Mark Jenkinson

Advances in functional and structural MR image analysis and implementation as FSL.

The techniques available for the interrogation and analysis of neuroimaging data have a large influence in determining the flexibility, sensitivity, and scope of neuroimaging experiments. The development of such methodologies has allowed investigators to address scientific questions that could not previously be answered and, as such, has become an important research area in its own right. In this paper, we present a review of the research carried out by the Analysis Group at the Oxford Centre for Functional MRI of the Brain (FMRIB). This research has focussed on the development of new methodologies for the analysis of both structural and functional magnetic resonance imaging data. The majority of the research laid out in this paper has been implemented as freely available software tools within FMRIBs Software Library (FSL).

IMPROVED OPTIMIZATION FOR THE ROBUST AND ACCURATE LINEAR REGISTRATION AND MOTION CORRECTION OF BRAIN IMAGES

Linear registration and motion correction are important components of structural and functional brain image analysis. Most modern methods optimize some intensity-based cost function to determine the best registration. To date, little attention has been focused on the optimization method itself, even though the success of most registration methods hinges on the quality of this optimization. This paper examines the optimization process in detail and demonstrates that the commonly used multiresolution local optimization methods can, and do, get trapped in local minima. To address this problem, two approaches are taken: (1) to apodize the cost function and (2) to employ a novel hybrid global-local optimization method. This new optimization method is specifically designed for registering whole brain images. It substantially reduces the likelihood of producing misregistrations due to being trapped by local minima. The increased robustness of the method, compared to other commonly used methods, is demonstrated by a consistency test. In addition, the accuracy of the registration is demonstrated by a series of experiments with motion correction. These motion correction experiments also investigate how the results are affected by different cost functions and interpolation methods.

A global optimisation method for robust affine registration of brain images

Registration is an important component of medical image analysis and for analysing large amounts of data it is desirable to have fully automatic registration methods. Many different automatic registration methods have been proposed to date, and almost all share a common mathematical framework - one of optimising a cost function. To date little attention has been focused on the optimisation method itself, even though the success of most registration methods hinges on the quality of this optimisation. This paper examines the assumptions underlying the problem of registration for brain images using inter-modal voxel similarity measures. It is demonstrated that the use of local optimisation methods together with the standard multi-resolution approach is not sufficient to reliably find the global minimum. To address this problem, a global optimisation method is proposed that is specifically tailored to this form of registration. A full discussion of all the necessary implementation details is included as this is an important part of any practical method. Furthermore, results are presented for inter-modal, inter-subject registration experiments that show that the proposed method is more reliable at finding the global minimum than several of the currently available registration packages in common usage.

Characterization and propagation of uncertainty in diffusion-weighted MR imaging.

A fully probabilistic framework is presented for estimating local probability density functions on parameters of interest in a model of diffusion. This technique is applied to the estimation of parameters in the diffusion tensor model, and also to a simple partial volume model of diffusion. In both cases the parameters of interest include parameters defining local fiber direction. A technique is then presented for using these density functions to estimate global connectivity (i.e., the probability of the existence of a connection through the data field, between any two distant points), allowing for the quantification of belief in tractography results. This technique is then applied to the estimation of the cortical connectivity of the human thalamus. The resulting connectivity distributions correspond well with predictions from invasive tracer methods in nonhuman primate. Magn Reson Med 50:1077–1088, 2003.

Accurate, robust, and automated longitudinal and cross-sectional brain change analysis.

Quantitative measurement of brain size, shape, and temporal change (for example, in order to estimate atrophy) is increasingly important in biomedical image analysis applications. New methods of structural analysis attempt to improve robustness, accuracy, and extent of automation. A fully automated method of longitudinal (temporal change) analysis, SIENA, was presented previously. In this paper, improvements to this method are described, and also an extension of SIENA to a new method for cross-sectional (single time point) analysis. The methods are fully automated, robust, and accurate: 0.15% brain volume change error (longitudinal): 0.5-1% brain volume accuracy for single-time point (cross-sectional). A particular advantage is the relative insensitivity to differences in scanning parameters. The methods provide easy manual review of their output by the automatic production of summary images which show the results of the brain extraction, registration, tissue segmentation, and final atrophy estimation.

Bayesian analysis of neuroimaging data in FSL.

Typically in neuroimaging we are looking to extract some pertinent information from imperfect, noisy images of the brain. This might be the inference of percent changes in blood flow in perfusion FMRI data, segmentation of subcortical structures from structural MRI, or inference of the probability of an anatomical connection between an area of cortex and a subthalamic nucleus using diffusion MRI. In this article we will describe how Bayesian techniques have made a significant impact in tackling problems such as these, particularly in regards to the analysis tools in the FMRIB Software Library (FSL). We shall see how Bayes provides a framework within which we can attempt to infer on models of neuroimaging data, while allowing us to incorporate our prior belief about the brain and the neuroimaging equipment in the form of biophysically informed or regularising priors. It allows us to extract probabilistic information from the data, and to probabilistically combine information from multiple modalities. Bayes can also be used to not only compare and select between models of different complexity, but also to infer on data using committees of models. Finally, we mention some analysis scenarios where Bayesian methods are impractical, and briefly discuss some practical approaches that we have taken in these cases.

A Bayesian model of shape and appearance for subcortical brain segmentation.

Automatic segmentation of subcortical structures in human brain MR images is an important but difficult task due to poor and variable intensity contrast. Clear, well-defined intensity features are absent in many places along typical structure boundaries and so extra information is required to achieve successful segmentation. A method is proposed here that uses manually labelled image data to provide anatomical training information. It utilises the principles of the Active Shape and Appearance Models but places them within a Bayesian framework, allowing probabilistic relationships between shape and intensity to be fully exploited. The model is trained for 15 different subcortical structures using 336 manually-labelled T1-weighted MR images. Using the Bayesian approach, conditional probabilities can be calculated easily and efficiently, avoiding technical problems of ill-conditioned covariance matrices, even with weak priors, and eliminating the need for fitting extra empirical scaling parameters, as is required in standard Active Appearance Models. Furthermore, differences in boundary vertex locations provide a direct, purely local measure of geometric change in structure between groups that, unlike voxel-based morphometry, is not dependent on tissue classification methods or arbitrary smoothing. In this paper the fully-automated segmentation method is presented and assessed both quantitatively, using Leave-One-Out testing on the 336 training images, and qualitatively, using an independent clinical dataset involving Alzheimers disease. Median Dice overlaps between 0.7 and 0.9 are obtained with this method, which is comparable or better than other automated methods. An implementation of this method, called FIRST, is currently distributed with the freely-available FSL package.

Multilevel linear modelling for FMRI group analysis using Bayesian inference.

Functional magnetic resonance imaging studies often involve the acquisition of data from multiple sessions and/or multiple subjects. A hierarchical approach can be taken to modelling such data with a general linear model (GLM) at each level of the hierarchy introducing different random effects variance components. Inferring on these models is nontrivial with frequentist solutions being unavailable. A solution is to use a Bayesian framework. One important ingredient in this is the choice of prior on the variance components and top-level regression parameters. Due to the typically small numbers of sessions or subjects in neuroimaging, the choice of prior is critical. To alleviate this problem, we introduce to neuroimage modelling the approach of reference priors, which drives the choice of prior such that it is noninformative in an information-theoretic sense. We propose two inference techniques at the top level for multilevel hierarchies (a fast approach and a slower more accurate approach). We also demonstrate that we can infer on the top level of multilevel hierarchies by inferring on the levels of the hierarchy separately and passing summary statistics of a noncentral multivariate t distribution between them.

The minimal preprocessing pipelines for the Human Connectome Project

The Human Connectome Project (HCP) faces the challenging task of bringing multiple magnetic resonance imaging (MRI) modalities together in a common automated preprocessing framework across a large cohort of subjects. The MRI data acquired by the HCP differ in many ways from data acquired on conventional 3 Tesla scanners and often require newly developed preprocessing methods. We describe the minimal preprocessing pipelines for structural, functional, and diffusion MRI that were developed by the HCP to accomplish many low level tasks, including spatial artifact/distortion removal, surface generation, cross-modal registration, and alignment to standard space. These pipelines are specially designed to capitalize on the high quality data offered by the HCP. The final standard space makes use of a recently introduced CIFTI file format and the associated grayordinate spatial coordinate system. This allows for combined cortical surface and subcortical volume analyses while reducing the storage and processing requirements for high spatial and temporal resolution data. Here, we provide the minimum image acquisition requirements for the HCP minimal preprocessing pipelines and additional advice for investigators interested in replicating the HCPs acquisition protocols or using these pipelines. Finally, we discuss some potential future improvements to the pipelines.

A multi-modal parcellation of human cerebral cortex

Understanding the amazingly complex human cerebral cortex requires a map (or parcellation) of its major subdivisions, known as cortical areas. Making an accurate areal map has been a century-old objective in neuroscience. Using multi-modal magnetic resonance images from the Human Connectome Project (HCP) and an objective semi-automated neuroanatomical approach, we delineated 180 areas per hemisphere bounded by sharp changes in cortical architecture, function, connectivity, and/or topography in a precisely aligned group average of 210 healthy young adults. We characterized 97 new areas and 83 areas previously reported using post-mortem microscopy or other specialized study-specific approaches. To enable automated delineation and identification of these areas in new HCP subjects and in future studies, we trained a machine-learning classifier to recognize the multi-modal ‘fingerprint’ of each cortical area. This classifier detected the presence of 96.6% of the cortical areas in new subjects, replicated the group parcellation, and could correctly locate areas in individuals with atypical parcellations. The freely available parcellation and classifier will enable substantially improved neuroanatomical precision for studies of the structural and functional organization of human cerebral cortex and its variation across individuals and in development, aging, and disease.