Infant Brain MR Images Research Articles

Practical Stepwise Approach to Performing Neonatal Brain MR Imaging in the Research Setting.

Magnetic resonance imaging (MRI) is a non-invasive imaging technique that is commonly used for the visualization of newborn infant brains, both for clinical and research purposes. One of the main challenges with scanning newborn infants, particularly when scanning without sedation in a research setting, is movement. Infant movement can affect MR image quality and therewith reliable image assessment and advanced image analysis. Applying a systematic, stepwise approach to MR scanning during the neonatal period, including the use of the feed-and-bundle technique, is effective in reducing infant motion and ensuring high-quality images. We provide recommendations for one such systematic approach, including the step-by-step preparation and infant immobilization, and highlight safety precautions to minimize any potential risks. The recommendations are primarily focused on scanning newborn infants for research purposes but may be used successfully for clinical purposes as well, granted the infant is medically stable. Using the stepwise approach in our local research setting, our success rate of acquiring high-quality, analyzable infant brain MR images during the neonatal period is as high as 91%.

IBEAT V2.0: a multisite-applicable, deep learning-based pipeline for infant cerebral cortical surface reconstruction.

The human cerebral cortex undergoes dramatic and critical development during early postnatal stages. Benefiting from advances in neuroimaging, many infant brain magnetic resonance imaging (MRI) datasets have been collected from multiple imaging sites with different scanners and imaging protocols for the investigation of normal and abnormal early brain development. However, it is extremely challenging to precisely process and quantify infant brain development with these multisite imaging data because infant brain MRI scans exhibit (a) extremely low and dynamic tissue contrast caused by ongoing myelination and maturation and (b) inter-site data heterogeneity resulting from the use of diverse imaging protocols/scanners. Consequently, existing computational tools and pipelines typically perform poorly on infant MRI data. To address these challenges, we propose a robust, multisite-applicable, infant-tailored computational pipeline that leverages powerful deep learning techniques. The main functionality of the proposed pipeline includes preprocessing, brain skull stripping, tissue segmentation, topology correction, cortical surface reconstruction and measurement. Our pipeline can handle both T1w and T2w structural infant brain MR images well in a wide age range (from birth to 6 years of age) and is effective for different imaging protocols/scanners, despite being trained only on the data from the Baby Connectome Project. Extensive comparisons with existing methods on multisite, multimodal and multi-age datasets demonstrate superior effectiveness, accuracy and robustness of our pipeline. We have maintained a website, iBEAT Cloud, for users to process their images with our pipeline ( http://www.ibeat.cloud ), which has successfully processed over 16,000 infant MRI scans from more than 100 institutions with various imaging protocols/scanners.

Recurrent Tissue-Aware Network for Deformable Registration of Infant Brain MR Images.

Deformable registration is fundamental to longitudinal and population-based image analyses. However, it is challenging to precisely align longitudinal infant brain MR images of the same subject, as well as cross-sectional infant brain MR images of different subjects, due to fast brain development during infancy. In this paper, we propose a recurrently usable deep neural network for the registration of infant brain MR images. There are three main highlights of our proposed method. (i) We use brain tissue segmentation maps for registration, instead of intensity images, to tackle the issue of rapid contrast changes of brain tissues during the first year of life. (ii) A single registration network is trained in a one-shot manner, and then recurrently applied in inference for multiple times, such that the complex deformation field can be recovered incrementally. (iii) We also propose both the adaptive smoothing layer and the tissue-aware anti-folding constraint into the registration network to ensure the physiological plausibility of estimated deformations without degrading the registration accuracy. Experimental results, in comparison to the state-of-the-art registration methods, indicate that our proposed method achieves the highest registration accuracy while still preserving the smoothness of the deformation field. The implementation of our proposed registration network is available online https://github.com/Barnonewdm/ACTA-Reg-Net.

A 4D infant brain volumetric atlas based on the UNC/UMN baby connectome project (BCP) cohort

Spatiotemporal (four-dimensional) infant-dedicated brain atlases are essential for neuroimaging analysis of early dynamic brain development. However, due to the substantial technical challenges in the acquisition and processing of infant brain MR images, 4D atlases densely covering the dynamic brain development during infancy are still scarce. Few existing ones generally have fuzzy tissue contrast and low spatiotemporal resolution, leading to degraded accuracy of atlas-based normalization and subsequent analyses. To address this issue, in this paper, we construct a 4D structural MRI atlas for infant brains based on the UNC/UMN Baby Connectome Project (BCP) dataset, which features a high spatial resolution, extensive age-range coverage, and densely sampled time points. Specifically, 542 longitudinal T1w and T2w scans from 240 typically developing infants up to 26-month of age were utilized for our atlas construction. To improve the co-registration accuracy of the infant brain images, which typically exhibit dynamic appearance with low tissue contrast, we employed the state-of-the-art registration method and leveraged our generated reliable brain tissue probability maps in addition to the intensity images to improve the alignment of individual images. To achieve consistent region labeling on both infant and adult brain images for facilitating region-based analysis across ages, we mapped the widely used Desikan cortical parcellation onto our atlas by following an age-decreasing mapping manner. Meanwhile, the typical subcortical structures were manually delineated to facilitate the studies related to the subcortex. Compared with the existing infant brain atlases, our 4D atlas has much higher spatiotemporal resolution and preserves more structural details, and thus can boost accuracy in neurodevelopmental analysis during infancy.

ABCnet: Adversarial bias correction network for infant brain MR images.

Automatic correction of intensity nonuniformity (also termed as the bias correction) is an essential step in brain MR image analysis. Existing methods are typically developed for adult brain MR images based on the assumption that the image intensities within the same brain tissue are relatively uniform. However, this assumption is not valid in infant brain MR images, due to the dynamic and regionally-heterogeneous image contrast and appearance changes, which are caused by the underlying spatiotemporally-nonuniform myelination process. Therefore, it is not appropriate to directly use existing methods to correct the infant brain MR images. In this paper, we propose an end-to-end 3D adversarial bias correction network (ABCnet), tailored for direct prediction of bias fields from the input infant brain MR images for bias correction. The "ground-truth" bias fields for training our network are carefully defined by an improved N4 method, which integrates manually-corrected tissue segmentation maps as anatomical prior knowledge. The whole network is trained alternatively by minimizing generative and adversarial losses. To handle the heterogeneous intensity changes, our generative loss includes a tissue-aware local intensity uniformity term to reduce the local intensity variation in the corrected image. Besides, it also integrates two additional terms to enhance the smoothness of the estimated bias field and to improve the robustness of the proposed method, respectively. Comprehensive experiments with different sizes of training datasets have been carried out on a total of 1492 T1w and T2w MR images from neonates, infants, and adults, respectively. Both qualitative and quantitative evaluations on simulated and real datasets consistently demonstrate the superior performance of our ABCnet in both accuracy and efficiency, compared with popularly available methods.

Performance investigations of filtering methods for T1 and T2 weighted infant brain MR images

Performance investigations of filtering methods for T1 and T2 weighted infant brain MR images

Basketball side cut and jumping shot biomechanical analysis as ACL injury screening

To better understand early brain development, accurate segmentation of infant brain MR images into regions of interest, such as white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF), is one of the most important steps. In the first postnatal year, brain development can be divided into three distinct phases due to myelination and maturation process, i.e., infantile phase (≤ 5 months), isointense phase (6–8 months), and early adult-like phase (≥ 9 months). Among these three phases, the isointense phase exhibits extremely low tissue contrast in both T1-weighted and T2-weighted images, making tissue segmentation extremely challenging. To address this issue, inspired by prior domain knowledge, we developed an anatomy-guided joint tissue segmentation and topological correction framework for 6-month infant brain segmentation, which was implemented with random forest and deep neural network technologies. Experiments showed the advantages of the proposed framework and also demonstrated that anatomical guidance is a key direction to explore for 6-month infant brain segmentation. Our method is available in iBEAT V2.0 Cloud (http://www.ibeat.cloud).

Topological correction of infant white matter surfaces using anatomically constrained convolutional neural network

Reconstruction of accurate cortical surfaces without topological errors (i.e., handles and holes) from infant brain MR images is very important in early brain development studies. However, infant brain MR images typically suffer extremely low tissue contrast and dynamic imaging appearance patterns. Thus, it is inevitable to have large amounts of topological errors in the segmented infant brain tissue images, which lead to inaccurately reconstructed cortical surfaces with topological errors. To address this issue, inspired by recent advances in deep learning, we propose an anatomically constrained network for topological correction on infant cortical surfaces. Specifically, in our method, we first locate regions of potential topological defects by leveraging a topology-preserving level set method. Then, we propose an anatomically constrained network to correct those candidate voxels in the located regions. Since infant cortical surfaces often contain large and complex handles or holes, it is difficult to completely correct all errors using one-shot correction. Therefore, we further enroll these two steps into an iterative framework to gradually correct large topological errors. To the best of our knowledge, this is the first work to introduce deep learning approach for topological correction of infant cortical surfaces. We compare our method with the state-of-the-art methods on both simulated topological errors and real topological errors in human infant brain MR images. Moreover, we also validate our method on the infant brain MR images of macaques. All experimental results show the superior performance of the proposed method.

Hippocampal Segmentation From Longitudinal Infant Brain MR Images via Classification-Guided Boundary Regression

Hippocampal segmentation from infant brain MR images is indispensable for studying early brain development. However, most of the hippocampal segmentation methods were developed for population-based adult brain images, which are not suitable for longitudinal infant brain images acquired in the first year of life due to the low image contrast and variable development patterns of the hippocampal structure. To address these challenges, we propose a classification-guided boundary regression method to first detect hippocampal boundaries in the longitudinal infant brain images and then use those detected boundaries to guide the deformable model for final segmentation. Specifically, we first employ a classification-guided regression forest to predict the 3D displacements from individual image voxels to the potential hippocampal boundaries. These predicted displacements then determine the boundary maps by a voting strategy. Second, we iteratively enhance the voted hippocampal boundary map by incorporating the spatial context information given the tentative boundary estimation of the current time point. Besides, the longitudinal context information from all time points of the temporal sequence of the same subject (i.e., given their tentative segmentation results) is also utilized to facilitate accurate segmentation. Finally, a deformable model is applied to the enhanced voted boundary maps for achieving the longitudinal hippocampal segmentation. The experiments on infant brain MR images acquired from 2-week-old to 1-year-old show promising hippocampal segmentation results, indicating the applicability of our method in early brain development study.

Learning-based deformable registration for infant MRI by integrating random forest with auto-context model.

Accurately analyzing the rapid structural evolution of human brain in the first year of life is a key step in early brain development studies, which requires accurate deformable image registration. However, due to (a) dynamic appearance and (b) large anatomical changes, very few methods in the literature can work well for the registration of two infant brain MR images acquired at two arbitrary development phases, such as birth and one-year-old. To address these challenging issues, we propose a learning-based registration method, which can handle the anatomical structures and the appearance changes between the two infant brain MR images with possible time gap. Specifically, in the training stage, we employ a multioutput random forest regression and auto-context model to learn the evolution of anatomical shape and appearance from a training set of longitudinal infant images. To make the learning procedure more robust, we further harness the multimodal MR imaging information. Then, in the testing stage, for registering the two new infant images scanned at two different development phases, the learned model will be used to predict both the deformation field and appearance changes between the images under registration. After that, it becomes much easier to deploy any conventional image registration method to complete the remaining registration since the above-mentioned challenges for state-of-the-art registration methods have been well addressed. We have applied our proposed registration method to intersubject registration of infant brain MR images acquired at 2-week-old, 3-month-old, 6-month-old, and 9-month-old with the images acquired at 12-month-old. Promising registration results have been achieved in terms of registration accuracy, compared with the counterpart nonlearning based registration methods. The proposed new learning-based registration method have tackled the challenging issues in registering infant brain images acquired from the first year of life, by leveraging the multioutput random forest regression with auto-context model, which can learn the evolution of shape and appearance from a training set of longitudinal infant images. Thus, for the new infant image, its deformation field to the template and also its template-like appearances can be predicted by the learned models. We have extensively compared our method with state-of-the-art deformable registration methods, as well as multiple variants of our method, which show that our method can achieve higher accuracy even for the difficult cases with large appearance and shape changes between subject and template images.

Accurate Anatomical Landmark Detection Based on Importance Sampling for Infant Brain MR Images

Accurate Anatomical Landmark Detection Based on Importance Sampling for Infant Brain MR Images

Automatic segmentation of infant brain MR images: With special reference to myelinated white matter

Automatic segmentation of infant brain images is faced with numerous challenges like poor image contrast, motion artifacts, and changes caused by progressive myelination of the infant brain. Since timely myelination points to normal brain maturity, monitoring the progress and degree of myelination is clinically significant. However, most of the existing segmentation methods do not segment myelinated portions of the infant brain. In this paper, we propose a segmentation approach focused on segmenting the myelinated white matter tissue in T1-weighted magnetic resonance images of the infant brain. The novelty of the algorithm lies in the introduction of a weighted localized Tsallis entropy based thresholding method. The proposed method is also tested on older babies beyond the one-year age mark to verify its utility and robustness. It is seen that the mean Dice coefficients obtained for myelin segmentation by the proposed weighted localized method are higher than that of the other methods, namely, the conventional Tsallis entropy thresholding and modified localized method.

LATEST: Local AdapTivE and Sequential Training for Tissue Segmentation of Isointense Infant Brain MR Images.

Accurate segmentation of isointense infant (~6 months of age) brain MRIs is of great importance, however, a very challenging task, due to extremely low tissue contrast caused by ongoing myelination processes. In this work, we propose a novel learning method based on Local AdapTivE and Sequential Training (LATEST) for segmentation. Specifically, random forest technique is employed to train a local classifier (a single decision tree) for each voxel in the common space based on the neighboring training samples from atlases. Then, for each given voxel, all trained nearby individual classifiers (decision trees) are grouped together to form a forest. Moreover, the estimated probabilities are further used as additional source images to train the next set of local classifiers for refining tissue classification. By iteratively training the subsequent classifiers based on the updated tissue probability maps, a sequence of local classifiers can be built for accurate tissue segmentation.

Scalable joint segmentation and registration framework for infant brain images

The first year of life is the most dynamic and perhaps the most critical phase of postnatal brain development. The ability to accurately measure structure changes is critical in early brain development study, which highly relies on the performances of image segmentation and registration techniques. However, either infant image segmentation or registration, if deployed independently, encounters much more challenges than segmentation/registration of adult brains due to dynamic appearance change with rapid brain development. In fact, image segmentation and registration of infant images can assists each other to overcome the above challenges by using the growth trajectories (i.e., temporal correspondences) learned from a large set of training subjects with complete longitudinal data. Specifically, a one-year-old image with ground-truth tissue segmentation can be first set as the reference domain. Then, to register the infant image of a new subject at earlier age, we can estimate its tissue probability maps, i.e., with sparse patch-based multi-atlas label fusion technique, where only the training images at the respective age are considered as atlases since they have similar image appearance. Next, these probability maps can be fused as a good initialization to guide the level set segmentation. Thus, image registration between the new infant image and the reference image is free of difficulty of appearance changes, by establishing correspondences upon the reasonably segmented images. Importantly, the segmentation of new infant image can be further enhanced by propagating the much more reliable label fusion heuristics at the reference domain to the corresponding location of the new infant image via the learned growth trajectories, which brings image segmentation and registration to assist each other. It is worth noting that our joint segmentation and registration framework is also flexible to handle the registration of any two infant images even with significant age gap in the first year of life, by linking their joint segmentation and registration through the reference domain. Thus, our proposed joint segmentation and registration method is scalable to various registration tasks in early brain development studies. Promising segmentation and registration results have been achieved for infant brain MR images aged from 2-week-old to 1-year-old, indicating the applicability of our method in early brain development study.

Consistent Spatial-Temporal Longitudinal Atlas Construction for Developing Infant Brains.

Brain atlases are an essential component in understanding the dynamic cerebral development, especially for the early postnatal period. However, longitudinal atlases are rare for infants, and the existing ones are generally limited by their fuzzy appearance. Moreover, since longitudinal atlas construction is typically performed independently over time, the constructed atlases often fail to preserve temporal consistency. This problem is further aggravated for infant images since they typically have low spatial resolution and insufficient tissue contrast. In this paper, we propose a novel framework for consistent spatial-temporal construction of longitudinal atlases for developing infant brain MR images. Specifically, for preserving structural details, the atlas construction is performed in spatial-temporal wavelet domain simultaneously. This is achieved by a patch-based combination of results from each frequency subband. Compared with the existing infant longitudinal atlases, our experimental results indicate that our approach is able to produce longitudinal atlases with richer structural details and also better longitudinal consistency, thus leading to higher performance when used for spatial normalization of a group of infant brain images.

Concatenated spatially-localized random forests for hippocampus labeling in adult and infant MR brain images

Automatic labeling of the hippocampus in brain MR images is highly demanded, as it has played an important role in imaging-based brain studies. However, accurate labeling of the hippocampus is still challenging, partially due to the ambiguous intensity boundary between the hippocampus and surrounding anatomies. In this paper, we propose a concatenated set of spatially-localized random forests for multi-atlas-based hippocampus labeling of adult/infant brain MR images. The contribution in our work is two-fold. First, each forest classifier is trained to label just a specific sub-region of the hippocampus, thus enhancing the labeling accuracy. Second, a novel forest selection strategy is proposed, such that each voxel in the test image can automatically select a set of optimal forests, and then dynamically fuses their respective outputs for determining the final label. Furthermore, we enhance the spatially-localized random forests with the aid of the auto-context strategy. In this way, our proposed learning framework can gradually refine the tentative labeling result for better performance. Experiments show that, regarding the large datasets of both adult and infant brain MR images, our method owns satisfactory scalability by segmenting the hippocampus accurately and efficiently.

Isointense Infant Brain Segmentation by Stacked Kernel Canonical Correlation Analysis.

Segmentation of isointense infant brain (at ~6-months-old) MR images is challenging due to the ongoing maturation and myelination process in the first year of life. In particular, signal contrast between white and gray matters inverses around 6 months of age, where brain tissues appear isointense and hence exhibit extremely low tissue contrast, thus posing significant challenges for automated segmentation. In this paper, we propose a novel segmentation method to address the above-mentioned challenges based on stacked kernel canonical correlation analysis (KCCA). Our main idea is to utilize the 12-month-old brain image with high tissue contrast to guide the segmentation of 6-month-old brain images with extremely low contrast. Specifically, we use KCCA to learn the common feature representations for both 6-month-old and the subsequent 12-month-old brain images of same subjects to make their features comparable in the common space. Note that the longitudinal 12-month-old brain images are not required in the testing stage, and they are required only in the KCCA based training stage to provide a set of longitudinal 6- and 12-month-old image pairs for training. Moreover, for optimizing the common feature representations, we propose a stacked KCCA mapping, instead of using only the conventional one-step of KCCA mapping. In this way, we can better use the 12-month-old brain images as multiple atlases to guide the segmentation of isointense brain images. Specifically, sparse patch-based multi-atlas labeling is used to propagate tissue labels in the (12-month-old) atlases and segment isointense brain images by measuring patch similarity between testing and atlas images with their learned common features. The proposed method was evaluated on 20 isointense brain images via leave-one-out cross-validation, showing much better performance than the state-of-the-art methods.

LINKS: Learning-based multi-source IntegratioN frameworK for Segmentation of infant brain images

Segmentation of infant brain MR images is challenging due to insufficient image quality, severe partial volume effect, and ongoing maturation and myelination processes. In the first year of life, the image contrast between white and gray matters of the infant brain undergoes dramatic changes. In particular, the image contrast is inverted around 6–8months of age, and the white and gray matter tissues are isointense in both T1- and T2-weighted MR images and thus exhibit the extremely low tissue contrast, which poses significant challenges for automated segmentation. Most previous studies used multi-atlas label fusion strategy, which has the limitation of equally treating the different available image modalities and is often computationally expensive. To cope with these limitations, in this paper, we propose a novel learning-based multi-source integration framework for segmentation of infant brain images. Specifically, we employ the random forest technique to effectively integrate features from multi-source images together for tissue segmentation. Here, the multi-source images include initially only the multi-modality (T1, T2 and FA) images and later also the iteratively estimated and refined tissue probability maps of gray matter, white matter, and cerebrospinal fluid. Experimental results on 119 infants show that the proposed method achieves better performance than other state-of-the-art automated segmentation methods. Further validation was performed on the MICCAI grand challenge and the proposed method was ranked top among all competing methods. Moreover, to alleviate the possible anatomical errors, our method can also be combined with an anatomically-constrained multi-atlas labeling approach for further improving the segmentation accuracy.

Simultaneous and consistent labeling of longitudinal dynamic developing cortical surfaces in infants.

The human cerebral cortex develops extremely dynamically in the first 2years of life. Accurate and consistent parcellation of longitudinal dynamic cortical surfaces during this critical stage is essential to understand the early development of cortical structure and function in both normal and high-risk infant brains. However, directly applying the existing methods developed for the cross-sectional studies often generates longitudinally-inconsistent results, thus leading to inaccurate measurements of the cortex development. In this paper, we propose a new method for accurate, consistent, and simultaneous labeling of longitudinal cortical surfaces in the serial infant brain MR images. The proposed method is explicitly formulated as a minimization problem with an energy function that includes a data fitting term, a spatial smoothness term, and a temporal consistency term. Specifically, inspired by multi-atlas based label fusion, the data fitting term is designed to integrate the contributions from multi-atlas surfaces adaptively, according to the similarities of their local cortical folding with that of the subject cortical surface. The spatial smoothness term is then designed to adaptively encourage label smoothness based on the local cortical folding geometries, i.e., allowing label discontinuity at sulcal bottoms (which often are the boundaries of cytoarchitecturally and functionally distinct regions). The temporal consistency term is to adaptively encourage the label consistency among the temporally-corresponding vertices, based on their similarity of local cortical folding. Finally, the entire energy function is efficiently minimized by a graph cuts method. The proposed method has been applied to the parcellation of longitudinal cortical surfaces of 13 healthy infants, each with 6 serial MRI scans acquired at 0, 3, 6, 9, 12 and 18months of age. Qualitative and quantitative evaluations demonstrated both accuracy and longitudinal consistency of the proposed method. By using our method, for the first time, we reveal several hitherto unseen properties of the dynamic and regionally heterogeneous development of the cortical surface area in the first 18months of life.

Measuring the dynamic longitudinal cortex development in infants by reconstruction of temporally consistent cortical surfaces

Quantitative measurement of the dynamic longitudinal cortex development during early postnatal stages is of great importance to understand the early cortical structural and functional development. Conventional methods usually reconstruct the cortical surfaces of longitudinal images from the same subject independently, which often generate longitudinally-inconsistent cortical surfaces and thus lead to inaccurate measurement of cortical changes, especially for vertex-wise mapping of cortical development. This paper aims to address this problem by presenting a method to reconstruct temporally-consistent cortical surfaces from longitudinal infant brain MR images, for accurate and consistent measurement of the dynamic cortex development in infants. Specifically, the longitudinal development of the inner cortical surface is first modeled by a deformable growth sheet with elasto-plasticity property to establish longitudinally smooth correspondences of the inner cortical surfaces. Then, the modeled longitudinal inner cortical surfaces are jointly deformed to locate both inner and outer cortical surfaces with a spatial–temporal deformable surface method. The method has been applied to 13 healthy infants, each with 6 serial MR scans acquired at 2weeks, 3months, 6months, 9months, 12months and 18months of age. Experimental results showed that our method with the incorporated longitudinal constraints can reconstruct the longitudinally-dynamic cortical surfaces from serial infant MR images more consistently and accurately than the previously published methods. By using our method, for the first time, we can characterize the vertex-wise longitudinal cortical thickness development trajectory at multiple time points in the first 18months of life. Specifically, we found the highly age-related and regionally-heterogeneous developmental trajectories of the cortical thickness during this period, with the cortical thickness increased most from 3 to 6months (16.2%) and least from 9 to 12months (less than 0.1%). Specifically, the central sulcus only underwent significant increase of cortical thickness from 6 to 9months and the occipital cortex underwent significant increase from 0 to 9months, while the frontal, temporal and parietal cortices grew continuously in this first 18months of life. The adult-like spatial patterns of cortical thickness were generally present at 18months of age. These results provided detailed insights into the dynamic trajectory of the cortical thickness development in infants.