Julia Krüger

Finn Behrendt, Debayan Bhattacharya, Julia Krüger et al.

The use of supervised deep learning techniques to detect pathologies in brain MRI scans can be challenging due to the diversity of brain anatomy and the need for annotated data sets. An alternative approach is to use unsupervised anomaly detection, which only requires sample-level labels of healthy brains to create a reference representation. This reference representation can then be compared to unhealthy brain anatomy in a pixel-wise manner to identify abnormalities. To accomplish this, generative models are needed to create anatomically consistent MRI scans of healthy brains. While recent diffusion models have shown promise in this task, accurately generating the complex structure of the human brain remains a challenge. In this paper, we propose a method that reformulates the generation task of diffusion models as a patch-based estimation of healthy brain anatomy, using spatial context to guide and improve reconstruction. We evaluate our approach on data of tumors and multiple sclerosis lesions and demonstrate a relative improvement of 25.1% compared to existing baselines.

Finn Behrendt, Marcel Bengs, Frederik Rogge et al.

The detection of lesions in magnetic resonance imaging (MRI)-scans of human brains remains challenging, time-consuming and error-prone. Recently, unsupervised anomaly detection (UAD) methods have shown promising results for this task. These methods rely on training data sets that solely contain healthy samples. Compared to supervised approaches, this significantly reduces the need for an extensive amount of labeled training data. However, data labelling remains error-prone. We study how unhealthy samples within the training data affect anomaly detection performance for brain MRI-scans. For our evaluations, we consider three publicly available data sets and use autoencoders (AE) as a well-established baseline method for UAD. We systematically evaluate the effect of impured training data by injecting different quantities of unhealthy samples to our training set of healthy samples from T1-weighted MRI-scans. We evaluate a method to identify falsely labeled samples directly during training based on the reconstruction error of the AE. Our results show that training with impured data decreases the UAD performance notably even with few falsely labeled samples. By performing outlier removal directly during training based on the reconstruction-loss, we demonstrate that falsely labeled data can be detected and removed to mitigate the effect of falsely labeled data. Overall, we highlight the importance of clean data sets for UAD in brain MRI and demonstrate an approach for detecting falsely labeled data directly during training.

Finn Behrendt, Debayan Bhattacharya, Robin Mieling et al.

Unsupervised Anomaly Detection (UAD) methods rely on healthy data distributions to identify anomalies as outliers. In brain MRI, a common approach is reconstruction-based UAD, where generative models reconstruct healthy brain MRIs, and anomalies are detected as deviations between input and reconstruction. However, this method is sensitive to imperfect reconstructions, leading to false positives that impede the segmentation. To address this limitation, we construct multiple reconstructions with probabilistic diffusion models. We then analyze the resulting distribution of these reconstructions using the Mahalanobis distance to identify anomalies as outliers. By leveraging information about normal variations and covariance of individual pixels within this distribution, we effectively refine anomaly scoring, leading to improved segmentation. Our experimental results demonstrate substantial performance improvements across various data sets. Specifically, compared to relying solely on single reconstructions, our approach achieves relative improvements of 15.9%, 35.4%, 48.0%, and 4.7% in terms of AUPRC for the BRATS21, ATLAS, MSLUB and WMH data sets, respectively.

Finn Behrendt, Debayan Bhattacharya, Robin Mieling et al.

The application of supervised models to clinical screening tasks is challenging due to the need for annotated data for each considered pathology. Unsupervised Anomaly Detection (UAD) is an alternative approach that aims to identify any anomaly as an outlier from a healthy training distribution. A prevalent strategy for UAD in brain MRI involves using generative models to learn the reconstruction of healthy brain anatomy for a given input image. As these models should fail to reconstruct unhealthy structures, the reconstruction errors indicate anomalies. However, a significant challenge is to balance the accurate reconstruction of healthy anatomy and the undesired replication of abnormal structures. While diffusion models have shown promising results with detailed and accurate reconstructions, they face challenges in preserving intensity characteristics, resulting in false positives. We propose conditioning the denoising process of diffusion models with additional information derived from a latent representation of the input image. We demonstrate that this conditioning allows for accurate and local adaptation to the general input intensity distribution while avoiding the replication of unhealthy structures. We compare the novel approach to different state-of-the-art methods and for different data sets. Our results show substantial improvements in the segmentation performance, with the Dice score improved by 11.9%, 20.0%, and 44.6%, for the BraTS, ATLAS and MSLUB data sets, respectively, while maintaining competitive performance on the WMH data set. Furthermore, our results indicate effective domain adaptation across different MRI acquisitions and simulated contrasts, an important attribute for general anomaly detection methods. The code for our work is available at https://github.com/FinnBehrendt/Conditioned-Diffusion-Models-UAD

Finn Behrendt, Debayan Bhattacharya, Lennart Maack et al.

Supervised deep learning techniques show promise in medical image analysis. However, they require comprehensive annotated data sets, which poses challenges, particularly for rare diseases. Consequently, unsupervised anomaly detection (UAD) emerges as a viable alternative for pathology segmentation, as only healthy data is required for training. However, recent UAD anomaly scoring functions often focus on intensity only and neglect structural differences, which impedes the segmentation performance. This work investigates the potential of Structural Similarity (SSIM) to bridge this gap. SSIM captures both intensity and structural disparities and can be advantageous over the classical $l1$ error. However, we show that there is more than one optimal kernel size for the SSIM calculation for different pathologies. Therefore, we investigate an adaptive ensembling strategy for various kernel sizes to offer a more pathology-agnostic scoring mechanism. We demonstrate that this ensembling strategy can enhance the performance of DMs and mitigate the sensitivity to different kernel sizes across varying pathologies, highlighting its promise for brain MRI anomaly detection.

Marcel Bengs, Finn Behrendt, Max-Heinrich Laves et al.

Lesion detection in brain Magnetic Resonance Images (MRIs) remains a challenging task. MRIs are typically read and interpreted by domain experts, which is a tedious and time-consuming process. Recently, unsupervised anomaly detection (UAD) in brain MRI with deep learning has shown promising results to provide a quick, initial assessment. So far, these methods only rely on the visual appearance of healthy brain anatomy for anomaly detection. Another biomarker for abnormal brain development is the deviation between the brain age and the chronological age, which is unexplored in combination with UAD. We propose deep learning for UAD in 3D brain MRI considering additional age information. We analyze the value of age information during training, as an additional anomaly score, and systematically study several architecture concepts. Based on our analysis, we propose a novel deep learning approach for UAD with multi-task age prediction. We use clinical T1-weighted MRIs of 1735 healthy subjects and the publicly available BraTs 2019 data set for our study. Our novel approach significantly improves UAD performance with an AUC of 92.60% compared to an AUC-score of 84.37% using previous approaches without age information.

Nils Gessert, Julia Krüger, Roland Opfer et al.

Multiple sclerosis is an inflammatory autoimmune demyelinating disease that is characterized by lesions in the central nervous system. Typically, magnetic resonance imaging (MRI) is used for tracking disease progression. Automatic image processing methods can be used to segment lesions and derive quantitative lesion parameters. So far, methods have focused on lesion segmentation for individual MRI scans. However, for monitoring disease progression, \textit{lesion activity} in terms of new and enlarging lesions between two time points is a crucial biomarker. For this problem, several classic methods have been proposed, e.g., using difference volumes. Despite their success for single-volume lesion segmentation, deep learning approaches are still rare for lesion activity segmentation. In this work, convolutional neural networks (CNNs) are studied for lesion activity segmentation from two time points. For this task, CNNs are designed and evaluated that combine the information from two points in different ways. In particular, two-path architectures with attention-guided interactions are proposed that enable effective information exchange between the two time point's processing paths. It is demonstrated that deep learning-based methods outperform classic approaches and it is shown that attention-guided interactions significantly improve performance. Furthermore, the attention modules produce plausible attention maps that have a masking effect that suppresses old, irrelevant lesions. A lesion-wise false positive rate of 26.4% is achieved at a true positive rate of 74.2%, which is not significantly different from the interrater performance.