Wiro Niessen

Ruisheng Su, Matthijs van der Sluijs, Sandra Cornelissen et al.

Cerebral X-ray digital subtraction angiography (DSA) is the standard imaging technique for visualizing blood flow and guiding endovascular treatments. The quality of DSA is often negatively impacted by body motion during acquisition, leading to decreased diagnostic value. Time-consuming iterative methods address motion correction based on non-rigid registration, and employ sparse key points and non-rigidity penalties to limit vessel distortion. Recent methods alleviate subtraction artifacts by predicting the subtracted frame from the corresponding unsubtracted frame, but do not explicitly compensate for motion-induced misalignment between frames. This hinders the serial evaluation of blood flow, and often causes undesired vasculature and contrast flow alterations, leading to impeded usability in clinical practice. To address these limitations, we present AngioMoCo, a learning-based framework that generates motion-compensated DSA sequences from X-ray angiography. AngioMoCo integrates contrast extraction and motion correction, enabling differentiation between patient motion and intensity changes caused by contrast flow. This strategy improves registration quality while being substantially faster than iterative elastix-based methods. We demonstrate AngioMoCo on a large national multi-center dataset (MR CLEAN Registry) of clinically acquired angiographic images through comprehensive qualitative and quantitative analyses. AngioMoCo produces high-quality motion-compensated DSA, removing motion artifacts while preserving contrast flow. Code is publicly available at https://github.com/RuishengSu/AngioMoCo.

Bo Li, Jeroen de Bresser, Wiro Niessen et al.

Lacunes of presumed vascular origin, also referred to as lacunar infarcts, are important to assess cerebral small vessel disease and cognitive diseases such as dementia. However, visual rating of lacunes from imaging data is challenging, time-consuming, and rater-dependent, owing to their small size, sparsity, and mimics. Whereas recent developments in automatic algorithms have shown to make the detection of lacunes faster while preserving sensitivity, they also showed a large number of false positives, which makes them impractical for use in clinical practice or large-scale studies. Here, we develop a novel framework that, in addition to lacune detection, outputs a categorical burden score. This score could provide a more practical estimate of lacune presence that simplifies and effectively accelerates the imaging assessment of lacunes. We hypothesize that the combination of detection and the categorical score makes the procedure less sensitive to noisy labels.

Xianjing Liu, Bo Li, Esther Bron et al.

Confounding bias is a crucial problem when applying machine learning to practice, especially in clinical practice. We consider the problem of learning representations independent to multiple biases. In literature, this is mostly solved by purging the bias information from learned representations. We however expect this strategy to harm the diversity of information in the representation, and thus limiting its prospective usage (e.g., interpretation). Therefore, we propose to mitigate the bias while keeping almost all information in the latent representations, which enables us to observe and interpret them as well. To achieve this, we project latent features onto a learned vector direction, and enforce the independence between biases and projected features rather than all learned features. To interpret the mapping between projected features and input data, we propose projection-wise disentangling: a sampling and reconstruction along the learned vector direction. The proposed method was evaluated on the analysis of 3D facial shape and patient characteristics (N=5011). Experiments showed that this conceptually simple method achieved state-of-the-art fair prediction performance and interpretability, showing its great potential for clinical applications.

Florian Dubost, Benjamin Collery, Antonin Renaudier et al.

Scoliosis is a condition defined by an abnormal spinal curvature. For diagnosis and treatment planning of scoliosis, spinal curvature can be estimated using Cobb angles. We propose an automated method for the estimation of Cobb angles from X-ray scans. First, the centerline of the spine was segmented using a cascade of two convolutional neural networks. After smoothing the centerline, Cobb angles were automatically estimated using the derivative of the centerline. We evaluated the results using the mean absolute error and the average symmetric mean absolute percentage error between the manual assessment by experts and the automated predictions. For optimization, we used 609 X-ray scans from the London Health Sciences Center, and for evaluation, we participated in the international challenge "Accurate Automated Spinal Curvature Estimation, MICCAI 2019" (100 scans). On the challenge's test set, we obtained an average symmetric mean absolute percentage error of 22.96.

Bo Li, Marius de Groot, Meike Vernooij et al.

Tract-specific diffusion measures, as derived from brain diffusion MRI, have been linked to white matter tract structural integrity and neurodegeneration. As a consequence, there is a large interest in the automatic segmentation of white matter tract in diffusion tensor MRI data. Methods based on the tractography are popular for white matter tract segmentation. However, because of the limited consistency and long processing time, such methods may not be suitable for clinical practice. We therefore developed a novel convolutional neural network based method to directly segment white matter tract trained on a low-resolution dataset of 9149 DTI images. The method is optimized on input, loss function and network architecture selections. We evaluated both segmentation accuracy and reproducibility, and reproducibility of determining tract-specific diffusion measures. The reproducibility of the method is higher than that of the reference standard and the determined diffusion measures are consistent. Therefore, we expect our method to be applicable in clinical practice and in longitudinal analysis of white matter microstructure.

Bo Li, Wiro Niessen, Stefan Klein et al.

To accurately analyze changes of anatomical structures in longitudinal imaging studies, consistent segmentation across multiple time-points is required. Existing solutions often involve independent registration and segmentation components. Registration between time-points is used either as a prior for segmentation in a subsequent time point or to perform segmentation in a common space. In this work, we propose a novel hybrid convolutional neural network (CNN) that integrates segmentation and registration into a single procedure. We hypothesize that the joint optimization leads to increased performance on both tasks. The hybrid CNN is trained by minimizing an integrated loss function composed of four different terms, measuring segmentation accuracy, similarity between registered images, deformation field smoothness, and segmentation consistency. We applied this method to the segmentation of white matter tracts, describing functionally grouped axonal fibers, using N=8045 longitudinal brain MRI data of 3249 individuals. The proposed method was compared with two multistage pipelines using two existing segmentation methods combined with a conventional deformable registration algorithm. In addition, we assessed the added value of the joint optimization for segmentation and registration separately. The hybrid CNN yielded significantly higher accuracy, consistency and reproducibility of segmentation than the multistage pipelines, and was orders of magnitude faster. Therefore, we expect it can serve as a novel tool to support clinical and epidemiological analyses on understanding microstructural brain changes over time.

Florian Dubost, Marleen de Bruijne, Marco Nardin et al.

Registration is a core component of many imaging pipelines. In case of clinical scans, with lower resolution and sometimes substantial motion artifacts, registration can produce poor results. Visual assessment of registration quality in large clinical datasets is inefficient. In this work, we propose to automatically assess the quality of registration to an atlas in clinical FLAIR MRI scans of the brain. The method consists of automatically segmenting the ventricles of a given scan using a neural network, and comparing the segmentation to the atlas' ventricles propagated to image space. We used the proposed method to improve clinical image registration to a general atlas by computing multiple registrations and then selecting the registration that yielded the highest ventricle overlap. Methods were evaluated in a single-site dataset of more than 1000 scans, as well as a multi-center dataset comprising 142 clinical scans from 12 sites. The automated ventricle segmentation reached a Dice coefficient with manual annotations of 0.89 in the single-site dataset, and 0.83 in the multi-center dataset. Registration via age-specific atlases could improve ventricle overlap compared to a direct registration to the general atlas (Dice similarity coefficient increase up to 0.15). Experiments also showed that selecting scans with the registration quality assessment method could improve the quality of average maps of white matter hyperintensity burden, instead of using all scans for the computation of the white matter hyperintensity map. In this work, we demonstrated the utility of an automated tool for assessing image registration quality in clinical scans. This image quality assessment step could ultimately assist in the translation of automated neuroimaging pipelines to the clinic.

Florian Dubost, Hieab Adams, Pinar Yilmaz et al.

Finding automatically multiple lesions in large images is a common problem in medical image analysis. Solving this problem can be challenging if, during optimization, the automated method cannot access information about the location of the lesions nor is given single examples of the lesions. We propose a new weakly supervised detection method using neural networks, that computes attention maps revealing the locations of brain lesions. These attention maps are computed using the last feature maps of a segmentation network optimized only with global image-level labels. The proposed method can generate attention maps at full input resolution without need for interpolation during preprocessing, which allows small lesions to appear in attention maps. For comparison, we modify state-of-the-art methods to compute attention maps for weakly supervised object detection, by using a global regression objective instead of the more conventional classification objective. This regression objective optimizes the number of occurrences of the target object in an image, e.g. the number of brain lesions in a scan, or the number of digits in an image. We study the behavior of the proposed method in MNIST-based detection datasets, and evaluate it for the challenging detection of enlarged perivascular spaces - a type of brain lesion - in a dataset of 2202 3D scans with point-wise annotations in the center of all lesions in four brain regions. In the brain dataset, the weakly supervised detection methods come close to the human intrarater agreement in each region. The proposed method reaches the best area under the curve in two out of four regions, and has the lowest number of false positive detections in all regions, while its average sensitivity over all regions is similar to that of the other best methods. The proposed method can facilitate epidemiological and clinical studies of enlarged perivascular spaces.

Florian Dubost, Gerda Bortsova, Hieab Adams et al.

Deep learning techniques are often criticized to heavily depend on a large quantity of labeled data. This problem is even more challenging in medical image analysis where the annotator expertise is often scarce. We propose a novel data-augmentation method to regularize neural network regressors that learn from a single global label per image. The principle of the method is to create new samples by recombining existing ones. We demonstrate the performance of our algorithm on two tasks: estimation of the number of enlarged perivascular spaces in the basal ganglia, and estimation of white matter hyperintensities volume. We show that the proposed method improves the performance over more basic data augmentation. The proposed method reached an intraclass correlation coefficient between ground truth and network predictions of 0.73 on the first task and 0.84 on the second task, only using between 25 and 30 scans with a single global label per scan for training. With the same number of training scans, more conventional data augmentation methods could only reach intraclass correlation coefficients of 0.68 on the first task, and 0.79 on the second task.

Lena Maier-Hein, Matthias Eisenmann, Annika Reinke et al.

International challenges have become the standard for validation of biomedical image analysis methods. Given their scientific impact, it is surprising that a critical analysis of common practices related to the organization of challenges has not yet been performed. In this paper, we present a comprehensive analysis of biomedical image analysis challenges conducted up to now. We demonstrate the importance of challenges and show that the lack of quality control has critical consequences. First, reproducibility and interpretation of the results is often hampered as only a fraction of relevant information is typically provided. Second, the rank of an algorithm is generally not robust to a number of variables such as the test data used for validation, the ranking scheme applied and the observers that make the reference annotations. To overcome these problems, we recommend best practice guidelines and define open research questions to be addressed in the future.

Florian Dubost, Hieab Adams, Gerda Bortsova et al.

Enlarged perivascular spaces (EPVS) in the brain are an emerging imaging marker for cerebral small vessel disease, and have been shown to be related to increased risk of various neurological diseases, including stroke and dementia. Automatic quantification of EPVS would greatly help to advance research into its etiology and its potential as a risk indicator of disease. We propose a convolutional network regression method to quantify the extent of EPVS in the basal ganglia from 3D brain MRI. We first segment the basal ganglia and subsequently apply a 3D convolutional regression network designed for small object detection within this region of interest. The network takes an image as input, and outputs a quantification score of EPVS. The network has significantly more convolution operations than pooling ones and no final activation, allowing it to span the space of real numbers. We validated our approach using a dataset of 2000 brain MRI scans scored visually. Experiments with varying sizes of training and test sets showed that a good performance can be achieved with a training set of only 200 scans. With a training set of 1000 scans, the intraclass correlation coefficient (ICC) between our scoring method and the expert's visual score was 0.74. Our method outperforms by a large margin - more than 0.10 - four more conventional automated approaches based on intensities, scale-invariant feature transform, and random forest. We show that the network learns the structures of interest and investigate the influence of hyper-parameters on the performance. We also evaluate the reproducibility of our network using a set of 60 subjects scanned twice (scan-rescan reproducibility). On this set our network achieves an ICC of 0.93, while the intrarater agreement reaches 0.80. Furthermore, the automatic EPVS scoring correlates similarly to age as visual scoring.

Florian Dubost, Gerda Bortsova, Hieab Adams et al.

We propose a novel convolutional neural network for lesion detection from weak labels. Only a single, global label per image - the lesion count - is needed for training. We train a regression network with a fully convolutional architecture combined with a global pooling layer to aggregate the 3D output into a scalar indicating the lesion count. When testing on unseen images, we first run the network to estimate the number of lesions. Then we remove the global pooling layer to compute localization maps of the size of the input image. We evaluate the proposed network on the detection of enlarged perivascular spaces in the basal ganglia in MRI. Our method achieves a sensitivity of 62% with on average 1.5 false positives per image. Compared with four other approaches based on intensity thresholding, saliency and class maps, our method has a 20% higher sensitivity.

Vikram Venkatraghavan, Esther Bron, Wiro Niessen et al.

The event-based model (EBM) for data-driven disease progression modeling estimates the sequence in which biomarkers for a disease become abnormal. This helps in understanding the dynamics of disease progression and facilitates early diagnosis by staging patients on a disease progression timeline. Existing EBM methods are all generative in nature. In this work we propose a novel discriminative approach to EBM, which is shown to be more accurate as well as computationally more efficient than existing state-of-the art EBM methods. The method first estimates for each subject an approximate ordering of events, by ranking the posterior probabilities of individual biomarkers being abnormal. Subsequently, the central ordering over all subjects is estimated by fitting a generalized Mallows model to these approximate subject-specific orderings based on a novel probabilistic Kendall's Tau distance. To evaluate the accuracy, we performed extensive experiments on synthetic data simulating the progression of Alzheimer's disease. Subsequently, the method was applied to the Alzheimer's Disease Neuroimaging Initiative (ADNI) data to estimate the central event ordering in the dataset. The experiments benchmark the accuracy of the new model under various conditions and compare it with existing state-of-the-art EBM methods. The results indicate that discriminative EBM could be a simple and elegant approach to disease progression modeling.