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In human neuroimaging studies, atlas registration enables mapping MRI scans to a common coordinate frame, which is necessary to aggregate data from multiple subjects. Machine learning registration methods have achieved excellent speed and accuracy but lack interpretability and flexibility at test time (since their deformation model is fixed). More recently, keypoint-based methods have been proposed to tackle these issues, but their accuracy is still subpar, particularly when fitting nonlinear transforms. Here we propose Registration by Regression (RbR), a novel atlas registration framework that: is highly robust and flexible; can be trained with cheaply obtained data; and operates on a single channel, such that it can also be used as pretraining for other tasks. RbR predicts the (x, y, z) atlas coordinates for every voxel of the input scan (i.e., every voxel is a keypoint), and then uses closed-form expressions to quickly fit transforms using a wide array of possible deformation models, including affine and nonlinear (e.g., Bspline, Demons, invertible diffeomorphic models, etc.). Robustness is provided by the large number of voxels informing the registration and can be further increased by robust estimators like RANSAC. Experiments on independent public datasets show that RbR yields more accurate registration than competing keypoint approaches, over a wide range of deformation models., Comment: 11 pages, 3 figures

Surface analysis of the cortex is ubiquitous in human neuroimaging with MRI, e.g., for cortical registration, parcellation, or thickness estimation. The convoluted cortical geometry requires isotropic scans (e.g., 1mm MPRAGEs) and good gray-white matter contrast for 3D reconstruction. This precludes the analysis of most brain MRI scans acquired for clinical purposes. Analyzing such scans would enable neuroimaging studies with sample sizes that cannot be achieved with current research datasets, particularly for underrepresented populations and rare diseases. Here we present the first method for cortical reconstruction, registration, parcellation, and thickness estimation for clinical brain MRI scans of any resolution and pulse sequence. The methods has a learning component and a classical optimization module. The former uses domain randomization to train a CNN that predicts an implicit representation of the white matter and pial surfaces (a signed distance function) at 1mm isotropic resolution, independently of the pulse sequence and resolution of the input. The latter uses geometry processing to place the surfaces while accurately satisfying topological and geometric constraints, thus enabling subsequent parcellation and thickness estimation with existing methods. We present results on 5mm axial FLAIR scans from ADNI and on a highly heterogeneous clinical dataset with 5,000 scans. Code and data are publicly available at https://surfer.nmr.mgh.harvard.edu/fswiki/recon-all-clinical

The varying cortical geometry of the brain creates numerous challenges for its analysis. Recent developments have enabled learning surface data directly across multiple brain surfaces via graph convolutions on cortical data. However, current graph learning algorithms do fail when brain surface data are misaligned across subjects, thereby affecting their ability to deal with data from multiple domains. Adversarial training is widely used for domain adaptation to improve the segmentation performance across domains. In this paper, adversarial training is exploited to learn surface data across inconsistent graph alignments. This novel approach comprises a segmentator that uses a set of graph convolution layers to enable parcellation directly across brain surfaces in a source domain, and a discriminator that predicts a graph domain from segmentations. More precisely, the proposed adversarial network learns to generalize a parcellation across both, source and target domains. We demonstrate an 8% mean improvement in performance over a non-adversarial training strategy applied on multiple target domains extracted from MindBoggle, the largest publicly available manually-labeled brain surface dataset.

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 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 convolution networks, with results improving the state-of-the-art in brain surface analysis.

The analysis of the brain surface modeled as a graph mesh is a challenging task. Conventional deep learning approaches often rely on data lying in the Euclidean space. As an extension to irregular graphs, convolution operations are defined in the Fourier or spectral domain. This spectral domain is obtained by decomposing the graph Laplacian, which captures relevant shape information. However, the spectral decomposition across different brain graphs causes inconsistencies between the eigenvectors of individual spectral domains, causing the graph learning algorithm to fail. Current spectral graph convolution methods handle this variance by separately aligning the eigenvectors to a reference brain in a slow iterative step. This paper presents a novel approach for learning the transformation matrix required for aligning brain meshes using a direct data-driven approach. Our alignment and graph processing method provides a fast analysis of brain surfaces. The novel Spectral Graph Transformer (SGT) network proposed in this paper uses very few randomly sub-sampled nodes in the spectral domain to learn the alignment matrix for multiple brain surfaces. We validate the use of this SGT network along with a graph convolution network to perform cortical parcellation. Our method on 101 manually-labeled brain surfaces shows improved parcellation performance over a no-alignment strategy, gaining a significant speed (1400 fold) over traditional iterative alignment approaches., Comment: Equal contribution of R. He and K. Gopinath

Segmentation of retinal layers from Optical Coherence Tomography (OCT) volumes is a fundamental problem for any computer aided diagnostic algorithm development. This requires preprocessing steps such as denoising, region of interest extraction, flattening and edge detection all of which involve separate parameter tuning. In this paper, we explore deep learning techniques to automate all these steps and handle the presence/absence of pathologies. A model is proposed consisting of a combination of Convolutional Neural Network (CNN) and Long Short Term Memory (LSTM). The CNN is used to extract layers of interest image and extract the edges, while the LSTM is used to trace the layer boundary. This model is trained on a mixture of normal and AMD cases using minimal data. Validation results on three public datasets show that the pixel-wise mean absolute error obtained with our system is 1.30 plus or minus 0.48 which is lower than the inter-marker error of 1.79 plus or minus 0.76. Our model's performance is also on par with the existing methods., Comment: Accepted in The 4th Asian Conference on Pattern Recognition (ACPR 2017)

Recently, dense connections have attracted substantial attention in computer vision because they facilitate gradient flow and implicit deep supervision during training. Particularly, DenseNet, which connects each layer to every other layer in a feed-forward fashion, has shown impressive performances in natural image classification tasks. We propose HyperDenseNet, a 3D 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 6-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 at https://www.github.com/josedolz/HyperDenseNet., Comment: Paper accepted at IEEE TMI in October 2018. Last version of this paper updates the reference to the IEEE TMI paper which compares the submissions to the iSEG 2017 MICCAI Challenge

Neuronal cell bodies mostly reside in the cerebral cortex. The study of this thin and highly convoluted surface is essential for understanding how the brain works. The analysis of surface data is, however, challenging due to the high variability of the cortical geometry. This paper presents a novel approach for learning and exploiting surface data directly across surface domains. Current approaches rely on geometrical simplifications, such as spherical inflations, a popular but costly process. For instance, the widely used FreeSurfer takes about 3 hours to parcellate brain surfaces on a standard machine. Direct learning of surface data via graph convolutions would provide a new family of fast algorithms for processing brain surfaces. However, the current limitation of existing state-of-the-art approaches is their inability to compare surface data across different surface domains. Surface bases are indeed incompatible between brain geometries. This paper leverages recent advances in spectral graph matching to transfer surface data across aligned spectral domains. This novel approach enables a direct learning of surface data across compatible surface bases. It exploits spectral filters over intrinsic representations of surface neighborhoods. We illustrate the benefits of this approach with an application to brain parcellation. We validate the algorithm over 101 manually labeled brain surfaces. The results show a significant improvement in labeling accuracy over recent Euclidean approaches, while gaining a drastic speed improvement over conventional methods., Comment: 8 pages, Under review in MICCAI 2018

SD-OCT is a non-invasive cross-sectional imaging modality used for diagnosis of macular defects. Efficient detection and segmentation of the abnormalities seen as biomarkers in OCT can help in analyzing the progression of the disease and advising effective treatment for the associated disease. In this work, we propose a fully automated Generalized Motion Pattern(GMP) based segmentation method using a cascade of fully convolutional networks for detection and segmentation of retinal fluids from SD-OCT scans. General methods for segmentation depend on domain knowledge-based feature extraction, whereas we propose a method based on Generalized Motion Pattern (GMP) which is derived by inducing motion to an image to suppress the background.The proposed method is parallelizable and handles inter-scanner variability efficiently. Our method achieves a mean Dice score of 0.61,0.70 and 0.73 during segmentation and a mean AUC of 0.85,0.84 and 0.87 during detection for the 3 types of fluids IRF, SRF and PDE respectively., Comment: 8 pages, 4th MICCAI Workshop on Ophthalmic Medical Image Analysis (OMIA)

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 3D 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 (CNN) 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 outperforms all benchmarks. These results underscore the strengths of the proposed method in handling variations in both data acquisition protocols and scanners., Comment: Under review in Journal of Biomedical and Health Informatics

3D imaging modalities are becoming increasingly popular and relevant in retinal imaging owing to their effectiveness in highlighting structures in sub-retinal layers. OCT is one such modality which has great importance in the context of analysis of cystoid structures in subretinal layers. Signal to noise ratio(SNR) of the images obtained from OCT is less and hence automated and accurate determination of cystoid structures from OCT is a challenging task. We propose an automated method for detecting/segmenting cysts in 3D OCT volumes. The proposed method is biologically inspired and fast aided by the domain knowledge about the cystoid structures. An ensemble learning methodRandom forests is learnt for classification of detected region into cyst region. The method achieves detection and segmentation in a unified setting. We believe the proposed approach with further improvements can be a promising starting point for more robust approach. This method is validated against the training set achieves a mean dice coefficient of 0.3893 with a standard deviation of 0.2987, Comment: The paper was accepted as an oral presentation in MICCAI-2015 OPTIMA Cyst Segmentation Challenge