Over recent years, deep learning based image registration has achieved impressive accuracy in many domains, including medical imaging and, specifically, human neuroimaging with magnetic resonance imaging (MRI). However, the uncertainty estimation associated with these methods has been largely limited to the application of generic techniques (e.g., Monte Carlo dropout) that do not exploit the peculiarities of the problem domain, particularly spatial modeling. Here, we propose a principled way to propagate uncertainties (epistemic or aleatoric) estimated at the level of spatial location by these methods, to the level of global transformation models, and further to downstream tasks. Specifically, we justify the choice of a Gaussian distribution for the local uncertainty modeling, and then propose a framework where uncertainties spread across hierarchical levels, depending on the choice of transformation model. Experiments on publicly available data sets show that Monte Carlo dropout correlates very poorly with the reference registration error, whereas our uncertainty estimates correlate much better. Crucially, the results also show that uncertainty-aware fitting of transformations improves the registration accuracy of brain MRI scans. Finally, we illustrate how sampling from the posterior distribution of the transformations can be used to propagate uncertainties to downstream neuroimaging tasks. Code is available at: https://github.com/HuXiaoling/Regre4Regis.

Brain surface analysis is essential to neuroscience, however, the complex geometry of the brain cortex hinders computational methods for this task. The difficulty arises from a discrepancy between 3D imaging data, which is represented in Euclidean space, and the non-Euclidean geometry of the highly-convoluted brain surface. Recent advances in machine learning have enabled the use of neural networks for non-Euclidean spaces. These facilitate the learning of surface data, yet pooling strategies often remain constrained to a single fixed-graph. This paper proposes a new learnable graph pooling method for processing multiple surface-valued data to output subject-based information. The proposed method innovates by learning an intrinsic aggregation of graph nodes based on graph spectral embedding. We illustrate the advantages of our approach with in-depth experiments on two large-scale benchmark datasets. The ablation study in the paper illustrates the impact of various factors affecting our learnable pooling method. The flexibility of the pooling strategy is evaluated on four different prediction tasks, namely, subject-sex classification, regression of cortical region sizes, classification of Alzheimer's disease stages, and brain age regression. Our experiments demonstrate the superiority of our learnable pooling approach compared to other pooling techniques for graph convolutional networks, with results improving the state-of-the-art in brain surface analysis.

Automated and accurate segmentation of cystoid structures in optical coherence tomography (OCT) is of interest in the early detection of retinal diseases. It is, however, a challenging task. We propose a novel method for localizing cysts in 3-D OCT volumes. The proposed work is biologically inspired and based on selective enhancement of the cysts, by inducing motion to a given OCT slice. A convolutional neural network is designed to learn a mapping function that combines the result of multiple such motions to produce a probability map for cyst locations in a given slice. The final segmentation of cysts is obtained via simple clustering of the detected cyst locations. The proposed method is evaluated on two public datasets and one private dataset. The public datasets include the one released for the OPTIMA cyst segmentation challenge (OCSC) in MICCAI 2015 and the DME dataset. After training on the OCSC train set, the method achieves a mean dice coefficient (DC) of 0.71 on the OCSC test set. The robustness of the algorithm was examined by cross validation on the DME and AEI (private) datasets and a mean DC values obtained were 0.69 and 0.79, respectively. Overall, the proposed system has the highest performance on all the benchmarks. These results underscore the strengths of the proposed method in handling variations in both data acquisition protocols and scanners.

Retinal swelling due to the accumulation of fluid is associated with the most vision-threatening retinal diseases. Optical coherence tomography (OCT) is the current standard of care in assessing the presence and quantity of retinal fluid and image-guided treatment management. Deep learning methods have made their impact across medical imaging, and many retinal OCT analysis methods have been proposed. However, it is currently not clear how successful they are in interpreting the retinal fluid on OCT, which is due to the lack of standardized benchmarks. To address this, we organized a challenge RETOUCH in conjunction with MICCAI 2017, with eight teams participating. The challenge consisted of two tasks: fluid detection and fluid segmentation. It featured for the first time: all three retinal fluid types, with annotated images provided by two clinical centers, which were acquired with the three most common OCT device vendors from patients with two different retinal diseases. The analysis revealed that in the detection task, the performance on the automated fluid detection was within the inter-grader variability. However, in the segmentation task, fusing the automated methods produced segmentations that were superior to all individual methods, indicating the need for further improvements in the segmentation performance.

Recently, dense connections have attracted substantial attention in computer vision because they facilitate gradient flow and implicit deep supervision during training. Particularly, DenseNet that connects each layer to every other layer in a feed-forward fashion and has shown impressive performances in natural image classification tasks. We propose HyperDenseNet, a 3-D fully convolutional neural network that extends the definition of dense connectivity to multi-modal segmentation problems. Each imaging modality has a path, and dense connections occur not only between the pairs of layers within the same path but also between those across different paths. This contrasts with the existing multi-modal CNN approaches, in which modeling several modalities relies entirely on a single joint layer (or level of abstraction) for fusion, typically either at the input or at the output of the network. Therefore, the proposed network has total freedom to learn more complex combinations between the modalities, within and in-between all the levels of abstraction, which increases significantly the learning representation. We report extensive evaluations over two different and highly competitive multi-modal brain tissue segmentation challenges, iSEG 2017 and MRBrainS 2013, with the former focusing on six month infant data and the latter on adult images. HyperDenseNet yielded significant improvements over many state-of-the-art segmentation networks, ranking at the top on both benchmarks. We further provide a comprehensive experimental analysis of features re-use, which confirms the importance of hyper-dense connections in multi-modal representation learning. Our code is publicly available.