Unsupervised Detection of Lesions in Brain MRI using constrained adversarial auto-encoders

Lesion detection in brain Magnetic Resonance Images (MRI) remains a challenging task. State-of-the-art approaches are mostly based on supervised learning making use of large annotated datasets. Human beings, on the other hand, even non-experts, can detect most abnormal lesions after seeing a handful of healthy brain images. Replicating this capability of using prior information on the appearance of healthy brain structure to detect lesions can help computers achieve human level abnormality detection, specifically reducing the need for numerous labeled examples and bettering generalization of previously unseen lesions. To this end, we study detection of lesion regions in an unsupervised manner by learning data distribution of brain MRI of healthy subjects using auto-encoder based methods. We hypothesize that one of the main limitations of the current models is the lack of consistency in latent representation. We propose a simple yet effective constraint that helps mapping of an image bearing lesion close to its corresponding healthy image in the latent space. We use the Human Connectome Project dataset to learn distribution of healthy-appearing brain MRI and report improved detection, in terms of AUC, of the lesions in the BRATS challenge dataset.Comment: 9 pages, 5 figures, accepted at MIDL 201

Temporal Interpolation via Motion Field Prediction

Navigated 2D multi-slice dynamic Magnetic Resonance (MR) imaging enables high contrast 4D MR imaging during free breathing and provides in-vivo observations for treatment planning and guidance. Navigator slices are vital for retrospective stacking of 2D data slices in this method. However, they also prolong the acquisition sessions. Temporal interpolation of navigator slices an be used to reduce the number of navigator acquisitions without degrading specificity in stacking. In this work, we propose a convolutional neural network (CNN) based method for temporal interpolation via motion field prediction. The proposed formulation incorporates the prior knowledge that a motion field underlies changes in the image intensities over time. Previous approaches that interpolate directly in the intensity space are prone to produce blurry images or even remove structures in the images. Our method avoids such problems and faithfully preserves the information in the image. Further, an important advantage of our formulation is that it provides an unsupervised estimation of bi-directional motion fields. We show that these motion fields can be used to halve the number of registrations required during 4D reconstruction, thus substantially reducing the reconstruction time.Comment: Submitted to 1st Conference on Medical Imaging with Deep Learning (MIDL 2018), Amsterdam, The Netherland

Canonical normalizing flows for manifold learning

Manifold learning flows are a class of generative modelling techniques that assume a low-dimensional manifold description of the data. The embedding of such a manifold into the high-dimensional space of the data is achieved via learnable invertible transformations. Therefore, once the manifold is properly aligned via a reconstruction loss, the probability density is tractable on the manifold and maximum likelihood can be used to optimize the network parameters. Naturally, the lower-dimensional representation of the data requires an injective-mapping. Recent approaches were able to enforce that the density aligns with the modelled manifold, while efficiently calculating the density volume-change term when embedding to the higher-dimensional space. However, unless the injective-mapping is analytically predefined, the learned manifold is not necessarily an efficient representation of the data. Namely, the latent dimensions of such models frequently learn an entangled intrinsic basis, with degenerate information being stored in each dimension. Alternatively, if a locally orthogonal and/or sparse basis is to be learned, here coined canonical intrinsic basis, it can serve in learning a more compact latent space representation. Toward this end, we propose a canonical manifold learning flow method, where a novel optimization objective enforces the transformation matrix to have few prominent and non-degenerate basis functions. We demonstrate that by minimizing the off-diagonal manifold metric elements $\ell_1$-norm, we can achieve such a basis, which is simultaneously sparse and/or orthogonal. Canonical manifold flow yields a more efficient use of the latent space, automatically generating fewer prominent and distinct dimensions to represent data, and a better approximation of target distributions than other manifold flow methods in most experiments we conducted, resulting in lower FID scores.Comment: NeurIPS 202

Clinical Prediction from Structural Brain MRI Scans: A Large-Scale Empirical Study

Multivariate pattern analysis (MVPA) methods have become an important tool in neuroimaging, revealing complex associations and yielding powerful prediction models. Despite methodological developments and novel application domains, there has been little effort to compile benchmark results that researchers can reference and compare against. This study takes a significant step in this direction. We employed three classes of state-of-the-art MVPA algorithms and common types of structural measurements from brain Magnetic Resonance Imaging (MRI) scans to predict an array of clinically relevant variables (diagnosis of Alzheimer’s, schizophrenia, autism, and attention deficit and hyperactivity disorder; age, cerebrospinal fluid derived amyloid-β levels and mini-mental state exam score). We analyzed data from over 2,800 subjects, compiled from six publicly available datasets. The employed data and computational tools are freely distributed (https://www.nmr.mgh.harvard.edu/lab/mripredict), making this the largest, most comprehensive, reproducible benchmark image-based prediction experiment to date in structural neuroimaging. Finally, we make several observations regarding the factors that influence prediction performance and point to future research directions. Unsurprisingly, our results suggest that the biological footprint (effect size) has a dramatic influence on prediction performance. Though the choice of image measurement and MVPA algorithm can impact the result, there was no universally optimal selection. Intriguingly, the choice of algorithm seemed to be less critical than the choice of measurement type. Finally, our results showed that cross-validation estimates of performance, while generally optimistic, correlate well with generalization accuracy on a new dataset.BrightFocus Foundation (Alzheimer’s Disease pilot grant (AHAF A2012333))National Institutes of Health (U.S.) (K25 grant (NIBIB 1K25EB013649-01))National Center for Research Resources (U.S.) (U24 RR021382)National Institutes of Health. National Institute for Biomedical Imaging and Bioengineering (R01EB006758)National Institute of Neurological Disorders and Stroke (U.S.) (R01 NS052585-01, 1R21NS072652-01, 1R01NS070963, R01NS083534)National Institutes of Health (U.S.) (Blueprint for Neuroscience Research (5U01-MH093765)

Unsupervised Lesion Detection via Image Restoration with a Normative Prior

Unsupervised lesion detection is a challenging problem that requires accurately estimating normative distributions of healthy anatomy and detecting lesions as outliers without training examples. Recently, this problem has received increased attention from the research community following the advances in unsupervised learning with deep learning. Such advances allow the estimation of high-dimensional distributions, such as normative distributions, with higher accuracy than previous methods.The main approach of the recently proposed methods is to learn a latent-variable model parameterized with networks to approximate the normative distribution using example images showing healthy anatomy, perform prior-projection, i.e. reconstruct the image with lesions using the latent-variable model, and determine lesions based on the differences between the reconstructed and original images. While being promising, the prior-projection step often leads to a large number of false positives. In this work, we approach unsupervised lesion detection as an image restoration problem and propose a probabilistic model that uses a network-based prior as the normative distribution and detect lesions pixel-wise using MAP estimation. The probabilistic model punishes large deviations between restored and original images, reducing false positives in pixel-wise detections. Experiments with gliomas and stroke lesions in brain MRI using publicly available datasets show that the proposed approach outperforms the state-of-the-art unsupervised methods by a substantial margin, +0.13 (AUC), for both glioma and stroke detection. Extensive model analysis confirms the effectiveness of MAP-based image restoration.Comment: Extended version of 'Unsupervised Lesion Detection via Image Restoration with a Normative Prior' (MIDL2019