Heinz Handels

Reuben Dorent, Roya Khajavi, Tagwa Idris et al.

Accurate assessment of lymph node size in 3D CT scans is crucial for cancer staging, therapeutic management, and monitoring treatment response. Existing state-of-the-art segmentation frameworks in medical imaging often rely on fully annotated datasets. However, for lymph node segmentation, these datasets are typically small due to the extensive time and expertise required to annotate the numerous lymph nodes in 3D CT scans. Weakly-supervised learning, which leverages incomplete or noisy annotations, has recently gained interest in the medical imaging community as a potential solution. Despite the variety of weakly-supervised techniques proposed, most have been validated only on private datasets or small publicly available datasets. To address this limitation, the Mediastinal Lymph Node Quantification (LNQ) challenge was organized in conjunction with the 26th International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI 2023). This challenge aimed to advance weakly-supervised segmentation methods by providing a new, partially annotated dataset and a robust evaluation framework. A total of 16 teams from 5 countries submitted predictions to the validation leaderboard, and 6 teams from 3 countries participated in the evaluation phase. The results highlighted both the potential and the current limitations of weakly-supervised approaches. On one hand, weakly-supervised approaches obtained relatively good performance with a median Dice score of $61.0\%$. On the other hand, top-ranked teams, with a median Dice score exceeding $70\%$, boosted their performance by leveraging smaller but fully annotated datasets to combine weak supervision and full supervision. This highlights both the promise of weakly-supervised methods and the ongoing need for high-quality, fully annotated data to achieve higher segmentation performance.

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.

Sofija Engelson, Jan Ehrhardt, Timo Kepp et al.

The evaluation of lymph node metastases plays a crucial role in achieving precise cancer staging, influencing subsequent decisions regarding treatment options. Lymph node detection poses challenges due to the presence of unclear boundaries and the diverse range of sizes and morphological characteristics, making it a resource-intensive process. As part of the LNQ 2023 MICCAI challenge, we propose the use of anatomical priors as a tool to address the challenges that persist in mediastinal lymph node segmentation in combination with the partial annotation of the challenge training data. The model ensemble using all suggested modifications yields a Dice score of 0.6033 and segments 57% of the ground truth lymph nodes, compared to 27% when training on CT only. Segmentation accuracy is improved significantly by incorporating a probabilistic lymph node atlas in loss weighting and post-processing. The largest performance gains are achieved by oversampling fully annotated data to account for the partial annotation of the challenge training data, as well as adding additional data augmentation to address the high heterogeneity of the CT images and lymph node appearance. Our code is available at https://github.com/MICAI-IMI-UzL/LNQ2023.

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.

Bennet Kahrs, Julia Andresen, Fenja Falta et al.

Routine clinical imaging of the retina using optical coherence tomography (OCT) is performed with large slice spacing, resulting in highly anisotropic images and a sparsely scanned retina. Most learning-based methods circumvent the problems arising from the anisotropy by using 2D approaches rather than performing volumetric analyses. These approaches inherently bear the risk of generating inconsistent results for neighboring B-scans. For example, 2D retinal layer segmentations can have irregular surfaces in 3D. Furthermore, the typically used convolutional neural networks are bound to the resolution of the training data, which prevents their usage for images acquired with a different imaging protocol. Implicit neural representations (INRs) have recently emerged as a tool to store voxelized data as a continuous representation. Using coordinates as input, INRs are resolution-agnostic, which allows them to be applied to anisotropic data. In this paper, we propose two frameworks that make use of this characteristic of INRs for dense 3D analyses of retinal OCT volumes. 1) We perform inter-B-scan interpolation by incorporating additional information from en-face modalities, that help retain relevant structures between B-scans. 2) We create a resolution-agnostic retinal atlas that enables general analysis without strict requirements for the data. Both methods leverage generalizable INRs, improving retinal shape representation through population-based training and allowing predictions for unseen cases. Our resolution-independent frameworks facilitate the analysis of OCT images with large B-scan distances, opening up possibilities for the volumetric evaluation of retinal structures and pathologies.

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.

Timo Kepp, Helge Sudkamp, Claus von der Burchard et al.

The treatment of age-related macular degeneration (AMD) requires continuous eye exams using optical coherence tomography (OCT). The need for treatment is determined by the presence or change of disease-specific OCT-based biomarkers. Therefore, the monitoring frequency has a significant influence on the success of AMD therapy. However, the monitoring frequency of current treatment schemes is not individually adapted to the patient and therefore often insufficient. While a higher monitoring frequency would have a positive effect on the success of treatment, in practice it can only be achieved with a home monitoring solution. One of the key requirements of a home monitoring OCT system is a computer-aided diagnosis to automatically detect and quantify pathological changes using specific OCT-based biomarkers. In this paper, for the first time, retinal scans of a novel self-examination low-cost full-field OCT (SELF-OCT) are segmented using a deep learning-based approach. A convolutional neural network (CNN) is utilized to segment the total retina as well as pigment epithelial detachments (PED). It is shown that the CNN-based approach can segment the retina with high accuracy, whereas the segmentation of the PED proves to be challenging. In addition, a convolutional denoising autoencoder (CDAE) refines the CNN prediction, which has previously learned retinal shape information. It is shown that the CDAE refinement can correct segmentation errors caused by artifacts in the OCT image.

Niclas Kath, Heinz Handels, Andre Mastmeyer

Purpose: Radio-frequency ablations play an important role in the therapy of malignant liver lesions. The navigation of a needle to the lesion poses a challenge for both the trainees and intervening physicians. Methods: This publication presents a new GPU-based, accurate method for the simulation of radio-frequency ablations for lesions at the needle tip in general and for an existing visuo-haptic 4D VR simulator. The method is implemented real-time capable with Nvidia CUDA. Results: It performs better than a literature method concerning the theoretical characteristic of monotonic convergence of the bioheat PDE and a in vitro gold standard with significant improvements (p < 0.05) in terms of Pearson correlations. It shows no failure modes or theoretically inconsistent individual simulation results after the initial phase of 10 seconds. On the Nvidia 1080 Ti GPU it achieves a very high frame rendering performance of >480 Hz. Conclusion: Our method provides a more robust and safer real-time ablation planning and intraoperative guidance technique, especially avoiding the over-estimation of the ablated tissue death zone, which is risky for the patient in terms of tumor recurrence. Future in vitro measurements and optimization shall further improve the conservative estimate.

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.

Jan Rühaak, Thomas Polzin, Stefan Heldmann et al.

We present a novel algorithm for the registration of pulmonary CT scans. Our method is designed for large respiratory motion by integrating sparse keypoint correspondences into a dense continuous optimization framework. The detection of keypoint correspondences enables robustness against large deformations by jointly optimizing over a large number of potential discrete displacements, whereas the dense continuous registration achieves subvoxel alignment with smooth transformations. Both steps are driven by the same normalized gradient fields data term. We employ curvature regularization and a volume change control mechanism to prevent foldings of the deformation grid and restrict the determinant of the Jacobian to physiologically meaningful values. Keypoint correspondences are integrated into the dense registration by a quadratic penalty with adaptively determined weight. Using a parallel matrix-free derivative calculation scheme, a runtime of about 5 min was realized on a standard PC. The proposed algorithm ranks first in the EMPIRE10 challenge on pulmonary image registration. Moreover, it achieves an average landmark distance of 0.82 mm on the DIR-Lab COPD database, thereby improving upon the state of the art in accuracy by 15%. Our algorithm is the first to reach the inter-observer variability in landmark annotation on this dataset.

Andre Mastmeyer, Matthias Wilms, Heinz Handels

Virtual reality (VR) training simulators of liver needle insertion in the hepatic area of breathing virtual patients currently need 4D data acquisitions as a prerequisite. Here, first a population-based breathing virtual patient 4D atlas can be built and second the requirement of a dose-relevant or expensive acquisition of a 4D data set for a new static 3D patient can be mitigated by warping the mean atlas motion. The breakthrough contribution of this work is the construction and reuse of population-based learned 4D motion models.

Andre Mastmeyer, Matthias Wilms, Heinz Handels

Current virtual reality (VR) training simulators of liver punctures often rely on static 3D patient data and use an unrealistic (sinusoidal) periodic animation of the respiratory movement. Existing methods for the animation of breathing motion support simple mathematical or patient-specific, estimated breathing models. However with personalized breathing models for each new patient, a heavily dose relevant or expensive 4D data acquisition is mandatory for keyframe-based motion modeling. Given the reference 4D data, first a model building stage using linear regression motion field modeling takes place. Then the methodology shown here allows the transfer of existing reference respiratory motion models of a 4D reference patient to a new static 3D patient. This goal is achieved by using non-linear inter-patient registration to warp one personalized 4D motion field model to new 3D patient data. This cost- and dose-saving new method is shown here visually in a qualitative proof-of-concept study.

Andre Mastmeyer, Dirk Fortmeier, Heinz Handels

This work presents an evaluation study using a force feedback evaluation framework for a novel direct needle force volume rendering concept in the context of liver puncture simulation. PTC/PTCD puncture interventions targeting the bile ducts have been selected to illustrate this concept. The haptic algorithms of the simulator system are based on (1) partially segmented patient image data and (2) a non-linear spring model effective at organ borders. The primary aim is to quantitatively evaluate force errors caused by our patient modeling approach, in comparison to haptic force output obtained from using gold-standard, completely manually-segmented data. The evaluation of the force algorithms compared to a force output from fully manually segmented gold-standard patient models, yields a low mean of 0.12 N root mean squared force error and up to 1.6 N for systematic maximum absolute errors. Force errors were evaluated on 31,222 preplanned test paths from 10 patients. Only twelve percent of the emitted forces along these paths were affected by errors. This is the first study evaluating haptic algorithms with deformable virtual patients in silico. We prove haptic rendering plausibility on a very high number of test paths. Important errors are below just noticeable differences for the hand-arm system.

Andre Mastmeyer, Guillaume Pernelle, Lauren Barber et al.

Accurate and reliable segmentation of catheters in MR-guided interventions remains a challenge, and a step of critical importance in clinical workflows. In this work, under reasonable assumptions, mechanical model based heuristics guide the segmentation process allows correct catheter identification rates greater than 98% (error 2.88 mm), and reduction in outliers to one-fourth compared to the state of the art. Given distal tips, searching towards the proximal ends of the catheters is guided by mechanical models that are estimated on a per-catheter basis. Their bending characteristics are used to constrain the image feature based candidate points. The final catheter trajectories are hybrid sequences of individual points, each derived from model and image features. We evaluate the method on a database of 10 patient MRI scans including 101 manually segmented catheters. The mean errors were 1.40 mm and the median errors were 1.05 mm. The number of outliers deviating more than 2 mm from the gold standard is 7, and the number of outliers deviating more than 3 mm from the gold standard is just 2.