training and test images in terms of their acquisition details, such as the scanner model or the protocol. Remarkable performance degradation of CNNs in this scenario is well documented in the literature. To address this problem, we design the segmentation CNN as a concatenation of two sub-networks: a relatively shallow image normalization CNN, followed by a deep CNN that segments the normalized image. We train both these sub-networks using a training dataset, consisting of annotated images from a particular scanner and protocol setting. Now, at test time, we adapt the image normalization sub-network for \emph{each test image}, guided by an implicit prior on the predicted segmentation labels. We employ an independently trained denoising autoencoder (DAE) in order to model such an implicit prior on plausible anatomical segmentation labels. We validate the proposed idea on multi-center Magnetic Resonance imaging datasets of three anatomies: brain, heart and prostate. The proposed test-time adaptation consistently provides performance improvement, demonstrating the promise and generality of the approach. Being agnostic to the architecture of the deep CNN, the second sub-network, the proposed design can be utilized with any segmentation network to increase robustness to variations in imaging scanners and protocols. Our code is available at: \url{https://github.com/neerakara/test-time-adaptable-neural-networks-for-domain-generalization}.

Sara Sangalli, Gary Sarwin, Ertunc Erdil et al.

Forecasting surgical instrument trajectories and predicting the next surgical action recently started to attract attention from the research community. Both these tasks are crucial for automation and assistance in endoscopy surgery. Given the safety-critical nature of these tasks, reliable uncertainty quantification is essential. Conformal prediction is a fast-growing and widely recognized framework for uncertainty estimation in machine learning and computer vision, offering distribution-free, theoretically valid prediction intervals. In this work, we explore the application of standard conformal prediction and conformalized quantile regression to estimate uncertainty in forecasting surgical instrument motion, i.e., predicting direction and magnitude of surgical instruments' future motion. We analyze and compare their coverage and interval sizes, assessing the impact of multiple hypothesis testing and correction methods. Additionally, we show how these techniques can be employed to produce useful uncertainty heatmaps. To the best of our knowledge, this is the first study applying conformal prediction to surgical guidance, marking an initial step toward constructing principled prediction intervals with formal coverage guarantees in this domain.

Neerav Karani, Georg Brunner, Ertunc Erdil et al.

Performance of convolutional neural networks (CNNs) in image analysis tasks is often marred in the presence of acquisition-related distribution shifts between training and test images. Recently, it has been proposed to tackle this problem by fine-tuning trained CNNs for each test image. Such test-time-adaptation (TTA) is a promising and practical strategy for improving robustness to distribution shifts as it requires neither data sharing between institutions nor annotating additional data. Previous TTA methods use a helper model to increase similarity between outputs and/or features extracted from a test image with those of the training images. Such helpers, which are typically modeled using CNNs, can be task-specific and themselves vulnerable to distribution shifts in their inputs. To overcome these problems, we propose to carry out TTA by matching the feature distributions of test and training images, as modelled by a field-of-experts (FoE) prior. FoEs model complicated probability distributions as products of many simpler expert distributions. We use 1D marginal distributions of a trained task CNN's features as experts in the FoE model. Further, we compute principal components of patches of the task CNN's features, and consider the distributions of PCA loadings as additional experts. We validate the method on 5 MRI segmentation tasks (healthy tissues in 4 anatomical regions and lesions in 1 one anatomy), using data from 17 clinics, and on a MRI registration task, using data from 3 clinics. We find that the proposed FoE-based TTA is generically applicable in multiple tasks, and outperforms all previous TTA methods for lesion segmentation. For healthy tissue segmentation, the proposed method outperforms other task-agnostic methods, but a previous TTA method which is specifically designed for segmentation performs the best for most of the tested datasets. Our code is publicly available.

Gustav Bredell, Ertunc Erdil, Bruno Weber et al.

Blind deconvolution is an ill-posed problem arising in various fields ranging from microscopy to astronomy. The ill-posed nature of the problem requires adequate priors to arrive to a desirable solution. Recently, it has been shown that deep learning architectures can serve as an image generation prior during unsupervised blind deconvolution optimization, however often exhibiting a performance fluctuation even on a single image. We propose to use Wiener-deconvolution to guide the image generator during optimization by providing it a sharpened version of the blurry image using an auxiliary kernel estimate starting from a Gaussian. We observe that the high-frequency artifacts of deconvolution are reproduced with a delay compared to low-frequency features. In addition, the image generator reproduces low-frequency features of the deconvolved image faster than that of a blurry image. We embed the computational process in a constrained optimization framework and show that the proposed method yields higher stability and performance across multiple datasets. In addition, we provide the code.

Krishna Chaitanya, Ertunc Erdil, Neerav Karani et al.

Supervised deep learning-based methods yield accurate results for medical image segmentation. However, they require large labeled datasets for this, and obtaining them is a laborious task that requires clinical expertise. Semi/self-supervised learning-based approaches address this limitation by exploiting unlabeled data along with limited annotated data. Recent self-supervised learning methods use contrastive loss to learn good global level representations from unlabeled images and achieve high performance in classification tasks on popular natural image datasets like ImageNet. In pixel-level prediction tasks such as segmentation, it is crucial to also learn good local level representations along with global representations to achieve better accuracy. However, the impact of the existing local contrastive loss-based methods remains limited for learning good local representations because similar and dissimilar local regions are defined based on random augmentations and spatial proximity; not based on the semantic label of local regions due to lack of large-scale expert annotations in the semi/self-supervised setting. In this paper, we propose a local contrastive loss to learn good pixel level features useful for segmentation by exploiting semantic label information obtained from pseudo-labels of unlabeled images alongside limited annotated images. In particular, we define the proposed loss to encourage similar representations for the pixels that have the same pseudo-label/ label while being dissimilar to the representation of pixels with different pseudo-label/label in the dataset. We perform pseudo-label based self-training and train the network by jointly optimizing the proposed contrastive loss on both labeled and unlabeled sets and segmentation loss on only the limited labeled set. We evaluated on three public cardiac and prostate datasets, and obtain high segmentation performance.

Sara Sangalli, Ertunc Erdil, Andreas Hoetker et al.

Deep neural networks (DNNs) are notorious for making more mistakes for the classes that have substantially fewer samples than the others during training. Such class imbalance is ubiquitous in clinical applications and very crucial to handle because the classes with fewer samples most often correspond to critical cases (e.g., cancer) where misclassifications can have severe consequences. Not to miss such cases, binary classifiers need to be operated at high True Positive Rates (TPRs) by setting a higher threshold, but this comes at the cost of very high False Positive Rates (FPRs) for problems with class imbalance. Existing methods for learning under class imbalance most often do not take this into account. We argue that prediction accuracy should be improved by emphasizing reducing FPRs at high TPRs for problems where misclassification of the positive, i.e. critical, class samples are associated with higher cost. To this end, we pose the training of a DNN for binary classification as a constrained optimization problem and introduce a novel constraint that can be used with existing loss functions to enforce maximal area under the ROC curve (AUC) through prioritizing FPR reduction at high TPR. We solve the resulting constrained optimization problem using an Augmented Lagrangian method (ALM). Going beyond binary, we also propose two possible extensions of the proposed constraint for multi-class classification problems. We present experimental results for image-based binary and multi-class classification applications using an in-house medical imaging dataset, CIFAR10, and CIFAR100. Our results demonstrate that the proposed method improves the baselines in majority of the cases by attaining higher accuracy on critical classes while reducing the misclassification rate for the non-critical class samples.

Marc Gantenbein, Ertunc Erdil, Ender Konukoglu

Quantifying segmentation uncertainty has become an important issue in medical image analysis due to the inherent ambiguity of anatomical structures and its pathologies. Recently, neural network-based uncertainty quantification methods have been successfully applied to various problems. One of the main limitations of the existing techniques is the high memory requirement during training; which limits their application to processing smaller field-of-views (FOVs) and/or using shallower architectures. In this paper, we investigate the effect of using reversible blocks for building memory-efficient neural network architectures for quantification of segmentation uncertainty. The reversible architecture achieves memory saving by exactly computing the activations from the outputs of the subsequent layers during backpropagation instead of storing the activations for each layer. We incorporate the reversible blocks into a recently proposed architecture called PHiSeg that is developed for uncertainty quantification in medical image segmentation. The reversible architecture, RevPHiSeg, allows training neural networks for quantifying segmentation uncertainty on GPUs with limited memory and processing larger FOVs. We perform experiments on the LIDC-IDRI dataset and an in-house prostate dataset, and present comparisons with PHiSeg. The results demonstrate that RevPHiSeg consumes ~30% less memory compared to PHiSeg while achieving very similar segmentation accuracy.

Anna Volokitin, Ertunc Erdil, Neerav Karani et al.

Probabilistic modelling has been an essential tool in medical image analysis, especially for analyzing brain Magnetic Resonance Images (MRI). Recent deep learning techniques for estimating high-dimensional distributions, in particular Variational Autoencoders (VAEs), opened up new avenues for probabilistic modeling. Modelling of volumetric data has remained a challenge, however, because constraints on available computation and training data make it difficult effectively leverage VAEs, which are well-developed for 2D images. We propose a method to model 3D MR brain volumes distribution by combining a 2D slice VAE with a Gaussian model that captures the relationships between slices. We do so by estimating the sample mean and covariance in the latent space of the 2D model over the slice direction. This combined model lets us sample new coherent stacks of latent variables to decode into slices of a volume. We also introduce a novel evaluation method for generated volumes that quantifies how well their segmentations match those of true brain anatomy. We demonstrate that our proposed model is competitive in generating high quality volumes at high resolutions according to both traditional metrics and our proposed evaluation.

Ertunc Erdil, Ali Ozgur Argunsah, Tolga Tasdizen et al.

Data driven segmentation is an important initial step of shape prior-based segmentation methods since it is assumed that the data term brings a curve to a plausible level so that shape and data terms can then work together to produce better segmentations. When purely data driven segmentation produces poor results, the final segmentation is generally affected adversely. One challenge faced by many existing data terms is due to the fact that they consider only pixel intensities to decide whether to assign a pixel to the foreground or to the background region. When the distributions of the foreground and background pixel intensities have significant overlap, such data terms become ineffective, as they produce uncertain results for many pixels in a test image. In such cases, using prior information about the spatial context of the object to be segmented together with the data term can bring a curve to a plausible stage, which would then serve as a good initial point to launch shape-based segmentation. In this paper, we propose a new segmentation approach that combines nonparametric context priors with a learned-intensity-based data term and nonparametric shape priors. We perform experiments for dendritic spine segmentation in both 2D and 3D 2-photon microscopy images. The experimental results demonstrate that using spatial context priors leads to significant improvements.

Ertunc Erdil, Sinan Yildirim, Tolga Tasdizen et al.

In this paper, we propose an efficient pseudo-marginal Markov chain Monte Carlo (MCMC) sampling approach to draw samples from posterior shape distributions for image segmentation. The computation time of the proposed approach is independent from the size of the training set used to learn the shape prior distribution nonparametrically. Therefore, it scales well for very large data sets. Our approach is able to characterize the posterior probability density in the space of shapes through its samples, and to return multiple solutions, potentially from different modes of a multimodal probability density, which would be encountered, e.g., in segmenting objects from multiple shape classes. Experimental results demonstrate the potential of the proposed approach.

Ertunc Erdil, Sinan Yıldırım, Müjdat Çetin et al.

Segmenting images of low quality or with missing data is a challenging problem. Integrating statistical prior information about the shapes to be segmented can improve the segmentation results significantly. Most shape-based segmentation algorithms optimize an energy functional and find a point estimate for the object to be segmented. This does not provide a measure of the degree of confidence in that result, neither does it provide a picture of other probable solutions based on the data and the priors. With a statistical view, addressing these issues would involve the problem of characterizing the posterior densities of the shapes of the objects to be segmented. For such characterization, we propose a Markov chain Monte Carlo (MCMC) sampling-based image segmentation algorithm that uses statistical shape priors. In addition to better characterization of the statistical structure of the problem, such an approach would also have the potential to address issues with getting stuck at local optima, suffered by existing shape-based segmentation methods. Our approach is able to characterize the posterior probability density in the space of shapes through its samples, and to return multiple solutions, potentially from different modes of a multimodal probability density, which would be encountered, e.g., in segmenting objects from multiple shape classes. We present promising results on a variety of data sets. We also provide an extension for segmenting shapes of objects with parts that can go through independent shape variations. This extension involves the use of local shape priors on object parts and provides robustness to limitations in shape training data size.

Muhammad Usman Ghani, Ertunc Erdil, Sumeyra Demir Kanik et al.

Functional properties of neurons are strongly coupled with their morphology. Changes in neuronal activity alter morphological characteristics of dendritic spines. First step towards understanding the structure-function relationship is to group spines into main spine classes reported in the literature. Shape analysis of dendritic spines can help neuroscientists understand the underlying relationships. Due to unavailability of reliable automated tools, this analysis is currently performed manually which is a time-intensive and subjective task. Several studies on spine shape classification have been reported in the literature, however, there is an on-going debate on whether distinct spine shape classes exist or whether spines should be modeled through a continuum of shape variations. Another challenge is the subjectivity and bias that is introduced due to the supervised nature of classification approaches. In this paper, we aim to address these issues by presenting a clustering perspective. In this context, clustering may serve both confirmation of known patterns and discovery of new ones. We perform cluster analysis on two-photon microscopic images of spines using morphological, shape, and appearance based features and gain insights into the spine shape analysis problem. We use histogram of oriented gradients (HOG), disjunctive normal shape models (DNSM), morphological features, and intensity profile based features for cluster analysis. We use x-means to perform cluster analysis that selects the number of clusters automatically using the Bayesian information criterion (BIC). For all features, this analysis produces 4 clusters and we observe the formation of at least one cluster consisting of spines which are difficult to be assigned to a known class. This observation supports the argument of intermediate shape types.