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Weili Lin

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53 papers
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53

YNIMG Journal 2025 Journal Article

STF: A spherical transformer for versatile cortical surfaces applications

  • Jiale Cheng
  • Fenqiang Zhao
  • Zhengwang Wu
  • Xinrui Yuan
  • Li Wang
  • John H Gilmore
  • Weili Lin
  • Xin Zhang

Inspired by the remarkable success of attention mechanisms in various applications, there is a growing need to adapt the Transformer architecture from conventional Euclidean domains to non-Euclidean spaces commonly encountered in medical imaging. Structures such as brain cortical surfaces, represented by triangular meshes, exhibit spherical topology and present unique challenges. To address this, we propose the Spherical Transformer (STF), a versatile backbone that leverages self-attention for analyzing cortical surface data. Our approach involves mapping cortical surfaces onto a sphere, dividing them into overlapping patches, and tokenizing both patches and vertices. By performing self-attention at patch and vertex levels, the model simultaneously captures global dependencies and preserves fine-grained contextual information within each patch. Overlapping regions between neighboring patches naturally enable efficient cross-patch information sharing. To handle longitudinal cortical surface data, we introduce the spatiotemporal self-attention mechanism, which jointly captures spatial context and temporal developmental patterns within a single layer. This innovation enhances the representational power of the model, making it well-suited for dynamic surface data. We evaluate the Spherical Transformer on key tasks, including cognition prediction at the surface level and two vertex-level tasks: cortical surface parcellation and cortical property map prediction. Across these applications, our model consistently outperforms state-of-the-art methods, demonstrating its ability to effectively model global dependencies and preserve detailed spatial information. The results highlight its potential as a general-purpose framework for cortical surface analysis.

JBHI Journal 2024 Journal Article

A Unified Multi-Modality Fusion Framework for Deep Spatio-Spectral-Temporal Feature Learning in Resting-State fMRI Denoising

  • Minjoo Lim
  • Keun-Soo Heo
  • Jun-Mo Kim
  • Bogyeong Kang
  • Weili Lin
  • Han Zhang
  • Dinggang Shen
  • Tae-Eui Kam

Resting-state functional magnetic resonance imaging (rs-fMRI) is a commonly used functional neuroimaging technique to investigate the functional brain networks. However, rs-fMRI data are often contaminated with noise and artifacts that adversely affect the results of rs-fMRI studies. Several machine/deep learning methods have achieved impressive performance to automatically regress the noise-related components decomposed from rs-fMRI data, which are expressed as the pairs of a spatial map and its associated time series. However, most of the previous methods individually analyze each modality of the noise-related components and simply aggregate the decision-level information (or knowledge) extracted from each modality to make a final decision. Moreover, these approaches consider only the limited modalities making it difficult to explore class-discriminative spectral information of noise-related components. To overcome these limitations, we propose a unified deep attentive spatio-spectral-temporal feature fusion framework. We first adopt a learnable wavelet transform module at the input-level of the framework to elaborately explore the spectral information in subsequent processes. We then construct a feature-level multi-modality fusion module to efficiently exchange the information from multi-modality inputs in the feature space. Finally, we design confidence-based voting strategies for decision-level fusion at the end of the framework to make a robust final decision. In our experiments, the proposed method achieved remarkable performance for noise-related component detection on various rs-fMRI datasets.

YNIMG Journal 2023 Journal Article

An attention-based context-informed deep framework for infant brain subcortical segmentation

  • Liangjun Chen
  • Zhengwang Wu
  • Fenqiang Zhao
  • Ya Wang
  • Weili Lin
  • Li Wang
  • Gang Li

Precise segmentation of subcortical structures from infant brain magnetic resonance (MR) images plays an essential role in studying early subcortical structural and functional developmental patterns and diagnosis of related brain disorders. However, due to the dynamic appearance changes, low tissue contrast, and tiny subcortical size in infant brain MR images, infant subcortical segmentation is a challenging task. In this paper, we propose a context-guided, attention-based, coarse-to-fine deep framework to precisely segment the infant subcortical structures. At the coarse stage, we aim to directly predict the signed distance maps (SDMs) from multi-modal intensity images, including T1w, T2w, and the ratio of T1w and T2w images, with an SDM-Unet, which can leverage the spatial context information, including the structural position information and the shape information of the target structure, to generate high-quality SDMs. At the fine stage, the predicted SDMs, which encode spatial-context information of each subcortical structure, are integrated with the multi-modal intensity images as the input to a multi-source and multi-path attention Unet (M2A-Unet) for achieving refined segmentation. Both the 3D spatial and channel attention blocks are added to guide the M2A-Unet to focus more on the important subregions and channels. We additionally incorporate the inner and outer subcortical boundaries as extra labels to help precisely estimate the ambiguous boundaries. We validate our method on an infant MR image dataset and on an unrelated neonatal MR image dataset. Compared to eleven state-of-the-art methods, the proposed framework consistently achieves higher segmentation accuracy in both qualitative and quantitative evaluations of infant MR images and also exhibits good generalizability in the neonatal dataset.

YNIMG Journal 2022 Journal Article

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

  • Liangjun Chen
  • Zhengwang Wu
  • Dan Hu
  • Ya Wang
  • Fenqiang Zhao
  • Tao Zhong
  • Weili Lin
  • Li Wang

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.

YNIMG Journal 2022 Journal Article

Deep attentive spatio-temporal feature learning for automatic resting-state fMRI denoising

  • Keun-Soo Heo
  • Dong-Hee Shin
  • Sheng-Che Hung
  • Weili Lin
  • Han Zhang
  • Dinggang Shen
  • Tae-Eui Kam

Resting-state functional magnetic resonance imaging (rs-fMRI) is a non-invasive functional neuroimaging modality that has been widely used to investigate functional connectomes in the brain. Since noise and artifacts generated by non-neuronal physiological activities are predominant in raw rs-fMRI data, effective noise removal is one of the most important preprocessing steps prior to any subsequent analysis. For rs-fMRI denoising, a common trend is to decompose rs-fMRI data into multiple components and then regress out noise-related components. Therefore, various machine learning techniques have been used in such analyses with predefined procedures and manually engineered features. However, the lack of a universal definition of a noise-related source or artifact complicates manual feature engineering. Manual feature selection can result in the failure to capture unknown types of noise. Furthermore, the possibility that the hand-crafted features will only work for the broader population (e.g., healthy adults) but not for "outliers" (e.g., infants or subjects that belong to a disease cohort) is quite high. In practice, we have limited knowledge of which features should be extracted; thus, multi-classifier assembly must be implemented to improve performance, although this process is quite time-consuming. However, in real rs-fMRI applications, fast and accurate automatic identification of noise-related components on different datasets is critical. To solve this problem, we propose a novel, automatic, and end-to-end deep learning framework dedicated to noise-related component identification via a faster and more effective multi-layer feature extraction strategy that learns deeply embedded spatio-temporal features of the components. In this study, we achieved remarkable performance on various rs-fMRI datasets, including multiple adult rs-fMRI datasets from different rs-fMRI studies and an infant rs-fMRI dataset, which is quite heterogeneous and differs from that of adults. Our proposed framework also dramatically increases the noise detection speed owing to its inherent ability for deep learning (< 1s for single-component classification). It can be easily integrated into any preprocessing pipeline, even those that do not use standard procedures but depend on alternative toolboxes.

YNIMG Journal 2021 Journal Article

The maturation and cognitive relevance of structural brain network organization from early infancy to childhood

  • Mackenzie Woodburn
  • Cheyenne L. Bricken
  • Zhengwang Wu
  • Gang Li
  • Li Wang
  • Weili Lin
  • Margaret A. Sheridan
  • Jessica R. Cohen

The interactions of brain regions with other regions at the network level likely provide the infrastructure necessary for cognitive processes to develop. Specifically, it has been theorized that in infancy brain networks become more modular, or segregated, to support early cognitive specialization, before integration across networks increases to support the emergence of higher-order cognition. The present study examined the maturation of structural covariance networks (SCNs) derived from longitudinal cortical thickness data collected between infancy and childhood (0-6 years). We assessed modularity as a measure of network segregation and global efficiency as a measure of network integration. At the group level, we observed trajectories of increasing modularity and decreasing global efficiency between early infancy and six years. We further examined subject-based maturational coupling networks (sbMCNs) in a subset of this cohort with cognitive outcome data at 8-10 years, which allowed us to relate the network organization of longitudinal cortical thickness maturation to cognitive outcomes in middle childhood. We found that lower global efficiency of sbMCNs throughout early development (across the first year) related to greater motor learning at 8-10 years. Together, these results provide novel evidence characterizing the maturation of brain network segregation and integration across the first six years of life, and suggest that specific trajectories of brain network maturation contribute to later cognitive outcomes.

JBHI Journal 2020 Journal Article

Hierarchical Rough-to-Fine Model for Infant Age Prediction Based on Cortical Features

  • Dan Hu
  • Zhengwang Wu
  • Weili Lin
  • Gang Li
  • Dinggang Shen

Prediction of the chronological age based on neuroimaging data is important for brain development analysis and brain disease diagnosis. Although many researches have been conducted for age prediction of older children and adults, little work has been dedicated to infants. To this end, this paper focuses on predicting infant age from birth to 2-year old using brain MR images, as well as identifying some related biomarkers. However, brain development during infancy is too rapid and heterogeneous to be accurately modeled by the conventional regression models. To address this issue, a two-stage prediction method is proposed. Specifically, our method first roughly predicts the age range of an infant and then finely predicts the accurate chronological age based on a learned, age-group-specific regression model. Combining this two-stage prediction method with another complementary one-stage prediction method, a hierarchical rough-to-fine (HRtoF) model is built. HRtoF effectively splits the rapid and heterogeneous changes during a long time period into several short time ranges and further mines the discrimination capability of cortical features, thus reaching high accuracy in infant age prediction. Taking 8 types of cortical morphometric features from structural MRI as predictors, the effectiveness of our proposed HRtoF model is validated using an infant dataset including 50 healthy subjects with 251 longitudinal MRI scans from 14 to 797 days. Comparing with five state-of-the-art regression methods, HRtoF model reduces the mean absolute error of the prediction from >48 days to 32. 1 days. The correlation coefficient of the predicted age and the chronological age reaches 0. 963. Moreover, based on HRtoF, the relative contributions of the eight types of cortical features for age prediction are also studied.

YNIMG Journal 2020 Journal Article

High-resolution 3D MR Fingerprinting using parallel imaging and deep learning

  • Yong Chen
  • Zhenghan Fang
  • Sheng-Che Hung
  • Wei-Tang Chang
  • Dinggang Shen
  • Weili Lin

MR Fingerprinting (MRF) is a relatively new imaging framework capable of providing accurate and simultaneous quantification of multiple tissue properties for improved tissue characterization and disease diagnosis. While 2D MRF has been widely available, extending the method to 3D MRF has been an actively pursued area of research as a 3D approach can provide a higher spatial resolution and better tissue characterization with an inherently higher signal-to-noise ratio. However, 3D MRF with a high spatial resolution requires lengthy acquisition times, especially for a large volume, making it impractical for most clinical applications. In this study, a high-resolution 3D MR Fingerprinting technique, combining parallel imaging and deep learning, was developed for rapid and simultaneous quantification of T1 and T2 relaxation times. Parallel imaging was first applied along the partition-encoding direction to reduce the amount of acquired data. An advanced convolutional neural network was then integrated with the MRF framework to extract features from the MRF signal evolution for improved tissue characterization and accelerated mapping. A modified 3D-MRF sequence was also developed in the study to acquire data to train the deep learning model that can be directly applied to prospectively accelerate 3D MRF scans. Our results of quantitative T1 and T2 maps demonstrate that improved tissue characterization can be achieved using the proposed method as compared to prior methods. With the integration of parallel imaging and deep learning techniques, whole-brain (26 × 26 × 18 cm3) quantitative T1 and T2 mapping with 1-mm isotropic resolution were achieved in ~7 min. In addition, a ~7-fold improvement in processing time to extract tissue properties was also accomplished with the deep learning approach as compared to the standard template matching method. All of these improvements make high-resolution whole-brain quantitative MR imaging feasible for clinical applications.

YNIMG Journal 2020 Journal Article

Morphology of perivascular spaces and enclosed blood vessels in young to middle-aged healthy adults at 7T: Dependences on age, brain region, and breathing gas

  • Xiaopeng Zong
  • Chunfeng Lian
  • Jordan Jimenez
  • Koji Yamashita
  • Dinggang Shen
  • Weili Lin

Perivascular spaces (PVSs) are fluid-filled spaces surrounding penetrating blood vessels in the brain and are an integral pathway of the glymphatic system. A PVS and the enclosed blood vessel are commonly visualized as a single vessel-like complex (denoted as PVSV) in high-resolution MRI images. Quantitative characterization of the PVSV morphology in MRI images in healthy subjects may serve as a reference for detecting disease related PVS and/or blood vessel alterations in patients with brain diseases. To this end, we evaluated the age dependences, spatial heterogeneities, and dynamic properties of PVSV morphological features in 45 healthy subjects (21–55 years old), using an ultra-high-resolution three-dimensional transverse relaxation time weighted MRI sequence (0. 41 ​× ​0. 41 ​× ​0. 4 ​mm3) at 7T. Quantitative PVSV parameters, including apparent diameter, count, volume fraction (VF), and relative contrast to noise ratio (rCNR) were calculated in the white matter and subcortical structures. Dynamic changes were induced by carbogen breathing which are known to induce vasodilation and increase the blood oxygenation level in the brain. PVSV count and VF significantly increased with age in basal ganglia (BG), so did rCNR in BG, midbrain, and white matter (WM). Apparent PVSV diameter also showed a positive association with age in the three brain regions, although it did not reach statistical significance. The PVSV VF and count showed large inter-subject variations, with coefficients of variation ranging from 0. 17 to 0. 74 after regressing out age and gender effects. Both apparent diameter and VF exhibited significant spatial heterogeneity, which cannot be explained solely by radio-frequency field inhomogeneities. Carbogen breathing significantly increased VF in BG and WM, and rCNR in thalamus, BG, and WM compared to air breathing. Our results are consistent with gradual dilation of PVSs with age in healthy adults. The PVSV morphology exhibited spatial heterogeneity and large inter-subject variations and changed during carbogen breathing compared to air breathing.

YNIMG Journal 2019 Journal Article

A review on neuroimaging studies of genetic and environmental influences on early brain development

  • Wei Gao
  • Karen Grewen
  • Rebecca C. Knickmeyer
  • Anqi Qiu
  • Andrew Salzwedel
  • Weili Lin
  • John H. Gilmore

The past decades witnessed a surge of interest in neuroimaging study of normal and abnormal early brain development. Structural and functional studies of normal early brain development revealed massive structural maturation as well as sequential, coordinated, and hierarchical emergence of functional networks during the infancy period, providing a great foundation for the investigation of abnormal early brain development mechanisms. Indeed, studies of altered brain development associated with either genetic or environmental risks emerged and thrived. In this paper, we will review selected studies of genetic and environmental risks that have been relatively more extensively investigated-familial risks, candidate risk genes, and genome-wide association studies (GWAS) on the genetic side; maternal mood disorders and prenatal drug exposures on the environmental side. Emerging studies on environment-gene interactions will also be reviewed. Our goal was not to perform an exhaustive review of all studies in the field but to leverage some representative ones to summarize the current state, point out potential limitations, and elicit discussions on important future directions.

YNIMG Journal 2019 Journal Article

Brain functional development separates into three distinct time periods in the first two years of life

  • Weiyan Yin
  • Meng-Hsiang Chen
  • Sheng-Che Hung
  • Kristine R. Baluyot
  • Tengfei Li
  • Weili Lin

Recently, resting functional MRI has provided invaluable insight into the brain developmental processes of early infancy and childhood. A common feature of previous functional development studies is the use of age to separate subjects into different cohorts for group comparisons. However, functional maturation paces vary tremendously from subject to subject. Since this is particularly true for the first years of life, an alternative to physical age alone is needed for cluster analysis. Here, a data-driven approach based on individual brain functional connectivity was employed to cluster typically developing children who were longitudinally imaged using MRI without sedation for the first two years of life. Specifically, three time periods were determined based on the distinction of brain functional connectivity patterns, including 0–1 month (group 1), 2–7 months (group 2), and 8–24 (group 3) of age, respectively. From groups 1 to 2, connection density increased by almost two-fold, local efficacy (LE) is significantly improved, and there was no change in global efficiency (GE). From groups 2 to 3, connection density increased slightly, LE showed no change, and a significant increase in GE were observed. Furthermore, 27 core brain regions were identified which yielded clustering results that resemble those obtained using all brain regions. These core regions were largely associated with the motor, visual and language functional domains as well as regions associated with higher order cognitive functional domains. Both visual and language functional domains exhibited a persistent and significant increase within domain connection from groups 1 to 3, while no changes were observed for the motor domain. In contrast, while a reduction of inter-domain connection was the general developmental pattern, the motor domain exhibited an interesting “V” shape pattern in its relationship to visual and language associated areas, showing a decrease from groups 1 to 2, followed by an increase from groups 2 to 3. In summary, our results offer new insights into functional brain development and identify 27 core brain regions critically important for early brain development.

YNIMG Journal 2019 Journal Article

Computational neuroanatomy of baby brains: A review

  • Gang Li
  • Li Wang
  • Pew-Thian Yap
  • Fan Wang
  • Zhengwang Wu
  • Yu Meng
  • Pei Dong
  • Jaeil Kim

The first postnatal years are an exceptionally dynamic and critical period of structural, functional and connectivity development of the human brain. The increasing availability of non-invasive infant brain MR images provides unprecedented opportunities for accurate and reliable charting of dynamic early brain developmental trajectories in understanding normative and aberrant growth. However, infant brain MR images typically exhibit reduced tissue contrast (especially around 6 months of age), large within-tissue intensity variations, and regionally-heterogeneous, dynamic changes, in comparison with adult brain MR images. Consequently, the existing computational tools developed typically for adult brains are not suitable for infant brain MR image processing. To address these challenges, many infant-tailored computational methods have been proposed for computational neuroanatomy of infant brains. In this review paper, we provide a comprehensive review of the state-of-the-art computational methods for infant brain MRI processing and analysis, which have advanced our understanding of early postnatal brain development. We also summarize publically available infant-dedicated resources, including MRI datasets, computational tools, grand challenges, and brain atlases. Finally, we discuss the limitations in current research and suggest potential future research directions.

YNIMG Journal 2019 Journal Article

Exploring folding patterns of infant cerebral cortex based on multi-view curvature features: Methods and applications

  • Dingna Duan
  • Shunren Xia
  • Islem Rekik
  • Yu Meng
  • Zhengwang Wu
  • Li Wang
  • Weili Lin
  • John H. Gilmore

The highly convoluted cortical folding of the human brain is intriguingly complex and variable across individuals. Exploring the underlying representative patterns of cortical folding is of great importance for many neuroimaging studies. At term birth, all major cortical folds are established and are minimally affected by the complicated postnatal environments; hence, neonates are the ideal candidates for exploring early postnatal cortical folding patterns, which yet remain largely unexplored. In this paper, we propose a novel method for exploring the representative regional folding patterns of infant brains. Specifically, first, multi-view curvature features are constructed to comprehensively characterize the complex characteristics of cortical folding. Second, for each view of curvature features, a similarity matrix is computed to measure the similarity of cortical folding in a specific region between any pair of subjects. Next, a similarity network fusion method is adopted to nonlinearly and adaptively fuse all the similarity matrices into a single one for retaining both shared and complementary similarity information of the multiple characteristics of cortical folding. Finally, based on the fused similarity matrix and a hierarchical affinity propagation clustering approach, all subjects are automatically grouped into several clusters to obtain the representative folding patterns. To show the applications, we have applied the proposed method to a large-scale dataset with 595 normal neonates and discovered representative folding patterns in several cortical regions, i. e. , the superior temporal gyrus (STG), inferior frontal gyrus (IFG), precuneus, and cingulate cortex. Meanwhile, we have revealed sex difference in STG, IFG, and cingulate cortex, as well as hemispheric asymmetries in STG and cingulate cortex in terms of cortical folding patterns. Moreover, we have also validated the proposed method on a public adult dataset, i. e. , the Human Connectome Project (HCP), and revealed that certain major cortical folding patterns of adults are largely established at term birth.

YNIMG Journal 2019 Journal Article

First-year development of modules and hubs in infant brain functional networks

  • Xuyun Wen
  • Han Zhang
  • Gang Li
  • Mingxia Liu
  • Weiyan Yin
  • Weili Lin
  • Jun Zhang
  • Dinggang Shen

The human brain develops rapidly in the first postnatal year, in which rewired functional brain networks could shape later behavioral and cognitive performance. Resting-state functional magnetic resonances imaging (rs-fMRI) and complex network analysis have been widely used for characterizing the developmental brain functional connectome. Yet, such studies focusing on the first year of postnatal life are still very limited. Leveraging normally developing longitudinal infant rs-fMRI scans from neonate to one year of age, we investigated how brain functional networks develop at a fine temporal scale (every 3 months). Considering challenges in the infant fMRI-based network analysis, we developed a novel algorithm to construct the robust, temporally consistent and modular structure augmented group-level network based on which functional modules were detected at each age. Our study reveals that the brain functional network is gradually subdivided into an increasing number of functional modules accompanied by the strengthened intra- and inter-modular connectivities. Based on the developing modules, we found connector hubs (the high-centrality regions connecting different modules) emerging and increasing, while provincial hubs (the high-centrality regions connecting regions in the same module) diminishing. Further region-wise longitudinal analysis validates that different hubs have distinct developmental trajectories of the intra- and inter-modular connections suggesting different types of role transitions in network, such as non-hubs to hubs or provincial hubs to connector hubs et al. All findings indicate that functional segregation and integration are both increased in the first year of postnatal life. The module reorganization and hub transition lead to more efficient brain networks, featuring increasingly segregated modular structure and more connector hubs. This study provides the first comprehensive report of the development of functional brain networks at a 3-month interval throughout the first postnatal year of life, which provides essential information to the future neurodevelopmental and developmental disorder studies.

YNIMG Journal 2019 Journal Article

MR fingerprinting enables quantitative measures of brain tissue relaxation times and myelin water fraction in the first five years of life

  • Yong Chen
  • Meng-Hsiang Chen
  • Kristine R. Baluyot
  • Taylor M. Potts
  • Jordan Jimenez
  • Weili Lin

Quantitative assessments of normative brain development using MRI are of critical importance to gain insights into healthy neurodevelopment. However, quantitative MR imaging poses significant technical challenges and requires prohibitively long acquisition times, making it impractical for pediatric imaging. This is particularly relevant for healthy subjects, where imaging under sedation is not clinically indicated. MR Fingerprinting (MRF), a novel MR imaging framework, provides rapid, efficient, and simultaneous quantification of multiple tissue properties. In this study, a 2D MR Fingerprinting method was developed that achieves a spatial resolution of 1 × 1 × 3 mm3 with rapid and simultaneous quantification of T1, T2 and myelin water fraction (MWF). Phantom experiments demonstrated that accurate measurements of T1 and T2 relaxation times were achieved over a wide range of T1 and T2 values. MRF images were acquired cross-sectionally from 28 typically developing children, 0 to five years old, who were enrolled in the UNC/UMN Baby Connectome Project. Differences associated with age of R1 (=1/T1), R2 (=1/T2) and MWF were obtained from several predefined white matter regions. Both R1 and R2 exhibit a marked increase until ∼20 months of age, followed by a slower increase for all WM regions. In contrast, the MWF remains at a negligible level until ∼6 months of age for all predefined ROIs and gradually increases afterwards. Depending on the brain region, rapid increases are observed between 6 and 12 months to 6–18 months, followed by a slower pace of increase in MWF. Neither relaxivities nor MWF were significantly different between the left and right hemispheres. However, regional differences in age-related R1 and MWF measures were observed across different white matter regions. In conclusion, our results demonstrate that the MRF technique holds great potential for multi-parametric assessments of normative brain development in early childhood.

YNIMG Journal 2019 Journal Article

Multi-task prediction of infant cognitive scores from longitudinal incomplete neuroimaging data

  • Ehsan Adeli
  • Yu Meng
  • Gang Li
  • Weili Lin
  • Dinggang Shen

Early postnatal brain undergoes a stunning period of development. Over the past few years, research on dynamic infant brain development has received increased attention, exhibiting how important the early stages of a child's life are in terms of brain development. To precisely chart the early brain developmental trajectories, longitudinal studies with data acquired over a long-enough period of infants' early life is essential. However, in practice, missing data from different time point(s) during the data gathering procedure is often inevitable. This leads to incomplete set of longitudinal data, which poses a major challenge for such studies. In this paper, prediction of multiple future cognitive scores with incomplete longitudinal imaging data is modeled into a multi-task machine learning framework. To efficiently learn this model, we account for selection of informative features (i. e. , neuroimaging morphometric measurements for different time points), while preserving the structural information and the interrelation between these multiple cognitive scores. Several experiments are conducted on a carefully acquired in-house dataset, and the results affirm that we can predict the cognitive scores measured at the age of four years old, using the imaging data of earlier time points, as early as 24 months of age, with a reasonable performance (i. e. , root mean square error of 0. 18).

YNIMG Journal 2019 Journal Article

Quantitative phase contrast MRI of penetrating arteries in centrum semiovale at 7T

  • Xiaopeng Zong
  • Weili Lin

Pathological changes of penetrating arteries (PA) within the centrum semiovale is an important contributing factor of cerebral small vessel disease (SVD). However, quantitative characterization of the PAs remains challenging due to their sub-voxel sizes. Here, we proposed a Model-based Analysis of Complex Difference images (MACD) of phase contrast MRI capable of measuring the mean velocities ( v mean ), diameters (D), and volume flow rates (VFR) of PAs without contamination from neighboring static tissues at 7 T. Simulation, phantom and in vivo studies were performed to evaluate the reproducibility and errors of the proposed method. For comparison, a Model-based Analysis of Phase difference images (MAP) was also carried out in the simulation. The proposed MACD analysis approach was applied in vivo to study the age dependence of PA properties in healthy subjects between 21 and 55 years old. Simulation showed that our proposed MACD approach yielded smaller errors than MAP, with errors increasing at lower velocities and diameters for both methods. In the phantom study, errors of the MACD-derived v mean, D, and VFR were ≤20% of their true values when v mean ≥ 1 cm/s and similar at different spatial resolutions. On the other hand, errors of the uncorrected apparent velocities were 24–60% and depended strongly on voxel size. The MACD errors linearly increased with the angle (α) between the vessel and slice normal direction at α ≤ 2° but remained almost constant at larger α. Results of the in vivo studies showed that the coefficients of repeatability for v mean, D, and VFR for PAs with α = 0° were 0. 67 cm/s, 0. 060 mm, and 0. 067 mm3/s, respectively. No significant age dependence was found for the number, v mean, D, and VFR of PAs. The mean v mean, D, and VFR over all PAs with α = 0° were 1. 79 ± 0. 62 cm/s, 0. 17 ± 0. 05 mm, and 0. 36 ± 0. 18 mm3/s, respectively. Quantitative measurements of PAs with the MACD method may serve as a useful tool for illuminating the vascular pathology in cerebral SVD.

YNIMG Journal 2019 Journal Article

Resting-state functional MRI studies on infant brains: A decade of gap-filling efforts

  • Han Zhang
  • Dinggang Shen
  • Weili Lin

Resting-state functional MRI (rs-fMRI) is one of the most prevalent brain functional imaging modalities. Previous rs-fMRI studies have mainly focused on adults and elderly subjects. Recently, infant rs-fMRI studies have become an area of active research. After a decade of gap filling studies, many facets of the brain functional development from early infancy to toddler has been uncovered. However, infant rs-fMRI is still in its infancy. The image analysis tools for neonates and young infants can be quite different from those for adults. From data analysis to result interpretation, more questions and issues have been raised, and new hypotheses have been formed. With the anticipated availability of unprecedented high-resolution rs-fMRI and dedicated analysis pipelines from the Baby Connectome Project (BCP), it is important now to revisit previous findings and hypotheses, discuss and comment existing issues and problems, and make a “to-do-list” for the future studies. This review article aims to comprehensively review a decade of the findings, unveiling hidden jewels of the fields of developmental neuroscience and neuroimage computing. Emphases will be given to early infancy, particularly the first few years of life. In this review, an end-to-end summary, from infant rs-fMRI experimental design to data processing, and from the development of individual functional systems to large-scale brain functional networks, is provided. A comprehensive summary of the rs-fMRI findings in developmental patterns is highlighted. Furthermore, an extensive summary of the neurodevelopmental disorders and the effects of other hazardous factors is provided. Finally, future research trends focusing on emerging dynamic functional connectivity and state-of-the-art functional connectome analysis are summarized. In next decade, early infant rs-fMRI and developmental connectome study could be one of the shining research topics.

YNIMG Journal 2019 Journal Article

The UNC/UMN Baby Connectome Project (BCP): An overview of the study design and protocol development

  • Brittany R. Howell
  • Martin A. Styner
  • Wei Gao
  • Pew-Thian Yap
  • Li Wang
  • Kristine Baluyot
  • Essa Yacoub
  • Geng Chen

The human brain undergoes extensive and dynamic growth during the first years of life. The UNC/UMN Baby Connectome Project (BCP), one of the Lifespan Connectome Projects funded by NIH, is an ongoing study jointly conducted by investigators at the University of North Carolina at Chapel Hill and the University of Minnesota. The primary objective of the BCP is to characterize brain and behavioral development in typically developing infants across the first 5 years of life. The ultimate goals are to chart emerging patterns of structural and functional connectivity during this period, map brain-behavior associations, and establish a foundation from which to further explore trajectories of health and disease. To accomplish these goals, we are combining state of the art MRI acquisition and analysis techniques, including high-resolution structural MRI (T1-and T2-weighted images), diffusion imaging (dMRI), and resting state functional connectivity MRI (rfMRI). While the overall design of the BCP largely is built on the protocol developed by the Lifespan Human Connectome Project (HCP), given the unique age range of the BCP cohort, additional optimization of imaging parameters and consideration of an age appropriate battery of behavioral assessments were needed. Here we provide the overall study protocol, including approaches for subject recruitment, strategies for imaging typically developing children 0–5 years of age without sedation, imaging protocol and optimization, a description of the battery of behavioral assessments, and QA/QC procedures. Combining HCP inspired neuroimaging data with well-established behavioral assessments during this time period will yield an invaluable resource for the scientific community.

YNIMG Journal 2019 Journal Article

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

  • Liang Sun
  • Daoqiang Zhang
  • Chunfeng Lian
  • Li Wang
  • Zhengwang Wu
  • WEI SHAO
  • Weili Lin
  • Dinggang Shen

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.

YNIMG Journal 2018 Journal Article

3D conditional generative adversarial networks for high-quality PET image estimation at low dose

  • Yan Wang
  • Biting Yu
  • Lei Wang
  • Chen Zu
  • David S. Lalush
  • Weili Lin
  • Xi Wu
  • Jiliu Zhou

Positron emission tomography (PET) is a widely used imaging modality, providing insight into both the biochemical and physiological processes of human body. Usually, a full dose radioactive tracer is required to obtain high-quality PET images for clinical needs. This inevitably raises concerns about potential health hazards. On the other hand, dose reduction may cause the increased noise in the reconstructed PET images, which impacts the image quality to a certain extent. In this paper, in order to reduce the radiation exposure while maintaining the high quality of PET images, we propose a novel method based on 3D conditional generative adversarial networks (3D c-GANs) to estimate the high-quality full-dose PET images from low-dose ones. Generative adversarial networks (GANs) include a generator network and a discriminator network which are trained simultaneously with the goal of one beating the other. Similar to GANs, in the proposed 3D c-GANs, we condition the model on an input low-dose PET image and generate a corresponding output full-dose PET image. Specifically, to render the same underlying information between the low-dose and full-dose PET images, a 3D U-net-like deep architecture which can combine hierarchical features by using skip connection is designed as the generator network to synthesize the full-dose image. In order to guarantee the synthesized PET image to be close to the real one, we take into account of the estimation error loss in addition to the discriminator feedback to train the generator network. Furthermore, a concatenated 3D c-GANs based progressive refinement scheme is also proposed to further improve the quality of estimated images. Validation was done on a real human brain dataset including both the normal subjects and the subjects diagnosed as mild cognitive impairment (MCI). Experimental results show that our proposed 3D c-GANs method outperforms the benchmark methods and achieves much better performance than the state-of-the-art methods in both qualitative and quantitative measures.

YNIMG Journal 2017 Journal Article

Joint prediction of longitudinal development of cortical surfaces and white matter fibers from neonatal MRI

  • Islem Rekik
  • Gang Li
  • Pew-Thian Yap
  • Geng Chen
  • Weili Lin
  • Dinggang Shen

The human brain can be modeled as multiple interrelated shapes (or a multishape), each for characterizing one aspect of the brain, such as the cortex and white matter pathways. Predicting the developing multishape is a very challenging task due to the contrasting nature of the developmental trajectories of the constituent shapes: smooth for the cortical surface and non-smooth for white matter tracts due to changes such as bifurcation. We recently addressed this problem and proposed an approach for predicting the multishape developmental spatiotemporal trajectories of infant brains based only on neonatal MRI data using a set of geometric, dynamic, and fiber-to-surface connectivity features. In this paper, we propose two key innovations to further improve the prediction of multishape evolution. First, for a more accurate cortical surface prediction, instead of simply relying on one neonatal atlas to guide the prediction of the multishape, we propose to use multiple neonatal atlases to build a spatially heterogeneous atlas using the multidirectional varifold representation. This individualizes the atlas by locally maximizing its similarity to the testing baseline cortical shape for each cortical region, thereby better representing the baseline testing cortical surface, which founds the multishape prediction process. Second, for temporally consistent fiber prediction, we propose to reliably estimate spatiotemporal connectivity features using low-rank tensor completion, thereby capturing the variability and richness of the temporal development of fibers. Experimental results confirm that the proposed variants significantly improve the prediction performance of our original multishape prediction framework for both cortical surfaces and fiber tracts shape at 3, 6, and 9 months of age. Our pioneering model will pave the way for learning how to predict the evolution of anatomical shapes with abnormal changes. Ultimately, devising accurate shape evolution prediction models that can help quantify and predict the severity of a brain disorder as it progresses will be of great aid in individualized treatment planning.

YNICL Journal 2016 Journal Article

Automated quantification of cerebral edema following hemispheric infarction: Application of a machine-learning algorithm to evaluate CSF shifts on serial head CTs

  • Yasheng Chen
  • Rajat Dhar
  • Laura Heitsch
  • Andria Ford
  • Israel Fernandez-Cadenas
  • Caty Carrera
  • Joan Montaner
  • Weili Lin

Although cerebral edema is a major cause of death and deterioration following hemispheric stroke, there remains no validated biomarker that captures the full spectrum of this critical complication. We recently demonstrated that reduction in intracranial cerebrospinal fluid (CSF) volume (∆CSF) on serial computed tomography (CT) scans provides an accurate measure of cerebral edema severity, which may aid in early triaging of stroke patients for craniectomy. However, application of such a volumetric approach would be too cumbersome to perform manually on serial scans in a real-world setting. We developed and validated an automated technique for CSF segmentation via integration of random forest (RF) based machine learning with geodesic active contour (GAC) segmentation. The proposed RF+GAC approach was compared to conventional Hounsfield Unit (HU) thresholding and RF segmentation methods using Dice similarity coefficient (DSC) and the correlation of volumetric measurements, with manual delineation serving as the ground truth. CSF spaces were outlined on scans performed at baseline (<6h after stroke onset) and early follow-up (FU) (closest to 24h) in 38 acute ischemic stroke patients. RF performed significantly better than optimized HU thresholding (p<10−4 in baseline and p<10−5 in FU) and RF+GAC performed significantly better than RF (p<10−3 in baseline and p<10−5 in FU). Pearson correlation coefficients between the automatically detected ∆CSF and the ground truth were r =0. 178 (p=0. 285), r =0. 876 (p<10−6) and r =0. 879 (p<10−6) for thresholding, RF and RF+GAC, respectively, with a slope closer to the line of identity in RF+GAC. When we applied the algorithm trained from images of one stroke center to segment CTs from another center, similar findings held. In conclusion, we have developed and validated an accurate automated approach to segment CSF and calculate its shifts on serial CT scans. This algorithm will allow us to efficiently and accurately measure the evolution of cerebral edema in future studies including large multi-site patient populations.

YNIMG Journal 2016 Journal Article

Multidirectional and Topography-based Dynamic-scale Varifold Representations with Application to Matching Developing Cortical Surfaces

  • Islem Rekik
  • Gang Li
  • Weili Lin
  • Dinggang Shen

The human cerebral cortex is marked by great complexity as well as substantial dynamic changes during early postnatal development. To obtain a fairly comprehensive picture of its age-induced and/or disorder-related cortical changes, one needs to match cortical surfaces to one another, while maximizing their anatomical alignment. Methods that geodesically shoot surfaces into one another as currents (a distribution of oriented normals) and varifolds (a distribution of non-oriented normals) provide an elegant Riemannian framework for generic surface matching and reliable statistical analysis. However, both conventional current and varifold matching methods have two key limitations. First, they only use the normals of the surface to measure its geometry and guide the warping process, which overlooks the importance of the orientations of the inherently convoluted cortical sulcal and gyral folds. Second, the ‘conversion’ of a surface into a current or a varifold operates at a fixed scale under which geometric surface details will be neglected, which ignores the dynamic scales of cortical foldings. To overcome these limitations and improve varifold-based cortical surface registration, we propose two different strategies. The first strategy decomposes each cortical surface into its normal and tangent varifold representations, by integrating principal curvature direction field into the varifold matching framework, thus providing rich information of the orientation of cortical folding and better characterization of the complex cortical geometry. The second strategy explores the informative cortical geometric features to perform a dynamic-scale measurement of the cortical surface that depends on the local surface topography (e. g. , principal curvature), thereby we introduce the concept of a topography-based dynamic-scale varifold. We tested the proposed varifold variants for registering 12 pairs of dynamically developing cortical surfaces from 0 to 6 months of age. Both variants improved the matching accuracy in terms of closeness to the target surface and the goodness of alignment with regional anatomical boundaries, when compared with three state-of-the-art methods: (1) diffeomorphic spectral matching, (2) conventional current-based surface matching, and (3) conventional varifold-based surface matching.

YNIMG Journal 2016 Journal Article

Segmentation of perivascular spaces in 7 T MR image using auto-context model with orientation-normalized features

  • Sang Hyun Park
  • Xiaopeng Zong
  • Yaozong Gao
  • Weili Lin
  • Dinggang Shen

Quantitative study of perivascular spaces (PVSs) in brain magnetic resonance (MR) images is important for understanding the brain lymphatic system and its relationship with neurological diseases. One of the major challenges is the accurate extraction of PVSs that have very thin tubular structures with various directions in three-dimensional (3D) MR images. In this paper, we propose a learning-based PVS segmentation method to address this challenge. Specifically, we first determine a region of interest (ROI) by using the anatomical brain structure and the vesselness information derived from eigenvalues of image derivatives. Then, in the ROI, we extract a number of randomized Haar features which are normalized with respect to the principal directions of the underlying image derivatives. The classifier is trained by the random forest model that can effectively learn both discriminative features and classifier parameters to maximize the information gain. Finally, a sequential learning strategy is used to further enforce various contextual patterns around the thin tubular structures into the classifier. For evaluation, we apply our proposed method to the 7T brain MR images scanned from 17 healthy subjects aged from 25 to 37. The performance is measured by voxel-wise segmentation accuracy, cluster-wise classification accuracy, and similarity of geometric properties, such as volume, length, and diameter distributions between the predicted and the true PVSs. Moreover, the accuracies are also evaluated on the simulation images with motion artifacts and lacunes to demonstrate the potential of our method in segmenting PVSs from elderly and patient populations. The experimental results show that our proposed method outperforms all existing PVS segmentation methods.

YNIMG Journal 2016 Journal Article

STGP: Spatio-temporal Gaussian process models for longitudinal neuroimaging data

  • Jung Won Hyun
  • Yimei Li
  • Chao Huang
  • Martin Styner
  • Weili Lin
  • Hongtu Zhu

Longitudinal neuroimaging data plays an important role in mapping the neural developmental profile of major neuropsychiatric and neurodegenerative disorders and normal brain. The development of such developmental maps is critical for the prevention, diagnosis, and treatment of many brain-related diseases. The aim of this paper is to develop a spatio-temporal Gaussian process (STGP) framework to accurately delineate the developmental trajectories of brain structure and function, while achieving better prediction by explicitly incorporating the spatial and temporal features of longitudinal neuroimaging data. Our STGP integrates a functional principal component model (FPCA) and a partition parametric space–time covariance model to capture the medium-to-large and small-to-medium spatio-temporal dependence structures, respectively. We develop a three-stage efficient estimation procedure as well as a predictive method based on a kriging technique. Two key novelties of STGP are that it can efficiently use a small number of parameters to capture complex non-stationary and non-separable spatio-temporal dependence structures and that it can accurately predict spatio-temporal changes. We illustrate STGP using simulated data sets and two real data analyses including longitudinal positron emission tomography data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and longitudinal lateral ventricle surface data from a longitudinal study of early brain development.

YNIMG Journal 2016 Journal Article

Visualization of perivascular spaces in the human brain at 7 T: sequence optimization and morphology characterization

  • Xiaopeng Zong
  • Sang Hyun Park
  • Dinggang Shen
  • Weili Lin

Noninvasive imaging of perivascular spaces (PVSs) may provide useful insights into their role in normal brain physiology and diseases. Fast MRI sequences with sub-millimeter spatial resolutions and high contrast-to-noise ratio (CNR) are required for accurate delineation of PVS in human. To achieve the optimal condition for PVS imaging at 7T, we carried out detailed simulation and experimental studies to characterize the dependence of CNR on imaging sequences (T1 versus T2-weighted) and sequence parameters. In addition, PVSs were segmented semi-automatically, which revealed much larger numbers of PVSs in young healthy subjects (age 21–37years) than previously reported. To the best of our knowledge, our study provides, for the first time, detailed length, volume, and diameter distributions of PVS in the white matter and subcortical nuclei, which can serve as a reference for future studies of PVS abnormalities under diseased conditions.

YNIMG Journal 2015 Journal Article

Deep convolutional neural networks for multi-modality isointense infant brain image segmentation

  • Wenlu Zhang
  • Rongjian Li
  • Houtao Deng
  • Li Wang
  • Weili Lin
  • Shuiwang Ji
  • Dinggang Shen

The segmentation of infant brain tissue images into white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) plays an important role in studying early brain development in health and disease. In the isointense stage (approximately 6–8 months of age), WM and GM exhibit similar levels of intensity in both T1 and T2 MR images, making the tissue segmentation very challenging. Only a small number of existing methods have been designed for tissue segmentation in this isointense stage; however, they only used a single T1 or T2 images, or the combination of T1 and T2 images. In this paper, we propose to use deep convolutional neural networks (CNNs) for segmenting isointense stage brain tissues using multi-modality MR images. CNNs are a type of deep models in which trainable filters and local neighborhood pooling operations are applied alternatingly on the raw input images, resulting in a hierarchy of increasingly complex features. Specifically, we used multi-modality information from T1, T2, and fractional anisotropy (FA) images as inputs and then generated the segmentation maps as outputs. The multiple intermediate layers applied convolution, pooling, normalization, and other operations to capture the highly nonlinear mappings between inputs and outputs. We compared the performance of our approach with that of the commonly used segmentation methods on a set of manually segmented isointense stage brain images. Results showed that our proposed model significantly outperformed prior methods on infant brain tissue segmentation. In addition, our results indicated that integration of multi-modality images led to significant performance improvement.

YNIMG Journal 2015 Journal Article

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

  • Li Wang
  • Yaozong Gao
  • Feng Shi
  • Gang Li
  • John H. Gilmore
  • Weili Lin
  • Dinggang Shen

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.

NeurIPS Conference 2015 Conference Paper

Statistical Topological Data Analysis - A Kernel Perspective

  • Roland Kwitt
  • Stefan Huber
  • Marc Niethammer
  • Weili Lin
  • Ulrich Bauer

We consider the problem of statistical computations with persistence diagrams, a summary representation of topological features in data. These diagrams encode persistent homology, a widely used invariant in topological data analysis. While several avenues towards a statistical treatment of the diagrams have been explored recently, we follow an alternative route that is motivated by the success of methods based on the embedding of probability measures into reproducing kernel Hilbert spaces. In fact, a positive definite kernel on persistence diagrams has recently been proposed, connecting persistent homology to popular kernel-based learning techniques such as support vector machines. However, important properties of that kernel which would enable a principled use in the context of probability measure embeddings remain to be explored. Our contribution is to close this gap by proving universality of a variant of the original kernel, and to demonstrate its effective use in two-sample hypothesis testing on synthetic as well as real-world data.

YNIMG Journal 2014 Journal Article

Integration of sparse multi-modality representation and anatomical constraint for isointense infant brain MR image segmentation

  • Li Wang
  • Feng Shi
  • Yaozong Gao
  • Gang Li
  • John H. Gilmore
  • Weili Lin
  • Dinggang Shen

Segmentation of infant brain MR images is challenging due to poor spatial resolution, severe partial volume effect, and the ongoing maturation and myelination processes. During the first year of life, the brain image contrast between white and gray matters undergoes dramatic changes. In particular, the image contrast inverses around 6–8months of age, where the white and gray matter tissues are isointense in T1 and T2 weighted images and hence exhibit the extremely low tissue contrast, posing significant challenges for automated segmentation. In this paper, we propose a general framework that adopts sparse representation to fuse the multi-modality image information and further incorporate the anatomical constraints for brain tissue segmentation. Specifically, we first derive an initial segmentation from a library of aligned images with ground-truth segmentations by using sparse representation in a patch-based fashion for the multi-modality T1, T2 and FA images. The segmentation result is further iteratively refined by integration of the anatomical constraint. The proposed method was evaluated on 22 infant brain MR images acquired at around 6months of age by using a leave-one-out cross-validation, as well as other 10 unseen testing subjects. Our method achieved a high accuracy for the Dice ratios that measure the volume overlap between automated and manual segmentations, i. e. , 0. 889±0. 008 for white matter and 0. 870±0. 006 for gray matter.

YNIMG Journal 2014 Journal Article

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

  • Gang Li
  • Jingxin Nie
  • Li Wang
  • Feng Shi
  • John H. Gilmore
  • Weili Lin
  • Dinggang Shen

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.

YNIMG Journal 2014 Journal Article

Prenatal cocaine effects on brain structure in early infancy

  • Karen Grewen
  • Margaret Burchinal
  • Clement Vachet
  • Sylvain Gouttard
  • John H. Gilmore
  • Weili Lin
  • Josephine Johns
  • Mala Elam

Prenatal cocaine exposure (PCE) is related to subtle deficits in cognitive and behavioral function in infancy, childhood and adolescence. Very little is known about the effects of in utero PCE on early brain development that may contribute to these impairments. The purpose of this study was to examine brain structural differences in infants with and without PCE. We conducted MRI scans of newborns (mean age=5weeks) to determine cocaine's impact on early brain structural development. Subjects were three groups of infants: 33 with PCE co-morbid with other drugs, 46 drug-free controls and 40 with prenatal exposure to other drugs (nicotine, alcohol, marijuana, opiates, SSRIs) but without cocaine. Infants with PCE exhibited lesser total gray matter (GM) volume and greater total cerebral spinal fluid (CSF) volume compared with controls and infants with non-cocaine drug exposure. Analysis of regional volumes revealed that whole brain GM differences were driven primarily by lesser GM in prefrontal and frontal brain regions in infants with PCE, while more posterior regions (parietal, occipital) did not differ across groups. Greater CSF volumes in PCE infants were present in prefrontal, frontal and parietal but not occipital regions. Greatest differences (GM reduction, CSF enlargement) in PCE infants were observed in dorsal prefrontal cortex. Results suggest that PCE is associated with structural deficits in neonatal cortical gray matter, specifically in prefrontal and frontal regions involved in executive function and inhibitory control. Longitudinal study is required to determine whether these early differences persist and contribute to deficits in cognitive functions and enhanced risk for drug abuse seen at school age and in later life.

YNIMG Journal 2014 Journal Article

Segmentation of neonatal brain MR images using patch-driven level sets

  • Li Wang
  • Feng Shi
  • Gang Li
  • Yaozong Gao
  • Weili Lin
  • John H. Gilmore
  • Dinggang Shen

The segmentation of neonatal brain MR image into white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF), is challenging due to the low spatial resolution, severe partial volume effect, high image noise, and dynamic myelination and maturation processes. Atlas-based methods have been widely used for guiding neonatal brain segmentation. Existing brain atlases were generally constructed by equally averaging all the aligned template images from a population. However, such population-based atlases might not be representative of a testing subject in the regions with high inter-subject variability and thus often lead to a low capability in guiding segmentation in those regions. Recently, patch-based sparse representation techniques have been proposed to effectively select the most relevant elements from a large group of candidates, which can be used to generate a subject-specific representation with rich local anatomical details for guiding the segmentation. Accordingly, in this paper, we propose a novel patch-driven level set method for the segmentation of neonatal brain MR images by taking advantage of sparse representation techniques. Specifically, we first build a subject-specific atlas from a library of aligned, manually segmented images by using sparse representation in a patch-based fashion. Then, the spatial consistency in the probability maps from the subject-specific atlas is further enforced by considering the similarities of a patch with its neighboring patches. Finally, the probability maps are integrated into a coupled level set framework for more accurate segmentation. The proposed method has been extensively evaluated on 20 training subjects using leave-one-out cross validation, and also on 132 additional testing subjects. Our method achieved a high accuracy of 0. 919±0. 008 for white matter and 0. 901±0. 005 for gray matter, respectively, measured by Dice ratio for the overlap between the automated and manual segmentations in the cortical region.

YNIMG Journal 2014 Journal Article

Spatial distribution and longitudinal development of deep cortical sulcal landmarks in infants

  • Yu Meng
  • Gang Li
  • Weili Lin
  • John H. Gilmore
  • Dinggang Shen

Sulcal pits, the locally deepest points in sulci of the highly convoluted and variable cerebral cortex, are found to be spatially consistent across human adult individuals. It is suggested that sulcal pits are genetically controlled and have close relationships with functional areas. To date, the existing imaging studies of sulcal pits are mainly focused on adult brains, yet little is known about the spatial distribution and temporal development of sulcal pits in the first 2years of life, which is the most dynamic and critical period of postnatal brain development. Studying sulcal pits during this period would greatly enrich our limited understandings of the origins and developmental trajectories of sulcal pits, and would also provide important insights into many neurodevelopmental disorders associated with abnormal cortical foldings. In this paper, by using surface-based morphometry, for the first time, we systemically investigated the spatial distribution and temporal development of sulcal pits in major cortical sulci from 73 healthy infants, each with three longitudinal 3T MR scans at term birth, 1year, and 2years of age. Our results suggest that the spatially consistent distributions of sulcal pits in major sulci across individuals have already existed at term birth and this spatial distribution pattern keeps relatively stable in the first 2years of life, despite that the cerebral cortex expands dramatically and the sulcal depth increases considerably during this period. Specially, the depth of sulcal pits increases regionally heterogeneously, with more rapid growth in the high-order association cortex, including the prefrontal and temporal cortices, than the sensorimotor cortex in the first 2years of life. Meanwhile, our results also suggest that there exist hemispheric asymmetries of the spatial distributions of sulcal pits in several cortical regions, such as the central, superior temporal and postcentral sulci, consistently from birth to 2years of age, which likely has close relationships with the lateralization of brain functions of these regions. This study provides detailed insights into the spatial distribution and temporal development of deep sulcal landmarks in infants.

YNIMG Journal 2013 Journal Article

Associations between white matter microstructure and infants' working memory

  • Sarah J. Short
  • Jed T. Elison
  • Barbara Davis Goldman
  • Martin Styner
  • Hongbin Gu
  • Mark Connelly
  • Eric Maltbie
  • Sandra Woolson

Working memory emerges in infancy and plays a privileged role in subsequent adaptive cognitive development. The neural networks important for the development of working memory during infancy remain unknown. We used diffusion tensor imaging (DTI) and deterministic fiber tracking to characterize the microstructure of white matter fiber bundles hypothesized to support working memory in 12-month-old infants (n =73). Here we show robust associations between infants' visuospatial working memory performance and microstructural characteristics of widespread white matter. Significant associations were found for white matter tracts that connect brain regions known to support working memory in older children and adults (genu, anterior and superior thalamic radiations, anterior cingulum, arcuate fasciculus, and the temporal–parietal segment). Better working memory scores were associated with higher FA and lower RD values in these selected white matter tracts. These tract-specific brain–behavior relationships accounted for a significant amount of individual variation above and beyond infants' gestational age and developmental level, as measured with the Mullen Scales of Early Learning. Working memory was not associated with global measures of brain volume, as expected, and few associations were found between working memory and control white matter tracts. To our knowledge, this study is among the first demonstrations of brain–behavior associations in infants using quantitative tractography. The ability to characterize subtle individual differences in infant brain development associated with complex cognitive functions holds promise for improving our understanding of normative development, biomarkers of risk, experience-dependent learning and neuro-cognitive periods of developmental plasticity.

YNIMG Journal 2013 Journal Article

Multiscale adaptive generalized estimating equations for longitudinal neuroimaging data

  • Yimei Li
  • John H. Gilmore
  • Dinggang Shen
  • Martin Styner
  • Weili Lin
  • Hongtu Zhu

Many large-scale longitudinal imaging studies have been or are being widely conducted to better understand the progress of neuropsychiatric and neurodegenerative disorders and normal brain development. The goal of this article is to develop a multiscale adaptive generalized estimation equation (MAGEE) method for spatial and adaptive analysis of neuroimaging data from longitudinal studies. MAGEE is applicable to making statistical inference on regression coefficients in both balanced and unbalanced longitudinal designs and even in twin and familial studies, whereas standard software platforms have several major limitations in handling these complex studies. Specifically, conventional voxel-based analyses in these software platforms involve Gaussian smoothing imaging data and then independently fitting a statistical model at each voxel. However, the conventional smoothing methods suffer from the lack of spatial adaptivity to the shape and spatial extent of region of interest and the arbitrary choice of smoothing extent, while independently fitting statistical models across voxels does not account for the spatial properties of imaging observations and noise distribution. To address such drawbacks, we adapt a powerful propagation–separation (PS) procedure to sequentially incorporate the neighboring information of each voxel and develop a new novel strategy to solely update a set of parameters of interest, while fixing other nuisance parameters at their initial estimators. Simulation studies and real data analysis show that MAGEE significantly outperforms voxel-based analysis.

YNIMG Journal 2012 Journal Article

Altered structural connectivity in neonates at genetic risk for schizophrenia: A combined study using morphological and white matter networks

  • Feng Shi
  • Pew-Thian Yap
  • Wei Gao
  • Weili Lin
  • John H. Gilmore
  • Dinggang Shen

Recently, an increasing body of evidence suggests that developmental abnormalities related to schizophrenia may occur as early as the neonatal stage. Impairments of brain gray matter and wiring problems of axonal fibers are commonly suspected to be responsible for the disconnection hypothesis in schizophrenia adults, but significantly less is known in neonates. In this study, we investigated 26 neonates who were at genetic risk for schizophrenia and 26 demographically matched healthy neonates using both morphological and white matter networks to examine possible brain connectivity abnormalities. The results showed that both populations exhibited small-world network topology. Morphological network analysis indicated that the brain structural associations of the high-risk neonates tended to have globally lower efficiency, longer connection distance, and less number of hub nodes and edges with relatively higher betweenness. Subgroup analysis showed that male neonates were significantly disease-affected, while the female neonates were not. White matter network analysis, however, showed that the fiber networks were globally unaffected, although several subcortical–cortical connections had significantly less number of fibers in high-risk neonates. This study provides new lines of evidence in support of the disconnection hypothesis, reinforcing the notion that the genetic risk of schizophrenia induces alterations in both gray matter structural associations and white matter connectivity.

YNIMG Journal 2012 Journal Article

LABEL: Pediatric brain extraction using learning-based meta-algorithm

  • Feng Shi
  • Li Wang
  • Yakang Dai
  • John H. Gilmore
  • Weili Lin
  • Dinggang Shen

Magnetic resonance imaging of pediatric brain provides valuable information for early brain development studies. Automated brain extraction is challenging due to the small brain size and dynamic change of tissue contrast in the developing brains. In this paper, we propose a novel Learning Algorithm for Brain Extraction and Labeling (LABEL) specially for the pediatric MR brain images. The idea is to perform multiple complementary brain extractions on a given testing image by using a meta-algorithm, including BET and BSE, where the parameters of each run of the meta-algorithm are effectively learned from the training data. Also, the representative subjects are selected as exemplars and used to guide brain extraction of new subjects in different age groups. We further develop a level-set based fusion method to combine multiple brain extractions together with a closed smooth surface for obtaining the final extraction. The proposed method has been extensively evaluated in subjects of three representative age groups, such as neonate (less than 2months), infant (1–2years), and child (5–18years). Experimental results show that, with 45 subjects for training (15 neonates, 15 infant, and 15 children), the proposed method can produce more accurate brain extraction results on 246 testing subjects (75 neonates, 126 infants, and 45 children), i. e. , at average Jaccard Index of 0. 953, compared to those by BET (0. 918), BSE (0. 902), ROBEX (0. 901), GCUT (0. 856), and other fusion methods such as Majority Voting (0. 919) and STAPLE (0. 941). Along with the largely-improved computational efficiency, the proposed method demonstrates its ability of automated brain extraction for pediatric MR images in a large age range.

YNIMG Journal 2012 Journal Article

Quantitative tract-based white matter development from birth to age 2 years

  • Xiujuan Geng
  • Sylvain Gouttard
  • Anuja Sharma
  • Hongbin Gu
  • Martin Styner
  • Weili Lin
  • Guido Gerig
  • John H. Gilmore

Few large-scale studies have been done to characterize the normal human brain white matter growth in the first years of life. We investigated white matter maturation patterns in major fiber pathways in a large cohort of healthy young children from birth to age two using diffusion parameters fractional anisotropy (FA), radial diffusivity (RD) and axial diffusivity (RD). Ten fiber pathways, including commissural, association and projection tracts, were examined with tract-based analysis, providing more detailed and continuous spatial developmental patterns compared to conventional ROI based methods. All DTI data sets were transformed to a population specific atlas with a group-wise longitudinal large deformation diffeomorphic registration approach. Diffusion measurements were analyzed along the major fiber tracts obtained in the atlas space. All fiber bundles show increasing FA values and decreasing radial and axial diffusivities during development in the first 2years of life. The changing rates of the diffusion indices are faster in the first year than the second year for all tracts. RD and FA show larger percentage changes in the first and second years than AD. The gender effects on the diffusion measures are small. Along different spatial locations of fiber tracts, maturation does not always follow the same speed. Temporal and spatial diffusion changes near cortical regions are in general smaller than changes in central regions. Overall developmental patterns revealed in our study confirm the general rules of white matter maturation. This work shows a promising framework to study and analyze white matter maturation in a tract-based fashion. Compared to most previous studies that are ROI-based, our approach has the potential to discover localized development patterns associated with fiber tracts of interest.

YNIMG Journal 2011 Journal Article

Automatic segmentation of neonatal images using convex optimization and coupled level sets

  • Li Wang
  • Feng Shi
  • Weili Lin
  • John H. Gilmore
  • Dinggang Shen

Accurate segmentation of neonatal brain MR images remains challenging mainly due to their poor spatial resolution, inverted contrast between white matter and gray matter, and high intensity inhomogeneity. Most existing methods for neonatal brain segmentation are atlas-based and voxel-wise. Although active contour/surface models with geometric information constraint have been successfully applied to adult brain segmentation, they are not fully explored in the neonatal image segmentation. In this paper, we propose a novel neonatal image segmentation method by combining local intensity information, atlas spatial prior, and cortical thickness constraint in a single level-set framework. Besides, we also provide a robust and reliable tissue surface initialization for the proposed method by using a convex optimization technique. Thus, tissue segmentation, as well as inner and outer cortical surface reconstruction, can be obtained simultaneously. The proposed method has been tested on a large neonatal dataset, and the validation on 10 neonatal brain images (with manual segmentations) shows very promising results.

YNIMG Journal 2011 Journal Article

Brain anatomical networks in early human brain development

  • Yong Fan
  • Feng Shi
  • Jeffrey Keith Smith
  • Weili Lin
  • John H. Gilmore
  • Dinggang Shen

Recent neuroimaging studies have demonstrated that human brain networks have economic small-world topology and modular organization, enabling efficient information transfer among brain regions. However, it remains largely unknown how the small-world topology and modular organization of human brain networks emerge and develop. Using longitudinal MRI data of 28 healthy pediatric subjects, collected at their ages of 1month, 1year, and 2years, we analyzed development patterns of brain anatomical networks derived from morphological correlations of brain regional volumes. The results show that the brain network of 1-month-olds has the characteristically economic small-world topology and nonrandom modular organization. The network's cost efficiency increases with the brain development to 1year and 2years, so does the modularity, providing supportive evidence for the hypothesis that the small-world topology and the modular organization of brain networks are established during early brain development to support rapid synchronization and information transfer with minimal rewiring cost, as well as to balance between local processing and global integration of information.

YNIMG Journal 2011 Journal Article

FADTTS: Functional analysis of diffusion tensor tract statistics

  • Hongtu Zhu
  • Linglong Kong
  • Runze Li
  • Martin Styner
  • Guido Gerig
  • Weili Lin
  • John H. Gilmore

The aim of this paper is to present a functional analysis of a diffusion tensor tract statistics (FADTTS) pipeline for delineating the association between multiple diffusion properties along major white matter fiber bundles with a set of covariates of interest, such as age, diagnostic status and gender, and the structure of the variability of these white matter tract properties in various diffusion tensor imaging studies. The FADTTS integrates five statistical tools: (i) a multivariate varying coefficient model for allowing the varying coefficient functions in terms of arc length to characterize the varying associations between fiber bundle diffusion properties and a set of covariates, (ii) a weighted least squares estimation of the varying coefficient functions, (iii) a functional principal component analysis to delineate the structure of the variability in fiber bundle diffusion properties, (iv) a global test statistic to test hypotheses of interest, and (v) a simultaneous confidence band to quantify the uncertainty in the estimated coefficient functions. Simulated data are used to evaluate the finite sample performance of FADTTS. We apply FADTTS to investigate the development of white matter diffusivities along the splenium of the corpus callosum tract and the right internal capsule tract in a clinical study of neurodevelopment. FADTTS can be used to facilitate the understanding of normal brain development, the neural bases of neuropsychiatric disorders, and the joint effects of environmental and genetic factors on white matter fiber bundles. The advantages of FADTTS compared with the other existing approaches are that they are capable of modeling the structured inter-subject variability, testing the joint effects, and constructing their simultaneous confidence bands. However, FADTTS is not crucial for estimation and reduces to the functional analysis method for the single measure.

YNIMG Journal 2011 Journal Article

Longitudinal regression analysis of spatial–temporal growth patterns of geometrical diffusion measures in early postnatal brain development with diffusion tensor imaging

  • Yasheng Chen
  • Hongyu An
  • Hongtu Zhu
  • Valerie Jewells
  • Diane Armao
  • Dinggang Shen
  • John H. Gilmore
  • Weili Lin

Although diffusion tensor imaging (DTI) has provided substantial insights into early brain development, most DTI studies based on fractional anisotropy (FA) and mean diffusivity (MD) may not capitalize on the information derived from the three principal diffusivities (e. g. eigenvalues). In this study, we explored the spatial and temporal evolution of white matter structures during early brain development using two geometrical diffusion measures, namely, linear (Cl) and planar (Cp) diffusion anisotropies, from 71 longitudinal datasets acquired from 29 healthy, full-term pediatric subjects. The growth trajectories were estimated with generalized estimating equations (GEE) using linear fitting with logarithm of age (days). The presence of the white matter structures in Cl and Cp was observed in neonates, suggesting that both the cylindrical and fanning or crossing structures in various white matter regions may already have been formed at birth. Moreover, we found that both Cl and Cp evolved in a temporally nonlinear and spatially inhomogeneous manner. The growth velocities of Cl in central white matter were significantly higher when compared to peripheral, or more laterally located, white matter: central growth velocity Cl =0. 0465±0. 0273/log(days), versus peripheral growth velocity Cl =0. 0198±0. 0127/log(days), p<10−6. In contrast, the growth velocities of Cp in central white matter were significantly lower than that in peripheral white matter: central growth velocity Cp= 0. 0014 ± 0. 0058/log(days), versus peripheral growth velocity Cp =0. 0289±0. 0101/log(days), p<10−6. Depending on the underlying white matter site which is analyzed, our findings suggest that ongoing physiologic and microstructural changes in the developing brain may exert different effects on the temporal evolution of these two geometrical diffusion measures. Thus, future studies utilizing DTI with correlative histological analysis in the study of early brain development are warranted.

YNIMG Journal 2011 Journal Article

Sex differences in grey matter atrophy patterns among AD and aMCI patients: Results from ADNI

  • Martha Skup
  • Hongtu Zhu
  • Yaping Wang
  • Kelly S. Giovanello
  • Ja-an Lin
  • Dinggang Shen
  • Feng Shi
  • Wei Gao

We used longitudinal magnetic resonance imaging (MRI) data to determine whether there are any gender differences in grey matter atrophy patterns over time in 197 individuals with probable Alzheimer's disease (AD) and 266 with amnestic mild cognitive impairment (aMCI), compared with 224 healthy controls participating in the Alzheimer's Disease Neuroimaging Initiative (ADNI). While previous research has differentiated probable AD and aMCI groups from controls in brain atrophy, it is unclear whether and how sex plays a role in patterns of change over time. Using regional volumetric maps, we fit longitudinal models to the grey matter data collected at repeated occasions, seeking differences in patterns of volume change over time by sex and diagnostic group in a voxel-wise analysis. Additionally, using a region-of-interest approach, we fit longitudinal models to the global volumetric data of predetermined brain regions to determine whether this more conventional approach is sufficient for determining sex and group differences in atrophy. Our longitudinal analyses revealed that, of the various grey matter regions investigated, males and females in the AD group and the aMCI group showed different patterns of decline over time compared to controls in the bilateral precuneus, bilateral caudate nucleus, right entorhinal gyrus, bilateral thalamus, bilateral middle temporal gyrus, left insula, and right amygdala. As one of the first investigation to model more than two time points of structural MRI data over time, our findings add insight into how AD and aMCI males and females differ from controls and from each other over time.

YNIMG Journal 2011 Journal Article

SPHERE: SPherical Harmonic Elastic REgistration of HARDI data

  • Pew-Thian Yap
  • Yasheng Chen
  • Hongyu An
  • Yang Yang
  • John H. Gilmore
  • Weili Lin
  • Dinggang Shen

In contrast to the more common Diffusion Tensor Imaging (DTI), High Angular Resolution Diffusion Imaging (HARDI) allows superior delineation of angular microstructures of brain white matter, and makes possible multiple-fiber modeling of each voxel for better characterization of brain connectivity. However, the complex orientation information afforded by HARDI makes registration of HARDI images more complicated than scalar images. In particular, the question of how much orientation information is needed for satisfactory alignment has not been sufficiently addressed. Low order orientation representation is generally more robust than high order representation, although the latter provides more information for correct alignment of fiber pathways. However, high order representation, when naïvely utilized, might not necessarily be conducive to improving registration accuracy since similar structures with significant orientation differences prior to proper alignment might be mistakenly taken as non-matching structures. We present in this paper a HARDI registration algorithm, called SPherical Harmonic Elastic REgistration (SPHERE), which in a principled means hierarchically extracts orientation information from HARDI data for structural alignment. The image volumes are first registered using robust, relatively direction invariant features derived from the Orientation Distribution Function (ODF), and the alignment is then further refined using spherical harmonic (SH) representation with gradually increasing orders. This progression from non-directional, single-directional to multi-directional representation provides a systematic means of extracting directional information given by diffusion-weighted imaging. Coupled with a template–subject-consistent soft-correspondence-matching scheme, this approach allows robust and accurate alignment of HARDI data. Experimental results show marked increase in accuracy over a state-of-the-art DTI registration algorithm.

YNIMG Journal 2010 Journal Article

Construction of multi-region-multi-reference atlases for neonatal brain MRI segmentation

  • Feng Shi
  • Pew-Thian Yap
  • Yong Fan
  • John H. Gilmore
  • Weili Lin
  • Dinggang Shen

Neonatal brain MRI segmentation is a challenging problem due to its poor image quality. Atlas-based segmentation approaches have been widely used for guiding brain tissue segmentation. Existing brain atlases are usually constructed by equally averaging pre-segmented images in a population. However, such approaches diminish local inter-subject structural variability and thus lead to lower segmentation guidance capability. To deal with this problem, we propose a multi-region-multi-reference framework for atlas-based neonatal brain segmentation. For each region of a brain parcellation, a population of spatially normalized pre-segmented images is clustered into a number of sub-populations. Each sub-population of a region represents an independent distribution from which a regional probability atlas can be generated. A selection of these regional atlases, across different sub-regions, will in the end be adaptively combined to form an overall atlas specific to the query image. Given a query image, the determination of the appropriate set of regional atlases is achieved by comparing the query image regionally with the reference, or exemplar, of each sub-population. Upon obtaining an overall atlas, an atlas-based joint registration–segmentation strategy is employed to segment the query image. Since the proposed method generates an atlas which is significant more similar to the query image than the traditional average-shape atlas, better tissue segmentation results can be expected. This is validated by applying the proposed method on a large set of neonatal brain images available in our institute. Experimental results on a randomly selected set of 10 neonatal brain images indicate that the proposed method achieves higher tissue overlap rates and lower standard deviations (SDs) in comparison with manual segmentations, i. e. , 0. 86 (SD 0. 02) for GM, 0. 83 (SD 0. 03) for WM, and 0. 80 (SD 0. 05) for CSF. The proposed method also outperforms two other average-shape atlas-based segmentation methods.

YNIMG Journal 2010 Journal Article

Neonatal brain image segmentation in longitudinal MRI studies

  • Feng Shi
  • Yong Fan
  • Songyuan Tang
  • John H. Gilmore
  • Weili Lin
  • Dinggang Shen

In the study of early brain development, tissue segmentation of neonatal brain MR images remains challenging because of the insufficient image quality due to the properties of developing tissues. Among various brain tissue segmentation algorithms, atlas-based brain image segmentation can potentially achieve good segmentation results on neonatal brain images. However, their performances rely on both the quality of the atlas and the spatial correspondence between the atlas and the to-be-segmented image. Moreover, it is difficult to build a population atlas for neonates due to the requirement of a large set of tissue-segmented neonatal brain images. To combat these obstacles, we present a longitudinal neonatal brain image segmentation framework by taking advantage of the longitudinal data acquired at late time-point to build a subject-specific tissue probabilistic atlas. Specifically, tissue segmentation of the neonatal brain is formulated as two iterative steps of bias correction and probabilistic-atlas-based tissue segmentation, along with the longitudinal atlas reconstructed by the late time image of the same subject. The proposed method has been evaluated qualitatively through visual inspection and quantitatively by comparing with manual delineations and two population-atlas-based segmentation methods. Experimental results show that the utilization of a subject-specific probabilistic atlas can substantially improve tissue segmentation of neonatal brain images.

YNIMG Journal 2009 Journal Article

A unified optimization approach for diffusion tensor imaging technique

  • Wei Gao
  • Hongtu Zhu
  • Weili Lin

An optimization approach for diffusion tensor imaging (DTI) technique is proposed, aiming to improve the estimates of tensors, fractional anisotropy (FA), and fiber directions. With the simulated annealing algorithm, the proposed approach simultaneously optimizes imaging parameters (gradient duration/separation, read-out time, and TE), b-values, and diffusion gradient directions either with or without incorporating prior knowledge of tensor fields. In addition, the method through which tensors are estimated, least squares in our study, was also considered in the optimization procedures. Monte-Carlo simulations were performed for three different scenarios of prior fiber distributions including fibers orientated in 1 (CONE1) and 3 (CONE3) cone areas (50 tensors orderly oriented within a diverging angle of 20° in each cone) and a uniform fiber distribution (UNIF). In addition, three imaging acquisition schemes together with different signal-to-noise ratios were tested, including M/N=1/6, 2/12, and 5/30 for each prior fiber distribution where M and N were the number of b=0 and b>0 images, respectively. Our results show that the optimal b-value ranges between 0. 7 and 1. 0×109 s/m2 for UNIF. However, the optimal b-value ranges become both higher and wider for CONE1 and CONE3 than that of UNIF. In addition, the biases and standard deviations (SD) of tensors, and SD of FA are substantially reduced and the accuracy of fiber directional estimates is improved using the proposed approach particularly in CONE1 when compared with the conventional approaches. Together, the proposed unified optimization approach may offer a direct and simultaneous means to optimize DTI experiments.

YNIMG Journal 2009 Journal Article

Computerized assessment of vessel morphological changes during treatment of glioblastoma multiforme: Report of a case imaged serially by MRA over four years

  • Elizabeth Bullitt
  • Matthew Ewend
  • James Vredenburgh
  • Allan Friedman
  • Weili Lin
  • Kathy Wilber
  • Donglin Zeng
  • Stephen R. Aylward

A patient with glioblastoma multiforme underwent serial computerized analysis of tumor-associated vasculature defined from magnetic resonance angiographic (MRA) scans obtained over almost a four year period. The clinical course included tumor resection with subsequent radiation therapy, a long symptom-free interval, emergence of a new malignant focus, resection of that focus, a stroke, and treatment with chemotherapy and anti-angiogenic therapy. Image analysis methods included segmentation of vessels from each MRA and statistical comparison of vessel morphology over 4 regions of interest (the initial tumor site, the second tumor site, a distant control region, and the entire brain) to the same 4 regions of interest in 50 healthy volunteers (26 females and 24 males; mean age 39 years). Results suggested that following completion of focal radiation therapy (RT) vessel shape abnormalities, if elevated at the time of RT completion, may progressively normalize for months in focal regions, that progressively severe vessel shape abnormalities can precede the emergence of a gadolinium enhancing lesion by months, that lesion resection can produce a dramatic but highly transient drop in abnormal vessel tortuosity both focally and globally, and that treatment with anti-angiogenic agents does not necessarily normalize vessel shape. Quantitative measurements of vessel morphology as defined from MRA may provide useful insights into tumor development and response to therapy.

YNIMG Journal 2009 Journal Article

TIMER: Tensor Image Morphing for Elastic Registration

  • Pew-Thian Yap
  • Guorong Wu
  • Hongtu Zhu
  • Weili Lin
  • Dinggang Shen

We propose a novel diffusion tensor imaging (DTI) registration algorithm, called Tensor Image Morphing for Elastic Registration (TIMER), which leverages the hierarchical guidance of regional distributions and local boundaries, both extracted directly from the tensors. Currently available DTI registration methods generally extract tensor scalar features from each tensor to construct scalar maps. Subsequently, regional integration and other operations such as edge detection are performed to extract more features to guide the registration. However, there are two major limitations with these approaches. First, the computed regional features might not reflect the actual regional tensor distributions. Second, by the same token, gradient maps calculated from the tensor-derived scalar feature maps might not represent the actual tissue tensor boundaries. To overcome these limitations, we propose a new approach which extracts regional and edge information directly from a tensor neighborhood. Regional tensor distribution information, such as mean and variance, is computed in a multiscale fashion directly from the tensors by taking into account the voxel neighborhood of different sizes, and hence capturing tensor information at different scales, which in turn can be employed to hierarchically guide the registration. Such multiscale scheme can help alleviate the problem of local minimum and is also more robust to noise since one can better determine the statistical properties of each voxel by taking into account the properties of its surrounding. Also incorporated in our method is edge information extracted directly from the tensors, which is crucial to facilitate registration of tissue boundaries. Experiments involving real subjects, simulated subjects, fiber tracking, and atrophy detection indicate that TIMER performs better than the other methods (Yang et al. , 2008; Zhang et al. , 2006).

YNIMG Journal 2009 Journal Article

White matter abnormalities revealed by diffusion tensor imaging in non-demented and demented HIV+ patients

  • Yasheng Chen
  • Hongyu An
  • Hongtu Zhu
  • Taylor Stone
  • J. Keith Smith
  • Colin Hall
  • Elizabeth Bullitt
  • Dinggang Shen

HIV associated dementia (HAD) is the most advanced stage of central nervous system disease caused by HIV infection. Previous studies have demonstrated that patients with HAD exhibit greater cerebral and basal ganglia atrophy than non-demented HIV+ (HND) patients. However, the extent to which white matter is affected in HAD patients compared to HND patients remains elusive. This study is designed to address the potential white matter abnormalities through the utilization of diffusion tensor imaging (DTI) in both HND and HAD patients. DTI and T1-weighted images were acquired from 18 healthy controls, 21 HND and 8 HAD patients. T1 image-based registration was performed to 1) parcellate the whole brain white matter into major white matter regions, including frontal, parietal, temporal and occipital white matter, corpus callosum and internal capsule for statistical comparisons of the mean DTI values, and 2) warp all DTI parametric images towards the common template space for voxel-based analysis. The statistical comparisons were performed with four DTI parameters including fractional anisotropy (FA), mean (MD), axial (AD), and radial (RD) diffusivities. With Whitney U tests on the mean DTI values, both HND and HAD demonstrated significant differences from the healthy control in multiple white matter regions. In addition, HAD patients exhibited significantly elevated MD and RD in the parietal white matter when compared to HND patients. In the voxel-based analysis, widespread abnormal regions were identified for both HND and HAD patients, although a much larger abnormal volume was observed in HAD patients for all four DTI parameters. Furthermore, both region of interest (ROI) based and voxel-based analyses revealed that RD was affected to a much greater extent than AD by HIV infection, which may suggest that demyelination is the prominent disease progression in white matter.

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