Neuroconductor: an R platform for medical imaging analysis

Neuroconductor (https://neuroconductor.org) is an open-source platform for rapid testing and dissemination of reproducible computational imaging software. The goals of the project are to: (i) provide a centralized repository of R software dedicated to image analysis, (ii) disseminate software updates quickly, (iii) train a large, diverse community of scientists using detailed tutorials and short courses, (iv) increase software quality via automatic and manual quality controls, and (v) promote reproducibility of image data analysis. Based on the programming language R (https://www.r-project.org/), Neuroconductor starts with 51 inter-operable packages that cover multiple areas of imaging including visualization, data processing and storage, and statistical inference. Neuroconductor accepts new R package submissions, which are subject to a formal review and continuous automated testing. We provide a description of the purpose of Neuroconductor and the user and developer experience

Multivariate MR Biomarkers Better Predict Cognitive Dysfunction in Mouse Models of Alzheimers Disease

To understand multifactorial conditions such as Alzheimers disease (AD) we need brain signatures that predict the impact of multiple pathologies and their interactions. To help uncover the relationships between brain circuits and cognitive markers we have used mouse models that represent, at least in part, the complex interactions altered in AD. In particular, we aimed to understand the relationship between vulnerable brain circuits and memory deficits measured in the Morris water maze, and we tested several predictive modeling approaches. We used in vivo manganese enhanced MRI voxel based analyses to reveal regional differences in volume (morphometry), signal intensity (activity), and magnetic susceptibility (iron deposition, demyelination). These regions included the hippocampus, olfactory areas, entorhinal cortex and cerebellum. The image based properties of these regions were used to predict spatial memory. We next used eigenanatomy, which reduces dimensionality to produce sets of regions that explain the variance in the data. For each imaging marker, eigenanatomy revealed networks underpinning a range of cognitive functions including memory, motor function, and associative learning. Finally, the integration of multivariate markers in a supervised sparse canonical correlation approach outperformed single predictor models and had significant correlates to spatial memory. Among a priori selected regions, the fornix also provided good predictors, raising the possibility of investigating how disease propagation within brain networks leads to cognitive deterioration. Our results support that modeling approaches integrating multivariate imaging markers provide sensitive predictors of AD-like behaviors. Such strategies for mapping brain circuits responsible for behaviors may help in the future predict disease progression, or response to interventions.Comment: 23 pages, 3 Tables, 6 Figures; submitted for publicatio

Neuroimaging Evidence of Major Morpho-Anatomical and Functional Abnormalities in the BTBR T+TF/J Mouse Model of Autism

BTBR T+tf/J (BTBR) mice display prominent behavioural deficits analogous to the defining symptoms of autism, a feature that has prompted a widespread use of the model in preclinical autism research. Because neuro-behavioural traits are described with respect to reference populations, multiple investigators have examined and described the behaviour of BTBR mice against that exhibited by C57BL/6J (B6), a mouse line characterised by high sociability and low self-grooming. In an attempt to probe the translational relevance of this comparison for autism research, we used Magnetic Resonance Imaging (MRI) to map in both strain multiple morpho-anatomical and functional neuroimaging readouts that have been extensively used in patient populations. Diffusion tensor tractography confirmed previous reports of callosal agenesis and lack of hippocampal commissure in BTBR mice, and revealed a concomitant rostro-caudal reorganisation of major cortical white matter bundles. Intact inter-hemispheric tracts were found in the anterior commissure, ventro-medial thalamus, and in a strain-specific white matter formation located above the third ventricle. BTBR also exhibited decreased fronto-cortical, occipital and thalamic gray matter volume and widespread reductions in cortical thickness with respect to control B6 mice. Foci of increased gray matter volume and thickness were observed in the medial prefrontal and insular cortex. Mapping of resting-state brain activity using cerebral blood volume weighted fMRI revealed reduced cortico-thalamic function together with foci of increased activity in the hypothalamus and dorsal hippocampus of BTBR mice. Collectively, our results show pronounced functional and structural abnormalities in the brain of BTBR mice with respect to control B6 mice. The large and widespread white and gray matter abnormalities observed do not appear to be representative of the neuroanatomical alterations typically observed in autistic patients. The presence of reduced fronto-cortical metabolism is of potential translational relevance, as this feature recapitulates previously-reported clinical observations

Asymmetric Image-Template Registration

Authors Manuscript received: 2010 May 4. 12th International Conference, London, UK, September 20-24, 2009, Proceedings, Part IA natural requirement in pairwise image registration is that the resulting deformation is independent of the order of the images. This constraint is typically achieved via a symmetric cost function and has been shown to reduce the effects of local optima. Consequently, symmetric registration has been successfully applied to pairwise image registration as well as the spatial alignment of individual images with a template. However, recent work has shown that the relationship between an image and a template is fundamentally asymmetric. In this paper, we develop a method that reconciles the practical advantages of symmetric registration with the asymmetric nature of image-template registration by adding a simple correction factor to the symmetric cost function. We instantiate our model within a log-domain diffeomorphic registration framework. Our experiments show exploiting the asymmetry in image-template registration improves alignment in the image coordinates.NAMIC (NIH NIBIB NAMIC U54-EB005149)NAC (NIH NCRR NAC P41- RR13218)mBIRN (NIH NCRR mBIRN U24-RR021382)NIH NINDS (R01-NS051826 Grant)National Science Foundation (U.S.) (CAREER Grant 0642971)NIBIB (R01 EB001550)NIBIB (R01EB006758)NCRR (R01 RR16594-01A1)NCRR (P41-RR14075)NINDS (R01 NS052585-01)Singapore. Agency for Science, Technology and Researc

Unsupervised Fiber Bundles Registration using Weighted Measures Geometric Demons

International audienceBrain image registration aims at reducing anatomical variability across subjects to create a common space for group analysis. Multi-modal approaches intend to minimize cortex shape variations along with internal structures, such as fiber bundles. A di ficulty is that it requires a prior identi fication of these structures, which remains a challenging task in the absence of a complete reference atlas. We propose an extension of the log-Geometric Demons for jointly registering images and fi ber bundles without the need of point or ber correspondences. By representing fi ber bundles as Weighted Measures we can register subjects with di fferent numbers of fiber bundles. The ef ficacy of our algorithm is demonstrated by registering simultaneously T1 images and between 37 and 88 ber bundles depending on each of the ten subject used. We compare results with a multi-modal T1 + Fractional Anisotropy (FA) and a tensor-based registration algorithms and obtain superior performance with our approach

Joint T1 and Brain Fiber Log-Demons Registration Using Currents to Model Geometry

International audienceWe present an extension of the diffeomorphic Geometric Demons algorithm which combines the iconic registration with geometric constraints. Our algorithm works in the log-domain space, so that one can efficiently compute the deformation field of the geometry. We represent the shape of objects of interest in the space of currents which is sensitive to both location and geometric structure of objects. Currents provides a distance between geometric structures that can be defined without specifying explicit point-to-point correspondences. We demonstrate this framework by registering simultaneously T1 images and 65 fiber bundles consistently extracted in 12 subjects and compare it against non-linear T1, tensor, and multi-modal T1+ Fractional Anisotropy (FA) registration algorithms. Results show the superiority of the Log-domain Geometric Demons over their purely iconic counterparts

Multi-start Method with Prior Learning for Image Registration

We propose an efficient image registration strategy that is based on learned prior distributions of transformation parameters. These priors are used to constrain a finite- time multi-start optimization method. Motivation for this approach comes from the fact that standard affine brain image registration methods, especially those based on gradient descent optimization alone, are affected by the initial search position. While global optimization methods can resolve this problem, they are are often very time consuming. Our goal is to build an explicit prior model of the gap between a typical registration solution and the solution gained by a global optimization method. We use this learned prior model to restrict randomized search in the relevant parameter space surrounding the initial solution. Global optimization in this restricted parameter space provides, in finite time, results that are superior to both gradient descent and the general multi-start strategy. The performance of our method is illustrated on a data set of 67 elderly and neurodegenerative brains. Our novel learning strategy and the associated registration method are shown to outperform other approaches. Theoretical, synthetic and real-world examples illustrate this improvement

Multivariate Normalization with Symmetric Diffeomorphisms for Multivariate Studies

Current clinical and research neuroimaging protocols acquire images using multiple modalities, for instance, T1, T2, diffusion tensor and cerebral blood flow magnetic resonance images (MRI). These multivariate datasets provide unique and often complementary anatomical and physiological information about the subject of interest. We present a method that uses fused multiple modality (scalar and tensor) datasets to perform intersubject spatial normalization. Our multivariate approach has the potential to eliminate inconsistencies that occur when normalization is performed on each modality separately. Furthermore, the multivariate approach uses a much richer anatomical and physiological image signature to infer image correspondences and perform multivariate statistical tests. In this initial study, we develop the theory for Multivariate Symmetric Normalization (MVSyN), establish its feasibility and discuss preliminary results on a multivariate statistical study of 22q deletion syndrome