Mid-space-independent deformable image registration.

Aligning images in a mid-space is a common approach to ensuring that deformable image registration is symmetric - that it does not depend on the arbitrary ordering of the input images. The results are, however, generally dependent on the mathematical definition of the mid-space. In particular, the set of possible solutions is typically restricted by the constraints that are enforced on the transformations to prevent the mid-space from drifting too far from the native image spaces. The use of an implicit atlas has been proposed as an approach to mid-space image registration. In this work, we show that when the atlas is aligned to each image in the native image space, the data term of implicit-atlas-based deformable registration is inherently independent of the mid-space. In addition, we show that the regularization term can be reformulated independently of the mid-space as well. We derive a new symmetric cost function that only depends on the transformation morphing the images to each other, rather than to the atlas. This eliminates the need for anti-drift constraints, thereby expanding the space of allowable deformations. We provide an implementation scheme for the proposed framework, and validate it through diffeomorphic registration experiments on brain magnetic resonance images.

An algorithm for optimal fusion of atlases with different labeling protocols.

In this paper we present a novel label fusion algorithm suited for scenarios in which different manual delineation protocols with potentially disparate structures have been used to annotate the training scans (hereafter referred to as "atlases"). Such scenarios arise when atlases have missing structures, when they have been labeled with different levels of detail, or when they have been taken from different heterogeneous databases. The proposed algorithm can be used to automatically label a novel scan with any of the protocols from the training data. Further, it enables us to generate new labels that are not present in any delineation protocol by defining intersections on the underling labels. We first use probabilistic models of label fusion to generalize three popular label fusion techniques to the multi-protocol setting: majority voting, semi-locally weighted voting and STAPLE. Then, we identify some shortcomings of the generalized methods, namely the inability to produce meaningful posterior probabilities for the different labels (majority voting, semi-locally weighted voting) and to exploit the similarities between the atlases (all three methods). Finally, we propose a novel generative label fusion model that can overcome these drawbacks. We use the proposed method to combine four brain MRI datasets labeled with different protocols (with a total of 102 unique labeled structures) to produce segmentations of 148 brain regions. Using cross-validation, we show that the proposed algorithm outperforms the generalizations of majority voting, semi-locally weighted voting and STAPLE (mean Dice score 83%, vs. 77%, 80% and 79%, respectively). We also evaluated the proposed algorithm in an aging study, successfully reproducing some well-known results in cortical and subcortical structures.

Heritability and interindividual variability of regional structure-function coupling.

White matter structural connections are likely to support flow of functional activation or functional connectivity. While the relationship between structural and functional connectivity profiles, here called SC-FC coupling, has been studied on a whole-brain, global level, few studies have investigated this relationship at a regional scale. Here we quantify regional SC-FC coupling in healthy young adults using diffusion-weighted MRI and resting-state functional MRI data from the Human Connectome Project and study how SC-FC coupling may be heritable and varies between individuals. We show that regional SC-FC coupling strength varies widely across brain regions, but was strongest in highly structurally connected visual and subcortical areas. We also show interindividual regional differences based on age, sex and composite cognitive scores, and that SC-FC coupling was highly heritable within certain networks. These results suggest regional structure-function coupling is an idiosyncratic feature of brain organisation that may be influenced by genetic factors.

Mid-Space-Independent Symmetric Data Term for Pairwise Deformable Image Registration.

Aligning a pair of images in a mid-space is a common approach to ensuring that deformable image registration is symmetric - that it does not depend on the arbitrary ordering of the input images. The results are, however, generally dependent on the choice of the mid-space. In particular, the set of possible solutions is typically affected by the constraints that are enforced on the two transformations (that deform the two images), which are to prevent the mid-space from drifting too far from the native image spaces. The use of an implicit atlas has been proposed to define the mid-space for pairwise registration. In this work, we show that by aligning the atlas to each image in the native image space, implicit-atlas-based pairwise registration can be made independent of the mid-space, thereby eliminating the need for anti-drift constraints. We derive a new symmetric cost function that only depends on a single transformation morphing one image to the other, and validate it through diffeomorphic registration experiments on brain magnetic resonance images.

A probabilistic, non-parametric framework for inter-modality label fusion.

Multi-atlas techniques are commonplace in medical image segmentation due to their high performance and ease of implementation. Locally weighting the contributions from the different atlases in the label fusion process can improve the quality of the segmentation. However, how to define these weights in a principled way in inter-modality scenarios remains an open problem. Here we propose a label fusion scheme that does not require voxel intensity consistency between the atlases and the target image to segment. The method is based on a generative model of image data in which each intensity in the atlases has an associated conditional distribution of corresponding intensities in the target. The segmentation is computed using variational expectation maximization (VEM) in a Bayesian framework. The method was evaluated with a dataset of eight proton density weighted brain MRI scans with nine labeled structures of interest. The results show that the algorithm outperforms majority voting and a recently published inter-modality label fusion algorithm.

Improved inference in Bayesian segmentation using Monte Carlo sampling: application to hippocampal subfield volumetry.

Many segmentation algorithms in medical image analysis use Bayesian modeling to augment local image appearance with prior anatomical knowledge. Such methods often contain a large number of free parameters that are first estimated and then kept fixed during the actual segmentation process. However, a faithful Bayesian analysis would marginalize over such parameters, accounting for their uncertainty by considering all possible values they may take. Here we propose to incorporate this uncertainty into Bayesian segmentation methods in order to improve the inference process. In particular, we approximate the required marginalization over model parameters using computationally efficient Markov chain Monte Carlo techniques. We illustrate the proposed approach using a recently developed Bayesian method for the segmentation of hippocampal subfields in brain MRI scans, showing a significant improvement in an Alzheimer's disease classification task. As an additional benefit, the technique also allows one to compute informative "error bars" on the volume estimates of individual structures.

Example-based restoration of high-resolution magnetic resonance image acquisitions.

Increasing scan resolution in magnetic resonance imaging is possible with advances in acquisition technology. The increase in resolution, however, comes at the expense of severe image noise. The current approach is to acquire multiple images and average them to restore the lost quality. This approach is expensive as it requires a large number of acquisitions to achieve quality comparable to lower resolution images. We propose an image restoration method for reducing the number of required acquisitions. The method leverages a high-quality lower-resolution image of the same subject and a database of pairs of high-quality low/high-resolution images acquired from different individuals. Experimental results show that the proposed method decreases noise levels and improves contrast differences between fine-scale structures, yielding high signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). Comparisons with the current standard method of averaging approach and state-of-the-art non-local means denoising demonstrate the method's advantages.

A GENERATIVE MODEL FOR MULTI-ATLAS SEGMENTATION ACROSS MODALITIES.

Current label fusion methods enhance multi-atlas segmentation by locally weighting the contribution of the atlases according to their similarity to the target volume after registration. However, these methods cannot handle voxel intensity inconsistencies between the atlases and the target image, which limits their application across modalities or even across MRI datasets due to differences in image contrast. Here we present a generative model for multi-atlas image segmentation, which does not rely on the intensity of the training images. Instead, we exploit the consistency of voxel intensities within regions in the target volume and their relation to the propagated labels. This is formulated in a probabilistic framework, where the most likely segmentation is obtained with variational expectation maximization (EM). The approach is demonstrated in an experiment where T1-weighted MRI atlases are used to segment proton-density (PD) weighted brain MRI scans, a scenario in which traditional weighting schemes cannot be used. Our method significantly improves the results provided by majority voting and STAPLE.

A Generative Model for Probabilistic Label Fusion of Multimodal Data.

The maturity of registration methods, in combination with the increasing processing power of computers, has made multi-atlas segmentation methods practical. The problem of merging the deformed label maps from the atlases is known as label fusion. Even though label fusion has been well studied for intramodality scenarios, it remains relatively unexplored when the nature of the target data is multimodal or when its modality is different from that of the atlases. In this paper, we review the literature on label fusion methods and also present an extension of our previously published algorithm to the general case in which the target data are multimodal. The method is based on a generative model that exploits the consistency of voxel intensities within the target scan based on the current estimate of the segmentation. Using brain MRI scans acquired with a multiecho FLASH sequence, we compare the method with majority voting, statistical-atlas-based segmentation, the popular package FreeSurfer and an adaptive local multi-atlas segmentation method. The results show that our approach produces highly accurate segmentations (Dice 86.3% across 22 brain structures of interest), outperforming the competing methods.

Incorporating parameter uncertainty in Bayesian segmentation models: application to hippocampal subfield volumetry.

Many successful segmentation algorithms are based on Bayesian models in which prior anatomical knowledge is combined with the available image information. However, these methods typically have many free parameters that are estimated to obtain point estimates only, whereas a faithful Bayesian analysis would also consider all possible alternate values these parameters may take. In this paper, we propose to incorporate the uncertainty of the free parameters in Bayesian segmentation models more accurately by using Monte Carlo sampling. We demonstrate our technique by sampling atlas warps in a recent method for hippocampal subfield segmentation, and show a significant improvement in an Alzheimer's disease classification task. As an additional benefit, the method also yields informative "error bars" on the segmentation results for each of the individual sub-structures.