Krishna Chaitanya

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.

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}.

Damola Agbelese, Krishna Chaitanya, Pushpak Pati et al.

Reliable uncertainty quantification (UQ) is essential in medical AI. Evidential Deep Learning (EDL) offers a computationally efficient way to quantify model uncertainty alongside predictions, unlike traditional methods such as Monte Carlo (MC) Dropout and Deep Ensembles (DE). However, all these methods often rely on a single expert's annotations as ground truth for model training, overlooking the inter-rater variability in healthcare. To address this issue, we propose MEGAN, a Multi-Expert Gating Network that aggregates uncertainty estimates and predictions from multiple AI experts via EDL models trained with diverse ground truths and modeling strategies. MEGAN's gating network optimally combines predictions and uncertainties from each EDL model, enhancing overall prediction confidence and calibration. We extensively benchmark MEGAN on endoscopy videos for Ulcerative colitis (UC) disease severity estimation, assessed by visual labeling of Mayo Endoscopic Subscore (MES), where inter-rater variability is prevalent. In large-scale prospective UC clinical trial, MEGAN achieved a 3.5% improvement in F1-score and a 30.5% reduction in Expected Calibration Error (ECE) compared to existing methods. Furthermore, MEGAN facilitated uncertainty-guided sample stratification, reducing the annotation burden and potentially increasing efficiency and consistency in UC trials.

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.

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.

Alexis Perakis, Ali Gorji, Samriddhi Jain et al.

Learning robust representations to discriminate cell phenotypes based on microscopy images is important for drug discovery. Drug development efforts typically analyse thousands of cell images to screen for potential treatments. Early works focus on creating hand-engineered features from these images or learn such features with deep neural networks in a fully or weakly-supervised framework. Both require prior knowledge or labelled datasets. Therefore, subsequent works propose unsupervised approaches based on generative models to learn these representations. Recently, representations learned with self-supervised contrastive loss-based methods have yielded state-of-the-art results on various imaging tasks compared to earlier unsupervised approaches. In this work, we leverage a contrastive learning framework to learn appropriate representations from single-cell fluorescent microscopy images for the task of Mechanism-of-Action classification. The proposed work is evaluated on the annotated BBBC021 dataset, and we obtain state-of-the-art results in NSC, NCSB and drop metrics for an unsupervised approach. We observe an improvement of 10% in NCSB accuracy and 11% in NSC-NSCB drop over the previously best unsupervised method. Moreover, the performance of our unsupervised approach ties with the best supervised approach. Additionally, we observe that our framework performs well even without post-processing, unlike earlier methods. With this, we conclude that one can learn robust cell representations with contrastive learning.

Hongwei Li, Fei-Fei Xue, Krishna Chaitanya et al.

Radiomic representations can quantify properties of regions of interest in medical image data. Classically, they account for pre-defined statistics of shape, texture, and other low-level image features. Alternatively, deep learning-based representations are derived from supervised learning but require expensive annotations from experts and often suffer from overfitting and data imbalance issues. In this work, we address the challenge of learning representations of 3D medical images for an effective quantification under data imbalance. We propose a \emph{self-supervised} representation learning framework to learn high-level features of 3D volumes as a complement to existing radiomics features. Specifically, we demonstrate how to learn image representations in a self-supervised fashion using a 3D Siamese network. More importantly, we deal with data imbalance by exploiting two unsupervised strategies: a) sample re-weighting, and b) balancing the composition of training batches. When combining our learned self-supervised feature with traditional radiomics, we show significant improvement in brain tumor classification and lung cancer staging tasks covering MRI and CT imaging modalities.

Christian F. Baumgartner, Kerem C. Tezcan, Krishna Chaitanya et al.

Segmentation of anatomical structures and pathologies is inherently ambiguous. For instance, structure borders may not be clearly visible or different experts may have different styles of annotating. The majority of current state-of-the-art methods do not account for such ambiguities but rather learn a single mapping from image to segmentation. In this work, we propose a novel method to model the conditional probability distribution of the segmentations given an input image. We derive a hierarchical probabilistic model, in which separate latent variables are responsible for modelling the segmentation at different resolutions. Inference in this model can be efficiently performed using the variational autoencoder framework. We show that our proposed method can be used to generate significantly more realistic and diverse segmentation samples compared to recent related work, both, when trained with annotations from a single or multiple annotators.

Krishna Chaitanya, Neerav Karani, Christian Baumgartner et al.

Supervised deep learning methods for segmentation require large amounts of labelled training data, without which they are prone to overfitting, not generalizing well to unseen images. In practice, obtaining a large number of annotations from clinical experts is expensive and time-consuming. One way to address scarcity of annotated examples is data augmentation using random spatial and intensity transformations. Recently, it has been proposed to use generative models to synthesize realistic training examples, complementing the random augmentation. So far, these methods have yielded limited gains over the random augmentation. However, there is potential to improve the approach by (i) explicitly modeling deformation fields (non-affine spatial transformation) and intensity transformations and (ii) leveraging unlabelled data during the generative process. With this motivation, we propose a novel task-driven data augmentation method where to synthesize new training examples, a generative network explicitly models and applies deformation fields and additive intensity masks on existing labelled data, modeling shape and intensity variations, respectively. Crucially, the generative model is optimized to be conducive to the task, in this case segmentation, and constrained to match the distribution of images observed from labelled and unlabelled samples. Furthermore, explicit modeling of deformation fields allow synthesizing segmentation masks and images in exact correspondence by simply applying the generated transformation to an input image and the corresponding annotation. Our experiments on cardiac magnetic resonance images (MRI) showed that, for the task of segmentation in small training data scenarios, the proposed method substantially outperforms conventional augmentation techniques.

Yigit B. Can, Krishna Chaitanya, Basil Mustafa et al.

Semantic segmentation of medical images is a crucial step for the quantification of healthy anatomy and diseases alike. The majority of the current state-of-the-art segmentation algorithms are based on deep neural networks and rely on large datasets with full pixel-wise annotations. Producing such annotations can often only be done by medical professionals and requires large amounts of valuable time. Training a medical image segmentation network with weak annotations remains a relatively unexplored topic. In this work we investigate training strategies to learn the parameters of a pixel-wise segmentation network from scribble annotations alone. We evaluate the techniques on public cardiac (ACDC) and prostate (NCI-ISBI) segmentation datasets. We find that the networks trained on scribbles suffer from a remarkably small degradation in Dice of only 2.9% (cardiac) and 4.5% (prostate) with respect to a network trained on full annotations.

Neerav Karani, Krishna Chaitanya, Christian Baumgartner et al.

Convolutional neural networks (CNNs) have shown promising results on several segmentation tasks in magnetic resonance (MR) images. However, the accuracy of CNNs may degrade severely when segmenting images acquired with different scanners and/or protocols as compared to the training data, thus limiting their practical utility. We address this shortcoming in a lifelong multi-domain learning setting by treating images acquired with different scanners or protocols as samples from different, but related domains. Our solution is a single CNN with shared convolutional filters and domain-specific batch normalization layers, which can be tuned to new domains with only a few ($\approx$ 4) labelled images. Importantly, this is achieved while retaining performance on the older domains whose training data may no longer be available. We evaluate the method for brain structure segmentation in MR images. Results demonstrate that the proposed method largely closes the gap to the benchmark, which is training a dedicated CNN for each scanner.