Fetal cortical surface atlas parcellation based on growth patterns.

Defining anatomically and functionally meaningful parcellation maps on cortical surface atlases is of great importance in surface-based neuroimaging analysis. The conventional cortical parcellation maps are typically defined based on anatomical cortical folding landmarks in adult surface atlases. However, they are not suitable for fetal brain studies, due to dramatic differences in brain size, shape, and properties between adults and fetuses. To address this issue, we propose a novel data-driven method for parcellation of fetal cortical surface atlases into distinct regions based on the dynamic "growth patterns" of cortical properties (e.g., surface area) from a population of fetuses. Our motivation is that the growth patterns of cortical properties indicate the underlying rapid changes of microstructures, which determine the molecular and functional principles of the cortex. Thus, growth patterns are well suitable for defining distinct cortical regions in development, structure, and function. To comprehensively capture the similarities of cortical growth patterns among vertices, we construct two complementary similarity matrices. One is directly based on the growth trajectories of vertices, and the other is based on the correlation profiles of vertices' growth trajectories in relation to a set of reference points. Then, we nonlinearly fuse these two similarity matrices into a single one, which can better capture both their common and complementary information than by simply averaging them. Finally, based on this fused similarity matrix, we perform spectral clustering to divide the fetal cortical surface atlases into distinct regions. By applying our method on 25 normal fetuses from 26 to 29 gestational weeks, we construct age-specific fetal cortical surface atlases equipped with biologically meaningful parcellation maps based on cortical growth patterns. Importantly, our generated parcellation maps reveal spatially contiguous, hierarchical and bilaterally relatively symmetric patterns of fetal cortical surface development.

Benchmark on Automatic 6-month-old Infant Brain Segmentation Algorithms: The iSeg-2017 Challenge.

Accurate segmentation of infant brain magnetic resonance (MR) images into white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) is an indispensable foundation for early studying of brain growth patterns and morphological changes in neurodevelopmental disorders. Nevertheless, in the isointense phase (approximately 6-9 months of age), due to inherent myelination and maturation process, WM and GM exhibit similar levels of intensity in both T1-weighted (T1w) and T2-weighted (T2w) MR images, making tissue segmentation very challenging. Despite many efforts were devoted to brain segmentation, only few studies have focused on the segmentation of 6-month infant brain images. With the idea of boosting methodological development in the community, iSeg-2017 challenge (http://iseg2017.web.unc.edu) provides a set of 6-month infant subjects with manual labels for training and testing the participating methods. Among the 21 automatic segmentation methods participating in iSeg-2017, we review the 8 top-ranked teams, in terms of Dice ratio, modified Hausdorff distance and average surface distance, and introduce their pipelines, implementations, as well as source codes. We further discuss limitations and possible future directions. We hope the dataset in iSeg-2017 and this review article could provide insights into methodological development for the community.

Patch spaces and fusion strategies in patch-based label fusion.

In the field of multi-atlas segmentation, patch-based approaches have shown promising results in the segmentation of biomedical images. In the most common approach, registration is used to warp the atlases to the target space and then the warped atlas labelmaps are fused into a consensus segmentation based on local appearance information encoded in form of patches. The registration step establishes spatial correspondence, which is important to obtain anatomical priors. Patch-based label fusion in the target space has shown to produce very accurate segmentations although at the expense of registering all atlases to each target image. Moreover, appearance (i.e., patches) and label information used by label fusion is extracted from the warped atlases, which are subject to interpolation errors. In this work, we revisit and extend the patch-based label fusion framework, exploring the role of extracting this information from the native space of both atlases and target images, thus avoiding interpolation artifacts, but at the same time, we do it in a way that it does not sacrifice the anatomical priors derived by registration. We further propose a common formulation for two widely-used label fusion strategies, i.e., similarity-based and a particular type of learning-based label fusion. The proposed framework is evaluated on subcortical structure segmentation in adult brains and tissue segmentation in fetal brain MRI. Our results indicate that using atlas patches in their native space yields superior performance than warping the atlases to the target image. The learning-based approach tends to outperform the similarity-based approach, with the particularity that using patches in native space lessens the computational requirements of learning. As conclusion, the combination of learning-based label fusion and native atlas patches yields the best performance with reduced test times than conventional similarity-based approaches.

FETAL CORTICAL PARCELLATION BASED ON GROWTH PATTERNS.

Dividing the human cerebral cortex into structurally and functionally distinct regions is important in many neuroimaging studies. Although many parcellations have been created for adults, they are not applicable for fetal studies, due to dramatic differences in brain size, shape and folding between adults and fetuses, as well as dynamic growth of fetal brains. To address this issue, we propose a novel method to divide a population of fetal cortical surfaces into distinct regions based on the dynamic growth patterns of cortical properties, which indicate the underlying changes of microstructures. As microstructures determine the molecular organization and functional principles of the cortex, growth patterns enable an accurate definition of distinct regions in development, microstructure, and function. To comprehensively capture the similarities of cortical growth patterns among vertices, we construct two complementary similarity matrices. One is directly based on the growth trajectories of vertices and the other is based on the correlation profiles of vertices' growth trajectories in relation to those of reference points. Then, we nonlinearly fuse these two similarity matrices into a single one, which can better captures both their common and complementary information than by simply averaging them. Finally, based on this fused matrix, we perform spectral clustering to divide fetal cortical surfaces into distinct regions. We have applied our method on 25 normal fetuses from 26 to 29 gestational weeks and generated biologically meaningful parcellations.

Learning to combine complementary segmentation methods for fetal and 6-month infant brain MRI segmentation.

Segmentation of brain structures during the pre-natal and early post-natal periods is the first step for subsequent analysis of brain development. Segmentation techniques can be roughly divided into two families. The first, which we denote as registration-based techniques, rely on initial estimates derived by registration to one (or several) templates. The second family, denoted as learning-based techniques, relate imaging (and spatial) features to their corresponding anatomical labels. Each approach has its own qualities and both are complementary to each other. In this paper, we explore two ensembling strategies, namely, stacking and cascading to combine the strengths of both families. We present experiments on segmentation of 6-month infant brains and a cohort of fetuses with isolated non-severe ventriculomegaly (INSVM). INSVM is diagnosed when ventricles are mildly enlarged and no other anomalies are apparent. Prognosis is difficult based solely on the degree of ventricular enlargement. In order to find markers for a more reliable prognosis, we use the resulting segmentations to find abnormalities in the cortical folding of INSVM fetuses. Segmentation results show that either combination strategy outperform all of the individual methods, thus demonstrating the capability of learning systematic combinations that lead to an overall improvement. In particular, the cascading strategy outperforms the ensembling one, the former one obtaining top 5, 7 and 13 results (out of 21 teams) in the segmentation of white matter, gray matter and cerebro-spinal fluid in the iSeg2017 MICCAI Segmentation Challenge. The resulting segmentations reveal that INSVM fetuses have a less convoluted cortex. This points to cortical folding abnormalities as potential markers of later neurodevelopmental outcomes.

Cortical folding alterations in fetuses with isolated non-severe ventriculomegaly.

Neuroimaging of brain diseases plays a crucial role in understanding brain abnormalities and early diagnosis. Of great importance is the study of brain abnormalities in utero and the assessment of deviations in case of maldevelopment. In this work, brain magnetic resonance images from 23 isolated non-severe ventriculomegaly (INSVM) fetuses and 25 healthy controls between 26 and 29 gestational weeks were used to identify INSVM-related cortical folding deviations from normative development. Since these alterations may reflect abnormal neurodevelopment, our working hypothesis is that markers of cortical folding can provide cues to improve the prediction of later neurodevelopmental problems in INSVM subjects. We analyzed the relationship of ventricular enlargement with cortical folding alterations in a regional basis using several curvature-based measures describing the folding of each cortical region. Statistical analysis (global and hemispheric) and sparse linear regression approaches were then used to find the cortical regions whose folding is associated with ventricular dilation. Results from both approaches were in great accordance, showing a significant cortical folding decrease in the insula, posterior part of the temporal lobe and occipital lobe. Moreover, compared to the global analysis, stronger ipsilateral associations of ventricular enlargement with reduced cortical folding were encountered by the hemispheric analysis. Our findings confirm and extend previous studies by identifying various cortical regions and emphasizing ipsilateral effects of ventricular enlargement in altered folding. This suggests that INSVM is an indicator of altered cortical development, and moreover, cortical regions with reduced folding constitute potential prognostic biomarkers to be used in follow-up studies to decipher the outcome of INSVM fetuses.

Revealing Regional Associations of Cortical Folding Alterations with In Utero Ventricular Dilation Using Joint Spectral Embedding.

Fetal ventriculomegaly (VM) is a condition with dilation of one or both lateral ventricles, and is diagnosed as an atrial diameter larger than 10 mm. Evidence of altered cortical folding associated with VM has been shown in the literature. However, existing studies use a holistic approach (i.e., ventricle as a whole) based on diagnosis or ventricular volume, thus failing to reveal the spatially-heterogeneous association patterns between cortex and ventricle. To address this issue, we develop a novel method to identify spatially fine-scaled association maps between cortical development and VM by leveraging vertex-wise correlations between the growth patterns of both ventricular and cortical surfaces in terms of area expansion and curvature information. Our approach comprises multiple steps. In the first step, we define a joint graph Laplacian matrix using cortex-to-ventricle correlations. Next, we propose a spectral embedding of the cortex-to-ventricle graph into a common underlying space where their joint growth patterns are projected. More importantly, in the joint ventricle-cortex space, the vertices of associated regions from both cortical and ventricular surfaces would lie close to each other. In the final step, we perform clustering in the joint embedded space to identify associated sub-regions between cortex and ventricle. Using a dataset of 25 healthy fetuses and 23 fetuses with isolated non-severe VM within the age range of 26-29 gestational weeks, our results show that the proposed approach is able to reveal clinically relevant and meaningful regional associations.

Learning non-linear patch embeddings with neural networks for label fusion.

In brain structural segmentation, multi-atlas strategies are increasingly being used over single-atlas strategies because of their ability to fit a wider anatomical variability. Patch-based label fusion (PBLF) is a type of such multi-atlas approaches that labels each target point as a weighted combination of neighboring atlas labels, where atlas points with higher local similarity to the target contribute more strongly to label fusion. PBLF can be potentially improved by increasing the discriminative capabilities of the local image similarity measurements. We propose a framework to compute patch embeddings using neural networks so as to increase discriminative abilities of similarity-based weighted voting in PBLF. As particular cases, our framework includes embeddings with different complexities, namely, a simple scaling, an affine transformation, and non-linear transformations. We compare our method with state-of-the-art alternatives in whole hippocampus and hippocampal subfields segmentation experiments using publicly available datasets. Results show that even the simplest versions of our method outperform standard PBLF, thus evidencing the benefits of discriminative learning. More complex transformation models tended to achieve better results than simpler ones, obtaining a considerable increase in average Dice score compared to standard PBLF.

Discriminative confidence estimation for probabilistic multi-atlas label fusion.

Quantitative neuroimaging analyses often rely on the accurate segmentation of anatomical brain structures. In contrast to manual segmentation, automatic methods offer reproducible outputs and provide scalability to study large databases. Among existing approaches, multi-atlas segmentation has recently shown to yield state-of-the-art performance in automatic segmentation of brain images. It consists in propagating the labelmaps from a set of atlases to the anatomy of a target image using image registration, and then fusing these multiple warped labelmaps into a consensus segmentation on the target image. Accurately estimating the contribution of each atlas labelmap to the final segmentation is a critical step for the success of multi-atlas segmentation. Common approaches to label fusion either rely on local patch similarity, probabilistic statistical frameworks or a combination of both. In this work, we propose a probabilistic label fusion framework based on atlas label confidences computed at each voxel of the structure of interest. Maximum likelihood atlas confidences are estimated using a supervised approach, explicitly modeling the relationship between local image appearances and segmentation errors produced by each of the atlases. We evaluate different spatial pooling strategies for modeling local segmentation errors. We also present a novel type of label-dependent appearance features based on atlas labelmaps that are used during confidence estimation to increase the accuracy of our label fusion. Our approach is evaluated on the segmentation of seven subcortical brain structures from the MICCAI 2013 SATA Challenge dataset and the hippocampi from the ADNI dataset. Overall, our results indicate that the proposed label fusion framework achieves superior performance to state-of-the-art approaches in the majority of the evaluated brain structures and shows more robustness to registration errors.

Toward the automatic quantification of in utero brain development in 3D structural MRI: A review.

Investigating the human brain in utero is important for researchers and clinicians seeking to understand early neurodevelopmental processes. With the advent of fast magnetic resonance imaging (MRI) techniques and the development of motion correction algorithms to obtain high-quality 3D images of the fetal brain, it is now possible to gain more insight into the ongoing maturational processes in the brain. In this article, we present a review of the major building blocks of the pipeline toward performing quantitative analysis of in vivo MRI of the developing brain and its potential applications in clinical settings. The review focuses on T1- and T2-weighted modalities, and covers state of the art methodologies involved in each step of the pipeline, in particular, 3D volume reconstruction, spatio-temporal modeling of the developing brain, segmentation, quantification techniques, and clinical applications. Hum Brain Mapp 38:2772-2787, 2017. © 2017 Wiley Periodicals, Inc.