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Delineating the normative developmental profile of functional connectome is important for both standardized assessment of individual growth and early detection of diseases. However, functional connectome has been mostly studied using functional connectivity (FC), where undirected connectivity strengths are estimated from statistical correlation of resting-state functional MRI (rs-fMRI) signals. To address this limitation, we applied regression dynamic causal modeling (rDCM) to delineate the developmental trajectories of effective connectivity (EC), the directed causal influence among neuronal populations, in whole-brain networks from infancy to adolescence (0-22 years old) based on high-quality rs-fMRI data from Baby Connectome Project (BCP) and Human Connectome Project Development (HCP-D). Analysis with linear mixed model demonstrates significant age effect on the mean nodal EC which is best fit by a "U" shaped quadratic curve with minimal EC at around 2 years old. Further analysis indicates that five brain regions including the left and right cuneus, left precuneus, left supramarginal gyrus and right inferior temporal gyrus have the most significant age effect on nodal EC ( p < 0.05, FDR corrected). Moreover, the frontoparietal control (FPC) network shows the fastest increase from early childhood to adolescence followed by the visual and salience networks. Our findings suggest complex nonlinear developmental profile of EC from infancy to adolescence, which may reflect dynamic structural and functional maturation during this critical growth period.

Most brain microstructure models are dedicated to the quantification of white matter microstructure, using for example sticks, cylinders, and zeppelins to model intra- and extra-axonal environments. Gray matter presents unique micro-architecture with cell bodies (somas) exhibiting diffusion characteristics that differ from axons in white matter. In this paper, we introduce a method to quantify soma microstructure, giving measures such as volume fraction, diffusivity, and kurtosis. Our method captures a spectrum of diffusion patterns and scales and does not rely on restrictive model assumptions. We show that our method yields unique and meaningful contrasts that are in agreement with histological data. We demonstrate its application in the mapping of the distinct spatial patterns of soma density in the cortex.

Diffusion MRI (dMRI) is typically time consuming as it involves acquiring a series of 3D volumes, each associated with a wave-vector in q-space that determines the diffusion direction and strength. The acquisition time is further increased when "blip-up blip-down" scans are acquired with opposite phase encoding directions (PEDs) to facilitate distortion correction. In this work, we show that geometric distortions can be corrected without acquiring with opposite PEDs for each wave-vector, and hence the acquisition time can be halved. Our method uses complimentary rotation-invariant contrasts across shells of different diffusion weightings. Distortion-free structural T1-/T2-weighted MRI is used as reference for nonlinear registration in correcting the distortions. Signal dropout and pileup are corrected with the help of spherical harmonics. To demonstrate that our method is robust to changes in image appearance, we show that distortion correction with good structural alignment can be achieved within minutes for dMRI data of infants between 1 to 24 months of age.

In this paper, we introduce a method for estimating patient-specific reference bony shape models for planning of reconstructive surgery for patients with acquired craniomaxillofacial (CMF) trauma. We propose an automatic bony shape estimation framework using pre-traumatic portrait photographs and post-traumatic head computed tomography (CT) scans. A 3D facial surface is first reconstructed from the patient's pre-traumatic photographs. An initial estimation of the patient's normal bony shape is then obtained with the reconstructed facial surface via sparse representation using a dictionary of paired facial and bony surfaces of normal subjects. We further refine the bony shape model by deforming the initial bony shape model to the post-traumatic 3D CT bony model, regularized by a statistical shape model built from a database of normal subjects. Experimental results show that our method is capable of effectively recovering the patient's normal facial bony shape in regions with defects, allowing CMF surgical planning to be performed precisely for a wider range of defects caused by trauma.

Precise quantification of brain tissue micro-architecture using diffusion MRI is hampered by the conflation of diffusion-attenuated signals from micro-environments that can be orientationally heterogeneous due to complex fiber configurations, such as crossing, fanning, and bending, and compartmentally heterogeneous due to variability in tissue organization. In this paper, we introduce a method, called Spherical Mean Spectrum Imaging (SMSI), for quantification of tissue microstructure. SMSI does not assume a fixed number of compartments, but characterizes the signal as a spectrum of fine- to coarse-scale diffusion processes. Using SMSI, multiple orientation distribution invariant indices can be computed, allowing for example the quantification of neurite density, microscopic fractional anisotropy ( μ FA), per-axon axial/radial diffusivity, and free/restricted isotropic diffusivity. We show that SMSI is fast, accurate, and can overcome biases in state-of-the-art microstructure models. We demonstrate its application in probing microstructural changes in the baby brain during the first two years of life.

Fast and automated image quality assessment (IQA) for diffusion MR images is crucial so that a rescan decision can be made swiftly during or after the scanning session. However, learning this task is challenging as the number of annotated data is limited and the annotated label is not always perfect. To this end, we introduce an automatic multistage IQA method for pediatric diffusion MR images. Our IQA is performed in three sequential stages, i.e., slice-wise quality assessment (QA) using a nonlocal residual network, volume-wise QA by agglomerating the extracted features of slices belonging to one volume using a nonlocal network, and subject-wise QA by ensembling the QA results of volumes belonging to one subject. In addition, we employ semi-supervised learning to make full use of a small amount of annotated data and a large amount of unlabeled data to train our network. Specifically, we first pretrain our network using labeled data, which are iteratively expanded by labeling the unlabeled data with the trained network. Furthermore, we devise a self-training strategy which iteratively relabels and prunes the labeled dataset when training the network to deal with noisy labels. Experimental results demonstrate that our network, trained using only samples of modest size, exhibits great generalizability and is capable of conducting large-scale rapid IQA with near-perfect accuracy.

Complex tissue microstructure involving various types of cells and their membranes can deviate the movement of water molecules from the typical Gaussian diffusion. This deviation can be quantified using excess kurtosis to characterize tissue structural complexity. However, true kurtosis measurements can be obscured by complex white matter configurations such as fiber crossing, bending, and branching, which are ubiquitous in the brain. In this paper, we extend diffusion kurtosis imaging (DKI) to allow characterization of diffusional kurtosis in microstructural environments that are oriented heterogeneously. Our method, called microscopic DKI ( μ DKI), fits a cylindrically symmetric kurtosis model to the spherical mean of the diffusion signal as a function of diffusion weighting. The spherical mean, computed for each b -shell, is invariant to the fiber orientation distribution and is a function of per-axon microstructural properties. Experimental results indicate that μ DKI yields significantly higher consistency in quantifying microstructure than the conventional DKI in the presence of orientation heterogeneity.

Recent studies have shown that fusing multi-modal neuroimaging data can improve the performance of Alzheimer's Disease (AD) diagnosis. However, most existing methods simply concatenate features from each modality without appropriate consideration of the correlations among multi-modalities. Besides, existing methods often employ feature selection (or fusion) and classifier training in two independent steps without consideration of the fact that the two pipelined steps are highly related to each other. Furthermore, existing methods that make prediction based on a single classifier may not be able to address the heterogeneity of the AD progression. To address these issues, we propose a novel AD diagnosis framework based on latent space learning with ensemble classifiers, by integrating the latent representation learning and ensemble of multiple diversified classifiers learning into a unified framework. To this end, we first project the neuroimaging data from different modalities into a common latent space, and impose a joint sparsity constraint on the concatenated projection matrices. Then, we map the learned latent representations into the label space to learn multiple diversified classifiers and aggregate their predictions to obtain the final classification result. Experimental results on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset show that our method outperforms other state-of-the-art methods.

It is vital to identify Mild Cognitive Impairment (MCI) subjects who will progress to Alzheimer's Disease (AD), so that early treatment can be administered. Recent studies show that using complementary information from multi-modality data may improve the model performance of the above prediction problem. However, multi-modality data is often incomplete, causing the prediction models that rely on complete data unusable. One way to deal with this issue is by first imputing the missing values, and then building a classifier based on the completed data. This two-step approach, however, may generate non-optimal classifier output, as the errors of the imputation may propagate to the classifier during training. To address this issue, we propose a unified framework that jointly performs feature selection, data denoising, missing values imputation, and classifier learning. To this end, we use a low-rank constraint to impute the missing values and denoise the data simultaneously, while using a regression model for feature selection and classification. The feature weights learned by the regression model are integrated into the low rank formulation to focus on discriminative features when denoising and imputing data, while the resulting low-rank matrix is used for classifier learning. These two components interact and correct each other iteratively using Alternating Direction Method of Multiplier (ADMM). The experimental results using incomplete multi-modality ADNI dataset shows that our proposed method outperforms other comparison methods.

In this paper, we aim to maximally utilize multimodality neuroimaging and genetic data to predict Alzheimer's disease (AD) and its prodromal status, i.e., a multi-status dementia diagnosis problem. Multimodality neuroimaging data such as MRI and PET provide valuable insights to abnormalities, and genetic data such as Single Nucleotide Polymorphism (SNP) provide information about a patient's AD risk factors. When used in conjunction, AD diagnosis may be improved. However, these data are heterogeneous (e.g., having different data distributions), and have different number of samples (e.g., PET data is having far less number of samples than the numbers of MRI or SNPs). Thus, learning an effective model using these data is challenging. To this end, we present a novel three-stage deep feature learning and fusion framework , where the deep neural network is trained stage-wise. Each stage of the network learns feature representations for different combination of modalities, via effective training using maximum number of available samples . Specifically, in the first stage, we learn latent representations (i.e., high-level features) for each modality independently, so that the heterogeneity between modalities can be better addressed and then combined in the next stage. In the second stage, we learn the joint latent features for each pair of modality combination by using the high-level features learned from the first stage. In the third stage, we learn the diagnostic labels by fusing the learned joint latent features from the second stage. We have tested our framework on Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset for multi-status AD diagnosis, and the experimental results show that the proposed framework outperforms other methods.

MGMT promoter methylation and IDH1 mutation in high-grade gliomas (HGG) have proven to be the two important molecular indicators associated with better prognosis. Traditionally, the statuses of MGMT and IDH1 are obtained via surgical biopsy, which is laborious, invasive and time-consuming. Accurate presurgical prediction of their statuses based on preoperative imaging data is of great clinical value towards better treatment plan. In this paper, we propose a novel Multi-label Inductive Matrix Completion (MIMC) model, highlighted by the online inductive learning strategy, to jointly predict both MGMT and IDH1 statuses. Our MIMC model not only uses the training subjects with possibly missing MGMT/IDH1 labels, but also leverages the unlabeled testing subjects as a supplement to the limited training dataset. More importantly, we learn inductive labels, instead of directly using transductive labels, as the prediction results for the testing subjects, to alleviate the overfitting issue in small-sample-size studies. Furthermore, we design an optimization algorithm with guaranteed convergence based on the block coordinate descent method to solve the multivariate non-smooth MIMC model. Finally, by using a precious single-center multi-modality presurgical brain imaging and genetic dataset of primary HGG, we demonstrate that our method can produce accurate prediction results, outperforming the previous widely-used single- or multi-task machine learning methods. This study shows the promise of utilizing imaging-derived brain connectome phenotypes for prognosis of HGG in a non-invasive manner.

It is challenging to use incomplete multimodality data for Alzheimer's Disease (AD) diagnosis. The current methods to address this challenge, such as low-rank matrix completion ( i.e ., imputing the missing values and unknown labels simultaneously) and multi-task learning ( i.e ., defining one regression task for each combination of modalities and then learning them jointly), are unable to model the complex data-to-label relationship in AD diagnosis and also ignore the heterogeneity among the modalities. In light of this, we propose a new Maximum Mean Discrepancy (MMD) based Multiple Kernel Learning (MKL) method for AD diagnosis using incomplete multimodality data. Specifically, we map all the samples from different modalities into a Reproducing Kernel Hilbert Space (RKHS), by devising a new MMD algorithm. The proposed MMD method incorporates data distribution matching, pair-wise sample matching and feature selection in an unified formulation, thus alleviating the modality heterogeneity issue and making all the samples comparable to share a common classifier in the RKHS. The resulting classifier obviously captures the nonlinear data-to-label relationship. We have tested our method using MRI and PET data from Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset for AD diagnosis. The experimental results show that our method outperforms other methods.

Effective utilization of heterogeneous multi-modal data for Alzheimer's Disease (AD) diagnosis and prognosis has always been hampered by incomplete data. One method to deal with this is low-rank matrix completion (LRMC), which simultaneous imputes missing data features and target values of interest. Although LRMC yields reasonable results, it implicitly weights features from all the modalities equally, ignoring the differences in discriminative power of features from different modalities. In this paper, we propose stability-weighted LRMC (swLRMC), an LRMC improvement that weights features and modalities according to their importance and reliability . We introduce a method, called stability weighting , to utilize subsampling techniques and outcomes from a range of hyper-parameters of sparse feature learning to obtain a stable set of weights. Incorporating these weights into LRMC, swLRMC can better account for differences in features and modalities for improving diagnosis. Experimental results confirm that the proposed method outperforms the conventional LRMC, feature-selection based LRMC, and other state-of-the-art methods.

This paper proposes a framework of fast neuroimaging-based retrieval and AD analysis, by three key steps: (1) landmark detection , which efficiently extracts landmark-based neuroimaging features without the need of nonlinear registration in testing stage; (2) landmark selection , which removes redundant/noisy landmarks via proposing a feature selection method that considers structural information among landmarks; and (3) hashing , which converts high-dimensional features of subjects into binary codes, for efficiently conducting approximate nearest neighbor search and diagnosis of AD. We have conducted experiments on Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, and demonstrated that our framework could achieve higher performance than the comparison methods, in terms of accuracy and speed (at least 100 times faster).

Neuroimaging data have been widely used to derive possible biomarkers for Alzheimer's Disease (AD) diagnosis. As only certain brain regions are related to AD progression, many feature selection methods have been proposed to identify informative features ( i.e. , brain regions) to build an accurate prediction model. These methods mostly only focus on the feature-target relationship to select features which are discriminative to the targets ( e.g. , diagnosis labels). However, since the brain regions are anatomically and functionally connected, there could be useful intrinsic relationships among features. In this paper, by utilizing both the feature-target and feature-feature relationships, we propose a novel sparse regression model to select informative features which are discriminative to the targets and also representative to the features. We argue that the features which are representative ( i.e. , can be used to represent many other features) are important, as they signify strong "connection" with other ROIs, and could be related to the disease progression. We use our model to select features for both binary and multi-class classification tasks, and the experimental results on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset show that the proposed method outperforms other comparison methods considered in this work.

Identifying progressive mild cognitive impairment (pMCI) patients and predicting when they will convert to Alzheimer's disease (AD) are important for early medical intervention. Multi-modality and longitudinal data provide a great amount of information for improving diagnosis and prognosis. But these data are often incomplete and noisy. To improve the utility of these data for prediction purposes, we propose an approach to denoise the data, impute missing values, and cluster the data into low-dimensional subspaces for pMCI prediction. We assume that the data reside in a space formed by a union of several low-dimensional subspaces and that similar MCI conditions reside in similar subspaces. Therefore, we first use incomplete low-rank representation (ILRR) and spectral clustering to cluster the data according to their representative low-rank subspaces. At the same time, we denoise the data and impute missing values. Then we utilize a low-rank matrix completion (LRMC) framework to identify pMCI patients and their time of conversion. Evaluations using the ADNI dataset indicate that our method outperforms conventional LRMC method.

Autism spectrum disorder (ASD) is a variety of developmental disorders that cause life-long communication and social deficits. However, ASD could only be diagnosed at children as early as 2 years of age, while early signs may emerge within the first year. White matter (WM) connectivity abnormalities have been documented in the first year of lives of ASD subjects. We introduce a novel multi-kernel support vector machine (SVM) framework to identify infants at high-risk for ASD at 6 months old, by utilizing the diffusion parameters derived from a hierarchical set of WM connectomes. Experiments show that the proposed method achieves an accuracy of 76%, in comparison to 70% with the best single connectome. The complementary information extracted from hierarchical networks enhances the classification performance, with the top discriminative connections consistent with other studies. Our framework provides essential imaging connectomic markers and contributes to the evaluation of ASD risks as early as 6 months.

In this paper, we propose a multi-view learning method using Magnetic Resonance Imaging (MRI) data for Alzheimer's Disease (AD) diagnosis. Specifically, we extract both Region-Of-Interest (ROI) features and Histograms of Oriented Gradient (HOG) features from each MRI image, and then propose mapping HOG features onto the space of ROI features to make them comparable and to impose high intra-class similarity with low inter-class similarity. Finally, both mapped HOG features and original ROI features are input to the support vector machine for AD diagnosis. The purpose of mapping HOG features onto the space of ROI features is to provide complementary information so that features from different views can not only be comparable ( i.e., homogeneous) but also be interpretable. For example, ROI features are robust to noise, but lack of reflecting small or subtle changes, while HOG features are diverse but less robust to noise. The proposed multi-view learning method is designed to learn the transformation between two spaces and to separate the classes under the supervision of class labels. The experimental results on the MRI images from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset show that the proposed multi-view method helps enhance disease status identification performance, outperforming both baseline methods and state-of-the-art methods.