Hristina Uzunova

Jan Boysen, Hristina Uzunova, Heinz Handels et al.

A precise spatial delivery of the radiation dose is crucial for the treatment success in radiotherapy. In the lung and upper abdominal region, respiratory motion introduces significant treatment uncertainties, requiring special motion management techniques. To address this, respiratory motion models are commonly used to infer the patient-specific respiratory motion and target the dose more efficiently. In this work, we investigate the possibility of using implicit neural representations (INR) for surrogate-based motion modeling. Therefore, we propose physics-regularized implicit surrogate-based modeling for respiratory motion (PRISM-RM). Our new integrated respiratory motion model is free of a fixed reference breathing state. Unlike conventional pairwise registration techniques, our approach provides a trajectory-aware spatio-temporally continuous and diffeomorphic motion representation, improving generalization to extrapolation scenarios. We introduce biophysical constraints, ensuring physiologically plausible motion estimation across time beyond the training data. Our results show that our trajectory-aware approach performs on par in interpolation and improves the extrapolation ability compared to our initially proposed INR-based approach. Compared to sequential registration-based approaches both our approaches perform equally well in interpolation, but underperform in extrapolation scenarios. However, the methodical features of INRs make them particularly effective for respiratory motion modeling, and with their performance steadily improving, they demonstrate strong potential for advancing this field.

Marc S. Seibel, Hristina Uzunova, Timo Kepp et al.

For a unified analysis of medical images from different modalities, data harmonization using image-to-image (I2I) translation is desired. We study this problem employing an optical coherence tomography (OCT) data set of Spectralis-OCT and Home-OCT images. I2I translation is challenging because the images are unpaired, and a bijective mapping does not exist due to the information discrepancy between both domains. This problem has been addressed by the Contrastive Learning for Unpaired I2I Translation (CUT) approach, but it reduces semantic consistency. To restore the semantic consistency, we support the style decoder using an additional segmentation decoder. Our approach increases the similarity between the style-translated images and the target distribution. Importantly, we improve the segmentation of biomarkers in Home-OCT images in an unsupervised domain adaptation scenario. Our data harmonization approach provides potential for the monitoring of diseases, e.g., age related macular disease, using different OCT devices.

Joshua Niemeijer, Jan Ehrhardt, Heinz Handels et al.

Generative Models are a valuable tool for the controlled creation of high-quality image data. Controlled diffusion models like the ControlNet have allowed the creation of labeled distributions. Such synthetic datasets can augment the original training distribution when discriminative models, like semantic segmentation, are trained. However, this augmentation effect is limited since ControlNets tend to reproduce the original training distribution. This work introduces a method to utilize data from unlabeled domains to train ControlNets by introducing the concept of uncertainty into the control mechanism. The uncertainty indicates that a given image was not part of the training distribution of a downstream task, e.g., segmentation. Thus, two types of control are engaged in the final network: an uncertainty control from an unlabeled dataset and a semantic control from the labeled dataset. The resulting ControlNet allows us to create annotated data with high uncertainty from the target domain, i.e., synthetic data from the unlabeled distribution with labels. In our scenario, we consider retinal OCTs, where typically high-quality Spectralis images are available with given ground truth segmentations, enabling the training of segmentation networks. The recent development in Home-OCT devices, however, yields retinal OCTs with lower quality and a large domain shift, such that out-of-the-pocket segmentation networks cannot be applied for this type of data. Synthesizing annotated images from the Home-OCT domain using the proposed approach closes this gap and leads to significantly improved segmentation results without adding any further supervision. The advantage of uncertainty-guidance becomes obvious when compared to style transfer: it enables arbitrary domain shifts without any strict learning of an image style. This is also demonstrated in a traffic scene experiment.

Joshua Niemeijer, Jan Ehrhardt, Hristina Uzunova et al.

The usage of medical image data for the training of large-scale machine learning approaches is particularly challenging due to its scarce availability and the costly generation of data annotations, typically requiring the engagement of medical professionals. The rapid development of generative models allows towards tackling this problem by leveraging large amounts of realistic synthetically generated data for the training process. However, randomly choosing synthetic samples, might not be an optimal strategy. In this work, we investigate the targeted generation of synthetic training data, in order to improve the accuracy and robustness of image classification. Therefore, our approach aims to guide the generative model to synthesize data with high epistemic uncertainty, since large measures of epistemic uncertainty indicate underrepresented data points in the training set. During the image generation we feed images reconstructed by an auto encoder into the classifier and compute the mutual information over the class-probability distribution as a measure for uncertainty.We alter the feature space of the autoencoder through an optimization process with the objective of maximizing the classifier uncertainty on the decoded image. By training on such data we improve the performance and robustness against test time data augmentations and adversarial attacks on several classifications tasks.

Hristina Uzunova, Jan Ehrhardt, Heinz Handels

Generative adversarial networks (GANs) are currently rarely applied on 3D medical images of large size, due to their immense computational demand. The present work proposes a multi-scale patch-based GAN approach for establishing unpaired domain translation by generating 3D medical image volumes of high resolution in a memory-efficient way. The key idea to enable memory-efficient image generation is to first generate a low-resolution version of the image followed by the generation of patches of constant sizes but successively growing resolutions. To avoid patch artifacts and incorporate global information, the patch generation is conditioned on patches from previous resolution scales. Those multi-scale GANs are trained to generate realistically looking images from image sketches in order to perform an unpaired domain translation. This allows to preserve the topology of the test data and generate the appearance of the training domain data. The evaluation of the domain translation scenarios is performed on brain MRIs of size 155x240x240 and thorax CTs of size up to 512x512x512. Compared to common patch-based approaches, the multi-resolution scheme enables better image quality and prevents patch artifacts. Also, it ensures constant GPU memory demand independent from the image size, allowing for the generation of arbitrarily large images.

Hristina Uzunova, Jan Ehrhardt, Fabian Jacob et al.

Currently generative adversarial networks (GANs) are rarely applied to medical images of large sizes, especially 3D volumes, due to their large computational demand. We propose a novel multi-scale patch-based GAN approach to generate large high resolution 2D and 3D images. Our key idea is to first learn a low-resolution version of the image and then generate patches of successively growing resolutions conditioned on previous scales. In a domain translation use-case scenario, 3D thorax CTs of size 512x512x512 and thorax X-rays of size 2048x2048 are generated and we show that, due to the constant GPU memory demand of our method, arbitrarily large images of high resolution can be generated. Moreover, compared to common patch-based approaches, our multi-resolution scheme enables better image quality and prevents patch artifacts.