Computational methods for prediction of the dynamic and complex development of the infant cerebral cortex are critical and highly desired for a better understanding of early brain development in health and disease. Although a few methods have been proposed, they are limited to predicting cortical surface maps at predefined ages and require a large amount of strictly paired longitudinal data at these ages for model training. However, longitudinal infant images are typically acquired at highly irregular and nonuniform scanning ages, thus leading to limited training data for these methods and low flexibility and accuracy. To address these issues, we propose a flexible framework for individualized prediction of cortical surface maps at arbitrary ages during infancy. The central idea is that a cortical surface map can be considered as an entangled representation of two distinct components: 1) the identity-related invariant features, which preserve the individual identity and 2) the age-related features, which reflect the developmental patterns. Our framework, called intensive triplet autoencoder, extracts the mixed latent feature and further disentangles it into two components with an attention-based module. Identity recognition and age estimation tasks are introduced as supervision for a reliable disentanglement. Thus, we can obtain the target individualized cortical property maps with disentangled identity-related information with specific age-related information. Moreover, an adversarial learning strategy is integrated to achieve a vivid and realistic prediction. Extensive experiments validate our method's superior capability in predicting early developing cortical surface maps flexibly and precisely, in comparison with existing methods.

Alzheimer's disease (AD) is a degenerative mental disorder of the central nervous system that affects people's ability of daily life. Unfortunately, there is currently no known cure for AD. Thus, the early detection of AD plays a key role in preventing and controlling its progression. Magnetic resonance imaging (MRI)-based measures of cerebral atrophy are regarded as valid markers of the AD state. As one of representative methods for measuring brain atrophy, image registration technique has been widely adopted for AD diagnosis. However, AD detection is sensitive to the accuracy of image registration. To address this problem, an AD assistant diagnosis framework based on joint registration and classification is proposed. Specifically, in order to capture more local deformation information, we propose a novel patch-based joint brain image registration and classification network (RClaNet) to estimate the local dense deformation fields (DDF) and disease risk probability maps that explain high-risk areas for AD patients. RClaNet consists of a registration network and a classification network, in which the deformation field from registration network is fed into the classification network to enhance the prediction accuracy of the disease. Then, the exponential distance weighting method is used to obtain the global DDF and the global disease risk probability map, and it can remove grid-like artifacts by uniformly weighting method. Finally, the global classification network uses the global disease risk probability map for the early detection of AD. We evaluate the proposed method on the OASIS-3, AIBL and ADNI datasets, and experimental results show that the proposed RClaNet achieves superior registration performances than several state-of-the-art methods. Early diagnosis of AD using the global disease risk probability map also yielded competitive results. To demonstrate the generality, we also evaluate the proposed method on a COVID-19 dataset and achieve decent registration and classification results. These experiments prove that the deformation information in the registration process can be used to characterize subtle changes of degenerative diseases and further assist clinicians in diagnosis.

Fetal Magnetic Resonance Imaging (MRI) is challenged by fetal movements and maternal breathing. Although fast MRI sequences allow artifact free acquisition of individual 2D slices, motion frequently occurs in the acquisition of spatially adjacent slices. Motion correction for each slice is thus critical for the reconstruction of 3D fetal brain MRI. In this paper, we propose a novel multi-task learning framework that adopts a coarse-to-fine strategy to jointly learn the pose estimation parameters for motion correction and tissue segmentation map of each slice in fetal MRI. Particularly, we design a regression-based segmentation loss as a deep supervision to learn anatomically more meaningful features for pose estimation and segmentation. In the coarse stage, a U-Net-like network learns the features shared for both tasks. In the refinement stage, to fully utilize the anatomical information, signed distance maps constructed from the coarse segmentation are introduced to guide the feature learning for both tasks. Finally, iterative incorporation of the signed distance maps further improves the performance of both regression and segmentation progressively. Experimental results of cross-validation across two different fetal datasets acquired with different scanners and imaging protocols demonstrate the effectiveness of the proposed method in reducing the pose estimation error and obtaining superior tissue segmentation results simultaneously, compared with state-of-the-art methods.

Brain tissue segmentation is essential for neuroscience and clinical studies. However, segmentation on longitudinal data is challenging due to dynamic brain changes across the lifespan. Previous researches mainly focus on self-supervision with regularizations and will lose longitudinal generalization when fine-tuning on a specific age group. In this paper, we propose a dual meta-learning paradigm to learn longitudinally consistent representations and persist when fine-tuning. Specifically, we learn a plug-and-play feature extractor to extract longitudinal-consistent anatomical representations by meta-feature learning and a well-initialized task head for fine-tuning by meta-initialization learning. Besides, two class-aware regularizations are proposed to encourage longitudinal consistency. Experimental results on the iSeg2019 and ADNI datasets demonstrate the effectiveness of our method. Our code is available at https://github.com/ladderlab-xjtu/DuMeta.

Segmenting breast tumors from dynamic contrast-enhanced magnetic resonance (DCE-MR) images is a critical step for early detection and diagnosis of breast cancer. However, variable shapes and sizes of breast tumors, as well as inhomogeneous background, make it challenging to accurately segment tumors in DCE-MR images. Therefore, in this article, we propose a novel tumor-sensitive synthesis module and demonstrate its usage after being integrated with tumor segmentation. To suppress false-positive segmentation with similar contrast enhancement characteristics to true breast tumors, our tumor-sensitive synthesis module can feedback differential loss of the true and false breast tumors. Thus, by following the tumor-sensitive synthesis module after the segmentation predictions, the false breast tumors with similar contrast enhancement characteristics to the true ones will be effectively reduced in the learned segmentation model. Moreover, the synthesis module also helps improve the boundary accuracy while inaccurate predictions near the boundary will lead to higher loss. For the evaluation, we build a very large-scale breast DCE-MR image dataset with 422 subjects from different patients, and conduct comprehensive experiments and comparisons with other algorithms to justify the effectiveness, adaptability, and robustness of our proposed method.

Studies have shown that there is a tight connection between cognition skills and brain morphology during infancy. Nonetheless, it is still a great challenge to predict individual cognitive scores using their brain morphological features, considering issues like the excessive feature dimension, small sample size and missing data. Due to the limited data, a compact but expressive feature set is desirable as it can reduce the dimension and avoid the potential overfitting issue. Therefore, we pioneer the path signature method to further explore the essential hidden dynamic patterns of longitudinal cortical features. To form a hierarchical and more informative temporal representation, in this work, a novel cortical feature based path signature neural network (CF-PSNet) is proposed with stacked differentiable temporal path signature layers for prediction of individual cognitive scores. By introducing the existence embedding in path generation, we can improve the robustness against the missing data. Benefiting from the global temporal receptive field of CF-PSNet, characteristics consisted in the existing data can be fully leveraged. Further, as there is no need for the whole brain to work for a certain cognitive ability, a top K selection module is used to select the most influential brain regions, decreasing the model size and the risk of overfitting. Extensive experiments are conducted on an in-house longitudinal infant dataset within 9 time points. By comparing with several recent algorithms, we illustrate the state-of-the-art performance of our CF-PSNet (i.e., root mean square error of 0.027 with the time latency of 518 milliseconds for each sample).

Cephalometric analysis relies on accurate detection of craniomaxillofacial (CMF) landmarks from cone-beam computed tomography (CBCT) images. However, due to the complexity of CMF bony structures, it is difficult to localize landmarks efficiently and accurately. In this paper, we propose a deep learning framework to tackle this challenge by jointly digitalizing 105 CMF landmarks on CBCT images. By explicitly learning the local geometrical relationships between the landmarks, our approach extends Mask R-CNN for end-to-end prediction of landmark locations. Specifically, we first apply a detection network on a down-sampled 3D image to leverage global contextual information to predict the approximate locations of the landmarks. We subsequently leverage local information provided by higher-resolution image patches to refine the landmark locations. On patients with varying non-syndromic jaw deformities, our method achieves an average detection accuracy of 1.38± 0.95mm, outperforming a related state-of-the-art method.

Infancy is a critical period for the human brain development, and brain age is one of the indices for the brain development status associated with neuroimaging data. The difference between the predicted age based on neuroimaging and the chronological age can provide an important early indicator of deviation from the normal developmental trajectory. In this study, we utilize the Graph Convolutional Network (GCN) to predict the infant brain age based on resting-state fMRI data. The brain connectivity obtained from rs-fMRI can be represented as a graph with brain regions as nodes and functional connections as edges. However, since the brain connectivity is a fully connected graph with features on edges, current GCN cannot be directly used for it is a node-based method for sparse graphs. Hence, we propose an edge-based Graph Path Convolution (GPC) method, which aggregates the information from different paths and can be naturally applied on dense graphs. We refer the whole model as Brain Connectivity Graph Convolutional Networks (BC-GCN). Further, two upgraded network structures are proposed by including the residual and attention modules, referred as BC-GCN-Res and BC-GCN-SE to emphasize the information of the original data and enhance influential channels. Moreover, we design a two-stage coarse-to-fine framework, which determines the age group first and then predicts the age using group-specific BC-GCN-SE models. To avoid accumulated errors from the first stage, a cross-group training strategy is adopted for the second stage regression models. We conduct experiments on infant fMRI scans from 6 to 811 days of age. The coarse-to-fine framework shows significant improvements when being applied to several models (reducing error over 10 days). Comparing with state-of-the-art methods, our proposed model BC-GCN-SE with coarse-to-fine framework reduces the mean absolute error of the prediction from >70 days to 49.9 days. The code is now available at https://github.com/SCUT-Xinlab/BC-GCN.

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 onlinehttps://github.com/Barnonewdm/ACTA-Reg-Net.

Accurately segmenting teeth and identifying the corresponding anatomical landmarks on dental mesh models are essential in computer-aided orthodontic treatment. Manually performing these two tasks is time-consuming, tedious, and, more importantly, highly dependent on orthodontists' experiences due to the abnormality and large-scale variance of patients' teeth. Some machine learning-based methods have been designed and applied in the orthodontic field to automatically segment dental meshes (e.g., intraoral scans). In contrast, the number of studies on tooth landmark localization is still limited. This paper proposes a two-stage framework based on mesh deep learning (called TS-MDL) for joint tooth labeling and landmark identification on raw intraoral scans. Our TS-MDL first adopts an end-to-end iMeshSegNet method (i.e., a variant of the existing MeshSegNet with both improved accuracy and efficiency) to label each tooth on the downsampled scan. Guided by the segmentation outputs, our TS-MDL further selects each tooth's region of interest (ROI) on the original mesh to construct a light-weight variant of the pioneering PointNet (i.e., PointNet-Reg) for regressing the corresponding landmark heatmaps. Our TS-MDL was evaluated on a real-clinical dataset, showing promising segmentation and localization performance. Specifically, iMeshSegNet in the first stage of TS-MDL reached an averaged Dice similarity coefficient (DSC) at 0.964±0.054 , significantly outperforming the original MeshSegNet. In the second stage, PointNet-Reg achieved a mean absolute error (MAE) of 0.597±0.761 mm in distances between the prediction and ground truth for 66 landmarks, which is superior compared with other networks for landmark detection. All these results suggest the potential usage of our TS-MDL in orthodontics.

Accurate prediction of clinical scores (of neuropsychological tests) based on noninvasive structural magnetic resonance imaging (MRI) helps understand the pathological stage of dementia (e.g., Alzheimer's disease (AD)) and forecast its progression. Existing machine/deep learning approaches typically preselect dementia-sensitive brain locations for MRI feature extraction and model construction, potentially leading to undesired heterogeneity between different stages and degraded prediction performance. Besides, these methods usually rely on prior anatomical knowledge (e.g., brain atlas) and time-consuming nonlinear registration for the preselection of brain locations, thereby ignoring individual-specific structural changes during dementia progression because all subjects share the same preselected brain regions. In this article, we propose a multi-task weakly-supervised attention network (MWAN) for the joint regression of multiple clinical scores from baseline MRI scans. Three sequential components are included in MWAN: 1) a backbone fully convolutional network for extracting MRI features; 2) a weakly supervised dementia attention block for automatically identifying subject-specific discriminative brain locations; and 3) an attention-aware multitask regression block for jointly predicting multiple clinical scores. The proposed MWAN is an end-to-end and fully trainable deep learning model in which dementia-aware holistic feature learning and multitask regression model construction are integrated into a unified framework. Our MWAN method was evaluated on two public AD data sets for estimating clinical scores of mini-mental state examination (MMSE), clinical dementia rating sum of boxes (CDRSB), and AD assessment scale cognitive subscale (ADAS-Cog). Quantitative experimental results demonstrate that our method produces superior regression performance compared with state-of-the-art methods. Importantly, qualitative results indicate that the dementia-sensitive brain locations automatically identified by our MWAN method well retain individual specificities and are biologically meaningful.

Batch effect correction is an essential step in the integrative analysis of multiple single-cell RNA-sequencing (scRNA-seq) data. One state-of-the-art strategy for batch effect correction is via unsupervised or supervised detection of mutual nearest neighbors (MNNs). However, both types of methods only detect MNNs across batches of uncorrected data, where the large batch effects may affect the MNN search. To address this issue, we presented a batch effect correction approach via iterative supervised MNN (iSMNN) refinement across data after correction. Our benchmarking on both simulation and real datasets showed the advantages of the iterative refinement of MNNs on the performance of correction. Compared to popular alternative methods, our iSMNN is able to better mix the cells of the same cell type across batches. In addition, iSMNN can also facilitate the identification of differentially expressed genes (DEGs) that are relevant to the biological function of certain cell types. These results indicated that iSMNN will be a valuable method for integrating multiple scRNA-seq datasets that can facilitate biological and medical studies at single-cell level.

An increasing number of studies are leveraging unsupervised cross-modality synthesis to mitigate the limited label problem in training medical image segmentation models. They typically transfer ground truth annotations from a label-rich imaging modality to a label-lacking imaging modality, under an assumption that different modalities share the same anatomical structure information. However, since these methods commonly use voxel/pixel-wise cycle-consistency to regularize the mappings between modalities, high-level semantic information is not necessarily preserved. In this paper, we propose a novel anatomy-regularized representation learning approach for segmentation-oriented cross-modality image synthesis. It learns a common feature encoding across different modalities to form a shared latent space, where 1) the input and its synthesis present consistent anatomical structure information, and 2) the transformation between two images in one domain is preserved by their syntheses in another domain. We applied our method to the tasks of cross-modality skull segmentation and cardiac substructure segmentation. Experimental results demonstrate the superiority of our method in comparison with state-of-the-art cross-modality medical image segmentation methods.

To better understand early brain development in health and disorder, it is critical to accurately segment infant brain magnetic resonance (MR) images into white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF). Deep learning-based methods have achieved state-of-the-art performance; h owever, one of the major limitations is that the learning-based methods may suffer from the multi-site issue, that is, the models trained on a dataset from one site may not be applicable to the datasets acquired from other sites with different imaging protocols/scanners. To promote methodological development in the community, the iSeg-2019 challenge (http://iseg2019.web.unc.edu) provides a set of 6-month infant subjects from multiple sites with different protocols/scanners for the participating methods. T raining/validation subjects are from UNC (MAP) and testing subjects are from UNC/UMN (BCP), Stanford University, and Emory University. By the time of writing, there are 30 automatic segmentation methods participated in the iSeg-2019. In this article, 8 top-ranked methods were reviewed by detailing their pipelines/implementations, presenting experimental results, and evaluating performance across different sites in terms of whole brain, regions of interest, and gyral landmark curves. We further pointed out their limitations and possible directions for addressing the multi-site issue. We find that multi-site consistency is still an open issue. We hope that the multi-site dataset in the iSeg-2019 and this review article will attract more researchers to address the challenging and critical multi-site issue in practice.

Convolutional Neural Networks (CNNs) have achieved overwhelming success in learning-related problems for 2D/3D images in the Euclidean space. However, unlike in the Euclidean space, the shapes of many structures in medical imaging have an inherent spherical topology in a manifold space, e.g., the convoluted brain cortical surfaces represented by triangular meshes. There is no consistent neighborhood definition and thus no straightforward convolution/pooling operations for such cortical surface data. In this paper, leveraging the regular and hierarchical geometric structure of the resampled spherical cortical surfaces, we create the 1-ring filter on spherical cortical triangular meshes and accordingly develop convolution/pooling operations for constructing Spherical U-Net for cortical surface data. However, the regular nature of the 1-ring filter makes it inherently limited to model fixed geometric transformations. To further enhance the transformation modeling capability of Spherical U-Net, we introduce the deformable convolution and deformable pooling to cortical surface data and accordingly propose the Spherical Deformable U-Net (SDU-Net). Specifically, spherical offsets are learned to freely deform the 1-ring filter on the sphere to adaptively localize cortical structures with different sizes and shapes. We then apply the SDU-Net to two challenging and scientifically important tasks in neuroimaging: cortical surface parcellation and cortical attribute map prediction. Both applications validate the competitive performance of our approach in accuracy and computational efficiency in comparison with state-of-the-art methods.

Cortical surface registration is an essential step and prerequisite for surface-based neuroimaging analysis. It aligns cortical surfaces across individuals and time points to establish cross-sectional and longitudinal cortical correspondences to facilitate neuroimaging studies. Though achieving good performance, available methods are either time consuming or not flexible to extend to multiple or high dimensional features. Considering the explosive availability of large-scale and multimodal brain MRI data, fast surface registration methods that can flexibly handle multimodal features are desired. In this study, we develop a Superfast Spherical Surface Registration (S3Reg) framework for the cerebral cortex. Leveraging an end-to-end unsupervised learning strategy, S3Reg offers great flexibility in the choice of input feature sets and output similarity measures for registration, and meanwhile reduces the registration time significantly. Specifically, we exploit the powerful learning capability of spherical Convolutional Neural Network (CNN) to directly learn the deformation fields in spherical space and implement diffeomorphic design with "scaling and squaring" layers to guarantee topology-preserving deformations. To handle the polar-distortion issue, we construct a novel spherical CNN model using three orthogonal Spherical U-Nets. Experiments are performed on two different datasets to align both adult and infant multimodal cortical features. Results demonstrate that our S3Reg shows superior or comparable performance with state-of-the-art methods, while improving the registration time from 1 min to 10 sec.

Quantitative assessment of retinal layer thickness in spectral domain-optical coherence tomography (SD-OCT) images is vital for clinicians to determine the degree of ophthalmic lesions. However, due to the complex retinal tissues, high-level speckle noises and low intensity constraint, how to accurately recognize the retinal layer structure still remains a challenge. To overcome this problem, this paper proposes an adaptive-guided-coupling-probability level set method for retinal layer segmentation in SD-OCT images. Specifically, based on Bayes's theorem, each voxel probability representation is composed of two probability terms in our method. The first term is constructed as neighborhood Gaussian fitting distribution to characterize intensity information for each intra-retinal layer. The second one is boundary probability map generated by combining anatomical priors and adaptive thickness information to ensure surfaces evolve within a proper range. Then, the voxel probability representation is introduced into the proposed segmentation framework based on coupling probability level set to detect layer boundaries. A total of 1792 retinal B-scan images from 4 SD-OCT cubes in healthy eyes, 5 cubes in abnormal eyes with central serous chorioretinaopathy and 5 SD-OCT cubes in abnormal eyes with age-related macular disease are used to evaluate the proposed method. The experiment demonstrates that the segmentation results obtained by the proposed method have a good consistency with ground truth, and the proposed method outperforms six methods in the layer segmentation of uneven retinal SD-OCT images.

Compared to computed tomography (CT), magnetic resonance imaging (MRI) delineation of craniomaxillofacial (CMF) bony structures can avoid harmful radiation exposure. However, bony boundaries are blurry in MRI, and structural information needs to be borrowed from CT during the training. This is challenging since paired MRI-CT data are typically scarce. In this paper, we propose to make full use of unpaired data, which are typically abundant, along with a single paired MRI-CT data to construct a one-shot generative adversarial model for automated MRI segmentation of CMF bony structures. Our model consists of a cross-modality image synthesis sub-network, which learns the mapping between CT and MRI, and an MRI segmentation sub-network. These two sub-networks are trained jointly in an end-to-end manner. Moreover, in the training phase, a neighbor-based anchoring method is proposed to reduce the ambiguity problem inherent in cross-modality synthesis, and a feature-matching-based semantic consistency constraint is proposed to encourage segmentation-oriented MRI synthesis. Experimental results demonstrate the superiority of our method both qualitatively and quantitatively in comparison with the state-of-the-art MRI segmentation methods.

Effective fusion of structural magnetic resonance imaging (sMRI) and functional magnetic resonance imaging (fMRI) data has the potential to boost the accuracy of infant age prediction thanks to the complementary information provided by different imaging modalities. However, functional connectivity measured by fMRI during infancy is largely immature and noisy compared to the morphological features from sMRI, thus making the sMRI and fMRI fusion for infant brain analysis extremely challenging. With the conventional multimodal fusion strategies, adding fMRI data for age prediction has a high risk of introducing more noises than useful features, which would lead to reduced accuracy than that merely using sMRI data. To address this issue, we develop a novel model termed as disentangled-multimodal adversarial autoencoder (DMM-AAE) for infant age prediction based on multimodal brain MRI. Specifically, we disentangle the latent variables of autoencoder into common and specific codes to represent the shared and complementary information among modalities, respectively. Then, cross-reconstruction requirement and common-specific distance ratio loss are designed as regularizations to ensure the effectiveness and thoroughness of the disentanglement. By arranging relatively independent autoencoders to separate the modalities and employing disentanglement under cross-reconstruction requirement to integrate them, our DMM-AAE method effectively restrains the possible interference cross modalities, while realizing effective information fusion. Taking advantage of the latent variable disentanglement, a new strategy is further proposed and embedded into DMM-AAE to address the issue of incompleteness of the multimodal neuroimages, which can also be used as an independent algorithm for missing modality imputation. By taking six types of cortical morphometric features from sMRI and brain functional connectivity from fMRI as predictors, the superiority of the proposed DMM-AAE is validated on infant age (35 to 848 days after birth) prediction using incomplete multimodal neuroimages. The mean absolute error of the prediction based on DMM-AAE reaches 37.6 days, outperforming state-of-the-art methods. Generally, our proposed DMM-AAE can serve as a promising model for prediction with multimodal data.

Precisely labeling teeth on digitalized 3D dental surface models is the precondition for tooth position rearrangements in orthodontic treatment planning. However, it is a challenging task primarily due to the abnormal and varying appearance of patients' teeth. The emerging utilization of intraoral scanners (IOSs) in clinics further increases the difficulty in automated tooth labeling, as the raw surfaces acquired by IOS are typically low-quality at gingival and deep intraoral regions. In recent years, some pioneering end-to-end methods (e.g., PointNet) have been proposed in the communities of computer vision and graphics to consume directly raw surface for 3D shape segmentation. Although these methods are potentially applicable to our task, most of them fail to capture fine-grained local geometric context that is critical to the identification of small teeth with varying shapes and appearances. In this paper, we propose an end-to-end deep-learning method, called MeshSegNet, for automated tooth labeling on raw dental surfaces. Using multiple raw surface attributes as inputs, MeshSegNet integrates a series of graph-constrained learning modules along its forward path to hierarchically extract multi-scale local contextual features. Then, a dense fusion strategy is applied to combine local-to-global geometric features for the learning of higher-level features for mesh cell annotation. The predictions produced by our MeshSegNet are further post-processed by a graph-cut refinement step for final segmentation. We evaluated MeshSegNet using a real-patient dataset consisting of raw maxillary surfaces acquired by 3D IOS. Experimental results, performed 5-fold cross-validation, demonstrate that MeshSegNet significantly outperforms state-of-the-art deep learning methods for 3D shape segmentation.

Medical image segmentation is a key step for various applications, such as image-guided radiation therapy and diagnosis. Recently, deep neural networks provided promising solutions for automatic image segmentation; however, they often perform good on regular samples (i.e., easy-to-segment samples), since the datasets are dominated by easy and regular samples. For medical images, due to huge inter-subject variations or disease-specific effects on subjects, there exist several difficult-to-segment cases that are often overlooked by the previous works. To address this challenge, we propose a difficulty-aware deep segmentation network with confidence learning for end-to-end segmentation. The proposed framework has two main contributions: 1) Besides the segmentation network, we also propose a fully convolutional adversarial network for confidence learning to provide voxel-wise and region-wise confidence information for the segmentation network. We relax the adversarial learning to confidence learning by decreasing the priority of adversarial learning, so that we can avoid the training imbalance between generator and discriminator. 2) We propose a difficulty-aware attention mechanism to properly handle hard samples or hard regions considering structural information, which may go beyond the shortcomings of focal loss. We further propose a fusion module to selectively fuse the concatenated feature maps in encoder-decoder architectures. Experimental results on clinical and challenge datasets show that our proposed network can achieve state-of-the-art segmentation accuracy. Further analysis also indicates that each individual component of our proposed network contributes to the overall performance improvement.

Accurate segmentation of infant brain images into different regions of interest is one of the most important fundamental steps in studying early brain development. In the isointense phase (approximately 6-8 months of age), white matter and gray matter exhibit similar levels of intensities in magnetic resonance (MR) images, due to the ongoing myelination and maturation. This results in extremely low tissue contrast and thus makes tissue segmentation very challenging. Existing methods for tissue segmentation in this isointense phase usually employ patch-based sparse labeling on single modality. To address the challenge, we propose a novel 3-D multimodal fully convolutional network (FCN) architecture for segmentation of isointense phase brain MR images. Specifically, we extend the conventional FCN architectures from 2-D to 3-D, and, rather than directly using FCN, we intuitively integrate coarse (naturally high-resolution) and dense (highly semantic) feature maps to better model tiny tissue regions, in addition, we further propose a transformation module to better connect the aggregating layers; we also propose a fusion module to better serve the fusion of feature maps. We compare the performance of our approach with several baseline and state-of-the-art methods on two sets of isointense phase brain images. The comparison results show that our proposed 3-D multimodal FCN model outperforms all previous methods by a large margin in terms of segmentation accuracy. In addition, the proposed framework also achieves faster segmentation results compared to all other methods. Our experiments further demonstrate that: 1) carefully integrating coarse and dense feature maps can considerably improve the segmentation performance; 2) batch normalization can speed up the convergence of the networks, especially when hierarchical feature aggregations occur; and 3) integrating multimodal information can further boost the segmentation performance.

Neonatal magnetic resonance (MR) images typically have low spatial resolution and insufficient tissue contrast. Interpolation methods are commonly used to upsample the images for the subsequent analysis. However, the resulting images are often blurry and susceptible to partial volume effects. In this paper, we propose a novel longitudinally guided super-resolution (SR) algorithm for neonatal images. This is motivated by the fact that anatomical structures evolve slowly and smoothly as the brain develops after birth. We propose a strategy involving longitudinal regularization, similar to bilateral filtering, in combination with low-rank and total variation constraints to solve the ill-posed inverse problem associated with image SR. Experimental results on neonatal MR images demonstrate that the proposed algorithm recovers clear structural details and outperforms state-of-the-art methods both qualitatively and quantitatively.

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.

Accurate segmentation of pelvic organs is important for prostate radiation therapy. Modern radiation therapy starts to use a magnetic resonance image (MRI) as an alternative to computed tomography image because of its superior soft tissue contrast and also free of risk from radiation exposure. However, segmentation of pelvic organs from MRI is a challenging problem due to inconsistent organ appearance across patients and also large intrapatient anatomical variations across treatment days. To address such challenges, we propose a novel deep network architecture, called "Spatially varying sTochastic Residual AdversarIal Network" (STRAINet), to delineate pelvic organs from MRI in an end-to-end fashion. Compared to the traditional fully convolutional networks (FCN), the proposed architecture has two main contributions: 1) inspired by the recent success of residual learning, we propose an evolutionary version of the residual unit, i.e., stochastic residual unit, and use it to the plain convolutional layers in the FCN. We further propose long-range stochastic residual connections to pass features from shallow layers to deep layers; and 2) we propose to integrate three previously proposed network strategies to form a new network for better medical image segmentation: a) we apply dilated convolution in the smallest resolution feature maps, so that we can gain a larger receptive field without overly losing spatial information; b) we propose a spatially varying convolutional layer that adapts convolutional filters to different regions of interest; and c) an adversarial network is proposed to further correct the segmented organ structures. Finally, STRAINet is used to iteratively refine the segmentation probability maps in an autocontext manner. Experimental results show that our STRAINet achieved the state-of-the-art segmentation accuracy. Further analysis also indicates that our proposed network components contribute most to the performance.

Segmenting organs at risk from head and neck CT images is a prerequisite for the treatment of head and neck cancer using intensity modulated radiotherapy. However, accurate and automatic segmentation of organs at risk is a challenging task due to the low contrast of soft tissue and image artifact in CT images. Shape priors have been proved effective in addressing this challenging task. However, conventional methods incorporating shape priors often suffer from sensitivity to shape initialization and also shape variations across individuals. In this paper, we propose a novel approach to incorporate shape priors into a hierarchical learning-based model. The contributions of our proposed approach are as follows: 1) a novel mechanism for critical vertices identification is proposed to identify vertices with distinctive appearances and strong consistency across different subjects; 2) a new strategy of hierarchical vertex regression is also used to gradually locate more vertices with the guidance of previously located vertices; and 3) an innovative framework of joint shape and appearance learning is further developed to capture salient shape and appearance features simultaneously. Using these innovative strategies, our proposed approach can essentially overcome drawbacks of the conventional shape-based segmentation methods. Experimental results show that our approach can achieve much better results than state-of-the-art methods.

Computed tomography (CT) imaging is an essential tool in various clinical diagnoses and radiotherapy treatment planning. Since CT image intensities are directly related to positron emission tomography (PET) attenuation coefficients, they are indispensable for attenuation correction (AC) of the PET images. However, due to the relatively high dose of radiation exposure in CT scan, it is advised to limit the acquisition of CT images. In addition, in the new PET and magnetic resonance (MR) imaging scanner, only MR images are available, which are unfortunately not directly applicable to AC. These issues greatly motivate the development of methods for reliable estimate of CT image from its corresponding MR image of the same subject. In this paper, we propose a learning-based method to tackle this challenging problem. Specifically, we first partition a given MR image into a set of patches. Then, for each patch, we use the structured random forest to directly predict a CT patch as a structured output, where a new ensemble model is also used to ensure the robust prediction. Image features are innovatively crafted to achieve multi-level sensitivity, with spatial information integrated through only rigid-body alignment to help avoiding the error-prone inter-subject deformable registration. Moreover, we use an auto-context model to iteratively refine the prediction. Finally, we combine all of the predicted CT patches to obtain the final prediction for the given MR image. We demonstrate the efficacy of our method on two datasets: human brain and prostate images. Experimental results show that our method can accurately predict CT images in various scenarios, even for the images undergoing large shape variation, and also outperforms two state-of-the-art methods.

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.

This paper proposes a new energy minimization framework for simultaneous estimation of the bias field and segmentation of tissues for magnetic resonance images. The bias field is modeled as a linear combination of a set of basis functions, and thereby parameterized by the coefficients of the basis functions. We define an energy that depends on the coefficients of the basis functions, the membership functions of the tissues in the image, and the constants approximating the true signal from the corresponding tissues. This energy is convex in each of its variables. Bias field estimation and image segmentation are simultaneously achieved as the result of minimizing this energy. We provide an efficient iterative algorithm for energy minimization, which converges to the optimal solution at a fast rate. A salient advantage of our method is that its result is independent of initialization, which allows robust and fully automated application. The proposed method has been successfully applied to 3-Tesla MR images with desirable results. Comparisons with other approaches demonstrate the superior performance of this algorithm.