Deep learning has achieved remarkable progress, particularly in neuroimaging analysis. Deep learning applications have also been extended from adult to pediatric medical images, and thus, this paper aims to present a systematic review of this recent research. We first introduce the commonly used deep learning methods and architectures in neuroimaging, such as convolutional neural networks, auto-encoders, and generative adversarial networks. A non-exhaustive list of commonly used publicly available pediatric neuroimaging datasets and repositories are included, followed by a categorical review of recent works in pediatric MRI-based deep learning studies in the past five years. These works are categorized into recognizing neurodevelopmental disorders, identifying brain and tissue structures, estimating brain age/maturity, predicting neurodevelopment outcomes, and optimizing MRI brain imaging and analysis. Finally, we also discuss the recent achievements and challenges on these applications of deep learning to pediatric neuroimaging.

/pdf/applications-of-deep-learning-to-neurodevelopment-in-21uu6tog.pdf

Applications of Deep Learning to Neurodevelopment in Pediatric Imaging: Achievements and Challenges


 A robust, fast, and accurate segmentation of neonatal brain images is highly desired to better understand and detect changes during development and disease, specifically considering the rise in imaging studies for this cohort. Yet, the limited availability of ground truth datasets, lack of standardized acquisition protocols, and wide variations of head positioning in the scanner pose challenges for method development. A few automated image analysis pipelines exist for newborn brain MRI segmentation, but they often rely on time-consuming non-linear spatial registration procedures and require resampling to a common resolution, subject to loss of information due to interpolation and down-sampling. Without registration and image resampling, variations with respect to head positions and voxel resolutions have to be addressed differently. In deep-learning, external augmentations such as rotation, translation, and scaling are traditionally used to artificially expand the representation of spatial variability, which subsequently increases both the training dataset size and robustness. However, these transformations in the image space still require resampling, reducing accuracy specifically in the context of label interpolation. We recently introduced the concept of resolution-independence with the Voxel-size Independent Neural Network framework, VINN. Here, we extend this concept by additionally shifting all rigid-transforms into the network architecture with a four degree of freedom (4-DOF) transform module, enabling resolution-aware internal augmentations (VINNA) for deep learning. In this work we show that VINNA (i) significantly outperforms state-of-the-art external augmentation approaches, (ii) effectively addresses the head variations present specifically in newborn datasets, and (iii) retains high segmentation accuracy across a range of resolutions (0.5-1.0mm). Furthermore, the 4-DOF transform module together with internal augmentations is a powerful, general approach to implement spatial augmentation without requiring image or label interpolation. The specific network application to newborns will be made publicly available as VINNA4neonates.

VINNA for Neonates – Orientation Independence through Latent Augmentations

Compared to monetary rewards, depressive symptoms are specifically associated with abnormal social reward processing. In addition, individuals with melancholic depression may exhibit more significant reward-related impairments. However, there is still limited understanding of the specific alterations in social reward processing in individuals with melancholic depression. 

Aberrant social reward dynamics in individuals with melancholic major depressive disorder: An ERP study

Reproducibility of neuroimaging research on infant brain development remains limited due to highly variable protocols and processing approaches. Progress towards reproducible pipelines is limited by a lack of benchmarks such as gold standard brain segmentations. Addressing this core limitation, we constructed the Baby Open Brains (BOBs) Repository, an open source resource comprising manually curated and expert-reviewed infant brain segmentations. Markers and expert reviewers manually segmented anatomical MRI data from 71 infant imaging visits across 51 participants, using both T1w and T2w images per visit. Anatomical images showed dramatic differences in myelination and intensities across the 1 to 9 month age range, emphasizing the need for densely sampled gold standard manual segmentations in these ages. The BOBs repository is publicly available through the Masonic Institute for the Developing Brain (MIDB) Open Data Initiative, which links S3 storage, Datalad for version control, and BrainBox for visualization. This repository represents an open-source paradigm, where new additions and changes can be added, enabling a community-driven resource that will improve over time and extend into new ages and protocols. These manual segmentations and the ongoing repository provide a benchmark for evaluating and improving pipelines dependent upon segmentations in the youngest populations. As such, this repository provides a vitally needed foundation for early-life large-scale studies such as HBCD. 

Baby Open Brains: An Open-Source Repository of Infant Brain Segmentations

In this paper, a critical analysis of recent trends and techniques for tissue segmentation of an pediatric brain Magnetic Resonance Imaging (MRI) is performed. A significant amount of research has recently been conducted in the field of medical image analysis. In medical image analysis, MRI is regarded as one of the primary imaging modalities. MRI is capable of providing a clear view of various organs in depth. Tissue segmentation is an important process in brain research, especially when the subjects are infants and defining normalcy is difficult. Our paper focuses on recent developments in this field. Deep learning technological advancements are assisting this field in moving forward with dataset availability via challenges such as iseg-2017 and iseg-2019. This paper compares methodology, dataset, and results obtained by various methods. The paper also discusses the limitations of all available approaches as well as possible future directions in the field. 

A Review of Recent Advancements in Infant Brain MRI Segmentation Using Deep Learning Approaches

Infant brain magnetic resonance imaging (MRI) is a promising approach for studying early neurodevelopment. However, segmenting small regions such as limbic structures is challenging due to their low inter-regional contrast and high curvature. MRI studies of the adult brain have successfully applied deep learning techniques to segment limbic structures, and similar deep learning models are being leveraged for infant studies. However, these deep learning-based infant MRI segmentation models have generally been derived from small datasets, and may suffer from generalization problems. Moreover, the accuracy of segmentations derived from these deep learning models relative to more standard Expectation-Maximization approaches has not been characterized. To address these challenges, we leveraged a large, public infant MRI dataset (n = 473) and the transfer-learning technique to first pre-train a deep convolutional neural network model on two limbic structures: amygdala and hippocampus. Then we used a leave-one-out cross-validation strategy to fine-tune the pre-trained model and evaluated it separately on two independent datasets with manual labels. We term this new approach the Infant Deep learning SEGmentation Framework (ID-Seg). ID-Seg performed well on both datasets with a mean dice similarity score (DSC) of 0.87, a mean intra-class correlation (ICC) of 0.93, and a mean average surface distance (ASD) of 0.31 mm. Compared to the Developmental Human Connectome pipeline (dHCP) pipeline, ID-Seg significantly improved segmentation accuracy. In a third infant MRI dataset (n = 50), we used ID-Seg and dHCP separately to estimate amygdala and hippocampus volumes and shapes. The estimates derived from ID-seg, relative to those from the dHCP, showed stronger associations with behavioral problems assessed in these infants at age 2. In sum, ID-Seg consistently performed well on two different datasets with an 0.87 DSC, however, multi-site testing and extension for brain regions beyond the amygdala and hippocampus are still needed. 

/pdf/id-seg-an-infant-deep-learning-based-segmentation-framework-19u0r32y.pdf

ID-Seg: an infant deep learning-based segmentation framework to improve limbic structure estimates

Blunted responses to reward feedback have been linked to major depressive disorder (MDD) and depression risk. Using a monetary incentive delay task (win, loss, break-even), we investigated the impact of family risk for depression and lifetime history of MDD and anxiety disorder with 72-channel electroencephalograms (EEG) recorded from 29 high-risk and 32 low-risk individuals (15-58 years, 30 male). Linked-mastoid surface potentials (ERPs) and their corresponding reference-free current source densities (CSDs) were quantified by temporal principal components analysis (PCA). Each PCA solution revealed a midfrontal feedback negativity (FN; peak around 310 ms) and a posterior feedback-P3 (fb-P3; 380 ms) as two distinct reward processing stages. Unbiased permutation tests and multilevel modeling of component scores revealed greater FN to loss than win and neutral for all stratification groups, confirming FN sensitivity to valence. Likewise, all groups had greater fb-P3 to win and loss than neutral, confirming that fb-P3 indexes motivational salience and allocation of attention. By contrast, group effects were subtle, dependent on data transformation (ERP, CSD), and did not confirm reduced FN or fb-P3 for at-risk individuals. Instead, CSD-based fb-P3 was overall reduced in individuals with than without MDD history, whereas ERP-based fb-P3 was greater for high-risk individuals than for low-risk individuals for monetary, but not neutral outcomes. While the present findings do not support blunted reward processing in depression and depression risk, our side-by-side comparison underscores how the EEG reference choice affects the characterization of subtle group differences, strongly advocating the use of reference-free techniques.

Feedback negativity and feedback-related P3 in individuals at risk for depression: Comparing surface potentials and current source densities.

56. Charting the Influence of Maternal Depression Throughout Pregnancy on Neonatal Thalamocortical White Matter Connectivity

21. How Genes and Environments Modify Intergenerational Risk for Depression – Using Polygenic Scores to Translate Between Rodents and Humans

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ID-Seg: an infant deep learning-based segmentation framework to improve limbic structure estimates

Feedback negativity and feedback-related P3 in individuals at risk for depression: Comparing surface potentials and current source densities.

56. Charting the Influence of Maternal Depression Throughout Pregnancy on Neonatal Thalamocortical White Matter Connectivity

21. How Genes and Environments Modify Intergenerational Risk for Depression – Using Polygenic Scores to Translate Between Rodents and Humans